551 research outputs found

    An Optimization Approach to Balancing Risk and Cost in Combatant Command Capability Advocacy

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    Unified Combatant Commands (UCCs) have broad continuing missions around the globe where they are tasked to provide functional expertise and defense of geographical areas.  Accomplishing these missions requires a robust portfolio of military capabilities (e.g., aircraft, spacecraft, command and control systems, radar systems).  UCCs routinely perform analyses to identify gaps between capabilities required to accomplish their mission and those currently at their disposal.  Each year they submit a prioritized list of required capabilities, including new systems and greater capacity with existing systems, to the Joint Staff in the costly and time-consuming Integrated Priority List (IPL) process.  This process relies on operational art and subject matter expertise, and sometimes fails to identify acquisition opportunities that achieve an optimal balance between risk and cost.  Because this IPL process affects all of the DOD’s personnel, material, systems and missions, it is arguably the most significant analytic challenge faced by the United States military.  This article presents an integer linear programming model that computes an optimal balance between operational risk and the cost of acquiring new capabilities, and allows decision makers to identify the real-world impact of their budgetary decisions.  We apply this model to the mission of providing aerospace defense of the United States and illustrate through sensitivity analysis the meaningful insights that can be gained by studying the relationship between the risk of not achieving 100 percent radar coverage and the opportunity cost of advocating for new capabilities

    Assigning Co-Regulated Human Genes and Regulatory Gene Clusters

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    Elucidating the role of genetic variation in the regulation of gene expression is key to understanding the pathobiology of complex diseases which, in consequence, is crucial in devising targeted treatment options. Expression quantitative trait locus (eQTL) analysis correlates a genetic variant with the strength of gene expression, thus defining thousands of regulated genes in a multitude of human cell types and tissues. Some eQTL may not act independently of each other but instead may be regulated in a coordinated fashion by seemingly independent genetic variants. To address this issue, we combined the approaches of eQTL analysis and colocalization studies. Gene expression was determined in datasets comprising 49 tissues from the Genotype-Tissue Expression (GTEx) project. From about 33,000 regulated genes, over 14,000 were found to be co-regulated in pairs and were assembled across all tissues to almost 15,000 unique clusters containing up to nine regulated genes affected by the same eQTL signal. The distance of co-regulated eGenes was, on average, 112 kilobase pairs. Of 713 genes known to express clinical symptoms upon haploinsufficiency, 231 (32.4%) are part of at least one of the identified clusters. This calls for caution should treatment approaches aim at an upregulation of a haploinsufficient gene. In conclusion, we present an unbiased approach to identifying co-regulated genes in and across multiple tissues. Knowledge of such common effects is crucial to appreciate implications on biological pathways involved, specifically when a treatment option targets a co-regulated disease gen

    Перспективи використання культивованих грибів у технології ковбасних виробів

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    In order to solve the problems associated with expanding range of sausage meat component of high biological value, a search was conducted for alternative, natural and affordable sources of protein. Protein deficiency in human nutrition has led to the search for ways to increase biological value. It was proposed the optimal ratio of components of sausage meat, consisting of meat and mushroom raw materials. The purpose of this combination is to achieve the composition of sausages to the desired approximation of the "ideal protein" with the established technological effects for this production. The main objective of this work is to study the food and taste qualities of the finished product to expand the range of functional sausages at meat processing enterprises in Ukraine and China. Analysis of these data shows that an increase in the level of meat substitution with mushroom raw materials leads to a redistribution of the mass fractions of moisture, protein, fat and ash. The redistribution of these same indicators is affected by the physical state of the introduced mushroom raw material: powder or finely crushed mass. It was recorded a decrease in the mass fraction of fat by approximately 3% and 6%, respectively. Therefore, it was noted a decrease in energy value from 362 kcal to 335-304 kcal. The proportion of carbohydrates in the experimental samples has increased by an average of 1-2%. The mass fraction of protein remained almost unchanged, but the composition of the protein was closer to the "ideal protein". According to the results of organoleptic evaluation, it was found that when developing recipes for cooked smoked sausages, it is advisable to add boiled mushrooms in an amount of 15 - 20% in finely crushed form. It is advisable to add in the amount of 3.0 - 7.0% at the mixing stage in the form of a dry powder of fried mushrooms. The data presented in this article make it possible to assess the prospects of t he food industry in the production of sausages enriched with semi-finished products of varying degrees of readiness based on cultivated mushrooms. The results of the analytical study reflect the unique degree of the cultivated mushrooms amino acid composition approximation to the "ideal protein". Particular attention was paid to essential (limiting) amino acids and their content in new types of sausages.Для вирішення проблем, пов'язаних з розширенням асортименту ковбасних виробів підвищеної біологічної цінності, був проведений пошук альтернативних, природних і доступних джерел білка. Такими пропонується розглядати культивовані гриби. Дефіцит білка в раціон харчування людей, давно вже став причиною пошуку способів підвищення біологічної цінності, тому ми пропонуємо оптимальні співвідношення компонентів ковбасного фаршу, що складається з м'ясного та грибного сировини. Метою такого комбінування є досягнення складу ковбасних виробів до бажаного наближення до "ідеального білку" при встановлених технологічних ефектах для даного виробництва. Основним завданням роботи є вивчення харчових і смакових якостей готової продукції для розширення асортименту функціональних ковбасних виробів на м'ясопереробних підприємствах України і Китаю. Аналіз наведених даних показує, що зі збільшенням рівня заміни м'яса грибним сировиною проходить перерозподіл масових часток вологи, білка, жиру і зольності. На перерозподіл цих же показників впливає фізичний стан внесеного грибного сировини: порошок або тонко подрібнена маса. Було зафіксовано зменшення масової частки жиру приблизно на 3% і 6% відповідно. Отже, зниження енергетичної цінності: з 362 ккал до 335 - 304 ккал. Частка вуглеводів у дослідних зразках збільшувалася в середньому на 1-2%. Масова частка білка залишалася практично незмінною, але склад білка був ближчий до "ідеального білку". За результатами органолептичної оцінки з'ясовано, що при розробці рецептур варено-копчених ковбас доцільно вносити варені гриби в кількості 15 - 20% в тонкоподрібненому вигляді. У вигляді сухого порошку з обсмажених грибів - в кількості 3,0 - 7,0% на етапі перемішування. Наведені в статті дані, дозволяють оцінити перспективу напрямків харчової промисловості в сфері виробництва ковбасних виробів, збагачених напівфабрикатами різного ступеня готовності на основі культивованих грибів. Результати аналітичного дослідження, відображають унікальну ступінь наближення амінокислотного складу культивованих грибів до "ідеального білку". Особливу увагу приділено есенціальним (лімітуючим) амінокислотам, їх вмісту в складі нових видів ковбасних виробів

    Retinal glycoprotein enrichment by concanavalin a enabled identification of novel membrane autoantigen synaptotagmin-1 in equine recurrent uveitis.

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    Complete knowledge of autoantigen spectra is crucial for understanding pathomechanisms of autoimmune diseases like equine recurrent uveitis (ERU), a spontaneous model for human autoimmune uveitis. While several ERU autoantigens were identified previously, no membrane protein was found so far. As there is a great overlap between glycoproteins and membrane proteins, the aim of this study was to test whether pre-enrichment of retinal glycoproteins by ConA affinity is an effective tool to detect autoantigen candidates among membrane proteins. In 1D Western blots, the glycoprotein preparation allowed detection of IgG reactions to low abundant proteins in sera of ERU patients. Synaptotagmin-1, a Ca2+-sensing protein in synaptic vesicles, was identified as autoantigen candidate from the pre-enriched glycoprotein fraction by mass spectrometry and was validated as a highly prevalent autoantigen by enzyme-linked immunosorbent assay. Analysis of Syt1 expression in retinas of ERU cases showed a downregulation in the majority of ERU affected retinas to 24%. Results pointed to a dysregulation of retinal neurotransmitter release in ERU. Identification of synaptotagmin-1, the first cell membrane associated autoantigen in this spontaneous autoimmune disease, demonstrated that examination of tissue fractions can lead to the discovery of previously undetected novel autoantigens. Further experiments will address its role in ERU pathology

    Recurrent short sleep, chronic insomnia symptoms and salivary cortisol: A 10-year follow-up in the Whitehall II study

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    Although an association between both sleep duration and disturbance with salivary cortisol has been suggested, little is known about the long term effects of poor quality sleep on diurnal cortisol rhythm. The aim of this study was to examine the association of poor quality sleep, categorised as recurrent short sleep duration and chronic insomnia symptoms, with the diurnal release of cortisol. We examined this in 3314 participants from an occupational cohort, originally recruited in 1985-1989. Salivary cortisol was measured in 2007-2009 and six saliva samples were collected: (1) waking, (2) waking + 0.5 h, (3) +2.5 h, (4) +8 h, (5) +12 h and (6) bedtime, for assessment of the cortisol awakening response and the diurnal slope in cortisol secretion. Participants with the first saliva sample collected within 15 min of waking and not on steroid medication were examined. Short sleep duration (≤5 h) and insomnia symptoms (Jenkins scale, highest quartile) were measured in 1997-1999, 2003-2004 and 2007-2009. Recurrent short sleep was associated with a flatter diurnal cortisol pattern. A steeper morning rise in cortisol was observed among those reporting chronic insomnia symptoms at three time points and among those reporting short sleep twice, compared to those who never reported sleep problems. Participants reporting short sleep on three occasions had higher levels of cortisol later in the day, compared to those never reporting short sleep, indicated by a positive interaction with hours since waking (β = 0.02 (95% CI: 0.01, 0.03)). We conclude that recurrent sleep problems are associated with adverse salivary cortisol patterns throughout the day

    The significance of peroxisomes in secondary metabolite biosynthesis in filamentous fungi

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    Peroxisomes are ubiquitous organelles characterized by a protein-rich matrix surrounded by a single membrane. In filamentous fungi, peroxisomes are crucial for the primary metabolism of several unusual carbon sources used for growth (e.g. fatty acids), but increasing evidence is presented that emphasize the crucial role of these organelles in the formation of a variety of secondary metabolites. In filamentous fungi, peroxisomes also play a role in development and differentiation whereas specialized peroxisomes, the Woronin bodies, play a structural role in plugging septal pores. The biogenesis of peroxisomes in filamentous fungi involves the function of conserved PEX genes, as well as genes that are unique for these organisms. Peroxisomes are also subject to autophagic degradation, a process that involves ATG genes. The interplay between organelle biogenesis and degradation may serve a quality control function, thereby allowing a continuous rejuvenation of the organelle population in the cells

    Excess Higgs Production in Neutralino Decays

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    The ATLAS and CMS experiments have recently claimed discovery of a Higgs boson-like particle at ~5 sigma confidence and are beginning to test the Standard Model predictions for its production and decay. In a variety of supersymmetric models, a neutralino NLSP can decay dominantly to the Higgs and the LSP. In natural SUSY models, a light third generation squark decaying through this chain can lead to large excess Higgs production while evading existing BSM searches. Such models can be observed at the 8 TeV LHC in channels exploiting the rare diphoton decays of the Higgs produced in the cascade decay. Identifying a diphoton resonance in association with missing energy, a lepton, or b-tagged jets is a promising search strategy for discovery of these models, and would immediately signal new physics involving production of a Higgs boson. We also discuss the possibility that excess Higgs production in these SUSY decays can be responsible for enhancements of up to 50% over the SM prediction for the observed rate in the existing inclusive diphoton searches, a scenario which would likely by the end of the 8 TeV run be accompanied by excesses in the diphoton + lepton/MET and SUSY multi-lepton/b searches and a potential discovery in a diphoton + 2b search.Comment: 42 pages, 19 figure
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