711 research outputs found

    Does text structure/summarization instruction facilitate learning from expository text?

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    The work upon which this publication is based was performed pursuant to Contract no. NIE-400-81-0030 of the National Institute of Educatio

    Local Percolation Probabilities for a Natural Sandstone

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    Local percolation probabilities are used to characterize the connectivity in porous and heterogeneous media. Together with local porosity distributions they allow to predict transport properties \cite{hil91d}. While local porosity distributions are readily obtained, measurements of the local percolation probabilities are more difficult and have not been attempted previously. First measurements of three dimensional local porosity distributions and percolation probabilities from a pore space reconstruction for a natural sandstone show that theoretical expectations and experimental results are consistent.Comment: 9 pages, see also http://www.ica1.uni-stuttgart.de , Physica

    Mutagenesis in rodents using the L1 retrotransposon

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    LINE1 (L1) retrotransposons are genetic elements that are present in all mammalian genomes. L1s are active in both humans and mice, and are capable of copying themselves and inserting the copy into a new genomic location. These de novo insertions occasionally result in disease. Endogenous L1 retrotransposons can be modified to increase their activity and mutagenic power in a variety of ways. Here we outline the advantages of using modified L1 retrotransposons for performing random mutagenesis in rodents and discuss several potential applications

    Rescaling Relations between Two- and Three-dimensional Local Porosity Distributions for Natural and Artificial Porous Media

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    Local porosity distributions for a three-dimensional porous medium and local porosity distributions for a two-dimensional plane-section through the medium are generally different. However, for homogeneous and isotropic media having finite correlation-lengths, a good degree of correspondence between the two sets of local porosity distributions can be obtained by rescaling lengths, and the mapping associating corresponding distributions can be found from two-dimensional observations alone. The agreement between associated distributions is good as long as the linear extent of the measurement cells involved is somewhat larger than the correlation length, and it improves as the linear extent increases. A simple application of the central limit theorem shows that there must be a correspondence in the limit of very large measurement cells, because the distributions from both sets approach normal distributions. A normal distribution has two independent parameters: the mean and the variance. If the sample is large enough, LPDs from both sets will have the same mean. Therefore corresponding distributions are found by matching variances of two- and three-dimensional local porosity distributions. The variance can be independently determined from correlation functions. Equating variances leads to a scaling relation for lengths in this limit. Three particular systems are examined in order to show that this scaling behavior persists at smaller length-scales.Comment: 15 PostScript figures, LaTeX, To be published in Physica

    When to discharge and when to voluntary or compulsory hospitalize? Factors associated with treatment decision after self-harm.

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    Clinicians assessing suicidal patients in emergency departments (EDs) must decide whether to admit the person to a psychiatric ward with voluntary or compulsory hospitalization or to discharge him/her as an outpatient. This cross-sectional study aimed to identify independent predictors of this decision among a large sample of self-harm (SH) patients. It used data from all patients admitted to four Swiss EDs between 2016 and 2019. Socio-demographic, clinical, and suicidal process-related characteristics data were evaluated against the decision for voluntary or compulsory hospitalization using t-tests, Chi-Square tests and logistic multiple regression. 2142 episodes from 1832 unique patients were evaluated. Independent predictors of decision to hospitalize included: male gender, advanced age, hospital location, depression and personality disorders, substance use, a difficult socio-economic condition, a clear intent to die, and a serious suicide attempt. Significant variables that emerged as independent predictors of compulsory hospitalization were hospital location, not having anxiety and personality disorders, being retired, having a clear intent to die, and making a serious suicide attempt. Hospital EDs had different rates of compulsory psychiatric admission. However, the decision to admit a patient for hospitalization, either voluntary or compulsory, was mainly based on clinical factors

    Longitudinal Bone Loss Occurs at the Radius in CKD.

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    Chronic kidney disease (CKD) exposes to an increased incidence of fragility fractures. International guidelines recommend performing bone mineral density (BMD) if the results will impact treatment decisions. It remains unknown where bone loss occurs and what would preclude the longitudinal loss in patients with CKD. Here, we aimed to investigate factors influencing BMD and to analyze the longitudinal BMD changes. In the NephroTest cohort, we measured BMD at the femoral neck, total hip, lumbar spine, and proximal radius, together with circulating biomarkers and standardized measured glomerular filtration rate (mGFR) by <sup>51</sup> Cr-EDTA in a subset of patients with CKD stage 1 to 5 followed during 4.3 ± 2.0 years. A linear mixed model explored the longitudinal bone loss and the relationship of associated factors with BMD changes. A total of 858 patients (mean age 58.9 ± 15.2 years) had at least 1 and 477 had at least 2 BMD measures. At baseline, cross-sectional analysis showed a significantly lower BMD at femoral neck and total hip and a significant higher serum parathyroid hormone (PTH) along with CKD stages. Baseline age, gender, tobacco, low body mass index (BMI), and high PTH levels were significantly associated with low BMD. Longitudinal analysis during the mean 4.3 years revealed a significant bone loss at the radius only. BMD changes at the femoral neck were associated with BMI, but not CKD stages or basal PTH levels. CKD is associated with low BMD and high PTH in the cross-sectional analysis. Longitudinal bone loss occurred at the proximal radius after 4.3 years

    Supramolecular Toxin Complexes for Targeted Pharmacological Modulation of Polymorphonuclear Leukocyte Functions

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    The targeted pharmacological modulation of polymorphonuclear leukocytes (PMNs) is of major medical interest. These innate immune cells play a central role in the defense against pathogenic microorganisms. However, their excessive chemotactic recruitment into tissues after traumatic injury is detrimental due to local and systemic inflammation. Rho-GTPases, being the master regulators of the actin cytoskeleton, regulate migration and chemotaxis of PMNs, are attractive pharmacological targets. Herein, supramolecular protein complexes are assembled in a “mix-and-match” approach containing the specific Rho-inhibiting clostridial C3 enzyme and three PMN-binding peptides using an avidin platform. Selective delivery of the C3 Rho-inhibitor with these complexes into the cytosol of human neutrophil-like NB-4 cells and primary human PMNs ex vivo is demonstrated, where they catalyze the adenosine diphosphate (ADP) ribosylation of Rho and induce a characteristic change in cell morphology. Notably, the complexes do not deliver C3 enzyme into human lung epithelial cells, A549 lung cancer cells, and immortalized human alveolar epithelial cells (hAELVi), demonstrating their cell type-selectivity. The supramolecular complexes represent attractive molecular tools to decipher the role of PMNs in infection and inflammation or for the development of novel therapeutic approaches for diseases that are associated with hyperactivity and reactivity of PMNs such as post-traumatic injury

    Antibodies to Serine Proteases in the Antiphospholipid Syndrome

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    It is generally accepted that the major autoantigen for antiphospholipid antibodies (aPL) in the antiphospholipid syndrome (APS) is β2-glycoprotein I (β2GPI). However, a recent study has revealed that some aPL bind to certain conformational epitope(s) on β2GPI shared by the homologous enzymatic domains of several serine proteases involved in hemostasis and fibrinolysis. Importantly, some serine protease–reactive aPL correspondingly hinder anticoagulant regulation and resolution of clots. These results extend several early findings of aPL binding to other coagulation factors and provide a new perspective about some aPL in terms of binding specificities and related functional properties in promoting thrombosis. Moreover, a recent immunological and pathological study of a panel of human IgG monoclonal aPL showed that aPL with strong binding to thrombin promote in vivo venous thrombosis and leukocyte adherence, suggesting that aPL reactivity with thrombin may be a good predictor for pathogenic potentials of aPL

    Somatic mosaicism in neuronal precursor cells mediated by L1 retrotransposition

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    Revealing the mechanisms for neuronal somatic diversification remains a central challenge for understanding individual differences in brain organization and function. Here we show that an engineered human LINE-1 (for long interspersed nuclear element-1; also known as L1) element can retrotranspose in neuronal precursors derived from rat hippocampus neural stem cells. The resulting retrotransposition events can alter the expression of neuronal genes, which, in turn, can influence neuronal cell fate in vitro. We further show that retrotransposition of a human L1 in transgenic mice results in neuronal somatic mosaicism. The molecular mechanism of action is probably mediated through Sox2, because a decrease in Sox2 expression during the early stages of neuronal differentiation is correlated with increases in both L1 transcription and retrotransposition. Our data therefore indicate that neuronal genomes might not be static, but some might be mosaic because of de novo L1 retrotransposition events.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62714/1/nature03663.pd
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