EFFECTIVENESS OF NAVAL INTRODUCTORY FLIGHT EVALUATION (NIFE)

The naval aviation training pipeline was modified in 2020 so that the first training phase is now the Naval Introductory Flight Evaluation (NIFE). Designed to reduce attrition and improve performance in the next phase of flight training, Primary, NIFE replaces the previous initial training phases, Introductory Flight Screening and Aviation Pre-flight Indoctrination. This research conducts statistical analysis on data from over 4,500 students to assess NIFE’s effectiveness and verify whether it is reducing attrition and improving performance in Primary. The results indicate that NIFE largely accomplished its program goals. The Chief of Naval Air Training should retain NIFE in its current form. Further analyses into NIFE’s impacts should account for the potential training decay effects and time-varying confounding. Additionally, a future cost benefit analysis of NIFE will provide further context to the results of this study and help decision makers assess the value of the NIFE program.Ensign, United States NavyApproved for public release. Distribution is unlimited

NRP2 as an Emerging Angiogenic Player; Promoting Endothelial Cell Adhesion and Migration by Regulating Recycling of α5 Integrin.

Angiogenesis relies on the ability of endothelial cells (ECs) to migrate over the extracellular matrix via integrin receptors to respond to an angiogenic stimulus. Of the two neuropilin (NRP) orthologs to be identified, both have been reported to be expressed on normal blood and lymphatic ECs, and to play roles in the formation of blood and lymphatic vascular networks during angiogenesis. Whilst the role of NRP1 and its interactions with integrins during angiogenesis has been widely studied, the role of NRP2 in ECs is poorly understood. Here we demonstrate that NRP2 promotes Rac-1 mediated EC adhesion and migration over fibronectin (FN) matrices in a mechanistically distinct fashion to NRP1, showing no dependence on β3 integrin (ITGB3) expression, or VEGF stimulation. Furthermore, we highlight evidence of a regulatory crosstalk between NRP2 and α5 integrin (ITGA5) in ECs, with NRP2 depletion eliciting an upregulation of ITGA5 expression and disruptions in ITGA5 cellular organization. Finally, we propose a mechanism whereby NRP2 promotes ITGA5 recycling in ECs; NRP2 depleted ECs were found to exhibit reduced levels of total ITGA5 subunit recycling compared to wild-type (WT) ECs. Our findings expose NRP2 as a novel angiogenic player by promoting ITGA5-mediated EC adhesion and migration on FN

A Sm(II)-mediated cascade approach to Dibenzoindolo[3,2-b]carbazoles:synthesis and evaluation

Previously unstudied dibenzoindolo[3,2-b]carbazoles have been prepared by two-directional, phase tag-assisted synthesis utilizing a connective-Pummerer cyclization and a SmI2-mediated tag cleavage-cyclization cascade. The use of a phase tag allows us to exploit unstable intermediates that would otherwise need to be avoided. The novel materials were characterized by X-ray, cyclic voltammetry, UV-vis spectroscopy, TGA, and DSC. Preliminary studies on the performance of OFET devices are also described

Carrageenan Is a Potent Inhibitor of Papillomavirus Infection

Certain sexually transmitted human papillomavirus (HPV) types are causally associated with the development of cervical cancer. Our recent development of high-titer HPV pseudoviruses has made it possible to perform high-throughput in vitro screens to identify HPV infection inhibitors. Comparison of a variety of compounds revealed that carrageenan, a type of sulfated polysaccharide extracted from red algae, is an extremely potent infection inhibitor for a broad range of sexually transmitted HPVs. Although carrageenan can inhibit herpes simplex viruses and some strains of HIV in vitro, genital HPVs are about a thousand-fold more susceptible, with 50% inhibitory doses in the low ng/ml range. Carrageenan acts primarily by preventing the binding of HPV virions to cells. This finding is consistent with the fact that carrageenan resembles heparan sulfate, an HPV cell-attachment factor. However, carrageenan is three orders of magnitude more potent than heparin, a form of cell-free heparan sulfate that has been regarded as a highly effective model HPV inhibitor. Carrageenan can also block HPV infection through a second, postattachment heparan sulfate–independent effect. Carrageenan is in widespread commercial use as a thickener in a variety of cosmetic and food products, ranging from sexual lubricants to infant feeding formulas. Some of these products block HPV infectivity in vitro, even when diluted a million-fold. Clinical trials are needed to determine whether carrageenan-based products are effective as topical microbicides against genital HPVs

Report on the 2013 Rapid Assessment Survey of Marine Species at New England Bays and Harbors

Introduced species (i.e., non-native species that have become established in a new location) have increasingly been recognized as a concern as they have become more prevalent in marine and terrestrial environments (Mooney and Cleland 2001; Simberloff et al. 2005). The ability of introduced species to alter population, community, and ecosystem structure and function, as well as cause significant economic damage is well documented (Carlton 1989, 1996b, 2000; Cohen and Carlton 1995; Cohen et al. 1995; Elton 1958; Meinesz et al. 1993; Occhipinti-Ambrogi and Sheppard 2007; Pimentel et al. 2005; Thresher 2000). The annual economic costs incurred from managing the approximately 50,000 introduced species in the United States alone are estimated to be over $120 billion (Pimentel et al. 2005). Having a monitoring network in place to track new introductions and distributional changes of introduced species is critical for effective management, as these efforts may be more successful when species are detected before they have the chance to become established. A rapid assessment survey is one such method for early detection of introduced species. With rapid assessment surveys, a team of taxonomic experts record and monitor marine species–providing a baseline inventory of native, introduced, and cryptogenic (i.e., unknown origin) species (as defined by Carlton 1996a)–and document range expansions of previously identified species. Since 2000, five rapid assessment surveys have been conducted in New England. These surveys focus on recording species at marinas, which often are in close proximity to transportation vectors (i.e., recreational boats). Species are collected from floating docks and piers because these structures are accessible regardless of the tidal cycle. Another reason for sampling floating docks and other floating structures is that marine introduced species are often found to be more prevalent on artificial surfaces than natural surfaces (Glasby and Connell 2001; Paulay et al. 2002). The primary objectives of these surveys are to: (1) identify native, introduced, and cryptogenic marine species, (2) expand on data collected in past surveys, (3) assess the introduction status and range extensions of documented introduced species, and (4) detect new introductions. This report presents the introduced, cryptogenic, and native species recorded during the 2013 survey

Antagonistic regulation of mRNA expression and splicing by CELF and MBNL proteins

RNA binding proteins of the conserved CUGBP1, Elav-like factor (CELF) family contribute to heart and skeletal muscle development and are implicated in myotonic dystrophy (DM). To understand their genome-wide functions, we analyzed the transcriptome dynamics following induction of CELF1 or CELF2 in adult mouse heart and of CELF1 in muscle by RNA-seq, complemented by crosslinking/immunoprecipitation-sequencing (CLIP-seq) analysis of mouse cells and tissues to distinguish direct from indirect regulatory targets. We identified hundreds of mRNAs bound in their 3′ UTRs by both CELF1 and the developmentally induced MBNL1 protein, a threefold greater overlap in target messages than expected, including messages involved in development and cell differentiation. The extent of 3′ UTR binding by CELF1 and MBNL1 predicted the degree of mRNA repression or stabilization, respectively, following CELF1 induction. However, CELF1's RNA binding specificity in vitro was not detectably altered by coincubation with recombinant MBNL1. These findings support a model in which CELF and MBNL proteins bind independently to mRNAs but functionally compete to specify down-regulation or localization/stabilization, respectively, of hundreds of mRNA targets. Expression of many alternative 3′ UTR isoforms was altered following CELF1 induction, with 3′ UTR binding associated with down-regulation of isoforms and genes. The splicing of hundreds of alternative exons was oppositely regulated by these proteins, confirming an additional layer of regulatory antagonism previously observed in a handful of cases. The regulatory relationships between CELFs and MBNLs in control of both mRNA abundance and splicing appear to have evolved to enhance developmental transitions in major classes of heart and muscle genes.Myotonic Dystrophy FoundationNational Institutes of Health (U.S.) (Grant OD017865-02)National Science Foundation (U.S.) (Award 0821391)National Institutes of Health (U.S.) (Grant R01GM085319)National Institutes of Health (U.S.) (Grant RC2HG005624

Observation of interstellar lithium in the low-metallicity Small Magellanic Cloud

The primordial abundances of light elements produced in the standard theory of Big Bang nucleosynthesis (BBN) depend only on the cosmic ratio of baryons to photons, a quantity inferred from observations of the microwave background. The predicted primordial 7Li abundance is four times that measured in the atmospheres of Galactic halo stars. This discrepancy could be caused by modification of surface lithium abundances during the stars' lifetimes or by physics beyond the Standard Model that affects early nucleosynthesis. The lithium abundance of low-metallicity gas provides an alternative constraint on the primordial abundance and cosmic evolution of lithium that is not susceptible to the in situ modifications that may affect stellar atmospheres. Here we report observations of interstellar 7Li in the low-metallicity gas of the Small Magellanic Cloud, a nearby galaxy with a quarter the Sun's metallicity. The present-day 7Li abundance of the Small Magellanic Cloud is nearly equal to the BBN predictions, severely constraining the amount of possible subsequent enrichment of the gas by stellar and cosmic-ray nucleosynthesis. Our measurements can be reconciled with standard BBN with an extremely fine-tuned depletion of stellar Li with metallicity. They are also consistent with non-standard BBN.Comment: Published in Nature. Includes main text and Supplementary Information. Replaced with final title and abstrac

Effect of a pharmacologically induced decrease in core temperature in rats resuscitated from cardiac arrest

Hypothermia is recommended by international guidelines for treatment of unconscious survivors of cardiac arrest to improve neurologic outcomes. However, temperature management is often underutilized because it may be difficult to implement. The present study evaluated the efficacy of pharmacologically induced hypothermia on survival and neurological outcome in rats resuscitated from cardiac arrest

Generic Mechanism of Emergence of Amyloid Protofilaments from Disordered Oligomeric aggregates

The presence of oligomeric aggregates, which is often observed during the process of amyloid formation, has recently attracted much attention since it has been associated with neurodegenerative conditions such as Alzheimer's and Parkinson's diseases. We provide a description of a sequence-indepedent mechanism by which polypeptide chains aggregate by forming metastable oligomeric intermediate states prior to converting into fibrillar structures. Our results illustrate how the formation of ordered arrays of hydrogen bonds drives the formation of beta-sheets within the disordered oligomeric aggregates that form early under the effect of hydrophobic forces. Initially individual beta-sheets form with random orientations, which subsequently tend to align into protofilaments as their lengths increases. Our results suggest that amyloid aggregation represents an example of the Ostwald step rule of first order phase transitions by showing that ordered cross-beta structures emerge preferentially from disordered compact dynamical intermediate assemblies.Comment: 14 pages, 4 figure