228 research outputs found

    Visualizing landscapes of the superconducting gap in heterogeneous superconductor thin films: geometric influences on proximity effects

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    The proximity effect is a central feature of superconducting junctions as it underlies many important applications in devices and can be exploited in the design of new systems with novel quantum functionality. Recently, exotic proximity effects have been observed in various systems, such as superconductor-metallic nanowires and graphene-superconductor structures. However, it is still not clear how superconducting order propagates spatially in a heterogeneous superconductor system. Here we report intriguing influences of junction geometry on the proximity effect for a 2D heterogeneous superconductor system comprised of 2D superconducting islands on top of a surface metal. Depending on the local geometry, the superconducting gap induced in the surface metal region can either be confined to the boundary of the superconductor, in which the gap decays within a short distance (~ 15 nm), or can be observed nearly uniformly over a distance of many coherence lengths due to non-local proximity effects.Comment: 17 pages, 4 figure

    Indexing Strategies for Rapid Searches of Short Words in Genome Sequences

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    Searching for matches between large collections of short (14–30 nucleotides) words and sequence databases comprising full genomes or transcriptomes is a common task in biological sequence analysis. We investigated the performance of simple indexing strategies for handling such tasks and developed two programs, fetchGWI and tagger, that index either the database or the query set. Either strategy outperforms megablast for searches with more than 10,000 probes. FetchGWI is shown to be a versatile tool for rapidly searching multiple genomes, whose performance is limited in most cases by the speed of access to the filesystem. We have made publicly available a Web interface for searching the human, mouse, and several other genomes and transcriptomes with oligonucleotide queries

    Percutaneous acetabuloplasty for metastatic acetabular lesions

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    Osteolytic metastases around the acetabulum are frequent in tumour patients, and may cause intense and drug-resistant pain of the hip. These lesions also cause structural weakening of the pelvis, limping, and poor quality of life. Percutaneous acetabuloplasty is a mini-invasive procedure for the management of metastatic lesions due to carcinoma of the acetabulum performed in patients who cannot tolerate major surgery, or in patients towards whom radiotherapy had already proved ineffective

    Routine Laboratory Results and Thirty Day and One-Year Mortality Risk Following Hospitalization with Acute Decompensated Heart Failure

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    INTRODUCTION: Several blood tests are performed uniformly in patients hospitalized with acute decompensated heart failure and are predictive of the outcomes: complete blood count, electrolytes, renal function, glucose, albumin and uric acid. We sought to evaluate the relationship between routine admission laboratory tests results, patient characteristics and 30-day and one-year mortality of patients admitted for decompensated heart failure and to construct a simple mortality prediction tool. METHODS: A retrospective population based study. Data from seven tertiary hospitals on all admissions with a principal diagnosis of heart failure during the years 2002-2005 throughout Israel were captured. RESULTS: 8,246 patients were included in the study cohort. Thirty day mortality rate was 8.5% (701 patients) and one-year mortality rate was 28.7% (2,365 patients). Addition of five routine laboratory tests results (albumin, sodium, blood urea, uric acid and WBC) to a set of clinical and demographic characteristics improved c-statistics from 0.76 to 0.81 for 30-days and from 0.72 to 0.76 for one-year mortality prediction (both p-values <0.0001). Three dichotomized abnormal laboratory results with highest odds ratio for one-year mortality (hypoalbuminaemia, hyponatremia and elevated blood urea) were used to construct a simple prediction score, capable of discriminating from 1.1% to 21.4% in 30-day and from 11.6% to 55.6% in one-year mortality rates between patients with a score of 0 (1,477 patients) vs. score of 3 (544 patients). DISCUSSION: A small set of abnormal routine laboratory results upon admission can risk-stratify and independently predict 30-day and one-year mortality in patients hospitalized with acute decompensated heart failure

    Serologic evidence of human orthopoxvirus infections in Sierra Leone

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    <p>Abstract</p> <p>Background</p> <p>Orthopoxviruses, including variola virus, vaccinia virus, and monkeypox virus, have previously been documented in humans in West Africa, however, no cases of human orthopoxvirus infection have been reported in the region since 1986. We conducted a serosurvey to determine whether human exposure to orthopoxviruses continues to occur in eastern Sierra Leone.</p> <p>Findings</p> <p>To examine evidence of exposure to orthopoxviruses in the Kenema District of Sierra Leone, we collected and tested sera from 1596 persons by IgG ELISA and a subset of 313 by IgM capture ELISA. Eleven persons born after the cessation of smallpox vaccination had high orthopoxvirus-specific IgG values, and an additional 6 persons had positive IgM responses. No geographic clustering was noted.</p> <p>Conclusions</p> <p>These data suggest that orthopoxviruses continue to circulate in Sierra Leone. Studies aimed at obtaining orthopoxvirus isolates and/or genetic sequences from rodents and symptomatic humans in the area are indicated.</p

    Syk-Mediated Translocation of PI3Kδ to the Leading Edge Controls Lamellipodium Formation and Migration of Leukocytes

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    The non-receptor tyrosine kinase Syk is mainly expressed in the hematopoietic system and plays an essential role in β2 integrin-mediated leukocyte activation. To elucidate the signaling pathway downstream of Syk during β2 integrin (CD11/CD18)-mediated migration and extravasation of polymorphonuclear neutrophils (PMN), we generated neutrophil-like differentiated HL-60 (dHL-60) cells expressing a fluorescently tagged Syk mutant lacking the tyrosine residue at the position 323 (Syk-Tyr323) that is known to be required for the binding of the regulatory subunit p85 of the phosphatidylinositol 3-kinase (PI3K) class IA. Syk-Tyr323 was found to be critical for the enrichment of the catalytic subunit p110δ of PI3K class IA as well as for the generation of PI3K products at the leading edge of the majority of polarized cells. In accordance, the translocation of PI3K p110δ to the leading edge was diminished in Syk deficient murine PMN. Moreover, the expression of EGFP-Syk Y323F interfered with proper cell polarization and it impaired efficient migration of dHL-60 cells. In agreement with a major role of β2 integrins in the recruitment of phagocytic cells to sites of lesion, mice with a Syk-deficient hematopoietic system demonstrated impaired PMN infiltration into the wounded tissue that was associated with prolonged cutaneous wound healing. These data imply a novel role of Syk via PI3K p110δ signaling for β2 integrin-mediated migration which is a prerequisite for efficient PMN recruitment in vivo

    Macrophage-Specific ApoE Gene Repair Reduces Diet-Induced Hyperlipidemia and Atherosclerosis in Hypomorphic Apoe Mice

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    Apolipoprotein (apo) E is best known for its ability to lower plasma cholesterol and protect against atherosclerosis. Although the liver is the major source of plasma apoE, extra-hepatic sources of apoE, including from macrophages, account for up to 10% of plasma apoE levels. This study examined the contribution of macrophage-derived apoE expression levels in diet-induced hyperlipidemia and atherosclerosis.Hypomorphic apoE (Apoe(h/h)) mice expressing wildtype mouse apoE at ∼2-5% of physiological levels in all tissues were derived by gene targeting in embryonic stem cells. Cre-mediated gene repair of the Apoe(h/h) allele in Apoe(h/h)LysM-Cre mice raised apoE expression levels by 26 fold in freshly isolated peritoneal macrophages, restoring it to 37% of levels seen in wildtype mice. Chow-fed Apoe(h/h)LysM-Cre and Apoe(h/h) mice displayed similar plasma apoE and cholesterol levels (55.53±2.90 mg/dl versus 62.70±2.77 mg/dl, n = 12). When fed a high-cholesterol diet (HCD) for 16 weeks, Apoe(h/h)LysM-Cre mice displayed a 3-fold increase in plasma apoE and a concomitant 32% decrease in plasma cholesterol when compared to Apoe(h/h) mice (602.20±22.30 mg/dl versus 888.80±24.99 mg/dl, n = 7). On HCD, Apoe(h/h)LysM-Cre mice showed increased apoE immunoreactivity in lesional macrophages and liver-associated Kupffer cells but not hepatocytes. In addition, Apoe(h/h)LysM-Cre mice developed 35% less atherosclerotic lesions in the aortic root than Apoe(h/h) mice (167×10(3)±16×10(3) µm(2) versus 259×10(3)±56×10(3) µm(2), n = 7). This difference in atherosclerosis lesions size was proportional to the observed reduction in plasma cholesterol.Macrophage-derived apoE raises plasma apoE levels in response to diet-induced hyperlipidemia and by such reduces atherosclerosis proportionally to the extent to which it lowers plasma cholesterol levels

    Health-seeking behaviors and self-care practices of Dominican women with lymphoedema of the leg: implications for lymphoedema management programs

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    BACKGROUND: In the Dominican Republic, a Latin American country with filariasis-endemic areas, more than 63,000 people have lymphatic filariasis and more than 400,000 people are at risk of future infection. In this paper, we explore the health beliefs, health-seeking behaviors and self-care practices of women with lymphoedema in filariasis-endemic areas to better understand the needs of women when developing lymphoedema morbidity control programs. METHODS: Qualitative data were collected through semi-structured interviews of 28 women, 3 focus group discussions with 28 women, field notes and photographs. RESULTS: Women described exhaustive and expensive attempts at seeking a cure for their lymphoedema. Family members were influential in providing women with initial care seeking referrals to indigenous healers credited with influence over physical, mental, spiritual and supernatural properties of illness. When indigenous treatments proved to be ineffectual, the women sought care from trained healthcare providers. Most healthcare providers incorrectly diagnosed the edema, failed to adequately treat and meet the needs of women and were viewed as expensive. Most women resorted to self-prescribing injectable, oral, or topical antibiotics along with oral analgesics as a standard practice of self-care. CONCLUSION: Healthcare providers must understand a woman's cultural perspectives of illness, her natural networks of support and referral, her behavioural practices of care-seeking and self-care and the financial burden of seeking care. In the culture of the Dominican Republic family members and traditional healthcare providers are influential advisors on initial health-seeking behaviors and self-care practices. For this reason family-oriented interventions, support groups for women and their families, community education and training on simple, low cost lymphoedema management techniques for indigenous healers are viable ways to influence the early detection, diagnosis and treatment of women with lymphoedema. The extensive use of injectable, oral and topical antibiotics by indigenous healers and women without medical supervision suggests a need for health education messages related to the risks of such practices

    Myeloid Heme Oxygenase-1 Haploinsufficiency Reduces High Fat Diet-Induced Insulin Resistance by Affecting Adipose Macrophage Infiltration in Mice

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    Increased adipose tissue macrophages contribute to obesity-induced metabolic syndrome. Heme oxygenase-1 (HO-1) is a stress-inducible enzyme with potent anti-inflammatory and proangiogenic activities in macrophages. However, the role of macrophage HO-1 on obesity-induced adipose inflammation and metabolic syndrome remains unclear. Here we show that high-fat diet (HFD) feeding in C57BL/6J mice induced HO-1 expression in the visceral adipose tissue, particularly the stromal vascular fraction. When the irradiated C57BL/6J mice reconstituted with wild-type or HO-1+/− bone marrow were fed with HFD for over 24 weeks, the HO-1+/− chimeras were protected from HFD-induced insulin resistance and this was associated with reduced adipose macrophage infiltration and angiogenesis, suggesting that HO-1 affects myeloid cell migration toward adipose tissue during obesity. In vivo and in vitro migration assays revealed that HO-1+/− macrophages exhibited an impaired migration response. Chemoattractant-induced phosphorylation of p38 and focal adhesion kinase (FAK) declined faster in HO-1+/− macrophages. Further experiments demonstrated that carbon monoxide and bilirubin, the byproducts derived from heme degradation by HO-1, enhanced macrophage migration by increasing phosphorylation of p38 and FAK, respectively. These data disclose a novel role of hematopoietic cell HO-1 in promoting adipose macrophage infiltration and the development of insulin resistance during obesity
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