Predicting the start week of respiratory syncytial virus outbreaks using real time weather variables

<p>Abstract</p> <p>Background</p> <p>Respiratory Syncytial Virus (RSV), a major cause of bronchiolitis, has a large impact on the census of pediatric hospitals during outbreak seasons. Reliable prediction of the week these outbreaks will start, based on readily available data, could help pediatric hospitals better prepare for large outbreaks.</p> <p>Methods</p> <p>Naïve Bayes (NB) classifier models were constructed using weather data from 1985-2008 considering only variables that are available in real time and that could be used to forecast the week in which an RSV outbreak will occur in Salt Lake County, Utah. Outbreak start dates were determined by a panel of experts using 32,509 records with ICD-9 coded RSV and bronchiolitis diagnoses from Intermountain Healthcare hospitals and clinics for the RSV seasons from 1985 to 2008.</p> <p>Results</p> <p>NB models predicted RSV outbreaks up to 3 weeks in advance with an estimated sensitivity of up to 67% and estimated specificities as high as 94% to 100%. Temperature and wind speed were the best overall predictors, but other weather variables also showed relevance depending on how far in advance the predictions were made. The weather conditions predictive of an RSV outbreak in our study were similar to those that lead to temperature inversions in the Salt Lake Valley.</p> <p>Conclusions</p> <p>We demonstrate that Naïve Bayes (NB) classifier models based on weather data available in real time have the potential to be used as effective predictive models. These models may be able to predict the week that an RSV outbreak will occur with clinical relevance. Their clinical usefulness will be field tested during the next five years.</p

Amyloid Plaques Beyond Aβ: A Survey of the Diverse Modulators of Amyloid Aggregation

Aggregation of the amyloid-β (Aβ) peptide is strongly correlated with Alzheimer’s disease (AD). Recent research has improved our understanding of the kinetics of amyloid fibril assembly and revealed new details regarding different stages in plaque formation. Presently, interest is turning toward studying this process in a holistic context, focusing on cellular components which interact with the Aβ peptide at various junctures during aggregation, from monomer to cross-β amyloid fibrils. However, even in isolation, a multitude of factors including protein purity, pH, salt content, and agitation affect Aβ fibril formation and deposition, often producing complicated and conflicting results. The failure of numerous inhibitors in clinical trials for AD suggests that a detailed examination of the complex interactions that occur during plaque formation, including binding of carbohydrates, lipids, nucleic acids, and metal ions, is important for understanding the diversity of manifestations of the disease. Unraveling how a variety of key macromolecular modulators interact with the Aβ peptide and change its aggregation properties may provide opportunities for developing therapies. Since no protein acts in isolation, the interplay of these diverse molecules may differentiate disease onset, progression, and severity, and thus are worth careful consideration

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration

Alzheimer's Aβ Peptides with Disease-Associated N-Terminal Modifications: Influence of Isomerisation, Truncation and Mutation on Cu2+ Coordination

coordination of various Aβ peptides has been widely studied. A number of disease-associated modifications involving the first 3 residues are known, including isomerisation, mutation, truncation and cyclisation, but are yet to be characterised in detail. In particular, Aβ in plaques contain a significant amount of truncated pyroglutamate species, which appear to correlate with disease progression. coordination modes between pH 6–9 with nominally the same first coordination sphere, but with a dramatically different pH dependence arising from differences in H-bonding interactions at the N-terminus. coordination of Aβ, which may be critical for alterations in aggregation propensity, redox-activity, resistance to degradation and the generation of the Aβ3–× (× = 40/42) precursor of disease-associated Aβ3[pE]–x species

Expansion and functional diversification of a leucyl aminopeptidase family that encodes the major protein constituents of Drosophila sperm

<p>Abstract</p> <p>Background</p> <p>The evolutionary diversification of gene families through gene creation (and loss) is a dynamic process believed to be critical to the evolution of functional novelty. Previous identification of a closely related family of eight annotated metalloprotease genes of the M17 Merops family in the <it>Drosophila </it>sperm proteome (termed, Sperm-LeucylAminoPeptidases, S-LAPs 1-8) led us to hypothesize that this gene family may have experienced such a diversification during insect evolution.</p> <p>Results</p> <p>To assess putative functional activities of S-LAPs, we (i) demonstrated that all S-LAPs are specifically expressed in the testis, (ii) confirmed their presence in sperm by two-dimensional gel electrophoresis and mass spectrometry, (iii) determined that they represent a major portion of the total protein in sperm and (iv) identified aminopeptidase enzymatic activity in sperm extracts using LAP-specific substrates. Functionally significant divergence at the canonical M17 active site indicates that the largest phylogenetic group of S-LAPs lost catalytic activity and likely acquired novel, as yet undetermined, functions in sperm prior to the expansion of the gene family.</p> <p>Conclusions</p> <p>Comparative genomic and phylogenetic analyses revealed the dramatic expansion of the S-LAP gene family during <it>Drosophila </it>evolution and copy number heterogeneity in the genomes of related insects. This finding, in conjunction with the loss of catalytic activity and potential neofunctionalization amongst some family members, extends empirical support for pervasive "revolving door" turnover in the evolution of reproductive gene family composition and function.</p

The role of dietary fibre in pig production, with a particular emphasis on reproduction

Abstract Fibres from a variety of sources are a common constituent of pig feeds. They provide a means to utilise locally-produced plant materials which are often a by-product of the food or drink industry. The value of a high fibre diet in terms of producing satiety has long been recognised. However the addition of fibre can reduce feed intake, which is clearly detrimental during stages of the production cycle when nutrient needs are high, for example in growing piglets and during lactation. More recently, fibre has been found to promote novel benefits to pig production systems, particularly given the reduction in antimicrobial use world-wide, concern for the welfare of animals fed a restricted diet and the need to ensure that such systems are more environmentally friendly. For example, inclusion of dietary fibre can alter the gut microbiota in ways that could reduce the need for antibiotics, while controlled addition of certain fibre types may reduce nitrogen losses into the environment and so reduce the environmental cost of pig production. Of particular potential value is the opportunity to use crude fibre concentrates as ‘functional’ feed additives to improve young pig growth and welfare. Perhaps the greatest opportunity for the use of high fibre diets is to improve the reproductive efficiency of pigs. Increased dietary fibre before mating improves oocyte maturation, prenatal survival and litter size; providing a consumer-acceptable means of increasing the amount of saleable meat produced per sow. The mechanisms responsible for these beneficial effects remain to be elucidated. However, changes in plasma and follicular fluid concentrations of key hormones and metabolites, as well as effects of the hypothalamic satiety centre on gonadotrophin secretion and epigenetic effects are strong candidates

Cognition based bTBI mechanistic criteria; a tool for preventive and therapeutic innovations

Blast-induced traumatic brain injury has been associated with neurodegenerative and neuropsychiatric disorders. To date, although damage due to oxidative stress appears to be important, the specific mechanistic causes of such disorders remain elusive. Here, to determine the mechanical variables governing the tissue damage eventually cascading into cognitive deficits, we performed a study on the mechanics of rat brain under blast conditions. To this end, experiments were carried out to analyse and correlate post-injury oxidative stress distribution with cognitive deficits on a live rat exposed to blast. A computational model of the rat head was developed from imaging data and validated against in vivo brain displacement measurements. The blast event was reconstructed in silico to provide mechanistic thresholds that best correlate with cognitive damage at the regional neuronal tissue level, irrespectively of the shape or size of the brain tissue types. This approach was leveraged on a human head model where the prediction of cognitive deficits was shown to correlate with literature findings. The mechanistic insights from this work were finally used to propose a novel helmet design roadmap and potential avenues for therapeutic innovations against blast traumatic brain injury

Studies on the production of branched-chain alcohols in engineered Ralstonia eutropha

Wild-type Ralstonia eutropha H16 produces polyhydroxybutyrate (PHB) as an intracellular carbon storage material during nutrient stress in the presence of excess carbon. In this study, the excess carbon was redirected in engineered strains from PHB storage to the production of isobutanol and 3-methyl-1-butanol (branched-chain higher alcohols). These branched-chain higher alcohols can directly substitute for fossil-based fuels and be employed within the current infrastructure. Various mutant strains of R. eutropha with isobutyraldehyde dehydrogenase activity, in combination with the overexpression of plasmid-borne, native branched-chain amino acid biosynthesis pathway genes and the overexpression of heterologous ketoisovalerate decarboxylase gene, were employed for the biosynthesis of isobutanol and 3-methyl-1-butanol. Production of these branched-chain alcohols was initiated during nitrogen or phosphorus limitation in the engineered R. eutropha. One mutant strain not only produced over 180 mg/L branched-chain alcohols in flask culture, but also was significantly more tolerant of isobutanol toxicity than wild-type R. eutropha. After the elimination of genes encoding three potential carbon sinks (ilvE, bkdAB, and aceE), the production titer improved to 270 mg/L isobutanol and 40 mg/L 3-methyl-1-butanol. Semicontinuous flask cultivation was utilized to minimize the toxicity caused by isobutanol while supplying cells with sufficient nutrients. Under this semicontinuous flask cultivation, the R. eutropha mutant grew and produced more than 14 g/L branched-chain alcohols over the duration of 50 days. These results demonstrate that R. eutropha carbon flux can be redirected from PHB to branched-chain alcohols and that engineered R. eutropha can be cultivated over prolonged periods of time for product biosynthesis.United States. Dept. of EnergyUnited States. Advanced Research Projects Agency-Energ

Functional redundancy and sensitivity of fish assemblages in European rivers, lakes and estuarine ecosystems

The impact of species loss on ecosystems functioning depends on the amount of trait similarity between species, i.e. functional redundancy, but it is also influenced by the order in which species are lost. Here we investigated redundancy and sensitivity patterns across fish assemblages in lakes, rivers and estuaries. Several scenarios of species extinction were simulated to determine whether the loss of vulnerable species (with high propensity of extinction when facing threats) causes a greater functional alteration than random extinction. Our results indicate that the functional redundancy tended to increase with species richness in lakes and rivers, but not in estuaries. We demonstrated that i) in the three systems, some combinations of functional traits are supported by non-redundant species, ii) rare species in rivers and estuaries support singular functions not shared by dominant species, iii) the loss of vulnerable species can induce greater functional alteration in rivers than in lakes and estuaries. Overall, the functional structure of fish assemblages in rivers is weakly buffered against species extinction because vulnerable species support singular functions. More specifically, a hotspot of functional sensitivity was highlighted in the Iberian Peninsula, which emphasizes the usefulness of quantitative criteria to determine conservation prioritiesinfo:eu-repo/semantics/publishedVersio