ORCID Profile
0000-0003-4350-5976
Current Organisation
University of Queensland
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Research Topics
In Research Link Australia (RLA), "Research Topics" refer to ANZSRC FOR and SEO codes. These topics are either sourced from ANZSRC FOR and SEO codes listed in researchers' related grants or generated by a large language model (LLM) based on their publications.
Top 5 Research Topics
ANZSRC Field of Research (FoR)
Geology | Tectonics | Geochronology | Magnetism and Palaeomagnetism | Geophysics | Geotectonics | Geodynamics | Isotope Geochemistry | Petroleum and Coal Geology | Geochronology | Geochemistry | Geomagnetism | Inorganic Geochemistry | Astronomical and Space Sciences | Biochemistry and Cell Biology | Basin Analysis | Marine Geoscience | Igneous and Metamorphic Petrology | Extraterrestrial Geology | Central Nervous System | Protein Targeting And Signal Transduction | Cell Neurochemistry | Planetary Science (excl. Extraterrestrial Geology) | Geochemistry Not Elsewhere Classified | Applied Mathematics | Palaeoclimatology | Quaternary Environments | Biological Mathematics | Geophysics Not Elsewhere Classified |
ANZSRC Socio-Economic Objective (SEO)
Expanding Knowledge in the Earth Sciences | Mineral Exploration not elsewhere classified | Earth sciences | Oil and Gas Exploration | Climate change | Precious (Noble) Metal Ore Exploration | Energy Exploration not elsewhere classified | Health related to ageing | Marine Oceanic Processes (excl. climate related) | Mining and Extraction of Iron Ores | Effects of Climate Change and Variability on Australia (excl. Social Impacts) | Climate Variability (excl. Social Impacts) | Climate Change Models | Nervous system and disorders | Higher education | Mineral Resources (excl. Energy Resources) not elsewhere classified | Expanding Knowledge in the Environmental Sciences | Titanium Minerals, Zircon, and Rare Earth Metal Ore (e.g. Monazite) Exploration | Expanding Knowledge in the Mathematical Sciences
Related Links
Publications
Paleomagnetic constraints on timing of the Neoproterozoic breakup of Rodinia and the Cambrian formation of Gondwana
Publisher: Geological Society of America
Date: 1993
Formation of the 1300-km-wide intracontinental orogen and postorogenic magmatic province in Mesozoic South China: A flat-slab subduction model
Publisher: Geological Society of America
Date: 2007
DOI: 10.1130/G23193A.1
The efficacy of intravitreal dexamethasone implants for non‐infectious posterior segment uveitis: Increasing the uveitis armamentarium
Publisher: Wiley
Date: 12-2019
DOI: 10.1111/CEO.13694
Formation of mantle “lone plumes” in the global downwelling zone — A multiscale modelling of subduction-controlled plume generation beneath the South China Sea
Publisher: Elsevier BV
Date: 2018
Assembly and break-up of Rodinia and Gondwana: Evidence from Eurasia and Gondwana: Introduction
Publisher: Elsevier BV
Date: 04-2003
Will Earth's next supercontinent assemble through the closure of the Pacific Ocean?
Publisher: Oxford University Press (OUP)
Date: 28-09-2022
DOI: 10.1093/NSR/NWAC205
Abstract: Earth's known supercontinents are believed to have formed in vastly different ways, with two endmembers being introversion and extroversion. The former involves the closure of the internal oceans formed during the break-up of the previous supercontinent, whereas the latter involves the closure of the previous external superocean. However, it is unclear what caused such erging behavior of supercontinent cycles that involved first-order interaction between subducting tectonic plates and the mantle. Here we address this question through 4D geodynamic modeling using realistic tectonic set-ups. Our results show that the strength of the oceanic lithosphere plays a critical role in determining the assembly path of a supercontinent. We found that high oceanic lithospheric strength leads to introversion assembly, whereas lower strength leads to extroversion assembly. A theoretically estimated reduction in oceanic crustal thickness, and thus its strength, during Earth's secular cooling indicates that introversion was only possible for the Precambrian time when the oceanic lithosphere was stronger, thus predicting the assembling of the next supercontinent Amasia through the closure of the Pacific Ocean instead of the Indian-Atlantic oceans. Our work provides a new understanding of the secular evolution of plate tectonics and geodynamics as the Earth cooled.
Abrogation of RAB27A expression transiently affects melanoma cell proliferation
Publisher: Wiley
Date: 26-06-2020
DOI: 10.1111/PCMR.12903
Quantitative analysis of tumour spheroid structure
Publisher: eLife Sciences Publications, Ltd
Date: 29-11-2021
DOI: 10.7554/ELIFE.73020
Abstract: Tumour spheroids are common in vitro experimental models of avascular tumour growth. Compared with traditional two-dimensional culture, tumour spheroids more closely mimic the avascular tumour microenvironment where spatial differences in nutrient availability strongly influence growth. We show that spheroids initiated using significantly different numbers of cells grow to similar limiting sizes, suggesting that avascular tumours have a limiting structure in agreement with untested predictions of classical mathematical models of tumour spheroids. We develop a novel mathematical and statistical framework to study the structure of tumour spheroids seeded from cells transduced with fluorescent cell cycle indicators, enabling us to discriminate between arrested and cycling cells and identify an arrested region. Our analysis shows that transient spheroid structure is independent of initial spheroid size, and the limiting structure can be independent of seeding density. Standard experimental protocols compare spheroid size as a function of time however, our analysis suggests that comparing spheroid structure as a function of overall size produces results that are relatively insensitive to variability in spheroid size. Our experimental observations are made using two melanoma cell lines, but our modelling framework applies across a wide range of spheroid culture conditions and cell lines.
Provenance Evolution of Age‐Calibrated Strata Reveals When and How South China Block Collided With Gondwana
Publisher: American Geophysical Union (AGU)
Date: 02-10-2020
DOI: 10.1029/2020GL090282
Pitfalls in using the geochronological information from the EarthChem Portal for Precambrian time-series analysis
Publisher: Elsevier BV
Date: 02-2022
Mathematical models incorporating a multi-stage cell cycle replicate normally-hidden inherent synchronization in cell proliferation
Publisher: The Royal Society
Date: 08-2019
Abstract: We present a suite of experimental data showing that cell proliferation assays, prepared using standard methods thought to produce asynchronous cell populations, persistently exhibit inherent synchronization. Our experiments use fluorescent cell cycle indicators to reveal the normally hidden cell synchronization, by highlighting oscillatory subpopulations within the total cell population. These oscillatory subpopulations would never be observed without these cell cycle indicators. On the other hand, our experimental data show that the total cell population appears to grow exponentially, as in an asynchronous population. We reconcile these seemingly inconsistent observations by employing a multi-stage mathematical model of cell proliferation that can replicate the oscillatory subpopulations. Our study has important implications for understanding and improving experimental reproducibility. In particular, inherent synchronization may affect the experimental reproducibility of studies aiming to investigate cell cycle-dependent mechanisms, including changes in migration and drug response.
Neoproterozoic bimodal magmatism in the Cathaysia Block of South China and its tectonic significance
Publisher: Elsevier BV
Date: 10-01-2005
Author response: Quantitative analysis of tumour spheroid structure
Publisher: eLife Sciences Publications, Ltd
Date: 19-11-2021
Primary treatment of choroidal amelanotic melanoma with photodynamic therapy
Publisher: Wiley
Date: 19-09-2005
DOI: 10.1111/J.1442-9071.2005.01083.X
Abstract: The management of choroidal melanoma involves a delicate balance between preserving vision and preventing metastasis. Plaque brachytherapy has become standard management of most small lesions however, this can result in radiation retinopathy and optic neuropathy. Transpupillary thermotherapy avoids these side-effects however, it can also result in visual loss and its effectiveness is limited in amelanotic lesions. Photodynamic therapy with verteporfin has shown promise in animal studies of choroidal melanoma, and has recently been used in the management of lesions that have failed to respond to conventional therapy. The authors report a case of primary treatment of a small choroidal amelanotic melanoma with photodynamic therapy using verteporfin.
Cell-cell contacts in melanoma and the tumor microenvironment
Publisher: Springer International Publishing
Date: 2017
Petrogenesis of the Early Eocene adakitic rocks in the Napuri area, southern Lhasa: Partial melting of thickened lower crust during slab break-off and implications for crustal thickening in southern T
Publisher: Elsevier BV
Date: 05-2014
Paleomagnetic and rock magnetic investigations of the Changxing Permian‐Triassic section, Zhejiang Province, China
Publisher: American Geophysical Union (AGU)
Date: 20-08-1993
DOI: 10.1029/93GL01242
Multiple desmoplastic melanomas in Birt-Hogg-Dubé syndrome and a proposed signaling link between folliculin, the mTOR pathway, and melanoma susceptibility
Publisher: American Medical Association (AMA)
Date: 11-2010
New Precambrian palaeomagnetic constraints on the position of the North China Block in Rodinia
Publisher: Elsevier BV
Date: 10-02-2006
Decoding Earth's rhythms: Modulation of supercontinent cycles by longer superocean episodes
Publisher: Elsevier BV
Date: 04-2019
Self demagnetisation corrections in magnetic modelling: Some examples
Publisher: Informa UK Limited
Date: 09-1998
DOI: 10.1071/EG998396
Quantitative analysis of tumour spheroid structure
Publisher: Cold Spring Harbor Laboratory
Date: 06-08-2021
DOI: 10.1101/2021.08.05.455334
Abstract: Tumour spheroids are common in vitro experimental models of avascular tumour growth. Compared with traditional two-dimensional culture, tumour spheroids more closely mimic the avascular tumour microenvironment where spatial differences in nutrient availability strongly influence growth. We show that spheroids initiated using significantly different numbers of cells grow to similar limiting sizes, suggesting that avascular tumours have a limiting structure in agreement with untested predictions of classical mathematical models of tumour spheroids. We develop a novel mathematical and statistical framework to study the structure of tumour spheroids seeded from cells transduced with fluorescent cell cycle indicators, enabling us to discriminate between arrested and cycling cells and identify an arrested region. Our analysis shows that transient spheroid structure is independent of initial spheroid size, and the limiting structure can be independent of seeding density. Standard experimental protocols compare spheroid size as a function of time however, our analysis suggests that comparing spheroid structure as a function of overall size produces results that are relatively insensitive to variability in spheroid size. Our experimental observations are made using two melanoma cell lines, but our modelling framework applies across a wide range of spheroid culture conditions and cell lines.
Aflibercept monotherapy versus aflibercept with targeted retinal laser to peripheral retinal ischemia for diabetic macular oedema (LADAMO)
Publisher: Springer Science and Business Media LLC
Date: 17-04-2023
DOI: 10.1038/S41433-023-02525-9
Abstract: We tested the hypothesis that targeted retinal laser photocoagulation (TPRP) to peripheral retinal ischaemia reduces the overall burden of aflibercept injections when treating diabetic macular oedema (DMO) over a 24-month period. Prospective, double-masked, multicentre, randomised controlled trial in Australia comparing aflibercept monotherapy, following a treat-and-extend protocol, or combination therapy of aflibercept and TPRP for DMO. The aflibercept monotherapy group received placebo laser. The primary outcome measure was the mean number of intravitreal aflibercept injections for each group at 24 months. Secondary outcome included: mean change in central macular thickness (CMT) and vision at trial completion, the proportion of eyes whose DMO resolved and the mean injection treatment interval. Ocular and systemic adverse events were recorded. We enrolled 48 eyes of 47 patients 27 eyes were randomised to combination therapy (aflibercept and TPRP) and 21 to aflibercept monotherapy. Thirty-two eyes (67%) completed the 2-year study. The number of intravitreal treatments given were similar for combination therapy (10.5 (SD 5.8) and monotherapy (11.8 (SD5.6)) ( P = 0.44). The mean visual improvement (+4.0 (−1.8, 9.8) and +7.8 (2.6, 12.9) letters, P = 0.32), mean decrease in CMT (−154 (−222,−87) µm and −152 (−218,−86) µm, P = 0.96), proportion of eyes with CMT 300 µm (48% and 67% P = 0.50) and safety outcomes were similar in both the combination and monotherapy treatment groups (respectively). Laser to areas of ischaemic peripheral retina does not reduce the burden of intravitreal aflibercept injections when treating diabetic macular oedema.
Neoproterozoic mafic dyke swarms at the northern margin of the Tarim Block, NW China: Age, geochemistry, petrogenesis and tectonic implications
Publisher: Elsevier BV
Date: 06-2009
Harmonic hierarchy of mantle and lithospheric convective cycles: Time series analysis of hafnium isotopes of zircon
Publisher: Elsevier BV
Date: 11-2019
Syn-collisional magmatic record of Indian steep subduction by 50 Ma
Publisher: Geological Society of America
Date: 15-09-2020
DOI: 10.1130/B35498.1
Abstract: Subduction of Indian continental lithosphere during the Asia-India collision played an important role in the formation and evolution of the Himalaya-Tibetan orogen. However, the geometry of early Indian continental subduction remains debated. Given that the Indian continent is characterized by enriched isotope ratios (87Sr/86Sr & 0.730, εNd(t) & −10), relative to those in subducted oceanic materials (87Sr/86Sr & 0.704, εNd(t) ≈ +8), changes in the composition of magmatic rocks with time, in particular their radiogenic isotope ratios, is used to constrain the timing and nature of continental subduction. This study reports the field relations, zircon U-Pb ages and geochemical composition of a syn-collisional batholith that crosscuts the central Indus-Yarlung Zangbu suture in the Saga area of southern Tibet. Zircon U/Pb ages for the batholith mainly range from 50 to 46 Ma. S les from the Lopu Range batholith have enriched zircon Hf (εHf(t) = −0.4 to −8.6) and whole rock 87Sr/86Sri = 0.7094–0.7121 and εNd(t) = −7.3 to −9.8, suggesting that they were derived from a mixture of juvenile Gangdese and isotopically enriched Indian crustal materials. This result indicates that subduction of Indian crustal rocks occurred before 50 Ma in the central Himalaya. The geochemical composition and distribution of high volume ca. 51 Ma magmatism in the Gangdese belt, combined with thermal models of the subduction zone, suggests a steepening of the subducted Indian continental lithosphere occurred between the onset of India-Asia collision (59 Ma) and 46 Ma in the central-eastern Himalaya.
Targeting Replication Stress Using CHK1 Inhibitor Promotes Innate and NKT Cell Immune Responses and Tumour Regression
Publisher: MDPI AG
Date: 25-07-2021
Abstract: Drugs selectively targeting replication stress have demonstrated significant preclinical activity, but this has not yet translated into an effective clinical treatment. Here we report that targeting increased replication stress with a combination of Checkpoint kinase 1 inhibitor (CHK1i) with a subclinical dose of hydroxyurea targets also promotes pro-inflammatory cytokine/chemokine expression that is independent of cGAS-STING pathway activation and immunogenic cell death in human and murine melanoma cells. In vivo, this drug combination induces tumour regression which is dependent on an adaptive immune response. It increases cytotoxic CD8+ T cell activity, but the major adaptive immune response is a pronounced NKT cell tumour infiltration. Treatment also promotes an immunosuppressive tumour microenvironment through CD4+ Treg and FoxP3+ NKT cells. The number of these accumulated during treatment, the increase in FoxP3+ NKT cells numbers correlates with the decrease in activated NKT cells, suggesting they are a consequence of the conversion of effector to suppressive NKT cells. Whereas tumour infiltrating CD8+ T cell PD-1 and tumour PD-L1 expression was increased with treatment, peripheral CD4+ and CD8+ T cells retained strong anti-tumour activity. Despite increased CD8+ T cell PD-1, combination with anti-PD-1 did not improve response, indicating that immunosuppression from Tregs and FoxP3+ NKT cells are major contributors to the immunosuppressive tumour microenvironment. This demonstrates that therapies targeting replication stress can be well tolerated, not adversely affect immune responses, and trigger an effective anti-tumour immune response.
Meeting report from the 2011 international melanoma congress, Tampa, Florida
Publisher: Wiley
Date: 09-12-2011
Position of South China and Indochina along northern Gondwana margin during the Ediacaran–Silurian period
Publisher: Elsevier BV
Date: 09-2022
Pre-Rodinia supercontinent Nuna shaping up: A global synthesis with new paleomagnetic results from North China
Publisher: Elsevier BV
Date: 11-2012
Patterns of Vitamin D Levels and Exposures in Active and Inactive Noninfectious Uveitis Patients
Publisher: Elsevier BV
Date: 02-2020
DOI: 10.1016/J.OPHTHA.2019.06.030
Abstract: To compare serum vitamin D levels and patterns of ultraviolet light and dietary exposure among patients with active and inactive noninfectious uveitis and population controls. Prospective case-control study. All participants (n = 151) underwent serum 25-hydroxy vitamin D measurement and completed a questionnaire on vitamin D intake and ultraviolet light exposure. Serum 25-hydroxy vitamin D levels were compared between active and inactive uveitis groups and with local population estimates. Adult patients with active and inactive noninfectious uveitis were recruited from 2 Victorian tertiary hospitals and 1 private ophthalmic practice. Serum 25-hydroxy vitamin D levels were compared between patients with active and inactive uveitis and population-based estimates of serum 25-hydroxy vitamin D levels, stratified by geographic region and season. Vitamin D intakes and exposures based on questionnaire results, including vitamin D supplementation and sunlight exposures on weekdays and weekends, were compared between active and inactive uveitis groups. Serum vitamin D levels, intake of vitamin D, and exposure to sources of vitamin D. The median level of serum vitamin D in those with active uveitis (n = 74) was 46 nmol/l (interquartile range [IQR], 29-70 nmol/l), significantly lower than in the inactive control group (n = 77) at 64 nmol/l (IQR, 52-79 nmol/l P < 0.001). The active uveitis group also showed lower median serum vitamin D levels than the local population median of 62 nmol/l (IQR, 46-77 nmol/l). Vitamin D supplementation also was associated significantly with uveitis inactivity (P = 0.026, Kendall's τ test). In a subanalysis of vitamin D-deficient participants, sun exposure was associated significantly with uveitis inactivity (P = 0.014 for weekday and weekend analyses). Participants with active uveitis showed significantly lower serum 25-hydroxy vitamin D levels than inactive uveitis patients and local population-based estimates. Vitamin D supplementation was found to be associated with decreased uveitis activity, as was sun exposure in those with vitamin D deficiency. These results suggest that vitamin D supplementation should be studied as an option for the prevention of uveitis relapse in at-risk patients.
Cell Cycle Checkpoint and DNA Damage Response Defects as Anticancer Targets: From Molecular Mechanisms to Therapeutic Opportunities
Publisher: Springer Netherlands
Date: 14-10-2014
Pupil Dilation May Affect Retinal Vessel Caliber Measures
Publisher: Informa UK Limited
Date: 29-11-2017
DOI: 10.1080/09286586.2017.1409360
Abstract: To assess the effect of pupil dilation on measures of retinal vessel caliber. Observational study with self-comparisons Methods: Retinal photographs were taken for both eyes of 25 subjects before and after pupil dilation. Three photographic graders, masked to pupil dilation status, measured the same set of images using a computer-assisted, semi-automatic method. We compared means (standard deviations) of retinal arteriolar caliber equivalent (CRAE) and retinal venular caliber equivalent (CRVE) of the same eyes between pre- and post-dilation images. We assessed concordance correlation coefficients (CC), Bland Altman limits-of-agreements, and used linear mixed models to assess CRAE and CRVE measures associated with pupil dilation (influencing image quality), graders (observers) and right-left eye variation. We found high CCs for CRAE (0.82-0.94) and CRVE (0.87-0.94) between pre- and post-dilation images of the same eyes across the graders. Bland Altman plots showed that mean differences ranged from 0.55-3.42μm for CRAE and 1.56-2.29μm for CRVE. After adjusting for right-left eye random variation, a significant fixed effect of dilation was evident in mean CRAE in two of the three graders. There was no significant fixed effect of dilation in mean CRVE across all graders. In models including data of both eyes' measures from pre- and post-dilation images by three graders, the fixed effect for dilation status contributed significantly to CRAE and CRVE variances whereas random effects for graders and dilation status contributed minimally. Contrary to our hypothesis, we found a systematic effect of pupil dilation on retinal vessel caliber measures.
Guidance on Noncorticosteroid Systemic Immunomodulatory Therapy in Noninfectious Uveitis
Publisher: Elsevier BV
Date: 05-2018
DOI: 10.1016/J.OPHTHA.2017.11.017
Abstract: An international, expert-led consensus initiative to develop systematic, evidence-based recommendations for the treatment of noninfectious uveitis in the era of biologics. The availability of biologic agents for the treatment of human eye disease has altered practice patterns for the management of noninfectious uveitis. Current guidelines are insufficient to assure optimal use of noncorticosteroid systemic immunomodulatory agents. An international expert steering committee comprising 9 uveitis specialists (including both ophthalmologists and rheumatologists) identified clinical questions and, together with 6 bibliographic fellows trained in uveitis, conducted a Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol systematic review of the literature (English language studies from January 1996 through June 2016 Medline [OVID], the Central Cochrane library, EMBASE, CINAHL, SCOPUS, BIOSIS, and Web of Science). Publications included randomized controlled trials, prospective and retrospective studies with sufficient follow-up, case series with 15 cases or more, peer-reviewed articles, and hand-searched conference abstracts from key conferences. The proposed statements were circulated among 130 international uveitis experts for review. A total of 44 globally representative group members met in late 2016 to refine these guidelines using a modified Delphi technique and assigned Oxford levels of evidence. In total, 10 questions were addressed resulting in 21 evidence-based guidance statements covering the following topics: when to start noncorticosteroid immunomodulatory therapy, including both biologic and nonbiologic agents what data to collect before treatment when to modify or withdraw treatment how to select agents based on in idual efficacy and safety profiles and evidence in specific uveitic conditions. Shared decision-making, communication among providers and safety monitoring also were addressed as part of the recommendations. Pharmacoeconomic considerations were not addressed. Consensus guidelines were developed based on published literature, expert opinion, and practical experience to bridge the gap between clinical needs and medical evidence to support the treatment of patients with noninfectious uveitis with noncorticosteroid immunomodulatory agents.
Quantified spatial relationships between gold mineralisation and key ore genesis controlling factors, and predictive mineralisation mapping, St Ives Goldfield, Western Australia
Publisher: Elsevier BV
Date: 10-2013
Intraplate crustal remelting as the genesis of Jurassic high-K granites in the coastal region of the Guangdong Province, SE China
Publisher: Elsevier BV
Date: 09-2013
Tissue expression of the vesicle protein pantophysin
Publisher: Springer Science and Business Media LLC
Date: 20-05-1999
Abstract: The cell-type restricted expression of cytoplasmic microvesicle membrane protein isoforms may be a consequence of the functional adaptation of these vesicles to the execution of specialized processes in cells of different specialization. To characterize the expression of the vesicle protein pantophysin, an isoform of the synaptic vesicle proteins synaptophysin and synaptoporin, we have prepared and characterized antibodies useful for the immunological detection of pantophysin in vitro and in situ. Using these reagents, we show by immunoblot analyses that pantophysin expression is not homogeneous but differs significantly between various bovine tissues. Furthermore, these differences are not exactly paralleled by the expression of other vesicle proteins of the SCAMP (secretory carrier-associated membrane protein) and VAMP (vesicle-associated membrane protein) types that have previously been localized to pantophysin vesicles in cultured cells. By immunofluorescence microscopy, pantophysin expression is seen predominantly in non-neuroendocrine cells with pronounced membrane traffic. Pantophysin staining codistributes with SCAMP and VAMP immunoreactivities in most instances but differs in some. Remarkably, pantophysin staining in liver is restricted to cells surrounding sinusoids and is not detectable in hepatocytes, similar to that of the SCAMP and VAMP isoforms as detected by our reagents in tissue sections.
Rapid Optical Clearing for High-Throughput Analysis of Tumour Spheroids
Publisher: MDPI AG
Date: 25-11-2021
DOI: 10.20944/PREPRINTS202111.0488.V1
Abstract: Tumour spheroids are fast becoming commonplace in basic cancer research and drug development. Obtaining high-quality data relating to the inner structure of spheroids is important for analysis, yet existing techniques often use equipment that is not commonly available, are expensive, laborious, cause significant size distortion, or are limited to relatively small spheroids. We present a high-throughput method of mounting, clearing, and imaging tumour spheroids that causes minimal size distortion. Spheroids are mounted in an agarose gel to prevent movement, cleared using a solution prepared from commonly available materials, and imaged using confocal microscopy. We find that our method yields high quality two- and three-dimensional images that provide information about the inner structure of spheroids.
Rapid Optical Clearing for High-Throughput Analysis of Tumour Spheroids
Publisher: MDPI AG
Date: 31-03-2022
DOI: 10.20944/PREPRINTS202111.0488.V2
Abstract: Tumour spheroids are fast becoming commonplace in basic cancer research and drug development. Obtaining high-quality data relating to the inner structure of spheroids is important for analysis, yet existing techniques often use equipment that is not commonly available, are expensive, laborious, cause significant size distortion, or are limited to relatively small spheroids. We present a high-throughput method of mounting, clearing, and imaging tumour spheroids that causes minimal size distortion. Spheroids are mounted in an agarose gel to prevent movement, cleared using a solution prepared from commonly available materials, and imaged using confocal microscopy. We find that our method yields high quality two- and three-dimensional images that provide information about the inner structure of spheroids.
New paleomagnetic results from the Yangzhuang Formation of the Jixian System, North China, and tectonic implications
Publisher: Science China Press., Co. Ltd.
Date: 2005
DOI: 10.1360/982005-809
Intravitreal Methotrexate as Adjunctive, Palliative Therapy in Intraocular T-cell Lymphoma
Publisher: Informa UK Limited
Date: 20-05-2010
DOI: 10.3109/09273941003637528
Abstract: To report on the rapid and sustained effect following injection of intravitreal methotrexate (IVTMTX) in intraocular T-cell lymphoma. Report of 2 cases. A young male with natural killer/T-cell lymphoma presented with infiltrative nodular iridocyclitis and received a single IVTMTX. An elderly female with peripheral T-cell lymphoma presented with a hypopyon, infiltrative iridocyclitis, and choroidal effusions and received 3 IVTMTX over 4 months. Both patients responded well after the first injection, with resolution of signs within 1 week and improvement in vision. IVTMTX may be effective as a palliative, vision-restoring measure in patients with systemic T-cell lymphoma.
New Paleointensity Data Suggest Possible Phanerozoic‐Type Paleomagnetic Variations in the Precambrian
Publisher: American Geophysical Union (AGU)
Date: 10-2021
DOI: 10.1029/2021GC009990
Abstract: The state of the geomagnetic field throughout the Precambrian era is largely unknown. Approximately 8% of global paleointensity records account for ∼4 billion years of Earth history. Despite this severe sparsity, the data are used to constrain models that predict the timing of significant deep earth events such as inner core nucleation. This carries with it the assumption that the Precambrian paleomagnetic field was less variable when compared to the Phanerozoic, or at least that the sparse data can be averaged to accurately represent a particular time period. This study reports new paleointensities from the West Australian Craton at 755 Ma (the Mundine Wells dyke swarm) and 1,070 Ma (the Bangemall Sills) both of which occurred within ∼30 Ma from times at which extremely weak and anomalously strong fields, respectively, have been reported. Virtual dipole moments of 6.3 ± 0.1 Am 2 × 10 22 and 1.8 ± 1.2 Am 2 × 10 22 have been obtained from the two suites of mafic rock units which are substantially different to the previous measurements for the two respective ages. The findings suggest that field variability over tens of Myrs in the Precambrian was greater than has previously been assumed. This is supported by comparisons of paleosecular variation and distributions of virtual dipole moments. If variability in the Precambrian field is similar to that observed in the Phanerozoic, spatial or temporal anomalies may introduce significant bias to statistical analyses and model constraints, implying that caution should be employed in the interpretation of the Precambrian dipole moment records.
SHRIMP zircon U-Pb geochronological and whole-rock geochemical evidence for an early Neoproterozoic Sibaoan magmatic arc along the southeastern margin of the Yangtze Block
Publisher: Elsevier BV
Date: 08-2007
U–Pb zircon, geochemical and Sr–Nd–Hf isotopic constraints on age and origin of Jurassic I- and A-type granites from central Guangdong, SE China: A major igneous event in response to foundering of a s
Publisher: Elsevier BV
Date: 06-2007
Ophthalmology subspecialty fellowships: town or gown?
Publisher: Wiley
Date: 2018
DOI: 10.1111/CEO.13123
Melanoma's connections to the tumour microenvironment
Publisher: Elsevier BV
Date: 08-2013
Collision between the North and South China blocks: A crustal-detachment model for suturing in the region east of the Tanlu fault: Comment and Reply
Publisher: Geological Society of America
Date: 1995
Head and neck cancer patient-derived tumouroid cultures: opportunities and challenges
Publisher: Springer Science and Business Media LLC
Date: 10-02-2023
DOI: 10.1038/S41416-023-02167-4
Abstract: Head and neck cancers (HNC) are the seventh most prevalent cancer type globally. Despite their common categorisation, HNCs are a heterogeneous group of malignancies arising in various anatomical sites within the head and neck region. These cancers exhibit different clinical and biological manifestations, and this heterogeneity also contributes to the high rates of treatment failure and mortality. To evaluate patients who will respond to a particular treatment, there is a need to develop in vitro model systems that replicate in vivo tumour status. Among the methods developed, patient-derived cancer organoids, also known as tumouroids, recapitulate in vivo tumour characteristics including tumour architecture. Tumouroids have been used for general disease modelling and genetic instability studies in pan-cancer research. However, a limited number of studies have thus far been conducted using tumouroid-based drug screening. Studies have concluded that tumouroids can play an essential role in bringing precision medicine for highly heterogenous cancer types such as HNC.
Mesoproterozoic paleogeography: Supercontinent and beyond
Publisher: Elsevier BV
Date: 05-2014
Was there a Cambrian ocean in South China? - Insight from detrital provenance analyses
Publisher: Cambridge University Press (CUP)
Date: 18-07-2015
DOI: 10.1017/S0016756814000338
Abstract: We use detrital provenance data from Cambrian sandstones to examine whether the Yangtze and Cathaysia blocks in South China were separated by an ocean during the Cambrian period. Zircons from the Cambrian sandstones exhibit a dominant ~ 800 Ma age peak in the central Yangtze Block, being sourced from the western Yangtze Block, whereas a ~ 980 Ma peak dominates in the northwestern Cathaysia Block, being sourced from an exotic continent once connected to Cathaysia. A mixed provenance with both age peaks is found in Cambrian sandstones from the southeastern Yangtze Block, indicating that detritus can travel from the Cathaysia Block to the Yangtze Block, and therefore arguing against the existence of a broad Cambrian ocean.
Cell–Cell and Cell–Matrix Contacts in Melanoma and the Tumor Microenvironment
Publisher: Springer Vienna
Date: 2011
The Interval between Treatments of Bevacizumab and Dexamethasone Implants for Diabetic Macular Edema Increased over Time in the BEVORDEX Trial.
Publisher: Elsevier BV
Date: 03-2017
DOI: 10.1016/J.ORET.2017.06.010
Abstract: To report increasing retreatment interval of intravitreal bevacizumab and dexamethasone implants for diabetic macular edema (DME) in the BEVORDEX trial. Multicenter randomized clinical trial. Sixty-eight eyes from 47 patients who completed 2 years of follow-up. The BEVORDEX study (www.clinicaltrials.gov identifier, NCT01298076), set in Australia, was the first head-to-head trial of bevacizumab (Avastin Genentech, South San Francisco, CA), with retreatment considered after 4 weeks, versus a slow-release dexamethasone implant (Ozurdex Allergan Inc., Irvine, CA), with retreatment possible after 16 weeks, for center-involving DME. Study eyes were assessed every 4 weeks for retreatment according to prespecified visual acuity and central macular thickness criteria. In this post hoc analysis, changes in treatment interval over time were examined using mixed-effects regression models. We assessed whether the mean treatment interval changed over time and if this depended on baseline characteristics or the treatment received. Of the 68 eyes from 47 patients, 67 study eyes received at least 1 retreatment (1 eye in the dexamethasone implant group did not require retreatment over 24 months). Thirty-two eyes received bevacizumab and 35 eyes received dexamethasone implants. Study eyes received a mean of 14.6 injections (standard deviation [SD], 7.8 injections) and 5.6 injections (SD, 1.4 injections) in the bevacizumab and dexamethasone groups, respectively, over 2 years. The mean retreatment interval over the 2-year follow-up period was 70.8 days (SD, 43.8 days) for the bevacizumab group and 145 days (SD, 45.4 days) for the dexamethasone implant group. The mean treatment interval increased over time for both drugs (P = 0.016), independent of which treatment was received (P = 0.808). Longer treatment interval over time was associated with younger age (P = 0.037) and better baseline visual acuity (P = 0.026), but not with gender (P = 0.907) or baseline central macular thickness (P = 0.900). The increase in treatment interval for both intravitreal bevacizumab and dexamethasone implants over time has implications when informing patients about potential treatment burden for DME, planning intravitreal injections services, and designing future clinical trials. For drugs with a disease-modifying effect, fixed-interval dosing may not be required beyond an initial loading phase.
Synorogenic hydrothermal origin for giant Hamersley iron oxide ore bodies
Publisher: Geological Society of America
Date: 1999
Multiple signaling pathways must be targeted to overcome drug resistance in cell lines derived from melanoma metastases
Publisher: American Association for Cancer Research (AACR)
Date: 05-2006
DOI: 10.1158/1535-7163.MCT-06-0084
Abstract: Although & % of melanomas harbor activating mutations in BRAF and exhibit constitutive activity in the mitogen-activated protein kinase/extracellular signal–regulated kinase kinase (MEK)/extracellular signal–regulated kinase signaling pathway, it is unclear how effective MEK inhibition will be as a sole therapeutic strategy for melanoma. We investigated the anticancer activity of MEK inhibition in a panel of cell lines derived from radial growth phase (WM35) and vertical growth phase (WM793) of primary melanomas and metastatic melanomas (1205Lu, 451Lu, WM164, and C8161) in a three-dimensional spheroid model and found that the metastatic lines were completely resistant to MEK inhibition (U0126 and PD98059) but the earlier stage cell lines were not. Similarly, these same metastatic melanoma lines were also resistant to inhibitors of the phosphatidylinositol 3-kinase/Akt pathway (LY294002 and wortmannin). Under adherent culture conditions, the MEK inhibitors blocked growth through the induction of cell cycle arrest and up-regulation of p27, but this was readily reversible following inhibitor washout. However, when the phosphatidylinositol 3-kinase and MEK inhibitors were combined, the growth and invasion of the metastatic melanoma three-dimensional spheroids were blocked. Taken together, these results suggest that the most aggressive melanomas are resistant to strategies targeting one signaling pathway and that multiple signaling pathways may need to be targeted for maximal therapeutic efficacy. It is further suggested that BRAF mutational status is not predictive of response to MEK inhibition under three-dimensional culture conditions. [Mol Cancer Ther 2006 (5):1136–44]
Rituximab Therapy for Refractory Scleritis
Publisher: Elsevier BV
Date: 10-2014
DOI: 10.1016/J.OPHTHA.2014.04.044
Abstract: To determine whether rituximab, a monoclonal antibody against the B-lymphocyte antigen CD20, is effective in the treatment of refractory noninfectious scleritis. Prospective, dose-ranging, randomized, double-masked phase I/II clinical trial. Twelve patients with noninfectious scleritis refractory to systemic corticosteroid and ≥1 other systemic immunosuppressive agent were enrolled from January 2007 to March 2010. Subjects were randomly assigned to 500 (n = 5) or 1000 mg (n = 7) dosing arms of rituximab intravenous infusions (500 or 1000 mg), given at study days 1 and 15. Initial responders with breakthrough inflammation after study week 24 were offered treatment with an additional cycle of 2 open-label rituximab 1000 mg infusions. Primary outcomes were reduction of inflammation, as measured with a validated scleritis disease grading scale (SGS) and reduction in corticosteroid dose by ≥50%. Patients were characterized as responders to study therapy if ≥1 of these endpoints showed improvement and neither showed evidence of worsening. Secondary outcomes were improvement in visual acuity, reduction in pain, and improvement in patient and physician-reported global health assessment. Of 12 enrolled patients, 9 met the SGS endpoint at or before week 24, and 4 additionally were able to reduce corticosteroid dose by ≥50%. With regard to secondary outcome measures, 11 and 9 patients showed improvement in patient and physician global health scores, respectively, and 7 patients had reduction in pain. Of 9 initial responders, 7 experienced breakthrough inflammation after 24 weeks and were treated with a second cycle of rituximab infusions. Four patients had significant objective or subjective worsening within 8 weeks of receiving rituximab this event was averted in subsequent patients by treatment with peri-infusional oral corticosteroid. No other significant adverse events were noted. No differences in efficacy, toxicity, or likelihood of retreatment were noted between the dosing arms. Rituximab was effective treatment for 9 of 12 enrolled patients with refractory, noninfectious scleritis at 24 weeks, although 7 required reinfusion with rituximab to maintain inflammatory control. The treatment was well-tolerated, and peri-infusional inflammatory exacerbations were managed successfully with oral corticosteroids. Further long-term studies are warranted to determine the safety and efficacy of rituximab in treating noninfectious scleritis and other ocular inflammatory diseases.
Nonglacial origin for low-delta O-18 Neoproterozoic magmas in the South China Block: Evidence from new in-situ oxygen isotope analyses using SIMS
Publisher: Geological Society of America
Date: 07-2011
DOI: 10.1130/G31991.1
Detection of Primary Melanoma in Individuals at Extreme High Risk A Prospective 5-Year Follow-up Study
Publisher: American Medical Association (AMA)
Date: 08-2014
DOI: 10.1001/JAMADERMATOL.2014.514
Abstract: The clinical phenotype and certain predisposing genetic mutations that confer increased melanoma risk are established however, no consensus exists regarding optimal screening for such in iduals. Early identification remains the most important intervention in reducing melanoma mortality. To evaluate the impact of full-body examinations every 6 months supported by dermoscopy and total-body photography (TBP) on all patients and sequential digital dermoscopy imaging (SDDI), when indicated, on detecting primary melanoma in an extreme-risk population. Prospective observational study from February 2006 to February 2011, with patients recruited from Sydney Melanoma Diagnostic Centre and Melanoma Institute Australia who had a history of invasive melanoma and dysplastic nevus syndrome, history of invasive melanoma and at least 3 first-degree or second-degree relatives with prior melanoma, history of at least 2 primary invasive melanomas, or a CDKN2A or CDK4 gene mutation. Six-month full-body examination compared with TBP. For equivocal lesions, SDDI short term (approximately 3 months) or long term (≥6 months), following established criteria, was performed. Atypical lesions were excised. New primary melanoma numbers, characteristics, and cumulative incidence in each patient subgroup effect of diagnostic aids on new melanoma identification. In 311 patients with a median (interquartile range [IQR]) follow-up of 3.5 (2.4-4.2) years, 75 primary melanomas were detected, 14 at baseline visit. Median (IQR) Breslow thickness of postbaseline incident melanomas was in situ (in situ to 0.60 mm). Thirty-eight percent were detected using TBP and 39% with SDDI. Five melanomas were greater than 1 mm Breslow thickness, 3 of which were histologically desmoplastic the other 2 had nodular components. The benign to malignant excision ratio was 1.6:1 for all lesions excised and 4.4:1 for melanocytic lesions. Cumulative risk of developing a novel primary melanoma was 12.7% by year 2, with new primary melanoma incidence during the final 3 years of follow-up half of that observed during the first 2 years (incidence density ratio, 0.43 [95% CI, 0.25-0.74] P = .002). Monitoring patients at extreme risk with TBP and SDDI assisted with early diagnosis of primary melanoma. Hypervigilance for difficult-to-detect thick melanoma subtypes is crucial.
Factors Predicting Visual Acuity Outcome in Intermediate, Posterior, and Panuveitis: The Multicenter Uveitis Steroid Treatment (MUST) Trial
Publisher: Elsevier BV
Date: 12-2015
South China in Rodinia — An Update
Publisher: Elsevier BV
Date: 10-2001
Designing and interpreting 4D tumour spheroid experiments
Publisher: Cold Spring Harbor Laboratory
Date: 19-08-2021
DOI: 10.1101/2021.08.18.456910
Abstract: Tumour spheroid experiments are routinely used to study cancer progression and treatment. Various and inconsistent experimental designs are used, leading to challenges in interpretation and reproducibility. Using multiple experimental designs, live-dead cell staining, and real-time cell cycle imaging, we measure necrotic and proliferation-inhibited regions in over 1000 4D tumour spheroids (3D space plus cell cycle status). By intentionally varying the initial spheroid size and temporal s ling frequencies across multiple cell lines, we collect an abundance of measurements of internal spheroid structure. These data are difficult to compare and interpret. However, using an objective mathematical modelling framework and statistical identifiability analysis we quantitatively compare experimental designs and identify design choices that produce reliable biological insight. Measurements of internal spheroid structure provide the most insight, whereas varying initial spheroid size and temporal measurement frequency is less important. Our general framework applies to spheroids grown in different conditions and with different cell types.
Transition from oceanic to continental lithosphere subduction in southern Tibet: Evidence from the Late Cretaceous–Early Oligocene (~91–30Ma) intrusive rocks in the Chanang–Zedong area, southern Gangd
Publisher: Elsevier BV
Date: 05-2014
Dexamethasone implant for the treatment of persistent diabetic macular oedema despite long-term treatment with bevacizumab.
Publisher: Wiley
Date: 11-11-2018
DOI: 10.1111/CEO.13371
Retrospective analysis of the natural history and management of serpiginous choroiditis in Australia and New Zealand.
Publisher: Wiley
Date: 23-01-2014
DOI: 10.1111/CEO.12283
Abstract: To examine the prevalence of serpiginous choroidopathy in a predominantly Caucasian community, to examine associations between serpiginous choroiditis and other systemic diseases, and to report on the effect of immunosuppression on the long-term course of serpiginous choroiditis. Retrospective cohort study with patients from tertiary care centres and private practices. 18 patients, mean age 48 years at baseline. One patient was seen only once. Median follow-up was 69 months (5.8 years, range 0.4-29.7 years). Patients were identified using the Australian and New Zealand Ophthalmic Surveillance Unit. A chart analysis was performed for all patients. Three treatment groups were identified: no treatment, prednisolone monotherapy, or combination of prednisolone and immunosuppression. Negative binomial regression was used to calculate incidence rate ratios for patient relapse. Patient demographics, clinical features, associated systemic diseases, treatments administered and dates of relapse. The disease prevalence in Australia and New Zealand is 1 case per 1.5 million people. Five cases (28%) had a positive QuantiFERON. A total of 32 relapses were observed: 14 while receiving no treatment, 11 on prednisolone and 7 on combination therapy. Compared with the no treatment group, the incidence rate ratio for prednisolone monotherapy and combination therapy was 1.29 and 2.92, respectively (95% confidence interval 0.40-4.14 and 0.96-8.88). Although the confidence intervals indicate that the difference in incidence rate ratios are not significant, these results suggest that there is a group of patients who have a benign course without long-term immunosuppression or corticosteroid treatment.
Age and chemical composition of Archean metapelites in the Zhongxiang Complex and implications for early crustal evolution of the Yangtze Craton
Publisher: Elsevier BV
Date: 11-2018
Multiple P–T–d–t paths reveal the evolution of the final Nuna assembly in northeast Australia
Publisher: Wiley
Date: 15-06-2020
DOI: 10.1111/JMG.12532
Palaeomagnetism of the Brewer Conglomerate in central Australia, and fast movement of Gondwanaland during the Late Devonian
Publisher: Oxford University Press (OUP)
Date: 11-1993
The course of uveitis in pregnancy and postpartum
Publisher: BMJ
Date: 25-07-2013
DOI: 10.1136/BJOPHTHALMOL-2013-303358
Abstract: To examine the course of non-infectious uveitis during pregnancy. This is a retrospective case series. The medical records of 47 subjects with a previous history of non-infectious uveitis pre-dating their pregnancy were reviewed. Uveitis activity during the periods 1 year before pregnancy, during pregnancy and 1 year postpartum, were recorded. Information on patient demographics, type of uveitis, medication use, sex of child and breastfeeding status were also collected. The main outcome measures were the events of flare-ups during the prepregnancy, pregnancy and postpartum periods. The rate of flare-up was 1.188 per person year prior to pregnancy, 0.540 per person year during pregnancy and 0.972 per person year in postpartum (p<0.001 for comparison between prepregnancy and pregnancy p=0.009 for comparison between pregnancy and postpartum). Rates of flare-up only began to decrease in the second trimester. After delivery, rates of flare-up rebounded and within 6 months postpartum, flare-up rates were not significantly different from prepregnancy levels (p=0.306). Even so, 40% of subjects were found to have remained inactive within 1 year postpartum. Uveitis activity decreased by mid-pregnancy, but returned to prepregnancy levels within 6 months postpartum. These findings may be used to adjust uveitis management during pregnancy and the postpartum period.
Dike Magmatism in the Evolution of the Transform Active Continental Margin of the Siberian Craton in the Ediacaran
Publisher: Pleiades Publishing Ltd
Date: 11-2019
Geochemistry of the 755Ma Mundine Well dyke swarm, northwestern Australia: Part of a Neoproterozoic mantle superplume beneath Rodinia?
Publisher: Elsevier BV
Date: 04-2006
Hit or miss: Glacial incisions of snowball Earth
Publisher: Wiley
Date: 17-05-2019
DOI: 10.1111/TER.12400
TTG generation by fluid-fluxed crustal melting: Direct evidence from the Proterozoic Georgetown Inlier, NE Australia
Publisher: Elsevier BV
Date: 11-2020
A stochastic mathematical model of 4D tumour spheroids with real-time fluorescent cell cycle labelling
Publisher: The Royal Society
Date: 04-2022
Abstract: In vitro tumour spheroids have been used to study avascular tumour growth and drug design for over 50 years. Tumour spheroids exhibit heterogeneity within the growing population that is thought to be related to spatial and temporal differences in nutrient availability. The recent development of real-time fluorescent cell cycle imaging allows us to identify the position and cell cycle status of in idual cells within the growing spheroid, giving rise to the notion of a four-dimensional (4D) tumour spheroid. We develop the first stochastic in idual-based model (IBM) of a 4D tumour spheroid and show that IBM simulation data compares well with experimental data using a primary human melanoma cell line. The IBM provides quantitative information about nutrient availability within the spheroid, which is important because it is difficult to measure these data experimentally.
Number of ocular syphilis cases creeps to record high
Publisher: Wiley
Date: 23-08-2017
DOI: 10.1111/CEO.13021
A Gravity Study of the Longmenshan Fault Zone: New Insights Into the Nature and Evolution of the Fault Zone and Extrusion‐Style Growth of the Tibetan Plateau Since 40 Ma
Publisher: American Geophysical Union (AGU)
Date: 2019
DOI: 10.1029/2018TC005272
Testing the Rodinia hypothesis: Records in its building blocks
Publisher: Elsevier BV
Date: 2008
The Mitogen-Activated Protein/Extracellular Signal-Regulated Kinase Kinase Inhibitor AZD6244 (ARRY-142886) Induces Growth Arrest in Melanoma Cells and Tumor Regression When Combined with Docetaxel
Publisher: American Association for Cancer Research (AACR)
Date: 2008
DOI: 10.1158/1078-0432.CCR-07-1440
Abstract: Purpose: Disseminated melanoma is highly therapy resistant. The finding that 66% of melanomas harbor the activating BRAFV600E mutation has raised expectations for targeting the Ras/RAF/mitogen-activated protein (MAP)/extracellular signal-regulated kinase (ERK) kinase (MEK)/ERK pathway in melanoma. This study addresses the anti-melanoma activity of the MEK inhibitor AZD6244 (ARRY-142886). Experimental Design: We recently have shown that growing melanoma cells as three-dimensional collagen-implanted spheroids enhances resistance to the MEK inhibitor U0126. Here, we investigated the anti-melanoma activity of AZD6244 in two-dimensional cell culture, the three-dimensional spheroid model, and an in vivo model. Results: In two-dimensional cell culture, AZD6244 was cytostatic and reduced the growth of melanoma cells in a concentration-dependent fashion through the induction of G1-phase cell cycle arrest. In our three-dimensional spheroid model, the effects of AZD6244 were largely cytostatic and reversible, with drug washout leading to spheroid regrowth. Finally, 1205Lu cells were grown as tumor xenografts in severe combined immunodeficient mice. After tumor establishment, mice were dosed twice daily with 0, 10, or 30 mg/kg AZD6244 p.o. AZD6244 treatment decreased phospho-ERK in the tumors and significantly suppressed tumor growth. The original tumors remained viable, suggesting that AZD6244 monotherapy was largely cytostatic, and not proapoptotic in this model. Further studies showed that co-administration of AZD6244 (30 mg/kg) with docetaxel (15 mg/kg) led to tumor regression, indicating the potential for MEK inhibitor/chemotherapy drug combinations. Conclusions: Inhibition of MEK is cytostatic as a monotherapy in melanoma, but cytotoxic when combined with docetaxel.
Induction of endoplasmic reticulum stress as a strategy for melanoma therapy: is there a future?
Publisher: Future Medicine Ltd
Date: 11-2014
DOI: 10.2217/MMT.14.16
Abstract: SUMMARY Melanoma cells employ several survival strategies, including induction of the unfolded protein response, which mediates resistance to endoplasmic reticulum (ER) stress-induced apoptosis. Activation of oncogenes specifically suppresses ER stress-induced apoptosis, while upregulation of ER chaperone proteins and antiapoptotic BCL-2 family members increases the protein folding capacity of the cell and the threshold for the induction of ER stress-induced apoptosis, respectively. Modulation of unfolded protein response signaling, inhibition of the protein folding machinery and/or active induction of ER stress may thus represent potential strategies for the therapeutic management of melanoma. To this aim, the present article focuses on the current understanding of how melanoma cells avoid or overcome ER stress-induced apoptosis, as well as therapeutic strategies through which to harness ER stress for therapeutic benefit.
Thermochronological record of Middle–Late Jurassic magmatic reheating to Eocene rift-related rapid cooling in the SE South China Block
Publisher: Elsevier BV
Date: 06-2017
EARLY CRETACEOUS APTIAN CHARCOAL FROM XINCHANG PETRIFIED WOOD NATIONAL GEOPARK OF ZHEJIANG PROVINCE, EASTERN SOUTH CHINA
Publisher: Society for Sedimentary Geology
Date: 13-10-2014
A tectonic model for the Transcontinental Arch: Progressive migration of a Laurentian drainage divide during the Neoproterozoic–Cambrian Sauk Transgression
Publisher: Wiley
Date: 30-03-2021
DOI: 10.1111/TER.12528
Abstract: A widespread provenance shift recorded by passive margin strata of western Laurentia, from predominant Stenian (1.2–1.0 Ga) detrital zircon age components to their absence, occurred during the Neoproterozoic–Cambrian Sauk transgression and is commonly used as a ca. 540 Ma chronostratigraphic marker throughout the west/south‐western United States. However, in Neoproterozoic–Cambrian strata of this region, we identify a probable shift from distal to more proximal Stenian‐age zircon sources before a diachronous loss of Stenian detrital zircon age components. We suggest these provenance patterns reflect progressive subsidence of the passive margins surrounding Laurentia and concomitant relative uplift of the Transcontinental Arch, a broad and segmented northeast–southwest trending topographic high across the Laurentian midcontinent possibly due to lithospheric flexure. The Transcontinental Arch segments align with transverse rift structures of the Neoproterozoic–Cambrian Iapetan margin and the Mesoproterozoic Midcontinent Rift, perhaps reflecting rejuvenation of midcontinent lithospheric weaknesses during the Sauk transgression and final Rodinia breakup.
Neoproterozoic glaciations in a revised global palaeogeography from the breakup of Rodinia to the assembly of Gondwanaland
Publisher: Elsevier BV
Date: 08-2013
Plasma levels of amyloid beta and other proinflammatory mediators in patients with age-related macular degeneration
Publisher: Springer Science and Business Media LLC
Date: 07-03-2015
DOI: 10.1007/S00417-015-2970-X
Abstract: To investigate the plasma levels of amyloid beta (Aβ) and select inflammatory mediators in patients with various stages of AMD compared to that of age-matched controls, and discern a relationship to disease severity. Plasma s les were obtained from AMD subjects at various stages of disease-early (drusen only), geographic atrophy (GA), neovascular AMD (CNV)-and from controls of similar age without AMD. S les were analyzed using a commercially available ELISA kit (sixteen cytokines) or LC/MS/MS (Aβ isotypes). Descriptive statistics were compiled on all analytes. Analysis of covariance (ANCOVA) was conducted to compare each analyte across AMD groups while adjusting for sex and age of the patients, and in comparison to the control group. Receiver operating characteristics plots were generated for the strongest predictor variables. Levels of alternative spliced CC3 proteins were significantly different between controls and CNV groups (p < 0.05), with median levels almost twice higher in CNV than in controls. There was an increasing trend for plasma levels of Αβ isotypes across AMD progressive stages (p values ranged from 0.052 to 0.0012) (ANCOVA). When adjusted for multiple comparisons analysis, plasma Aβ 1-42 levels, and its ratio with Aβ 1-40 were the most significantly associated with late AMD stages. Consistently with the ANCOVA results for Αβ isotypes, the ROC curve showed a moderate prediction (AUC = - ~ 0.78) of AMD vs control using the Aβ 1-42 isotype. Plasma Aβ 1-42 may have utility as a systemic biomarker for AMD.
Adhesion, migration and communication in melanocytes and melanoma
Publisher: Wiley
Date: 12-05-2005
DOI: 10.1111/J.1600-0749.2005.00235.X
Abstract: Under normal conditions, homeostasis determines whether a cell remains quiescent, proliferates, differentiates, or undergoes apoptosis. In this state of homeostasis, keratinocytes control melanocyte growth and behaviour through a complex system of paracrine growth factors and cell-cell adhesion molecules. Alteration of this delicate homeostatic balance and can lead to altered expression of cell-cell adhesion and cell communication molecules and to the development of melanoma. Melanoma cells escape from this control by keratinocytes through three major mechanisms: (1) down-regulation of receptors important for communication with keratinocytes such as E-cadherin, P-cadherin, desmoglein and connexins, which is achieved through growth factors produced by fibroblasts or keratinocytes (2) up-regulation of receptors and signalling molecules not found on melanocytes but important for melanoma-melanoma and melanoma-fibroblast interactions such as N-cadherin, Mel-CAM, and zonula occludens protein-1 (ZO-1) (3) loss of anchorage to the basement membrane because of an altered expression of the extracellular-matrix binding integrin family. In the current review, we describe the alterations in cell-cell adhesion and communication associated with melanoma development and progression, and discuss how a greater understanding of these processes may aid the future therapy of this disease.
Assembly and Breakup of Rodinia (Some results of IGCP project 440)
Publisher: Pleiades Publishing Ltd
Date: 06-2009
Archean geodynamics: Ephemeral supercontinents or long-lived supercratons
Publisher: Geological Society of America
Date: 22-03-2021
DOI: 10.1130/G48575.1
Abstract: Many Archean cratons exhibit Paleoproterozoic rifted margins, implying they were pieces of some ancestral landmass(es). The idea that such an ancient continental assembly represents an Archean supercontinent has been proposed but remains to be justified. Starkly contrasting geological records between different clans of cratons have inspired an alternative hypothesis where cratons were clustered in multiple, separate “supercratons.” A new ca. 2.62 Ga paleomagnetic pole from the Yilgarn craton of Australia is compatible with either two successive but ephemeral supercontinents or two long-lived supercratons across the Archean-Proterozoic transition. Neither interpretation supports the existence of a single, long-lived supercontinent, suggesting that Archean geodynamics were fundamentally different from subsequent times (Proterozoic to present), which were influenced largely by supercontinent cycles.
Magmatic switch-on and switch-off along the South China continental margin since the Permian: Transition from an Andean-type to a Western Pacific-type plate boundary
Publisher: Elsevier BV
Date: 04-2012
An early Paleoproterozoic high-K intrusive complex in southwestern Tarim Block, NW China: Age, geochemistry, and tectonic implications
Publisher: Elsevier BV
Date: 08-2007
Uveitis and Gender: The Course of Uveitis in Pregnancy
Publisher: Hindawi Limited
Date: 2014
DOI: 10.1155/2014/401915
Abstract: The hormonal and immunological changes in pregnancy have a key role in maintaining maternal tolerance of the semiallogeneic foetus. These pregnancy-associated changes may also influence the course of maternal autoimmune diseases. Noninfectious uveitis tends to improve during pregnancy. Specifically, uveitis activity tends to ameliorate from the second trimester onwards, with the third trimester being associated with the lowest disease activity. The mechanism behind this phenomenon is likely to be multifactorial and complex. Possible mechanisms include Th1/Th2 immunomodulation, regulatory T-cell phenotype plasticity, and immunosuppressive cytokines. This clearly has management implications for patients with chronic sight threatening disease requiring systemic treatment, as most medications are not recommended during pregnancy due to lack of safety data or proven teratogenicity. Given that uveitis activity is expected to decrease in pregnancy, systemic immunosuppressants could be tapered during pregnancy in these patients, with flare-ups being managed with local corticosteroids till delivery. In the postpartum period, as uveitis activity is expected to rebound, patients should be reviewed closely and systemic medications recommenced, depending on uveitis activity and the patient’s breastfeeding status. This review highlights the current understanding of the course of uveitis in pregnancy and its management to help guide clinicians in managing their uveitis patients during this special time in life.
Retinal vascular calibre changes after intravitreal bevacizumab or dexamethasone implant treatment for diabetic macular oedema.
Publisher: BMJ
Date: 22-02-2017
DOI: 10.1136/BJOPHTHALMOL-2016-309882
Abstract: To compare changes in retinal vascular calibre after 2 years of treatment with intravitreal bevacizumab (BVZ) or dexamethasone implant (DEX) in patients with centre-involving diabetic macular oedema (DMO). At baseline, 88 eyes of 61 patients with DMO were recruited in a prospective, multicentre, randomised, single-masked clinical trial. Of these subjects, 22 BVZ-treated (52%) and 22 DEX-treated (48%) eyes of 34 patients (56%) had gradable retinal photographs at both the baseline and 24-month visits. Retinal vascular calibre was measured from digital fundus photographs and summarised as central retinal artery (CRAE) and vein (CRVE) equivalents in all gradable eyes at baseline and 24 months. At 24 months, 40.9% of BVZ and 45.5% of DEX eyes gained 10 or more letters (p=0.77). There was concurrent reduction in mean central macular thickness, -157.7 μm in BVZ and -192.5 μm in DEX-treated eyes (p=0.40). DEX-treated eyes showed a statistically significant reduction in CRVE compared with BVZ-treated eyes, with a mean change from baseline of -31.78 to +4.34 µm, respectively (p<0.001). CRAE showed a non-statistically significant trend towards reduction over time in DEX-treated eyes compared with BVZ-treated eyes, with a mean change from baseline of -6.09 and +1.66, respectively (p=0.077). DEX had a significant narrowing effect on venular diameter in eyes with DMO not seen with BVZ. The changes in retinal vascular calibre suggest that these agents have a differing actions effects retinal vasculature and thereby suggest a potentially different mechanism of action on reducing DMO. NCT01298076.
Early Mesozoic ferroan (A-type) and magnesian granitoids in eastern South China: Tracing the influence of flat-slab subduction at the western Pacific margin
Publisher: Elsevier BV
Date: 2016
Long-Term Safety and Efficacy of Adalimumab in Patients with Noninfectious Intermediate Uveitis, Posterior Uveitis, or Panuveitis
Publisher: Elsevier BV
Date: 06-2021
Indian-derived sediments deposited in Australia during Gondwana assembly
Publisher: Elsevier BV
Date: 07-2018
HDAC inhibitors restore BRAF‐inhibitor sensitivity by altering PI3K and survival signalling in a subset of melanoma
Publisher: Wiley
Date: 20-12-2017
DOI: 10.1002/IJC.31199
Abstract: Mutations in BRAF activate oncogenic MAPK signalling in almost half of cutaneous melanomas. Inhibitors of BRAF (BRAFi) and its target MEK are widely used to treat melanoma patients with BRAF mutations but unfortunately acquired resistance occurs in the majority of patients. Resistance results from mutations or non-genomic changes that either reactivate MAPK signalling or activate other pathways that provide alternate survival and growth signalling. Here, we show the histone deacetylase inhibitor (HDACi) panobinostat overcomes BRAFi resistance in melanoma, but this is dependent on the resistant cells showing a partial response to BRAFi treatment. Using patient- and in vivo-derived melanoma cell lines with acquired BRAFi resistance, we show that combined treatment with the BRAFi encorafenib and HDACi panobinostat in 2D and 3D culture systems synergistically induced caspase-dependent apoptotic cell death. Key changes induced by HDAC inhibition included decreased PI3K pathway activity associated with a reduction in the protein level of a number of receptor tyrosine kinases, and cell line dependent upregulation of pro-apoptotic BIM or NOXA together with reduced expression of anti-apoptotic proteins. Independent of these changes, panobinostat reduced c-Myc and pre-treatment of cells with siRNA against c-Myc reduced BRAFi/HDACi drug-induced cell death. These results suggest that a combination of HDAC and MAPK inhibitors may play a role in treatment of melanoma where the resistance mechanisms are due to activation of MAPK-independent pathways.
Formation of high δ18O fayalite-bearing A-type granite by hightemperature melting of granulitic metasedimentary rocks, southern China
Publisher: Geological Society of America
Date: 02-09-2011
DOI: 10.1130/G32080.1
Paleomagnetism of the Hervey Group, Central New South Wales and its tectonic implications
Publisher: American Geophysical Union (AGU)
Date: 06-1988
Obduction-type granites within the NE Jiangxi Ophiolite: Implications for the final amalgamation between the Yangtze and Cathaysia Blocks
Publisher: Elsevier BV
Date: 04-2008
Timing and genesis of Hamersley iron-ore deposits
Publisher: Informa UK Limited
Date: 09-1993
DOI: 10.1071/EG993631
Coupled supercontinent-mantle plume events evidenced by oceanic plume record
Publisher: Geological Society of America
Date: 22-11-2020
DOI: 10.1130/G46754.1
Abstract: The most dominant features in the present-day lower mantle are the two antipodal African and Pacific large low-shear-velocity provinces (LLSVPs). How and when these two structures formed, and whether they are fixed and long lived through Earth history or dynamic and linked to the supercontinent cycles, remain first-order geodynamic questions. Hotspots and large igneous provinces (LIPs) are mostly generated above LLSVPs, and it is widely accepted that the African LLSVP existed by at least ca. 200 Ma beneath the supercontinent Pangea. Whereas the continental LIP record has been used to decipher the spatial and temporal variations of plume activity under the continents, plume records of the oceanic realm before ca. 170 Ma are mostly missing due to oceanic subduction. Here, we present the first compilation of an Oceanic Large Igneous Provinces database (O-LIPdb), which represents the preserved oceanic LIP and oceanic island basalt occurrences preserved in ophiolites. Using this database, we are able to reconstruct and compare the record of mantle plume activity in both the continental and oceanic realms for the past 2 b.y., spanning three supercontinent cycles. Time-series analysis reveals hints of similar cyclicity of the plume activity in the continent and oceanic realms, both exhibiting a periodicity of ∼500 m.y. that is comparable to the supercontinent cycle, albeit with a slight phase delay. Our results argue for dynamic LLSVPs where the supercontinent cycle and global subduction geometry control the formation and locations of the plumes.
Formation of high δ 18O fayalite-bearing A-type granite by high-temperature melting of granulitic metasedimentary rocks, southern China: Reply
Publisher: Geological Society of America
Date: 13-09-2012
DOI: 10.1130/G33526Y.1
RAB27A-mediated melanoma exosomes: promoters of invasion and metastasis
Publisher: AME Publishing Company
Date: 06-2019
A trans-Iapetus transform fault control for the evolution of the Rheic Ocean: Implications for an early Paleozoic transition of accretionary tectonics
Publisher: Geological Society of America
Date: 28-02-2022
DOI: 10.1130/B36158.1
Abstract: The Paleozoic era begins with the final assembly of Gondwana and ends with the amalgamation of the supercontinent Pangea. Although this tectonic progression is generally well documented, one fundamental but under-studied phenomenon during this era is the transition from two-way to one-way (northward) migration of peripheral terranes between Gondwana and Laurentia-Baltica from Cambrian to Ordovician time. The two-way terrane accretion was likely initiated during the opening of the Rheic Ocean at ca. 510 Ma when several Gondwana-derived terranes comprising Carolinia, Ganderia, Avalonia, and Meguma sequentially drifted from the northern margin of Gondwana and eventually collided with Laurentia or Baltica. Over the same time interval, the Laurentia-derived Cuyania terrane (a.k.a., the “Precordillera terrane” is commonly believed to have accreted to the proto-Andean margin of Gondwana, whereas the peri-Laurentian/Dashwoods ribbon continent separated from, then re-accreted to, the Laurentian margin after being trapped during the collision of the Taconic arc. Alternatively, the Cuyania terrane is suggested to have remained attached to the Ouachita Embayment throughout the Cambrian–Ordovician, and then passed onto Gondwana during the collision between the proto-Andean margin and the hypothesized Texas Plateau at the leading edge of Cuyania. Here we explain the enigmatic, pene-contemporaneous migration of these peripheral terranes by a trans-Iapetus transform fault that was likely active between 510 and 450 Ma and extended from the proto-Appalachian margin of Laurentia to the proto-Andean margin of Gondwana. The trans-Iapetus transform fault terminated after the respective accretion of Carolinia and Ganderia to the proto-Appalachian margin and of Cuyania to the proto-Andean margin. We interpret the development of the trans-Iapetus transform during the Cambrian–Ordovician to be a consequence of the global geodynamic transition from the break-up of Rodinia (continents/terranes drifting away from Laurentia) to Pangea amalgamation (continents/terranes drifting toward assembling Laurussia).
Trading partners: Tectonic ancestry of southern Africa and western Australia, in Archean supercratons Vaalbara and Zimgarn
Publisher: Elsevier BV
Date: 2013
Risk Factors for Glaucoma in a Cohort of Patients with Fuchs Heterochromic Iridocyclitis
Publisher: Informa UK Limited
Date: 05-08-2016
DOI: 10.1080/09273948.2016.1199712
Abstract: To describe the incidence and risk factors for ocular hypertension and/or glaucoma in patients with Fuchs heterochromic iridocyclitis (FHC). Retrospective analysis of 88 patients with FHC. Kaplan-Meier curves estimated the time to develop cataract and ocular hypertension/glaucoma. Possible prognostic factors were investigated in univariate Kaplan-Meier analyses using the Mantel-Cox logrank test. At presentation with FHC, 52% of patients had a cataract and 26% of patients had ocular hypertension/glaucoma. The estimated percentage of patients with a cataract or ocular hypertension/glaucoma by 4 years after presentation was 71% (CI: 58-81%) and 39% (CI: 28-51%), respectively. Patients aged ≥50 years had significantly greater risk of developing glaucoma (p = 0.0065). After adjusting for age-group, having a cataract at presentation was associated with increased risk of glaucoma (p = 0.032). Risk factors for development of ocular hypertension/glaucoma were increasing patient age and having a cataract at presentation with FHC.
Laurentian crust in northeast Australia: Implications for the assembly of the supercontinent Nuna
Publisher: Geological Society of America
Date: 17-01-2018
DOI: 10.1130/G39980.1
Microbial keratitis associated with extended wear of silicone hydrogel contact lenses
Publisher: BMJ
Date: 03-2002
DOI: 10.1136/BJO.86.3.355
The Long-Wavelength Mantle Structure, and the supercontinent Evolution since the Paleozoic
Publisher: Wiley
Date: 10-2016
Compression-dependent microtubule reinforcement comprises a mechanostat which enables cells to navigate confined environments
Publisher: Cold Spring Harbor Laboratory
Date: 09-02-2022
DOI: 10.1101/2022.02.08.479516
Abstract: Cells migrating through complex 3D environments experience considerable physical challenges including tensile stress and compression. To move, cells need to resist these forces whilst also squeezing the large nucleus through confined spaces. This requires highly coordinated cortical contractility. Microtubules can both resist compressive forces and sequester key actomyosin regulators to ensure appropriate activation of contractile forces. Yet, how these two roles are integrated to achieve nuclear transmigration in 3D is largely unknown. Here, we demonstrate that compression triggers reinforcement of a dedicated microtubule structure at the rear of the nucleus by the mechanoresponsive recruitment of CLASPs (cytoplasmic linker-associated proteins) which dynamically strengthens and repairs the lattice. These reinforced microtubules form the mechanostat: an adaptive feedback mechanism that allows the cell to both withstand compressive force and spatiotemporally organise contractility signalling pathways. The microtubule mechanostat facilitates nuclear positioning and coordinates force production to enable the cell to pass through constrictions. Disruption of the mechanostat imbalances cortical contractility, stalling migration and ultimately resulting in catastrophic cell rupture. Our findings reveal a new role for microtubules as cellular sensors which detect and respond to compressive forces, enabling movement and ensuring survival in mechanically demanding environments. Mechanically tuned microtubules form a mechanostat to coordinate contractility and nuclear positioning in confined migration.
Age and origin of middle Neoproterozoic mafic magmatism in southern Yangtze Block and relevance to the break-up of Rodinia
Publisher: Elsevier BV
Date: 08-2007
Oroclinal bending and block rotations in South China since the Mesozoic - Geological and paleomagnetic evidence
Publisher: Springer Science and Business Media LLC
Date: 1997
DOI: 10.1007/BF03182786
Combined use of subclinical hydroxyurea and CHK1 inhibitor effectively controls melanoma and lung cancer progression, with reduced normal tissue toxicity compared to gemcitabine
Publisher: Wiley
Date: 14-06-2019
Abstract: Drugs such as gemcitabine that increase replication stress are effective chemotherapeutics in a range of cancer settings. These drugs effectively block replication and promote DNA damage, triggering a cell cycle checkpoint response through the ATR–CHK1 pathway. Inhibiting this signalling pathway sensitises cells to killing by replication stress‐inducing drugs. Here, we investigated the effect of low‐level replication stress induced by low concentrations ( 0.2 m m ) of the reversible ribonucleotide reductase inhibitor hydroxyurea (HU), which slows S‐phase progression but has little effect on cell viability or proliferation. We demonstrate that HU effectively synergises with CHK1, but not ATR inhibition, in 70% of melanoma and non‐small‐cell lung cancer cells assessed, resulting in apoptosis and complete loss of proliferative potential in vitro and in vivo . Normal fibroblasts and haemopoietic cells retain viability and proliferative potential following exposure to CHK1 inhibitor plus low doses of HU, but normal cells exposed to CHK1 inhibitor combined with submicromolar concentrations of gemcitabine exhibited complete loss of proliferative potential. The effects of gemcitabine on normal tissue correlate with irreversible ATR–CHK1 pathway activation, whereas low doses of HU reversibly activate CHK1 independently of ATR. The combined use of CHK1 inhibitor and subclinical HU also triggered an inflammatory response involving the recruitment of macrophages in vivo . These data indicate that combining CHK1 inhibitor with subclinical HU is superior to combination with gemcitabine, as it provides equal anticancer efficacy but with reduced normal tissue toxicity. These data suggest a significant proportion of melanoma and lung cancer patients could benefit from treatment with this drug combination.
Identification of an ancient mantle reservoir and young recycled materials in the source region of a young mantle plume: Implications for potential linkages between plume and plate tectonics
Publisher: Elsevier BV
Date: 09-2013
Revisiting the C-type adakites of the Lower Yangtze River Belt, central eastern China: In-situ zircon Hf-O isotope and geochemical constraints
Publisher: Elsevier BV
Date: 05-2013
The supercontinent cycle
Publisher: Springer Science and Business Media LLC
Date: 20-04-2021
Subduction of Indian continent beneath southern Tibet in the latest Eocene (~ 35 Ma): Insights from the Quguosha gabbros in southern Lhasa block
Publisher: Elsevier BV
Date: 2017
Revisiting the "Yanbian Terrane": Implications for Neoproterozoic tectonic evolution of the western Yangtze Block, South China
Publisher: Elsevier BV
Date: 12-2006
New palaeomagnetic results from the 'cap dolomite' of the Neoproterozoic Walsh Tillite, northwestern Australia
Publisher: Elsevier BV
Date: 03-2000
Examining Go-or-Grow Using Fluorescent Cell-Cycle Indicators and Cell-Cycle-Inhibiting Drugs
Publisher: Elsevier BV
Date: 03-2020
Rapid Optical Clearing for Semi-High-Throughput Analysis of Tumor Spheroids
Publisher: MyJove Corporation
Date: 23-08-2022
DOI: 10.3791/64103
Abstract: Tumor spheroids are fast becoming commonplace in basic cancer research and drug development. Obtaining data regarding protein expression within the spheroid at the cellular level is important for analysis, yet existing techniques are often expensive, laborious, use non-standard equipment, cause significant size distortion, or are limited to relatively small spheroids. This protocol presents a new method of mounting and clearing spheroids that address these issues while allowing for confocal analysis of the inner structure of spheroids. In contrast to existing approaches, this protocol provides for rapid mounting and clearing of a large number of spheroids using standard equipment and laboratory supplies. Mounting spheroids in a pH-neutral agarose-PBS gel solution before introducing a refractive-index-matched clearing solution minimizes size distortion common to other similar techniques. This allows for detailed quantitative and statistical analysis where the accuracy of size measurements is paramount. Furthermore, compared to liquid clearing solutions, the agarose gel technique keeps spheroids fixed in place, allowing for the collection of three-dimensional (3D) confocal images. The present article elaborates how the method yields high-quality two- and 3D images that provide information about inter-cell variability and inner spheroid structure.
Modeling the Inception of Supercontinent Breakup: Stress State and the Importance of Orogens
Publisher: American Geophysical Union (AGU)
Date: 11-2019
DOI: 10.1029/2019GC008538
The Willouran basic province of South Australia: Its relation to the Guibei large igneous province in South China and the breakup of Rodinia
Publisher: Elsevier BV
Date: 10-2010
Ca. 1.5Ga mafic magmatism in South China during the break-up of the supercontinent Nuna/Columbia: The Zhuqing Fe–Ti–V oxide ore-bearing mafic intrusions in western Yangtze Block
Publisher: Elsevier BV
Date: 05-2013
Reassessing zircon-monazite thermometry with thermodynamic modelling: insights from the Georgetown igneous complex, NE Australia
Publisher: Springer Science and Business Media LLC
Date: 05-11-2020
DOI: 10.1007/S00410-020-01752-7
Abstract: Accessory mineral thermometry and thermodynamic modelling are fundamental tools for constraining petrogenetic models of granite magmatism. U–Pb geochronology on zircon and monazite from S-type granites emplaced within a semi-continuous, whole-crust section in the Georgetown Inlier (GTI), NE Australia, indicates synchronous crystallisation at 1550 Ma. Zircon saturation temperature ( T zr ) and titanium-in-zircon thermometry ( T (Ti–zr) ) estimate magma temperatures of ~ 795 ± 41 °C ( T zr ) and ~ 845 ± 46 °C ( T (Ti-zr) ) in the deep crust, ~ 735 ± 30 °C ( T zr ) and ~ 785 ± 30 °C ( T (Ti-zr) ) in the middle crust, and ~ 796 ± 45 °C ( T zr ) and ~ 850 ± 40 °C ( T (Ti-zr) ) in the upper crust. The differing averages reflect ambient temperature conditions ( T zr ) within the magma chamber, whereas the higher T (Ti-zr) values represent peak conditions of hotter melt injections. Assuming thermal equilibrium through the crust and adiabatic ascent, shallower magmas contained 4 wt% H 2 O, whereas deeper melts contained 7 wt% H 2 O. Using these H 2 O contents, monazite saturation temperature ( T mz ) estimates agree with T zr values. Thermodynamic modelling indicates that plagioclase, garnet and biotite were restitic phases, and that compositional variation in the GTI suites resulted from entrainment of these minerals in silicic (74–76 wt% SiO 2 ) melts. At inferred emplacement P–T conditions of 5 kbar and 730 °C, additional H 2 O is required to produce sufficient melt with compositions similar to the GTI granites. Drier and hotter magmas required additional heat to raise adiabatically to upper-crustal levels. S-type granites are low- T mushes of melt and residual phases that stall and equilibrate in the middle crust, suggesting that discussions on the unreliability of zircon-based thermometers should be modulated.
First evidence of Archean mafic dykes at 2.62 Ga in the Yilgarn Craton, Western Australia: Links to cratonisation and the Zimbabwe Craton
Publisher: Elsevier BV
Date: 10-2018
Association between diabetes-related eye complications and symptoms of anxiety and depression
Publisher: American Medical Association (AMA)
Date: 09-2016
DOI: 10.1001/JAMAOPHTHALMOL.2016.2213
Abstract: This study is needed to clarify inconsistent findings regarding the association between diabetes-related eye complications and psychological well-being. To examine the association between severity of diabetic retinopathy (DR) and diabetic macular edema (DME) with symptoms of depression and anxiety in adults with diabetes. A cross-sectional study was conducted in a tertiary eye hospital in Melbourne, Australia. The study comprised 519 participants with diabetes. The median duration of diabetes was 13.0 (interquartile range, 14.0) years. The study was conducted from March 1, 2009, to December 24, 2010. Patients underwent a comprehensive eye examination in which dilated fundus photographs (disc and macula centered) were obtained and graded for the presence and severity of DR and DME. Presenting distance uniocular and binocular visual acuity were assessed using a 3-m logMAR chart. Symptoms of depression and anxiety were measured using the Hospital Anxiety and Depression Scale (HADS), which comprises 7 questions specific to anxiety and 7 specific to depression with scores ranging from 0 to 21 scores higher than 8 signify possible anxiety or depression. The ordinal raw scores of the HADS questionnaire were transformed to estimates of interval measure using Rasch analysis and evaluated as continuous variables. Participants also completed standardized interview-administered questionnaires. Blood s les were assessed for hemoglobin A1c, fasting blood glucose, and serum lipids. Multiple linear regression models were used to determine the associations between the severity of DR and DME with symptoms of anxiety and depression and commonality analysis was used to quantify the unique variance explained. Of the 519 participants in the study, 170 in iduals (32.8%) were female mean (SD) age was 64.9 (11.6) years. Raw scores indicated that 80 in iduals (15.4%) screened positive for depressive symptoms and 118 persons (22.7%) screened positive for symptoms of anxiety. In multivariate analysis using Rasch scores, severe nonproliferative DR (NPDR)/PDR was independently associated with greater depressive symptoms (regression coefficient [β] = 0.69 95% CI, 0.03-1.34) after controlling for sociodemographic factors and clinical characteristics, including visual acuity. A history of depression or anxiety accounted for 60.6% (95% CI, 23.9%-83.2%) of the unique variance in depressive symptoms, and severe NPDR or PDR contributed to 19.1% (95% CI, 1.7%-44.4%) of the total explained variance of depressive symptoms. Diabetic macular edema was not associated with depressive symptoms. No association between DR and symptoms of anxiety was identified. Severe NPDR or PDR, but not DME, was independently associated with depressive symptoms. The severity of DR could be an indicator to prompt monitoring of depression in at-risk in iduals with diabetes. Further work is required to replicate these findings and determine the clinical significance of the association.
The Early Permian active continental margin and crustal growth of the Cathaysia Block: In situ U-Pb, Lu-Hf and O isotope analyses of detrital zircons
Publisher: Elsevier BV
Date: 10-2012
South China in Rodinia: part of the missing link between Australia- East Antarctica and Laurentia?
Publisher: Geological Society of America
Date: 1995
Late Carboniferous high εNd(t)–εHf(t) granitoids, enclaves and dikes in western Junggar, NW China: Ridge-subduction-related magmatism and crustal growth
Publisher: Elsevier BV
Date: 05-2012
PLX4032, a potent inhibitor of the B‐Raf V600E oncogene, selectively inhibits V600E‐positive melanomas
Publisher: Wiley
Date: 13-10-2010
New paleomagnetic results from the Neoproterozoic successions in southern North China Block and paleogeographic implications
Publisher: Springer Science and Business Media LLC
Date: 12-2000
DOI: 10.1007/BF02911948
Reply to the comment: Mantle plume-, but not arc-related Neoproterozoic magmatism in South China
Publisher: Elsevier BV
Date: 07-2004
Continental flood basalt weathering as a trigger for Neoproterozoic Snowball Earth
Publisher: Elsevier BV
Date: 07-2016
Mathematical Model of Tumour Spheroid Experiments with Real-Time Cell Cycle Imaging
Publisher: Springer Science and Business Media LLC
Date: 20-03-2021
Precambrian evolution and cratonization of the Tarim Block, NW China: Petrology, geochemistry, Nd-isotopes and U–Pb zircon geochronology from Archaean gabbro-TTG–potassic granite suite and Paleoproter
Publisher: Elsevier BV
Date: 03-2012
Tolerating Subretinal Fluid in Neovascular Age-Related Macular Degeneration Treated with Ranibizumab Using a Treat-and-Extend Regimen
Publisher: Elsevier BV
Date: 05-2019
DOI: 10.1016/J.OPHTHA.2018.11.025
Abstract: To test the hypothesis that tolerating some subretinal fluid (SRF) in patients with neovascular age-related macular degeneration (nAMD) treated with ranibizumab using a treat-and-extend (T&E) regimen can achieve similar visual acuity (VA) outcomes as treatment aimed at resolving all SRF. Multicenter, randomized, 24-month, phase 4, single-masked, noninferiority clinical trial. Participants with treatment-naïve active subfoveal choroidal neovascularization (CNV). Participants were randomized to receive ranibizumab 0.5 mg monthly until either complete resolution of SRF and intraretinal fluid (IRF intensive arm: SRF intolerant) or resolution of all IRF only (relaxed arm: SRF tolerant except for SRF >200 μm at the foveal center) before extending treatment intervals. A 5-letter noninferiority margin was applied to the primary outcome. Mean change in best-corrected VA (BCVA), and central subfield thickness and number of injections from baseline to month 24. Of the 349 participants randomized (intensive arm, n = 174 relaxed arm, n = 175), 279 (79.9%) completed the month 24. The mean change in BCVA from baseline to month 24 was 3.0 letters (standard deviation, 16.3 letters) in the intensive group and 2.6 letters (standard deviation, 16.3 letters) in the relaxed group, demonstrating noninferiority of the relaxed compared with the intensive treatment (P = 0.99). Similar proportions of both groups achieved 20/40 or better VA (53.5% and 56.6%, respectively P = 0.92) and 20/200 or worse VA (8.7% and 8.1%, respectively P = 0.52). Participants in the relaxed group received fewer ranibizumab injections over 24 months (mean, 15.8 [standard deviation, 5.9]) than those in the intensive group (mean, 17 [standard deviation, 6.5] P = 0.001). Significantly more participants in the intensive group never extended beyond 4-week treatment intervals (13.5%) than in the relaxed group (2.8% P = 0.003), and significantly more participants in the relaxed group extended to and maintained 12-week treatment intervals (29.6%) than the intensive group (15.0% P = 0.005). Patients treated with a ranibizumab T&E protocol who tolerated some SRF achieved VA that is comparable, with fewer injections, with that achieved when treatment aimed to resolve all SRF completely.
Distinct formation history for deep-mantle domains reflected in geochemical differences
Publisher: Springer Science and Business Media LLC
Date: 29-06-2020
850-790 Ma bimodal volcanic and intrusive rocks in northern Zhejiang, South China: A major episode of continental rift magmatism during the breakup of Rodinia
Publisher: Elsevier BV
Date: 04-2008
Episodic Precambrian crust growth: Evidence from U-Pb ages and Hf-O isotopes of zircon in the Nanhua Basin, central South China
Publisher: Elsevier BV
Date: 12-2012
Permo-Triassic magnetostratigraphy in China: The type section near Taiyuan, Shanxi Province, North China
Publisher: Oxford University Press (OUP)
Date: 08-1996
Uveitis in Patients with Multiple Sclerosis in Clinical Trials of Fingolimod: Incidence, Prevalence, and Impact on Disease Course
Publisher: Elsevier BV
Date: 03-2019
DOI: 10.1016/J.OPHTHA.2018.10.013
Abstract: To determine the incidence and prevalence of uveitis and its effect on multiple sclerosis (MS) disease activity and outcomes in patients with MS who participated in the fingolimod clinical trial program. Analysis of pooled data (N = 27 528) from patients enrolled in fingolimod clinical studies and their extensions. Patients were stratified into 4 cohorts based on the history of uveitis at baseline and uveitis events during the observation period: no history and no uveitis events ("no uveitis") history and no uveitis events ("history") no history and uveitis events ("first event") history and uveitis events ("recurrent event"). Adult patients diagnosed with relapsing or primary progressive MS. Patients received fingolimod (0.5, 1.25, or 5 mg/day), placebo, or intramuscular interferon beta-1a (IFNβ-1a IM) during the core studies patients receiving placebo or IFNβ-1a IM were switched to fingolimod 0.5 mg therapy for study extensions. Incidence and prevalence of uveitis, and MS outcome measures, including annualized relapse rate (ARR), time to first relapse, change in Expanded Disability Status Scale (EDSS) score from baseline, and proportion of patients with 6-month confirmed disability progression. A total of 189 patients in the analysis population had uveitis. Of these, 162 patients had a history of uveitis (prevalence, 0.59%). Uveitis occurred as a first event in 27 patients (incidence, 0.1 per 100 patient-years) and as a recurrent event in 10 of 162 patients (prevalence, 6.17%). Patients with uveitis had a significantly shorter time to first relapse (mean, 2.11 vs. 8.12 years P = 0.047) and a significantly higher ARR (0.31 vs. 0.21 P = 0.025) than those without uveitis. Mean increase in EDSS score at month 120 and the proportions of patients with 6-month confirmed disability progression, and with EDSS score ≥4 during follow-up, were similar in patients with uveitis compared with those without uveitis. This pooled analysis involving a large patient cohort showed that patients with MS and uveitis had increased MS relapse activity compared with those without uveitis.
A Permian large igneous province in Tarim and Central Asian orogenic belt, NW China: Results of a ca. 275 Ma mantle plume?
Publisher: Geological Society of America
Date: 09-2010
DOI: 10.1130/B30007.1
Expression of Bcl-xL and Mcl-1 in the nonmelanoma skin cancers of renal transplant recipients
Publisher: Oxford University Press (OUP)
Date: 04-2015
The oldest known rocks in south-western China: SHRIMP U-Pb magmatic crystallisation age and detrital provenance analysis of the Paleoproterozoic Dahongshan Group
Publisher: Elsevier BV
Date: 08-2008
Designing and interpreting 4D tumour spheroid experiments
Publisher: Springer Science and Business Media LLC
Date: 24-01-2022
DOI: 10.1038/S42003-022-03018-3
Abstract: Tumour spheroid experiments are routinely used to study cancer progression and treatment. Various and inconsistent experimental designs are used, leading to challenges in interpretation and reproducibility. Using multiple experimental designs, live-dead cell staining, and real-time cell cycle imaging, we measure necrotic and proliferation-inhibited regions in over 1000 4D tumour spheroids (3D space plus cell cycle status). By intentionally varying the initial spheroid size and temporal s ling frequencies across multiple cell lines, we collect an abundance of measurements of internal spheroid structure. These data are difficult to compare and interpret. However, using an objective mathematical modelling framework and statistical identifiability analysis we quantitatively compare experimental designs and identify design choices that produce reliable biological insight. Measurements of internal spheroid structure provide the most insight, whereas varying initial spheroid size and temporal measurement frequency is less important. Our general framework applies to spheroids grown in different conditions and with different cell types.
Poly-phase metamorphism of garnet-bearing mafic granulite from the Larsemann Hills, East Antarctica: P-T path, U-Pb ages and tectonic implications
Publisher: Elsevier BV
Date: 06-2019
Understanding dual geochemical characters in a geological context for the Gaojiacun intrusion: Response to Munteanu and Yao's discussion [Precambrian Res. 154 (2007) 164-167]
Publisher: Elsevier BV
Date: 06-2007
Formation of the Jurassic South China Large Granitic Province: Insights from the genesis of the Jiufeng pluton
Publisher: Elsevier BV
Date: 04-2015
Intravitreal Injection Rates for Neovascular Age-Related Macular Degeneration in Australia During the 2020 COVID-19 Lockdowns
Publisher: Informa UK Limited
Date: 15-02-2023
Abrogation of RAB27A expression transiently affects melanoma cell proliferation
Publisher: Cold Spring Harbor Laboratory
Date: 27-12-2219
DOI: 10.1101/2019.12.27.889329
Abstract: The role of the small GTPase RAB27A as an essential melanosome trafficking regulator in melanocytes is well-accepted. A decade ago, RAB27A was identified as a tumor dependency gene that promotes melanoma cell proliferation. RAB27A has since been linked to another propeller of cancer progression: exosome secretion. We have recently demonstrated that RAB27A is overexpressed in a subset of melanomas. High RAB27A gene and protein expression correlates with poor prognosis in melanoma patients. Mechanistic investigations revealed that the generation of pro-invasive exosomes was RAB27A-dependent and, therefore, silencing RAB27A reduced melanoma cell invasion in vitro and in vivo . However, previous studies have implicated RAB27A to be involved in both proliferation and invasion of melanoma cells. In this study, we demonstrate that the effects of abrogating RAB27A expression on proliferation are temporary, in contrast to the previously reported persistent effects on tumor invasion and metastasis. Therefore, we assist in the dissection of the short-term versus long-term effects of RAB27A knockdown on melanoma cell proliferation, invasion, and metastasis. We believe that our findings provide novel insights into the effects of RAB27A blockade. RAB27A is known to serve as an essential regulator for melanosome trafficking. However, to date its role in melanoma biology has not been completely deciphered. While there are consistent independent reports on the pro-invasive effects of RAB27A, there are conflicting data on its impact on cell proliferation. Here we show that indeed abrogation of RAB27A does reduce cellular proliferation however, this effect is only transient, while the impact on invasion as reported previously is persistent. This finding offers an explanation for the apparent contradiction in the literature and provides a deeper understanding of RAB27A function in melanoma cell biology.
Reply to the comment by Zhou et al. on: Revisiting the Yanbian Terrane: Implications for Neoproterozoic tectonic evolution of the western Yangtze Block, South China [Precambrian Res. 151 (2006) 14-30] [Precambrian Res. 154 (2007) 153-157]
Publisher: Elsevier BV
Date: 06-2007
Microenvironment-driven dynamic heterogeneity and phenotypic plasticity as a mechanism of melanoma therapy resistance
Publisher: Frontiers Media SA
Date: 24-05-2018
JNK–ERK signalling in melanoma: rewired or entangled?
Publisher: Oxford University Press (OUP)
Date: 12-2016
DOI: 10.1111/BJD.14903
Seismic reflection data support episodic and simultaneous growth of the Tibetan Plateau since 25Myr
Publisher: Springer Science and Business Media LLC
Date: 02-02-0011
DOI: 10.1038/NCOMMS6453
Abstract: The spectacular topography of the Tibetan Plateau is the result of collision between India and Eurasia over some 50 Myr, but how the plateau grew to its present size remains a topic of debate. Work along its eastern margin suggests a two-stage uplift (thus growth of the plateau) since 30-25 Myr. Here we report high-resolution seismic reflection and drill core results from the southern Tarim Basin that indicate a similar pattern for the northern margin of the plateau. The data suggest that uplift in northern Tibet started at ~23 Myr from near sea level, with the first episode finished by ~10 Myr, followed by a post-5-Myr episode of rapid uplift along the present plateau margin. The growth of the Tibetan Plateau after the Eocene thus appears to have been episodic in nature, and near-synchronous along both eastern and northern margins.
Bevacizumab or Dexamethasone Implants for DME: 2-year Results (The BEVORDEX Study).
Publisher: Elsevier BV
Date: 06-2016
Diverse Permian magmatism in the Tarim Block, NW China: Genetically linked to the Permian Tarim mantle plume?
Publisher: Elsevier BV
Date: 10-2010
The South China piece in the Rodinian puzzle: A reply to the comment by Munteanu and Wilson
Publisher: Elsevier BV
Date: 06-2009
Newly identified 1.89 Ga mafic dyke swarm in the Archean Yilgarn Craton, Western Australia suggests a connection with India
Publisher: Elsevier BV
Date: 08-2019
Neoproterozoic ultramafic-mafic-carbonatite complex and granitoids in Quruqtagh of northeastern Tarim Block, western China: Geochronology, geochemistry and tectonic implications
Publisher: Elsevier BV
Date: 20-01-2007
Geochemical fingerprinting of continental and oceanic basalts: A machine learning approach
Publisher: Elsevier BV
Date: 10-2022
Variable involvements of mantle plumes in the genesis of mid-Neoproterozoic basaltic rocks in South China: A review
Publisher: Elsevier BV
Date: 06-2009
A palaeogeographic context for Neoproterozoic glaciation
Publisher: Elsevier BV
Date: 06-2009
Detrital zircon U-Pb geochronology, Hf isotopes and geochemistry constraints on crustal growth and Mesozoic tectonics of southeastern China
Publisher: Elsevier BV
Date: 06-2015
Vertical‐axis block rotations in southwestern China since the Cretaceous: New Paleomagnetic results from Hainan Island
Publisher: American Geophysical Union (AGU)
Date: 15-11-1995
DOI: 10.1029/95GL03169
A pre-2.2 Ga age for giant hematite ores of the Hamersley province, Australia
Publisher: Society of Economic Geologists
Date: 11-1998
Geochemical and Hf-Nd isotope data of Nanhua rift sedimentary and volcaniclastic rocks indicate a Neoproterozoic continental flood basalt provenance
Publisher: Elsevier BV
Date: 12-2011
Melanoma never says die
Publisher: Wiley
Date: 07-2014
DOI: 10.1111/EXD.12400
Abstract: Drug resistance in melanoma is commonly attributed to ineffective apoptotic pathways. Targeting apoptosis regulators is thus considered a promising approach to sensitizing melanoma to therapy. In the previous issue of Experimental Dermatology, Plötz and Eberle discuss the role that apoptosis plays in melanoma progression and drug resistance and the utility of apoptosis-inducing BH3-mimetics as targeted therapy. There are a number of compounds in clinical development and the field seems close to translating recent findings into benefits for patients with melanoma. Thus, this viewpoint is timely and achieves a valuable summary of the current state of apoptosis-inducing therapy of melanoma.
Geochronology and geochemistry of Late Paleozoic magmatic rocks in the Lamasu–Dabate area, northwestern Tianshan (west China): Evidence for a tectonic transition from arc to post-collisional setting
Publisher: Elsevier BV
Date: 10-2010
Imaging- and flow cytometry-based analysis of cell position and the cell cycle in 3d melanoma spheroids
Publisher: MyJove Corporation
Date: 28-12-2015
DOI: 10.3791/53486
Normal human melanocyte homeostasis as a paradigm for understanding melanoma.
Publisher: Elsevier BV
Date: 11-2005
Approximating nonlinear relations between susceptibility and magnetic contents in rocks using neural networks
Publisher: Tsinghua University Press
Date: 06-2010
Positions of the East Asian cratons in the Neoproterozoic supercontinent Rodinia
Publisher: Informa UK Limited
Date: 12-1996
Detrital zircon U-Pb age and Hf isotope constrains on the generation and reworking of Precambrian continental crust in the Cathaysia Block, South China: A synthesis
Publisher: Elsevier BV
Date: 04-2014
Formation of the Jinchuan ultramafic intrusion and the world's third largest Ni‐Cu sulfide deposit: Associated with the ∼825 Ma south China mantle plume?
Publisher: American Geophysical Union (AGU)
Date: 11-2005
DOI: 10.1029/2005GC001006
A plate-tectonic speed limit?
Publisher: Springer Science and Business Media LLC
Date: 05-1993
DOI: 10.1038/363216A0
Mathematical models for cell migration with real-time cell cycle dynamics
Publisher: Elsevier BV
Date: 03-0055
Palaeomagnetic study of Neoproterozoic glacial rocks of the Yangzi Block: Palaeolatitude and configuration of South China in the late Proterozoic supercontinent
Publisher: Elsevier BV
Date: 03-1999
Pannotia: in defence of its existence and geodynamic significance
Publisher: Geological Society of London
Date: 27-08-2020
Rituximab Therapy for Refractory Orbital Inflammation
Publisher: American Medical Association (AMA)
Date: 05-2014
Age and paleomagnetism of the 1210Ma Gnowangerup–Fraser dyke swarm, Western Australia, and implications for late Mesoproterozoic paleogeography
Publisher: Elsevier BV
Date: 06-2014
Stratigraphic evolution of a Late Triassic to Early Jurassic intracontinental basin in southeastern South China: A consequence of flat-slab subduction?
Publisher: Elsevier BV
Date: 04-2014
Trial by fire: Testing the paleolongitude of Pangea of competing reference frames with the African LLSVP
Publisher: Elsevier BV
Date: 07-2020
Magnetostratigraphic record of the late miocene onset of the East Asian monsoon, and pliocene uplift of northern Tibet
Publisher: Elsevier BV
Date: 04-2001
Time to Uveitis Control with Methotrexate and Mycophenolate Mofetil
Publisher: Elsevier BV
Date: 06-2022
Development of New Proliferative Diabetic Retinopathy in the BEVORDEX Trial.
Publisher: Elsevier BV
Date: 03-2018
Paleogeographic record of Eocene Farallon slab rollback beneath western North America
Publisher: Geological Society of America
Date: 04-2015
DOI: 10.1130/G36733C.1
Optical coherence tomography analysis of patients with untreated diabetic macular edema.
Publisher: Springer Science and Business Media LLC
Date: 26-12-2019
DOI: 10.1007/S00417-019-04549-Y
Abstract: Diabetic macular edema (DME) is a major cause of vision loss. Diabetes patients with mild macular edema and good visual acuity are often observed carefully so that treatment can be instituted when central vision is threatened. Optimal frequency of monitoring of these patients is unknown. Our study aimed to gather more information to determine a safe interval for monitoring of patients with eyes that were not undergoing active treatment for DME and to correlate outcomes with clinical risk factors. Study population: Ninety-seven eyes with optical coherence tomography (OCT) evidence of DME of 97 patients with diabetes. Study procedures: Retrospective review of medical records and macular OCT scans at a 6-12-month interval. Primary outcomes: Change in visual acuity and change in central subfield thickness (CSFT) between the initial and follow-up OCT scans. There was no significant change from median baseline visual acuity 6/9 (inter-quartile range 6/6-6/12) or from median baseline CSFT (290 μm, inter-quartile range 270-312 μm) over a median duration of 8 months (inter-quartile range 7-10 months). The numbers of eyes where CSFT had increased ≥ 25 μm, reduced ≥ 25 μm, or remained unchanged were 16 (16%), 6 (6%), and 74 (76%), respectively. Patients with hemoglobin A1c ≥ 8.5% were 5.7 times more likely to develop central subfield thickening (95% CI 1.1-30.1, P = 0.038). Majority of eyes with DME on OCT had stable CSFT without treatment over a median duration of 8 months. Hemoglobin A1c may be useful for risk stratification.
The magnificent seven: A proposal for modest revision of the quality index
Publisher: Elsevier BV
Date: 09-2020
Antineutrophil Cytoplasmic Antibody–Associated Active Scleritis
Publisher: American Medical Association (AMA)
Date: 05-2008
DOI: 10.1001/ARCHOPHT.126.5.651
Abstract: To determine whether antineutrophil cytoplasmic antibody (ANCA) testing provides prognostic information in evaluating scleritis. Retrospective medical record review of patients evaluated at a tertiary care center from January 1, 1995, to June 30, 2006, was performed to compare clinical features, treatments, and associated systemic disease in patients who test positive for ANCA vs patients whose ANCA tests are negative. Among 78 patients identified, 14 tested positive for ANCA. Patients with positive ANCA test results were more likely to have an associated systemic disorder (10 of 14 or 71%) than were patients who tested negative for ANCA (26 of 64 or 41% P = .04), and the disorder was more likely to have been diagnosed as a result of scleritis work-up (2 of 10 or 20% vs 19 of 26 or 73% P = .007). Patients with positive ANCA test results had significantly more ocular complications (21 of 14 or 86% vs 20 of 64 or 31% P < .001), including keratopathy (5 of 14 or 36% vs 6 of 64 or 9% P = .02), visual acuity of 20/50 or worse (8 of 14 or 57% vs 11 of 64 or 17% P = .001), and vascular pannus (3 of 14 or 21% vs 1 of 64 or 2% P = .02). Aggressive therapy, such as chronic systemic corticosteroids (9 of 14 or 64% vs 9 of 64 or 14% P < .001) and alkylator therapy (8 of 14 or 57% vs 7 of 64 or 11% P < .001), was more likely to be recommended for patients who tested positive for ANCA. A substantial subset of patients with scleritis are also positive for ANCA. These patients are more likely to have severe ocular disease and undiagnosed primary vasculitic disease, thereby requiring more aggressive therapy. An ANCA test may be useful in the evaluation and treatment of patients with scleritis.
Targeting endothelin receptor signalling overcomes heterogeneity driven therapy failure
Publisher: EMBO
Date: 12-06-2017
Abstract: Approaches to prolong responses to BRAF targeting drugs in melanoma patients are challenged by phenotype heterogeneity. Melanomas of a “MITF‐high” phenotype usually respond well to BRAF inhibitor therapy, but these melanomas also contain subpopulations of the de novo resistance “AXL‐high” phenotype. 50% of melanomas progress with enriched “AXL‐high” populations, and because AXL is linked to de‐differentiation and invasiveness avoiding an “AXL‐high relapse” is desirable. We discovered that phenotype heterogeneity is supported during the response phase of BRAF inhibitor therapy due to MITF‐induced expression of endothelin 1 (EDN1). EDN1 expression is enhanced in tumours of patients on treatment and confers drug resistance through ERK re‐activation in a paracrine manner. Most importantly, EDN1 not only supports MITF‐high populations through the endothelin receptor B (EDNRB), but also AXL‐high populations through EDNRA, making it a master regulator of phenotype heterogeneity. Endothelin receptor antagonists suppress AXL‐high‐expressing cells and sensitize to BRAF inhibition, suggesting that targeting EDN1 signalling could improve BRAF inhibitor responses without selecting for AXL‐high cells.
Early differentiation of the bulk silicate Earth as recorded by the oldest mantle reservoir
Publisher: Elsevier BV
Date: 11-2013
Reduction in Herpes Zoster Antiviral Use Since the Introduction of the Live-Attenuated Zoster Vaccine on Australia’s National Immunisation Program: A Population-Based Study from 1994 to 2019
Publisher: Springer Science and Business Media LLC
Date: 10-01-2023
A quantitative approach to histopathological dissection of elastin-related disorders using multiphoton microscopy
Publisher: Oxford University Press (OUP)
Date: 10-2013
DOI: 10.1111/BJD.12430
Abstract: Multiphoton microscopy (MPM) is a novel imaging technology that has recently become applicable for diagnostic purposes. The use of (near) infrared light in MPM allows for deep tissue imaging. In addition, this modality exploits the autofluorescent nature of extracellular matrix fibres within the skin. To quantitate the structure and abundance of elastic fibres in human dermis in three dimensions utilizing autofluorescent signals generated by MPM for the objective examination of elastin-related skin disorders. Cross-sections of skin s les from elastin-related disorders were analysed by MPM and correlated to histopathology. In situ visualization of elastic fibres by MPM was conducted by en face imaging of ex vivo skin s les through the intact epidermis. Image analysis software was used to quantify elastic fibres in three dimensions. Based on the MPM-detected elastin-specific autofluorescence, we developed the Dermal Elastin Morphology Index (DEMI), calculated as the ratio of elastic fibre surface area and volume. This enabled objective three-dimensional quantification of elastic fibres. Quantitative scoring of sun-damaged skin using DEMI correlated with qualitative histopathological grading of the severity of solar elastosis. Furthermore, this approach was applied to changes in elastic fibre architecture in other disorders, such as pseudoxanthoma elasticum (PXE), PXE-like syndrome, elastofibroma, focal dermal elastosis, anetoderma, mid-dermal elastolysis and striae distensae. We imaged elastic fibres in intact ex vivo skin imaged en face through the epidermis, indicating that this approach could be used in vivo. MPM has the potential for noninvasive in vivo visualization of elastic fibres in the dermis with near histological resolution. DEMI allows objective assessment of elastic fibres to support diagnosis and monitoring of disease progress or therapy of elastin-related skin disorders.
Palaeomagnetic dating of mineral deposits; a brief review and a Western Australian perspective
Publisher: Informa UK Limited
Date: 03-1992
DOI: 10.1071/EG992373
Pre-Alpine contrasting tectono-metamorphic evolutions within the Southern Steep Belt, Central Alps
Publisher: Elsevier BV
Date: 06-2018
Outcome of Treatment of Uveitic Macular Edema
Publisher: Elsevier BV
Date: 11-2201
Reciprocal Regulation of BRN2 and NOTCH1/2 Signaling Synergistically Drives Melanoma Cell Migration and Invasion
Publisher: Elsevier BV
Date: 07-2022
DOI: 10.1016/J.JID.2020.12.039
Abstract: Phenotypic plasticity drives cancer progression, impacts treatment response, and is a major driver of therapeutic resistance. In melanoma, a regulatory axis between the MITF and BRN2 transcription factors has been reported to promote tumor heterogeneity by mediating switching between proliferative and invasive phenotypes, respectively. Despite strong evidence that subpopulations of cells that exhibit a BRN2
Paleomagnetic Evidence for a Paleoproterozoic Rotational Assembly of the North Australian Craton in the Leadup to Supercontinent Formation
Publisher: American Geophysical Union (AGU)
Date: 17-11-2022
DOI: 10.1029/2022GL099842
Abstract: The kinematics of the Paleoproterozoic assembly of Earth's first supercontinent, Nuna, are still debated. We present new paleomagnetic results from two Paleoproterozoic rock formations in the North Australia Craton (NAC) that exemplify cratonic assembly processes in the leadup to Nuna formation. Our new paleomagnetic data for the 1,825 Ma Plum Tree Creek Volcanics of the proto‐NAC and the layered mafic‐ultramafic 1,855 Ma Toby intrusion of the Kimberley Craton suggest their amalgamation just prior to ca. 1.8 Ga through a scissor‐like ocean closure to form the NAC, in accord with geological records. Comparing these new results with extant poles from Australia and other major cratons suggests similarly minor relative plate motions between ca. 1.9 and 1.65 Ga during craton and supercontinent formation. A global reconstruction suggests that these events could be related to a major slab‐suction event leading to Nuna formation.
Decoding earth's plate tectonic history using sparse geochemical data
Publisher: Elsevier BV
Date: 2020
Ki67 expression levels are a better marker of reduced melanoma growth following MEK inhibitor treatment than phospho-ERK levels
Publisher: Springer Science and Business Media LLC
Date: 23-01-2007
BCL-XL and MCL-1 are the key BCL-2 family proteins in melanoma cell survival
Publisher: Springer Science and Business Media LLC
Date: 24-04-2019
DOI: 10.1038/S41419-019-1568-3
Abstract: Malignant melanoma is one of the most difficult cancers to treat due to its resistance to chemotherapy. Despite recent successes with BRAF inhibitors and immune checkpoint inhibitors, many patients do not respond or become resistant to these drugs. Hence, alternative treatments are still required. Due to the importance of the BCL-2-regulated apoptosis pathway in cancer development and drug resistance, it is of interest to establish which proteins are most important for melanoma cell survival, though the outcomes of previous studies have been conflicting. To conclusively address this question, we tested a panel of established and early passage patient-derived cell lines against several BH3-mimetic drugs designed to target in idual or subsets of pro-survival BCL-2 proteins, alone and in combination, in both 2D and 3D cell cultures. None of the drugs demonstrated significant activity as single agents, though combinations targeting MCL-1 plus BCL-XL, and to a lesser extent BCL-2, showed considerable synergistic killing activity that was elicited via both BAX and BAK. Genetic deletion of BFL-1 in cell lines that express it at relatively high levels only had minor impact on BH3-mimetic drug sensitivity, suggesting it is not a critical pro-survival protein in melanoma. Combinations of MCL-1 inhibitors with BRAF inhibitors also caused only minimal additional melanoma cell killing over each drug alone, whilst combinations with the proteasome inhibitor bortezomib was more effective in multiple cell lines. Our data show for the first time that therapies targeting specific combinations of BCL-2 pro-survival proteins, namely MCL-1 plus BCL-XL and MCL-1 plus BCL-2, could have significant benefit for the treatment of melanoma.
Uveitis in Patients with Autoimmune Hepatitis
Publisher: Elsevier BV
Date: 02-2009
DOI: 10.1016/J.AJO.2008.08.019
Abstract: To report seven cases of uveitis occurring in patients with autoimmune hepatitis (AIH), raising the possibility that uveitis may be an extrahepatic feature of AIH. Multicenter, retrospective, observational case series of patients with AIH and uveitis. One index case was identified at Oregon Health & Science University. Further cases were identified by a web-based survey of members of the American Uveitis Society, the International Uveitis Study Group, the Proctor Foundation mailing list server, and the First SUN International Workshop. Respondents were asked to provide clinical information about uveitis phenotype, AIH features, and treatment. Clinical information was obtained for seven in iduals (four females and three males age range, seven to 67 years) who suffered from AIH and uveitis. Average duration of follow-up was 5.5 years. All patients had chronic, persistent bilateral uveitis that was anterior (n = 3), intermediate (n = 1), or pan (n = 3) in location. Every patient had complications arising from his or her uveitis, including cataract (n = 5), glaucoma (n = 3), cystoid macular edema (n = 3), and posterior synechiae (n = 3). Final visual acuities ranged from 20/16 to hand movements. To treat the uveitis and/or AIH, the majority of patients required oral prednisone and all seven patients were treated with systemic immunosuppression. Despite the small size of this study, our findings suggest an association between AIH and uveitis. The uveitis is chronic, bilateral, and associated with sight-threatening complications, necessitating systemic immunosuppression in some in iduals.
The Role of Melanoma Cell-Stroma Interaction in Cell Motility, Invasion, and Metastasis
Publisher: Frontiers Media SA
Date: 06-11-2018
A model for the evolution of the Earth's mantle structure since the Early Paleozoic
Publisher: American Geophysical Union (AGU)
Date: 04-06-2010
DOI: 10.1029/2009JB006896
Zircon SHRIMP U–Pb geochronology of potassic felsic intrusions in western Yunnan, SW China: Constraints on the relationship of magmatism to the Jinsha suture
Publisher: Elsevier BV
Date: 09-2012
Synchronized oscillations in growing cell populations are explained by demographic noise
Publisher: Elsevier BV
Date: 04-2021
Uplift of the West Kunlun Range, northern Tibetan Plateau, dominated by brittle thickening of the upper crust
Publisher: Geological Society of America
Date: 20-02-2013
DOI: 10.1130/G33890.1
Proof of Concept, Randomized, Placebo-Controlled Study of the Effect of Simvastatin on the Course of Age-Related Macular Degeneration
Publisher: Public Library of Science (PLoS)
Date: 31-12-2013
Up-Regulated Expression of Zonula Occludens Protein-1 in Human Melanoma Associates with N-Cadherin and Contributes to Invasion and Adhesion
Publisher: Elsevier BV
Date: 05-2005
A treat and extend protocol with Aflibercept for cystoid macular oedema secondary to central retinal vein occlusion – an 18-month prospective cohort study
Publisher: Springer Science and Business Media LLC
Date: 24-02-2020
DOI: 10.1186/S12886-020-01346-8
Abstract: To evaluate the safety and efficacy of a treat-and-extend protocol of aflibercept for cystoid macular oedema (CMO) secondary to central retinal vein occlusion (CRVO). Twenty patients with CMO secondary to CRVO were included in this prospective cohort study. After 3 loading 4-weekly injections, treatment intervals were increased by 2 weeks if there was no clinical activity, to a maximum of 12 weeks. If clinical activity recurred or persisted, the interval between injections was shortened by 2 weeks, to a minimum of 4 weeks. Main outcome measures were change in visual acuity and the proportion of patients gaining 15 or more Early Treatment of Diabetic Retinopathy Study (ETDRS) letters from baseline at 6, 12 and 18 months. Mean BCVA gain from baseline was 19.7 ± 13.8, 22.2 ± 13.9 and 21.9 ± 15.8 ETDRS letters at 6, 12 and 18 months, respectively. Sixty-five percent of patients gained 15 or more ETDRS letters at 6 months, increasing to 70.6% at 12 and 18 months. Patients received 5.0 [4.0 to 6.0], 8.5 [8.0 to 10.3] and 11.0 [9.0 to 12.5] injections by 6, 12 and 18 months, respectively. The visual outcomes achieved with a treat-and-extend protocol in this study were similar to the pivotal trials of aflibercept for CMO secondary to CRVO, which used monthly and then as-needed protocols. Australian and New Zealand Clinical Trials Registry, registration number ACTR N12615000417583 , 01/05/2015.
Early Late Cretaceous (ca. 93Ma) norites and hornblendites in the Milin area, eastern Gangdese: Lithosphere–asthenosphere interaction during slab roll-back and an insight into early Late Cretaceous (c
Publisher: Elsevier BV
Date: 07-2013
Do Supercontinent-Superplume Cycles Control the Growth and Evolution of Continental Crust?
Publisher: Springer Science and Business Media LLC
Date: 27-10-2020
First Precambrian palaeomagnetic data from the Mawson Craton (East Antarctica) and tectonic implications
Publisher: Springer Science and Business Media LLC
Date: 06-11-2018
DOI: 10.1038/S41598-018-34748-2
Abstract: A pilot palaeomagnetic study was conducted on the recently dated with in situ SHRIMP U-Pb method at 1134 ± 9 Ma (U-Pb, zircon and baddeleyite) Bunger Hills dykes of the Mawson Craton (East Antarctica). Of the six dykes s led, three revealed meaningful results providing the first well-dated Mesoproterozoic palaeopole at 40.5°S, 150.1°E (A 95 = 20°) for the Mawson Craton. Discordance between this new pole and two roughly coeval poles from Dronning Maud Land and Coats Land (East Antarctica) demonstrates that these two terranes were not rigidly connected to the Mawson Craton ca. 1134 Ma. Comparison between the new pole and that of the broadly coeval Lakeview dolerite from the North Australian Craton supports the putative ~40° late Neoproterozoic relative rotation between the North Australian Craton and the combined South and West Australian cratons. A mean ca. 1134 Ma pole for the Proto-Australia Craton is calculated by combining our new pole and that of the Lakeview dolerite after restoring the 40° intracontinental rotation. A comparison of this mean pole with the roughly coeval Abitibi dykes pole from Laurentia confirms that the SWEAT reconstruction of Australia and Laurentia was not viable for ca. 1134 Ma.
Relationship between northwestern Tasmania and East Gondwanaland in the Late Cambrian/Early Ordovician: Paleomagnetic evidence
Publisher: American Geophysical Union (AGU)
Date: 02-1997
DOI: 10.1029/96TC02729
Surgical outcomes of trabeculectomy and glaucoma drainage implant for uveitic glaucoma and relationship with uveitis activity
Publisher: Wiley
Date: 27-02-2017
DOI: 10.1111/CEO.12916
Abstract: This study provides ophthalmologists who manage uveitic glaucoma with important information on factors that can affect the success of surgical management of this challenging disease. This study examines surgical outcomes of trabeculectomy and glaucoma device implant (GDI) surgery for uveitic glaucoma, in particular the effect of uveitis activity on surgical outcomes. Retrospective chart review at a tertiary institution. Eighty-two cases with uveitic glaucoma (54 trabeculectomies and 28 (GDI) surgeries) performed between 1 December 2006 and 30 November 2014. Associations of factors with surgical outcomes were examined using univariate and multivariate analysis. Surgical outcomes as defined in Guidelines from World Glaucoma Association. Average follow up was 26.4 ± 21.5 months. Overall qualified success rate of the trabeculectomies was not statistically different from GDI, being 67% and 75%, respectively (P = 0.60). Primary and secondary GDI operations showed similar success rates. The most common postoperative complication was hypotony (~30%). Active uveitis at the time of operation was higher in trabeculectomy compared with GDI group (35% vs. 14%). Active uveitis at the time of surgery did not significantly increase risk of failure for trabeculectomies. Recurrence of uveitis was significantly associated with surgical failure in trabeculectomy group (odds ratio 4.8, P = 0.02) but not in GDI group. Surgical success rate of GDI was not significantly different from trabeculectomy for uveitic glaucoma in this study. Regular monitoring, early and prolonged intensive treatment of ocular inflammation is important for surgical success particularly following trabeculectomy.
A palaeomagnetic study of Empress 1A, a stratigraphic drillhole in the Officer Basin: Evidence for a low-latitude position of Australia in the Neoproterozoic
Publisher: Elsevier BV
Date: 08-2001
1.39 Ga mafic dyke swarm in southwestern Yilgarn Craton marks Nuna to Rodinia transition in the West Australian Craton
Publisher: Elsevier BV
Date: 10-2018
Palaeomagnetic tests of tectonic models of the Tasman Fold Belt during the Neoproterozoic and palaeozoic
Publisher: Informa UK Limited
Date: 06-1993
DOI: 10.1071/EG993243
Late Cretaceous (100–89Ma) magnesian charnockites with adakitic affinities in the Milin area, eastern Gangdese: Partial melting of subducted oceanic crust and implications for crustal growth in southe
Publisher: Elsevier BV
Date: 08-2013
Proterozoic tectonics of Hainan Island in supercontinent cycles: New insights from geochronological and isotopic results
Publisher: Elsevier BV
Date: 03-2017
Palaeomagnetic results from the ca. 1130 Ma Borgmassivet intrusions in the Ahlmannryggen region of Dronning Maud Land, Antarctica, and tectonic implications
Publisher: Elsevier BV
Date: 11-2003
Genome-wide gain-of-function screen for genes that induce epithelial-to-mesenchymal transition in breast cancer.
Publisher: Impact Journals, LLC
Date: 16-08-2016
The 600-580 Ma continental rift basalts in North Qilian Shan, northwest China: Links between the Qilian-Qaidam block and SE Australia, and the reconstruction of East Gondwana
Publisher: Elsevier BV
Date: 02-2015
Post-collisional magmatism in NE Australia during Mesoproterozoic supercontinent Nuna: Insights from new zircon U Pb and Lu Hf data
Publisher: Elsevier BV
Date: 11-2022
U-Pb zircon geochronology, and geochemistry and Nd isotopic study of Neoproterozoic bimodal volcanic rocks in the Kangdian Rift of South China: Implications for the initial rifting of Rodinia
Publisher: Elsevier BV
Date: 2002
Combined poor diabetes control indicators are associated with higher risks of diabetic retinopathy and macular edema than poor glycemic control alone
Publisher: Public Library of Science (PLoS)
Date: 29-06-2017
Adalimumab for the treatment of refractory active and inactive non-infectious uveitis
Publisher: BMJ
Date: 19-02-2018
DOI: 10.1136/BJOPHTHALMOL-2017-311234
Abstract: To compare the efficacy of adalimumab in eyes with active and inactive non-infectious uveitis in the real-world setting. Multicentre, retrospective, chart review of patients with refractory non-infectious uveitis treated with adalimumab. Main outcome measures included reduction of prednisolone dose, ability to taper immunosuppressives and a composite endpoint of treatment failure encompassing active inflammatory chorioretinal or retinal vascular lesions, intraocular inflammation grade and visual acuity. Thirty-seven eyes of 22 patients were studied. Mean follow-up was 20.1 months (median: 13). Most had either posterior or panuveitis (n=12, 55%). Mean duration of uveitis at baseline was 83.2 months (median: 61), where the majority (n=15, 68%) had already been treated with two or more conventional immunosuppressive agents in addition to prednisolone. Oral prednisolone was reduced to ≤10 mg/day in 9 of 12 patients (75%) by 6 weeks. At 6 months of therapy, nine (90%) of the active eyes achieved a 2-step improvement in anterior chamber inflammation, with six (60%) demonstrating a similar improvement in vitreous haze grade. Almost all (n=17, 94%) of the initially inactive eyes maintained clinical quiescence at this time point. The incidence rate of treatment failure during follow-up was 88 per 100 eye-years for the active eyes and 24 per 100 eye-years for the initially inactive eyes. There were no serious adverse effects. Adalimumab appears to reduce the corticosteroid burden in active and inactive non-infectious uveitis in the real-world setting. Inflammatory activity at the time of adalimumab commencement may determine long-term treatment success.
Supercontinent cycles, true polar wander, and very long-wavelength mantle convection
Publisher: Elsevier BV
Date: 09-2007
Targeting the intrinsic apoptosis pathway as a strategy for melanoma therapy
Publisher: Wiley
Date: 09-04-2014
DOI: 10.1111/PCMR.12242
Cell cycle-tailored targeting of metastatic melanoma: Challenges and opportunities
Publisher: Wiley
Date: 20-04-2017
DOI: 10.1111/EXD.13303
Abstract: The advent of targeted therapies of metastatic melanoma, such as MAPK pathway inhibitors and immune checkpoint antagonists, has turned dermato-oncology from the "bad guy" to the "poster child" in oncology. Current targeted therapies are effective, although here is a clear need to develop combination therapies to delay the onset of resistance. Many antimelanoma drugs impact on the cell cycle but are also dependent on certain cell cycle phases resulting in cell cycle phase-specific drug insensitivity. Here, we raise the question: Have combination trials been abandoned prematurely as ineffective possibly only because drug scheduling was not optimized? Firstly, if both drugs of a combination hit targets in the same melanoma cell, cell cycle-mediated drug insensitivity should be taken into account when planning combination therapies, timing of dosing schedules and choice of drug therapies in solid tumors. Secondly, if the combination is designed to target different tumor cell subpopulations of a heterogeneous tumor, one drug effective in a particular subpopulation should not negatively impact on the other drug targeting another subpopulation. In addition to the role of cell cycle stage and progression on standard chemotherapeutics and targeted drugs, we discuss the utilization of cell cycle checkpoint control defects to enhance chemotherapeutic responses or as targets themselves. We propose that cell cycle-tailored targeting of metastatic melanoma could further improve therapy outcomes and that our real-time cell cycle imaging 3D melanoma spheroid model could be utilized as a tool to measure and design drug scheduling approaches.
The amalgamation of Pangea: Paleomagnetic and geological observations revisited
Publisher: Geological Society of America
Date: 24-07-2020
DOI: 10.1130/B35633.1
Abstract: The supercontinent Pangea formed by the subduction of the Iapetus and Rheic oceans between Gondwana, Laurentia, and Baltica during mid-to-late Paleozoic times. However, there remains much debate regarding how this amalgamation was achieved. Most paleogeographic models based on paleomagnetic data argue that the juxtaposition of Gondwana and Laurussia (Laurentia-Baltica) was achieved via long-lasting highly oblique convergence in the late Paleozoic. In contrast, many geology-based reconstructions suggest that the collision between the two continents was likely initiated via a Gondwanan promontory comprising the Iberian, Armorican, and Bohemian massifs, and parts of the basement units in the Alpine orogen during the Early Devonian. To help resolve this discrepancy, we present an updated compilation of high-quality paleopoles of mid-to-late Paleozoic ages (spanning Middle Ordovician and Carboniferous times) from Gondwana, Laurentia, and Baltica. These paleopoles were evaluated with the Van der Voo selection criteria, corrected for inclination error where necessary, and were used to revise their apparent polar wander (APW) paths. The revised APW paths were constructed using an innovative approach in which age errors, A95 ovals, and Q-factors of in idual paleopoles are taken into account. By combining the resulting APW paths with existing geological data and field relationships in the European Variscides, we provide mid-to-late Paleozoic paleogeographic reconstructions which indicate that the formation of Pangea was likely initiated at 400 Ma via the collision between Laurussia and a ribbon-like Gondwanan promontory that was itself formed by a scissor-like opening of the Paleotethys Ocean, and that the amalgamation culminated in the mostly orthogonal convergence between Gondwana and Laurussia.
Amalgamation between the Yangtze and Cathaysia Blocks in South China: Constraints from SHRIMP U–Pb zircon ages, geochemistry and Nd–Hf isotopes of the Shuangxiwu volcanic rocks
Publisher: Elsevier BV
Date: 10-2009
A novel mathematical model of heterogeneous cell proliferation
Publisher: Springer Science and Business Media LLC
Date: 12-03-2021
Weak orogenic lithosphere guides the pattern of plume-triggered supercontinent break-up
Publisher: Springer Science and Business Media LLC
Date: 19-11-2020
DOI: 10.1038/S43247-020-00052-Z
Abstract: The importance of nonrigid geological features (such as orogens) inside tectonic plates on Earth’s dynamic evolution lacks thorough investigation. In particular, the influence of continent-spanning orogens on (super)continental break-up remains unclear. Here we reconstruct global orogens and model their controlling effects on Pangea break-up. We show that while loci of Pangea break-up are linked to mantle plumes, development of continental rifts is guided by orogens. Rifting at Central Atlantic is driven by the modelled plume responsible for the Central Atlantic Magmatic Province (CAMP) within Pangea-forming orogens. South Atlantic rifting is controlled by necking between Pangea- and Gondwana-forming orogens with the assistance of plume-induced lithospheric weakening. Without CAMP-induced weakening, South Atlantic rifting fails between the West African and Amazonian cratons, but occurs between the West African and Saharan cratons instead. Our modeling on Pangea break-up is able to recreate present-day continental geometry through the combined effect of orogens and plume center-locations.
Oceanic and super-deep continental diamonds share a transition zone origin and mantle plume transportation
Publisher: Springer Science and Business Media LLC
Date: 20-08-2021
DOI: 10.1038/S41598-021-96286-8
Abstract: Rare oceanic diamonds are believed to have a mantle transition zone origin like super-deep continental diamonds. However, oceanic diamonds have a homogeneous and organic-like light carbon isotope signature (δ 13 C − 28 to − 20‰) instead of the extremely variable organic to lithospheric mantle signature of super-deep continental diamonds (δ 13 C − 25‰ to + 3.5‰). Here, we show that with rare exceptions, oceanic diamonds and the isotopically lighter cores of super-deep continental diamonds share a common organic δ 13 C composition reflecting carbon brought down to the transition zone by subduction, whereas the rims of such super-deep continental diamonds have the same δ 13 C as peridotitic diamonds from the lithospheric mantle. Like lithospheric continental diamonds, almost all the known occurrences of oceanic diamonds are linked to plume-induced large igneous provinces or ocean islands, suggesting a common connection to mantle plumes. We argue that mantle plumes bring the transition zone diamonds to shallower levels, where only those emplaced at the base of the continental lithosphere might grow rims with lithospheric mantle carbon isotope signatures.
Targeting glutamine transport to suppress melanoma cell growth
Publisher: Wiley
Date: 17-02-2014
DOI: 10.1002/IJC.28749
Abstract: Amino acids, especially leucine and glutamine, are important for tumor cell growth, survival and metabolism. A range of different transporters deliver each specific amino acid into cells, some of which are increased in cancer. These amino acids consequently activate the mTORC1 pathway and drive cell cycle progression. The leucine transporter LAT1/4F2hc heterodimer assembles as part of a large complex with the glutamine transporter ASCT2 to transport amino acids. In this study, we show that the expression of LAT1 and ASCT2 is significantly increased in human melanoma s les and is present in both BRAF(WT) (C8161 and WM852) and BRAF(V600E) mutant (1205Lu and 451Lu) melanoma cell lines. While inhibition of LAT1 by BCH did not suppress melanoma cell growth, the ASCT2 inhibitor BenSer significantly reduced both leucine and glutamine transport in melanoma cells, leading to inhibition of mTORC1 signaling. Cell proliferation and cell cycle progression were significantly reduced in the presence of BenSer in melanoma cells in 2D and 3D cell culture. This included reduced expression of the cell cycle regulators CDK1 and UBE2C. The importance of ASCT2 expression in melanoma was confirmed by shRNA knockdown, which inhibited glutamine uptake, mTORC1 signaling and cell proliferation. Taken together, our study demonstrates that ASCT2-mediated glutamine transport is a potential therapeutic target for both BRAF(WT) and BRAF(V600E) melanoma.
A Permian layered intrusive complex in the western Tarim Block, northwestern China: Product of a Ca. 275-Ma mantle plume?
Publisher: University of Chicago Press
Date: 05-2008
DOI: 10.1086/587726
Age and origin of high Ba-Sr appinite-granites at the northwestern margin of the Tibet Plateau: Implications for early Paleozoic tectonic evolution of the Western Kunlun orogenic belt
Publisher: Elsevier BV
Date: 2008
Middle Neoproterozoic syn-rifting volcanic rocks in Guangfeng, South China: Petrogenesis and tectonic significance
Publisher: Cambridge University Press (CUP)
Date: 08-04-2008
DOI: 10.1017/S0016756808004561
Abstract: Middle Neoproterozoic igneous rocks are widespread in South China, but their petrogenesis and tectonic implications are still highly controversial. The Guangfeng middle Neoproterozoic volcano-sedimentary succession was developed on a rare Sibaoan metamorphic basement (the Tianli Schists) in the southeastern Yangtze Block, South China. This paper reports geochronological, geochemical and Nd isotopic data for the volcanic rocks in this succession. The volcanic rocks consist of alkaline basalts, andesites and peraluminous rhyolites. SHRIMP U–Pb zircon age determinations indicate that they were erupted at 827±14 Ma, coeval with a widespread episode of anorogenic magmatism in South China. Despite showing Nb–Ta depletion relative to La and Th, the alkaline basalts are characterized by highly positive ɛNd(T) values (+3.1 to +6.0), relatively high TiO 2 and Nb contents and high Zr/Y and super-chondritic Nb/Ta ratios, suggesting their derivation from a slab melt-metasomatized subcontinental lithospheric mantle source in an intracontinental rifting setting. The andesites have significantly negative ɛNd(T) values (−9.3 to −11.1) and a wide range of SiO 2 contents (57.6–65.6%). They were likely generated by the mixing of fractionated basaltic melts with felsic melts derived from the Archaean metasedimentary rocks in the middle to lower crust. The rhyolites are highly siliceous and peraluminous. They are characterized by depletion in Nb, Ta, Sr, P and Ti and relatively high ɛNd(T) values (−3.0 to −4.8), broadly similar to those of the adjacent c. 820 Ma peraluminous granitoids derived from the Mesoproterozoic to earliest Neoproterozoic sedimentary source at relatively shallow levels. We conclude that the Guangfeng volcanic suite is a magmatic response of variant levels of continental lithosphere (including lithospheric mantle and the lower-middle to upper crust) to the middle Neoproterozoic intracontinental rifting possibly caused by mantle plume activity.
Eocene north–south trending dikes in central Tibet: New constraints on the timing of east–west extension with implications for early plateau uplift?
Publisher: Elsevier BV
Date: 09-2010
Late Neoproterozoic 40 intraplate rotation within Australia allows for a tighter-fitting and longer-lasting Rodinia
Publisher: Geological Society of America
Date: 03-12-2010
DOI: 10.1130/G31461.1
Primary retinoschisis with vascular changes mimicking neovascularization, illustrated with multimodal imaging
Publisher: Wiley
Date: 04-10-2016
DOI: 10.1111/CEO.12819
Cell Cycle Phase-Specific Drug Resistance as an Escape Mechanism of Melanoma Cells
Publisher: Elsevier BV
Date: 07-2016
DOI: 10.1016/J.JID.2016.02.805
Abstract: The tumor microenvironment is characterized by cancer cell subpopulations with heterogeneous cell cycle profiles. For ex le, hypoxic tumor zones contain clusters of cancer cells that arrest in G1 phase. It is conceivable that neoplastic cells exhibit differential drug sensitivity based on their residence in specific cell cycle phases. In this study, we used two-dimensional and organotypic melanoma culture models in combination with fluorescent cell cycle indicators to investigate the effects of cell cycle phases on clinically used drugs. We demonstrate that G1-arrested melanoma cells, irrespective of the underlying cause mediating G1 arrest, are resistant to apoptosis induced by the proteasome inhibitor bortezomib or the alkylating agent temozolomide. In contrast, G1-arrested cells were more sensitive to mitogen-activated protein kinase pathway inhibitor-induced cell death. Of clinical relevance, pretreatment of melanoma cells with a mitogen-activated protein kinase pathway inhibitor, which induced G1 arrest, resulted in resistance to temozolomide or bortezomib. On the other hand, pretreatment with temozolomide, which induced G2 arrest, did not result in resistance to mitogen-activated protein kinase pathway inhibitors. In summary, we established a model to study the effects of the cell cycle on drug sensitivity. Cell cycle phase-specific drug resistance is an escape mechanism of melanoma cells that has implications on the choice and timing of drug combination therapies.
CA. 850 MA BIMODAL VOLCANIC ROCKS IN NORTHEASTERN JIANGXI PROVINCE, SOUTH CHINA: INITIAL EXTENSION DURING THE BREAKUP OF RODINIA?
Publisher: American Journal of Science (AJS)
Date: 11-2010
DOI: 10.2475/09.2010.08
Long-lived connection between the North China and North Australian cratons in supercontinent Nuna: paleomagnetic and geological constraints
Publisher: Elsevier BV
Date: 07-2019
New late Palaeozoic palaeomagnetic results from Cratonic Australia, and revision of the Gondwanan apparent polar wander path
Publisher: Informa UK Limited
Date: 06-1993
DOI: 10.1071/EG993263
Decoupling between Oxygen and Radiogenic Isotopes: Evidence for Generation of Juvenile Continental Crust by Partial Melting of Subducted Oceanic Crust
Publisher: Springer Science and Business Media LLC
Date: 10-2021
Discovery of a selective inhibitor of oncogenic B-Raf kinase with potent antimelanoma activity
Publisher: Proceedings of the National Academy of Sciences
Date: 26-02-2008
Abstract: BRAF V600E is the most frequent oncogenic protein kinase mutation known. Furthermore, inhibitors targeting “active” protein kinases have demonstrated significant utility in the therapeutic repertoire against cancer. Therefore, we pursued the development of specific kinase inhibitors targeting B-Raf, and the V600E allele in particular. By using a structure-guided discovery approach, a potent and selective inhibitor of active B-Raf has been discovered. PLX4720, a 7-azaindole derivative that inhibits B-Raf V600E with an IC 50 of 13 nM, defines a class of kinase inhibitor with marked selectivity in both biochemical and cellular assays. PLX4720 preferentially inhibits the active B-Raf V600E kinase compared with a broad spectrum of other kinases, and potent cytotoxic effects are also exclusive to cells bearing the V600E allele. Consistent with the high degree of selectivity, ERK phosphorylation is potently inhibited by PLX4720 in B-Raf V600E -bearing tumor cell lines but not in cells lacking oncogenic B-Raf. In melanoma models, PLX4720 induces cell cycle arrest and apoptosis exclusively in B-Raf V600E -positive cells. In B-Raf V600E -dependent tumor xenograft models, orally dosed PLX4720 causes significant tumor growth delays, including tumor regressions, without evidence of toxicity. The work described here represents the entire discovery process, from initial identification through structural and biological studies in animal models to a promising therapeutic for testing in cancer patients bearing B-Raf V600E -driven tumors.
Four-dimensional context of Earth's supercontinents
Publisher: Geological Society of London
Date: 2016
DOI: 10.1144/SP424.12
Palaeomagnetism and geochronology of mid-neoproterozoic yanbian dykes, South China: Implications for a c. 820-800 Ma true polar wander event and the reconstruction of Rodinia
Publisher: Geological Society of London
Date: 10-12-2016
DOI: 10.1144/SP424.11
Primary Sclerosing Cholangitis and Uveitis: A Case Series
Publisher: Elsevier BV
Date: 03-2007
DOI: 10.1016/J.AJO.2006.09.055
Abstract: To report the cases of six patients with primary sclerosing cholangitis and uveitis. Retrospective observational case series. Two index cases were identified from the Uveitis Clinic of the Casey Eye Institute, Oregon Health and Science University and another from the Portland area. Additional cases were identified through a web-based survey of members of the American Uveitis Society. Three males and three females were identified. Five of six patients were diagnosed with uveitis prior to primary sclerosing cholangitis. Four had unilateral eye involvement. Five had insidious onset. All had persistent duration. Clinical course was chronic for three, recurrent for two, and chronic-recurrent in one. Vitreous inflammation was prominent in five. Although the number of patients who were studied is limited, there appears to be an association between primary sclerosing cholangitis and uveitis. Further studies are required to confirm such an association.
Australian Palaeozoic palaeomagnetism and tectonics-II. A revised apparent polar wander path and palaeogeography
Publisher: Elsevier BV
Date: 1990
Friends or foes: IL ‐10 and TGF ‐β in melanoma
Publisher: Wiley
Date: 27-03-2015
DOI: 10.1111/EXD.12661
Persister state-directed transitioning and vulnerability in melanoma
Publisher: Cold Spring Harbor Laboratory
Date: 04-2020
DOI: 10.1101/2020.04.01.999847
Abstract: Melanoma is a highly plastic tumor characterized by dynamic interconversion of different cell identities depending on the biological context. For ex le, melanoma cells with high expression of the H3K4 demethylase KDM5B (JARID1B) rest in a slow-cycling, yet reversible persister state. Over time, KDM5B high cells can promote rapid tumor repopulation with equilibrated KDM5B expression heterogeneity. The cellular identity of KDM5B high persister cells has not been studied so far, missing an important cell state-directed treatment opportunity in melanoma. Here, we have established a doxycycline-titratable system for genetic induction of permanent intratumor expression of KDM5B and screened for chemical agents that phenocopy this effect. Transcriptional profiling and cell functional assays confirmed that the dihydropyridine phenoxyethyl 4-(2-fluorophenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexa-hydro-quinoline-3-carboxylate (termed Cpd1) supports high KDM5B expression and directs melanoma cells towards differentiation along the melanocytic lineage and to cell cycle-arrest. The high KDM5B state additionally prevents cell proliferation through negative regulation of cytokinetic abscission. Moreover, treatment with Cpd1 promoted the expression of the melanocyte-specific tyrosinase gene specifically sensitizing melanoma cells for the tyrosinase-processed antifolate prodrug 3-O-(3,4,5-trimethoxybenzoyl)-(-)-epicatechin (TMECG). In summary, our study provides proof-of-concept for a new dual hit strategy in melanoma, in which persister state-directed transitioning limits tumor growth and plasticity and primes melanoma cells towards lineage-specific elimination.
Petrogenesis of early Jurassic basalts in southern Jiangxi Province, South China: Implications for the thermal state of the Mesozoic mantle beneath South China
Publisher: Elsevier BV
Date: 07-2016
Clinical controversy: to treat, or not to treat? That is the tuberculosis question
Publisher: Wiley
Date: 09-2012
Grenvillian continental collision in South China: New SHRIMP U-Pb zircon results and implications for the configuration of Rodinia
Publisher: Geological Society of America
Date: 2002
Modulation of NOXA and MCL-1 as a strategy for sensitizing melanoma cells to the BH3-mimetic ABT-737.
Publisher: American Association for Cancer Research (AACR)
Date: 31-01-2012
DOI: 10.1158/1078-0432.CCR-11-1166
Abstract: Purpose: Drug resistance in melanoma is commonly attributed to ineffective apoptotic pathways. Inhibiting antiapoptotic BCL-2 and its relatives is an attractive strategy for sensitizing lymphoid malignancies to drugs but it has been largely unsuccessful for melanoma and other solid tumors. ABT-737, a small-molecule BH3-mimetic, selectively inhibits BCL-2, BCL-XL, and BCL-w and shows promise for treating leukemia, lymphoma, and small-cell lung cancer. Melanoma cells are insensitive to ABT-737, but MCL-1 inhibition reportedly increases the sensitivity of other tumors to the compound. Experimental Design: The efficacy of MCL-1 and BFL-1 inhibition for sensitizing melanoma cells to ABT-737 was investigated by short hairpin RNA–mediated knockdown or overexpression of their antagonist NOXA in two-dimensional cell culture, a three-dimensional organotypic spheroid model, and an in vivo model. Results: MCL-1 downregulation or NOXA overexpression strongly sensitized melanoma cells to ABT-737 in vitro. NOXA-inducing cytotoxic drugs also strongly sensitized melanomas to ABT-737 but, surprisingly, not vice versa. The drugs most suitable are not necessarily those normally used to treat melanoma. Resistance to ABT-737 occurred quickly in three-dimensional melanoma spheroids through reduced NOXA expression, although experiments with both xenografts and three-dimensional spheroids suggest that penetration of ABT-737 into tumor masses may be the principal limitation, which may be obviated through use of more diffusible BH3-mimetics. Conclusion: Sensitization of tumors to BH3-mimetics by cytotoxic drugs that induce NOXA is a therapeutic strategy worth exploring for the treatment of melanoma and other solid cancers. Clin Cancer Res 18(3) 783–95. ©2011 AACR.
PTEN: A novel target for vitamin D in melanoma
Publisher: Elsevier BV
Date: 04-2022
DOI: 10.1016/J.JSBMB.2022.106059
Abstract: Melanoma is the most dangerous form of skin cancer, with poor prognosis in advanced stages. Vitamin D, also produced by ultraviolet radiation, is known for its anti-proliferative properties in some cancers including melanoma. While vitamin D deficiency has been associated with advanced melanoma stage and higher levels of vitamin D have been associated with better outcomes, the role for vitamin D in melanoma remains unclear. Vitamin D synthesis is initiated upon UVB exposure of skin cells and results in formation of the active metabolite 1,25-dihydroxyvitamin D3 (1,25D). We have previously demonstrated that 1,25D plays a role in protection against ultraviolet radiation-induced DNA damage, immune suppression, and skin carcinogenesis. In this study 1,25D significantly reduced cell viability and increased caspase levels in human melanoma cell lines. This effect was not present in cells that lacked both phosphatase and tensin homolog deleted on chromosome 10 (PTEN), a well-known tumour suppressor, and the vitamin D receptor (VDR). PTEN is frequently lost or mutated in melanoma. Incubation of selected melanoma cell lines with 1,25D resulted in significant increases in PTEN levels and downregulation of the AKT pathway and its downstream effectors. This suggests that 1,25D may act to reduce melanoma cell viability by targeting PTEN.
Rising trends of endogenous Klebsiella pneumoniae endophthalmitis in Australia
Publisher: Wiley
Date: 15-09-2016
DOI: 10.1111/CEO.12827
Abstract: Endogenous Klebsiella pneumoniae endophthalmitis (EKPE) is a well-known entity in South-East Asia. We demonstrate a range of differing clinical features and outcomes of EKPE, and highlight the increasing incidence of EKPE in major centres in Sydney and Melbourne, Australia. Retrospective observational case study and case series in the hospital setting. Four cases of EKPE. EKPE cases from 2005 to 2015 were identified through established endophthalmitis databases as well as hospital-based microbiological searches. EKPE cases were confirmed with positive K. pneumoniae intraocular s les. Rising trends of EKPE were noted in major centres in Australia. Six eyes of four patients with EKPE from January 2011 to December 2015 are reported. The mean age was 49 years (range 43-58 years). Two patients had bilateral involvement. There were systemic symptoms up to 10 days prior to ocular symptoms. The source of sepsis in all cases was a hepatic abscess. Two patients had diabetes mellitus. Five eyes had hypopyon panuveitis on presentation. All eyes underwent vitrectomy. The patient with the most delayed presentation underwent enucleation following globe perforation. Final best corrected visual acuity (BCVA) in one patient with bilateral EKPE was light perception (LP) only. The other three eyes had BCVA in at least one eye of 6/24 or better. EKPE is an emerging condition in Australia. Although rare, EKPE is a sight-threatening and potentially life-threatening emergency that can initially present to ophthalmologists. One should suspect EKPE in septic patients with a B-scan showing a vitreous or retinal abscess.
Intracontinental eocene-oligocene porphyry Cu mineral systems of Yunnan, Western Yangtze Craton, China: Compositional characteristics, sources, and implications for continental collision metallogeny
Publisher: Society of Economic Geologists
Date: 30-09-2013
Phenotypic melanoma heterogeneity is regulated through cell-matrix interaction-dependent changes in tumor microarchitecture
Publisher: Cold Spring Harbor Laboratory
Date: 11-06-2020
DOI: 10.1101/2020.06.09.141747
Abstract: Phenotypic heterogeneity of cancer cells plays a critical role in shaping treatment response. This type of heterogeneity is organized spatially with specific phenotypes, such as sharply demarcated clusters of proliferating and cell cycle-arrested cells, predominating within discrete domains within a tumor. What determines the occurrence of specific tumor cell phenotypes in distinct microdomains of solid cancers is poorly understood. Here, we show that in melanoma spatial organization of phenotypic heterogeneity is dictated by the expression and activity of MITF. We reveal that this lineage survival oncogene controls ECM composition and organization, and ROCK-driven mechanotransduction through focal adhesion maturation and actin cytoskeleton functionality. In turn, altered tumor microarchitecture and structural integrity impact tumor solid stress which then mediates phenotypic heterogeneity through p27 Kip1 . Rho-ROCK-myosin signaling is necessary to transmit the effect of the reciprocal cell-ECM regulation into phenotypic heterogeneity. Our findings place cell-ECM crosstalk as a central driver of phenotypic tumor heterogeneity. Phenotypic heterogeneity is a major culprit of cancer therapy failure. We demonstrate that phenotypic heterogeneity is controlled through tumor cell-ECM crosstalk resulting in altered tumor microarchitecture, mechanotransduction and Rho-ROCK-myosin signaling. Melanoma shares these physical properties with any solid cancer underscoring the importance of our findings for therapeutically targeting this phenomenon.
Geochemical evidence for a widespread mantle re-enrichment 3.2 billion years ago: implications for global-scale plate tectonics
Publisher: Springer Science and Business Media LLC
Date: 11-06-2020
DOI: 10.1038/S41598-020-66324-Y
Abstract: Progressive mantle melting during the Earth’s earliest evolution led to the formation of a depleted mantle and a continental crust enriched in highly incompatible elements. Re-enrichment of Earth’s mantle can occur when continental crustal materials begin to founder into the mantle by either subduction or, to a lesser degree, by delamination processes, profoundly affecting the mantle’s trace element and volatile compositions. Deciphering when mantle re-enrichment/refertilization became a global-scale process would reveal the onset of efficient mass transfer of crust to the mantle and potentially when plate tectonic processes became operative on a global-scale. Here we document the onset of mantle re-enrichment/refertilization by comparing the abundances of petrogenetically significant isotopic values and key ratios of highly incompatible elements compared to lithophile elements in Archean to Early-Proterozoic mantle-derived melts (i.e., basalts and komatiites). Basalts and komatiites both record a rapid-change in mantle chemistry around 3.2 billion years ago (Ga) signifying a fundamental change in Earth geodynamics. This rapid-change is recorded in Nd isotopes and in key trace element ratios that reflect a fundamental shift in the balance between fluid-mobile and incompatible elements (i.e., Ba/La, Ba/Nb, U/Nb, Pb/Nd and Pb/Ce) in basaltic and komatiitic rocks. These geochemical proxies display a significant increase in magnitude and variability after ~3.2 Ga. We hypothesize that rapid increases in mantle heterogeneity indicate the recycling of supracrustal materials back into Earth’s mantle via subduction. Our new observations thus point to a ≥ 3.2 Ga onset of global subduction processes via plate tectonics.
Breakup of rodinia
Publisher: Springer Netherlands
Date: 2011
A stochastic mathematical model of 4D tumour spheroids with real-time fluorescent cell cycle labelling
Publisher: Cold Spring Harbor Laboratory
Date: 29-11-2021
DOI: 10.1101/2021.11.28.470300
Abstract: In vitro tumour spheroid experiments have been used to study avascular tumour growth and drug design for the last 50 years. Unlike simpler two-dimensional cell cultures, tumour spheroids exhibit heterogeneity within the growing population of cells that is thought to be related to spatial and temporal differences in nutrient availability. The recent development of real-time fluorescent cell cycle imaging allows us to identify the position and cell cycle status of in idual cells within the growing population, giving rise to the notion of a four-dimensional (4D) tumour spheroid. In this work we develop the first stochastic in idual-based model (IBM) of a 4D tumour spheroid and show that IBM simulation data qualitatively and quantitatively compare very well with experimental data from a suite of 4D tumour spheroid experiments performed with a primary human melanoma cell line. The IBM provides quantitative information about nutrient availability within the spheroid, which is important because it is very difficult to measure these data in standard tumour spheroid experiments. Software required to implement the IBM is available on GitHub, github.com/ProfMJSimpson/4DFUCCI .
Asthenosphere–lithosphere interaction triggered by a slab window during ridge subduction: Trace element and Sr–Nd–Hf–Os isotopic evidence from Late Carboniferous tholeiites in the western Junggar area
Publisher: Elsevier BV
Date: 05-2012
Magnetic fabric in mid-Cambrian rocks of the Central Flinders Zone and implications for the regional tectonic history
Publisher: Elsevier BV
Date: 08-1993
Endogenous Replication Stress Marks Melanomas Sensitive to CHEK1 Inhibitors In Vivo
Publisher: American Association for Cancer Research (AACR)
Date: 14-06-2018
DOI: 10.1158/1078-0432.CCR-17-2701
Abstract: Purpose: Checkpoint kinase 1 inhibitors (CHEK1i) have single-agent activity in vitro and in vivo. Here, we have investigated the molecular basis of this activity. Experimental Design: We have assessed a panel of melanoma cell lines for their sensitivity to the CHEK1i GNE-323 and GDC-0575 in vitro and in vivo. The effects of these compounds on responses to DNA replication stress were analyzed in the hypersensitive cell lines. Results: A subset of melanoma cell lines is hypersensitive to CHEK1i-induced cell death in vitro, and the drug effectively inhibits tumor growth in vivo. In the hypersensitive cell lines, GNE-323 triggers cell death without cells entering mitosis. CHEK1i treatment triggers strong RPA2 hyperphosphorylation and increased DNA damage in only hypersensitive cells. The increased replication stress was associated with a defective S-phase cell-cycle checkpoint. The number and intensity of pRPA2 Ser4/8 foci in untreated tumors appeared to be a marker of elevated replication stress correlated with sensitivity to CHEK1i. Conclusions: CHEK1i have single-agent activity in a subset of melanomas with elevated endogenous replication stress. CHEK1i treatment strongly increased this replication stress and DNA damage, and this correlated with increased cell death. The level of endogenous replication is marked by the pRPA2Ser4/8 foci in the untreated tumors, and may be a useful marker of replication stress in vivo. Clin Cancer Res 24(12) 2901–12. ©2018 AACR.
Petrology, geochronology and geochemistry of ca. 780Ma A-type granites in South China: Petrogenesis and implications for crustal growth during the breakup of the supercontinent Rodinia
Publisher: Elsevier BV
Date: 04-2010
Basin redox and primary productivity within the Mesoproterozoic Roper Seaway
Publisher: Elsevier BV
Date: 11-2016
H3K4me3 remodeling induced acquired resistance through O-GlcNAc transferase
Publisher: Elsevier BV
Date: 11-2023
Interobserver Agreement Among Uveitis Experts on Uveitic Diagnoses: The Standardization of Uveitis Nomenclature Experience
Publisher: Elsevier BV
Date: 02-2018
The Influence of Intravitreal Ranibizumab on Inflammation-associated Cytokine Concentrations in Eyes With Diabetic Macular Edema
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 14-11-2018
Abstract: To evaluate the effect of intravitreal ranibizumab injections on aqueous concentrations of angiogenic or inflammatory cytokines in patients with diabetic macular edema (DME). Thirty eyes of 25 patients with center-involved DME were recruited to the study. All had a central macular thickness (CMT) of >300 μm and best-corrected visual acuity (BCVA) between 28 and 70 logMAR letters (Snellen equivalent 20/320-20/40). At baseline, all eyes had 0.1 mL of aqueous collected before ranibizumab treatment. At week 4, a second ranibizumab injection was administered and at week 8, aqueous s ling was repeated before a third ranibizumab injection. From week 12, all eyes were followed at 4-weekly intervals and the need for ranibizumab treatment was determined by BCVA and CMT measurements. Levels of 32 cytokines were assessed at baseline and at week 8 using a multiplex array assay. Following two consecutive ranibizumab injections, there was a statistically significant reduction in VEGF (P < 0.00001), as well as IL-1β (P = 0.00006), IL-7 (P = 0.00002), IL-8 (P = 0.00023), IL-10 (P < 0.00001), IL-12 (P < 0.00001), IL-17 (P = 0.00024), MCP-1 (P = 0.00023), and TNF-α (P < 0.00001). There was also an upregulation of soluble VEGF receptor-2 (P = 0.00004). A P < 0.0015 was considered significant in this study. Ranibizumab treatment influences various inflammatory cytokine concentrations in addition to reducing aqueous VEGF concentrations in patients with DME. This may contribute to its therapeutic effect in patients with DME.
From Rodinia to Gondwanaland: A tale of detrital zircon provenance analyses from the southern Nanhua Basin, South China
Publisher: American Journal of Science (AJS)
Date: 2014
DOI: 10.2475/01.2014.08
Real‐time cell cycle imaging during melanoma growth, invasion, and drug response
Publisher: Wiley
Date: 27-06-2014
DOI: 10.1111/PCMR.12274
Abstract: Solid cancers are composed of heterogeneous zones containing proliferating and quiescent cells. Despite considerable insight into the molecular mechanisms underlying aberrant cell cycle progression, there is limited understanding of the relationship between the cell cycle on the one side, and melanoma cell motility, invasion, and drug sensitivity on the other side. Utilizing the fluorescent ubiquitination-based cell cycle indicator (FUCCI) to longitudinally monitor proliferation and migration of melanoma cells in 3D culture and in vivo, we found that invading melanoma cells cycle actively, while G1-arrested cells showed decreased invasion. Melanoma cells in a hypoxic environment or treated with mitogen-activated protein kinase pathway inhibitors remained G1-arrested for extended periods of time, with proliferation and invasion resuming after re-exposure to a more favorable environment. We challenge the idea that the invasive and proliferative capacity of melanoma cells are mutually exclusive and further demonstrate that a reversibly G1-arrested subpopulation survives in the presence of targeted therapies.
On the genetic classification and tectonic implications of the Early Yanshanian granitoids in the Nanling Range, South China
Publisher: Springer Science and Business Media LLC
Date: 07-2007
Origin of arc magmatic signature: A temperature-dependent process for trace element (re)-mobilization in subduction zones
Publisher: Springer Science and Business Media LLC
Date: 08-05-2019
DOI: 10.1038/S41598-019-43605-9
Abstract: Serpentinite is a major carrier of fluid-mobile elements in subduction zones, which influences the geochemical signature of arc magmatism (e.g. high abundances of Li, Ba, Sr, B, As, Mo and Pb). Based on results from Neoproterozoic serpentinites in the Arabian-Nubian Shield, we herein report the role of antigorite in the transportation of fluid-mobile elements (FME) and light rare earth elements (LREE) from the subducted slab to arc-related magma during subduction. The serpentinites contain two generations of antigorites: the older generation is coarse-grained, formed at a temperature range of 165–250 °C and is enriched in Li, Rb, Ba and Cs, whereas the younger generation is finer-grained, formed at higher temperature conditions (425–475 °C) and has high concentrations of B, As, Sb, Mo, Pb, Sr and LREE. Magnesite, on the other hand, remains stable at sub-arc depths beyond the stability field of both antigorites, and represents a potential reservoir of FME and LREE for deeper mantle melts. Magnesite has high FME and LREE absorbing capacity (over 50–60%) higher than serpentine phases. Temperature is the main controlling factor for stability of these minerals and therefore the release of these elements from subducted slabs into arc magmatism. As the liberation of these elements varies along the length of the slab, the resulting cross-arc geochemical variation trend can help to determine the subduction polarity of ancient arcs.
Formation of juvenile continental crust in northern Nubian Shield: New evidence from granitic zircon U-Pb-Hf-O isotopes
Publisher: Elsevier BV
Date: 09-2022
Australian Palaeozoic palaeomagnetism and tectonics-I. Tectonostratigraphic terrane constraints from the Tasman Fold Belt
Publisher: Elsevier BV
Date: 1990
A Mesozoic Andean-type orogenic cycle in southeastern China as recorded by granitoid evolution
Publisher: American Journal of Science (AJS)
Date: 2014
DOI: 10.2475/01.2014.06
SIMS zircon U–Pb ages, geochemistry and Nd–Hf isotopes of ca. 1.0Ga mafic dykes and volcanic rocks in the Huili area, SW China: Origin and tectonic significance
Publisher: Elsevier BV
Date: 02-2016
Reliability of Palaeozoic palaeomagnetic poles and APWP of Gondwanaland
Publisher: Elsevier BV
Date: 11-1990
Cell–Cell and Cell–Matrix Contacts in Melanoma and the Tumor Microenvironment
Publisher: Springer Vienna
Date: 2011
Systemic Associations of Sarcoid Uveitis: Correlation With Uveitis Phenotype and Ethnicity
Publisher: Elsevier BV
Date: 09-2021
DOI: 10.1016/J.AJO.2021.03.003
Abstract: To examine systemic associations of sarcoid uveitis and association with uveitis clinical phenotype and ethnicity. Retrospective cross-sectional study. A total of 362 subjects with definite or presumed sarcoid uveitis from Moorfields Eye Hospital, Royal Victorian Eye and Ear, and Auckland District Health Board. Data were collected from the review of clinical notes, imaging, and investigations. Sarcoidosis was diagnosed in accordance with the International Workshop on Ocular Sarcoidosis guidelines. Diagnosis of associated systemic disease secondary to sarcoidosis. A total of 362 subjects with sarcoid uveitis were identified. Median age was 46 years, and 226 (62.4%) were female. Granulomatous anterior uveitis (47.8%), intermediate uveitis with snowballs (46.4%), and multifocal choroiditis (43.1%) were the most frequent clinical presentations, and disease was bilateral in 313 (86.5%). Periphlebitis was observed in 21.0%, and solitary optic nerve or choroidal granuloma in 11.3%. Lung parenchymal disease was diagnosed in 200 subjects (55.2%), cutaneous sarcoid in 98 (27.1%), sarcoid arthritis in 57 (15.7%), liver involvement in 21 (5.8%), neurosarcoid in 49 (13.5%), and cardiac sarcoid in 16 subjects (4.4%). Subjects with cardiac sarcoid were less likely to have granulomatous anterior uveitis (P = .017). Caucasian subjects were older at presentation (48 vs 41 years P = .009), had less granulomatous anterior uveitis (26.4% vs 51.7% P < .001), and were less likely to present with cutaneous involvement (23.1% vs 35.4% P = .040). Ophthalmologists need to be aware of the systemic associations of sarcoid uveitis, in particular potentially life-threatening complications such as cardiac sarcoidosis. Differences observed in uveitis phenotype and between ethnicities require further investigation.
Clinical Features of Scleritis Across the Asia-Pacific Region
Publisher: Informa UK Limited
Date: 28-06-2018
Paleomagnetism of the Hart Dolerite (Kimberley, Western Australia) - A two-stage assembly of the supercontinent Nuna?
Publisher: Elsevier BV
Date: 08-2019
Post-250 Ma thermal evolution of the central Cathaysia Block (SE China) in response to flat-slab subduction at the proto-Western Pacific margin
Publisher: Elsevier BV
Date: 11-2019
Onset of aridity in southern Western Australia - A preliminary palaeomagnetic appraisal
Publisher: Elsevier BV
Date: 09-1998
Diabetic Macular Edema at the time of Cataract Surgery trial: a prospective, randomized clinical trial of intravitreous bevacizumab versus triamcinolone in patients with diabetic macular oedema at the time of cataract surgery – preliminary 6 month results
Publisher: Wiley
Date: 29-03-2016
DOI: 10.1111/CEO.12720
Abstract: To compare visual and anatomical outcomes between intravitreous bevacizumab (BVB, Avastin) and triamcinolone (TA, Triesence) when administered at the time of cataract surgery in patients with diabetic macular oedema (DME). Prospective, single-masked, randomized clinical trial at The Royal Victorian Eye and Ear Hospital, Melbourne. Patients with clinically significant cataract and either centre-involving DME or DME treated within the previous 24 months. Participants were randomized 1:1 to receive intravitreous BVB 1.25 mg or TA 4 mg during cataract surgery, and at subsequent review if required over 6 months. Change in central macular thickness (CMT) and best corrected visual acuity at 6 months. Forty-one patients (mean age 66.4 years, 73.2% male) were recruited. Visual acuity and CMT were similar between groups at baseline (P > 0.2).After six months, both groups gained vision (mean +21.4 letters in TA group P < 0.0001, +12.5 letters in BVB, P = 0.002), with no significant difference between groups (P = 0.085). In addition, 60.9% of eyes receiving TA achieved a VA of ≥6/12 compared to 73.3% in the BVB group (P = 0.501). However, only TA was associated with a sustained reduction in CMT (-43.8-µm reduction TA vs. +37.3-µm increase BVB, P = 0.006 over 6 months). Following surgery, additional injections were required in 70.6% of participants in the BVB group, compared to 16.7% in the TA group (P < 0.0001). Three patients in the TA group experienced a rise of IOP over 21 mmHg (12.5%) during the 6-month follow-up BVB had no cases (P = 0.130). There were no cases of endophthalmitis in either group. When administered at the time of cataract surgery in patients with DME, at 6 months both TA and BVB improve visual acuity however, only TA results in a sustained reduction in CMT. Further follow-up will determine whether this translates into better long-term visual outcomes in the TA group.
Geochemical, Sr-Nd-Pb, and Zircon Hf-O Isotopic Compositions of Eocene-Oligocene Shoshonitic and Potassic Adakite-like Felsic Intrusions in Western Yunnan, SW China: Petrogenesis and Tectonic Implicat
Publisher: Oxford University Press (OUP)
Date: 15-03-2013
Takotsubo syndrome caused by subconjunctival injection of a mydricaine analogue
Publisher: Wiley
Date: 06-04-2016
DOI: 10.1111/CEO.12729
Precambrian tectonics of East Asia and relevance to supercontinent evolution
Publisher: Elsevier BV
Date: 10-04-2003
Real-time cell cycle imaging in a 3D cell culture model of melanoma
Publisher: Springer New York
Date: 2017
DOI: 10.1007/978-1-4939-7021-6_29
Abstract: Aberrant cell cycle progression is a hallmark of solid tumors therefore, cell cycle analysis is an invaluable technique to study cancer cell biology. However, cell cycle progression has been most commonly assessed by methods that are limited to temporal snapshots or that lack spatial information. Here, we describe a technique that allows spatiotemporal real-time tracking of cell cycle progression of in idual cells in a multicellular context. The power of this system lies in the use of 3D melanoma spheroids generated from melanoma cells engineered with the fluorescent ubiquitination-based cell cycle indicator (FUCCI). This technique allows us to gain further and more detailed insight into several relevant aspects of solid cancer cell biology, such as tumor growth, proliferation, invasion, and drug sensitivity.
Sarcoidosis-related Uveitis: Clinical Presentation, Disease Course, and Rates of Systemic Disease Progression After Uveitis Diagnosis
Publisher: Elsevier BV
Date: 02-2019
DOI: 10.1016/J.AJO.2018.09.013
Abstract: To document the clinical presentation, treatment, and visual outcome of sarcoid uveitis and to determine the timing and potential risk factors of sarcoidosis progression to symptomatic systemic disease from the time of sarcoid uveitis diagnosis. Retrospective, interventional case series. Subjects: Patients with dual diagnoses of uveitis and presumed/biopsy-proven sarcoidosis. Retrospective review of 143 patient records from the Royal Victorian Eye and Ear Hospital and Eye Surgery Associates in Melbourne, Australia, between October 1990 and April 2014 coded with the dual diagnoses of uveitis and sarcoidosis. Only patients with uveitis and presumed or biopsy-proven sarcoidosis (N = 113) were included. Ascertainment of rate and time (months) to the development of symptomatic systemic sarcoidosis from uveitis onset comparison of the patient demographics, characteristics of uveitis, treatment, and visual outcome between those who developed systemic sarcoidosis and those who remained systemically asymptomatic. Uveitis was the initial presenting complaint of sarcoidosis in 78.8% (n = 89). Twenty-three patients had concurrent undiagnosed systemic disease at presentation and 29 subsequently developed symptomatic sarcoidosis in an organ uninvolved at uveitis onset. The median time to the development of symptomatic systemic sarcoidosis was 12 months. No statistically significant association was ascertained between any particular uveitis characteristic and extraocular sarcoidosis progression. Uveitis was the initial presentation of sarcoidosis in the vast majority of our subjects. Concurrent undiagnosed systemic sarcoidosis was common at the time of uveitis onset. A high index of suspicion for subsequent systemic progression should also be maintained, especially within the first 5 years of the uveitis diagnosis.
Rational laboratory testing in uveitis: A Bayesian analysis
Publisher: Elsevier BV
Date: 09-2021
DOI: 10.1016/J.SURVOPHTHAL.2021.02.002
Abstract: Uveitis encompasses a heterogeneous group of clinical entities with the common feature of intraocular inflammation. In addition to patient history and examination, a focused set of laboratory investigations is frequently necessary to establish a specific diagnosis. There is limited consensus among uveitis specialists regarding appropriate laboratory evaluation for many distinct patient presentations. The appropriateness of a laboratory test for a given case of uveitis will depend on patient-specific as well as epidemiologic factors. Bayesian analysis is a widely used framework for the interpretation of laboratory testing, but is seldom adhered to in clinical practice. Bayes theorem states that the predictive value of a particular laboratory test depends on the sensitivity and specificity of that test, as well as the prevalence of disease in the population being tested. In this review we will summarize the performance of commonly-utilized laboratory tests for uveitis, as well as the prevalence of uveitic diagnoses in different geographic practice settings. We will propose a logical framework for effective laboratory testing in uveitic disease through rigorous application of Bayesian analysis. Finally, we will demonstrate that while many highly sensitive laboratory tests offer an effective means to rule out associated systemic disease, limited test specificity and low pretest probability often preclude the diagnosis of systemic disease association with any high degree of certainty, even in the face of positive testing.
Natural History of Central Retinal Vein Occlusion: An Evidence-Based Systematic Review
Publisher: Elsevier BV
Date: 06-2010
DOI: 10.1016/J.OPHTHA.2010.01.060
Abstract: To describe the natural history of central retinal vein occlusion (CRVO) based on the best available evidence from the literature. Central retinal vein occlusion is a common sight-threatening retinal vascular disease. Despite the introduction of new interventions, the natural history of CRVO is unclear. Systemic review of all English language articles retrieved using a keyword search of MEDLINE, EMBASE, Current Contents, and the Cochrane Library to November 13, 2008. This was supplemented by hand-searching references of review articles published within the last 5 years. Two investigators independently identified all relevant observational studies evaluating the natural history of RVO and all clinical trials evaluating interventions for CRVO an untreated control arm was included. Of 5966 citations retrieved, 53 studies were reviewed, providing 3271 eyes with CRVO for analysis of its natural history. Visual acuity (VA) was generally poor at baseline (<20/40) and decreased further over time. Although 6 studies reported an improvement in VA, none of these improvements resulted in VA better than 20/40. Up to 34% of eyes with nonischemic CRVO converted to ischemic CRVO over a 3-year period. In ischemic CRVO cases, neovascular glaucoma developed in at least 23% of eyes within 15 months. In nonischemic CRVO cases, macular edema resolved in approximately 30% of eyes over time, and subsequent neovascular glaucoma was rare. Untreated eyes with CRVO generally had poor VA, which declined further over time. One quarter of eyes with nonischemic CRVO converted to ischemic CRVO.
GGCX mutations in a patient with overlapping pseudoxanthoma elasticum/cutis laxa‐like phenotype
Publisher: Oxford University Press (OUP)
Date: 08-11-2020
DOI: 10.1111/BJD.19576
Cr-spinel records metasomatism not petrogenesis of mantle rocks
Publisher: Springer Science and Business Media LLC
Date: 08-11-2019
DOI: 10.1038/S41467-019-13117-1
Abstract: Mantle melts provide a window on processes related to global plate tectonics. The composition of chromian spinel (Cr-spinel) from mafic-ultramafic rocks has been widely used for tracing the geotectonic environments, the degree of mantle melting and the rate of mid-ocean ridge spreading. The assumption is that Cr-spinel’s core composition (Cr# = Cr/(Cr + Al)) is homogenous, insensitive to post-formation modification and therefore a robust petrogenetic indicator. However, we demonstrate that the composition of Cr-spinel can be modified by fluid/melt-rock interactions in both sub-arc and sub-mid oceanic mantle. Metasomatism can produce Al-Cr heterogeneity in Cr-spinel that lowers the Cr/Al ratio, and therefore modifies the Cr#, making Cr# ineffective as a geotectonic and mantle melting indicator. Our analysis also demonstrates that Cr-spinel is a potential sink for fluid-mobile elements, especially in subduction zone environments. The heterogeneity of Cr# in Cr-spinel can, therefore, be used as an excellent tracer for metasomatic processes.
Neoproterozoic bimodal intrusive complex in the southwestern Tarim Block, northwest China: Age, geochemistry, and implications for the rifting of Rodinia
Publisher: Informa UK Limited
Date: 02-2006
Global geochemical fingerprinting of plume intensity suggests coupling with the supercontinent cycle
Publisher: Springer Science and Business Media LLC
Date: 21-11-2019
DOI: 10.1038/S41467-019-13300-4
Abstract: Plate tectonics and mantle plumes are two of the most fundamental solid-Earth processes that have operated through much of Earth history. For the past 300 million years, mantle plumes are known to derive mostly from two large low shear velocity provinces (LLSVPs) above the core-mantle boundary, referred to as the African and Pacific superplumes, but their possible connection with plate tectonics is debated. Here, we demonstrate that transition elements (Ni, Cr, and Fe/Mn) in basaltic rocks can be used to trace plume-related magmatism through Earth history. Our analysis indicates the presence of a direct relationship between the intensity of plume magmatism and the supercontinent cycle, suggesting a possible dynamic coupling between supercontinent and superplume events. In addition, our analysis shows a consistent sudden drop in MgO, Ni and Cr at ~3.2–3.0 billion years ago, possibly indicating an abrupt change in mantle temperature at the start of global plate tectonics.
Treosulfan and gemcitabine in metastatic uveal melanoma patients: Results of a multicenter feasibility study
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2003
DOI: 10.1097/00001813-200306000-00002
Abstract: No effective treatment currently exists for metastatic uveal melanoma. However, recent results obtained by an ATP-based tumor chemosensitivity assay have shown consistent activity of treosulfan+gemcitabine in up to 80% of tumor specimens tested. In this study we describe the first clinical results observed with this drug combination at different European centers in patients with metastatic uveal melanoma. Clinical case series of patients with metastatic uveal melanoma were treated with treosulfan+gemcitabine at seven different centers. Fourteen patients, 13 previously untreated and one pretreated with chemoimmunotherapy, were included in the study. Patients received treosulfan+gemcitabine in four different dose regimens. The response rates, progression-free and overall survival, and toxicity were evaluated. The analysis of 14 patients revealed one complete response, three partial responses and a stable disease in eight cases. The objective response rate was 28.6%, the median overall survival was 61 weeks [95% confidence interval (CI) 54-133 weeks], the progression-free survival was 28.5 weeks (95% CI 13-62 weeks) and the 1-year survival rate was 80%. The drugs were well tolerated. The most common side-effects were leuko- and thrombocytopenia. These preliminary results suggest potential therapeutic benefit of treosulfan+gemcitabine treatment in metastatic uveal melanoma and warrant further controlled studies.
A high-quality mid-Neoproterozoic paleomagnetic pole from South China, with implications for ice ages and the breakup configuration of Rodinia
Publisher: Elsevier BV
Date: 03-2000
Local delivery of corticosteroids in clinical ophthalmology: A review
Publisher: Wiley
Date: 22-01-2020
DOI: 10.1111/CEO.13702
Thermochronology of the Sulu ultrahigh-pressure metamorphic terrane: Implications for continental collision and lithospheric thinning
Publisher: Elsevier BV
Date: 08-2017
Natural History of Branch Retinal Vein Occlusion: An Evidence-Based Systematic Review
Publisher: Elsevier BV
Date: 06-2010
DOI: 10.1016/J.OPHTHA.2010.01.058
Abstract: To describe the natural history of branch retinal vein occlusion (BRVO) based on the best available evidence from the literature. Branch retinal vein occlusion is the second most frequent major retinal vascular disease. Although several new treatments for BRVO are currently being introduced, data on its natural history are sparse. English language articles were retrieved using a keyword search of MEDLINE, EMBASE, Current Contents, and the Cochrane Library to November 13, 2008, supplemented by manually searching the references of review articles published within the last 5 years. All relevant observational studies evaluating the natural history of BRVO and all clinical trials evaluating BRVO interventions with an untreated control arm were independently identified by 2 investigators. Of a total of 5965 citations retrieved, 24 eligible studies were identified and reviewed, providing 1608 eyes with BRVO with data on natural history. Visual acuity (VA) was moderately poor at baseline (<20/40). Although VA generally improved, with mean improvement ranging from 1 letter at 6 weeks to 28 letters up to 24 months, few studies reported improvement beyond 20/40. Over a 1-year period, 5% to 15% of eyes developed macular edema (ME), but of those with ME at baseline, 18% to 41% resolved. At baseline, 5% to 6% of eyes had bilateral BRVO, with 10% developing fellow eye involvement over time. There were few high-quality studies on other outcomes, including development of new vessels. Visual acuity generally improved in eyes with BRVO without intervention, although clinically significant improvement beyond 20/40 was uncommon.
In situ U-Pb geochronology and geochemistry of a 1.13 Ga mafic dyke suite at Bunger Hills, East Antarctica: The end of the Albany-Fraser Orogeny
Publisher: Elsevier BV
Date: 06-2018
Crustal Melting and Flow beneath Northern Tibet: Evidence from Mid-Miocene to Quaternary Strongly Peraluminous Rhyolites in the Southern Kunlun Range
Publisher: Oxford University Press (OUP)
Date: 04-10-2012
Palaeomagnetic evidence for unification of the North and West Australian cratons by ca.1.7 Ga: New results from the Kimberley Basin of northwestern Australia
Publisher: Oxford University Press (OUP)
Date: 07-2000
The Role of Altered Cell–Cell Communication in Melanoma Progression
Publisher: Springer Science and Business Media LLC
Date: 03-2003
DOI: 10.1023/B:HIJO.0000032362.35354.BB
Abstract: Under normal homeostasis, melanocyte growth and behaviour is tightly controlled by the surrounding keratinocytes. Keratinocytes regulate melanocyte behaviour through a complex system of paracrine growth factors and cell-cell adhesion molecules. Pathological changes, leading to development of malignant melanoma, upset this delicate homeostatic balance and can lead to altered expression of cell-cell adhesion and cell-cell communication molecules. In particular, there is a switch from the E-cadherin-mediated keratinocyte-melanocyte partnership to the N-cadherin-mediated melanoma-melanoma and melanoma-fibroblast interaction. Other changes include the alteration in the gap junctions formed between the melanocyte and keratinocyte. Changes in the connexin expression, in particular the loss of connexin 43, may result in a reduction or a loss of gap junctional activity, which is thought to contribute towards tumour progression. In the current review we describe the alterations in cell-cell adhesion and communication associated with melanoma development and progression, and discuss how a greater understanding of these processes may aid the future therapy of this disease.
Growth and adaptation mechanisms of tumour spheroids with time-dependent oxygen availability
Publisher: Cold Spring Harbor Laboratory
Date: 24-04-2022
DOI: 10.1101/2022.04.24.489294
Abstract: Tumours are subject to external environmental variability. However, in vitro tumour spheroid experiments, used to understand cancer progression and develop cancer therapies, have been routinely performed for the past fifty years in constant external environments. Furthermore, spheroids are typically grown in ambient atmospheric oxygen (normoxia), whereas most in vivo tumours exist in hypoxic environments. Therefore, there are clear discrepancies between in vitro and in vivo conditions. We explore these discrepancies by combining tools from experimental biology, mathematical modelling, and statistical uncertainty quantification. Focusing on oxygen variability to develop our framework, we reveal key biological mechanisms governing tumour spheroid growth. Growing spheroids in time-dependent conditions, we identify and quantify novel biological adaptation mechanisms, including unexpected necrotic core removal, and transient reversal of the tumour spheroid growth phases.
Tectonic evolution of the tibetan plateau: A working hypothesis based on the archipelago model of orogenesis
Publisher: Informa UK Limited
Date: 06-1995
Magnetic petrophysical results from the hamersley basin and their implications for interpretation of magnetic surveys
Publisher: Informa UK Limited
Date: 06-2011
Erratum: A stress-induced early innate response causes multidrug tolerance in melanoma
Publisher: Springer Science and Business Media LLC
Date: 26-01-2015
DOI: 10.1038/ONC.2014.432
Abstract: Correction to: Oncogene (2015) 34, 4448–4459 doi:10.1038/onc.2014.372 published online 24 November 2014. In this article, published online 24 November 2014, the authors have noticed that the latest supplementary information was not used. The corrected supplementary information (Supplementary Materials) appears online together with this corrigendum. The authors would like to apologise for any inconvenience this may cause
Formation and growth of co-culture tumour spheroids: new compartment-based mathematical models and experiments
Publisher: Cold Spring Harbor Laboratory
Date: 22-12-2022
DOI: 10.1101/2022.12.21.521515
Abstract: Co-culture tumour spheroid experiments are routinely performed to investigate cancer progression and test anti-cancer therapies. Therefore, methods to characterise and interpret coculture spheroid growth are of great interest. However, co-culture spheroid growth is complex. Multiple biological processes occur on overlapping timescales and different cell types within the spheroid may have different characteristics, for ex le proliferation rate or response to nutrient availability. There is no standard, widely-accepted mathematical model of such complex spatio-temporal growth processes. Typical approaches to analyse these experiments focus on the late-time temporal evolution of spheroid size and overlook early-time spheroid formation, spheroid structure and geometry. Here we make theoretical and practical contributions. We develop a general framework, based on mathematical and statistical modelling, to analyse a series of co-culture experiments. Using a range of different mathematical models we provide new biological insights about spheroid formation, growth, and structure. In addition, we extend a general class of compartment-based monoculture spheroid mathematical models to describe multiple populations and provide mechanistic biological insight. The framework is well-suited to analyse spheroids grown with multiple different cell types and the new class of mathematical models provide opportunities for further mathematical and biological insights.
A Mesozoic Andean-type active continental margin along coastal South China: New geological records from the basement of the northern South China Sea
Publisher: Elsevier BV
Date: 11-2021
Sequence Stratigraphy and Evolution of the Neoproterozoic Marginal Basins Along Southeastern Yangtze Craton, South China
Publisher: Elsevier BV
Date: 2001
Characterization of autoimmune eye disease in association with Down’s syndrome
Publisher: Springer Science and Business Media LLC
Date: 19-08-2023
An early Carboniferous paleomagnetic pole for Gondwanaland: new results from the Mount Eclipse Sandstone in the Ngalia Basin, central Australia
Publisher: American Geophysical Union (AGU)
Date: 10-02-1994
DOI: 10.1029/93JB02215
A randomized clinical trial of intravitreal bevacizumab versus intravitreal dexamethasone for diabetic macular edema: the BEVORDEX study.
Publisher: Elsevier BV
Date: 12-2014
DOI: 10.1016/J.OPHTHA.2014.07.002
Abstract: To report the 12-month results of the first head-to-head comparison of a dexamethasone implant (Ozurdex Allergan, Inc., Irvine, CA) versus bevacizumab (Avastin Genentech, South San Francisco, CA) for center-involving diabetic macular edema (DME). Phase 2, prospective, multicenter, randomized, single-masked clinical trial (clinicaltrials.gov identifier NCT01298076). We enrolled 88 eyes of 61 patients with center-involving DME. Forty-two eyes were randomized to receive bevacizumab every 4 weeks and 46 eyes were randomized to receive a dexamethasone implant every 16 weeks, both pro re nata. Results were analyzed using linear regression with generalized estimation equation methods to account for between-eye correlation. The primary outcome was the proportion of eyes that improved vision by 10 logarithm of minimum angle of resolution letters. Secondary outcomes included mean change in best-corrected visual acuity (BCVA), change in central macular thickness (CMT), injection frequency, and adverse events. Patient-reported outcomes were measured using the Impact of Vision Impairment (IVI) questionnaire. Improvement in BCVA of 10 or more letters was found in 17 of 42 eyes (40%) treated with bevacizumab compared with 19 of 46 dexamethasone implant-treated eyes (41% P = 0.83). None of the 42 bevacizumab eyes lost 10 letters or more, whereas 5 of 46 (11%) dexamethasone implant eyes did, mostly because of cataract. Mean CMT decreased by 122 μm for bevacizumab eyes and by 187 μm for dexamethasone implant eyes (P = 0.015). Bevacizumab-treated eyes received a mean of 8.6 injections compared with 2.7 injections for dexamethasone implant eyes. Significant improvement in IVI scores occurred for both treatment groups. Dexamethasone implant achieved similar rates of visual acuity improvement compared with bevacizumab for DME, with superior anatomic outcomes and fewer injections. Both treatments were associated with improvement in visual quality-of-life scores. However, more dexamethasone implant-treated eyes lost vision, mainly because of cataract.
Persister state-directed transitioning and vulnerability in melanoma
Publisher: Springer Science and Business Media LLC
Date: 06-2022
DOI: 10.1038/S41467-022-30641-9
Abstract: Melanoma is a highly plastic tumor characterized by dynamic interconversion of different cell identities depending on the biological context. Melanoma cells with high expression of the H3K4 demethylase KDM5B (JARID1B) rest in a slow-cycling, yet reversible persister state. Over time, KDM5B high cells can promote rapid tumor repopulation with equilibrated KDM5B expression heterogeneity. The cellular identity of KDM5B high persister cells has not been studied so far, missing an important cell state-directed treatment opportunity in melanoma. Here, we have established a doxycycline-titratable system for genetic induction of permanent intratumor expression of KDM5B and screened for chemical agents that phenocopy this effect. Transcriptional profiling and cell functional assays confirmed that the dihydropyridine 2-phenoxyethyl 4-(2-fluorophenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexa-hydro-quinoline-3-carboxylate (termed Cpd1) supports high KDM5B expression and directs melanoma cells towards differentiation along the melanocytic lineage and to cell cycle-arrest. The high KDM5B state additionally prevents cell proliferation through negative regulation of cytokinetic abscission. Moreover, treatment with Cpd1 promoted the expression of the melanocyte-specific tyrosinase gene specifically sensitizing melanoma cells for the tyrosinase-processed antifolate prodrug 3-O-(3,4,5-trimethoxybenzoyl)-(–)-epicatechin (TMECG). In summary, our study provides proof-of-concept for a dual hit strategy in melanoma, in which persister state-directed transitioning limits tumor plasticity and primes melanoma cells towards lineage-specific elimination.
Late Mesoproterozoic to earliest Neoproterozoic basin record of the Sibao orogenesis in western South China and relationship to the assembly of Rodinia
Publisher: Elsevier BV
Date: 12-2006
The 1.24–1.21 Ga Licheng Large Igneous Province in the North China Craton
Publisher: American Geophysical Union (AGU)
Date: 04-2020
DOI: 10.1029/2019JB019005
Genetics of basal cell carcinoma
Publisher: Wiley
Date: 05-2010
DOI: 10.1111/J.1440-0960.2009.00579.X
Abstract: Basal cell carcinoma is the most common human malignancy in populations of European origin, and Australia has the highest incidence of basal cell carcinoma in the world. Great advances in the understanding of the genetics of this cancer have occurred in recent years. Mutations of the patched 1 gene (PTCH1) lead to basal cell carcinoma predisposition in Gorlin syndrome. PTCH1 is part of the hedgehog signalling pathway, and derangements within this pathway are now known to be important in the carcinogenesis of many different cancers including sporadic basal cell carcinoma. The molecular biology of the hedgehog pathway is discussed, and mouse models of basal cell carcinoma based on this pathway are explored. New developments in non-surgical treatment of basal cell carcinoma are based on this knowledge. Other genes of importance to basal cell carcinoma development include the tumour suppressor gene P53 and the melanocortin-1 receptor gene. In addition, we discuss molecules of possible importance such as the glutathione-S-transferases, DNA repair genes, cyclin-dependent kinase inhibitor 2A, Brahma and connexins. Evidence of familial aggregation of this cancer is explored and supports the possibility of genetic predisposition to this common malignancy.
Kerguelen carbonatite tuff sourced from deep recycled material
Publisher: Elsevier BV
Date: 11-2023
Late Triassic melting of a thickened crust in southeastern China: Evidence for flat-slab subduction of the Paleo-Pacific plate
Publisher: Elsevier BV
Date: 09-2013
Borrelia Hermsii Causing Relapsing Fever and Uveitis
Publisher: Elsevier BV
Date: 08-2006
DOI: 10.1016/J.AJO.2006.03.030
Abstract: To describe a case of uveitis that is associated with Borrelia hermsii relapsing fever. Interventional case report. A 12-year-old boy with two weeks of relapsing fevers 10 days after c ing in remote eastern Oregon was examined. Borrelia hermsii immunoglobulin M and G levels were markedly elevated. Intravenous ceftriaxone, followed by four weeks of oral cephuroxime was administered, but the patient developed unilateral floaters and blurred vision in association with anterior and intermediate uveitis. Doxycycline was administered for presumed residual infection. Four weeks later, the visual acuity had improved. The anterior chamber was quiet, and topical corticosteroid was tapered successfully. Although rare, Borrelia hermsii should be included in the list of spirochetal diseases that are associated with uveitis.
A 90° spin on Rodinia: possible causal links between the Neoproterozoic supercontinent, superplume, true polar wander and low-latitude glaciation
Publisher: Elsevier BV
Date: 04-2004
Editorial: Recent Developments in Therapies and Diagnostic Tools for Melanoma and Non-melanoma Skin Cancer
Publisher: Frontiers Media SA
Date: 12-11-2020
RAB27A promotes melanoma cell invasion and metastasis via regulation of pro‐invasive exosomes
Publisher: Wiley
Date: 03-01-2019
DOI: 10.1002/IJC.32064
Abstract: Despite recent advances in targeted and immune-based therapies, advanced stage melanoma remains a clinical challenge with a poor prognosis. Understanding the genes and cellular processes that drive progression and metastasis is critical for identifying new therapeutic strategies. Here, we found that the GTPase RAB27A was overexpressed in a subset of melanomas, which correlated with poor patient survival. Loss of RAB27A expression in melanoma cell lines inhibited 3D spheroid invasion and cell motility in vitro, and spontaneous metastasis in vivo. The reduced invasion phenotype was rescued by RAB27A-replete exosomes, but not RAB27A-knockdown exosomes, indicating that RAB27A is responsible for the generation of pro-invasive exosomes. Furthermore, while RAB27A loss did not alter the number of exosomes secreted, it did change exosome size and altered the composition and abundance of exosomal proteins, some of which are known to regulate cancer cell movement. Our data suggest that RAB27A promotes the biogenesis of a distinct pro-invasive exosome population. These findings support RAB27A as a key cancer regulator, as well as a potential prognostic marker and therapeutic target in melanoma.
Non-Invasive Detection of Multinucleated Giant Cells in the Conjunctiva of Patients with Sarcoidosis by In-Vivo Confocal Microscopy
Publisher: Informa UK Limited
Date: 2006
DOI: 10.1080/09273940600826471
Abstract: To explore the use of in-vivo confocal microscopy (IVCM) as a potential non-invasive adjunctive tool for diagnosing sarcoidosis. Conjunctivae were imaged using confocal microscopy in 10 patients with sarcoidosis and 27 control subjects. We utilized the ASL-1000 Scanning Confocal Microscope (Advanced Scanning Ltd., New Orleans, LA) and the Confoscan 3 (Nidek Co. Ltd., Gamagori, Japan). Two masked observers reviewed the in-vivo confocal images of the conjunctivae in these subjects. One masked observer was experienced in reviewing confocal images. The most striking and obvious feature seen in granulomatous inflammation on confocal microscopy is the presence of multinucleated giant cells (MGCs). Unmasked observation of the scans revealed MGCs in six of the 10 sarcoid patients and no MGCs in the controls. One experienced masked observer found MGCs in five of the 10 patients with sarcoidosis and had no false-positive results (Fisher's exact test, p = 0.001 specificity = 1 sensitivity = 50% for the diagnosis of sarcoidosis and 83% compared to the unmasked observer). The second less-experienced masked observer detected MGCs in three of the 10 patients and three of the 27 controls (11.1% of the controls) (p = 0.186 specificity = 0.89 sensitivity = 30% of all patients with sarcoidosis and 50% compared to the unmasked observer). The utilization of IVCM to visualize the basic histology and pathology in sarcoidosis of the conjunctiva is novel. Initial results indicate that trained observers can detect MGCs in granulomatous inflammation. The ASL-1000 microscope tends to have better resolution and deeper penetration of the conjunctiva compared with the Confoscan 3.
Palaeomagnetism of the 1.89 Ga Boonadgin dykes of the Yilgarn Craton: Possible connection with India
Publisher: Elsevier BV
Date: 08-2019
Magmatic and metamorphic events during the early Paleozoic Wuyi-Yunkai orogeny, southeastern South China: New age constraints and pressure-temperature conditions
Publisher: Geological Society of America
Date: 30-12-2010
DOI: 10.1130/B30021.1
Magnolol induces cell death through PI3K/Akt‐mediated epigenetic modifications boosting treatment of BRAF‐ and NRAS‐mutant melanoma
Publisher: Wiley
Date: 21-02-2019
DOI: 10.1002/CAM4.1978
Climatic and tectonic controls on Late Triassic to Middle Jurassic sedimentation in northeastern Guangdong Province, South China
Publisher: Elsevier BV
Date: 05-2016
Early history of the eastern Sibao Orogen (South China) during the assembly of Rodinia: New mica 40Ar/39Ar dating and SHRIMP U–Pb detrital zircon provenance constraints
Publisher: Elsevier BV
Date: 10-2007
A Novel Class of Anticancer Compounds Targets the Actin Cytoskeleton in Tumor Cells
Publisher: American Association for Cancer Research (AACR)
Date: 13-08-2013
DOI: 10.1158/0008-5472.CAN-12-4501
Abstract: The actin cytoskeleton is a potentially vulnerable property of cancer cells, yet chemotherapeutic targeting attempts have been h ered by unacceptable toxicity. In this study, we have shown that it is possible to disrupt specific actin filament populations by targeting isoforms of tropomyosin, a core component of actin filaments, that are selectively upregulated in cancers. A novel class of anti-tropomyosin compounds has been developed that preferentially disrupts the actin cytoskeleton of tumor cells, impairing both tumor cell motility and viability. Our lead compound, TR100, is effective in vitro and in vivo in reducing tumor cell growth in neuroblastoma and melanoma models. Importantly, TR100 shows no adverse impact on cardiac structure and function, which is the major side effect of current anti-actin drugs. This proof-of-principle study shows that it is possible to target specific actin filament populations fundamental to tumor cell viability based on their tropomyosin isoform composition. This improvement in specificity provides a pathway to the development of a novel class of anti-actin compounds for the potential treatment of a wide variety of cancers. Cancer Res 73(16) 5169–82. ©2013 AACR.
Diabetic retinopathy in pregnancy: a review
Publisher: Wiley
Date: 05-2016
DOI: 10.1111/CEO.12760
Abstract: The prevalence of diabetes in pregnancy is increasing. Pre-existing diabetes is present in 1 in 167 pregnancies in Australia, ided equally between type 1 and type 2 diabetes. Diabetic retinopathy is a leading cause of blindness in women during their childbearing years, and pregnancy increases the short-term risk of diabetic retinopathy progression. We examine the risk factors for progression of diabetic retinopathy during pregnancy including duration of diabetes, baseline level of retinopathy, level of glycaemic control and hypertension. We also examine current screening and management guidelines and their levels of evidence, current treatment options for diabetic retinopathy and avenues for further research.
A geodynamic framework for 2 billion years of tectonic evolution: From cratonic amalgamation to the age of supercontinent cycle
Publisher: Copernicus GmbH
Date: 15-05-2023
DOI: 10.5194/EGUSPHERE-EGU23-10404
Abstract: An advanced understanding of how tectonic plates have moved since deep time is essential for understanding how Earth& #8217 s geodynamic system has evolved and interacted with the plate tectonic system, i.e., the longstanding question of what & #8220 drives& #8221 plate tectonics. In this work, we take advantage of the rapidly improving database and knowledge about the Precambrian world, and the conceptual breakthroughs both regarding the presence of a supercontinent cycle and possible dynamic coupling between the supercontinent cycle and mantle dynamics, to establish a full-plate global reconstruction back to 2000 Ma. We utilise a variety of global geotectonic databases to constrain our reconstruction, and use palaeomagnetically recorded true polar wander events and global plume records to help evaluate competing geodynamic models regarding the origin and evolution of first-order mantle structures, and provide new constraints on the absolute longitude of continents and supercontinents. After revising the configuration and life span of both supercontinents Nuna (1600& #8211 Ma) and Rodinia (900& #8211 Ma), we present here a 2000& #8211 Ma animation featuring the rapid assembly of large cratons and supercratons (or megacontinents) between 2000 Ma and 1800 Ma after billion years of dominance by many small cratons, that kick started the ensuing Nuna and Rodinia supercontinent cycles and the emergence of hemisphere-scale (long-wavelength) degree-1/degree-2 mantle structures. We further use the geodynamically-defined type-1 and type-2 inertia interchange true polar wander (IITPW) events, which likely occurred during Nuna (type-1) and Rodinia (type-2) times as shown by the palaeomagnetic record, to argue that Nuna assembled at about the same longitude as the latest supercontinent Pangea (320& #8211 Ma), whereas Rodinia formed through introversion assembly over the legacy Nuna subduction girdle either ca. 90& #176 to the west (our preferred model) or to the east before the migrated subduction girdle surround it generated its own degree-2 mantle structure. Our interpretation is broadly consistent with the global LIP record. Using TPW and LIP observations and geodynamic model predictions, we further argue that the Phanerozoic supercontinent Pangaea assembled through extroversion on a legacy Rodinia subduction girdle with a geographic centre at around 0& #176 E longitude before the formation of its own degree-2 mantle structure, the legacy of which is still present in present-day mantle. & &
In vitrothree-dimensional tumor microenvironment models for anticancer drug discovery
Publisher: Informa Healthcare
Date: 19-12-2007
Abstract: Anticancer drug discovery has long been h ered by the poor predictivity of the preclinical models. There is a growing realization that the tumor microenvironment is a critical determinant of the response of cancer cells to therapeutic agents. The past 5 years have seen a great deal of progress in our understanding of how the three-dimensional microenvironment modulates the signaling behavior of tumor cells. The present review discusses how three-dimensional in vitro cell culture models can benefit cancer drug discovery through an accurate modeling of the tumor microenvironment, leading to more physiologically relevant experimental outcomes.
Paleogene post-collisional lamprophyres in western Yunnan, western Yangtze Craton: Mantle source and tectonic implications
Publisher: Elsevier BV
Date: 09-2014
In Vivo Laser Confocal Microscopy Using the HRT-Rostock Cornea Module: Diversity and Diagnostic Implications in Patients with Uveitis
Publisher: Informa UK Limited
Date: 31-05-2017
DOI: 10.1080/09273948.2017.1298818
Abstract: Keratic precipitates (KP) are a common feature of uveitis. We prospectively examined KP with the Heidelberg Retinal Tomograph II confocal laser scanning microscope and Rostock Corneal Module (HRT-RCM) to explore their diagnostic implications. Prospective, observational, multicenter study. HRT-RCM images were classified by two masked observers. 120 scans on 120 eyes from 110 subjects were included. The majority (N = 93) had non-infectious uveitis. Sixty eyes had active disease at scanning. Eight KP morphologies were defined. Agreement between the two masked graders was high (Kappa value across all categories = 0.81). Cluster and nodular KP were associated with active infectious uveitis (p < 0.01): patients with cluster KP (odds ratio [OR] = 3.03, 95% confidence interval [CI]: 1.43, 6.45) and nodular KP (OR = 3.89, 95% CI: 1.42, 10.65) were more likely to have infectious uveitis than those without. Laser confocal microscopy of KP may have a role in determining between infectious and non-infectious uveitis.
SHRIMP U-Pb zircon age of tuff at the bottom of the Lower Cambrian Niutitang Formation, Zunyi, South China
Publisher: Springer Science and Business Media LLC
Date: 02-2008
Late Triassic high-Mg andesite/dacite suites from northern Hohxil, North Tibet: Geochronology, geochemical characteristics, petrogenetic processes and tectonic implications
Publisher: Elsevier BV
Date: 09-2011
Metasomatized lithosphere–asthenosphere interaction during slab roll-back: Evidence from Late Carboniferous gabbros in the Luotuogou area, Central Tianshan
Publisher: Elsevier BV
Date: 12-2012
Revisiting Mesozoic felsic intrusions in eastern South China: spatial and temporal variations and tectonic significance
Publisher: Elsevier BV
Date: 12-2017
Switching the sphingolipid rheostat in the treatment of diabetes and cancer comorbidity from a problem to an advantage
Publisher: Hindawi Limited
Date: 2015
DOI: 10.1155/2015/165105
Abstract: Cancer and diabetes are among the most common diseases in western societies. Epidemiological studies have shown that diabetic patients have a significantly higher risk of developing a number of different types of cancers and that in iduals with comorbidity (cancer and diabetes rediabetes) have a poorer prognosis relative to nondiabetic cancer patients. The increasing frequency of comorbidity of cancer and diabetes mellitus, mainly type 2 diabetes, has driven the development of therapeutic interventions that target both disease states. There is strong evidence to suggest that balancing the sphingolipid rheostat, ceramide—sphingosine—sphingosine-1-phosphate (S1P) is crucial in the prevention of diabetes and cancer and sphingosine kinase/S1P modulators are currently under development for the treatment of cancer and diabetes. This paper will highlight some of the complexities inherent in the use of the emerging sphingosine kinase/S1P modulators in the treatment of comorbidity of diabetes and cancer.
Ocular coherence tomography in acute posterior multifocal placoid pigment epitheliopathy
Publisher: Wiley
Date: 31-10-2006
DOI: 10.1111/J.1442-9071.2006.01357.X
Abstract: The authors report a case of typical acute posterior multifocal placoid pigment epitheliopathy in which an ocular coherence tomographic scan was performed through an acute lesion and then repeated through the same lesion 12 months later. The initial ocular coherence tomographic scan showed marked anterior displacement of both neuroretina and outer reflective band. A subsequent ocular coherence tomographic scan revealed resolution of the prior displacement, increased reflectance of the outer reflective band and mild disruption of the outer retinal layers. These findings are consistent with a primary choroiditis.
The largest plagiogranite on Earth formed by re-melting of juvenile proto-continental crust
Publisher: Springer Science and Business Media LLC
Date: 05-07-2021
DOI: 10.1038/S43247-021-00205-8
Abstract: The growth of continental crust through melt extraction from the mantle is a critical component of the chemical evolution of the Earth and the development of plate tectonics. However, the mechanisms involved remain debated. Here, we conduct petrological and geochemical analyses on a large (up to 5000 km 2 ) granitoid body in the Arabian-Nubian shield near El-Shadli, Egypt. We identify these rocks as the largest known plagiogranitic complex on Earth, which shares characteristics such as low potassium, high sodium and flat rare earth element chondrite-normalized patterns with spatially associated gabbroic rocks. The hafnium isotopic compositions of zircon indicate a juvenile source for the magma. However, low zircon δ 18 O values suggest interaction with hydrothermal fluids. We propose that the El-Shadli plagiogranites were produced by extensive partial melting of juvenile, previously accreted oceanic crust and that this previously overlooked mechanism for the formation of plagiogranite is also responsible for the transformation of juvenile crust into a chemically stratified continental crust.
Early crustal evolution of the Yangtze Craton, South China: New constraints from zircon U-Pb-Hf isotopes and geochemistry of ca. 2.9–2.6 Ga granitic rocks in the Zhongxiang Complex
Publisher: Elsevier BV
Date: 09-2018
The dominant driving force for supercontinent breakup: Plume push or subduction retreat?
Publisher: Elsevier BV
Date: 07-2018
Palaeomagnetic dating and tectonic significance of dolerite intrusions in the Albany Mobile Belt, Western Australia
Publisher: Elsevier BV
Date: 04-1995
Vision-Related Quality of Life Outcomes in the BEVORDEX Study: A Clinical Trial Comparing Ozurdex Sustained Release Dexamethasone Intravitreal Implant and Bevacizumab Treatment for Diabetic Macular Edema.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 21-10-2016
Abstract: To determine the patient-centered effectiveness of treatment with the slow-release dexamethasone intravitreal implant (DEX implant) and intravitreal bevacizumab using the Impact of Vision Impairment Questionnaire (IVI), a vision-related quality of life (VRQoL) measure, in patients with visual impairment secondary to center-involving diabetic macular edema (DME). Patients with DME were enrolled in a phase 2, prospective, multicenter, randomized, single-masked clinical trial and received either DEX implant 4 monthly or bevacizumab monthly, both pro re nata. Vision-related quality of life was measured at baseline and 24 months, using the IVI's three component scales, namely reading, mobility, and emotional well-being. Rasch analysis was used to generate interval-level estimates of VRQoL, which were then analyzed using t-tests to assess changes over time. Forty-eight patients completed the main study 43 (90%) answered the IVI at the baseline and 24-month (final efficacy) visits. Vision-related quality of life improved significantly, with average increases of 1.44, 0.99, and 1.49 logits, for the reading, mobility, and emotional well-being scales respectively, from baseline to 24 months, (P 0.1.). We found that both DEX implant and bevacizumab treatment result in significant and similar improvements in VRQoL in patients with DME over a 24-month period. (Clinicaltrials.gov identifier NCT01298076).
Multimodal tumor suppression by miR-302 cluster in melanoma and colon cancer
Publisher: Elsevier BV
Date: 12-2016
DOI: 10.1016/J.BIOCEL.2016.11.004
Abstract: The miR-302 family is one of the main groups of microRNAs, which are highly expressed in embryonic stem cells (ESCs). Previous reports have indicated that miR-302 can reduce the proliferation rate of some cancer cells while compromising on their oncogenic potential at the same time without having the same effect on normal somatic cells. In this study we aimed to further investigate the role of the miR-302 cluster in multiple cancer signaling pathways using A-375 melanoma and HT-29 colorectal cancer cells. Our results indicate that the miR-302 cluster has the potential to modulate oncogenic properties of cancer cells through inhibition of proliferation, angiogenesis and invasion, and through reversal of the epithelial-to-mesenchymal transition (EMT) in these cells. We showed for the first time that overexpression of miR-302 cluster sensitized A-375 and HT-29 cells to hypoxia and also to the selective BRAF inhibitor vemurafenib. MiR-302 is a pleiotropically acting miRNA family which may have significant implications in controlling cancer progression and invasion. It acts through a reprogramming process, which has a global effect on a multitude of cellular pathways and events. We propose that reprogramming of cancer cells by epigenetic factors, especially miRNAs might provide an efficient tool for controlling cancer and especially for those with more invasive nature.
An outline of the palaeogeographic evolution of the Australasian region since the beginning of the Neoproterozoic
Publisher: Elsevier BV
Date: 04-2001
Syn-deformational and drilling-induced remanent magnetizations from diamond drill cores of the Mt Eclipse Sandstone, central Australia
Publisher: Informa UK Limited
Date: 09-1991
Dendritic Mesoporous Silica Nanoparticles for pH‐Stimuli‐Responsive Drug Delivery of TNF‐Alpha
Publisher: Wiley
Date: 29-05-2017
Abstract: Tumor necrosis factor-alpha (TNF-α) is a pleiotropic immune stimulatory cytokine and natural endotoxin that can induce necrosis and regression in solid tumors. However, systemic administration of TNF-α is not feasible due to its short half-life and acute toxicity, preventing its widespread use in cancer treatment. Dendritic mesoporous silica nanoparticles (DMSN) are used coated with a pH-responsive block copolymer gate system combining charged hyperbranched polyethylenimine and nonionic hydrophilic polyethylenglycol to encapsulate TNF-α and deliver it into various cancer cell lines and dendritic cells. Half-maximal effective concentration (EC
Detrital provenance evolution of the Ediacaran–Silurian Nanhua foreland basin, South China
Publisher: Elsevier BV
Date: 12-2015
Possible association between scleritis and lymphoma
Publisher: BMJ
Date: 16-11-2007
Late Early Cretaceous adakitic granitoids and associated magnesian and potassium‐rich mafic enclaves and dikes in the Tunchang–Fengmu area, Hainan Province (South China): Partial melting of lower crus
Publisher: Elsevier BV
Date: 10-2012
New Crustal Vs Model Along an Array in South‐East China: Seismic Characters and Paleo‐Tethys Continental Amalgamation
Publisher: American Geophysical Union (AGU)
Date: 07-2020
DOI: 10.1029/2020GC009024
Abstract: The assembly of East Asia was closely linked to the closure of the Tethyan oceans. In south‐east China, the closure of the Paleo‐Tethys ocean led to a continental collision between the South China and North China blocks (SCB and NCB), forming the world renowned (ultra‐) high pressure (UHP) metamorphic belt of the Dabie‐Sulu Orogen. The region was subsequently reworked by postorogenic extensional processes. These tectonic processes likely have left lithospheric scars identifiable by seismic imaging techniques. Here we characterize seismic structures across the orogen and analyze processes related to the closure of the Paleo‐Tethys. Using cutting‐edge tomographic approaches and ambient noise dispersion data, we developed a fine‐scale crustal shear‐wave velocity model beneath key crustal domains in the region. Distinct crustal scale velocity domains are identified, corresponding to the normal Precambrian crust, slow‐velocity suture zones and fault systems, and fast‐velocity orogens, suggesting a deep root of the corresponding surface geological features. By combining recent models of active‐source, gravity and magnetotellurics, characteristic lithospheric deformation patterns such as crustal thrust systems and lithospheric wedges can be inferred, which are attributed to a northward subduction of the SCB lithosphere and the eventual continental collision after the closure of the Paleo‐Tethys Ocean.
Review of seafloor spreading around Australia. II. marine magnetic anomaly modelling
Publisher: Informa UK Limited
Date: 09-1991
Tectonostratigraphy and provenance analysis to define the edge and evolution of the eastern Wuyi-Yunkai orogen, South China
Publisher: Cambridge University Press (CUP)
Date: 02-10-2019
DOI: 10.1017/S0016756817000784
Abstract: We report three Palaeozoic sedimentary successions in northeastern South China that display markedly different tectonostratigraphic characteristics: the Jiangshan section exhibits an angular unconformity between the Upper Ordovician and Carboniferous stratra the Shuangming section exhibits a disconformity between the lower Silurian and Upper Devonian strata and the Xinqiao section exhibits a disconformity between the upper Silurian and Upper Devonian strata. The Shuangming and Xinqiao sections are interpreted to represent the remnant Nanhua foreland basin, whereas the Jiangshan section is in the fold-and-thrust zone of the Wuyi-Yunkai orogen. The Lizhu-Changshan thrust fault in between is interpreted to be the frontal thrust and the boundary of the orogen. Detrital provenance analysis of the Ordovician–Devonian sandstones from the Shuangming and Xinqiao sections shows that the Ordovician–Silurian, mid- to late-orogenic sandstones contain dominantly 860–780 Ma zircon populations and subordinate 2.5 Ga, 1.89–1.78 Ga, 980–950 Ma, 630–540 Ma and 430 Ma populations, indicating nearby sources including the early Neoproterozoic Sibao orogen, inverted Neoproterozoic rift basins and related plutons, recycled Ediacaran–Cambrian strata and, increasing with time, exposed Cathaysia basement and minor syn- to late-orogenic plutonic intrusions. The Devonian post-orogenic sandstones exhibit a dominant 440 Ma population with minor 2.5 Ga, 1.89–1.78 Ga, 860–780 Ma and 630–540 Ma populations, suggesting a dominant contribution from now widely exposed, mid- to late-orogenic plutonic intrusions (with or without contributions from rare volcanism of similar ages) in a residual topographic high SE of the Lizhu-Changshan fault. This residual topographic high of the Wuyi-Yunkai orogen had completely perished by early Carboniferous time, c. 60Myr after the end of the orogenic event.
Structural Evolution of a 1.6 Ga Orogeny Related to the Final Assembly of the Supercontinent Nuna: Coupling of Episodic and Progressive Deformation
Publisher: American Geophysical Union (AGU)
Date: 10-2020
DOI: 10.1029/2020TC006162
The breakup of Rodinia: Did it start with a mantle plume beneath South China?
Publisher: Elsevier BV
Date: 11-1999
Patients’ Causal Beliefs About Diabetic Retinopathy
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2013
Early Ediacaran Magmatism in the Yenisei Ridge and Evolution of the Southwestern Margin of the Siberian Craton
Publisher: MDPI AG
Date: 23-06-2020
DOI: 10.3390/MIN10060565
Abstract: We present the first comprehensive data for the early Ediacaran stage of evolution of the western active continental margin of the Siberian Craton (Yenisei Ridge). U-Pb (SHRIMP-II SIMS) data for zircons from dikes of picrodolerites, quartz diorites, and leucocratic granites show that they were emplaced at 625 ± 5, 623 ± 8, and 626 ± 5 Ma, respectively, which indicates a narrow time window of Ediacaran magmatic events. The mafic tholeiitic rocks have OIB and E-MORB mantle components in their magmatic sources. Mineralogical and geochemical observations showed that the mantle-sourced mafic melts assimilated some crustal material, forming Th-enriched dikes of intermediate composition and K- and Rb-enriched felsic rocks. The possible geodynamic conditions for the formation of these early Ediacaran dikes are shown and a geodynamic model is presented for the development of the Yenisei Ridge orogen from the late Cryogenian to the late Ediacaran.
Two-stage crustal growth in the Arabian-Nubian shield: Initial arc accretion followed by plume-induced crustal reworking
Publisher: Elsevier BV
Date: 07-2021
Effect of Corticosteroid-Sparing Treatment With Mycophenolate Mofetil vs Methotrexate on Inflammation in Patients With Uveitis
Publisher: American Medical Association (AMA)
Date: 10-09-2019
Epidemiology of uveitis in urban Australia
Publisher: Wiley
Date: 02-05-2019
DOI: 10.1111/CEO.13517
Abstract: Few prior studies have described the epidemiology of uveitis in the Australian population. To report the incidence and period prevalence of active uveitis in Melbourne and detail their subtypes and aetiologies. Cross-sectional study using retrospective medical record review in a tertiary hospital. Patients with a coded diagnosis of uveitis who attended the emergency department or specialist ocular immunology clinic at the Royal Victorian Eye and Ear Hospital between November 2014 through October 2015 (N = 1752). Medical records were reviewed to confirm the date of diagnosis and subtype of uveitis. Incidence and prevalence rates were calculated utilizing estimates of the adult population residing in areas of greater Melbourne with more than 30 ocular-related presentations to the emergency department annually. Presence and date of onset, anatomical distribution and aetiology of uveitis. During the study period, 734 new cases of uveitis and 502 cases of pre-existing uveitis requiring active treatment were confirmed. These figures yielded an incidence of 21.54 (CI 20.03, 23.15) per 100 000 person-years and a period prevalence of 36.27 (CI 34.30, 38.35) per 100 000 persons. The distribution of prevalent uveitis cases was anterior (75%), intermediate (6%), posterior (15%) and panuveitis (4%). An infectious aetiology accounted for 13.4% of cases, a systemic associated disease for 26.4% of cases, and no cause was identified in 60.2% of cases. The incidence and prevalence rates of uveitis in urban Australia were lower than recent studies from the United States and Europe.
Neoproterozoic granitoids in South China: Crustal melting above a mantle plume at ca. 825 Ma?
Publisher: Elsevier BV
Date: 10-04-2003
FGFR2-activating mutations disrupt cell polarity to potentiate migration and invasion in endometrial cancer cell models.
Publisher: The Company of Biologists
Date: 2018
DOI: 10.1242/JCS.213678
Abstract: Fibroblast growth factor receptors (FGFRs) are a family of receptor tyrosine kinases that control a erse range of biological processes during development and in adult tissues. We recently reported that somatic FGFR2 mutations are associated with shorter survival in endometrial cancer. However, little is known about how these FGFR2 mutations contribute to endometrial cancer metastasis. Here, we report that expression of the activating mutations FGFR2
Ca. 825 Ma komatiitic basalts in South China: First evidence for > 1500 degrees C mantle melts by a Rodinian mantle plume
Publisher: Geological Society of America
Date: 2007
DOI: 10.1130/G23878A.1
Syn‐deformational remanent magnetization of the Mount Eclipse Sandstone, central Australia
Publisher: Oxford University Press (OUP)
Date: 10-1989
Contrasting zircon Hf and O isotopes in the two episodes of Neoproterozoic granitoids in South China: Implications for growth and reworking of continental crust
Publisher: Elsevier BV
Date: 06-2007
Estimation of Cell Cycle States of Human Melanoma Cells with Quantitative Phase Imaging and Deep Learning
Publisher: IEEE
Date: 04-2020
Epidemiology of episcleritis and scleritis in urban Australia
Publisher: Wiley
Date: 03-05-2020
DOI: 10.1111/CEO.13761
Genesis of the 1.21 Ga Marnda Moorn large igneous province by plume–lithosphere interaction
Publisher: Elsevier BV
Date: 02-2014
Reply to the comment of Clarke and Pillans Onset of aridity in Southern Western Australia - A preliminary palaeomagnetic appraisal [Global and planetary change 18 (1998) 175-187]
Publisher: Elsevier BV
Date: 15-04-2002
Fluorescence-Based Quantitative and Spatial Analysis of Tumour Spheroids: A Proposed Tool to Predict Patient-Specific Therapy Response
Publisher: Frontiers Media SA
Date: 28-05-2021
DOI: 10.3389/FDGTH.2021.668390
Abstract: Tumour spheroids are widely used to pre-clinically assess anti-cancer treatments. They are an excellent compromise between the lack of microenvironment encountered in adherent cell culture conditions and the great complexity of in vivo animal models. Spheroids recapitulate intra-tumour microenvironment-driven heterogeneity, a pivotal aspect for therapy outcome that is, however, often overlooked. Likely due to their ease, most assays measure overall spheroid size and/or cell death as a readout. However, as different tumour cell subpopulations may show a different biology and therapy response, it is paramount to obtain information from these distinct regions within the spheroid. We describe here a methodology to quantitatively and spatially assess fluorescence-based microscopy spheroid images by semi-automated software-based analysis. This provides a fast assay that accounts for spatial biological differences that are driven by the tumour microenvironment. We outline the methodology using detection of hypoxia, cell death and PBMC infiltration as ex les, and we propose this procedure as an exploratory approach to assist therapy response prediction for personalised medicine.
Dealing with co‐existent cataract and diabetic macular oedema: An increasingly common conundrum now solved?
Publisher: Wiley
Date: 05-2020
DOI: 10.1111/CEO.13764
Differences in practice of ophthalmology by gender in Australia
Publisher: Wiley
Date: 16-05-2019
DOI: 10.1111/CEO.13523
Abstract: The number of females practising ophthalmology is rising. It is known that practice patterns between female and male ophthalmologists differ. Understanding the differences will help to inform future workforce planning. To investigate the differences in clinical practice between female and male ophthalmologists in Australia. Cross-sectional study. Ophthalmologists participating in the Royal Australian & New Zealand College of Ophthalmologists workforce survey, and/or Medicine in Australia: Balancing Employment and Life survey, and those who made claims from Medicare Benefits Schedule Australia. Combined analysis of de-identified 2014 data from the surveys and Medicare Benefits Schedule. Hours worked, service provision, remuneration and social circumstances. Female ophthalmologists provided 35% fewer services per ophthalmologist per year (2834 vs 4328) than male ophthalmologists. Female ophthalmologists received approximately half the annual income of male ophthalmologists median self-reported net personal annual income was AUD122 500 (interquartile range [IQR] 96 000-225 000) for females compared to AUD245 000 (IQR 180 000-365 000) for males (P = .01). The median self-reported hours worked per week was 35.0 (IQR 28.0-46.0) for females and 41.8 (IQR 36.5-48.5) for males (P = 0.04). A higher proportion of females practise in medical subspecialties, while a higher proportion of males practise in surgical subspecialties. Female ophthalmologists earn less compared to male ophthalmologists after accounting for lower service provision and hours worked. Difference in income may be partially accounted for by higher total number of services and procedural services provided by male ophthalmologists. Understanding differences between female and male ophthalmologists will help to inform future medical workforce planning.
Biologic therapies for inflammatory eye disease
Publisher: Wiley
Date: 05-2006
DOI: 10.1111/J.1442-9071.2006.01225.X
Abstract: The era of biologic medical therapies provides new options for patients with treatment-resistant inflammatory eye disease. In this review, the authors summarize current published experience in a rapidly progressing clinical field, including the use of biologics, such as the tumour necrosis factor blockers, daclizumab and rituximab, and related agents, interferons and intravenous immunoglobulin, for the treatment of uveitis, scleritis and orbital inflammation. Reports of dramatic recoveries in patients with recalcitrant ocular inflammation who have received such therapies must be balanced against the high cost of biologics and the potential for serious, and at times unanticipated, complications of this treatment.
From Rodinia to Pangea: an extroversion process driven first by plume push followed by downwelling pull, absorption and merging
Publisher: Copernicus GmbH
Date: 23-03-2020
DOI: 10.5194/EGUSPHERE-EGU2020-12348
Abstract: & & Numerous works also suggested that mantle plumes or mantle upwellings associated with LLSVPs in a degree-2 mantle state play a major role in driving the break-up of a supercontinent. However, subduction and mantle downwelling may play an increasing role in the leadup to the assembly of the next supercontinent. Anderson (1994) noticed that continents tend to gather at mantle downwelling zones, which was later developed into the hypothesis of orthoversion assembly of supercontinents by Mitchell (2012). Zhong et al. (2007) conceptualised the assembly of supercontinents through the merger or absorption of mantle downwellings, leading to the assembly of supercontinents over a superdownwelling in a degree-1 mantle. Here we present a revised global paleogeographic reconstruction featuring an extroversion assembly of Pangea (i.e. through the closure of the Mirovoi superocean) over a pre-existing yet dynamic mantle downwelling zone (Li et al., 2019). In particular, we show that the Paleozoic world was dominated by two major subduction (dowelling) cells, one associated with the newly assembled Gondwana, and the other associated with the assembly of Laurasia. The two cells gradually merged together by the Carboniferous time, forming the supercontinent Pangea over a mantle superdownwelling (Zhang et al., 2010). It was during the merger of the two dowelling cells that continental and arc terranes was successively transported from Gondwana margin to future Laurasia.& & & & & strong& References:& /strong& & & & & Anderson, D.L., 1994. Superplume or supercontinents? Geology 22, 39-42.& & & & Huang, C., Zhang, N., Li, Z.-X., Ding, M., Dang, Z., Pourteau, A., Zhong, S., 2019. Modeling the Inception of Supercontinent Breakup: Stress State and the Importance of Orogens. Geochemistry, Geophysics, Geosystems 20, 4830-4848.& & & & Li, Z.X., Mitchell, R.N., Spencer, C.J., Ernst, R., Pisarevsky, S., Kirscher, U., Murphy, J.B., 2019. Decoding Earth& #8217 s rhythms: Modulation of supercontinent cycles by longer superocean episodes. Precambrian Research 323, 1-5.& & & & Mitchell, R.N., Kilian, T.M., Evans, D.A.D., 2012. Supercontinent cycles and the calculation of absolute palaeolongitude in deep time. Nature 482, 208-211.& & & & Zhang, N., Zhong, S., Leng, W., Li, Z.-X., 2010. A model for the evolution of the Earth's mantle structure since the Early Paleozoic. Journal of Geophysical Research: Solid Earth 115, B06401.& & & & Zhong, S., Zhang, N., Li, Z.-X., Roberts, J.H., 2007. Supercontinent cycles, true polar wander, and very long-wavelength mantle convection. Earth and Planetary Science Letters 261, 551-564.& &
Temperature, Pressure, and Composition of the Mantle Source Region of Late Cenozoic Basalts in Hainan Island, SE Asia: a Consequence of a Young Thermal Mantle Plume close to Subduction Zones?
Publisher: Oxford University Press (OUP)
Date: 13-12-2012
Geophysical surveys for strata-bound Outokumpu-type CU-CO-ZN deposits at Kylylahti, Eastern Finland
Publisher: Informa UK Limited
Date: 06-1995
DOI: 10.1071/EG995066
In vivo overexpression of Emi1 promotes chromosome instability and tumorigenesis
Publisher: Springer Science and Business Media LLC
Date: 11-04-2016
DOI: 10.1038/ONC.2016.94
Abstract: Cell cycle genes are often aberrantly expressed in cancer, but how their misexpression drives tumorigenesis mostly remains unclear. From S phase to early mitosis, EMI1 (also known as FBXO5) inhibits the anaphase-promoting complex/cyclosome, which controls cell cycle progression through the sequential degradation of various substrates. By analyzing 7403 human tumor s les, we find that EMI1 overexpression is widespread in solid tumors but not in blood cancers. In solid cancers, EMI1 overexpression is a strong prognostic marker for poor patient outcome. To investigate causality, we generated a transgenic mouse model in which we overexpressed Emi1. Emi1-overexpressing animals develop a wide variety of solid tumors, in particular adenomas and carcinomas with inflammation and lymphocyte infiltration, but not blood cancers. These tumors are significantly larger and more penetrant, abundant, proliferative and metastatic than control tumors. In addition, they are highly aneuploid with tumor cells frequently being in early mitosis and showing mitotic abnormalities, including lagging and incorrectly segregating chromosomes. We further demonstrate in vitro that even though EMI1 overexpression may cause mitotic arrest and cell death, it also promotes chromosome instability (CIN) following delayed chromosome alignment and anaphase onset. In human solid tumors, EMI1 is co-expressed with many markers for CIN and EMI1 overexpression is a stronger marker for CIN than most well-established ones. The fact that Emi1 overexpression promotes CIN and the formation of solid cancers in vivo indicates that Emi1 overexpression actively drives solid tumorigenesis. These novel mechanistic insights have important clinical implications.
A stress-induced early innate response causes multidrug tolerance in melanoma
Publisher: Springer Science and Business Media LLC
Date: 24-11-2014
DOI: 10.1038/ONC.2014.372
Stochastic models of cell invasion with fluorescent cell cycle indicators
Publisher: Elsevier BV
Date: 11-2018
Short-term vision gains at 12 weeks correlate with long-term vision gains at 2 years: results from the BEVORDEX randomised clinical trial of bevacizumab versus dexamethasone implants for diabetic macular oedema.
Publisher: BMJ
Date: 04-08-2017
DOI: 10.1136/BJOPHTHALMOL-2017-310737
Abstract: To determine whether early vision gains predict long-term visual outcomes in the BEVORDEX randomised clinical trial of bevacizumab or dexamethasone implants for diabetic macular oedema. Post hoc analysis of 68 study eyes (77%) that completed 2 years follow-up of the BEVORDEX multicentre randomised clinical trial set in Australia (ClinicalTrials.gov identifier: NCT01298076 ). Study eyes from both groups were combined and stratified by visual acuity (VA) change in the first 12 weeks in to three groups: (a) suboptimal gain: letters gain (includes VA loss), (b) moderate gain: 5–9 letters gain, (c) pronounced gain: ≥10 letters gain. This was correlated with VA outcome at 104 weeks taking into account treatment allocation and baseline lens status. The change in VA in the first 12 weeks was significantly correlated with VA change at 104 weeks (p .001). This was independent of treatment allocation (p=0.353) and lens status at baseline (p=0.593). The change in central macular thickness at 12 weeks did not correlate with VA gain at 104 weeks (p=0.847). Short-term visual gain at 12 weeks was strongly correlated with long-term vision improvement independent of treatment allocation or baseline lens status. Early improvement in central macular thickness was not predictive of long-term visual outcomes. NCT01298076, Post-results.
Reply to Comment by Steinberger on ‘Will Earth's next supercontinent assemble through the closure of the Pacific Ocean?’
Publisher: Oxford University Press (OUP)
Date: 09-11-2022
DOI: 10.1093/NSR/NWAC254
Rapid initiation of cell cycle reentry processes protects neurons from amyloid-β toxicity
Publisher: Proceedings of the National Academy of Sciences
Date: 18-03-2021
Abstract: The FUCCI reporter system allows live monitoring of the cell cycle via temporal expression of fluorescence markers of G0/1 or S/G2/M cell cycle phases. We found transient FUCCI reporter activity in naive neurons but not cell ision, suggesting that the postmitotic state of neurons is rather a dynamic process of suppressing the cell cycle than a definite G0 state. Exposing neurons to amyloid-β resulted in death of the majority of neurons without cell cycle contribution. A subset of neurons that entered early stages of cell cycle and maintained this state were protected from amyloid-β-induced cell death. Consistently, we found high FUCCI reporter activity in the brains of mice that form amyloid-β through transgenic expression of the amyloid-β precursor protein.
Melanoma progression exhibits a significant impact on connexin expression patterns in the epidermal tumor microenvironment
Publisher: Springer Science and Business Media LLC
Date: 21-10-2009
DOI: 10.1007/S00418-009-0654-5
Abstract: Melanoma depends on, interacts with and reacts to the stroma in which it is embedded, including fibroblasts, extracellular matrix, endothelial cells and immune cells. However, the impact of melanoma on the epidermal tumor microenvironment-the multilayered epithelium of the skin-is poorly understood. Gap junctions are essential for intercellular communication and involved in proliferation, differentiation and homeostasis of keratinocytes. We have shown previously that the gap junction proteins connexin 26 and 30 (Cx26 and Cx30) are induced in the epidermal tumor microenvironment of skin cancers including melanoma. This study compares the extent of Cx26, Cx30 and Cx43 expression in the epidermal microenvironment of melanocytic nevi and melanomas and its association with melanoma thickness, proliferative index of the tumor and its microenvironment, and with 5-year metastasis and survival. We found that induction of Cx26 and Cx30 cell-cell border expression in the epidermal tumor microenvironment correlates to malignancy. Importantly, there was a significant correlation of tumor thickness with the vertical epidermal Cx26 and Cx30 expression pattern and the horizontal Cx26 dissemination. Furthermore, horizontal Cx26 expression correlated with metastasis. Vertical epidermal expression patterns of Cx26 and Cx30 significantly correlated with the proliferative index in the epidermal tumor microenvironment but not with the proliferative index in the tumor. In contrast, Cx43 did not correlate with malignancy, thickness or proliferative index. In summary, here we show for the first time a significant association between the progression of melanoma and alterations in its epithelial tumor microenvironment.
Diabetic retinopathy progression 6 months post‐cataract surgery with intravitreous bevacizumab vs triamcinolone: A secondary analysis of the DiMECAT trial
Publisher: Wiley
Date: 31-05-2020
DOI: 10.1111/CEO.13771
Cytomegalovirus retinitis after treatment with Lenalidomide for multiple myeloma
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2013
Use of intravitreal rituximab for treatment of vitreoretinal lymphoma
Publisher: BMJ
Date: 24-10-2014
DOI: 10.1136/BJOPHTHALMOL-2013-304043
Abstract: Vitreoretinal lymphoma is a diffuse large B cell non-Hodgkin lymphoma. Targeting malignant cells with rituximab is being used increasingly as local chemotherapy, but information on this treatment is scant. We aimed to describe current therapeutic approaches, as well as responses to and complications of, intravitreal rituximab in patients with vitreoretinal lymphoma. Clinical data were collected in a standardised manner retrospectively on patients with vitreoretinal lymphoma treated with intravitreal rituximab. 48 eyes (34 patients) with vitreoretinal lymphoma were treated with a median of 3.5 intravitreal injections of rituximab (1 mg/0.1 mL) for new diagnosis (68.8%), progressive disease (29.9%) and maintenance therapy (2.1%). Intravitreal rituximab±methotrexate was the sole treatment in 19 eyes (39.6%). 31 eyes (64.6%) eyes achieved complete remission, after a median of 3 injections 7 of these eyes developed recurrent disease. 11 eyes (22.9%) achieved partial remission. Although rituximab may have contributed to complications reported in 12 eyes (25.0%), a 2-line loss of Snellen visual acuity occurred in only 2 of those eyes (4.2%). Approaches in rituximab-based intravitreal chemotherapy vary widely, but our findings suggest that this treatment may be safe and effective in inducing remission in a majority of eyes with vitreoretinal lymphoma.
Was Cathaysia part of Proterozoic Laurentia? - New data from Hainan Island, South China
Publisher: Wiley
Date: 18-03-2008
Recycling oceanic crust for continental crustal growth: Sr–Nd–Hf isotope evidence from granitoids in the western Junggar region, NW China
Publisher: Elsevier BV
Date: 2012
Author Correction: Global geochemical fingerprinting of plume intensity suggests coupling with the supercontinent cycle
Publisher: Springer Science and Business Media LLC
Date: 05-06-2020
DOI: 10.1038/S41467-020-16730-7
Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Geochronology of Neoproterozoic syn-rift magmatism in the Yangtze Craton, South China and correlations with other continents: Evidence for a mantle superplume that broke up Rodinia
Publisher: Elsevier BV
Date: 10-04-2003
The South China and Indochina neighborhood in the assembled Gondwana
Publisher: Copernicus GmbH
Date: 23-03-2020
DOI: 10.5194/EGUSPHERE-EGU2020-12874
Abstract: & & Investigations on the late Neoproterozoic to early Paleozoic sedimentary strata of western South China and northern Indochina reveal a provenance affinity between the two, which was mainly derived from the local western part of South China. The newly discovered provenance featured differently from that of the typical Indian-Australian Gondwana siliciclastic source. Basin types and sedimentation histories of the two sedimentary basins in western South China and northern Indochina are also comparable. Furthermore, previous studies discovered the geochronological, petrological and geochemical similarities of the early Paleozoic magmatic rocks between these two regions, suggesting a connection between the two during the subduction of the proto-Tethys ocean towards the northern Gondwana and the accretion of Asian continents onto the Gondwana mainland. Utilizing all such geological information, we speculate in this study that South China and Indochina were probably in the neighbourhood on the northern Gondwana margin when the Gondwana semi-supercontinent was assembled. Specifically, Indochina was likely located to the southwest of South China during the late Neoproterozoic to early Paleozoic. Apart from sedimentation, neither Indochina nor the western part of South China got much deformational and metamorphic impaction from the collision between South China and northern Gondwana during that time.& &
Middle Cambrian granites in the Dunhuang Block (NW China) mark the early subduction of the southernmost Paleo-Asian Ocean
Publisher: Elsevier BV
Date: 11-2020
microRNA-7-5p inhibits melanoma cell proliferation and metastasis by suppressing RelA/NF-?B
Publisher: Impact Journals, LLC
Date: 17-05-2016
The MC1R r allele does not increase melanoma risk in MITF E318K carriers
Publisher: Oxford University Press (OUP)
Date: 05-03-2023
DOI: 10.1093/BJD/LJAD041
Abstract: Population-wide screening for melanoma is not cost-effective, but genetic characterization could facilitate risk stratification and targeted screening. Common Melanocortin-1 receptor (MC1R) red hair colour (RHC) variants and Microphthalmia-associated transcription factor (MITF) E318K separately confer moderate melanoma susceptibility, but their interactive effects are relatively unexplored. To evaluate whether MC1R genotypes differentially affect melanoma risk in MITF E318K+ vs. E318K– in iduals. Melanoma status (affected or unaffected) and genotype data (MC1R and MITF E318K) were collated from research cohorts (five Australian and two European). In addition, RHC genotypes from E318K+ in iduals with and without melanoma were extracted from databases (The Cancer Genome Atlas and Medical Genome Research Bank, respectively). χ2 and logistic regression were used to evaluate RHC allele and genotype frequencies within E318K+/– cohorts depending on melanoma status. Replication analysis was conducted on 200 000 general-population exomes (UK Biobank). The cohort comprised 1165 MITF E318K– and 322 E318K+ in iduals. In E318K– cases MC1R R and r alleles increased melanoma risk relative to wild type (wt), P & 0.001 for both. Similarly, each MC1R RHC genotype (R/R, R/r, R/wt, r/r and r/wt) increased melanoma risk relative to wt/wt (P & 0.001 for all). In E318K+ cases, R alleles increased melanoma risk relative to the wt allele [odds ratio (OR) 2.04 (95% confidence interval 1.67–2.49) P = 0.01], while the r allele risk was comparable with the wt allele [OR 0.78 (0.54–1.14) vs. 1.00, respectively]. E318K+ cases with the r/r genotype had a lower but not significant melanoma risk relative to wt/wt [OR 0.52 (0.20–1.38)]. Within the E318K+ cohort, R genotypes (R/R, R/r and R/wt) conferred a significantly higher risk compared with non-R genotypes (r/r, r/wt and wt/wt) (P & 0.001). UK Biobank data supported our findings that r did not increase melanoma risk in E318K+ in iduals. RHC alleles/genotypes modify melanoma risk differently in MITF E318K– and E318K+ in iduals. Specifically, although all RHC alleles increase risk relative to wt in E318K– in iduals, only MC1R R increases melanoma risk in E318K+ in iduals. Importantly, in the E318K+ cohort the MC1R r allele risk is comparable with wt. These findings could inform counselling and management for MITF E318K+ in iduals.
Collision between the north and south China blocks: a crustal- detachment model for suturing in the region east of the Tanlu Fault
Publisher: Geological Society of America
Date: 1994
Melanocytes: From morphology to application
Publisher: S. Karger AG
Date: 2009
DOI: 10.1159/000178870
Abstract: Melanocytes in human skin are intricately regulated by keratinocytes and the surrounding stroma. The development of melanoma is thought to arise from disrupted melanocyte homeostasis. It is now known that microenvironment plays a major role in maintenance of cellular homeostasis and can contribute to tumor initiation and tumor progression. Historically, melanocyte studies have been performed in two-dimensional culture systems, and often with melanocytes cultured in the absence of keratinocytes. Here we present the biological basis for the use of organotypic, three-dimensional model systems in the study of melanoma, and highlight the features of the most utilized organotypic model sytems.
Spontaneous Dissociation and Dislocation of Retisert Pellet
Publisher: Informa UK Limited
Date: 02-2013
DOI: 10.3109/09273948.2012.736585
Abstract: To report 4 cases of spontaneous Retisert pellet dislocation. Retrospective case series. Description of cases. In all 4 cases, the time of Retisert implantation was 3-6 years prior to presentation. One case was complicated by retinal commotio and a retinal tear another was complicated by corneal endothelial failure, due to dislocation of the pellet into the anterior chamber. Spontaneous pellet separation may occur with Retisert as a late complication. It is unclear whether these dislocations are from a manufacturing fault or are related to extended intraocular exposure.
The Bikou basalts in the northwestern Yangtze block, South China: Remnants of 820-810 Ma continental flood basalts?
Publisher: Geological Society of America
Date: 11-2008
DOI: 10.1130/B26310.1
Choroidal lesions preceding symptom onset in birdshot chorioretinopathy
Publisher: American Medical Association (AMA)
Date: 07-2006
Younger Siblings, C-Reactive Protein, and Risk of Age-Related Macular Degeneration
Publisher: Oxford University Press (OUP)
Date: 04-2013
DOI: 10.1093/AJE/KWS332
Abstract: In this study, we examined the relationship between exposure to siblings and 1) the risk of age-related macular degeneration (AMD) and 2) C-reactive protein levels. We retrospectively analyzed pooled cross-sectional data from 2 studies: the Cardiovascular Health and Age-Related Maculopathy Study (2001-2002) and the Age-Related Maculopathy Statin Study (2004-2006). Associations between number of siblings and AMD were assessed by using multinomial logistic regression. Associations between number of siblings and C-reactive protein levels were examined by using a generalized linear model for γ distribution. A higher number of younger siblings was associated with significantly lower odds of early AMD in those with a family history of AMD (odds ratio = 0.2, 95% confidence interval: 0.1, 0.8) (P = 0.022) but was unrelated to AMD for those who had no family history of the disease (odds ratio = 1.0, 95% confidence interval: 0.9, 1.2) (P = 0.874). A higher number of younger siblings correlated with lower C-reactive protein levels (β = -0.19, 95% confidence interval: -0.38, -0.01) (P = 0.036). This supports the theory that immune modulation contributes to AMD pathogenesis and suggests that exposure to younger siblings might be protective when there is a family history of AMD.
Corrigendum to “Post-kinematic lithospheric delamination of the Wuyi–Yunkai orogen in South China: Evidence from ca. 435 Ma high-Mg basalts” [Lithos 154 (2012) 115–129]
Publisher: Elsevier BV
Date: 11-2014
Ocular, Aural, and Oral Manifestations
Publisher: Elsevier
Date: 2013
The BH3-mimetic ABT-737 sensitizes human melanoma cells to apoptosis induced by selective BRAF inhibitors but does not reverse acquired resistance
Publisher: Oxford University Press (OUP)
Date: 20-10-2013
Abstract: Although the introduction of selective v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) inhibitors has been a major advance in treatment of metastatic melanoma, approximately 50% of patients have limited responses including stabilization of disease or no response at all. This study aims to identify a novel means of overcoming resistance of melanoma to killing by BRAF inhibitors. We examined the influence of the BH3-mimetic ABT-737 on induction of apoptosis by the selective BRAF inhibitor PLX4720 in melanoma cells with or without BRAF V600E mutation. Included were cell lines established from four patients before and during treatment with selective BRAF inhibitors and 3D spheroids derived from these cell lines. Cell lines with no or low sensitivity to PLX4720 underwent synergistic increases and increased rates of apoptosis when combined with ABT-737. This degree of synergism was not seen in cell lines without BRAF V600E mutations. Apoptosis was mediated through the mitochondrial pathway and was due in part to upregulation of Bim as shown by inhibition of apoptosis following small interfering RNA knockdown of Bim. Similar effects were seen in cell lines established from patients prior to treatment but not in lines from patients clinically resistant to the selective BRAF inhibitors and in 3D spheroids derived from these cell lines. These results suggest that combination of selective BRAF inhibitors with ABT-737 or the related orally available compound ABT-263 may increase the degree and rate of responses in previously untreated patients with V600E melanoma but not in those with acquired resistance to these agents.
Safety and Efficacy of Adalimumab in Patients with Noninfectious Uveitis in an Ongoing Open-Label Study: VISUAL III
Publisher: Elsevier BV
Date: 07-2018
DOI: 10.1016/J.OPHTHA.2017.12.039
Abstract: To evaluate safety and efficacy of adalimumab in patients with noninfectious intermediate, posterior, or panuveitis. Phase 3, open-label, multicenter clinical trial extension (VISUAL III). Adults meeting treatment failure (TF) criteria or who completed VISUAL I or II (phase 3, randomized, double-masked, placebo-controlled) without TF. Patients received adalimumab 40 mg every other week. Interim follow-up data were described from VISUAL III weeks 0 through 78. Disease quiescence, steroid-free quiescence, active inflammatory chorioretinal/retinal vascular lesions, anterior chamber cell grade, vitreous haze grade, best-corrected visual acuity (BCVA), and corticosteroid dose. Binary data were reported using nonresponder imputation (NRI), continuous data using last observation carried forward and as-observed analysis, and corticosteroid dose using observed-case analysis. Adverse events (AEs) were reported from first adalimumab dose in VISUAL III through interim cutoff. Of 424 patients enrolled, 371 were included in intent-to-treat analysis. At study entry, 242 of 371 (65%) patients had active uveitis 60% (145/242, NRI) achieved quiescence at week 78, and 66% (95/143, as-observed) of those were corticosteroid free. At study entry, 129 of 371 (35%) patients had inactive uveitis 74% (96/129, NRI) achieved quiescence at week 78, and 93% (89/96, as-observed) of those were corticosteroid free. Inflammatory lesions, anterior chamber grade, and vitreous haze grade showed initial improvement followed by decline in patients with active uveitis and remained stable in patients with inactive uveitis. BCVA improved in patients with active uveitis from weeks 0 to 78 (0.27 to 0.14 logMAR left and right eyes as-observed) and remained stable in patients with inactive uveitis. Mean corticosteroid dose decreased from 13.6 mg/day (week 0) to 2.6 mg/day (week 78) in patients with active uveitis and remained stable in those with inactive uveitis (1.5-1.2 mg/day). AEs (424 events/100 patient-years) and serious AEs (16.5 events/100 patient-years) were comparable with previous VISUAL trials. Patients with active uveitis at study entry who received adalimumab therapy were likely to achieve quiescence, improve visual acuity, and reduce their daily uveitis-related systemic corticosteroid use. Most patients with inactive uveitis at study entry sustained quiescence without a systemic corticosteroid dose increase. No new safety signals were identified.
Acetylsalicylic Acid Governs the Effect of Sorafenib in RAS-Mutant Cancers
Publisher: American Association for Cancer Research (AACR)
Date: 28-02-2018
DOI: 10.1158/1078-0432.CCR-16-2118
Abstract: Purpose: Identify and characterize novel combinations of sorafenib with anti-inflammatory painkillers to target difficult-to-treat RAS-mutant cancer. Experimental Design: The cytotoxicity of acetylsalicylic acid (aspirin) in combination with the multikinase inhibitor sorafenib (Nexavar) was assessed in RAS-mutant cell lines in vitro. The underlying mechanism for the increased cytotoxicity was investigated using selective inhibitors and shRNA-mediated gene knockdown. In vitro results were confirmed in RAS-mutant xenograft mouse models in vivo. Results: The addition of aspirin but not isobutylphenylpropanoic acid (ibruprofen) or celecoxib (Celebrex) significantly increased the in vitro cytotoxicity of sorafenib. Mechanistically, combined exposure resulted in increased BRAF/CRAF dimerization and the simultaneous hyperactivation of the AMPK and ERK pathways. Combining sorafenib with other AMPK activators, such as metformin or A769662, was not sufficient to decrease cell viability due to sole activation of the AMPK pathway. The cytotoxicity of sorafenib and aspirin was blocked by inhibition of the AMPK or ERK pathways through shRNA or via pharmacologic inhibitors of RAF (LY3009120), MEK (trametinib), or AMPK (compound C). The combination was found to be specific for RAS/RAF–mutant cells and had no significant effect in RAS/RAF–wild-type keratinocytes or melanoma cells. In vivo treatment of human xenografts in NSG mice with sorafenib and aspirin significantly reduced tumor volume compared with each single-agent treatment. Conclusions: Combination sorafenib and aspirin exerts cytotoxicity against RAS/RAF–mutant cells by simultaneously affecting two independent pathways and represents a promising novel strategy for the treatment of RAS-mutant cancers. Clin Cancer Res 24(5) 1090–102. ©2017 AACR.
Paleomagnetism of the Upper Devonian reef complexes, Canning Basin, Western Australia
Publisher: American Geophysical Union (AGU)
Date: 02-1995
DOI: 10.1029/94TC01622
Detrital zircon U–Pb and Hf signatures of Paleo-Mesoproterozoic strata in the Priest River region, northwestern USA: A record of Laurentia assembly and Nuna tenure
Publisher: Elsevier BV
Date: 12-2021
South Australian record of a Rodinian epicontinental basin and its mid-neoproterozoic breakup (∼700 Ma) to form the Palaeo-Pacific Ocean
Publisher: Elsevier BV
Date: 10-1994
Reconstruction of the Panthalassan margin of Gondwanaland
Publisher: Geological Society of America
Date: 1994
DOI: 10.1130/MEM184-P5
Supercontinent-superplume coupling, true polar wander and plume mobility: Plate dominance in whole-mantle tectonics
Publisher: Elsevier BV
Date: 10-2009
Melanoma: From tumor-specifi c mutations to a new molecular taxonomy and innovative therapeutics
Publisher: Springer Berlin Heidelberg
Date: 2015
Late Cretaceous (ca. 90Ma) adakitic intrusive rocks in the Kelu area, Gangdese Belt (southern Tibet): Slab melting and implications for Cu–Au mineralization
Publisher: Elsevier BV
Date: 07-2012
Initiation of the Indosinian Orogeny in South China: Evidence for a Permian magmatic arc on Hainan Island
Publisher: University of Chicago Press
Date: 05-2006
DOI: 10.1086/501222
An Organometallic Protein Kinase Inhibitor Pharmacologically Activates p53 and Induces Apoptosis in Human Melanoma Cells
Publisher: American Association for Cancer Research (AACR)
Date: 2007
DOI: 10.1158/0008-5472.CAN-06-1538
Abstract: Unlike other tumors, melanomas harbor wild-type (WT) p53 but exhibit impaired p53-dependent apoptosis. The mechanisms for the impaired p53 activation are poorly understood but may be linked to the high expression of the p53 suppressor Mdm2, which is found in & % of melanoma lesions. Here, we describe an organometallic glycogen synthase kinase 3β (GSK3β) inhibitor (DW1/2) as a potent activator of p53 and inducer of cell death in otherwise highly chemoresistant melanoma cells. Using RNA interference and pharmacologic approaches, we show that p53 is required for the cytotoxic effects of this organometallic inhibitor. The DW1/2 compound was barely able to induce cell death in melanoma cells with p53 mutations, further confirming the requirement for p53-WT in the cytotoxic effects of the GSK3β inhibition. Mechanistic analysis of the p53-dependent cell death indicated an apoptotic mechanism involving depolarization of mitochondrial membrane potential, caspase cleavage, and elevated NOXA expression. The effect of p53 was not simply due to passive up-regulation of protein expression as adenoviral-mediated overexpression of p53 was not able to induce cell death. Treatment of melanoma cells with DW1/2 was instead found to decrease levels of Mdm2 and Mdm4. The importance of Mdm2 down-regulation in DW1/2-induced apoptosis was confirmed by treating the p53-WT cells with the p53/Mdm2 antagonist Nutlin-3. Taken together, our data provide a new strategy for the pharmacologic activation of p53 in melanoma, which may be a viable approach for overcoming apoptotic resistance in melanoma and offer new hope for rational melanoma therapy. [Cancer Res 2007 (1):209–17]
How not to build a supercontinent: A reply to J.D.A. Piper
Publisher: Elsevier BV
Date: 10-2009
Global record of 1600–700Ma Large Igneous Provinces (LIPs): Implications for the reconstruction of the proposed Nuna (Columbia) and Rodinia supercontinents
Publisher: Elsevier BV
Date: 2008
Post-kinematic lithospheric delamination of the Wuyi-Yunkai orogen in South China: Evidence from ca. 435 Ma high-Mg basalts
Publisher: Elsevier BV
Date: 12-2012
Erratum: AMD: To supplement or not? (Clinical and Experimental Ophthalmology (2004) vol. 32 (341-3))
Publisher: Wiley
Date: 10-2004
Paleogeographic forcing of the strontium isotopic cycle in the Neoproterozoic
Publisher: Elsevier BV
Date: 02-2017
Pliocene-Quaternary crustal melting in central and northern Tibet and insights into crustal flow
Publisher: Springer Science and Business Media LLC
Date: 16-06-2016
DOI: 10.1038/NCOMMS11888
Abstract: There is considerable controversy over the nature of geophysically recognized low-velocity–high-conductivity zones (LV–HCZs) within the Tibetan crust, and their role in models for the development of the Tibetan Plateau. Here we report petrological and geochemical data on magmas erupted 4.7–0.3 Myr ago in central and northern Tibet, demonstrating that they were generated by partial melting of crustal rocks at temperatures of 700–1,050 °C and pressures of 0.5–1.5 GPa. Thus Pliocene-Quaternary melting of crustal rocks occurred at depths of 15–50 km in areas where the LV–HCZs have been recognized. This provides new petrological evidence that the LV–HCZs are sources of partial melt. It is inferred that crustal melting played a key role in triggering crustal weakening and outward crustal flow in the expansion of the Tibetan Plateau.
Closing the “North American Magmatic” Gap: Crustal evolution of the Clearwater Block from multi-isotope and trace element zircon data
Publisher: Elsevier BV
Date: 02-2022
Geochronological and geochemical results from Mesozoic basalts in southern South China Block support the flat-slab subduction model
Publisher: Elsevier BV
Date: 02-2012
History of neoproterozoic rift basins in South China: Implications for Rodinia break-up
Publisher: Elsevier BV
Date: 10-04-2003
1.6 Ga crustal thickening along the final Nuna suture
Publisher: Geological Society of America
Date: 25-09-2018
DOI: 10.1130/G45198.1
Assembly, configuration, and break-up history of Rodinia: A synthesis
Publisher: Elsevier BV
Date: 2008
Paleomagnetic constraints on the duration of the Australia-Laurentia connection in the core of the Nuna supercontinent
Publisher: Geological Society of America
Date: 23-09-2020
DOI: 10.1130/G47823.1
Abstract: The Australia-Laurentia connection in the Paleoproterozoic to Mesoproterozoic supercontinent Nuna is thought to have initiated by ca. 1.6 Ga when both continents were locked in a proto-SWEAT (southwestern U.S.–East Antarctic) configuration. However, the longevity of that configuration is poorly constrained. Here, we present a new high-quality paleomagnetic pole from the ca. 1.3 Ga Derim Derim sills of northern Australia that suggests Australia and Laurentia were in the same configuration at that time. This new paleopole also supports a connection between Australia and North China and, in conjunction with previously reported data from all continents, indicates that the breakup of Nuna largely occurred between ca. 1.3 and 1.2 Ga.
Tectonostratigraphic history of the Ediacaran-Silurian Nanhua foreland basin in South China
Publisher: Elsevier BV
Date: 04-2016
SEROUS RETINAL DETACHMENT AS A COMPLICATION OF ACUTE POSTERIOR MULTIFOCAL PLACOID PIGMENT EPITHELIOPATHY
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2010
NFIB Mediates BRN2 Driven Melanoma Cell Migration and Invasion Through Regulation of EZH2 and MITF
Publisher: Elsevier BV
Date: 02-2017
Mutual complement between statistical and neural network approaches for rock magnetism data analysis
Publisher: Elsevier BV
Date: 08-2009
Recalibrating Rodinian rifting in the northwestern United States
Publisher: Geological Society of America
Date: 05-02-2021
DOI: 10.1130/G48435.1
Abstract: A lack of precise age constraints for Neoproterozoic strata in the northwestern United States (Washington State), including the Buffalo Hump Formation (BHF), has resulted in conflicting interpretations of Rodinia amalgamation and breakup processes. Previous detrital zircon (DZ) studies identified a youngest ca. 1.1 Ga DZ age population in the BHF, interpreted to reflect mostly first-cycle sourcing of unidentified but proximal magmatic rocks intruded during the amalgamation of Rodinia at ca. 1.0 Ga. Alternatively, the ca. 1.1 Ga DZ population has been suggested to represent a distal source with deposition occurring during the early phases of Rodinia rifting, more than 250 m.y. after zircon crystallization. We combined conventional laser-ablation split-stream analyses of U-Pb/Lu-Hf isotopes in zircon with a method of rapid (8 s per spot) U-Pb analysis to evaluate these opposing models. Our study of ∼2000 DZ grains from the BHF identified for the first time a minor (∼1%) yet significant ca. 760 Ma population, which constrains the maximum depositional age. This new geochronology implies that the BHF records early rift deposition during the breakup of Rodinia and correlates with sedimentary rocks found in other late Tonian basins of southwestern Laurentia.
Short-term suppression of A315T mutant human TDP-43 expression improves functional deficits in a novel inducible transgenic mouse model of FTLD-TDP and ALS
Publisher: Springer Science and Business Media LLC
Date: 05-10-2015
DOI: 10.1007/S00401-015-1486-0
Abstract: The nuclear transactive response DNA-binding protein 43 (TDP-43) undergoes relocalization to the cytoplasm with formation of cytoplasmic deposits in neurons in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Pathogenic mutations in the TDP-43-encoding TARDBP gene in familial ALS as well as non-mutant human TDP-43 have been utilized to model FTD/ALS in cell culture and animals, including mice. Here, we report novel A315T mutant TDP-43 transgenic mice, iTDP-43(A315T), with controlled neuronal over-expression. Constitutive expression of human TDP-43(A315T) resulted in pronounced early-onset and progressive neurodegeneration, which was associated with compromised motor performance, spatial memory and disinhibition. Muscle atrophy resulted in reduced grip strength. Cortical degeneration presented with pronounced astrocyte activation. Using differential protein extraction from iTDP-43(A315T) brains, we found cytoplasmic localization, fragmentation, phosphorylation and ubiquitination and insolubility of TDP-43. Surprisingly, suppression of human TDP-43(A315T) expression in mice with overt neurodegeneration for only 1 week was sufficient to significantly improve motor and behavioral deficits, and reduce astrogliosis. Our data suggest that functional deficits in iTDP-43(A315T) mice are at least in part a direct and transient effect of the presence of TDP-43(A315T). Furthermore, it illustrates the compensatory capacity of compromised neurons once transgenic TDP-43 is removed, with implications for future treatments.
The Incidence of Ocular Tuberculosis in Australia Over the Past 10 Years (2006–2015)
Publisher: Informa UK Limited
Date: 13-09-2017
DOI: 10.1080/09286586.2017.1336562
Abstract: To determine the incidence and clinical phenotype of ocular tuberculosis in Australia based on the mandatory jurisdictional health notification records for TB. A whole population retrospective case series (Australia). Patients diagnosed with ocular tuberculosis were identified over the past 10 years (1 January 2006 to 31 December 2015) as recorded by in idual Health Department jurisdictions per mandatory health notifications. The incidence rates were calculated based on the available Australian census data. Incidence rates were age and sex standardized. A total of 162 cases of ocular tuberculosis were identified across Australia over a 10-year time period. Of these, 156 participants were overseas born. The 10-year Australian incidence of ocular tuberculosis was 0.77 per 100,000 people. While there has been a downward trend in overall TB annual incidence rates from 2010 to 2015, over the same period the annual incidence of ocular TB has increased compared to the 4 previous years. Descriptive clinical data regarding the ocular manifestations of TB was available in 73/157 patients. In these 73 patients the commonest manifestations of ocular TB were unspecified uveitis (50.1%), focal, multifocal or serpiginous choroiditis or chorioretinitis (12.3%) and retinal vasculitis (11.0%). Of patients with ocular TB, 4/162 (2.47%) had associated pulmonary TB and 8/162 (4.94%) had associated systemic (non-pulmonary) TB. Systemic anti-TB therapy was administered to 161 patients. The annual Australian incidence of ocular tuberculosis was 0.077 per 100,000 people. Increasing notifications in the past 6 years may demonstrate increased awareness and changing diagnostic criteria of the disease in the Australian population.
Meeting report from the 7th International Melanoma Congress, Sydney, November, 2010
Publisher: Wiley
Date: 22-12-2010
Spatio–temporal evolution of Mesoproterozoic magmatism in NE Australia: A hybrid tectonic model for final Nuna assembly
Publisher: Elsevier BV
Date: 05-2022
Growth and adaptation mechanisms of tumour spheroids with time-dependent oxygen availability
Publisher: Public Library of Science (PLoS)
Date: 12-01-2023
DOI: 10.1371/JOURNAL.PCBI.1010833
Abstract: Tumours are subject to external environmental variability. However, in vitro tumour spheroid experiments, used to understand cancer progression and develop cancer therapies, have been routinely performed for the past fifty years in constant external environments. Furthermore, spheroids are typically grown in ambient atmospheric oxygen (normoxia), whereas most in vivo tumours exist in hypoxic environments. Therefore, there are clear discrepancies between in vitro and in vivo conditions. We explore these discrepancies by combining tools from experimental biology, mathematical modelling, and statistical uncertainty quantification. Focusing on oxygen variability to develop our framework, we reveal key biological mechanisms governing tumour spheroid growth. Growing spheroids in time-dependent conditions, we identify and quantify novel biological adaptation mechanisms, including unexpected necrotic core removal, and transient reversal of the tumour spheroid growth phases.
Heterogeneous Exhumation of the Mount Isa Orogen in NE Australia After 1.6 Ga Nuna Assembly: New High-Precision 40Ar/39Ar Thermochronological Constraints
Publisher: American Geophysical Union (AGU)
Date: 12-2020
DOI: 10.1029/2020TC006129
Paleo- to Mesoproterozoic magmatic and tectonic evolution of the southwestern Yangtze Block, south China: New constraints from ca. 1.7–1.5 Ga mafic rocks in the Huili-Dongchuan area
Publisher: Elsevier BV
Date: 11-2020
Differential induction of connexins 26 and 30 in skin tumors and their adjacent epidermis
Publisher: SAGE Publications
Date: 02-2006
Abstract: Gap junctions (GJs) have been shown to play a role in tumor progression including a variety of keratinocyte-derived and non-keratinocyte-derived skin tumors. Here we show that the synthesis of the GJ proteins connexin 26 and connexin 30 (Cx26 and Cx30) is induced in keratinocyte-derived epithelial skin tumors whereas there is either no change or a downregulation of Cx43. Cx26, Cx30, and Cx43 are absent in non-epithelial skin tumors. Further, Cx26 and Cx30 are induced in the epidermis adjacent to malignant melanoma but absent in the epidermis adjacent to benign non-epithelial skin lesions (melanocytic nevi and angioma). The keratinocyte-derived skin tumors are very heterogeneous regarding the Cx26/Cx30 pattern in the epidermis at the periphery of the tumors. We did not observe any difference in the localization of the very similar proteins Cx26 and Cx30 but a variation in intensity of immunoreactivity. As the staining patterns of Cx26 and Cx30 antibodies are not identical to those of CK6, a marker for hyperproliferation, and CK17, a marker for trauma, we discuss that the induction of these gap junctional proteins exceeds a reflection of reactive hyperproliferative or traumatized epidermis. We further discuss the putative roles of these gap junctional proteins in tumor progression.
Multimodal investigation of thermally induced changes in magnetic fabric and magnetic mineralogy
Publisher: Oxford University Press (OUP)
Date: 12-1998
Ridge subduction and crustal growth in the Central Asian Orogenic Belt: Evidence from Late Carboniferous adakites and high-Mg diorites in the western Junggar region, northern Xinjiang (west China)
Publisher: Elsevier BV
Date: 10-2010
Nanhua Rift: A Story of Continental Rift Related to Rodinia Break-up
Publisher: Elsevier BV
Date: 10-1999
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