Quantized time correlation function approach to non-adiabatic decay rates in condensed phase: Application to solvated electrons in water and methanol

A new, alternative form of the golden rule formula defining the non-adiabatic transition rate between two quantum states in condensed phase is presented. The formula involves the quantum time correlation function of the energy gap, of the non-adiabatic coupling, and their cross terms. Those quantities can be inferred from their classical counterparts, determined via MD simulations. The formalism is applied to the problem of the non-adiabatic relaxation of an equilibrated p-electron in water and methanol. We find that, in both solvent, the relaxation is induced by the coupling to the vibrational modes and the quantum effects modify the rate by a factor of 2-10 depending on the quantization procedure applied. The resulting p-state lifetime for a hypothetical equilibrium excited state appears extremely short, in the sub-100 fs regime. Although this result is in contrast with all previous theoretical predictions, we also illustrate that the lifetimes computed here are very sensitive to the simulated electronic quantum gap and to the strongly correlated non-adiabatic coupling

Genome engineering of isogenic human ES cells to model autism disorders.

Isogenic pluripotent stem cells are critical tools for studying human neurological diseases by allowing one to study the effects of a mutation in a fixed genetic background. Of particular interest are the spectrum of autism disorders, some of which are monogenic such as Timothy syndrome (TS); others are multigenic such as the microdeletion and microduplication syndromes of the 16p11.2 chromosomal locus. Here, we report engineered human embryonic stem cell (hESC) lines for modeling these two disorders using locus-specific endonucleases to increase the efficiency of homology-directed repair (HDR). We developed a system to: (1) computationally identify unique transcription activator-like effector nuclease (TALEN) binding sites in the genome using a new software program, TALENSeek, (2) assemble the TALEN genes by combining golden gate cloning with modified constructs from the FLASH protocol, and (3) test the TALEN pairs in an amplification-based HDR assay that is more sensitive than the typical non-homologous end joining assay. We applied these methods to identify, construct, and test TALENs that were used with HDR donors in hESCs to generate an isogenic TS cell line in a scarless manner and to model the 16p11.2 copy number disorder without modifying genomic loci with high sequence similarity

Pathogen-specific risk of chronic gastrointestinal disorders following bacterial causes of foodborne illness

BACKGROUND: The US CDC estimates over 2 million foodborne illnesses are annually caused by 4 major enteropathogens: non-typhoid Salmonella spp., Campylobacter spp., Shigella spp. and Yersinia enterocoltica. While data suggest a number of costly and morbid chronic sequelae associated with these infections, pathogen-specific risk estimates are lacking. We utilized a US Department of Defense medical encounter database to evaluate the risk of several gastrointestinal disorders following select foodborne infections. METHODS: We identified subjects with acute gastroenteritis between 1998 to 2009 attributed to Salmonella (nontyphoidal) spp., Shigella spp., Campylobacter spp. or Yersinia enterocolitica and matched each with up to 4 unexposed subjects. Medical history was analyzed for the duration of military service time (or a minimum of 1 year) to assess for incident chronic gastrointestinal disorders. Relative risks were calculated using modified Poisson regression while controlling for the effect of covariates. RESULTS: A total of 1,753 pathogen-specific gastroenteritis cases (Campylobacter: 738, Salmonella: 624, Shigella: 376, Yersinia: 17) were identified and followed for a median of 3.8 years. The incidence (per 100,000 person-years) of PI sequelae among exposed was as follows: irritable bowel syndrome (IBS), 3.0; dyspepsia, 1.8; constipation, 3.9; gastroesophageal reflux disease (GERD), 9.7. In multivariate analyses, we found pathogen-specific increased risk of IBS, dyspepsia, constipation and GERD. CONCLUSIONS: These data confirm previous studies demonstrating risk of chronic gastrointestinal sequelae following bacterial enteric infections and highlight additional preventable burden of disease which may inform better food security policies and practices, and prompt further research into pathogenic mechanisms

Thermal physiological traits in tropical lowland amphibians: Vulnerability to climate warming and cooling

Climate change is affecting biodiversity and ecosystem function worldwide, and the lowland tropics are of special concern because organisms living in this region experience temperatures that are close to their upper thermal limits. However, it remains unclear how and whether tropical lowland species will be able to cope with the predicted pace of climate warming. Additionally, there is growing interest in examining how quickly thermal physiological traits have evolved across taxa, and whether thermal physiological traits are evolutionarily conserved or labile. We measured critical thermal maximum (CTmax) and minimum (CTmin) in 56 species of lowland Amazonian frogs to determine the extent of phylogenetic conservatism in tolerance to heat and cold, and to predict species’ vulnerability to climate change. The species we studied live in sympatry and represent ~65% of the known alpha diversity at our study site. Given that critical thermal limits may have evolved differently in response to different temperature constraints, we tested whether CTmax and CTmin exhibit different rates of evolutionary change. Measuring both critical thermal traits allowed us to estimate species’ thermal breadth and infer their potential to respond to abrupt changes in temperature (warming and cooling). Additionally, we assessed the contribution of life history traits and found that both critical thermal traits were correlated with species’ body size and microhabitat use. Specifically, small direct-developing frogs in the Strabomantidae family appear to be at highest risk of thermal stress while tree frogs (Hylidae) and narrow mouthed frogs (Microhylidae) tolerate higher temperatures. While CTmax and CTmin had considerable variation within and among families, both critical thermal traits exhibited similar rates of evolutionary change. Our results suggest that 4% of lowland rainforest frogs assessed will experience temperatures exceeding their CTmax, 25% might be moderately affected and 70% are unlikely to experience pronounced heat stress under a hypothetical 3°C temperature increase

Accurate PCR detection of influenza A/B and respiratory syncytial viruses by use of Cepheid Xpert Flu+RSV Xpress Assay in point-of-care settings: Comparison to Prodesse ProFlu+

ABSTRACT The Xpert Flu+RSV Xpress Assay is a fast, automated in vitro diagnostic test for qualitative detection and differentiation of influenza A and B viruses and respiratory syncytial virus (RSV) performed on the Cepheid GeneXpert Xpress System. The objective of this study was to establish performance characteristics of the Xpert Flu+RSV Xpress Assay compared to those of the Prodesse ProFlu+ real-time reverse transcription-PCR (RT-PCR) assay (ProFlu+) for the detection of influenza A and B viruses as well as RSV in a Clinical Laboratory Improvement Amendments (CLIA)-waived (CW) setting. Overall, the assay, using fresh and frozen nasopharyngeal (NP) swabs, demonstrated high concordance with results of the ProFlu+ assay in the combined CW and non-CW settings with positive percent agreements (PPA) (100%, 100%, and 97.1%) and negative percent agreements (NPA) (95.2%, 99.5%, and 99.6%) for influenza A and B viruses and RSV, respectively. In conclusion, this multicenter study using the Cepheid Xpert Flu+RSV Xpress Assay demonstrated high sensitivities and specificities for influenza A and B viruses and RSV in ∼60 min for use at the point-of-care in the CW setting. </jats:p

Response to Questions in the First White Paper, \u27Modernizing the Communications Act\u27

The House Energy and Commerce Committee has begun a process to review and update the Communications Act of 1934, last revised in any material way in 1996. As the Committee begins the review process, this paper responds to questions posed by the Committee that all relate, in fundamental ways, to the question: What should a modern Communications Act look like? The Response advocates a clean slate approach under which the regulatory silos that characterize the current statute would be eliminated, along with almost all of the ubiquitous \u27public interest\u27 delegation of authority found throughout the Communications Act. The replacement regime would have at its core a new competition-based standard that, except in limited circumstances, would require that the FCC\u27s regulatory activities be tied to findings of consumer harm resulting from lack of sufficient competition. The FCC\u27s authority to adopt broad anticipatory rules on an ex ante basis would be substantially circumscribed, and the agency would be required to rely more heavily than is presently the case on ex post adjudication of individual complaints alleging specific abuses of market power and consumer harm. Some aspects of the FCC\u27s current jurisdiction, such as privacy and data security regulation, might be transferred to the FTC in light of the FTC\u27s institutional competence in these areas

Response to Questions in the First White Paper, \u27Modernizing the Communications Act\u27

The House Energy and Commerce Committee has begun a process to review and update the Communications Act of 1934, last revised in any material way in 1996. As the Committee begins the review process, this paper responds to questions posed by the Committee that all relate, in fundamental ways, to the question: What should a modern Communications Act look like? The Response advocates a clean slate approach under which the regulatory silos that characterize the current statute would be eliminated, along with almost all of the ubiquitous \u27public interest\u27 delegation of authority found throughout the Communications Act. The replacement regime would have at its core a new competition-based standard that, except in limited circumstances, would require that the FCC\u27s regulatory activities be tied to findings of consumer harm resulting from lack of sufficient competition. The FCC\u27s authority to adopt broad anticipatory rules on an ex ante basis would be substantially circumscribed, and the agency would be required to rely more heavily than is presently the case on ex post adjudication of individual complaints alleging specific abuses of market power and consumer harm. Some aspects of the FCC\u27s current jurisdiction, such as privacy and data security regulation, might be transferred to the FTC in light of the FTC\u27s institutional competence in these areas

MetaGOmics: A Web-Based Tool for Peptide-Centric Functional and Taxonomic Analysis of Metaproteomics Data

Metaproteomics is the characterization of all proteins being expressed by a community of organisms in a complex biological sample at a single point in time. Applications of metaproteomics range from the comparative analysis of environmental samples (such as ocean water and soil) to microbiome data from multicellular organisms (such as the human gut). Metaproteomics research is often focused on the quantitative functional makeup of the metaproteome and which organisms are making those proteins. That is: What are the functions of the currently expressed proteins? How much of the metaproteome is associated with those functions? And, which microorganisms are expressing the proteins that perform those functions? However, traditional protein-centric functional analysis is greatly complicated by the large size, redundancy, and lack of biological annotations for the protein sequences in the database used to search the data. To help address these issues, we have developed an algorithm and web application (dubbed MetaGOmics ) that automates the quantitative functional (using Gene Ontology) and taxonomic analysis of metaproteomics data and subsequent visualization of the results. MetaGOmics is designed to overcome the shortcomings of traditional proteomics analysis when used with metaproteomics data. It is easy to use, requires minimal input, and fully automates most steps of the analysis-including comparing the functional makeup between samples

An Atlas of Warm AGN and Starbursts from the IRAS Deep Fields

We present 180 AGN candidates based on color selection from the IRAS slow-scan deep observations, with color criteria broadened from the initial Point-Source Catalog samples to include similar objects with redshifts up to z=1 and allowing for two-band detections. Spectroscopic identifications have been obtained for 80 (44%); some additional ones are secure based on radio detections or optical morphology, although yet unobserved spectroscopically. These spectroscopic identifications include 13 Sy 1 galaxies, 17 Sy 2 Seyferts, 29 starbursts, 7 LINER systems, and 13 emission-line galaxies so heavily reddened as to remain of ambiguous classification. The optical magnitudes range from R=12.0-20.5; counts suggest that incompleteness is important fainter than R=15.5. Redshifts extend to z=0.51, with a significant part of the sample at z>0.2. The sample includes slightly more AGN than star-forming systems among those where the spectra contain enough diagnostic feature to make the distinction. The active nuclei include several broad-line objects with strong Fe II emission, and composite objects with the absorption-line signatures of fading starbursts. These AGN with warm far-IR colors have little overlap with the "red AGN" identified with 2MASS; only a single Sy 1 was detected by 2MASS with J-K > 2. Some reliable IRAS detections have either very faint optical counterparts or only absorption-line galaxies, potentially being deeply obscured AGN. The IRAS detections include a newly identified symbiotic star, and several possible examples of the "Vega phenomenon", including dwarfs as cool as type K. Appendices detail these candidate stars, and the optical-identification content of a particularly deep set of high-latitude IRAS scans (probing the limits of optical identification from IRAS data alone).Comment: ApJ Suppl, in press. Figures converted to JPEG/GIF for better compression; PDF with full-resolution figures available before publication at http://www.astr.ua.edu/keel/aoagn.pd