Study of a unified hardware and software fault-tolerant architecture

A unified architectural concept, called the Fault Tolerant Processor Attached Processor (FTP-AP), that can tolerate hardware as well as software faults is proposed for applications requiring ultrareliable computation capability. An emulation of the FTP-AP architecture, consisting of a breadboard Motorola 68010-based quadruply redundant Fault Tolerant Processor, four VAX 750s as attached processors, and four versions of a transport aircraft yaw damper control law, is used as a testbed in the AIRLAB to examine a number of critical issues. Solutions of several basic problems associated with N-Version software are proposed and implemented on the testbed. This includes a confidence voter to resolve coincident errors in N-Version software. A reliability model of N-Version software that is based upon the recent understanding of software failure mechanisms is also developed. The basic FTP-AP architectural concept appears suitable for hosting N-Version application software while at the same time tolerating hardware failures. Architectural enhancements for greater efficiency, software reliability modeling, and N-Version issues that merit further research are identified

Challenges in identifying cancer genes by analysis of exome sequencing data.

Massively parallel sequencing has permitted an unprecedented examination of the cancer exome, leading to predictions that all genes important to cancer will soon be identified by genetic analysis of tumours. To examine this potential, here we evaluate the ability of state-of-the-art sequence analysis methods to specifically recover known cancer genes. While some cancer genes are identified by analysis of recurrence, spatial clustering or predicted impact of somatic mutations, many remain undetected due to lack of power to discriminate driver mutations from the background mutational load (13-60% recall of cancer genes impacted by somatic single-nucleotide variants, depending on the method). Cancer genes not detected by mutation recurrence also tend to be missed by all types of exome analysis. Nonetheless, these genes are implicated by other experiments such as functional genetic screens and expression profiling. These challenges are only partially addressed by increasing sample size and will likely hold even as greater numbers of tumours are analysed

New age data on the geological evolution of Southern India

The Peninsular Gneisses of Southern India developed over a period of several hundred Ma in the middle-to-late Archaean. Gneisses in the Gorur-Hassan area of southern Karnataka are the oldest recognized constituents: Beckinsale et al. reported a preliminary Rb-Sr whole-rock isochron age of 33558 + or - 66 Ma, but further Rb-Sr and Pb/Pb whole-rock isochron determinations indicate a slightly younger, though more precise age of ca 3305 Ma (R. D. Beckinsale, Pers. Comm.). It is well established that the Peninsular Gneisses constitute basement on which the Dharwar schist belts were deposited. Well-documented exposures of unconformities, with basal quartz pebble conglomerates of the Dharwar Supergroup overlying Peninsular Gneisses, have been reported from the Chikmagalur and Chitradurga areas, and basement gneisses in these two areas have been dated by Rb-Sr and Pb/Pb whole-rock isochron methods at ca 3150 Ma and ca 3000 Ma respectively. Dharwar supracrustal rocks of the Chitradurga schist belt are intruded by the Chitradurga Granite, dated by a Pb/Pb whole-rock isochron at 2605 + or - 18 Ma. These results indicate that the Dharwar Supergroup in the Chitradurga belt was deposited between 3000 Ma and 2600 Ma

Developing Predictive Molecular Maps of Human Disease through Community-based Modeling

The failure of biology to identify the molecular causes of disease has led to disappointment in the rate of development of new medicines. By combining the power of community-based modeling with broad access to large datasets on a platform that promotes reproducible analyses we can work towards more predictive molecular maps that can deliver better therapeutics

The mPower Study, Parkinson Disease Mobile Data Collected Using Researchkit

Current measures of health and disease are often insensitive, episodic, and subjective. Further, these measures generally are not designed to provide meaningful feedback to individuals. The impact of high-resolution activity data collected from mobile phones is only beginning to be explored. Here we present data from mPower, a clinical observational study about Parkinson disease conducted purely through an iPhone app interface. The study interrogated aspects of this movement disorder through surveys and frequent sensor-based recordings from participants with and without Parkinson disease. Benefitting from large enrollment and repeated measurements on many individuals, these data may help establish baseline variability of real-world activity measurement collected via mobile phones, and ultimately may lead to quantification of the ebbs-and-flows of Parkinson symptoms. App source code for these data collection modules are available through an open source license for use in studies of other conditions. We hope that releasing data contributed by engaged research participants will seed a new community of analysts working collaboratively on understanding mobile health data to advance human health

A Critical Role for Induced IgM in the Protection against West Nile Virus Infection

In humans, the elderly and immunocompromised are at greatest risk for disseminated West Nile virus (WNV) infection, yet the immunologic basis for this remains unclear. We demonstrated previously that B cells and IgG contributed to the defense against disseminated WNV infection (Diamond, M.S., B. Shrestha, A. Marri, D. Mahan, and M. Engle. 2003. J. Virol. 77:2578–2586). In this paper, we addressed the function of IgM in controlling WNV infection. C57BL/6J mice (sIgM−/−) that were deficient in the production of secreted IgM but capable of expressing surface IgM and secreting other immunoglobulin isotypes were vulnerable to lethal infection, even after inoculation with low doses of WNV. Within 96 h, markedly higher levels of infectious virus were detected in the serum of sIgM−/− mice compared with wild-type mice. The enhanced viremia correlated with higher WNV burdens in the central nervous system, and was also associated with a blunted anti-WNV IgG response. Passive transfer of polyclonal anti-WNV IgM or IgG protected sIgM−/− mice against mortality, although administration of comparable amounts of a nonneutralizing monoclonal anti-WNV IgM provided no protection. In a prospective analysis, a low titer of anti-WNV IgM antibodies at day 4 uniformly predicted mortality in wild-type mice. Thus, the induction of a specific, neutralizing IgM response early in the course of WNV infection limits viremia and dissemination into the central nervous system, and protects against lethal infection