264 research outputs found

    Plasmon Modes and Correlation Functions in Quantum Wires and Hall Bars

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    We present microscopic derivations of the one-dimensional low-energy boson effective Hamiltonians of quantum wire and quantum Hall bar systems. The quantum Hall system is distinguished by its spatial separation of oppositely directed electrons. We discuss qualitative differences in the plasmon collective mode dispersions and the ground state correlation functions of the two systems which are consequences of this difference. The slowly-decaying quasi-solid correlations expected in a quantum wire are strongly suppressed in quantum Hall bar systems.Comment: 7 pages, RevTex, 3 figures and 1 table included; references updated and minor typos correcte

    A randomized feasibility trial comparing four antimalarial drug regimens to induce Plasmodium falciparum gametocytemia in the controlled human malaria infection model

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    Background: Malaria elimination strategies require a thorough understanding of parasite transmission from human to mosquito. A clinical model to induce gametocytes to understand their dynamics and evaluate transmission-blocking interventions (TBI) is currently unavailable. Here, we explore the use of the well-established Controlled Human Malaria Infection model (CHMI) to induce gametocyte carriage with different antimalarial drug regimens. Methods: In a single centre, open-label randomised tr

    Safety, Immunogenicity, and Protective Efficacy of Intradermal Immunization with Aseptic, Purified, Cryopreserved Plasmodium falciparum Sporozoites in Volunteers Under Chloroquine Prophylaxis

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    Immunization of volunteers under chloroquine prophylaxis by bites of *Plasmodium falciparum* sporozoite (PfSPZ)–infected mosquitoes induces > 90% protection against controlled human malaria infection (CHMI). We studied intradermal immunization with cryopreserved, infectious PfSPZ in volunteers taking chloroquine (PfSPZ chemoprophylaxis vaccine [CVac]). Vaccine groups 1 and 3 received 3x monthly immunizations with 7.5 x 10^4 PfSPZ. Control groups 2 and 4 received normal saline. Groups 1 and 2 underwent CHMI (#1) by mosquito bite 60 days after the third immunization. Groups 3 and 4 were boosted 168 days after the third immunization and underwent CHMI (#2) 137 days later. Vaccinees (11/20, 55%) and controls (6/10, 60%) had the same percentage of mild to moderate solicited adverse events. After CHMI #1, 8/10 vaccinees (group 1) and 5/5 controls (group 2) became parasitemic by microscopy; the two negatives were positive by quantitative real-time polymerase chain reaction (qPCR). After CHMI #2, all vaccinees in group 3 and controls in group 4 were parasitemic by qPCR. Vaccinees showed weak antibody and no detectable cellular immune responses. Intradermal immunization with up to 3 x 10^5 PfSPZ-CVac was safe, but induced only minimal immune responses and no sterile protection against Pf CHMI. INTRODUCTIO

    P. falciparum Modulates Erythroblast Cell Gene Expression in Signaling and Erythrocyte Production Pathways

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    Global, genomic responses of erythrocytes to infectious agents have been difficult to measure because these cells are e-nucleated. We have previously demonstrated that in vitro matured, nucleated erythroblast cells at the orthochromatic stage can be efficiently infected by the human malaria parasite Plasmodium falciparum. We now show that infection of orthochromatic cells induces change in 609 host genes. 592 of these transcripts are up-regulated and associated with metabolic and chaperone pathways unique to P. falciparum infection, as well as a wide range of signaling pathways that are also induced in related apicomplexan infections of mouse hepatocytes or human fibroblast cells. Our data additionally show that polychromatophilic cells, which precede the orthochromatic stage and are not infected when co-cultured with P. falciparum, up-regulate a small set of genes, at least two of which are associated with pathways of hematopoiesis and/or erythroid cell development. These data support the idea that P. falciparum affects erythropoiesis at multiple stages during erythroblast differentiation. Further P. falciparum may modulate gene expression in bystander erythroblasts and thus influence pathways of erythrocyte development. This study provides a benchmark of the host erythroblast cell response to infection by P. falciparum

    Severe Dengue Is Associated with Consumption of von Willebrand Factor and Its Cleaving Enzyme ADAMTS-13

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    Severe dengue infections are characterized by thrombocytopenia, clinical bleeding and plasma leakage. Activation of the endothelium, the inner lining of blood vessels, leads to the secretion of storage granules called Weibel Palade bodies (WPBs). We demonstrated that severe dengue in Indonesian children is associated with a strong increase in plasma levels of the WPB constituents von Willebrand factor (VWF), VWF propeptide and osteoprotegerin (OPG). An increased amount of the hemostatic protein VWF was in a hyperreactive, platelet binding conformation, and this was most pronounced in the children who died. VWF levels at enrollment were lower than expected from concurrent VWF propeptide and OPG levels and VWF levels did not correlate well with markers of disease severity. Together, this suggests that VWF is being consumed during severe dengue. Circulating levels of the VWF-cleaving enzyme ADAMTS-13 were reduced. VWF is a multimeric protein and a subset of children had a decrease in large and intermediate VWF multimers at discharge. In conclusion, severe dengue is associated with exocytosis of WPBs with consumption of VWF and low ADAMTS-13 activity levels. This may contribute to the thrombocytopenia and complications of dengue

    Prevalence, risk factors, and long-term outcomes of cerebral ischemia in hospitalized COVID-19 patients - study rationale and protocol of the CORONIS study: a multicentre prospective cohort study

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    Background: COVID-19 is often complicated by thrombo-embolic events including ischemic stroke. The underlying mechanisms of COVID-19-associated ischemic stroke, the incidence and risk factors of silent cerebral ischemia, and the long-term functional outcome in these patients are currently unknown. Patients and methods: CORONavirus and Ischemic Stroke (CORONIS) is a multicentre prospective cohort study investigating the prevalence, risk factors and long-term incidence of (silent) cerebral ischemia, and the long-term functional outcome among patients with COVID-19. We aim to include 200 adult patients hospitalized with COVID-19 without symptomatic ischemic stroke to investigate the prevalence of silent cerebral ischemia compared with 60 (matched) controls with MRI. In addition, we will identify potential risk factors and/or causes of cerebral ischemia in COVID-19 patients with (n = 70) or without symptomatic stroke (n = 200) by means of blood sampling, cardiac workup and brain MRI. We will measure functional outcome and cognitive function after 3 and 12 months with standardized questionnaires in all patients with COVID-19. Finally, the long-term incidence of (new) silent cerebral ischemia in patients with COVID-19 will be assessed with follow up MRI (n = 120). The CORONIS study is designed to add further insight into the prevalence, long-term incidence and risk factors of cerebral ischemia, and the long-term functional outcome in hospitalized adult patients with COVID-19.Clinical epidemiolog

    Atherosclerotic renal artery stenosis is prevalent in cardiorenal patients but not associated with left ventricular function and myocardial fibrosis as assessed by cardiac magnetic resonance imaging

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    <p>Abstract</p> <p>Background</p> <p>Atherosclerotic renal artery stenosis (ARAS) is common in cardiovascular diseases and associated with hypertension, renal dysfunction and/or heart failure. There is a paucity of data about the prevalence and the role of ARAS in the pathophysiology of combined chronic heart failure (CHF) and chronic kidney disease (CKD). We investigated the prevalence in patients with combined CHF/CKD and its association with renal function, cardiac dysfunction and the presence and extent of myocardial fibrosis.</p> <p>Methods</p> <p>The EPOCARES study (ClinTrialsNCT00356733) investigates the role of erythropoietin in anaemic patients with combined CHF/CKD. Eligible subjects underwent combined cardiac magnetic resonance imaging (cMRI), including late gadolinium enhancement, with magnetic resonance angiography of the renal arteries (MRA).</p> <p>Results</p> <p>MR study was performed in 37 patients (median age 74 years, eGFR 37.4 ± 15.6 ml/min, left ventricular ejection fraction (LVEF) 43.3 ± 11.2%), of which 21 (56.8%) had ARAS (defined as stenosis >50%). Of these 21 subjects, 8 (21.6%) had more severe ARAS >70% and 8 (21.6%) had a bilateral ARAS >50% (or previous bilateral PTA). There were no differences in age, NT-proBNP levels and medication profile between patients with ARAS versus those without. Renal function declined with the severity of ARAS (p = 0.03), although this was not significantly different between patients with ARAS versus those without. Diabetes mellitus was more prevalent in patients without ARAS (56.3%) against those with ARAS (23.8%) (p = 0.04). The presence and extent of late gadolinium enhancement, depicting myocardial fibrosis, did not differ (p = 0.80), nor did end diastolic volume (p = 0.60), left ventricular mass index (p = 0.11) or LVEF (p = 0.15). Neither was there a difference in the presence of an ischemic pattern of late enhancement in patients with ARAS versus those without.</p> <p>Conclusions</p> <p>ARAS is prevalent in combined CHF/CKD and its severity is associated with a decline in renal function. However, its presence does not correlate with a worse LVEF, a higher left ventricular mass or with the presence and extent of myocardial fibrosis. Further research is required for the role of ARAS in the pathophysiology of combined chronic heart and renal failure.</p
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