100 research outputs found

    Economically Optimal Distiller Grain Inclusion in Beef Feedlot Rations: Recognition of Omitted Factors

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    With the rapid expansion of the ethanol industry, the feeding landscape familiar to the feedlot industry is changing. While concerns regarding rising corn prices persist, many within the industry are looking at distiller’s grains, a by-product of ethanol production, to serve as a feed substitute. The question remains as to what extent these two feed sources are substitutable. The purpose of this study is to identify the economically optimal inclusion rate of distiller’s grains in beef feedlot rations, considering an array of often omitted factors. Most currently prevailing recommendation rates are strictly biologically based and frequently reference only one feeding trial. Unique economic factors considered in this research include the impact of by-product inclusion rates on animal performance (utilizing recently conducted meta-analysis from 17 relevant feeding trials), enhanced likelihood of death loss from heightened sulfur content, and manure disposal costs. Results indicate that excluding these factors can significantly impact optimal inclusion levels and that reliance on a single or few feeding trials may greatly bias results.distiller’s grains, livestock rations, manure disposal cost,

    ECONOMICS OF ALTERNATIVE STOCKING DENSITIES FOR DIRECT-SEEDED CENTRAL MICHIGAN ALFALFA PASTURES

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    A framework which permits estimation of economically optimal stocking rates for alternative economic parameters and alfalfa forage availability was developed and applied to a controlled grazing experiment conducted with Holstein steers (243 kg) placed on direct seeded alfalfa pastures in Central Michigan. Responses of ADG to alternative levels of forage availability per standard livestock unit (FA) were summarized by a quadratic function and the associated gains/ha were calculated. The ADG decreased as standard stocking rate (SSR; SLU/ha) increased except for the combination of the lowest observed SSR and highest FA, where ADG was curvilinear as SSR increased. The trend for gain/ha was curvilinear for all FA. The SSR which maximized gain/ha increased with FA and was greater than that which maximized ADG. Net returns to fixed resources(NRFR)/ha ($/ha)were calculated for alternative SSR and the economically optimal SSR were identified under various levels of herbage mass (kg/d). The SSR's which maximized NRFR were between the SSR's which maximized ADG and gain/ha. The magnitude of the sale price discount for heavier weight calves (slide) influenced the economically optimal SSR and the sensitivity of net return to SSR. The economically optimal SSR increased as slide increased because animals stocked under higher SSR weighed less off pasture and therefore received less price discount.Crop Production/Industries,

    Economically Optimal Distiller Grain Inclusion in Beef Feedlot Rations: Recognition of Omitted Factors

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    With the rapid expansion of the ethanol industry, the feeding landscape familiar to the feedlot industry is changing. While concerns regarding rising corn prices persist, many within the industry are looking at distillers grains, a by-product of ethanol production, to serve as a feed substitute. The question remains as to what extent these two feed sources are substitutable. The purpose of this study is to identify the economically optimal inclusion rate of distillers grains in beef feedlot rations, considering an array of often omitted factors. Most currently prevailing recommendation rates are strictly biologically based and frequently reference only one feeding trial. Unique economic factors considered in this research include the impact of by-product inclusion rates on animal performance (utilizing recently conducted meta-analysis from 17 relevant feeding trials), enhanced likelihood of death loss from heightened sulfur content, and manure disposal costs. Results indicate that excluding these factors can significantly impact optimal inclusion levels and that reliance on a single or few feeding trials may greatly bias results.Livestock Production/Industries,

    Phenotypic screening reveals TNFR2 as a promising target for cancer immunotherapy.

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    Antibodies that target cell-surface molecules on T cells can enhance anti-tumor immune responses, resulting in sustained immune-mediated control of cancer. We set out to find new cancer immunotherapy targets by phenotypic screening on human regulatory T (Treg) cells and report the discovery of novel activators of tumor necrosis factor receptor 2 (TNFR2) and a potential role for this target in immunotherapy. A diverse phage display library was screened to find antibody mimetics with preferential binding to Treg cells, the most Treg-selective of which were all, without exception, found to bind specifically to TNFR2. A subset of these TNFR2 binders were found to agonise the receptor, inducing iκ-B degradation and NF-κB pathway signalling in vitro. TNFR2 was found to be expressed by tumor-infiltrating Treg cells, and to a lesser extent Teff cells, from three lung cancer patients, and a similar pattern was also observed in mice implanted with CT26 syngeneic tumors. In such animals, TNFR2-specific agonists inhibited tumor growth, enhanced tumor infiltration by CD8+ T cells and increased CD8+ T cell IFN-γ synthesis. Together, these data indicate a novel mechanism for TNF-α-independent TNFR2 agonism in cancer immunotherapy, and demonstrate the utility of target-agnostic screening in highlighting important targets during drug discovery.GW, BM, SG, JC-U, AS, AG-M, CB, JJ, RL, AJL, SR, RS, LJ, VV-A, RM and RWW were funded by MedImmune; JP and VB were funded by AstraZeneca PLC; JW, RSA-L and JB were funded by NIHR Cambridge Biomedical Research Centre and Kidney Research UK; JS and JF were funded by Retrogenix Ltd

    The motion of trees in the wind : a data synthesis

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    Interactions between wind and trees control energy exchanges between the atmosphere and forest canopies. This energy exchange can lead to the widespread damage of trees, and wind is a key disturbance agent in many of the world’s forests. However, most research on this topic has focused on conifer plantations, where risk management is economically important, rather than broadleaf forests, which dominate the forest carbon cycle. This study brings together tree motion time-series data to systematically evaluate the factors influencing tree responses to wind loading, including data from both broadleaf and coniferous trees in forests and open environments. Wefoundthatthetwomostdescriptive features of tree motion were (a) the fundamental frequency, which is a measure of the speed at which a tree sways and is strongly related to tree height, and (b) the slope of the power spectrum, which is related to the efficiency of energy transfer from wind to trees. Intriguingly, the slope of the power spectrum was found to remain constant from medium to high wind speeds for all trees in this study. This suggests that, contrary to some predictions, damping or amplification mechanisms do not change dramatically at high wind speeds, and therefore wind damage risk is related, relatively simply, to wind speed. Conifers from forests were distinct from broadleaves in terms of their response to wind loading. Specifically, the fundamental frequency of forest conifers was related to their size according to the cantilever beam model (i.e. vertically distributed mass), whereas broadleaves were better approximated by the simple pendulum model (i.e. dominated by the crown). Forest conifers also had a steeper slope of the power spectrum. We interpret these finding as being strongly related to tree architecture; i.e. conifers generally have a simple shape due to their apical dominance, whereas broadleaves exhibit a much wider range of architectures with more dominant crowns

    Discovery of a new class of inhibitors for the protein arginine deiminase type 4 (PAD4) by structure-based virtual screening

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    <p>Abstract</p> <p>Background</p> <p>Rheumatoid arthritis (RA) is an autoimmune disease with unknown etiology. Anticitrullinated protein autoantibody has been documented as a highly specific autoantibody associated with RA. Protein arginine deiminase type 4 (PAD4) is the enzyme responsible for catalyzing the conversion of peptidylarginine into peptidylcitrulline. PAD4 is a new therapeutic target for RA treatment. In order to search for inhibitors of PAD4, structure-based virtual screening was performed using LIDAEUS (Ligand discovery at Edinburgh university). Potential inhibitors were screened experimentally by inhibition assays.</p> <p>Results</p> <p>Twenty two of the top-ranked water-soluble compounds were selected for inhibitory screening against PAD4. Three compounds showed significant inhibition of PAD4 and their IC<sub>50 </sub>values were investigated. The structures of the three compounds show no resemblance with previously discovered PAD4 inhibitors, nor with existing drugs for RA treatment.</p> <p>Conclusion</p> <p>Three compounds were discovered as potential inhibitors of PAD4 by virtual screening. The compounds are commercially available and can be used as scaffolds to design more potent inhibitors against PAD4.</p

    Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes.

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    OBJECTIVE: Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS: We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS: Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10(-8)). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10(-4)), improved β-cell function (P = 1.1 × 10(-5)), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10(-6)). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS: We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis

    Large expert-curated database for benchmarking document similarity detection in biomedical literature search

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    Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe
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