711 research outputs found
Does text structure/summarization instruction facilitate learning from expository text?
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
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
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
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.
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.
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
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
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
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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