1,037 research outputs found

    Efficient calculation of the worst-case error and (fast) component-by-component construction of higher order polynomial lattice rules

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    We show how to obtain a fast component-by-component construction algorithm for higher order polynomial lattice rules. Such rules are useful for multivariate quadrature of high-dimensional smooth functions over the unit cube as they achieve the near optimal order of convergence. The main problem addressed in this paper is to find an efficient way of computing the worst-case error. A general algorithm is presented and explicit expressions for base~2 are given. To obtain an efficient component-by-component construction algorithm we exploit the structure of the underlying cyclic group. We compare our new higher order multivariate quadrature rules to existing quadrature rules based on higher order digital nets by computing their worst-case error. These numerical results show that the higher order polynomial lattice rules improve upon the known constructions of quasi-Monte Carlo rules based on higher order digital nets

    Quality Of Antenatal Care In Rural Southern Tanzania: A Reality Check.

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    Counselling on the danger signs of unpredictable obstetric complications and the appropriate management of such complications are crucial in reducing maternal mortality. The objectives of this study were to identify gaps in the provision of ANC services and knowledge of danger signs as well as the quality of care women receive in case of complications. The study took place in the Rufiji District of Tanzania in 2008 and was conducted in seven health facilities. The study used (1) observations from 63 antenatal care (ANC) sessions evaluated with an ANC checklist, (2) self-assessments of 11 Health workers, (3) interviews with 28 pregnant women and (4) follow-up of 12 women hospitalized for pregnancy-related conditions.Blood pressure measurements and abdominal examinations were common during ANC visits while urine testing for albumin or sugar or haemoglobin levels was rare which was often explained as due to a lack of supplies. The reasons for measuring blood pressure or abdominal examinations were usually not explained to the women. Only 15/28 (54%) women were able to mention at least one obstetric danger sign requiring medical attention. The outcomes of ten complicated cases were five stillbirths and three maternal complications. There was a considerable delay in first contact with a health professional or the start of timely interventions including checking vital signs, using a partograph, and detailed record keeping. Linking danger signs to clinical and laboratory examination results during ANC with the appropriate follow up and avoiding delays in emergency obstetric care are crucial to the delivery of coordinated, effective care interventions

    Honey bee foraging distance depends on month and forage type

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    To investigate the distances at which honey bee foragers collect nectar and pollen, we analysed 5,484 decoded waggle dances made to natural forage sites to determine monthly foraging distance for each forage type. Firstly, we found significantly fewer overall dances made for pollen (16.8 %) than for non-pollen, presumably nectar (83.2 %; P < 2.2 × 10−23). When we analysed distance against month and forage type, there was a significant interaction between the two factors, which demonstrates that in some months, one forage type is collected at farther distances, but this would reverse in other months. Overall, these data suggest that distance, as a proxy for forage availability, is not significantly and consistently driven by need for one type of forage over the other

    Pathophysiology of acute experimental pancreatitis: Lessons from genetically engineered animal models and new molecular approaches

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    The incidence of acute pancreatitis is growing and worldwide population-based studies report a doubling or tripling since the 1970s. 25% of acute pancreatitis are severe and associated with histological changes of necrotizing pancreatitis. There is still no specific medical treatment for acute pancreatitis. The average mortality resides around 10%. In order to develop new specific medical treatment strategies for acute pancreatitis, a better understanding of the pathophysiology during the onset of acute pancreatitis is necessary. Since it is difficult to study the early acinar events in human pancreatitis, several animal models of acute pancreatitis have been developed. By this, it is hoped that clues into human pathophysiology become possible. In the last decade, while employing molecular biology techniques, a major progress has been made. The genome of the mouse was recently sequenced. Various strategies are possible to prove a causal effect of a single gene or protein, using either gain-of-function (i.e., overexpression of the protein of interest) or loss-of-function studies (i.e., genetic deletion of the gene of interest). The availability of transgenic mouse models and gene deletion studies has clearly increased our knowledge about the pathophysiology of acute pancreatitis and enables us to study and confirm in vitro findings in animal models. In addition, transgenic models with specific genetic deletion or overexpression of genes help in understanding the role of one specific protein in a cascade of inflammatory processes such as pancreatitis where different proteins interact and co-react. This review summarizes the recent progress in this field. Copyright (c) 2005 S. Karger AG, Basel

    NMR Derived Model of GTPase Effector Domain (GED) Self Association: Relevance to Dynamin Assembly

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    Self-association of dynamin to form spiral structures around lipidic vesicles during endocytosis is largely mediated by its ‘coiled coil’ GTPase Effector Domain (GED), which, in vitro, self-associates into huge helical assemblies. Residue-level structural characterizations of these assemblies and understanding the process of association have remained a challenge. It is also impossible to get folded monomers in the solution phase. In this context, we have developed here a strategy to probe the self-association of GED by first dissociating the assembly using Dimethyl Sulfoxide (DMSO) and then systematically monitoring the refolding into helix and concomitant re-association using NMR spectroscopy, as DMSO concentration is progressively reduced. The short segment, Arg109 - Met116, acts as the nucleation site for helix formation and self-association. Hydrophobic and complementary charge interactions on the surfaces drive self-association, as the helices elongate in both the directions resulting in an antiparallel stack. A small N-terminal segment remains floppy in the assembly. Following these and other published results on inter-domain interactions, we have proposed a plausible mode of dynamin self assembly

    Accuracy of magnetic resonance studies in the detection of chondral and labral lesions in femoroacetabular impingement : systematic review and meta-analysis

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    Background: Several types of Magnetic resonance imaging (MRI) are commonly used in imaging of femoroacetabular impingement (FAI), however till now there are no clear protocols and recommendations for each type. The aim of this meta-analysis is to detect the accuracy of conventional magnetic resonance imaging (cMRI), direct magnetic resonance arthrography (dMRA) and indirect magnetic resonance arthrography (iMRA) in the diagnosis of chondral and labral lesions in femoroacetabular impingement (FAI). Methods: A literature search was finalized on the 17th of May 2016 to collect all studies identifying the accuracy of cMRI, dMRA and iMRA in diagnosing chondral and labral lesions associated with FAI using surgical results (arthroscopic or open) as a reference test. Pooled sensitivity and specificity with 95% confidence intervals using a random-effects meta-analysis for MRI, dMRA and iMRA were calculated also area under receiver operating characteristic (ROC) curve (AUC) was retrieved whenever possible where AUC is equivocal to diagnostic accuracy. Results: The search yielded 192 publications which were reviewed according inclusion and exclusion criteria then 21 studies fulfilled the eligibility criteria for the qualitative analysis with a total number of 828 cases, lastly 12 studies were included in the quantitative meta-analysis. Meta-analysis showed that as regard labral lesions the pooled sensitivity, specificity and AUC for cMRI were 0.864, 0.833 and 0.88 and for dMRA were 0.91, 0.58 and 0.92. While in chondral lesions the pooled sensitivity, specificity and AUC for cMRI were 0.76, 0.72 and 0.75 and for dMRA were 0.75, 0.79 and 0.83, while for iMRA were sensitivity of 0.722 and specificity of 0.917. Conclusions: The present meta-analysis showed that the diagnostic test accuracy was superior for dMRA when compared with cMRI for detection of labral and chondral lesions. The diagnostic test accuracy was superior for labral lesions when compared with chondral lesions in both cMRI and dMRA. Promising results are obtained concerning iMRA but further studies still needed to fully assess its diagnostic accuracy

    A new rhynchocephalian from the late jurassic of Germany with a dentition that is unique amongst tetrapods.

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    Rhynchocephalians, the sister group of squamates (lizards and snakes), are only represented by the single genus Sphenodon today. This taxon is often considered to represent a very conservative lineage. However, rhynchocephalians were common during the late Triassic to latest Jurassic periods, but rapidly declined afterwards, which is generally attributed to their supposedly adaptive inferiority to squamates and/or Mesozoic mammals, which radiated at that time. New finds of Mesozoic rhynchocephalians can thus provide important new information on the evolutionary history of the group. A new fossil relative of Sphenodon from the latest Jurassic of southern Germany, Oenosaurus muehlheimensis gen. et sp. nov., presents a dentition that is unique amongst tetrapods. The dentition of this taxon consists of massive, continuously growing tooth plates, probably indicating a crushing dentition, thus representing a previously unknown trophic adaptation in rhynchocephalians. The evolution of the extraordinary dentition of Oenosaurus from the already highly specialized Zahnanlage generally present in derived rhynchocephalians demonstrates an unexpected evolutionary plasticity of these animals. Together with other lines of evidence, this seriously casts doubts on the assumption that rhynchocephalians are a conservative and adaptively inferior lineage. Furthermore, the new taxon underlines the high morphological and ecological diversity of rhynchocephalians in the latest Jurassic of Europe, just before the decline of this lineage on this continent. Thus, selection pressure by radiating squamates or Mesozoic mammals alone might not be sufficient to explain the demise of the clade in the Late Mesozoic, and climate change in the course of the fragmentation of the supercontinent of Pangaea might have played a major role

    Proteomics: in pursuit of effective traumatic brain injury therapeutics

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    Effective traumatic brain injury (TBI) therapeutics remain stubbornly elusive. Efforts in the field have been challenged by the heterogeneity of clinical TBI, with greater complexity among underlying molecular phenotypes than initially conceived. Future research must confront the multitude of factors comprising this heterogeneity, representing a big data challenge befitting the coming informatics age. Proteomics is poised to serve a central role in prescriptive therapeutic development, as it offers an efficient endpoint within which to assess post-TBI biochemistry. We examine rationale for multifactor TBI proteomic studies and the particular importance of temporal profiling in defining biochemical sequences and guiding therapeutic development. Lastly, we offer perspective on repurposing biofluid proteomics to develop theragnostic assays with which to prescribe, monitor and assess pharmaceutics for improved translation and outcome for TBI patients

    Expression of the RNA helicase DDX3 and the hypoxia response in breast cancer

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    &lt;p&gt;Aims: DDX3 is an RNA helicase that has antiapoptotic properties, and promotes proliferation and transformation. In addition, DDX3 was shown to be a direct downstream target of HIF-1α (the master regulatory of the hypoxia response) in breast cancer cell lines. However, the relation between DDX3 and hypoxia has not been addressed in human tumors. In this paper, we studied the relation between DDX3 and the hypoxic responsive proteins in human breast cancer.&lt;/p&gt; &lt;p&gt;Methods and Results: DDX3 expression was investigated by immunohistochemistry in breast cancer in comparison with hypoxia related proteins HIF-1α, GLUT1, CAIX, EGFR, HER2, Akt1, FOXO4, p53, ERα, COMMD1, FER kinase, PIN1, E-cadherin, p21, p27, Transferrin receptor, FOXO3A, c-Met and Notch1. DDX3 was overexpressed in 127 of 366 breast cancer patients, and was correlated with overexpression of HIF-1α and its downstream genes CAIX and GLUT1. Moreover, DDX3 expression correlated with hypoxia-related proteins EGFR, HER2, FOXO4, ERα and c-Met in a HIF-1α dependent fashion, and with COMMD1, FER kinase, Akt1, E-cadherin, TfR and FOXO3A independent of HIF-1α.&lt;/p&gt; &lt;p&gt;Conclusions: In invasive breast cancer, expression of DDX3 was correlated with overexpression of HIF-1α and many other hypoxia related proteins, pointing to a distinct role for DDX3 under hypoxic conditions and supporting the oncogenic role of DDX3 which could have clinical implication for current development of DDX3 inhibitors.&lt;/p&gt
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