An Appstore for Java

We describe a new App store for Java that makes use of OpenWebstart technologies to deploy Java to Windows, Mac and Unix. Apps are signed with certificates that are sourced from a Certificate Authority. The store is responsible for establishing developer identity. Once identity is established, the developer pays one low yearly fee to distribute up to 6 applications. The signing is done in a semi-automatic manner. If clients claim that harm is done by an application, the application is isolated until an examination is performed. Trusted Jar files can be run outside of the “sandbox” and thus be given full access to the target system. The Java app store addresses a subproblem of the Initium project. Initium is a Latin word that means: “at the start

Conservation of Human Microsatellites across 450 Million Years of Evolution

The sequencing and comparison of vertebrate genomes have enabled the identification of widely conserved genomic elements. Chief among these are genes and cis-regulatory regions, which are often under selective constraints that promote their retention in related organisms. The conservation of elements that either lack function or whose functions are yet to be ascribed has been relatively little investigated. In particular, microsatellites, a class of highly polymorphic repetitive sequences considered by most to be neutrally evolving junk DNA that is too labile to be maintained in distant species, have not been comprehensively studied in a comparative genomic framework. Here, we used the UCSC alignment of the human genome against those of 11 mammalian and five nonmammalian vertebrates to identify and examine the extent of conservation of human microsatellites in vertebrate genomes. Out of 696,016 microsatellites found in human sequences, 85.39% were conserved in at least one other species, whereas 28.65% and 5.98% were found in at least one and three nonprimate species, respectively. An exponential decline of microsatellite conservation with increasing evolutionary time, a comparable distribution of conserved versus nonconserved microsatellites in the human genome, and a positive correlation between microsatellite conservation and overall sequence conservation, all suggest that most microsatellites are only maintained in genomes by chance, although exceptionally conserved human microsatellites were also found in distant mammals and other vertebrates. Our findings provide the first comprehensive survey of microsatellite conservation across deep evolutionary timescales, in this case 450 Myr of vertebrate evolution, and provide new tools for the identification of functional conserved microsatellites, the development of cross-species microsatellite markers and the study of microsatellite evolution above the species level

Does reductive metabolism predict response to tirapazamine (SR 4233) in human non-small-cell lung cancer cell lines?

The bioreductive drug tirapazamine (TPZ, SR 4233, WIN 59075) is a lead compound in a series of potent cytotoxins that selectively kill hypoxic rodent and human solid tumour cells in vitro and in vivo. Phases II and III trials have demonstrated its efficacy in combination with both fractionated radiotherapy and some chemotherapy. We have evaluated the generality of an enzyme-directed approach to TPZ toxicity by examining the importance of the one-electron reducing enzyme NADPH:cytochrome P450 reductase (P450R) in the metabolism and toxicity of this lead prodrug in a panel of seven human non-small-cell lung cancer cell lines. We relate our findings on TPZ sensitivity in these lung lines with our previously published results on TPZ sensitivity in six human breast cancer cell lines (Patterson et al (1995) Br J Cancer 72: 1144–1150) and with the sensitivity of all these cell types to eight unrelated cancer chemotherapeutic agents with diverse modes of action. Our results demonstrate that P450R plays a significant role in the activation of TPZ in this panel of lung lines, which is consistent with previous observations in a panel of breast cancer cell lines (Patterson et al (1995) Br J Cancer 72: 1144–1150; Patterson et al (1997) Br J Cancer 76: 1338–1347). However, in the lung lines it is likely that it is the inherent ability of these cells to respond to multiple forms of DNA damage, including that arising from P450R-dependent TPZ metabolism, that underlies the ultimate expression of toxicity. © 1999 Cancer Research Campaig

Coordinated repression of BIM and PUMA by Epstein-Barr virus latent genes maintains the survival of Burkitt lymphoma cells.

While the association of Epstein-Barr virus (EBV) with Burkitt lymphoma (BL) has long been recognised, the precise role of the virus in BL pathogenesis is not fully resolved. EBV can be lost spontaneously from some BL cell lines, and these EBV-loss lymphoma cells reportedly have a survival disadvantage. Here we have generated an extensive panel of EBV-loss clones from multiple BL backgrounds and examined their phenotype comparing them to their isogenic EBV-positive counterparts. We report that, while loss of EBV from BL cells is rare, it is consistently associated with an enhanced predisposition to undergo apoptosis and reduced tumorigenicity in vivo. Importantly, reinfection of EBV-loss clones with EBV, but surprisingly not transduction with individual BL-associated latent viral genes, restored protection from apoptosis. Expression profiling and functional analysis of apoptosis-related proteins and transcripts in BL cells revealed that EBV inhibits the upregulation of the proapoptotic BH3-only proteins, BIM and PUMA. We conclude that latent EBV genes cooperatively enhance the survival of BL cells by suppression of the intrinsic apoptosis pathway signalling via inhibition of the potent apoptosis initiators, BIM and PUMA.Cell Death and Differentiation advance online publication, 29 September 2017; doi:10.1038/cdd.2017.150

Epidemiology and interactions of Human Immunodeficiency Virus - 1 and Schistosoma mansoni in sub-Saharan Africa.

Human Immunodeficiency Virus-1/AIDS and Schistosoma mansoni are widespread in sub-Saharan Africa and co-infection occurs commonly. Since the early 1990s, it has been suggested that the two infections may interact and potentiate the effects of each other within co-infected human hosts. Indeed, S. mansoni infection has been suggested to be a risk factor for HIV transmission and progression in Africa. If so, it would follow that mass deworming could have beneficial effects on HIV-1 transmission dynamics. The epidemiology of HIV in African countries is changing, shifting from urban to rural areas where the prevalence of Schistosoma mansoni is high and public health services are deficient. On the other side, the consequent pathogenesis of HIV-1/S. mansoni co-infection remains unknown. Here we give an account of the epidemiology of HIV-1 and S. mansoni, discuss co-infection and possible biological causal relationships between the two infections, and the potential impact of praziquantel treatment on HIV-1 viral loads, CD4+ counts and CD4+/CD8+ ratio. Our review of the available literature indicates that there is evidence to support the hypothesis that S. mansoni infections can influence the replication of the HIV-1, cell-to-cell transmission, as well as increase HIV progression as measured by reduced CD4+ T lymphocytes counts. If so, then deworming of HIV positive individuals living in endemic areas may impact on HIV-1 viral loads and CD4+ T lymphocyte counts.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Active Tectonics Around Almaty and along the Zailisky Alatau Rangefront

This is the author accepted manuscript. The final version is available from Wiley via http://onlinelibrary.wiley.com/doi/10.1002/2017TC004657/abstractThe Zailisky Alatau is a >250-km-long mountain range in Southern Kazakhstan. Its northern rangefront around the major city of Almaty has more than 4 km topographic relief, yet in contrast to other large mountain fronts in the Tien Shan, little is known about its Late Quaternary tectonic activity despite several destructive earthquakes in the historical record. We analyse the tectonic geomorphology of the rangefront fault using field observations, differential GPS measurements of fault scarps, historical and recent satellite imagery, metre-scale topography derived from stereo satellite images, and decimetre-scale elevation models from UAV surveys. Fault scarps ranging in height from ~2 m to >20 m in alluvial fans indicate surface rupturing earthquakes occurred along the rangefront fault since the Last Glacial Maximum (LGM). Minimum estimated magnitudes for those earthquakes are M6.8- 7. Radiocarbon dating results from charcoal layers in uplifted river terraces indicate a Holocene slip rate of ~1.2-2.2 mm/a. We find additional evidence for active tectonic deformation all along the Almaty rangefront, basinward in the Kazakh platform, and in the interior of the Zailisky mountain range. Our data indicate the seismic hazard faced by Almaty comes from a variety of sources, and we emphasize the problems related to urban growth into the loess-covered foothills and secondary earthquake effects. With our structural and geochronologic framework we present a schematic evolution of the Almaty rangefront that may be applicable to similar settings of tectonic shortening in the mountain ranges of Central Asia

Summary of cognitive, affective and behavioural outcomes of consuming prestigious sports events

In this paper, the authors explore the range of cognitive, affective, and behavioural outcomes of consuming prestigious sports event experiences. The authors obtained means-end chains from 19 individuals from across a range of ages and both genders. A total of 39 examples of events were discussed by participants encompassing 25 unique events and 11 different sports. Outcomes were multi-dimensional. At the cognitive level, consumers developed outer- and inner-directed outcomes. At the affective level, prestigious sports events made consumers feel positive emotions, while at the same time energising them to attend in order to avoid negative emotional states. At the behavioural level, four types of outcomes served as a consequence of attending prestigious events: patronage, financial, communication and experiential. By recognising the multiple outcomes associated with the consumption of prestigious sports event experiences, managers will be better equipped to design experiences that satisfy consumer requirements