12,968 research outputs found
Evolution of a stream ecosystem in recently deglaciated terrain
Climate change and associated glacial recession create new stream habitat that leads to the assembly of new riverine communities through primary succession. However, there are still very few studies of the patterns and processes of community assembly during primary succession for stream ecosystems. We illustrate the rapidity with which biotic communities can colonize and establish in recently formed streams by examining Stonefly Creek in Glacier Bay, Alaska (USA), which began to emerge from a remnant glacial ice mass between 1976 and 1979. By 2002, 57 macroinvertebrate and 27 microcrustacea species had become established. Within 10 years of the stream's formation, pink salmon and Dolly Varden charr colonized, followed by other fish species, including juvenile red and silver salmon, Coast Range sculpin, and sticklebacks. Stable-isotope analyses indicate that marine-derived nitrogen from the decay of salmon carcasses was substantially assimilated within the aquatic food web by 2004. The findings from Stonefly Creek are compared with those from a long-term study of a similarly formed but older stream (12 km to the northeast) to examine possible similarities in macroinvertebrate community and biological trait composition between streams at similar stages of development. Macroinvertebrate community assembly appears to have been initially strongly deterministic owing to low water temperature associated with remnant ice masses. In contrast, microcrustacean community assembly appears to have been more stochastic. However, as stream age and water temperature increased, macroinvertebrate colonization was also more stochastic, and taxonomic similarity between Stonefly Creek and a stream at the same stage of development was,<50%. However the most abundant taxa were similar, and functional diversity of the two communities was almost identical. Tolerance is suggested as the major mechanism of community assembly. The rapidity with which salmonids and invertebrate communities have become established across an entire watershed has implications for the conservation of biodiversity in freshwater habitats
The constant background bag model of the hadron
We have constructed the bag model having a central constant color field. The
motion of the quark is studied in this bag and the Dirac equation is solved for
it. The energy spectrum found has a branching due to the interaction of the
quarks with the color background. It is pointed out that this model can be
applied for taking into account, in the mass spectrum of hadrons, the coupling
of the constituent quarks with the gluon condensation as the interaction with
the color background.Comment: 10 pages, improved English, will be published in the Eur. Phys. Jour.
Boltzmann Suppression of Interacting Heavy Particles
Matsumoto and Yoshimura have recently argued that the number density of heavy
particles in a thermal bath is not necessarily Boltzmann-suppressed for T << M,
as power law corrections may emerge at higher orders in perturbation theory.
This fact might have important implications on the determination of WIMP relic
densities. On the other hand, the definition of number densities in a
interacting theory is not a straightforward procedure. It usually requires
renormalization of composite operators and operator mixing, which obscure the
physical interpretation of the computed thermal average. We propose a new
definition for the thermal average of a composite operator, which does not
require any new renormalization counterterm and is thus free from such
ambiguities. Applying this definition to the model of Matsumoto and Yoshimura
we find that it gives number densities which are Boltzmann-suppressed at any
order in perturbation theory. We discuss also heavy particles which are
unstable already at T=0, showing that power law corrections do in general
emerge in this case.Comment: 7 pages, 5 figures. New section added, with the discussion of the
case of an unstable heavy particle. Version to appear on Phys. Rev.
Struggling to be Fit: Identity, Integrity, and the Law
This interdisciplinary co-authored Analysis piece introduces identity and integrity, which are argued to sit at the core of the person. It analyses approaches taken to these concepts by legal regimes, particularly in the context of individuals using artificial limbs or digital avatars. The piece concludes that law engages with identity and integrity to a limited and incomplete extent; and that law is thus inadequate in its engagement with the person, and its meaning making in this respect. This piece draws on two interdisciplinary funded projects, funded by the Wellcome Trust and the Arts and Humanities Research Council
Modeling meiotic chromosomes indicates a size dependent contribution of telomere clustering and chromosome rigidity to homologue juxtaposition.
Meiosis is the cell division that halves the genetic component of diploid cells to form gametes or spores. To achieve this, meiotic cells undergo a radical spatial reorganisation of chromosomes. This reorganisation is a prerequisite for the pairing of parental homologous chromosomes and the reductional division, which halves the number of chromosomes in daughter cells. Of particular note is the change from a centromere clustered layout (Rabl configuration) to a telomere clustered conformation (bouquet stage). The contribution of the bouquet structure to homologous chromosome pairing is uncertain. We have developed a new in silico model to represent the chromosomes of Saccharomyces cerevisiae in space, based on a worm-like chain model constrained by attachment to the nuclear envelope and clustering forces. We have asked how these constraints could influence chromosome layout, with particular regard to the juxtaposition of homologous chromosomes and potential nonallelic, ectopic, interactions. The data support the view that the bouquet may be sufficient to bring short chromosomes together, but the contribution to long chromosomes is less. We also find that persistence length is critical to how much influence the bouquet structure could have, both on pairing of homologues and avoiding contacts with heterologues. This work represents an important development in computer modeling of chromosomes, and suggests new explanations for why elucidating the functional significance of the bouquet by genetics has been so difficult
Identification of 2-Aminothiazole-4-Carboxylate Derivatives Active against Mycobacterium tuberculosis H37Rv and the β-Ketoacyl-ACP Synthase mtFabH
Background
Tuberculosis (TB) is a disease which kills two million people every year and infects approximately over one-third of the world's population. The difficulty in managing tuberculosis is the prolonged treatment duration, the emergence of drug resistance and co-infection with HIV/AIDS. Tuberculosis control requires new drugs that act at novel drug targets to help combat resistant forms of Mycobacterium tuberculosis and reduce treatment duration.
Methodology/Principal Findings
Our approach was to modify the naturally occurring and synthetically challenging antibiotic thiolactomycin (TLM) to the more tractable 2-aminothiazole-4-carboxylate scaffold to generate compounds that mimic TLM's novel mode of action. We report here the identification of a series of compounds possessing excellent activity against M. tuberculosis H37Rv and, dissociatively, against the β-ketoacyl synthase enzyme mtFabH which is targeted by TLM. Specifically, methyl 2-amino-5-benzylthiazole-4-carboxylate was found to inhibit M. tuberculosis H37Rv with an MIC of 0.06 µg/ml (240 nM), but showed no activity against mtFabH, whereas methyl 2-(2-bromoacetamido)-5-(3-chlorophenyl)thiazole-4-carboxylateinhibited mtFabH with an IC50 of 0.95±0.05 µg/ml (2.43±0.13 µM) but was not active against the whole cell organism.
Conclusions/Significance
These findings clearly identify the 2-aminothiazole-4-carboxylate scaffold as a promising new template towards the discovery of a new class of anti-tubercular agents
The spirit of sport: the case for criminalisation of doping in the UK
This article examines public perceptions of doping in sport, critically evaluates the effectiveness of current anti-doping sanctions and proposes the criminalisation of doping in sport in the UK as part of a growing global movement towards such criminalisation at national level. Criminalising doping is advanced on two main grounds: as a stigmatic deterrent and as a form of retributive punishment enforced through the criminal justice system. The ‘spirit of sport’ defined by the World Anti-Doping Agency (WADA) as being based on the values of ethics, health and fair-play is identified as being undermined by the ineffectiveness of existing anti-doping policy in the current climate of doping revelations, and is assessed as relevant to public perceptions and the future of sport as a whole. The harm-reductionist approach permitting the use of certain performance enhancing drugs (PEDs) is considered as an alternative to anti-doping, taking into account athlete psychology, the problems encountered in containing doping in sport through anti-doping measures and the effect of these difficulties on the ‘spirit of sport’. This approach is dismissed in favour of criminalising doping in sport based on the offence of fraud. It will be argued that the criminalisation of doping could act as a greater deterrent than existing sanctions imposed by International Federations, and, when used in conjunction with those sanctions, will raise the overall ‘price’ of doping. The revelations of corruption within the existing system of self-governance within sport have contributed to a disbelieving public and it will be argued that the criminalisation of doping in sport could assist in satisfying the public that justice is being done and in turn achieve greater belief in the truth of athletic performances
Inspiratory muscle warm-up does not improve cycling time-trial performance
Purpose: This study examined the effects of an active cycling warm-up, with and without the addition of an inspiratory muscle warm-up (IMW), on 10-km cycling time-trial performance
Epigenetics as a mechanism driving polygenic clinical drug resistance
Aberrant methylation of CpG islands located at or near gene promoters is associated with inactivation of gene expression during tumour development. It is increasingly recognised that such epimutations may occur at a much higher frequency than gene mutation and therefore have a greater impact on selection of subpopulations of cells during tumour progression or acquisition of resistance to anticancer drugs. Although laboratory-based models of acquired resistance to anticancer agents tend to focus on specific genes or biochemical pathways, such 'one gene : one outcome' models may be an oversimplification of acquired resistance to treatment of cancer patients. Instead, clinical drug resistance may be due to changes in expression of a large number of genes that have a cumulative impact on chemosensitivity. Aberrant CpG island methylation of multiple genes occurring in a nonrandom manner during tumour development and during the acquisition of drug resistance provides a mechanism whereby expression of multiple genes could be affected simultaneously resulting in polygenic clinical drug resistance. If simultaneous epigenetic regulation of multiple genes is indeed a major driving force behind acquired resistance of patients' tumour to anticancer agents, this has important implications for biomarker studies of clinical outcome following chemotherapy and for clinical approaches designed to circumvent or modulate drug resistance
Developing a manually annotated clinical document corpus to identify phenotypic information for inflammatory bowel disease
<p>Abstract</p> <p>Background</p> <p>Natural Language Processing (NLP) systems can be used for specific Information Extraction (IE) tasks such as extracting phenotypic data from the electronic medical record (EMR). These data are useful for translational research and are often found only in free text clinical notes. A key required step for IE is the manual annotation of clinical corpora and the creation of a reference standard for (1) training and validation tasks and (2) to focus and clarify NLP system requirements. These tasks are time consuming, expensive, and require considerable effort on the part of human reviewers.</p> <p>Methods</p> <p>Using a set of clinical documents from the VA EMR for a particular use case of interest we identify specific challenges and present several opportunities for annotation tasks. We demonstrate specific methods using an open source annotation tool, a customized annotation schema, and a corpus of clinical documents for patients known to have a diagnosis of Inflammatory Bowel Disease (IBD). We report clinician annotator agreement at the document, concept, and concept attribute level. We estimate concept yield in terms of annotated concepts within specific note sections and document types.</p> <p>Results</p> <p>Annotator agreement at the document level for documents that contained concepts of interest for IBD using estimated Kappa statistic (95% CI) was very high at 0.87 (0.82, 0.93). At the concept level, F-measure ranged from 0.61 to 0.83. However, agreement varied greatly at the specific concept attribute level. For this particular use case (IBD), clinical documents producing the highest concept yield per document included GI clinic notes and primary care notes. Within the various types of notes, the highest concept yield was in sections representing patient assessment and history of presenting illness. Ancillary service documents and family history and plan note sections produced the lowest concept yield.</p> <p>Conclusion</p> <p>Challenges include defining and building appropriate annotation schemas, adequately training clinician annotators, and determining the appropriate level of information to be annotated. Opportunities include narrowing the focus of information extraction to use case specific note types and sections, especially in cases where NLP systems will be used to extract information from large repositories of electronic clinical note documents.</p
- …