195 research outputs found

    Membrane Protein Function

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    Supersymmetric 3-branes on smooth ALE manifolds with flux

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    We construct a new family of classical BPS solutions of type IIB supergravity describing 3-branes transverse to a 6-dimensional space with topology R^2*ALE. They are characterized by a non-trivial flux of the supergravity 2-forms through the homology 2-cycles of a generic smooth ALE manifold. Our solutions have two Killing spinors and thus preserve N=2 supersymmetry. They are expressed in terms of a quasi harmonic function H (the ``warp factor''), whose properties we study in the case of the simplest ALE, namely the Eguchi-Hanson manifold. The equation for H is identified as an instance of the confluent Heun equation. We write explicit power series solutions and solve the recurrence relation for the coefficients, discussing also the relevant asymptotic expansions. While, as in all such N=2 solutions, supergravity breaks down near the brane, the smoothing out of the vacuum geometry has the effect that the warp factor is regular in a region near the cycle. We interpret the behavior of the warp factor as describing a three-brane charge ``smeared'' over the cycle and consider the asymptotic form of the geometry in that region, showing that conformal invariance is broken even when the complex type IIB 3-form field strength is assumed to vanish. We conclude with a discussion of the basic features of the gauge theory dual.Comment: latex, 36 pages (26 + appendix). Some statements on the gauge dual made more precise. Final version to appear on NP

    Locomotor adaptability in persons with unilateral transtibial amputation

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    Background Locomotor adaptation enables walkers to modify strategies when faced with challenging walking conditions. While a variety of neurological injuries can impair locomotor adaptability, the effect of a lower extremity amputation on adaptability is poorly understood. Objective Determine if locomotor adaptability is impaired in persons with unilateral transtibial amputation (TTA). Methods The locomotor adaptability of 10 persons with a TTA and 8 persons without an amputation was tested while walking on a split-belt treadmill with the parallel belts running at the same (tied) or different (split) speeds. In the split condition, participants walked for 15 minutes with the respective belts moving at 0.5 m/s and 1.5 m/s. Temporal spatial symmetry measures were used to evaluate reactive accommodations to the perturbation, and the adaptive/de-adaptive response. Results Persons with TTA and the reference group of persons without amputation both demonstrated highly symmetric walking at baseline. During the split adaptation and tied post-adaptation walking both groups responded with the expected reactive accommodations. Likewise, adaptive and de-adaptive responses were observed. The magnitude and rate of change in the adaptive and de-adaptive responses were similar for persons with TTA and those without an amputation. Furthermore, adaptability was no different based on belt assignment for the prosthetic limb during split adaptation walking. Conclusions Reactive changes and locomotor adaptation in response to a challenging and novel walking condition were similar in persons with TTA to those without an amputation. Results suggest persons with TTA have the capacity to modify locomotor strategies to meet the demands of most walking conditions despite challenges imposed by an amputation and use of a prosthetic limb

    Classical integrability and quantum aspects of the AdS(3) x S(3) x S(3) x S(1) superstring

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    In this paper we continue the investigation of aspects of integrability of the type IIA AdS(3) x S(3) x S(3) x S(1) and AdS(3) x S(3) x T(4) superstrings. By constructing a one parameter family of flat connections we prove that the Green-Schwarz string is classically integrable, at least to quadratic order in fermions, without fixing the kappa-symmetry. We then compare the quantum dispersion relation, fixed by integrability up to an unknown interpolating function h(lambda), to explicit one-loop calculations on the string worldsheet. For AdS(3) x S(3) x S(3) x S(1) the spectrum contains heavy, as well as light and massless modes, and we find that the one-loop contribution differs depending on how we treat these modes showing that similar regularization ambiguities as appeared in AdS(4)/CFT(3) occur also here.Comment: 29 pages; v2: updated references and acknowledgmen

    Benefits and problems of electronic information exchange as perceived by health care professionals: an interview study

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    <p>Abstract</p> <p>Background</p> <p>Various countries are currently implementing a national electronic patient record (n-EPR). Despite the assumed positive effects of n-EPRs, their overall adoption remains low and meets resistance from health care providers. This study aims to increase our understanding of health care providers' attitude towards the n-EPR, by investigating their perceptions of the benefits and problems of electronic information exchange in health care and the n-EPR in particular.</p> <p>Methods</p> <p>The study was conducted in three Dutch health care settings: acute care, diabetes care, and ambulatory mental health care. Two health care organisations were included per setting. Between January and June 2010, interviews were conducted with 17 stakeholders working in these organisations. Relevant themes were deduced by means of thematic qualitative analysis.</p> <p>Results</p> <p>Health care providers perceived electronic information exchange to promote the efficiency and quality of care. The problems they perceived in electronic information exchange mainly concerned the confidentiality and safety of information exchange and the reliability and quality of patient data. Many problems perceived by health care providers did not specifically apply to the n-EPR, but to electronic information exchange in general.</p> <p>Conclusions</p> <p>The implementation of the Dutch n-EPR has mainly followed a top-down approach, thereby neglecting the fact that the perceptions and preferences of its users (health care providers) need to be addressed in order to achieve successful implementation. The results of this study provide valuable suggestions about how to promote health care providers' willingness to adopt electronic information exchange, which can be useful for other countries currently implementing an n-EPR. Apart from providing information about the benefits and usefulness of electronic information exchange, efforts should be focused on minimising the problems as perceived by health care providers. The safety and confidentiality of electronic information exchange can be improved by developing tools to evaluate the legitimacy of access to electronic records, by increasing health care providers' awareness of the need to be careful when using patient data, and by measures to limit access to sensitive patient data. Improving health care providers' recording behaviour is important to improve the reliability and quality of electronically exchanged patient data.</p

    Trastuzumab Mediated T-Cell Response against HER-2/Neu Overexpressing Esophageal Adenocarcinoma Depends on Intact Antigen Processing Machinery

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    BACKGROUND: Esophageal adenocarcinoma (EAC) is a highly aggressive disease with poor prognosis, which frequently exhibits HER-2 gene amplification. Trastuzumab, the humanized antibody against HER-2, has potent growth inhibitory effects on HER-2 overexpressing cancers. One effect of trastuzumab is that it causes HER-2 receptor internalization and degradation, enhancing presentation of HER-2 epitopes on MHC-Class I molecules. This enhances the ability of HER-2 specific cytotoxic T lymphocytes (CTLs) to recognize and kill cancer cells. Novel strategies targeting the HER-2 receptor either directly by trastuzumab and/or indirectly by inducing a CTL response against HER-2 epitopes with, for instance, DC immunotherapy and consequently combining these strategies might prove to be very effective. METHODOLOGY/PRINCIPAL FINDINGS: In this study we report that trastuzumab has potent growth inhibitory effects on two HER-2 overexpressing EAC cell lines OE33 and OE19. However, we found that trastuzumab and HER-2 specific CTLs act synergistically in inducing tumor lysis in OE33 but not in OE19. We discovered that in OE19 this deficient response is due to a down-regulation of the Transporter Associated with Antigen Processing-2 (TAP-2). TAP-2 is an important member of the Antigen Processing Machinery (APM), and is one of the essential elements for loading antigens on MHC class I molecules. Importantly, we demonstrated that by inducing re-expression of TAP-2 in OE19 with INF-γ treatment or by incubating the cells with INF-γ producing CTLs, the specific anti HER-2 CTL tumor lysis response and synergistic effect with trastuzumab can be restored. CONCLUSION: An inefficient response of HER-2 overexpressing EAC to trastuzumab and/or DC immunotherapy can be due to a down-regulated TAP-2 expression and thus a deficient APM. Future studies combining trastuzumab with IFN-γ and/or immune-therapies inducing potent anti HER-2 CTL responses could lead to an effective combinatorial strategy for successful treatment of HER-2 overexpressing but APM defective cancer

    Similar TKA designs with differences in clinical outcome: A randomized, controlled trial of 77 knees with a mean follow-up of 6 years

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    Contains fulltext : 96347.pdf (publisher's version ) (Open Access)Background and purpose To try to improve the outcome of our TKAs, we started to use the CKS prosthesis. However, in a retrospective analysis this design tended to give worse results. We therefore conducted a randomized, controlled trial comparing this CKS prosthesis and our standard PFC prosthesis. Because many randomized studies between different TKA concepts generally fail to show superiority of a particular design, we hypothesized that these seemingly similar designs would not lead to any difference in clinical outcome. Patients and methods 82 patients (90 knees) were randomly allocated to one or other prosthesis, and 39 CKS prostheses and 38 PFC prostheses could be followed for mean 5.6 years. No patients were lost to follow-up. At each follow-up, patients were evaluated clinically and radiographically, and the KSS, WOMAC, VAS patient satisfaction scores and VAS for pain were recorded. Results With total Knee Society score (KSS) as primary endpoint, there was a difference in favor of the PFC group at final follow-up (p = 0.04). Whereas there was one revision in the PFC group, there were 6 revisions in the CKS group (p = 0.1). The survival analysis with any reoperation as endpoint showed better survival in the PFC group (97% (95% CI: 92-100) for the PFC group vs. 79% (95% CI: 66-92) for the CKS group) (p = 0.02). Interpretation Our hypothesis that there would be no difference in clinical outcome was rejected in this study. The PFC system showed excellent results that were comparable to those in previous reports. The CKS design had differences that had considerable negative consequences clinically. The relatively poor results have discouraged us from using this design
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