1,603 research outputs found

    Establishment of the Minimum Biological Capacity for Nitrogen Excretion in Pigs

    Get PDF
    To determine the minimum biological capacity for nitrogen (N) excretion for pigs, dietary regimens were created and fed that were designed to eliminate fecal excretion of undigested feed N, minimize endogenous N secretions and minimize intakes of nitrogenous compounds (amino acids) above those of the pigs biological needs. Excretion of undigested fecal N was eliminated by feeding ingredients containing highly digestible (≈100%) sources of nitrogen and by eliminating compounds that bind N. Endogenous secretions were minimized by eliminating antinutritional factors from the diet and by minimizing enteric bacterial populations. Intakes of amino acids above the animal\u27s needs were minimized by providing a pattern of amino acids that closely matched that needed by the pig. Furthermore, dietary amino acids were provided to the pigs in amounts above, at, and below their biological needs based on the amounts of urea N excreted in the urine and the amounts of N accrued in the body. From two-slope breakpoint analysis, apparent digestible N intake resulting in maximum N retention (2.58g⋅kg-1BW.75⋅d-1) was determined to be 3.66g⋅kg-1BW.75⋅d-1. When daily apparent digestible nitrogen intakes were below the pigs\u27 determined need, the amount of digestible N (mg⋅kg-1BW.75⋅d-1) lost for body maintenance processes was estimated as .239 in urine and .080 in feces. The amount lost in urine as unusable for body N accretion was .206 g⋅kg-1BW.75⋅d-1 of each gram of digestible N consumed above body maintenance needs. When daily apparent digestible N intakes were above the pigs determined need, .900 g of each gram of additional N consumed above that needed for body N accretion was excreted. The minimum biological capacity for N excretion in pigs, defined as total (urinary plus fecal) obligatory losses of N, is estimated to be .287g⋅kg-1BW.75⋅d-1 to support pigs at N maintenance and 1.11 g⋅kg-1BW.75⋅d-1 for pigs at maximum body N accretion. Using these estimates, the minimal biological capacity for N excretion can be calculated for pigs at various stages of growth. For example, in 60 kg pigs, minimum capacity for N excretion is estimated at .10 and .39 g/kg body weight/day in pigs in states of N maintenance and maximum body N accretion, respectively. These values are 12 and 44%, respectively, of N excretion relative to published standards (ASAE D384.1). Similarly, the N content of excreta from animals excreting N at their biological minimum was determined to be 2.57 g N/liter, or 18% of standard excreta N content (corrected for volatilization, ASAE D384.1). Based on these data, the minimum biological capacity for the excretion of N in pigs is substantially less than current estimates of N excretion and can be achieved by eliminating dietary factors that contribute to N excretion. Furthermore, dietary regimens that allow the minimum biological capacity for N excretion to be achieved are biologically capable of supporting maximum rates of body accretion (i.e., lean tissue growth) in pigs

    Epidemics with multistrain interactions: The interplay between cross immunity and antibody-dependent enhancement

    Get PDF
    This paper examines the interplay of the effect of cross immunity and antibody-dependent enhancement (ADE) in multistrain diseases. Motivated by dengue fever, we study a model for the spreading of epidemics in a population with multistrain interactions mediated by both partial temporary cross immunity and ADE. Although ADE models have previously been observed to cause chaotic outbreaks, we show analytically that weak cross immunity has a stabilizing effect on the system. That is, the onset of disease fluctuations requires a larger value of ADE with small cross immunity than without. However, strong cross immunity is shown numerically to cause oscillations and chaotic outbreaks even for low values of ADE. (C) 2009 American Institute of Physics. [doi: 10.1063/1.3270261

    Treatment exhaustion of highly active antiretroviral therapy (HAART) among individuals infected with HIV in the United Kingdon: multicentre cohort study

    Get PDF
    Objectives: To investigate whether there is evidence that an increasing proportion of HIV infected patients is starting to experience increases in viral load and decreases in CD4 cell count that are consistent with exhaustion of available treatment options. Design: Multicentre cohort study. Setting: Six large HIV treatment centres in southeast England. Participants: All individuals seen for care between 1 January 1996 and 31 December 2002. Main outcome measures: Exposure to individual antiretroviral drugs and drug classes, CD4 count, plasma HIV RNA burden. Results: Information is available on 16 593 individuals (13 378 (80.6%) male patients, 10 340 (62.3%) infected via homosexual or bisexual sex, 4426 (26.7%) infected via heterosexual sex, median age 34 years). Overall, 10 207 of the 16 593 patients (61.5%) have been exposed to any antiretroviral therapy. This proportion increased from 41.2% of patients under follow up at the end of 1996 to 71.3% of those under follow up in 2002. The median CD4 count and HIV RNA burden of patients under follow up in each year changed from 270 cells/mm3 and 4.34 log10 copies/ml in 1996 to 408 cells/mm3 and 1.89 log10 copies/ml, respectively, in 2002. By 2002, 3060 (38%) of patients who had ever been treated with antiretroviral therapy had experienced all three main classes. Of these, around one quarter had evidence of “viral load failure” with all these three classes. Patients with three class failure were more likely to have an HIV RNA burden > 2.7 log10 copies/ml and a CD4 count < 200 cells/mm3. Conclusions: The proportion of individuals with HIV infection in the United Kingdom who have been treated has increased gradually over time. A substantial proportion of these patients seem to be in danger of exhausting their options for antiretroviral treatment. New drugs with low toxicity, which are not associated with cross resistance to existing drugs, are urgently needed for such patients

    Dicer-2 Processes Diverse Viral RNA Species

    Get PDF
    RNA silencing pathways play critical roles in gene regulation, virus infection, and transposon control. RNA interference (RNAi) is mediated by small interfering RNAs (siRNAs), which are liberated from double-stranded (ds)RNA precursors by Dicer and guide the RNA-induced silencing complex (RISC) to targets. Although principles governing small RNA sorting into RISC have been uncovered, the spectrum of RNA species that can be targeted by Dicer proteins, particularly the viral RNAs present during an infection, are poorly understood. Dicer-2 potently restricts viral infection in insects by generating virus-derived siRNAs from viral RNA. To better characterize the substrates of Dicer-2, we examined the virus-derived siRNAs produced during the Drosophila antiviral RNAi response to four different viruses using high-throughput sequencing. We found that each virus was uniquely targeted by the RNAi pathway; dicing substrates included dsRNA replication intermediates and intramolecular RNA stem loops. For instance, a putative intergenic RNA hairpin encoded by Rift Valley Fever virus generates abundant small RNAs in both Drosophila and mosquito cells, while repetitive sequences within the genomic termini of Vaccinia virus, which give rise to abundant small RNAs in Drosophila, were found to be transcribed in both insect and mammalian cells. Moreover, we provide evidence that the RNA species targeted by Dicer-2 can be modulated by the presence of a viral suppressor of RNAi. This study uncovered several novel, heavily targeted features within viral genomes, offering insight into viral replication, viral immune evasion strategies, and the mechanism of antiviral RNAi. © 2013 Sabin et al

    Virus-induced translational arrest through 4EBP1/2-dependent decay of 5'-TOP mRNAs restricts viral infection

    Get PDF
    The mosquito-transmitted bunyavirus, Rift Valley fever virus (RVFV), is a highly successful pathogen for which there are no vaccines or therapeutics. Translational arrest is a common antiviral strategy used by hosts. In response, RVFV inhibits two well-known antiviral pathways that attenuate translation during infection, PKR and type I IFN signaling. Despite this, translational arrest occurs during RVFV infection by unknown mechanisms. Here, we find that RVFV infection triggers the decay of core translation machinery mRNAs that possess a 5'-terminal oligopyrimidine (5'-TOP) motif in their 5'-UTR, including mRNAs encoding ribosomal proteins, which leads to a decrease in overall ribosomal protein levels. We find that the RNA decapping enzyme NUDT16 selectively degrades 5'-TOP mRNAs during RVFV infection and this decay is triggered in response to mTOR attenuation via the translational repressor 4EBP1/2 axis. Translational arrest of 5'-TOPs via 4EBP1/2 restricts RVFV replication, and this increased RNA decay results in the loss of visible RNA granules, including P bodies and stress granules. Because RVFV cap-snatches in RNA granules, the increased level of 5'-TOP mRNAs in this compartment leads to snatching of these targets, which are translationally suppressed during infection. Therefore, translation of RVFV mRNAs is compromised by multiple mechanisms during infection. Together, these data present a previously unknown mechanism for translational shutdown in response to viral infection and identify mTOR attenuation as a potential therapeutic avenue against bunyaviral infection

    Estimating the risk of mortality attributable to recent late HIV diagnosis following admission to the intensive care unit: A single-centre observational cohort study

    Get PDF
    OBJECTIVES: Despite improvements in survival of people with HIV admitted to the intensive care unit (ICU), late diagnosis continues to contribute to in-ICU mortality. We quantify the population attributable fraction (PAF) of in-ICU mortality for recent late diagnosis among people with HIV admitted to a London ICU. METHODS: Index ICU admissions among people with HIV were considered from 2000 to 2019. Recent late diagnosis was a CD4 T-cell count < 350 cells/μL and/or AIDS-defining illness at/within 6 months prior to ICU admission. Univariate comparisons were conducted using Wilcoxon rank-sum/Cochran-Armitage/χ2 /Fisher's exact tests. We used Poisson regression (robust standard errors) to estimate unadjusted/adjusted (age, sex, calendar year of ICU admission) risk ratios (RRs) and regression standardization to estimate the PAF. RESULTS: In all, 207 index admissions were included [median (interquartile range) age: 46 (38-53) years; 72% male]; 58 (28%) had a recent late diagnosis, all of whom had a CD4 count < 350 cells/μL, and 95% had advanced HIV (CD4 count < 200 cells/μL and/or AIDS at admission) as compared with 57% of those who did not have a recent late diagnosis (p < 0.001). In-ICU mortality was 27% (55/207); 38% versus 22% in those who did and did not have a recent late diagnosis, respectively (p = 0.02). Recent late diagnosis was independently associated with increased in-ICU mortality risk (adjusted RR = 1.75) (95% confidence interval: 1.05-2.91), with 17.08% (16.04-18.12%) of deaths being attributable to this. CONCLUSIONS: There is a need for improved public health efforts focused on HIV testing and reporting of late diagnosis to better understand potentially missed opportunities for earlier HIV diagnosis in healthcare services

    Extended H? emission line sources from UWISH2

    Get PDF
    We present the extended source catalogue for the UKIRT Wide Field Infrared Survey for H2 (UWISH2). The survey is unbiased along the inner Galactic Plane from l ? 357° to l ? 65° and |b| ? 1.5° and covers 209 deg2. A further 42.0 and 35.5 deg2 of high dust column density regions have been targeted in Cygnus and Auriga. We have identified 33 200 individual extended H2 features. They have been classified to be associated with about 700 groups of jets and outflows, 284 individual (candidate) planetary nebulae, 30 supernova remnants and about 1300 photodissociation regions. We find a clear decline of star formation activity (traced by H2 emission from jets and photodissociation regions) with increasing distance from the Galactic Centre. About 60 per cent of the detected candidate planetary nebulae have no known counterpart and 25 per cent of all supernova remnants have detectable H2 emission associated with them

    The impact of COVID-19 lockdown measures on the Indian summer monsoon

    Get PDF
    Aerosol concentrations over Asia play a key role in modulating the Indian summer monsoon (ISM) rainfall. Lockdown measures imposed to prevent the spread of the COVID-19 pandemic led to substantial reductions in observed Asian aerosol loadings. Here, we use bottom-up estimates of anthropogenic emissions based on national mobility data from Google and Apple, along with simulations from the ECHAM6-HAMMOZ state-of-the-art aerosol-chemistry-climate model to investigate the impact of the reduced aerosol and gases pollution loadings on the ISM. We show that the decrease in anthropogenic emissions led to a 4 W m−2 increase in surface solar radiation over parts of South Asia, which resulted in a strengthening of the ISM. Simultaneously, while natural emission parameterizations are kept the same in all our simulations, the anthropogenic emission reduction led to changes in the atmospheric circulation, causing accumulation of dust over the Tibetan plateau (TP) during the pre-monsoon and monsoon seasons. This accumulated dust has intensified the warm core over the TP that reinforced the intensification of the Hadley circulation. The associated cross-equatorial moisture influx over the Indian landmass led to an enhanced amount of rainfall by 4% (0.2 mm d−1) over the Indian landmass and 5%–15% (0.8–3 mm d−1) over central India. These estimates may vary under the influence of large-scale coupled atmosphere–ocean oscillations (e.g. El Nino Southern Oscillation, Indian Ocean Dipole). Our study indicates that the reduced anthropogenic emissions caused by the unprecedented COVID-19 restrictions had a favourable effect on the hydrological cycle over South Asia, which has been facing water scarcity during the past decades. This emphasizes the need for stringent measures to limit future anthropogenic emissions in South Asia for protecting one of the world's most densely populated regions

    First release of the IPHAS catalogue of new extended planetary nebulae

    Get PDF
    Date of Acceptance: 30/06/2014We present the first results of our search for new, extended planetary nebulae (PNe) based on careful, systematic, visual scrutiny of the imaging data from the Isaac Newton Telescope Photometric Ha Survey of the Northern Galactic plane (IPHAS). The newly uncovered PNe will help to improve the census of this important population of Galactic objects that serve as key windows into the late-stage evolution of low- to intermediate-mass stars. They will also facilitate study of the faint end of the ensemble Galactic PN luminosity function. The sensitivity and coverage of IPHAS allows PNe to be found in regions of greater extinction in the Galactic plane and/or those PNe in a more advanced evolutionary state and at larger distances compared to the general Galactic PN population. Using a set of newly revised optical diagnostic diagrams in combination with access to a powerful, new, multiwavelength imaging data base, we have identified 159 true, likely and possible PNe for this first catalogue release. The ability of IPHAS to unveil PNe at low Galactic latitudes and towards the Galactic Anticentre, compared to previous surveys, makes this survey an ideal tool to contribute to the improvement of our knowledge of the whole Galactic PN population.Peer reviewe

    Introducing LoCo, a Logic for Configuration Problems

    Full text link
    In this paper we present the core of LoCo, a logic-based high-level representation language for expressing configuration problems. LoCo shall allow to model these problems in an intuitive and declarative way, the dynamic aspects of configuration notwithstanding. Our logic enforces that configurations contain only finitely many components and reasoning can be reduced to the task of model construction.Comment: In Proceedings LoCoCo 2011, arXiv:1108.609
    corecore