ORCID Profile
0009-0008-6595-9972
Current Organisation
University of Cambridge
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Publisher: Elsevier BV
Date: 02-1996
DOI: 10.1016/0166-6851(95)02569-3
Abstract: The coronavirus disease (COVID-19) has rapidly spread throughout the world and while pregnant women present the same adverse outcome rates, they are underrepresented in clinical research. We collected clinical data of 155 test-positive COVID-19 pregnant women at Stony Brook University Hospital. Many of these collected data are of multivariate categorical type, where the number of possible outcomes grows exponentially as the dimension of data increases. We modeled the data within the unsupervised Bayesian framework and mapped them into a lower dimensional space using latent Gaussian processes. The latent features in the lower dimensional space were further used for predicting if a pregnant woman would be admitted to a hospital due to COVID-19 or would remain with mild symptoms. We compared the prediction accuracy with the dummy/one-hot encoding of categorical data and found that the latent Gaussian process had better accuracy.
Publisher: The Royal Society
Date: 29-01-2002
Abstract: The 35 Mb genome of Leishmania should be sequenced by late 2002. It contains approximately 8500 genes that will probably translate into more than 10 000 proteins. In the laboratory we have been piloting strategies to try to harness the power of the genome–proteome for rapid screening of new vaccine candidate. To this end, microarray analysis of 1094 unique genes identified using an EST analysis of 2091 cDNA clones from spliced leader libraries prepared from different developmental stages of Leishmania has been employed. The plan was to identify amastigote–expressed genes that could be used in high–throughput DNA–vaccine screens to identify potential new vaccine candidates. Despite the lack of transcriptional regulation that polycistronic transcription in Leishmania dictates, the data provide evidence for a high level of post–transcriptional regulation of RNA abundance during the developmental cycle of promastigotes in culture and in lesion–derived amastigotes of Leishmania major . This has provided 147 candidates from the 1094 unique genes that are specifically upregulated in amastigotes and are being used in vaccine studies. Using DNA vaccination, it was demonstrated that pooling strategies can work to identify protective vaccines, but it was found that some potentially protective antigens are masked by other disease–exacerbatory antigens in the pool. A total of 100 new vaccine candidates are currently being tested separately and in pools to extend this analysis, and to facilitate retrospective bioinformatic analysis to develop predictive algorithms for sequences that constitute potentially protective antigens. We are also working with other members of the Leishmania Genome Network to determine whether RNA expression determined by microarray analyses parallels expression at the protein level. We believe we are making good progress in developing strategies that will allow rapid translation of the sequence of Leishmania into potential interventions for disease control in humans.
Publisher: Elsevier BV
Date: 06-2004
Publisher: Portland Press Ltd.
Date: 09-1989
DOI: 10.1042/CS0770323
Abstract: 1. Endogenous opioids have been implicated in the control of breathing in neonates, but their role in ventilatory control in adults remains unclear. 2. We studied the relationship between circulating immunoreactive β-endorphin and the ventilatory and mouth occlusion pressure responses to hypercapnia in 12 healthy male subjects. In addition, we examined the effect of repetitive hypercapnia on plasma β-endorphin and Cortisol levels. 3. A weak but significant negative relationship between the ventilatory response to hypercapnia and basal plasma β-endorphin levels was observed (r = −0.35, P & 0.01). A similar negative relationship was noted between mouth occlusion pressure response to hypercapnia and basal plasma β-endorphin levels (r = −0.36, P & 0.01). 4. Repetitive hypercapnia prevented the fall in plasma Cortisol that occurred under control conditions (P & 0.02) but had no effect on plasma β-endorphin. 5. We conclude that plasma β-endorphin may play a role in the central chemical control of breathing in man.
Publisher: Elsevier BV
Date: 10-1998
DOI: 10.1016/S0166-6851(98)00122-4
Abstract: Leishmania spp. encounter damaging oxygen metabolites from endogenous metabolic processes as well as from exogenous sources, such as inside the gut of the sandfly vector and within host macrophages. The recently described peroxidoxin protein family form part of a novel pathway for metabolising hydrogen peroxide that, in trypanosomatids, links peroxide reduction to NADPH oxidation via trypanothione. Here we report the cloning and characterisation of the Leishmania major peroxidoxin gene, tryparedoxin peroxidase (TryP). TryP is a multi-copy gene arranged in a complex tandem array located on the size polymorphic homologues of chromosome 15. Northern analysis showed that TryP expresses a single 1.6 kb mRNA throughout promastigote development. TryP encodes a 22-kDa protein with two conserved cysteine-containing domains that defines it as a 2-Cys peroxidoxin. Purified recombinant TryP protein catabolised hydrogen peroxide in the presence of the tryparedoxin homologue from Crithidia fasciculata (Cf-TryX), trypanothione, trypanothione reductase and NADPH. The demonstration that L. major utilises a three-protein peroxidase system confirms that this is a mechanism of protection against oxidative damage in this parasite.
Publisher: Elsevier BV
Date: 08-1998
Publisher: Springer Science and Business Media LLC
Date: 10-2007
Abstract: Drug discovery might be better termed drug invention. Discoveries take place globally, and many arise from academia and research institutes. The job of the biotechnology and pharmaceutical industry is to identify those that stand the greatest chance of being turned into medicines to improve health-in other words, to invent a practical outcome on the basis of discovery. In this commentary we identify some of the areas in which molecular medicine has had the greatest impact and continues to change the invention of medicines.
Publisher: Elsevier BV
Date: 07-2004
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Mark Levick.