173 research outputs found
Metal-insulator transition in vanadium dioxide nanobeams: probing sub-domain properties of strongly correlated materials
Many strongly correlated electronic materials, including high-temperature
superconductors, colossal magnetoresistance and metal-insulator-transition
(MIT) materials, are inhomogeneous on a microscopic scale as a result of domain
structure or compositional variations. An important potential advantage of
nanoscale samples is that they exhibit the homogeneous properties, which can
differ greatly from those of the bulk. We demonstrate this principle using
vanadium dioxide, which has domain structure associated with its dramatic MIT
at 68 degrees C. Our studies of single-domain vanadium dioxide nanobeams reveal
new aspects of this famous MIT, including supercooling of the metallic phase by
50 degrees C; an activation energy in the insulating phase consistent with the
optical gap; and a connection between the transition and the equilibrium
carrier density in the insulating phase. Our devices also provide a
nanomechanical method of determining the transition temperature, enable
measurements on individual metal-insulator interphase walls, and allow general
investigations of a phase transition in quasi-one-dimensional geometry.Comment: 9 pages, 3 figures, original submitted in June 200
Genome-wide sexually antagonistic variants reveal long-standing constraints on sexual dimorphism in fruit flies
The evolution of sexual dimorphism is constrained by a shared genome, leading to βsexual
antagonismβ, in which different alleles at given loci are favoured by selection in males and
females. Despite its wide taxonomic incidence, we know little about the identity, genomic
location, and evolutionary dynamics of antagonistic genetic variants. To address these deficits, we use sex-specific fitness data from 202 fully sequenced hemiclonal Drosophila melanogaster fly lines to perform a genome-wide association study (GWAS) of sexual
antagonism. We identify approximately 230 chromosomal clusters of candidate antagonistic
single nucleotide polymorphisms (SNPs). In contradiction to classic theory, we find no clear
evidence that the X chromosome is a hot spot for sexually antagonistic variation. Characterising antagonistic SNPs functionally, we find a large excess of missense variants but little
enrichment in terms of gene function. We also assess the evolutionary persistence of antagonistic variants by examining extant polymorphism in wild D. melanogaster populations and
closely related species. Remarkably, antagonistic variants are associated with multiple signatures of balancing selection across the D. melanogaster distribution range and in their sister species D. simulans, indicating widespread and evolutionarily persistent (about 1 million
years) genomic constraints on the evolution of sexual dimorphism. Based on our results, we
propose that antagonistic variation accumulates because of constraints on the resolution of
sexual conflict over protein coding sequences, thus contributing to the long-term maintenance of heritable fitness variation
Dynamical Mean-Field Theory
The dynamical mean-field theory (DMFT) is a widely applicable approximation
scheme for the investigation of correlated quantum many-particle systems on a
lattice, e.g., electrons in solids and cold atoms in optical lattices. In
particular, the combination of the DMFT with conventional methods for the
calculation of electronic band structures has led to a powerful numerical
approach which allows one to explore the properties of correlated materials. In
this introductory article we discuss the foundations of the DMFT, derive the
underlying self-consistency equations, and present several applications which
have provided important insights into the properties of correlated matter.Comment: Chapter in "Theoretical Methods for Strongly Correlated Systems",
edited by A. Avella and F. Mancini, Springer (2011), 31 pages, 5 figure
Rapid genotype imputation from sequence without reference panels
Inexpensive genotyping methods are essential for genetic studies requiring large sample sizes. In human studies, array-based microarrays and high-density haplotype reference panels allow efficient genotype imputation for this purpose. However, these resources are typically unavailable in non-human settings. Here we describe a method (STITCH) for imputation based only on sequencing read data, without requiring additional reference panels or array data. We demonstrate its applicability even in settings of extremely low sequencing coverage, by accurately imputing 5.7 million SNPs at a mean r(2) value of 0.98 in 2,073 outbred laboratory mice (0.15Γ sequencing coverage). In a sample of 11,670 Han Chinese (1.7Γ coverage), we achieve accuracy similar to that of alternative approaches that require a reference panel, demonstrating that our approach can work for genetically diverse populations. Our method enables straightforward progression from low-coverage sequence to imputed genotypes, overcoming barriers that at present restrict the application of genome-wide association study technology outside humans
Reassuring and managing patients with concerns about swine flu: Qualitative interviews with callers to NHS Direct
<p>Abstract</p> <p>Background</p> <p>During the early stages of the 2009 swine flu (influenza H1N1) outbreak, the large majority of patients who contacted the health services about the illness did not have it. In the UK, the NHS Direct telephone service was used by many of these patients. We used qualitative interviews to identify the main reasons why people approached NHS Direct with concerns about swine flu and to identify aspects of their contact which were reassuring, using a framework approach.</p> <p>Methods</p> <p>33 patients participated in semi-structured interviews. All patients had telephoned NHS Direct between 11 and 14 May with concerns about swine flu and had been assessed as being unlikely to have the illness.</p> <p>Results</p> <p>Reasons for seeking advice about swine flu included: the presence of unexpectedly severe flu-like symptoms; uncertainties about how one can catch swine flu; concern about giving it to others; pressure from friends or employers; and seeking 'peace of mind.' Most participants found speaking to NHS Direct reassuring or useful. Helpful aspects included: having swine flu ruled out; receiving an alternative explanation for symptoms; clarification on how swine flu is transmitted; and the perceived credibility of NHS Direct. No-one reported anything that had increased their anxiety and only one participant subsequently sought additional advice about swine flu from elsewhere.</p> <p>Conclusions</p> <p>Future major incidents involving other forms of chemical, biological or radiological hazards may also cause large numbers of unexposed people to seek health advice. Our data suggest that providing telephone triage and information is helpful in such instances, particularly where advice can be given via a trusted, pre-existing service.</p
Differential branching fraction and angular analysis of decays
The differential branching fraction of the rare decay is measured as a function of , the
square of the dimuon invariant mass. The analysis is performed using
proton-proton collision data, corresponding to an integrated luminosity of 3.0
\mbox{ fb}^{-1}, collected by the LHCb experiment. Evidence of signal is
observed in the region below the square of the mass. Integrating
over 15 < q^{2} < 20 \mbox{ GeV}^2/c^4 the branching fraction is measured as
d\mathcal{B}(\Lambda^{0}_{b} \rightarrow \Lambda \mu^+\mu^-)/dq^2 = (1.18 ^{+
0.09} _{-0.08} \pm 0.03 \pm 0.27) \times 10^{-7} ( \mbox{GeV}^{2}/c^{4})^{-1},
where the uncertainties are statistical, systematic and due to the
normalisation mode, , respectively.
In the intervals where the signal is observed, angular distributions are
studied and the forward-backward asymmetries in the dimuon ()
and hadron () systems are measured for the first time. In the
range 15 < q^2 < 20 \mbox{ GeV}^2/c^4 they are found to be A^{l}_{\rm FB} =
-0.05 \pm 0.09 \mbox{ (stat)} \pm 0.03 \mbox{ (syst)} and A^{h}_{\rm FB} =
-0.29 \pm 0.07 \mbox{ (stat)} \pm 0.03 \mbox{ (syst)}.Comment: 27 pages, 10 figures, Erratum adde
Deficiency of the Metalloproteinase-Disintegrin ADAM8 Is Associated with Thymic Hyper-Cellularity
Thymopoiesis requires thymocyte-stroma interactions and proteases that promote cell migration by degrading extracellular matrix and releasing essential cytokines and chemokines. A role for several members of the A Disintegrin and Metalloprotease (ADAM) family in T cell development has been reported in the past
Schistosoma haematobium Treatment in 1β5 Year Old Children: Safety and Efficacy of the Antihelminthic Drug Praziquantel
Urogenital schistosomiasis is an important, but neglected, infectious disease affecting over 100 million people, mainly in Africa. Children carry the heaviest burden of infection with children as young as 1 year old showing signs of infection. Children aged 5 years and below are currently excluded from schistosome control programmes for several reasons, including operational difficulties associated with accessing preschool children, misconceptions about their level of exposure to infective water and lack of safety data on the drug of choice for schistosome control, praziquantel, in children aged 5 years and below. This study was one of a small number of studies recently funded by the World Health Organization to investigate the need for praziquantel treatment in preschool children (aged 1β5 years) and to subsequently assess the safety and efficacy of the drug praziquantel in this age group. This study confirmed that preschool children carry significant levels of schistosome infection, exceeding those carried by their parents/guardians, highlighting the urgent need for their immediate inclusion in schistosome control programmes. The study also showed that praziquantel treatment is as safe and efficacious in children aged 1β5 years as it is in older children aged 6β10 years who are currently the target for mass drug administration
A domain-based approach to predict protein-protein interactions
<p>Abstract</p> <p>Background</p> <p>Knowing which proteins exist in a certain organism or cell type and how these proteins interact with each other are necessary for the understanding of biological processes at the whole cell level. The determination of the protein-protein interaction (PPI) networks has been the subject of extensive research. Despite the development of reasonably successful methods, serious technical difficulties still exist. In this paper we present DomainGA, a quantitative computational approach that uses the information about the domain-domain interactions to predict the interactions between proteins.</p> <p>Results</p> <p>DomainGA is a multi-parameter optimization method in which the available PPI information is used to derive a quantitative scoring scheme for the domain-domain pairs. Obtained domain interaction scores are then used to predict whether a pair of proteins interacts. Using the yeast PPI data and a series of tests, we show the robustness and insensitivity of the DomainGA method to the selection of the parameter sets, score ranges, and detection rules. Our DomainGA method achieves very high explanation ratios for the positive and negative PPIs in yeast. Based on our cross-verification tests on human PPIs, comparison of the optimized scores with the structurally observed domain interactions obtained from the iPFAM database, and sensitivity and specificity analysis; we conclude that our DomainGA method shows great promise to be applicable across multiple organisms.</p> <p>Conclusion</p> <p>We envision the DomainGA as a first step of a multiple tier approach to constructing organism specific PPIs. As it is based on fundamental structural information, the DomainGA approach can be used to create potential PPIs and the accuracy of the constructed interaction template can be further improved using complementary methods. Explanation ratios obtained in the reported test case studies clearly show that the false prediction rates of the template networks constructed using the DomainGA scores are reasonably low, and the erroneous predictions can be filtered further using supplementary approaches such as those based on literature search or other prediction methods.</p
Targeting Cattle-Borne Zoonoses and Cattle Pathogens Using a Novel Trypanosomatid-Based Delivery System
Trypanosomatid parasites are notorious for the human diseases they cause throughout Africa and South America. However, non-pathogenic trypanosomatids are also found worldwide, infecting a wide range of hosts. One example is Trypanosoma (Megatrypanum) theileri, a ubiquitous protozoan commensal of bovids, which is distributed globally. Exploiting knowledge of pathogenic trypanosomatids, we have developed Trypanosoma theileri as a novel vehicle to deliver vaccine antigens and other proteins to cattle. Conditions for the growth and transfection of T. theileri have been optimised and expressed heterologous proteins targeted for secretion or specific localisation at the cell interior or surface using trafficking signals from Trypanosoma brucei. In cattle, the engineered vehicle could establish in the context of a pre-existing natural T. theileri population, was maintained long-term and generated specific immune responses to an expressed Babesia antigen at protective levels. Building on several decades of basic research into trypanosomatid pathogens, Trypanosoma theileri offers significant potential to target multiple infections, including major cattle-borne zoonoses such as Escherichia coli, Salmonella spp., Brucella abortus and Mycobacterium spp. It also has the potential to deliver therapeutics to cattle, including the lytic factor that protects humans from cattle trypanosomiasis. This could alleviate poverty by protecting indigenous African cattle from African trypanosomiasis
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