332 research outputs found

    Eddy current probe design for second-layer cracks under installed fasteners

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    The United States Air Force has an operational need to reliably detect second-layer cracks around fastener holes in two-layer airframe structures with the fasteners in place. Because access to the second layer is usually not available, the inspection must be performed by placing a probe on the outer surface of the structure and detecting cracks through the first layer. Eddy current methods have been applied to this inspection problem [1–6], and have met with some success; however, much improvement is still needed to achieve the desired sensitivity to cracks and rejection of signals caused by the geometry of the structure under inspection

    Greybody factors in a rotating black-hole background-II : fermions and gauge bosons

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    We study the emission of fermion and gauge boson degrees of freedom on the brane by a rotating higher-dimensional black hole. Using matching techniques, for the near-horizon and far-field regime solutions, we solve analytically the corresponding field equations of motion. From this, we derive analytical results for the absorption probabilities and Hawking radiation emission rates, in the low-energy and low-rotation case, for both species of fields. We produce plots of these, comparing them to existing exact numerical results with very good agreement. We also study the total absorption cross-section and demonstrate that, as in the non-rotating case, it has a different behaviour for fermions and gauge bosons in the low-energy limit, while it follows a universal behaviour -- reaching a constant, spin-independent, asymptotic value -- in the high-energy regime.Comment: 22 pages, 8 figures, added reference

    Benznidazole biotransformation and multiple targets in <i>Trypanosoma</i> cruzi revealed by metabolomics

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    &lt;b&gt;Background&lt;/b&gt;&lt;p&gt;&lt;/p&gt; The first line treatment for Chagas disease, a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi, involves administration of benznidazole (Bzn). Bzn is a 2-nitroimidazole pro-drug which requires nitroreduction to become active, although its mode of action is not fully understood. In the present work we used a non-targeted MS-based metabolomics approach to study the metabolic response of T. cruzi to Bzn.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Methodology/Principal findings&lt;/b&gt;&lt;p&gt;&lt;/p&gt; Parasites treated with Bzn were minimally altered compared to untreated trypanosomes, although the redox active thiols trypanothione, homotrypanothione and cysteine were significantly diminished in abundance post-treatment. In addition, multiple Bzn-derived metabolites were detected after treatment. These metabolites included reduction products, fragments and covalent adducts of reduced Bzn linked to each of the major low molecular weight thiols: trypanothione, glutathione, γ-glutamylcysteine, glutathionylspermidine, cysteine and ovothiol A. Bzn products known to be generated in vitro by the unusual trypanosomal nitroreductase, TcNTRI, were found within the parasites, but low molecular weight adducts of glyoxal, a proposed toxic end-product of NTRI Bzn metabolism, were not detected.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusions/significance&lt;/b&gt;&lt;p&gt;&lt;/p&gt; Our data is indicative of a major role of the thiol binding capacity of Bzn reduction products in the mechanism of Bzn toxicity against T. cruzi

    Consequences of HIV for children: avoidable or inevitable?

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    The HIV/AIDS epidemic has many serious consequences for children. These consequences are, however, rarely inevitable. Families can provide a protective barrier that deflects blows, or minimises their impact and a supportive nurturing environment that can help children recover from harm. If strong enough, and with sufficient access to quality services and support from communities, families can reduce the impacts of HIV/AIDS on children to negligible levels in most areas of impact. It is apparent that the impacts felt by children are not simply unfortunate, inevitable consequences of this epidemic. A strong and supported family with good access to quality services can deflect almost all of the impact. It is as a result of an interaction of the context of poverty, which weakens families, and a failure to adequately respond, that impacts are felt by children

    Hawking emission from quantum gravity black holes

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    We address the issue of modelling quantum gravity effects in the evaporation of higher dimensional black holes in order to go beyond the usual semi-classical approximation. After reviewing the existing six families of quantum gravity corrected black hole geometries, we focus our work on non-commutative geometry inspired black holes, which encode model independent characteristics, are unaffected by the quantum back reaction and have an analytical form compact enough for numerical simulations. We consider the higher dimensional, spherically symmetric case and we proceed with a complete analysis of the brane/bulk emission for scalar fields. The key feature which makes the evaporation of non-commutative black holes so peculiar is the possibility of having a maximum temperature. Contrary to what happens with classical Schwarzschild black holes, the emission is dominated by low frequency field modes on the brane. This is a distinctive and potentially testable signature which might disclose further features about the nature of quantum gravity.Comment: 36 pages, 18 figures, v2: updated reference list, minor corrections, version matching that published on JHE

    Mapping an atlas of tissue-specific drosophila melanogaster metabolomes by high resolution mass spectrometry

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    Metabolomics can provide exciting insights into organismal function, but most work on simple models has focussed on the whole organism metabolome, so missing the contributions of individual tissues. Comprehensive metabolite profiles for ten tissues from adult Drosophila melanogaster were obtained here by two chromatographic methods, a hydrophilic interaction (HILIC) method for polar metabolites and a lipid profiling method also based on HILIC, in combination with an Orbitrap Exactive instrument. Two hundred and forty two polar metabolites were putatively identified in the various tissues, and 251 lipids were observed in positive ion mode and 61 in negative ion mode. Although many metabolites were detected in all tissues, every tissue showed characteristically abundant metabolites which could be rationalised against specific tissue functions. For example, the cuticle contained high levels of glutathione, reflecting a role in oxidative defence; the alimentary canal (like vertebrate gut) had high levels of acylcarnitines for fatty acid metabolism, and the head contained high levels of ether lipids. The male accessory gland uniquely contained decarboxylated S-adenosylmethionine. These data thus both provide valuable insights into tissue function, and a reference baseline, compatible with the FlyAtlas.org transcriptomic resource, for further metabolomic analysis of this important model organism, for example in the modelling of human inborn errors of metabolism, aging or metabolic imbalances such as diabetes

    Minimum length effects in black hole physics

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    We review the main consequences of the possible existence of a minimum measurable length, of the order of the Planck scale, on quantum effects occurring in black hole physics. In particular, we focus on the ensuing minimum mass for black holes and how modified dispersion relations affect the Hawking decay, both in four space-time dimensions and in models with extra spatial dimensions. In the latter case, we briefly discuss possible phenomenological signatures.Comment: 29 pages, 12 figures. To be published in "Quantum Aspects of Black Holes", ed. X. Calmet (Springer, 2014

    Structure-based design and synthesis of antiparasitic pyrrolopyrimidines targeting pteridine reductase 1

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    The treatment of Human African Trypanosomiasis remains a major unmet health need in sub-Saharan Africa. Approaches involving new molecular targets are important and pteridine reductase 1 (PTR1), an enzyme that reduces dihydrobiopterin in Trypanosoma spp. has been identified as a candidate target and it has been shown previously that substituted pyrrolo[2,3-d]pyrimidines are inhibitors of PTR1 from T. brucei (J. Med. Chem. 2010, 53, 221-229). In this study, 61 new pyrrolo[2,3-d]pyrimidines have been prepared, designed with input from new crystal structures of 23 of these compounds complexed with PTR1, and evaluated in screens for enzyme inhibitory activity against PTR1 and in vitro antitrypanosomal activity. 8 compounds were sufficiently active in both screens to take forward to in vivo evaluation. Thus although evidence for trypanocidal activity in a stage I disease model in mice was obtained, the compounds were too toxic to mice for further development

    Early Infant Diagnosis of HIV in Three Regions in Tanzania; Successes and Challenges.

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    By the end of 2009 an estimated 2.5 million children worldwide were living with HIV-1, mostly as a consequence of vertical transmission, and more than 90% of these children live in sub-Saharan Africa. In 2008 the World Health Organization (WHO), recommended early initiation of Highly Active Antiretroviral Therapy (HAART) to all HIV infected infants diagnosed within the first year of life, and since 2010, within the first two years of life, irrespective of CD4 count or WHO clinical stage. The study aims were to describe implementation of EID programs in three Tanzanian regions with differences in HIV prevalences and logistical set-up with regard to HIV DNA testing. Data were obtained by review of the prevention from mother to child transmission of HIV (PMTCT) registers from 2009-2011 at the Reproductive and Child Health Clinics (RCH) and from the databases from the Care and Treatment Clinics (CTC) in all the three regions; Kilimanjaro, Mbeya and Tanga. Statistical tests used were Poisson regression model and rank sum test. During the period of 2009 - 2011 a total of 4,860 exposed infants were registered from the reviewed sites, of whom 4,292 (88.3%) were screened for HIV infection. Overall proportion of tested infants in the three regions increased from 77.2% in 2009 to 97.8% in 2011. A total of 452 (10.5%) were found to be HIV infected (judged by the result of the first test). The prevalence of HIV infection among infants was higher in Mbeya when compared to Kilimanjaro region RR = 1.872 (95%CI = 1.408 - 2.543) p < 0.001. However sample turnaround time was significantly shorter in both Mbeya (2.7 weeks) and Tanga (5.0 weeks) as compared to Kilimanjaro (7.0 weeks), p=<0.001. A substantial of loss to follow-up (LTFU) was evident at all stages of EID services in the period of 2009 to 2011. Among the infants who were receiving treatment, 61% were found to be LFTU during the review period. The study showed an increase in testing of HIV exposed infants within the three years, there is large variations of HIV prevalence among the regions. Challenges like; sample turnaround time and LTFU must be overcome before this can translate into the intended goal of early initiation of lifelong lifesaving antiretroviral therapy for the infants

    Co-constructing desired activities : Small-scale activity decisions in occupational therapy

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    Social inclusion and exclusion are buzzwords in today’s political discourse. While there are many causes of social exclusion, one of the factors repeatedly shown to lead to social exclusion is mental illness, which may hinder people in developing themselves in accordance with their wishes and abilities. Participation is a key dimension of social inclusion—and one that we particularly seek to increase understanding of in this volume. We focus on participation taking place in face-to-face social encounters, seeking to get to the root of the preconditions and consequences of participation by unraveling the interactional processes that underlie what makes it possible. We presuppose that participation in any social or societal sphere presupposes social interaction, which in turn requires the capacity to coordinate with and make sense of others’ actions. Thus, drawing on joint decision-making as a specific arena of social interaction, where the participants’ collaborative management of the turn-by-turn sequential unfolding of interaction can have tangible consequences for the participants’ social and economic circumstances, we seek to increase understanding of the specific vulnerabilities that individuals with mental illness have in this context.In occupational therapy, a therapist and client engage in shared activities that they perform collaboratively during therapeutic sessions. An important part of this joint performance involves providing the client with the opportunity to make short-term decisions on the activities they wish to perform. Analyzing 15 occupational therapy encounters at psychiatric outpatient clinics, in the chapter I explore the functions of these small-scale decisions. The analysis demonstrates that therapists (1) make room for the client’s proposals by shaping the activity context and (2) make proposals themselves on the ways the performance should be accomplished. To summarize, clients are given decision-making power over the content of the activity, whereas therapists use their decision-making power to assist the client’s performance. The analysis shows how small-scale decisions can be employed to construct the occupational performance as shared endeavors and to position the clients as active subjects rather than objects of the professionals’ performance.Peer reviewe
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