294 research outputs found

    Alloying, de-alloying and reentrant alloying in (sub-)monolayer growth of Ag on Pt(111)

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    An in-situ nanoscopic investigation of the prototypical surface alloying system Ag/Pt(111) is reported. The morphology and the structure of the ultrathin Ag-Pt film is studied using Low Energy Electron Microscopy during growth at about 800 K. An amazingly rich dynamic behaviour is uncovered in which stress relieve plays a governing role. Initial growth leads to surface alloying with prolonged and retarded nucleation of ad-islands. Beyond 50% coverage de-alloying proceeds, joined by partial segregation of Pt towards the centre of large islands in violent processes. Upon coalescence the irregularly shaped vacancy clusters are filled by segregating Pt, which then take a compact shape (black spots). As a result at around 85% coverage the strain of the initially pseudo-morphological film is almost completely relieved and Pt-segregation is at its maximum. Further deposition of Ag leads to transient re-entrant alloying and recovery of the pseudo-morphological layer. The black spots persist even in/on several layers thick films. Ex-situ atomic force microscopy data confirm that these are constituted by probably amorphous Pt(-rich) structures. The (sub-)monolayer films are very much heterogeneous

    Niemann-Pick C1 (NPC1)/NPC1-like1 Chimeras Define Sequences Critical for NPC1’s Function as a Filovirus Entry Receptor

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    We recently demonstrated that Niemann-Pick C1 (NPC1), a ubiquitous 13-pass cellular membrane protein involved in lysosomal cholesterol transport, is a critical entry receptor for filoviruses. Here we show that Niemann-Pick C1-like1 (NPC1L1), an NPC1 paralog and hepatitis C virus entry factor, lacks filovirus receptor activity. We exploited the structural similarity between NPC1 and NPC1L1 to construct and analyze a panel of chimeras in which NPC1L1 sequences were replaced with cognate sequences from NPC1. Only one chimera, NPC1L1 containing the second luminal domain (C) of NPC1 in place of its own, bound to the viral glycoprotein, GP. This engineered protein mediated authentic filovirus infection nearly as well as wild-type NPC1, and more efficiently than did a minimal NPC1 domain C-based receptor recently described by us. A reciprocal chimera, NPC1 containing NPC1L1’s domain C, was completely inactive. Remarkably, an intra-domain NPC1L1-NPC1 chimera bearing only a ~130-amino acid N–terminal region of NPC1 domain C could confer substantial viral receptor activity on NPC1L1. Taken together, these findings account for the failure of NPC1L1 to serve as a filovirus receptor, highlight the central role of the luminal domain C of NPC1 in filovirus entry, and reveal the direct involvement of N–terminal domain C sequences in NPC1’s function as a filovirus receptor

    Multifaceted Role of Heme during Severe Plasmodium falciparum Infections in India

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    Several immunomodulatory factors are involved in malaria pathogenesis. Among them, heme has been shown to play a role in the pathophysiology of severe malaria in rodents, but its role in human severe malaria remains unclear. Circulating levels of total heme and its main scavenger, hemopexin, along with cytokine/chemokine levels and biological parameters, including hemoglobin and creatinine levels, as well as transaminase activities, were measured in the plasma of 237 Plasmodium falciparum-infected patients living in the state of Odisha, India, where malaria is endemic. All patients were categorized into well-defined groups of mild malaria, cerebral malaria (CM), or severe noncerebral malaria, which included acute renal failure (ARF) and hepatopathy. Our results show a significant increase in total plasma heme levels with malaria severity, especially for CM and malarial ARF. Spearman rank correlation and canonical correlation analyses have shown a correlation between total heme, hemopexin, interleukin-10, tumor necrosis factor alpha, gamma interferon-induced protein 10 (IP-10), and monocyte chemotactic protein 1 (MCP-1) levels. In addition, canonical correlations revealed that heme, along with IP-10, was associated with the CM pathophysiology, whereas both IP-10 and MCP-1 together with heme discriminated ARF. Altogether, our data indicate that heme, in association with cytokines and chemokines, is involved in the pathophysiology of both CM and ARF but through different mechanisms.Indo-French Centre for the Promotion of Advanced Research, Associated International Laboratory Systems (LIA; CNRS), Immunology and Genetics of Infectious Diseases (SIGID), Department of Biotechnology from the Ministry of Science and Technology of India (DBT), Tata Institute of Fundamental Research (TIFR) (intramural funds), Université Lille (doctoral contract), IFCPAR (Raman-Charpak award), College Doctoral Lille Nord de France (AAP n10 award), Fondation des Treille, Conseil Régional du Nord-Pas de Calais

    Professional learning in mathematical reasoning: reflections of a primary teacher

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    Reasoning is an important aspect in the understanding and learning of mathematics. This paper reports on a case study presenting one Australian primary teacher’s reflections regarding the role played by a professional learning program in her developing understanding of mathematical reasoning. Examination of the transcripts of two interviews identified changes in her perceptions of mathematical reasoning by mapping interview responses against the Mathematical Reasoning Framework (Herbert et al., 2015). This change indicates that a well planned program of professional learning based on a demsonstration is efficacious in developing teachers’ understanding of mathematical reasoning

    Functional recovery after treatment of extra-articular distal radius fractures in the elderly using the IlluminOss® System (IO-Wrist); A multicenter prospective observational study

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    Background: Approximately 17 % of all fractures involve the distal radius. Two-thirds require reduction due to displacement. High redislocation rates and functional disability remain a significant problem after non-operative treatment, with up to 30 % of patients suffering long-term functional restrictions. Whether operative correction is superior to non-operative treatment with respect to functional outcome has not unequivocally been confirmed. The IlluminOss® System was introduced in 2009 as a novel, patient-specific, and minimally invasive intramedullary fracture fixation. This minimally invasive technique has a much lower risk of iatrogenic soft tissue complications. Because IlluminOss® allows for early mobilization, it may theoretically lead to earlier functional recovery and ADL independence than non-operative immobilization. The main aim of this study is to examine outcome in elderly patients who sustained a unilateral, displaced, extra-articular distal radius fracture that was treated with IlluminOss®. Methods/design: The design of the study will be a multicenter, prospective, observational study (case series). The study population comprises elderly (60 years or older; independent in activities of daily living) with a unilateral, displaced, extra-articular distal radius fracture (AO/OTA type 23-A2 and A3) that after successful closed reduction was fixed within 2 weeks after the injury with IlluminOss®. Critical elements of treatment will be registered, and outcome will be monitored until 1 year after surgery. The Disabilities of the Arm, Shoulder, and Hand score will serve as primary outcome measure. The Patient-Rated Wrist Evaluation score, level of pain, health-related quality of life (Short Form-36 and EuroQoL-5D), time to ADL independence, time to activities/work resumption, range of motion of the wrist, radiological outcome, and complications are secondary outcome measures. Health care consumption and lost productivity will be used for a cost analysis. The cost analysis will be performed from a societal perspective. Descriptive data will be r

    The Pennsylvania Dutchman Vol. 8, No. 1

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    â—Ź The Summer House â—Ź Drinks in Dutchland â—Ź Yesteryear in Dutchland â—Ź Moshey and Bellyguts â—Ź Rise of Interest in Dutch Antiques â—Ź Diaper Lore â—Ź Lititz â—Ź Witchcraft in Cow and Horse â—Ź Dorothy Kalbach â—Ź Plain Dutch and Gay Dutch â—Ź Dialect Folksay â—Ź Pennsylvania Dutch Pioneers â—Ź About the Authors â—Ź What\u27s New in Dutchlandhttps://digitalcommons.ursinus.edu/dutchmanmag/1008/thumbnail.jp

    Progression criteria in trials with an internal pilot : an audit of publicly funded randomised controlled trials

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    Background With millions of pounds spent annually on medical research in the UK, it is important that studies are spending funds wisely. Internal pilots offer the chance to stop a trial early if it becomes apparent that the study will not be able to recruit enough patients to show whether an intervention is clinically effective. This study aims to assess the use of internal pilots in individually randomised controlled trials funded by the Health Technology Assessment (HTA) programme and to summarise the progression criteria chosen in these trials. Methods Studies were identified from reports of the HTA committees’ funding decisions from 2012 to 2016. In total, 242 trials were identified of which 134 were eligible to be included in the audit. Protocols for the eligible studies were located on the NIHR Journals website, and if protocols were not available online then study managers were contacted to provide information. Results Over two-thirds (72.4%) of studies said in their protocol that they would include an internal pilot phase for their study and 37.8% of studies without an internal pilot had done an external pilot study to assess the feasibility of the full study. A typical study with an internal pilot has a target sample size of 510 over 24 months and aims to recruit one-fifth of their total target sample size within the first one-third of their recruitment time. There has been an increase in studies adopting a three-tiered structure for their progression rules in recent years, with 61.5% (16/26) of studies using the system in 2016 compared to just 11.8% (2/17) in 2015. There was also a rise in the number of studies giving a target recruitment rate in their progression criteria: 42.3% (11/26) in 2016 compared to 35.3% (6/17) in 2015. Conclusions Progression criteria for an internal pilot are usually well specified but targets vary widely. For the actual criteria, red/amber/green systems have increased in popularity in recent years. Trials should justify the targets they have set, especially where targets are low

    Primary hemiarthroplasty versus conservative treatment for comminuted fractures of the proximal humerus in the elderly (ProCon): A Multicenter Randomized Controlled trial

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    Background. Fractures of the proximal humerus are associated with a profound temporary and sometimes permanent, impairment of function and quality of life. The treatment of comminuted fractures of the proximal humerus like selected three-or four-part fractures and split fractures of the humeral head is a demanding and unresolved problem, especially in the elderly. Locking plates appear to offer improved fixation; however, screw cut-out rates ranges due to fracture collapse are high. As this may lead to higher rates of revision surgery, it may be preferable to treat comminuted fractures in the elderly primarily with a prosthesis or non-operatively. Results from case series and a small-sample randomized controlled trial (RCT) suggest improved function and less pain after primary hemiarthroplasty (HA); however these studies had some limitations and a RCT is needed. The primary aim of this study is to compare the Constant scores (reflecting functional outcome and pain) at one year after primary HA versus non-operative treatment in elderly patients who sustained a comminuted proximal humeral fracture. Secondary aims include effects on functional outcome, pain, complications, quality of life, and cost-effectiveness. Methods/Design. A prospective, multi-center RCT will be conducted in nine centers in the Netherlands and Belgium. Eighty patients over 65 years of age, who have sustained a three-or four part, or split head proximal humeral fracture will be randomized between primary hemiarthroplasty and conservative treatment. The primary outcome is the Constant score, which indicates pain and function. Secondary outcomes include the Disability of the Arm and Shoulder (DASH) score, Visual Analogue Scale (VAS) for pain, radiographic healing, health-related quality of life (Short-form-36, EuroQol-5D) and healthcare consumption. Cost-effectiveness ratios wi
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