julilili42/papers huggingface dataset:
Low Responsiveness to Clopidogrel Increases Risk among CKD Patients Undergoing Coronary Intervention
2011-01-28

Patients with CKD are at higher risk for major events after percutaneous coronary intervention (PCI) compared with subjects with normal renal function. The aims of this study were to evaluate responsiveness to clopidogrel in patients with CKD and to examine the effect of antiplatelet drug response on post-PCI outcome. We retrospectively evaluated a consecutive cohort of 1567 patients with symptomatic coronary artery disease undergoing PCI, 648 (41%) of whom had stage 3 to 5 CKD. We assessed responsiveness to clopidogrel by ADP-induced platelet aggregation after oral administration of a 600-mg clopidogrel loading dose and 100 mg of aspirin. In a multivariate survival analysis that included 1335 (85%) of the cohort, stage 3 to 5 CKD and low response to clopidogrel were independent predictors of the primary end point (composite of myocardial infarction, ischemic stroke, and death within 1 year). In summary, a low response to clopidogrel might be an additional risk factor for the poorer outcomes in patients with stage 3 to 5 CKD compared with patients with better renal function.
Staphylococcus aureus α-Toxin Triggers the Synthesis of B-Cell Lymphoma 3 by Human Platelets
2011-01-28

The frequency and severity of bacteremic infections has increased over the last decade and bacterial endovascular infections (i.e., sepsis or endocarditis) are associated with high morbidity and mortality. Bacteria or secreted bacterial products modulate platelet function and, as a result, affect platelet accumulation at sites of vascular infection and inflammation. However, whether bacterial products regulate synthetic events in platelets is not known. In the present study, we determined if prolonged contact with staphylococcal α-toxin signals platelets to synthesize B-cell lymphoma (Bcl-3), a protein that regulates clot retraction in murine and human platelets. We show that α-toxin induced αIIbβ3-dependent aggregation (EC50 2.98 μg/mL ± 0.64 μg/mL) and, over time, significantly altered platelet morphology and stimulated de novo accumulation of Bcl-3 protein in platelets. Adherence to collagen or fibrinogen also increased the expression of Bcl-3 protein by platelets. α-toxin altered Bcl-3 protein expression patterns in platelets adherent to collagen, but not fibrinogen. Pretreatment of platelets with inhibitors of protein synthesis or the mammalian Target of Rapamycin (mTOR) decreased Bcl-3 protein expression in α-toxin stimulated platelets. In conclusion, Staphylococcus aureus-derived α-toxin, a pore forming exotoxin, exerts immediate (i.e., aggregation) and prolonged (i.e., protein synthesis) responses in platelets, which may contribute to increased thrombotic events associated with gram-positive sepsis or endocarditis.
A hospital-initiated multisectoral road safety campaign with speed-adapted coconut drop test in Northern Laos
2011-01-28

We investigate the efficacy of a multisectoral road safety campaign initiated at Luang Namtha Provincial Hospital (LNPH), North-Laos. Road safety days (RSD) with helmet promotion were organised prior to the Lao and International New Year 2007. Motorbike helmet protectiveness was demonstrated by dropping peeled versus unpeeled coconuts from 6-m high sticks simulating city speed-limit (40 km/h). The primary outcome was the number of road traffic injuries (RTI) needing admission (severe RTI) before and after the first RSD. Secondary outcomes were helmet usage, total RTI, hospital staff's behavioural changes and law enforcement. Neighbouring Bokeo Provincial Hospital (BPH) had no intervention. Severe RTI dropped by 34.7% within 12 months (from 449 to 293, p ≤ 0.0001, BPH +123% [from 88 to 196]). Total RTI increased by 10.8% (from 772 to 855, p = 0.0396, BPH +260.8% [from 186 to 671]). Police started the law enforcement right after the RSD. Helmet use increased from 11.2 to 42.5% (p < 0.0001). Coconut test was the main reason for safer behaviour among RSD participants seven months later (16/32). The intervention effectively prevented severe RTI. The speed-adapted coconut drop test was a simple, convincing and efficient educational tool, easily adaptable to other settings.
Expression of C-Kit and its Ligand SCF in Primary Uveal Melanoma
2011-01-28

Purpose To evaluate the concurrent rate of expression of c-Kit and its ligand stem cell factor (SCF) in uveal melanoma in respect to the further clinical course and the correlation of these markers. Methods Paraffin sections from 35 primary uveal melanomas were evaluated immunohistochemically for the expression of c-Kit and SCF. Sixteen cases developed systemic metastasis during the follow-up (median: 5 years after diagnosis). The patients who did not develop metastasis (n=19) had a mean follow-up of 10.6 (9–13) years. Radiation was performed in 6 patients. Results c-Kit and SCF were expressed in all patients who did or did not develop metastasis in the further clinical course. A mean SCF expression of 77.2% (range 52.7%-97.5%) of tumors that did not develop systemic metastasis and 30.1 % (range 2.9%-61.5%) of tumors with systemic metastasis were evident. Uveal melanomas revealing an increased SCF expression were found to develop no metastasis more frequently (p&lt;0.0001; hazard ratio (HR)=0.963, 95% confidence interval (CI) 0.945–0.981). A mean c-Kit expression of 58.01% (range 5.9%-97.9%) in the group who did not develop metastasis and 48.9% (range 5.0%-95.9%) in the group with systemic metastasis were observed. c-Kit expression was not associated with increased rates of metastasis formation (p=0.7329; HR=0.997, 95% CI 0.982–1.013). The correlation between SCF and c-Kit is weak (0.39; 95% CI 0.06–0.63). Conclusions c-Kit expression was not found to be associated with metastasis formation. A high SCF expression of primary choroidal melanomas was significantly associated with a lower incidence of systemic metastasis, which indicated SCF as a benign prognostic factor in the further clinical course.
Atypical teratoid/rhabdoid tumors may show morphological and immunohistochemical features seen in choroid plexus tumors
2011-01-30

Atypical teratoid/rhabdoid tumors (AT/RT) are aggressive embryonal tumors having a poor prognosis and are associated with mutations in the tumor suppressor gene hSNF5 /SMARCB1/INI1. Differential diagnosis includes choroid plexus carcinoma which has occasionally been attributed as showing an inactivation of INI1/SMARCB1 nuclear staining in immunohistochemistry. However, these findings have been challenged by others. We therefore examined eight AT/RTs from six patients by immunohistochemistry for membranous expression of the inward rectifier potassium channel Kir7.1, which was in the central nervous system so far considered specific for choroid plexus tumors and normal choroid plexus epithelium. Two AT/RT cases exhibited membranous staining of Kir7.1, indicating a plexus epithelial differentiation of these tumors. The implications of these results on tumor diagnosis are discussed.
Structural Fine-Tuning of a Multifunctional Cytochrome P450 Monooxygenase
2011-01-31

AurH is a unique cytochrome P450 monooxygenase catalyzing the stepwise formation of a homochiral oxygen heterocycle, a key structural and pharmacophoric component of the antibiotic aureothin. The exceptional enzymatic reaction involves a tandem oxygenation process including a regio- and stereospecific hydroxylation, followed by heterocyclization. For the structural and biochemical basis of this unparalleled sequence, four crystal structures of AurH variants in different conformational states and in complex with the P450 inhibitor ancymidol were solved, which represent the first structures of the CYP151A group. Structural data in conjunction with computational docking, site-directed mutagenesis, and chemical analyses unveiled a switch function when recognizing the two substrates, deoxyaureothin and the hydroxylated intermediate, thus allowing the second oxygenation-heterocyclization step. Furthermore, we were able to modify the chemo- and regioselectivity of AurH, yielding mutants that catalyze the regioselective six-electron transfer of a nonactivated methyl group to a carboxylic acid via hydroxyl and aldehyde intermediates.
Isotope-shift measurements of stable and short-lived lithium isotopes for nuclear-charge-radii determination
2011-01-31

Changes in the mean square nuclear charge radii along the lithium isotopic chain were determined using a combination of precise isotope shift measurements and theoretical atomic structure calculations. Nuclear charge radii of light elements are of high interest due to the appearance of the nuclear halo phenomenon in this region of the nuclear chart. During the past years we have developed a laser spectroscopic approach to determine the charge radii of lithium isotopes which combines high sensitivity, speed, and accuracy to measure the extremely small field shift of an 8-ms-lifetime isotope with production rates on the order of only 10 000 atoms/s. The method was applied to all bound isotopes of lithium including the two-neutron halo isotope Li11 at the on-line isotope separators at GSI, Darmstadt, Germany, and at TRIUMF, Vancouver, Canada. We describe the laser spectroscopic method in detail, present updated and improved values from theory and experiment, and discuss the results. © 2011 American Physical Society.
nocoRNAc: Characterization of non-coding RNAs in prokaryotes
2011-01-31

We have developed NOCORNAc, a framework that facilitates the automated characterization of functional ncRNAs. NOCORNAc increases the confidence of predicted ncRNA loci, especially if they contain transcribed ncRNAs. NOCORNAc is not restricted to intergenic regions, but it is applicable to the prediction of ncRNA transcripts in whole microbial genomes. The software as well as a user guide and example data is available at http://www.zbit.uni-tuebingen.de/pas/nocornac.htm.
Prenatal evaluation of the position of the fetal conus medullaris
2011-01-31

Abstract Objectives To determine the position of the fetal conus medullaris during pregnancy in relation to the last vertebral body and to examine its use in detecting skin‐covered spinal dysraphism. Methods This was a retrospective study involving 300 consecutive ultrasound examinations between 15 weeks of gestation and term. Two operators independently assessed images of the spine to determine whether the conus medullaris and the last vertebral body could be visualized in a single image in a midsagittal plane. The distance between these two landmarks (the conus distance) was measured twice by both operators who were not aware of any previous measurements. Intra‐ and interobserver variability was assessed by 95% limits of agreement. Linear regression analysis was used to determine the relevant contributors to the conus distance and a normal range was computed based on the best‐fit model. The normal results were compared with five cases of prenatally detected skin‐covered spinal dysraphism. Results In 84.7% of the 300 cases, both operators were able to visualize the conus medullaris and the last vertebral body. Ninety‐five percent limits of agreement for the intraobserver variability in measurement of conus distance were ± 1.9 mm. For the interobserver variability, they were − 3.7 and 2.5 mm. We found a linear relationship between conus distance and gestational age, biparietal diameter and abdominal circumference. The strongest relationship was observed for femur length ( conusdistance = − 8.2 + femur length (mm)). In the five abnormal cases, conus distance was well below the 5 th percentile. Conclusions Determination of conus distance allows for an objective and feasible assessment of the conus medullaris position. This parameter promises to be useful in the prenatal detection of skin‐covered spinal dysraphism. Copyright © 2011 ISUOG. Published by John Wiley &amp; Sons, Ltd.
Mayday SeaSight: Combined Analysis of Deep Sequencing and Microarray Data
2011-01-31

Recently emerged deep sequencing technologies offer new high-throughput methods to quantify gene expression, epigenetic modifications and DNA-protein binding. From a computational point of view, the data is very different from that produced by the already established microarray technology, providing a new perspective on the samples under study and complementing microarray gene expression data. Software offering the integrated analysis of data from different technologies is of growing importance as new data emerge in systems biology studies. Mayday is an extensible platform for visual data exploration and interactive analysis and provides many methods for dissecting complex transcriptome datasets. We present Mayday SeaSight, an extension that allows to integrate data from different platforms such as deep sequencing and microarrays. It offers methods for computing expression values from mapped reads and raw microarray data, background correction and normalization and linking microarray probes to genomic coordinates. It is now possible to use Mayday's wealth of methods to analyze sequencing data and to combine data from different technologies in one analysis.
A novel clinical syndrome revealing a deficiency of the muscarinic M3 receptor
2011-01-31

The presented clinical syndrome suggests a deficiency of the muscarinic M3 receptor. These results and future evaluation of patients with autonomic deficits may provide insights into the site and functional role of the muscarinic M3 receptor in humans.
Modeling and Benchmark Data Set for the Inhibition of c-Jun N-terminal Kinase-3
2011-01-31

The goal of this paper is to present and describe a novel 2D- and 3D-QSAR (quantitative structure-activity relationship) binary classification data set for the inhibition of c-Jun N-terminal kinase-3 with previously unpublished activities for a diverse set of compounds. JNK3 is an important pharmaceutical target because it is involved in many neurological disorders. Accordingly, the development of JNK3 inhibitors has gained increasing interest. 2D and 3D versions of the data set were used, consisting of 313 (70 actives) and 249 (60 actives) compounds, respectively. All compounds, for which activity was only determined for the racemate, were removed from the 3D data set. We investigated the diversity of the data sets by an agglomerative clustering with feature trees and show that the data set contains several different scaffolds. Furthermore, we show that the benchmarks can be tackled with standard supervised learning algorithms with a convincing performance. For the 2D problem, a random decision forest classifier achieves a Matthew's correlation coefficient of 0.744, the 3D problem could be modeled with a Matthew's correlation coefficient of 0.524 with 3D pharmacophores and a support vector machine. The performance of both data sets was evaluated within a nested 10-fold cross-validation. We therefore suggest that the data set is a reasonable basis for generating QSAR models for JNK3 because of its diverse composition and the performance of the classifiers presented in this study.
ClC-2 Channels in Erythrocytes
2011-01-31

ClC-2 is a ubiquitously expressed plasma membrane Cl- channel that reportedly controls the ionic environment in mouse retina and testis. Beyond that, ClC-2 might sense cellular energy status and cellular stress by its carboxyterminal cystathionine-beta-synthase (CBS) domains and by its molecular interaction with the heat shock protein Hsp90, respectively. In mature human and mouse erythrocytes, ClC-2 is activated by oxidative stress and by malaria infection. This article describes possible function of erythrocyte ClC-2 channels for the programmed death of oxidatively injured erythrocytes and for the regulatory volume decrease of malaria-infected erythrocytes.
Therapeutic Efficacy of Intranasally Delivered Mesenchymal Stem Cells in a Rat Model of Parkinson Disease
2011-02-01

Safe and effective cell delivery remains one of the main challenges in cell-based therapy of neurodegenerative disorders. Graft survival, sufficient enrichment of therapeutic cells in the brain, and avoidance of their distribution throughout the peripheral organs are greatly influenced by the method of delivery. Here we demonstrate for the first time noninvasive intranasal (IN) delivery of mesenchymal stem cells (MSCs) to the brains of unilaterally 6-hydroxydopamine (6-OHDA)–lesioned rats. IN application (INA) of MSCs resulted in the appearance of cells in the olfactory bulb, cortex, hippocampus, striatum, cerebellum, brainstem, and spinal cord. Out of 1 × 10 6 MSCs applied intranasally, 24% survived for at least 4.5 months in the brains of 6-OHDA rats as assessed by quantification of enhanced green fluorescent protein (EGFP) DNA. Quantification of proliferating cell nuclear antigen-positive EGFP-MSCs showed that 3% of applied MSCs were proliferative 4.5 months after application. INA of MSCs increased the tyrosine hydroxylase level in the lesioned ipsilateral striatum and substantia nigra, and completely eliminated the 6-OHDA–induced increase in terminal deoxynucleotidyl transferase (TdT)-mediated 2′-deoxyuridine, 5′-triphosphate (dUTP)-biotin nick end labeling (TUNEL) staining of these areas. INA of EGFP-labeled MSCs prevented any decrease in the dopamine level in the lesioned hemisphere, whereas the lesioned side of the control animals revealed significantly lower levels of dopamine 4.5 months after 6-OHDA treatment. Behavioral analyses revealed significant and substantial improvement of motor function of the Parkinsonian forepaw to up to 68% of the normal value 40–110 days after INA of 1 × 10 6 cells. MSC-INA decreased the concentrations of inflammatory cytokines—interleukin-1 β (IL-1 β ), IL-2, -6, -12, tumor necrosis factor (TNF), interferon-γ (IFN-γ, and granulocyte-macrophage colony-stimulating factor (GM-CSF)—in the lesioned side to their levels in the intact hemisphere. IN administration provides a highly promising noninvasive alternative to the traumatic surgical procedure of transplantation and allows targeted delivery of cells to the brain with the option of chronic application.
The compositional variability of eudialyte-group minerals
2011-02-01

Abstract Eudialyte-group minerals (EGM) represent the most important index minerals of persodic agpaitic systems. Results are presented here of a combined EPMA, Mössbauer spectroscopy and LA-ICP-MS study and EGM which crystallized in various fractionation stages from different parental melts and mineral assemblages in silica over- and undersaturated systems are compared. Compositional variability is closely related to texture, allowing for reconstruction of locally acting magmatic to hydrothermal processes. Early-magmatic EGM are invariably dominated by Fe whereas hydrothermal EGM can be virtually Fe-free and form pure Mn end-members. Hence the Mn/Fe ratio is the most suitable fractionation indicator, although crystal chemistry effects and co-crystallizing phases play a secondary role in the incorporation of Fe and Mn into EGM. Mössbauer spectroscopy of EGM from three selected occurrences indicates the Fe 3+ /ΣFe ratio to be governed by the hydration state of EGM rather than by the oxygen fugacity of the coexisting melt. Negative Eu anomalies are restricted to EGM that crystallized from alkali basaltic parental melts while EGM from nephelinitic parental melts invariably lack negative Eu anomalies. Even after extensive differentiation intervals, EGM reflect properties of their respective parental melts and the fractionation of plagioclase and other minerals such as Fe-Ti oxides, amphibole and sulphides.
Transverse mixing of conservative and reactive tracers in porous media: Quantification through the concepts of flux‐related and critical dilution indices
2011-02-01

The correct quantification of mixing is of utmost importance for modeling reactive transport in porous media and for assessing the fate and transport of contaminants in the subsurface. An appropriate measure of mixing in heterogeneous porous formations should correctly capture the effects on mixing intensity of various processes at different scales, such as local dispersion and the mixing enhancement due to heterogeneities. In this work, we use the concept of flux‐related dilution index as a measure of transverse mixing. This quantity expresses the dilution of the mass flux of a conservative tracer solution over the total discharge of the system, and is particularly suited to address problems where a compound is continuously injected into the domain. We focus our attention on two‐dimensional systems under steady state flow conditions and investigate both conservative and reactive transport in homogeneous and heterogeneous porous media at different scales. For mixing‐controlled reactive systems, we introduce and illustrate the concept of critical dilution index, which represents the amount of mixing required for complete degradation of a continuously emitted plume undergoing decay upon mixing with ambient water. We perform two‐dimensional numerical experiments at bench and field scales in homogeneous and heterogeneous conductivity fields. These numerical simulations show that the flux‐related dilution index quantifies mixing and that the concept of critical dilution index is a useful measure to relate the mixing of conservative tracers to mixing‐controlled degradation of reactive compounds.
Cyclin D1 positive diffuse large B-cell lymphoma is a post-germinal center-type lymphoma without alterations in theCCND1gene locus
2011-02-01

The aims of this study were to analyze the incidence and morphology of cyclin D1+ DLBCL and cases of Richter transformation (RT), and to elucidate possible molecular mechanisms of cyclin D1 overexpression. Seventy-two cases of de novo DLBCL and 12 cases of RT were included in this study. Cyclin D1 positivity was found in 10/66 (15%) cases of unselected de novo DLBCL and in 2/11 (18%) cases of RT. Seven independently identified cases of cyclin D1+ DLBCL, including one RT, were added to the study. Centroblastic morphology was found in 17/19 (89%) cases of cyclin D1+, most with a post-germinal center phenotype (CD10-, BCL6+, MUM1+). No alterations in the CCND1 gene indicative for a translocation t(11;14) were identified by FISH. Analysis of the MYC locus yielded gene copy alterations in five cases and no disruption of the gene locus in any case, suggesting an alternative mechanism of cyclin D1 deregulation.
Field-scale geometries of Upper Khuff reservoir geobodies in an outcrop analogue (Oman Mountains, Sultanate of Oman)
2011-02-01

ABSTRACT This paper provides data on the lateral continuity and geometry of potential reservoir geobodies in outcrops of Upper Khuff Formation time-equivalent strata in the Jebel Al Akhdar area (Oman Mountains, Sultanate of Oman). It presents outcrop-based quantitative data of shoal-associated grainstone bodies in a sequence stratigraphic framework on the scale of an average Khuff gas field. Such data may be useful for correlation and modelling of subsurface reservoirs. A stratigraphic correlation of five outcrop sections, based on facies, sequence analysis and gamma-ray pattern, was used as a framework for mapping the distribution and lateral extent of grainstone geobodies over an area of 8 × 8 km. Four grainstone bodies were traced laterally along distinct marker beds over several hundreds of metres. The stratigraphic architecture shows a general layer-cake pattern. The thickness and lateral extent of reservoir geobodies is strongly influenced by their stratigraphic position. High-energy shoal facies developed preferentially in the regressive parts of cycles of multiple hierarchies. Individual grainstone bodies may reach a thickness of 6 m, and those thicker than 3 m extend across the area of interest. Clinoforms or shingle-type geometries were explicitly searched for, but were not present. The observed systematic variations in extent and two-dimensional sedimentary architecture of Khuff grainstone bodies were used as input for 3D static facies modelling. Outcomes of this study have been used to reduce uncertainty on grainstone geometries, production-scale correlation strategies and definition of lateral facies successions in subsurface models of the Khuff reservoir.