A titanium-nitride near-infrared kinetic inductance photon-counting detector and its anomalous electrodynamics

We demonstrate single-photon counting at 1550 nm with titanium-nitride (TiN) microwave kinetic inductance detectors. Energy resolution of 0.4 eV and arrival-time resolution of 1.2 microseconds are achieved. 0-, 1-, 2-photon events are resolved and shown to follow Poisson statistics. We find that the temperature-dependent frequency shift deviates from the Mattis-Bardeen theory, and the dissipation response shows a shorter decay time than the frequency response at low temperatures. We suggest that the observed anomalous electrodynamics may be related to quasiparticle traps or subgap states in the disordered TiN films. Finally, the electron density-of-states is derived from the pulse response.Comment: 4 pages, 3 figure

Monopoles and Knots in Skyrme Theory

We show that the Skyrme theory actually is a theory of monopoles which allows a new type of solitons, the topological knots made of monopole-anti-monopole pair,which is different from the well-known skyrmions. Furthermore, we derive a generalized Skyrme action from the Yang-Mills action of QCD, which we propose to be an effective action of QCD in the infra-red limit. We discuss the physical implications of our results.Comment: 4 pages. Phys. Rev. Lett. in pres

The Self Model and the Conception of Biological Identity in Immunology

The self/non-self model, first proposed by F.M. Burnet, has dominated immunology for sixty years now. According to this model, any foreign element will trigger an immune reaction in an organism, whereas endogenous elements will not, in normal circumstances, induce an immune reaction. In this paper we show that the self/non-self model is no longer an appropriate explanation of experimental data in immunology, and that this inadequacy may be rooted in an excessively strong metaphysical conception of biological identity. We suggest that another hypothesis, one based on the notion of continuity, gives a better account of immune phenomena. Finally, we underscore the mapping between this metaphysical deflation from self to continuity in immunology and the philosophical debate between substantialism and empiricism about identity

Accounting for employment outcomes following traumatic brain injury (TBI): The implications for delivering TBI vocational rehabilitation in the UK

This thesis arises out of personal experience of the employment problems faced by people sustaining traumatic brain injury (TBI). Through tracking the post-injury experience of 54 subjects it aims to test the opinion that, generally, there is a lack of expert support to facilitate a return to work and, for young people, inadequate mechanisms to facilitate a transition from education into employment. In particular, it is maintained that generic vocational rehabilitation (VR) services provided by Jobcentre Plus fail to meet the needs of many TBI customers ( to use their terminology). In the circumstances it is contested that a return to work following TBI may follow a random pattern, but that an appropriate programme of VR, objectively identified within the thesis and based upon best practice and research based evidence, should improve resettlement rates. Following a review of research methodologies commonly found in employment and disability studies the thesis relies upon a combined methodological strategy to test the above opinions. The literature review, and the experience of the study sample, are used to identify a) significant demographic and clinical variables to be taken into account when planning vocational intervention, b) difficulties in accessing appropriate VR programmes. A non-experimental survey research design relied on a fixed format questionnaire to collect study sample data, evaluated through the use of description and association statistics. Three case studies are further analysed through a realist approach identifying the circumstances in which measures taken to resume employment contributed to the final outcomes. The thesis identifies an inaccurate recording of the brain-injured population within the DWP and a significant job retention problem amongst the study sample. It establishes why generic vocational rehabilitation services are failing this population and why many potentially employable people find themselves receiving long-term incapacity benefits. The conclusion presents a theoretical model VR programme, deliverable within the context of current developments for joint NHS/Jobcentre Plus condition management (VR) programmes. It argues the case for TBI VR programmes in the UK moving away from a focus on pre-placement treatment and job-search activity towards one incorporating lengthy occupational trials and on-site support for both the employee and employer. It establishes the need for both ’joined-up’ services, from hospital to employment, and trained job coaches. Finally there are recommendations for enhancing future research in the employment and disability sector

Accidentally on purpose: denying any responsibility for the accidental archive

NWO342-69-001Medieval and Early Modern Studie

Factors influencing success of clinical genome sequencing across a broad spectrum of disorders

To assess factors influencing the success of whole-genome sequencing for mainstream clinical diagnosis, we sequenced 217 individuals from 156 independent cases or families across a broad spectrum of disorders in whom previous screening had identified no pathogenic variants. We quantified the number of candidate variants identified using different strategies for variant calling, filtering, annotation and prioritization. We found that jointly calling variants across samples, filtering against both local and external databases, deploying multiple annotation tools and using familial transmission above biological plausibility contributed to accuracy. Overall, we identified disease-causing variants in 21% of cases, with the proportion increasing to 34% (23/68) for mendelian disorders and 57% (8/14) in family trios. We also discovered 32 potentially clinically actionable variants in 18 genes unrelated to the referral disorder, although only 4 were ultimately considered reportable. Our results demonstrate the value of genome sequencing for routine clinical diagnosis but also highlight many outstanding challenges

The anti-bacterial iron-restriction defence mechanisms of egg white; the potential role of three lipocalin-like proteins in resistance against Salmonella

Salmonella enterica serovar Enteritidis (SE) is the most frequently-detected Salmonella in foodborne outbreaks in the European Union. Among such outbreaks, egg and egg products were identified as the most common vehicles of infection. Possibly, the major antibacterial property of egg white is iron restriction, which results from the presence of the iron-binding protein, ovotransferrin. To circumvent iron restriction, SE synthesise catecholate siderophores (i.e. enterobactin and salmochelin) that can chelate iron from host iron-binding proteins. Here, we highlight the role of lipocalin-like proteins found in egg white that could enhance egg-white iron restriction through sequestration of certain siderophores, including enterobactin. Indeed, it is now apparent that the egg-white lipocalin, Ex-FABP, can inhibit bacterial growth via its siderophore-binding capacity in vitro. However, it remains unclear whether ex-FABP performs such a function in egg white or during bird infection. Regarding the two other lipocalins of egg white (Cal-γ and α-1-glycoprotein), there is currently no evidence to indicate that they sequester siderophores

Fate of Allochthonous Dissolved Organic Carbon in Lakes: A Quantitative Approach

Inputs of dissolved organic carbon (DOC) to lakes derived from the surrounding landscape can be stored, mineralized or passed to downstream ecosystems. The balance among these OC fates depends on a suite of physical, chemical, and biological processes within the lake, as well as the degree of recalcintrance of the allochthonous DOC load. The relative importance of these processes has not been well quantified due to the complex nature of lakes, as well as challenges in scaling DOC degradation experiments under controlled conditions to the whole lake scale. We used a coupled hydrodynamic-water quality model to simulate broad ranges in lake area and DOC, two characteristics important to processing allochthonous carbon through their influences on lake temperature, mixing depth and hydrology. We calibrated the model to four lakes from the North Temperate Lakes Long Term Ecological Research site, and simulated an additional 12 ‘hypothetical’ lakes to fill the gradients in lake size and DOC concentration. For each lake, we tested several mineralization rates (range: 0.001 d−1 to 0.010 d−1) representative of the range found in the literature. We found that mineralization rates at the ecosystem scale were roughly half the values from laboratory experiments, due to relatively cool water temperatures and other lake-specific factors that influence water temperature and hydrologic residence time. Results from simulations indicated that the fate of allochthonous DOC was controlled primarily by the mineralization rate and the hydrologic residence time. Lakes with residence times <1 year exported approximately 60% of the DOC, whereas lakes with residence times >6 years mineralized approximately 60% of the DOC. DOC fate in lakes can be determined with a few relatively easily measured factors, such as lake morphometry, residence time, and temperature, assuming we know the recalcitrance of the DOC

Oestrogen inactivation in the colon: analysis of the expression and regulation of 17 β -hydroxysteroidehydrogenase isozymes in normal colon and colonic cancer

Epidemiological data suggest that oestrogen contributes to the aetiology of colonic cancer. Furthermore, recent studies have suggested that local hormone metabolism may play a key role in determining colonic responsiveness to oestrogen. To further clarify this mechanism we have characterized the expression and regulation of isozymes of 17β-hydroxysteroid dehydrogenase (17β-HSD) in vitro and in situ. Immunohistochemistry was used to confirm expression of the type 2 and 4 isozymes of 17β-HSD (17β-HSD2 and 4) in normal colonic epithelial cells. Parallel studies suggested that both isozymes were abnormally expressed in colonic tumours and this was confirmed by Western blot analyses. Abnormal expression of 17β-HSD2 and 4 proteins was also observed in Caco-2, HT-29 and SW620 colonic cancer cell lines, although the overall pattern of oestrogen metabolism in these cells was similar to that seen in primary colonic mucosal tissue. The predominant activity (conversion of oestradiol to oestrone) was highest in Caco-2>SW620>HT-29, which correlated inversely with the rate of proliferation of the cell lines. Regulatory studies using SW620 cells indicated that the most potent stimulator of oestradiol to oestrone inactivation was the antiproliferative agent 1,25-dihydroxyvitamin D 3(1,25D 3), whilst oestradiol itself inhibited 17β-HSD activity. Both oestradiol and 1,25D 3 decreased mRNA for 17β-HSD2 and 4. Data indicate that the high capacity for inactivation of oestrogens in the colon is associated with the presence of 17β-HSD2 and 4 in epithelial cells. Abnormal expression of both isozymes in colonic cancer cells and the stimulation of oestrogen inactivation by the antiproliferative agent 1,25D 3 highlights a possible role for 17β-HSD isozymes as modulators of colonic cell proliferation. © 2000 Cancer Research Campaig

Identification of a BRCA2-Specific modifier locus at 6p24 related to breast cancer risk

Common genetic variants contribute to the observed variation in breast cancer risk for BRCA2 mutation carriers; those known to date have all been found through population-based genome-wide association studies (GWAS). To comprehensively identify breast cancer risk modifying loci for BRCA2 mutation carriers, we conducted a deep replication of an ongoing GWAS discovery study. Using the ranked P-values of the breast cancer associations with the imputed genotype of 1.4 M SNPs, 19,029 SNPs were selected and designed for inclusion on a custom Illumina array that included a total of 211,155 SNPs as part of a multi-consortial project. DNA samples from 3,881 breast cancer affected and 4,330 unaffected BRCA2 mutation carriers from 47 studies belonging to the Consortium of Investigators of Modifiers of BRCA1/2 were genotyped and available for analysis. We replicated previously reported breast cancer susceptibility alleles in these BRCA2 mutation carriers and for several regions (including FGFR2, MAP3K1, CDKN2A/B, and PTHLH) identified SNPs that have stronger evidence of association than those previously published. We also identified a novel susceptibility allele at 6p24 that was inversely associated with risk in BRCA2 mutation carriers (rs9348512; per allele HR = 0.85, 95% CI 0.80-0.90, P = 3.9×10−8). This SNP was not associated with breast cancer risk either in the general population or in BRCA1 mutation carriers. The locus lies within a region containing TFAP2A, which encodes a transcriptional activation protein that interacts with several tumor suppressor genes. This report identifies the first breast cancer risk locus specific to a BRCA2 mutation background. This comprehensive update of novel and previously reported breast cancer susceptibility loci contributes to the establishment of a panel of SNPs that modify breast cancer risk in BRCA2 mutation carriers. This panel may have clinical utility for women with BRCA2 mutations weighing options for medical prevention of breast cancer