SADI, SHARE, and the in silico scientific method

<p>Abstract</p> <p>Background</p> <p>The emergence and uptake of Semantic Web technologies by the Life Sciences provides exciting opportunities for exploring novel ways to conduct <it>in silico</it> science. Web Service Workflows are already becoming first-class objects in “the new way”, and serve as explicit, shareable, referenceable representations of how an experiment was done. In turn, Semantic Web Service projects aim to facilitate workflow construction by biological domain-experts such that workflows can be edited, re-purposed, and re-published by non-informaticians. However the aspects of the scientific method relating to explicit discourse, disagreement, and hypothesis generation have remained relatively impervious to new technologies.</p> <p>Results</p> <p>Here we present SADI and SHARE - a novel Semantic Web Service framework, and a reference implementation of its client libraries. Together, SADI and SHARE allow the semi- or fully-automatic discovery and pipelining of Semantic Web Services in response to <it>ad hoc</it> user queries.</p> <p>Conclusions</p> <p>The semantic behaviours exhibited by SADI and SHARE extend the functionalities provided by Description Logic Reasoners such that novel assertions can be automatically added to a data-set without logical reasoning, but rather by analytical or annotative services. This behaviour might be applied to achieve the “semantification” of those aspects of the <it>in silico</it> scientific method that are not yet supported by Semantic Web technologies. We support this suggestion using an example in the clinical research space.</p

Animals can assign novel odours to a known category

The ability to identify a novel stimulus as a member of a known category allows an organism torespond appropriately towards it. Categorisation is thus a fundamental component of cognition andan essential tool for processing and responding to unknown stimuli. Therefore, one might expectto observe it throughout the animal kingdom and across sensory domains. There is much evidenceof visual categorisation in non-human animals, but we currently know little about this process inother modalities. In this experiment, we investigated categorisation in the olfactory domain. Dogswere trained to discriminate between 40 odours; the presence or absence of accelerants formed thecategorical rule. Those in the experimental group were rewarded for responding to substrates withaccelerants (either burnt or un-burnt) and inhibit responses to the same substrates (either burnt or unburnt)without accelerants (S+ counterbalanced). The pseudocategory control group was trained onthe same stimuli without the categorical rule. The experimental group learned the discrimination andanimals were able to generalise to novel stimuli from the same category. None of the control animalswere able to learn the discrimination within the maximum number of trials. This study provides the firstevidence that non-human animals can learn to categorise non-biologically relevant odour information

Relationships between plant traits, soil properties and carbon fluxes differ between monocultures and mixed communities in temperate grassland

1. The use of plant traits to predict ecosystem functions has been gaining growing attention. Above‐ground plant traits, such as leaf nitrogen (N) content and specific leaf area (SLA), have been shown to strongly relate to ecosystem productivity, respiration and nutrient cycling. Furthermore, increasing plant functional trait diversity has been suggested as a possible mechanism to increase ecosystem carbon (C) storage. However, it is uncertain whether below‐ground plant traits can be predicted by above‐ground traits, and if both above‐ and below‐ground traits can be used to predict soil properties and ecosystem‐level functions. 2. Here, we used two adjacent field experiments in temperate grassland to investigate if above‐ and below‐ground plant traits are related, and whether relationships between plant traits, soil properties and ecosystem C fluxes (i.e. ecosystem respiration and net ecosystem exchange) measured in potted monocultures could be detected in mixed field communities. 3. We found that certain shoot traits (e.g. shoot N and C, and leaf dry matter content) were related to root traits (e.g. root N, root C:N and root dry matter content) in monocultures, but such relationships were either weak or not detected in mixed communities. Some relationships between plant traits (i.e. shoot N, root N and/or shoot C:N) and soil properties (i.e. inorganic N availability and microbial community structure) were similar in monocultures and mixed communities, but they were more strongly linked to shoot traits in monocultures and root traits in mixed communities. Structural equation modelling showed that above‐ and below‐ground traits and soil properties improved predictions of ecosystem C fluxes in monocultures, but not in mixed communities on the basis of community‐weighted mean traits. 4. Synthesis. Our results from a single grassland habitat detected relationships in monocultures between above‐ and below‐ground plant traits, and between plant traits, soil properties and ecosystem C fluxes. However, these relationships were generally weaker or different in mixed communities. Our results demonstrate that while plant traits can be used to predict certain soil properties and ecosystem functions in monocultures, they are less effective for predicting how changes in plant species composition influence ecosystem functions in mixed communities

A PAX5-OCT4-PRDM1 developmental switch specifies human primordial germ cells.

Dysregulation of genetic pathways during human germ cell development leads to infertility. Here, we analysed bona fide human primordial germ cells (hPGCs) to probe the developmental genetics of human germ cell specification and differentiation. We examined the distribution of OCT4 occupancy in hPGCs relative to human embryonic stem cells (hESCs). We demonstrated that development, from pluripotent stem cells to germ cells, is driven by switching partners with OCT4 from SOX2 to PAX5 and PRDM1. Gain- and loss-of-function studies revealed that PAX5 encodes a critical regulator of hPGC development. Moreover, an epistasis analysis indicated that PAX5 acts upstream of OCT4 and PRDM1. The PAX5-OCT4-PRDM1 proteins form a core transcriptional network that activates germline and represses somatic programmes during human germ cell differentiation. These findings illustrate the power of combined genome editing, cell differentiation and engraftment for probing human developmental genetics that have historically been difficult to study

Viral inhibition of bacterial phagocytosis by human macrophages: redundant role of CD36

Macrophages are essential to maintaining lung homoeostasis and recent work has demonstrated that influenza-infected lung macrophages downregulate their expression of the scavenger receptor CD36. This receptor has also been shown to be involved in phagocytosis of Streptococcus pneumoniae, a primary agent associated with pneumonia secondary to viral infection. The aim of this study was to investigate the role of CD36 in the effects of viral infection on macrophage phagocytic function. Human monocyte-derived macrophages (MDM) were exposed to H3N2 X31 influenza virus, M37 respiratory syncytial virus (RSV) or UV-irradiated virus. No infection of MDM was seen upon exposure to UV-irradiated virus but incubation with live X31 or M37 resulted in significant levels of viral detection by flow cytometry or RT-PCR respectively. Infection resulted in significantly diminished uptake of S. pneumoniae by MDM and significantly decreased expression of CD36 at both the cell surface and mRNA level. Concurrently, there was a significant increase in IFN? gene expression in response to infection and we observed a significant decrease in bacterial phagocytosis (p = 0.031) and CD36 gene expression (p = 0.031) by MDM cultured for 24 h in 50IU/ml IFN?. Knockdown of CD36 by siRNA resulted in decreased phagocytosis, but this was mimicked by transfection reagent alone. When MDM were incubated with CD36 blocking antibodies no effect on phagocytic ability was observed. These data indicate that autologous IFN? production by virally-infected cells can inhibit bacterial phagocytosis, but that decreased CD36 expression by these cells does not play a major role in this functional deficiency

Is the contemporary care of the older persons with acute coronary syndrome evidence-based?

Globally, ischaemic heart disease is the leading cause of death, with a higher mortality burden amongst older adults. Although advancing age is associated with a higher risk of adverse outcomes following acute coronary syndrome (ACS), older patients are less likely to receive evidence-based medications and coronary angiography. Guideline recommendations for managing ACS are often based on studies that exclude older patients, and more contemporary trials have been underpowered and produced inconsistent findings. There is also limited evidence for how frailty and comorbidity should influence management decisions. This review focuses on the current evidence base for the medical and percutaneous management of ACS in older patients and highlights the distinct need to enrol older patients with ACS into well-powered, large-scale randomized trials

Characterization of Clinically-Attenuated Burkholderia mallei by Whole Genome Sequencing: Candidate Strain for Exclusion from Select Agent Lists

is an understudied biothreat agent responsible for glanders which can be lethal in humans and animals. Research with this pathogen has been hampered in part by constraints of Select Agent regulations for safety reasons. Whole genomic sequencing (WGS) is an apt approach to characterize newly discovered or poorly understood microbial pathogens. genome. Therefore, the strain by itself is unlikely to revert naturally to its virulent phenotype. There were other genes present in one strain and not the other and vice-versa. was both avirulent in the natural host ponies, and did not possess T3SS associated genes may be fortuitous to advance biodefense research. The deleted virulence-essential T3SS is not likely to be re-acquired naturally. These findings may provide a basis for exclusion of SAVP1 from the Select Agent regulation or at least discussion of what else would be required for exclusion. This exclusion could accelerate research by investigators not possessing BSL-3 facilities and facilitate the production of reagents such as antibodies without the restraints of Select Agent regulation

Measurement of the lepton charge asymmetry in W-boson decays produced in p-pbar collisions

We describe a measurement of the charge asymmetry of leptons from W boson decays in the rapidity range 0 enu, munu events from 110+/-7 pb^{-1}of data collected by the CDF detector during 1992-95. The asymmetry data constrain the ratio of d and u quark momentum distributions in the proton over the x range of 0.006 to 0.34 at Q2 \approx M_W^2. The asymmetry predictions that use parton distribution functions obtained from previously published CDF data in the central rapidity region (0.0<|y_l|<1.1) do not agree with the new data in the large rapidity region (|y_l|>1.1).Comment: 13 pages, 3 tables, 1 figur

Observation of Hadronic W Decays in t-tbar Events with the Collider Detector at Fermilab

We observe hadronic W decays in t-tbar -> W (-> l nu) + >= 4 jet events using a 109 pb-1 data sample of p-pbar collisions at sqrt{s} = 1.8 TeV collected with the Collider Detector at Fermilab (CDF). A peak in the dijet invariant mass distribution is obtained that is consistent with W decay and inconsistent with the background prediction by 3.3 standard deviations. From this peak we measure the W mass to be 77.2 +- 4.6 (stat+syst) GeV/c^2. This result demonstrates the presence of two W bosons in t-tbar candidates in the W (-> l nu) + >= 4 jet channel.Comment: 20 pages, 4 figures, submitted to PR

Search for Chargino-Neutralino Associated Production at the Fermilab Tevatron Collider

We have searched in $p \bar{p}$ collisions at $\sqrt{s}$ = 1.8 TeV for events with three charged leptons and missing transverse energy. In the Minimal Supersymmetric Standard Model, we expect trilepton events from chargino-neutralino (\chione \chitwo) pair production, with subsequent decay into leptons. We observe no candidate $e^+e^-e^\pm$, $e^+e^-\mu^\pm$, $e^\pm\mu^+\mu^-$ or $\mu^+\mu^-\mu^\pm$ events in 106 pb$^{-1}$ integrated luminosity. We present limits on the sum of the branching ratios times cross section for the four channels: \sigma_{\chione\chitwo}\cdot BR(\chione\chitwo\to 3\ell+X) 81.5 \mgev\sp and M_\chitwo > 82.2 \mgev\sp for $\tan\beta=2$, $\mu =-600$~\mgev\sp and M_\squark= M_\gluino.Comment: 9 pages and 3 figure