Acumentrics (United States)

A continuum model of the transport and reaction processes occurring during decontamination of the chemical warfare agent (CWA) [2-(diisopropylamino)ethyl]-O-ethyl methylphosphonothioate (VX) absorbed in a silicone elastomer using solutions of sodium hydroxide in water, methanol, and mixtures thereof is presented. This model is based on the Maxwell-Stefan formulation of multicomponent diffusion along with the Flory-Huggins model of thermodynamic equilibrium in the polymer. It was found that, as methanol from the decontaminant absorbs into the silicone, the diffusivity of VX increases, accelerating its flux from the polymer phase to the decontaminant liquid phase. This composition dependence of the diffusivity was accurately described by the Vignes equation. Although the decontamination kinetics were slower for the methanol-based decontaminant in a well-stirred liquid-phase reactor, the overall performance was superior compared to the aqueous-based decontaminant due to the enhanced extraction rate from the polymer. These findings highlight the need to consider extraction dynamics on equal footing with reaction kinetics when formulating decontaminants intended for use on absorbing polymer materials.

BackgroundThe detection of pathogens in complex sample backgrounds has been revolutionized by wide access to next-generation sequencing (NGS) platforms. However, analytical methods to support NGS platforms are not as uniformly available. Pathosphere (found at Pathosphere.org) is a cloud - based open - sourced community tool that allows for communication, collaboration and sharing of NGS analytical tools and data amongst scientists working in academia, industry and government. The architecture allows for users to upload data and run available bioinformatics pipelines without the need for onsite processing hardware or technical support.ResultsThe pathogen detection capabilities hosted on Pathosphere were tested by analyzing pathogen-containing samples sequenced by NGS with both spiked human samples as well as human and zoonotic host backgrounds. Pathosphere analytical pipelines developed by Edgewood Chemical Biological Center (ECBC) identified spiked pathogens within a common sample analyzed by 454, Ion Torrent, and Illumina sequencing platforms. ECBC pipelines also correctly identified pathogens in human samples containing arenavirus in addition to animal samples containing flavivirus and coronavirus. These analytical methods were limited in the detection of sequences with limited homology to previous annotations within NCBI databases, such as parvovirus. Utilizing the pipeline-hosting adaptability of Pathosphere, the analytical suite was supplemented by analytical pipelines designed by the United States Army Medical Research Insititute of Infectious Diseases and Walter Reed Army Institute of Research (USAMRIID-WRAIR). These pipelines were implemented and detected parvovirus sequence in the sample that the ECBC iterative analysis previously failed to identify.ConclusionsBy accurately detecting pathogens in a variety of samples, this work demonstrates the utility of Pathosphere and provides a platform for utilizing, modifying and creating pipelines for a variety of NGS technologies developed to detect pathogens in complex sample backgrounds. These results serve as an exhibition for the existing pipelines and web-based interface of Pathosphere as well as the plug-in adaptability that allows for integration of newer NGS analytical software as it becomes available.Electronic supplementary materialThe online version of this article (doi:10.1186/s12859-015-0840-5) contains supplementary material, which is available to authorized users.

Plague disease caused by the Gram-negative bacterium Yersinia pestis routinely affects animals and occasionally humans, in the western United States. The strains native to the North American continent are thought to be derived from a single introduction in the late 19th century. The degree to which these isolates have diverged genetically since their introduction is not clear, and new genomic markers to assay the diversity of North American plague are highly desired. To assay genetic diversity of plague isolates within confined geographic areas, draft genome sequences were generated by 454 pyrosequencing from nine environmental and clinical plague isolates. In silico assemblies of Variable Number Tandem Repeat (VNTR) loci were compared to laboratory-generated profiles for seven markers. High-confidence SNPs and small Insertion/Deletions (Indels) were compared to previously sequenced Y. pestis isolates. The resulting panel of mutations allowed clustering of the strains and tracing of the most likely evolutionary trajectory of the plague strains. The sequences also allowed the identification of new putative SNPs that differentiate the 2009 isolates from previously sequenced plague strains and from each other. In addition, new insertion points for the abundant insertion sequences (IS) of Y. pestis are present that allow additional discrimination of strains; several of these new insertions potentially inactivate genes implicated in virulence. These sequences enable whole-genome phylogenetic analysis and allow the unbiased comparison of closely related isolates of a genetically monomorphic pathogen.

Sepsis is defined by the systemic response to an infection, governed by dynamic interactions between the tissues, immune cells and inflammatory mediators. We used the Immunetrics platform to build a large-scale mathematical model that encompasses these biological components. The model incorporates a virtual clinician, an automated system to examine simulated patients' status at clinically relevant intervals and administer standard of care interventions as necessary, thereby altering the dynamics of the disease state. The model reproduces many characteristics of systemic response to an infection, including the time course of cytokines, coagulation factors, clinical markers, early and late organ failure, and early versus late deaths.

A mathematical model involving a system of ordinary differential equations has been developed with the goal of assisting the design of therapies directed against the inflammatory consequences of infection and trauma. Though the aim is to build a model of greater complexity, which would eventually overcome some existing limitations (such as a reduced subset of inflammatory interactions, the use of mass action kinetics, and calibration to circulating but not local levels of cytokines), the model can at this time simulate certain disease scenarios qualitatively as well as predicting the time course of cytokine levels in distinct paradigms of inflammation in mice. A parameter search algorithm is developed that aids in the identification of different regimes of behaviour of the model and helps with its calibration to data. Extending this mathematical model, with validation in humans, may lead to the in silico development of novel therapeutic approaches and real-time diagnostics.

A technology for the low cost production of continuous tone gray scale photomasks for deep UV photolithography applications has been demonstrated. This technology is based on the use of a photosensitive spin-on-glass (SOG) thin film deposited onto a UV transparent substrate such as quartz. Different light exposure energies, from either a lithography setup or a laser pattern generator, onto the photosensitive SOG film changes the UV absorption spectrum at both H and I mercury emission lines. The amount of photo induced attenuation on the film is directly proportional to light exposure energy, hence allowing the formation of fully continuous tone patterns. Once the image pattern is photo-generated with a resolution of 0.1 to 1 micrometer, it is permanently fixed by a thermal treatment step without the need of an etching step. This new continuous tone deep UV photomask technology offers new cost effective opportunities for the production of micro-electro-mechanical systems (MEMS) structures, diffractive optical elements (DOEs), computer generated holograms (CGHs), and kinoform optics.