Accurate ab initio anharmonic force field and heat of formation for silane, SiH_4

From large basis set coupled cluster calculations and a minor empirical adjustment, an anharmonic force field for silane has been derived that is consistently of spectroscopic quality ($\pm 1 cm^{-1}$ on vibrational fundamentals) for all isotopomers of silane studied. Inner-shell polarization functions have an appreciable effect on computed properties and even on anharmonic corrections. From large basis set coupled cluster calculations and extrapolations to the infinite-basis set limit, we obtain TAE_0=303.80 \pm 0.18 kcal/mol, which includes an anharmonic zero-point energy (19.59 kcal/mol), inner-shell correlation (-0.36 kcal/mol), scalar relativistic corrections (-0.70 kcal/mol), and atomic spin-orbit corrections (-0.43 kcal/mol). In combination with the recently revised \HVSI{0}, we obtain $\Delta H^{\circ}_{f,0}[SiH_4(g)]=9.9 \pm 0.4 kcal/mol$, in between the two established experimental values.Comment: Mol. Phys., in pres

Expression of Ifnlr1 on intestinal epithelial cells is critical to the antiviral effects of IFN-lambda against norovirus and reovirus

Lambda interferon (IFN-λ) has potent antiviral effects against multiple enteric viral pathogens, including norovirus and rotavirus, in both preventing and curing infection. Because the intestine includes a diverse array of cell types, however, the cell(s) upon which IFN-λ acts to exert its antiviral effects is unclear. Here, we sought to identify IFN-λ-responsive cells by generation of mice with lineage-specific deletion of the receptor for IFN-λ, Ifnlr1. We found that expression of IFNLR1 on intestinal epithelial cells (IECs) in the small intestine and colon is required for enteric IFN-λ antiviral activity. IEC Ifnlr1 expression also determines the efficacy of IFN-λ in resolving persistent murine norovirus (MNoV) infection and regulates fecal shedding and viral titers in tissue. Thus, the expression of Ifnlr1 by IECs is necessary for the response to both endogenous and exogenous IFN-λ. We further demonstrate that IEC Ifnlr1 expression is required for the sterilizing innate immune effects of IFN-λ by extending these findings in Rag1-deficient mice. Finally, we assessed whether our findings pertained to multiple viral pathogens by infecting mice specifically lacking IEC Ifnlr1 expression with reovirus. These mice phenocopied Ifnlr1-null animals, exhibiting increased intestinal tissue titers and enhanced reovirus fecal shedding. Thus, IECs are the critical cell type responding to IFN-λ to control multiple enteric viruses. This is the first genetic evidence that supports an essential role for IECs in IFN-λ-mediated control of enteric viral infection, and these findings provide insight into the mechanism of IFN-λ-mediated antiviral activity. IMPORTANCE Human noroviruses (HNoVs) are the leading cause of epidemic gastroenteritis worldwide. Type III interferons (IFN-λ) control enteric viral infections in the gut and have been shown to cure mouse norovirus, a small-animal model for HNoVs. Using a genetic approach with conditional knockout mice, we identified IECs as the dominant IFN-λ-responsive cells in control of enteric virus infection in vivo. Upon murine norovirus or reovirus infection, Ifnlr1 depletion in IECs largely recapitulated the phenotype seen in Ifnlr1(−/−) mice of higher intestinal tissue viral titers and increased viral shedding in the stool. Moreover, IFN-λ-mediated sterilizing immunity against murine norovirus requires the capacity of IECs to respond to IFN-λ. These findings clarify the mechanism of action of this cytokine and emphasize the therapeutic potential of IFN-λ for treating mucosal viral infections

Constructions of generalized complex structures in dimension four

Four-manifold theory is employed to study the existence of (twisted) generalized complex structures. It is shown that there exist (twisted) generalized complex structures that have more than one type change loci. In an example-driven fashion, (twisted) generalized complex structures are constructed on a myriad of four-manifolds, both simply and non-simply connected, which are neither complex nor symplectic

Commonalities across computational workflows for uncovering explanatory variants in undiagnosed cases

PURPOSE: Genomic sequencing has become an increasingly powerful and relevant tool to be leveraged for the discovery of genetic aberrations underlying rare, Mendelian conditions. Although the computational tools incorporated into diagnostic workflows for this task are continually evolving and improving, we nevertheless sought to investigate commonalities across sequencing processing workflows to reveal consensus and standard practice tools and highlight exploratory analyses where technical and theoretical method improvements would be most impactful. METHODS: We collected details regarding the computational approaches used by a genetic testing laboratory and 11 clinical research sites in the United States participating in the Undiagnosed Diseases Network via meetings with bioinformaticians, online survey forms, and analyses of internal protocols. RESULTS: We found that tools for processing genomic sequencing data can be grouped into four distinct categories. Whereas well-established practices exist for initial variant calling and quality control steps, there is substantial divergence across sites in later stages for variant prioritization and multimodal data integration, demonstrating a diversity of approaches for solving the most mysterious undiagnosed cases. CONCLUSION: The largest differences across diagnostic workflows suggest that advances in structural variant detection, noncoding variant interpretation, and integration of additional biomedical data may be especially promising for solving chronically undiagnosed cases

Disability Severity, Professional Isolation Perceptions, and Career Outcomes: When Does Leader–Member Exchange Quality Matter?

Employees with disability-related communication impairment often experience isolation from professional connections that can negatively affect their careers. Management research suggests that having lower quality leader relationships can be an obstacle to the development of professional connections for employees with disabilities. However, in this paper we suggest that lower quality leader–member exchange (LMX) relationships may not be a uniform hurdle for the professional isolation of employees with disability-related communication impairment. Drawing on psychological disengagement theory, we predict that employees with more severe, rather than less severe, communication impairment develop resilience to challenges in lower quality LMX relationships by psychologically disengaging from professional connections and, in turn, bear fewer negative consequences of professional isolation on career outcomes. In two studies of deaf and hard of hearing employees, we find that in lower quality LMX relationships employees with more severe communication impairment perceive being less isolated than employees with less severe communication impairment, and, in turn, report better career outcomes. Overall, our findings suggest that employees with more severe communication impairment may develop effective coping strategies to manage challenges of perceived professional isolation for career outcomes when in lower quality LMX relationships

Utilizing Skylab data in on-going resources management programs in the state of Ohio

The author has identified the following significant results. The use of Skylab imagery for total area woodland surveys was found to be more accurate and cheaper than conventional surveys using aerial photo-plot techniques. Machine-aided (primarily density slicing) analyses of Skylab 190A and 190B color and infrared color photography demonstrated the feasibility of using such data for differentiating major timber classes including pines, hardwoods, mixed, cut, and brushland providing such analyses are made at scales of 1:24,000 and larger. Manual and machine-assisted image analysis indicated that spectral and spatial capabilities of Skylab EREP photography are adequate to distinguish most parameters of current, coal surface mining concern associated with: (1) active mining, (2) orphan lands, (3) reclaimed lands, and (4) active reclamation. Excellent results were achieved when comparing Skylab and aerial photographic interpretations of detailed surface mining features. Skylab photographs when combined with other data bases (e.g., census, agricultural land productivity, and transportation networks), provide a comprehensive, meaningful, and integrated view of major elements involved in the urbanization/encroachment process