41 research outputs found

    Population and molecular level studies of malaria transmission

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    © 2017 Dr. Charlie JennisonCharlie Jennison investigated the population genetics of two human malaria species in Papua New Guinea, revealing greater structure in Plasmodium falciparum than in P. vivax populations. He also discovered a role for the parasite protein Thrombospondin Related Sporozoite Protein in the motility and infectivity of P. falciparum sporozoites

    Fourier transforms: and convolutions for the experimentalist

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    Fourier Transforms and Convolutions for the Experimentalist provides the experimentalist with a guide to the principles and practical uses of the Fourier transformation. It aims to bridge the gap between the more abstract account of a purely mathematical approach and the rule of thumb calculation and intuition of the practical worker. The monograph springs from a lecture course which the author has given in recent years and for which he has drawn upon a number of sources, including a set of notes compiled by the late Dr. I. C. Browne from a series of lectures given by Mr. J . A. Ratcliffe of

    Village Roadshow Limited : commissioned history of Village Roadshow Corporation

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    This thesis was scanned from the print manuscript for digital preservation and is copyright the author. Researchers can access this thesis by asking their local university, institution or public library to make a request on their behalf. Monash staff and postgraduate students can use the link in the References field

    Inhibition of Plasmepsin V Activity Blocks Plasmodium falciparum Gametocytogenesis and Transmission to Mosquitoes

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    Plasmodium falciparum gametocytes infect mosquitoes and are responsible for malaria transmission. New interventions that block transmission could accelerate malaria elimination. Gametocytes develop within erythrocytes and activate protein export pathways that remodel the host cell. Plasmepsin V (PMV) is an aspartyl protease that is required for protein export in asexual parasites, but its function and essentiality in gametocytes has not been definitively proven, nor has PMV been assessed as a transmission-blocking drug target. Here, we show that PMV is expressed and can be inhibited specifically in P. falciparum stage I-II gametocytes. PMV inhibitors block processing and export of gametocyte effector proteins and inhibit development of stage II-V gametocytes. Gametocytogenesis in the presence of sublethal inhibitor concentrations results in stage V gametocytes that fail to infect mosquitoes. Therefore, PMV primes gametocyte effectors for export, which is essential for the development and fitness of gametocytes for transmission to mosquitoes.Full Tex

    Computer and information technologies resources for the postsecondary education of students with disabilities : final report to the Office of learning technologies

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    Comprend des références bibliographiques."Results of an empirical study investigating the views and concerns about computer and adaptive computer technologies of postsecondary disability service providers are presented. The study was carried out in both French and English in the spring of 2000. Based on structured interviews with 156 Canadians who provide disability related services to students, the responses represent an 80% participation rate. Key findings in the following areas are highlighted: characteristics of postsecondary disability service providers; presence of students with disabilities on campus, availability and accessibility of campus computers to students with disabilities, important factors in meeting the computer related needs of students with disabilities, and the presence and needs of postsecondary faculty and staff with disabilities. An extensive listing of useful resources is provided and recommendations are made to guide decision making to ensure that Canadian colleges and universities are technologically welcoming of the whole campus community." -- Provided by author

    Generation of a transgenic P. cynomolgi parasite expressing P. vivax circumsporozoite protein for testing pre-erythrocytic malaria vaccines in non-human primates

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    Malaria, caused by infection with Plasmodium parasites, exacts a heavy toll worldwide. There are two licensed vaccines for malaria as well as two monoclonal antibodies that have shown promising efficacy in field trials. Both vaccines and monoclonals target the major surface protein (circumsporozoite protein, CSP) of Plasmodium falciparum. Yet Pf is only one of the four major species of Plasmodium that infects humans. Plasmodium vivax is the second leading cause of malaria but Pv vaccine and monoclonal development lags far behind P. falciparum owing to the lack of basic preclinical tools such as in vitro culture or mouse models that replicate the key biological features of P. vivax. Notably among these features is the ability to form dormant liver stages (hypnozoites) that reactivate and drive the majority of P. vivax malaria burden. Plasmodium cynomolgi is a simian parasite which is genotypically and phenotypically very close to P. vivax, can infect common research non-human primates and replicates many features of Pv including relapsing hypnozoites. Recently, a strain of Pc has been adapted to in vitro culture allowing parasite transgenesis. Here, we created a transgenic P. cynomolgi parasite in which the endogenous Pc CSP has been replaced with Pv CSP with the goal of enabling preclinical study of anti-Pv CSP interventions to protect against primary and relapse infections. We show that the in vitro-generated transgenic Pc[PvCSP] parasite expresses both serotypes of Pv CSP and retains full functionality in vivo including the ability to transmit to laboratory-reared Anopheles mosquitos and cause relapsing infection in rhesus macaques. To our knowledge, this is the first gene replacement in a relapsing Plasmodium species. This work can directly enable in vivo development of anti-Pv CSP interventions and provide a blueprint for the study of relapsing malaria through reverse genetics

    Socio-economic inequality in small area use of elective total hip replacement in the English NHS in 1991 and 2001

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    International evidence suggests that there are substantial socio-economic inequalities in the delivery of specialist health services, even in the UK and other high-income countries with publicly funded health systems (Goddard and Smith 2001, Dixon et al. 2003, Van Doorslaer, Koolman and Jones 2004, Van Doorslaer et al. 2000). Studies of total hip replacement in the English NHS have yielded particularly striking examples, given that hip replacement is such a common, effective and longestablished health technology. Administrative data show that people living in deprived areas are less likely to receive hip replacement (Chaturvedi and Ben-Shlomo 1995, Dixon et al. 2004) while survey data suggest they may be more likely to need it (Milner et al. 2004). However, previous studies have not examined change in inequality over time. This paper presents evidence on the change in socio-economic inequality in small area use of elective total hip replacement in the English NHS, comparing 1991 with 2001. This was a period of important large-scale health care reform in England, involving at least two significant reforms that might potentially have influenced socio-economic inequality in health care delivery: (1) the introduction and subsequent abolition of the Conservative “internal market” 1991-7, and (2) the introduction in 1995 of a revised NHS resource allocation formula designed to reduce geographical inequalities in health care delivery. Two datasets, for 1991 and 2001, were assembled from routine NHS data sources: Hospital Episode Statistics (HES) on hospital utilisation in England and the corresponding decennial National Censuses in 1991 and 2001. Both datasets contain information on over 8,000 electoral wards in England (over 95% of the total). To improve comparability, a common geography of frozen 1991 wards was adopted. The Townsend deprivation score was employed as an indicator of socio-economic status. Inequality was analysed in two ways. First, for comparability with previous small area studies of hip replacement, by using simple range measures based on indirectly age-sex standardised utilisation ratios (SURs) by deprivation quintile groups. Second, using concentration indices of deprivationrelated inequality in use based on indirectly age-sex standardised utilisation ratios for each individual small area. Each SUR is the observed use divided by the expected use, if each age and sex group in the study population had the same rates of use as the national population.

    Multi-dimensional key generation of ICMetrics for cloud computing

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    Despite the rapid expansion and uptake of cloud based services, lack of trust in the provenance of such services represents a significant inhibiting factor in the further expansion of such service. This paper explores an approach to assure trust and provenance in cloud based services via the generation of digital signatures using properties or features derived from their own construction and software behaviour. The resulting system removes the need for a server to store a private key in a typical Public/Private-Key Infrastructure for data sources. Rather, keys are generated at run-time by features obtained as service execution proceeds. In this paper we investigate several potential software features for suitability during the employment of a cloud service identification system. The generation of stable and unique digital identity from features in Cloud computing is challenging because of the unstable operation environments that implies the features employed are likely to vary under normal operating conditions. To address this, we introduce a multi-dimensional key generation technology which maps from multi-dimensional feature space directly to a key space. Subsequently, a smooth entropy algorithm is developed to evaluate the entropy of key space

    Author Correction: Discovery of drug–omics associations in type 2 diabetes with generative deep-learning models (<em>Nature Biotechnology</em>, (2023), 41, 3, (399-408), 10.1038/s41587-022-01520-x)

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    \ua9 2023, The Author(s).In the version of this article initially published, Cristina Leal Rodr\uedguez (Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark) was omitted from the author list. The error has been corrected in the HTML and PDF versions of the article
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