In vivo evaluation of pathogenicity and transmissibility of influenza A(H1N1)pdm09 hemagglutinin receptor binding domain 222 intrahost variants isolated from a single immunocompromised patient

AbstractThe influenza A(H1N1)pdm09 virus has circulated worldwide and continued to cause complicated infections and deaths. Reports have identified an increased prevalence of the hemagglutinin receptor binding domain D222G mutation in viruses isolated from individuals who have suffered such severe infections, but this association is still unclear. Virus isolated from a nasopharyngeal wash of a severely ill immunocompromised patient at the time of diagnosis contained the D222, but isolates collected later in his course from a bronchoalveolar lavage contained primarily the G222 mutation and was mixed with a minor population of D222. These clinical isolates were compared to a G222 plaque purified virus in the ferret model. The G222 predominant clinical isolate was the most pathogenic in ferrets and developed the most diversity at the 222 amino acid position during infection, suggesting that increased diversity and not a specific polymorphism at HA 222 may be important in predicting pathogenic potential

Characterizing and Diminishing Autofluorescence in Formalin-fixed Paraffin-embedded Human Respiratory Tissue

The article of record as published may be found at http://dx.doi.org/10.1369/0022155414531549Tissue autofluorescence frequently hampers visualization of immunofluorescent markers in formalin-fixed paraffin-embedded respiratory tissues. We assessed nine treatments reported to have efficacy in reducing autofluorescence in other tissue types. The three most efficacious were Eriochrome black T, Sudan black B and sodium borohydride, as measured using white light laser confocal Ʌ² (multi-lambda) analysis. We also assessed the impact of steam antigen retrieval and serum application on human tracheal tissue autofluorescence. Functionally fitting this Ʌ² data to 2-dimensional Gaussian surfaces revealed that steam antigen retrieval and serum application contribute minimally to autofluorescence and that the three treatments are disparately efficacious. Together, these studies provide a set of guidelines for diminishing autofluorescence in formalin-fixed paraffin-embedded human respiratory tissue. Additionally, these characterization techniques are transferable to similar questions in other tissue types, as demonstrated on frozen human liver tissue and paraffin-embedded mouse lung tissue fixed in different fixatives.NIHNIAI

Irreducible characters of GSp(4, q) and dimensions of spaces of fixed vectors

In this paper, we compute the conjugacy classes and the list of irreducible characters of GSp(4,q), where q is odd. We also determine precisely which irreducible characters are non-cuspidal and which are generic. These characters are then used to compute dimensions of certain subspaces of fixed vectors of smooth admissible non-supercuspidal representations of GSp(4,F), where F is a non-archimedean local field of characteristic zero with residue field of order q.Comment: 48 pages, 21 tables. Corrected an error in Table 16 for type V* representations (theta_11 and theta_12 were switched

Computational Component Build-Up for the X-57 Distributed Electric Propulsion Aircraft

A computational study of the wing for the distributed electric propulsion X-57 Maxwell airplane configuration at cruise and takeoff/landing conditions was completed. Three unstructured-mesh, Navier-Stokes computational fluid dynamics methods, FUN3D, USM3D and Kestrel, were used to predict the performance buildup of components to the full X-57 configuration. The goal of the X-57 wing and distributed electric propulsion system design was to meet or exceed the required lift coefficient of 3.95 for a stall speed of 58 knots. The X-57 Maxwell airplane was designed with a small, high aspect ratio cruise wing that was designed for a high cruise lift coefficient of 0.75 at a cruise speed of 150 knots and altitude of 8,000 ft, with an angle of attack of approximately 0deg. The computational data indicates that the X-57 full aircraft drag would meet the cruise drag goal with a 25 count drag margin. The cruise configuration maximum lift coefficient is 2.07 and without including the stabilator is 1.86 at an angle of attack of 14 deg, predicted with the USM3D flow solver using the Spalart-Allmaras turbulence model. The maximum lift coefficient for the high-lift wing (with the 30deg flap deflection) without the stabilator contribution is 2.60 at an angle of attack of 13 deg. For high-lift blowing conditions with 13.7 hp/prop, the maximum lift coefficient excluding the stabilator is 4.426 at (alpha) = 13 deg. Therefore, the lift augmentation from the high-lift propellers is 1.7 and the total lift augmentation from the high-lift system (30 deg flap deflection and the high-lift blowing) is 2.38. The drag for the high-lift wing with 30 deg flap deflection is much higher than the cruise wing configuration, but the high-lift system is used only during a small portion of the flight envelope. The pitching moment is relatively constant for both blown and unblown conditions when the stabilator is excluded. Modeling the full geometry has indicated some adverse effects from the fuselage on the wing and stabilator. At high angles of attack, the solutions with the USM3D flow solver using the Spalart-Allmaras turbulence model indicates large flow separation on the wing upper surface between the two high-lift nacelles near the fuselage, and also a reduction in sectional lift on the stabilator in the first 50 percent of the stabilator semispan. However, the large flow separation near the fuselage is mostly eliminated in the solutions predicted with two codes, USM3D and Kestrel, using Hybrid Reynolds-averaged Navier Stokes/Large Eddy Simulation turbulence models

Lake-size dependency of wind shear and convection as controls on gas exchange

High-frequency physical observations from 40 temperate lakes were used to examine the relative contributions of wind shear (u*) and convection (w*) to turbulence in the surface mixed layer. Seasonal patterns of u* and w* were dissimilar; u* was often highest in the spring, while w * increased throughout the summer to a maximum in early fall. Convection was a larger mixed-layer turbulence source than wind shear (u */w*-1 for lakes* and w* differ in temporal pattern and magnitude across lakes, both convection and wind shear should be considered in future formulations of lake-air gas exchange, especially for small lakes. © 2012 by the American Geophysical Union.Jordan S. Read, David P. Hamilton, Ankur R. Desai, Kevin C. Rose, Sally MacIntyre, John D. Lenters, Robyn L. Smyth, Paul C. Hanson, Jonathan J. Cole, Peter A. Staehr, James A. Rusak, Donald C. Pierson, Justin D. Brookes, Alo Laas, and Chin H. W

The multi-layered nature of the internet-based democratization of brand management

The evolution of the internet, including developments such as Web 2.0, has led to new relationship realities between organizations and their stakeholders. One manifestation of these complex new realities has been the emergence of an internet-based democratization of brand management. Research about this phenomenon has so far mainly focused on investigating just one or more individual themes and thereby disregarded the inherent multi-layered nature of the internet-based democratization of brand management as a holistic, socio-technological phenomenon. The aim of this paper is to address this limitation through an investigation of the various socio-technological democratization developments of the phenomenon. To achieve this aim, a balanced and stakeholder-oriented perspective on brand management has been adopted to conduct an integrative literature review. The review reveals three key developments, which together form the essential parts of the phenomenon: (I) the democratization of internet technology, (II) the democratization of information, and (III) the democratization of social capital. The insights gained help to clarify the basic structures of the multi-layered phenomenon. The findings contribute also to the substantiation of a call for a new brand management paradigm: one that takes not only company-initiated but also stakeholder-initiated brand management activities into accoun

Recombinant expression of Aryl Hydrocarbon Receptor for quantitative ligand-binding analysis

Recombinant expression of the Aryl Hydrocarbon Receptor (AhR) yields small amounts of ligand-binding competent AhR. Therefore, Spodoptera frugiperda (Sf9) cells and baculovirushave been evaluated for high level and functional expression of AhR. Rat and human AhR wereexpressed as soluble protein in significant amounts. Expression of ligand-binding competentAhR was sensitive to the protein concentration of Sf9 extract, and co-expression of the chaperonep23 failed to affect the yield of functional ligand-binding AhR. The expression systemyielded high levels of functional protein, with the ligand-binding capacity (Bmax) typically 20-fold higher than that obtained with rat liver cytosol. Quantitative estimates of the ligand-bindingaffinity of human and rat AhR were obtained; the Kd for recombinant rat AhR was indistinguishablefrom that of native rat AhR, thereby validating the expression system as a faithfulmodel for native AhR. The human AhR bound TCDD with significantly lower affinity than therat AhR. These findings demonstrate high-level expression of ligand-binding competent AhR,and sufficient AhR for quantitative analysis of ligand-binding

Tinman/Nkx2-5 acts via miR-1 and upstream of Cdc42 to regulate heart function across species

Cdc42 regulates cardiac function in mice and flies downstream of a conserved Tinman/Nkx2-5–miR-1 signaling network

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead