1,202 research outputs found
Blending and shaking : Chinese studentsā perceptions of blended learning in a hospitality and tourism course
Best Refereed Paper Award of the conferenceRefereed conference paper2007-2008 > Academic research: refereed > Refereed conference paperOther VersionPublishe
Amniotic fl uid embolism in an HIV-positive parturient
We present a case of a parturient infected with human immunode ciency virus, who developed amniotic fluid embolism during the delivery of her twins by elective Caesarean section. Our management and the available literature are briefly discussed, and consideration is given to a possible association between the two pathologies.Keywords: amniotic fluid embolism; anaphylaxis; human immunodeĀ ciency viru
Nonparametric Bayesian inference for perturbed and orthologous gene regulatory networks
Motivation: The generation of time series transcriptomic datasets collected under multiple experimental conditions has proven to be a powerful approach for disentangling complex biological processes, allowing for the reverse engineering of gene regulatory networks (GRNs). Most methods for reverse engineering GRNs from multiple datasets assume that each of the time series were generated from networks with identical topology. In this study, we outline a hierarchical, non-parametric Bayesian approach for reverse engineering GRNs using multiple time series that can be applied in a number of novel situations including: (i) where different, but overlapping sets of transcription factors are expected to bind in the different experimental conditions; that is, where switching events could potentially arise under the different treatments and (ii) for inference in evolutionary related species in which orthologous GRNs exist. More generally, the method can be used to identify context-specific regulation by leveraging time series gene expression data alongside methods that can identify putative lists of transcription factors or transcription factor targets.
Results: The hierarchical inference outperforms related (but non-hierarchical) approaches when the networks used to generate the data were identical, and performs comparably even when the networks used to generate data were independent. The method was subsequently used alongside yeast one hybrid and microarray time series data to infer potential transcriptional switches in Arabidopsis thaliana response to stress. The results confirm previous biological studies and allow for additional insights into gene regulation under various abiotic stresses.
Availability: The methods outlined in this article have been implemented in Matlab and are available on request
Inferring orthologous gene regulatory networks using interspecies data fusion
MOTIVATION:
The ability to jointly learn gene regulatory networks (GRNs) in, or leverage GRNs between related species would allow the vast amount of legacy data obtained in model organisms to inform the GRNs of more complex, or economically or medically relevant counterparts. Examples include transferring information from Arabidopsis thaliana into related crop species for food security purposes, or from mice into humans for medical applications. Here we develop two related Bayesian approaches to network inference that allow GRNs to be jointly inferred in, or leveraged between, several related species: in one framework, network information is directly propagated between species; in the second hierarchical approach, network information is propagated via an unobserved 'hypernetwork'. In both frameworks, information about network similarity is captured via graph kernels, with the networks additionally informed by species-specific time series gene expression data, when available, using Gaussian processes to model the dynamics of gene expression.
RESULTS:
Results on in silico benchmarks demonstrate that joint inference, and leveraging of known networks between species, offers better accuracy than standalone inference. The direct propagation of network information via the non-hierarchical framework is more appropriate when there are relatively few species, while the hierarchical approach is better suited when there are many species. Both methods are robust to small amounts of mislabelling of orthologues. Finally, the use of Saccharomyces cerevisiae data and networks to inform inference of networks in the budding yeast Schizosaccharomyces pombe predicts a novel role in cell cycle regulation for Gas1 (SPAC19B12.02c), a 1,3-beta-glucanosyltransferase
CSI : A nonparametric Bayesian approach to network inference from multiple perturbed time series gene expression data
How an organism responds to the environmental challenges it faces is heavily influenced by its gene regulatory networks (GRNs). Whilst most methods for inferring GRNs from time series mRNA expression data are only able to cope with single time series (or single perturbations with biological replicates), it is becoming increasingly common for several time series to be generated under different experimental conditions. The CSI algorithm (Klemm, 2008) represents one approach to inferring
GRNs from multiple time series data, which has previously been shown to perform well on a variety of datasets (Penfold and Wild, 2011). Another challenge in network inference is the identification of condition specific GRNs i.e., identifying how a GRN is rewired under different conditions or different individuals. The Hierarchical Causal Structure Identification (HCSI) algorithm (Penfold et al., 2012) is one approach that allows inference of condition specific networks (Hickman et al.,
2013), that has been shown to be more accurate at reconstructing known networks than inference on the individual datasets alone. Here we describe a MATLAB implementation of CSI/HCSI that includes fast approximate solutions to CSI as well as Markov Chain Monte Carlo implementations of both CSI and HCSI, together with a user-friendly GUI, with the intention of making the analysis of networks from multiple perturbed time series datasets more accessible to the wider community.1 The GUI itself guides the user through each stage of the analysis, from loading in the data, to parameter selection and visualisation of networks, and can be launched by typing >> csi into the MATLAB command line. For each step of the analysis, links to documentation and tutorials are available within the GUI, which includes documentation on visualisation and interacting with output file
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Clinician identification of youth abusing over-the-counter products for weight control in a large U.S. integrated health system
Background: Abuse of over-the-counter (OTC) products, such as diet pills and laxatives, for weight control by adolescents is well-documented and can precipitate serious medical conditions. Yet only a small percentage of youth with disordered weight control behaviors receive treatment. The objective of this study was to examine how often clinicians communicate with youth with symptoms consistent with abuse of OTC products for weight control about possible use of these products. We used electronic medical records and administrative claims for services for 53,229 12 to 17 year old patients receiving care from an integrated health system in the U.S. Northwest from August 2007 to December 2010. We examined electronic text of clinical notes to identify encounters in which the clinician noted one of 10 metabolic conditions potentially associated with abuse of OTC products (diet pills, laxatives, diuretics, ipecac, orlistat, and alliĀ®) for weight control and then assessed whether clinicians noted communication with adolescent patients about possible use of OTC products for weight control. Results: We identified 130 (0.2% of sample) patients with clinical notes indicating one or more of the metabolic conditions. In clinical notes for only four (3.1%) of these patients did clinicians document suspicion or communication about possible abuse of the OTC products. All four had a previous eating disorder diagnosis. In the 12 months subsequent to the clinical encounter in which a metabolic disturbance was identified, medical notes for only three (2.3%) of the 130 patients indicated clinician suspicion or communication about possible abuse of these products or an eating disorder. Conclusions: Clinicians are missing a critical window of opportunity to query adolescents when presenting with suspicious metabolic disturbances about possible abuse of OTC products for weight control. Clinicians may need more training to detect OTC product abuse, and electronic medical records should prompt more thorough enquiry
Bringing numerous methods for expression and promoter analysis to a public cloud computing service
Every year, a large number of novel algorithms are introduced to the scientific community for a myriad of applications, but using these across different research groups is often troublesome, due to suboptimal implementations and specific dependency requirements. This does not have to be the case, as public cloud computing services can easily house tractable implementations within self-contained dependency environments, making the methods easily accessible to a wider public. We have taken 14 popular methods, the majority related to expression data or promoter analysis, developed these up to a good implementation standard and housed the tools in isolated Docker containers which we integrated into the CyVerse Discovery Environment, making these easily usable for a wide community as part of the CyVerse UK project
What dictates the spatial distribution of nanoparticles within calcite?
Crystallization is widely used by synthetic chemists as a purification technique because it usually involves the expulsion of impurities. In this context, the efficient occlusion of guest nanoparticles within growing host crystals can be regarded as a formidable technical challenge. Indeed, although there are various reports of successful nanoparticle occlusion within inorganic crystals in the literature, robust design rules remain elusive. Herein, we report the synthesis of two pairs of sterically stabilized diblock copolymer nanoparticles with identical compositions but varying particle size, morphology, stabilizer chain length, and stabilizer chain surface density via polymerization-induced self-assembly (PISA). The mean degree of polymerization of the stabilizer chains dictates the spatial distribution of these model anionic nanoparticles within calcite (CaCO3): relatively short stabilizer chains merely result in near-surface occlusion, whereas sufficiently long stabilizer chains are essential to achieve uniform occlusion. This study reconciles the various conflicting literature reports of occluded nanoparticles being either confined to surface layers or uniformly occluded throughout the host matrix and hence provides important new insights regarding the criteria required for efficient nanoparticle occlusion within inorganic crystals
Decreased ovarian reserve, dysregulation of mitochondrial biogenesis, and increased lipid peroxidation in female mouse offspring exposed to an obesogenic maternal diet.
Maternal diet during pregnancy influences the later life reproductive potential of female offspring. We investigate the molecular mechanisms underlying the depletion of ovarian follicular reserve in young adult females following exposure to obesogenic diet in early life. Furthermore, we explore the interaction between adverse maternal diet and postweaning diet in generating reduced ovarian reserve. Female mice were exposed to either maternal obesogenic (high fat/high sugar) or maternal control dietin uteroand during lactation, then weaned onto either obesogenic or control diet. At 12 wk of age, the offspring ovarian reserve was depleted following exposure to maternal obesogenic diet (P< 0.05), but not postweaning obesogenic diet. Maternal obesogenic diet was associated with increased mitochondrial DNA biogenesis (copy numberP< 0.05; transcription factor A, mitochondrial expressionP< 0.05), increased mitochondrial antioxidant defenses [manganese superoxide dismutase (MnSOD)P< 0.05; copper/zinc superoxide dismutaseP< 0.05; glutathione peroxidase 4P< 0.01] and increased lipoxygenase expression (arachidonate 12-lipoxygenaseP< 0.05; arachidonate 15-lipoxygenaseP< 0.05) in the ovary. There was also significantly increased expression of the transcriptional regulator NF-ĪŗB (P< 0.05). There was no effect of postweaning diet on any measured ovarian parameters. Maternal diet thus plays a central role in determining follicular reserve in adult female offspring. Our observations suggest that lipid peroxidation and mitochondrial biogenesis are the key intracellular pathways involved in programming of ovarian reserve.-Aiken, C. E., Tarry-Adkins, J. L., Penfold, N. C., Dearden, L., Ozanne, S. E. Decreased ovarian reserve, dysregulation of mitochondrial biogenesis, and increased lipid peroxidation in female mouse offspring exposed to an obesogenic maternal diet.This study was funded jointly by grants from the Academy of Medical Sciences, the Addenbrookeās Charitable Trust, an Isaac Newton Trust/Wellcome Trust ISSF/University of Cambridge Joint Research Grant and the MRC (MRC_MC_UU_12012/4).This is the final version of the article. It first appeared from the Federation of American Societies for Experimental Biology via http://dx.doi.org/10.1096/fj.15-28080
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Negotiated, contested and political: the disruptive Third Spaces of youth media production
Traditionally media production with young people has been characterised by an aspiration to āgive voiceā or āempower youthā, but this core value is under threat. Recently, the rationale for undertaking youth media production has shifted to focus instead on enabling young people to acquire digital skills to serve the needs of rapidly changing creative industries to be entrepreneurs in a gig economy. In this paper, we share qualitative data from a young peopleās media production project run in libraries in a city in the United Kingdom where participants were invited to create videogames/stories. We adopt Potter and McDougallās notion of Third Spaces as negotiated, contested and political to enable us to identify the ways in which pedagogical choices of setting, software and style of facilitation combined to support young peopleās critical and creative engagement with digital media and society. We reframe notions of third spaces, seeing less a bridge between linguistic and cultural domains and instead of arguing that Third Spaces are productively disruptive. We conclude by proposing a new set of pedagogical principles for critical reflection in the development and funding of digital media production with young people
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