360 research outputs found

    Solving multi-scale low frequency electromagnetic problems

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    In this paper, we will discuss two methods to tackle the low-frequency, multi-scale electromagnetics problem. First we will discuss the augmented electric field integral equation (AEFIE), and then, we will discuss the equivalence principle algorithm (EPA). The AEFIE allows the solution of such problems without the need to perform a loop search of a complex structure. The EPA allows the separation of circuit physics from wave physics in a multiscale problem. Hybridization of these two methods will be discussed.published_or_final_versionThe 4th European Conference on Antennas and Propagation (EuCAP) 2010, Barcelona, Spain, 12-16 April 2010. In Proceedings of the 4th EuCAP, 2010, p. 1-

    Review of multi-scale electromagnetic modeling

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    This paper reviews various methods to solve multiscale problems ranging from low-frequency methods to very high-frequency methods. ©2010 IEEE.published_or_final_versionThe 2010 International Conference on Electromagnetics in Advanced Applications (ICEAA), Sydney, N.S.W., 20-24 September 2010. In Proceedings of ICEAA'10, 2010, p. 641-64

    Challenges and Opportunities: What Can We Learn from Patients Living with Chronic Musculoskeletal Conditions, Health Professionals and Carers about the Concept of Health Literacy Using Qualitative Methods of Inquiry?

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    The field of health literacy continues to evolve and concern public health researchers and yet remains a largely overlooked concept elsewhere in the healthcare system. We conducted focus group discussions in England UK, about the concept of health literacy with older patients with chronic musculoskeletal conditions (mean age = 73.4 years), carers and health professionals. Our research posed methodological, intellectual and practical challenges. Gaps in conceptualisation and expectations were revealed, reiterating deficiencies in predominant models for understanding health literacy and methodological shortcomings of using focus groups in qualitative research for this topic. Building on this unique insight into what the concept of health literacy meant to participants, we present analysis of our findings on factors perceived to foster and inhibit health literacy and on the issue of responsibility in health literacy. Patients saw health literacy as a result of an inconsistent interactive process and the implications as wide ranging; healthcare professionals had more heterogeneous views. All focus group discussants agreed that health literacy most benefited from good inter-personal communication and partnership. By proposing a needs-based approach to health literacy we offer an alternative way of conceptualising health literacy to help improve the health of older people with chronic conditions

    The E3 ubiquitin ligase WWP2 regulates pro-fibrogenic monocyte infiltration and activity in heart fibrosis

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    Non-ischemic cardiomyopathy (NICM) can cause left ventricular dysfunction through interstitial fibrosis, which corresponds to the failure of cardiac tissue remodeling. Recent evidence implicates monocytes/macrophages in the etiopathology of cardiac fibrosis, but giving their heterogeneity and the antagonizing roles of macrophage subtypes in fibrosis, targeting these cells has been challenging. Here we focus on WWP2, an E3 ubiquitin ligase that acts as a positive genetic regulator of human and murine cardiac fibrosis, and show that myeloid specific deletion of WWP2 reduces cardiac fibrosis in hypertension-induced NICM. By using single cell RNA sequencing analysis of immune cells in the same model, we establish the functional heterogeneity of macrophages and define an early pro-fibrogenic phase of NICM that is driven by Ccl5-expressing Ly6chigh monocytes. Among cardiac macrophage subtypes, WWP2 dysfunction primarily affects Ly6chigh monocytes via modulating Ccl5, and consequentially macrophage infiltration and activation, which contributes to reduced myofibroblast trans-differentiation. WWP2 interacts with transcription factor IRF7, promoting its non-degradative mono-ubiquitination, nuclear translocation and transcriptional activity, leading to upregulation of Ccl5 at transcriptional level. We identify a pro-fibrogenic macrophage subtype in non-ischemic cardiomyopathy, and demonstrate that WWP2 is a key regulator of IRF7-mediated Ccl5/Ly6chigh monocyte axis in heart fibrosis

    Appendix perforation in appendix duplication in a man: a case report

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    <p>Abstract</p> <p>Introduction</p> <p>Although appendix duplication is diagnosed as a rare congenital anomaly of the alimentary tract in childhood, a few adult cases have also been reported. Here we report a case of appendix duplication with perforated appendicitis co-existing with acute appendicitis in an adult patient.</p> <p>Case presentation</p> <p>A 33-year-old Caucasian man was admitted to our Emergency Department with right-sided lower-quadrant pain that we explored for presumed complicated appendicitis. On exploration, a perforated inflamed appendix was found coexisting with a second inflamed appendix which was subserosal and retrocecal. Appendectomies were performed, and the pathological examination confirmed the signs of acute inflammation in both appendixes.</p> <p>Conclusion</p> <p>Surgeons in emergency services should be aware of anatomical anomalies such as duplication and malposition of the appendix, even in patients with a history of previous appendectomy, because misdiagnosis of appendix duplication may lead to a poor clinical outcome and medicolegal issues.</p

    Validation of Self-Reported Health Literacy Questions Among Diverse English and Spanish-Speaking Populations

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    BackgroundLimited health literacy (HL) contributes to poor health outcomes and disparities, and direct measurement is often time-intensive. Self-reported HL questions have not been validated among Spanish-speaking and diverse English-speaking populations.ObjectiveTo evaluate three self-reported questions: 1 "How confident are you filling out medical forms?"; 2 "How often do you have problems learning about your medical condition because of difficulty understanding written information?"; and 3 "How often do you have someone help you read hospital materials?" Answers were based on a 5-point Likert scale.DesignThis was a validation study nested within a trial of diabetes self-management support in the San Francisco Department of Public Health.ParticipantsEnglish and Spanish-speaking adults with type 2 diabetes receiving primary care.MethodsUsing the Test of Functional Health Literacy in Adults (s-TOFHLA) in English and Spanish as the reference, we classified HL as inadequate, marginal, or adequate. We calculated the C-index and test characteristics of the three questions and summative scale compared to the s-TOFHLA and assessed variations in performance by language, race/ethnicity, age, and education.Key resultsOf 296 participants, 48% were Spanish-speaking; 9% were White, non-Hispanic; 47% had inadequate HL and 12% had marginal HL. Overall, 57% reported being confident with forms "somewhat" or less. The "confident with forms" question performed best for detecting inadequate (C-index = 0.82, (0.77-0.87)) and inadequate plus marginal HL (C index = 0.81, (0.76-0.86); p&lt;0.01 for differences from other questions), and performed comparably to the summative scale. The "confident with forms" question and scale also performed best across language, race/ethnicity, educational attainment, and age.ConclusionsA single self-reported HL question about confidence with forms and a summative scale of three questions discriminated between Spanish and English speakers with adequate HL and those with inadequate and/or inadequate plus marginal HL. The "confident with forms" question or the summative scale may be useful for estimating HL in clinical research involving Spanish-speaking and English-speaking, chronically-ill, diverse populations

    Transmutations and spectral parameter power series in eigenvalue problems

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    We give an overview of recent developments in Sturm-Liouville theory concerning operators of transmutation (transformation) and spectral parameter power series (SPPS). The possibility to write down the dispersion (characteristic) equations corresponding to a variety of spectral problems related to Sturm-Liouville equations in an analytic form is an attractive feature of the SPPS method. It is based on a computation of certain systems of recursive integrals. Considered as families of functions these systems are complete in the L2L_{2}-space and result to be the images of the nonnegative integer powers of the independent variable under the action of a corresponding transmutation operator. This recently revealed property of the Delsarte transmutations opens the way to apply the transmutation operator even when its integral kernel is unknown and gives the possibility to obtain further interesting properties concerning the Darboux transformed Schr\"{o}dinger operators. We introduce the systems of recursive integrals and the SPPS approach, explain some of its applications to spectral problems with numerical illustrations, give the definition and basic properties of transmutation operators, introduce a parametrized family of transmutation operators, study their mapping properties and construct the transmutation operators for Darboux transformed Schr\"{o}dinger operators.Comment: 30 pages, 4 figures. arXiv admin note: text overlap with arXiv:1111.444

    A Functional Taxonomy of Tumor Suppression in Oncogenic KRAS-Driven Lung Cancer

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    Cancer genotyping has identified a large number of putative tumor suppressor genes. Carcinogenesis is a multistep process, but the importance and specific roles of many of these genes during tumor initiation, growth, and progression remain unknown. Here we use a multiplexed mouse model of oncogenic KRAS–driven lung cancer to quantify the impact of 48 known and putative tumor suppressor genes on diverse aspects of carcinogenesis at an unprecedented scale and resolution. We uncover many previously understudied functional tumor suppressors that constrain cancer in vivo. Inactivation of some genes substantially increased growth, whereas the inactivation of others increases tumor initiation and/or the emergence of exceptionally large tumors. These functional in vivo analyses revealed an unexpectedly complex landscape of tumor suppression that has implications for understanding cancer evolution, interpreting clinical cancer genome sequencing data, and directing approaches to limit tumor initiation and progression. SIGNIFICANCE: Our high-throughput and high-resolution analysis of tumor suppression uncovered novel genetic determinants of oncogenic KRAS–driven lung cancer initiation, overall growth, and exceptional growth. This taxonomy is consistent with changing constraints during the life history of cancer and highlights the value of quantitative in vivo genetic analyses in autochthonous cancer models

    Licensing Virus-Specific T Cells to Secrete the Neutrophil Attracting Chemokine CXCL-8 during Hepatitis B Virus Infection

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    T cell functional plasticity helps tailor antiviral immunity during different phases of infections. We tested whether, during different phases of HBV infection, virus-specific T cells can acquire specific proinflammatory functions that could drive granulocyte/mononuclear cell liver infiltration. Multifunctional analysis of HBV-specific T cells during acute and chronic HBV infection revealed that HBV-specific T cells had the capacity to produce the neutrophil chemokine CXCL-8 but not IL-17. CXCL-8 producing T cells were detectable in the liver of chronic HBV patients with active hepatitis; while in acute HBV patients CXCL-8 production by T cells was temporally limited to the acute phase of disease, concomitant with the peak of liver inflammation. Characterization of the conditions necessary for the development of CXCL-8 producing T cells showed a requirement for IL-7 and IL-15 during T cell expansion. These data show that functional plasticity of virus-specific T cells spontaneously occurs during HBV infection and that an environment rich IL-7 and IL-15 can license T cells with the ability to produce CXCL-8 and potentially influence liver pathology

    LIM and SH3 Protein -1 Modulates CXCR2-Mediated Cell Migration

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    BACKGROUND: The chemokine receptor CXCR2 plays a pivotal role in migration of neutrophils, macrophages and endothelial cells, modulating several biological responses such as angiogenesis, wound healing and acute inflammation. CXCR2 is also involved in pathogenesis of chronic inflammation, sepsis and atherosclerosis. The ability of CXCR2 to associate with a variety of proteins dynamically is responsible for its effects on directed cell migration or chemotaxis. The dynamic network of such CXCR2 binding proteins is termed as "CXCR2 chemosynapse". Proteomic analysis of proteins that co-immunoprecipitated with CXCR2 in neutrophil-like dHL-60 cells revealed a novel protein, LIM and SH3 protein 1 (LASP-1), binds CXCR2 under both basal and ligand activated conditions. LASP-1 is an actin binding cytoskeletal protein, involved in the cell migration. METHODOLOGY/PRINCIPAL FINDINGS: We demonstrate that CXCR2 and LASP-1 co-immunoprecipitate and co-localize at the leading edge of migrating cells. The LIM domain of LASP-1 directly binds to the carboxy-terminal domain (CTD) of CXCR2. Moreover, LASP-1 also directly binds the CTD of CXCR1, CXCR3 and CXCR4. Using a site-directed and deletion mutagenesis approach, Iso323-Leu324 of the conserved LKIL motif on CXCR2-CTD was identified as the binding site for LASP-1. Interruption of the interaction between CXCR2-CTD and LIM domain of LASP-1 by dominant negative and knock down approaches inhibited CXCR2-mediated chemotaxis. Analysis for the mechanism for inhibition of CXCR2-mediated chemotaxis indicated that LASP-1/CXCR2 interaction is essential for cell motility and focal adhesion turnover involving activation of Src, paxillin, PAK1, p130CAS and ERK1/2. CONCLUSIONS/SIGNIFICANCE: We demonstrate here for the first time that LASP-1 is a key component of the "CXCR2 chemosynapse" and LASP-1 interaction with CXCR2 is critical for CXCR2-mediated chemotaxis. Furthermore, LASP-1 also directly binds the CTD of CXCR1, CXCR3 and CXCR4, suggesting that LASP-1 is a general mediator of CXC chemokine mediated chemotaxis. Thus, LASP-1 may serve as a new link coordinating the flow of information between chemokine receptors and nascent focal adhesions, especially at the leading edge. Thus the association between the chemokine receptors and LASP-1 suggests to the presence of a CXC chemokine receptor-LASP-1 pro-migratory module in cells governing the cell migration
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