julilili42/papers huggingface dataset:
Platelet Glycoprotein VI: A Novel Marker for Acute Coronary Syndrome
2007-03-01

The platelet collagen receptor glycoprotein (GP) VI is critical for the formation of arterial thrombosis. GPVI platelet surface expression was examined in patients with stable angina and in patients with acute coronary syndrome (ACS). Surface expression of platelet activation markers such as P-selectin, GPIbalpha, and platelet GPVI was determined by flow cytometry. Patients with ACS showed a significantly enhanced GPVI expression compared with patients with stable angina and healthy controls. The expression of GPVI correlated well with CD62P. Elevated platelet GPVI expression was associated with ACS independent of markers of myocardial necrosis such as troponin and creatine kinase. In ACS, platelet surface GPVI expression was already elevated several hours before troponin and creatine kinase indicated myocardial injury. We conclude that the determination of the platelet-specific thrombotic marker GPVI may help to identify patients at risk before myocardial ischemia is evident.
Prediction Error of the Chain Ladder Reserving Method applied to Correlated Run-off Triangles
2007-03-01

ABSTRACT In Buchwalder et al . (2006) we revisited Mack's (1993) and Murphy's (1994) estimates for the mean square error of prediction (MSEP) of the chain ladder claims reserving method. This was done using a time series model for the chain ladder method. In this paper we extend the time series model to determine an estimate for the MSEP of a portfolio of N correlated run-off triangles. This estimate differs in the special case N = 2 from the estimate given by Braun (2004). We discuss the differences between the estimates.
Experimental studies of nuclear fission dynamics near the scission point
2007-03-01

Conditions for formation of angular and energy distributions of light particles emitted in ternary fission of 233, 235U, 239Pu, and 245Cm nuclei induced by cold polarized neutrons have been studied in the course of investigating T-odd asymmetry in emission of these particles with respect to the plane formed by the fission axis and the polarization axis of the fissioning nucleus. The results obtained lead to the conclusion that in ternary fission charged particles are emitted by the fissioning nuclear system rotating around the polarization direction.
In vitrometabolite identification of ML3403, a 4-pyridinylimidazole-type p38 MAP kinase inhibitor by LC-Qq-TOF-MS and LC-SPE-cryo-NMR/MS
2007-03-01

Prediction of the metabolic profile of a potential new drug is recommended at an early stage in industrial drug discovery process to determine whether or not any potentially reactive or toxic metabolites are formed. In the present study, we investigated the in vitro metabolism of ML3403 ({4- [5-(4-Fluorophenyl)-2-methylsulfanyl-3H-imidazol-4-yl]-pyridin-2-yl -(1-phenylethyl)-amine), a potent and selective p38 MAP kinase inhibitor using mouse liver microsomes. The combination of LC-ESI-Qq-TOF (tandem quadrupole time-of-flight)-MS (mass spectrometer) and LC-SPE (solid phase extraction)-cryo-NMR (nuclear magnetic resonance)/MS at 600 MHz has been applied for comprehensive and straightforward structural elucidation of ML3403 metabolites. It was possible to determine the metabolic profile of ML3403, revealing eight different metabolites formed by N-desalkylation, S-mono- and di-oxidation, aliphatic hydroxylation and pyridine-N-oxidation. The ESI-Qq-TOF-MS data yielded elemental compositions of all metabolites and their fragments by evaluation of the accurate mass and isotopic pattern information using the sigma-fit algorithm. Evaluation of 2D NMR spectra obtained from pure ML3403 an its major metabolite ML3603 allowed the unequivocal assignment of the resonances in 1D NMR spectra obtained directly from the microsomal incubation by LC-SPE-cryo-NMR/MS. The presented method significantly decreases the time required for a complete structural assignment of metabolites from microsomal in vitro assays.
In vitro photodynamic therapy of childhood rhabdomyosarcoma
2007-03-01

Treatment of childhood rhabdomyosarcoma is limited by recurrent disease and the development of multidrug resistance. Therefore, novel treatment options are desirable. Photodynamic therapy (PDT) using the photodynamic agent hypericin is proposed as an alternative approach for intraoperative visualization and treatment of this disease. The aim of this study was to investigate in vitro effects of hypericin on childhood rhabdomyosarcoma and to evaluate photodynamic therapy as a possible basis for treatment. Rhabdomyosarcoma cells and fibroblasts (control) were incubated with increasing concentrations of hypericin. in vitro uptake and visualization of hypericin was evaluated by fluorescence microscopy and FACS. For photodynamic therapy, cells were exposed to white light for different time periods. Cytopathologic effects were assessed using standard histology. Cancer cells were investigated for cell viability (MTT assay), proliferative activity (Ki-67 assay), and apoptosis (TUNEL test). A 100% uptake of hypericin was found within the population of rhabdomyosarcoma cells. Uptake of hypericin in the fibroblasts was much less than in rhabdomyosarcoma cells. Hypericin without exposure to white light had no effect on tumor cell viability. After irradiation, PDT resulted in a nearly complete inhibition of cell proliferation of rhabdomyosarcoma cells with a corresponding increase in the frequency of apoptosis. In fibroblasts, PDT was less effective compared to tumor cells. Our data suggest hypericin as a novel tool for visualization and photodynamic therapy of childhood rhabdomyosarcoma.
Variable Response to Clopidogrel in Patients with Coronary Artery Disease
2007-03-01

Antiplatelet drug resistance is a multifactorial phenomenon that affects a large number of cardiovascular patients with symptomatic coronary artery disease. Although unique definitions for aspirin and clopidogrel resistance are missing, there is growing evidence for a clinical importance of response to antiplatelet therapy. The prevalence for aspirin and clopidogrel resistance has been reported to be between 5 and 30% in literature. Moreover, recent data suggest a high rate of dual antiplatelet drug resistance. Although there are convincing data about an association of aspirin resistance and clinical outcome, little is known about the clinical relevance of clopidogrel hyporesponsiveness. This article reviews the evidence for the clinical impact of antiplatelet drug resistance, with particular attention on the clinical outcome of clopidogrel low response according to current clinical data. Additional systematic studies are needed to evaluate the effects of alternative antiplatelet therapies in patients identified as low responders.
Improvement of Psychosocial Adjustment to HIV-1 Infection through a Cognitive-Behavioral Oriented Group Psychotherapy Program: A Pilot Study
2007-03-01

The present study evaluated the efficacy of a group therapy program in improving psychosocial adjustment to HIV infection, and tried to identify variables predictive of greater improvement. The outcome of 47 completing patients was analyzed, comparing the measures between T1 (1 month before therapy), and T2 (first session), and between T2 and T3 (last session) using the Wilcoxon matched-pairs signed-ranks test for each dimension of the Psychosocial Adjustment to Illness Scale (PAIS). The therapy consisted of 16 weekly 2-hour sessions following a structured time-limited cognitive-behavioral group psychotherapy program. During the intervention (between T2 and T3) a significant improvement was observed in health care orientation, vocational environment, domestic environment, sexual relation, extended family relationships, social environment, and total PAIS. There were no changes during baseline (between T1 and T2) in any of the PAIS subscales, or in the total PAIS score. Sexual route of transmission was independently associated with an improvement in health care orientation (beta = 2.525). Time since HIV diagnosis (beta = 0.022) and being employed (beta = 2.548) were independently associated with an improvement in adjustment to vocational environment. Men who have sex with men showed a poorer improvement in adjusting to family relations after the intervention (beta = -2.548). Finally, a lower CD4 count (beta = -0.005) and being employed (beta = 3.054) were independently associated with an improvement in adjustment to social environment. Our psychotherapy program improved psychosocial functioning in a heterogeneous sample of HIV-1-infected patients referred to a consultation-liaison psychiatry unit.
H.E.S.S.: Status and future plan
2007-03-01

The H.E.S.S. (High Energy Stereoscopic System) experiment has been in operation in its current set-up since the beginning of 2004. The construction of the extension of H.E.S.S. ("Phase II") has started: A telescope with a mirror surface of 600 m2 in the center of the four existing H.E.S.S. Phase I telescopes This "Large Cherenkov Telescope" (LCT) will operate stand-alone as well as in coincidence together with the Phase I telescopes. The LCT will start triggering on gamma-ray initiated air showers at an energy of 20 GeV. In this contribution, a status of the existing installation and plan for the future will be given.
Noninvasive Plaque Imaging Using Multislice Detector Spiral Computed Tomography
2007-03-01

Multislice detector spiral computed tomography (MSCT) is a noninvasive modality for visualization and evaluation of atherosclerosis in vivo in different arterial beds. Rapid technical advances led to a significant improvement of the diagnostic accuracy of coronary MSCT angiography. The most popular clinical application with best scientific Medical evidence of MSCT is the noninvasive detection and quantification of coronary calcifications. In particular, the concept of determining coronary artery age by evaluating an individual's biological age, rather than his or her chronological age, is attractive and currently under scientific evaluation. In addition to evaluating contrast-enhanced coronary arteries, different stages of atherosclerosis can be visualized. By comparative studies with intracoronary ultrasound, it could be shown that echogenicity corresponds well with the density measured within atherosclerotic plaques expressed by Hounsfield units using MSCT. Although the method is improving continuously and is still under development, the potential of MSCT to evaluate plaque composition and plaque volumes noninvasively in vivo is promising.
Molecular Imaging of Vulnerable Plaque by Cardiac Magnetic Resonance Imaging
2007-03-01

Coronary atherosclerosis is known to be the major cause for morbidity and mortality in the industrial world. In Europe, every year approximately 600,000 persons die from coronary artery disease, a majority of them without any prior symptoms. Plaque rupture, mostly of noncalcified vulnerable plaques, is supposed to play a major role in this setting, and noninvasive techniques are mandatory to stratify the individual risk for experiencing an acute coronary event. During the last decade, magnetic resonance imaging has gained importance as a noninvasive imaging technique in cardiology. Continuous technical improvements enabled a rapidly expanding field of application, and recently noninvasive imaging of plaques has been introduced. In addition to morphological characterization, functional imaging of plaques has gained interest for a more specific risk assessment. This article summarizes pathophysiological aspects of the concept of vulnerable plaque, technical requirements for noninvasive plaque imaging, and characterization with magnetic resonance imaging.
Perfusionists in the world of tissue engineering — a quick and easy method for safe isolation of huge quantities of porcine cardiomyocytes
2007-03-01

Isolation of huge quantities of primary cells from whole organs like the heart becomes increasingly important, especially for the emerging research field of tissue engineering and regenerative medicine. This study deals with the isolation of pig cardiomyocytes, in contrast to the standard mouse or rat models, because we aimed to draw attention to the species, which are genetically more closely related to the human organism. The bigger operative and veterinary expenditure of the pig-heart model can only be justified by a technique that supplies a big amount of qualitative high-grade cardiomyocytes. In our model, the quality is guaranteed by protection of the heart, already in situ, by a cardioplegia and a careful application of collagenase to soften the tissue. The construction of a new apparatus which includes enormous costs was not necessary, since the perfusion equipment was realized from two commercially available HLMsets, which were modified and connected to each other. Our model makes it possible to rinse the whole myocardium, which leads to a better output than models that only prepare a part of the myocardium around a coronary artery. The careful harvesting of high-grade cardiomyocytes is an important source of successful cell cultures to be used for numerous experimental applications, may reduce animal experiments and, additionally, represents a chance for perfusionists to become an important partner in interdisciplinary research projects. Perfusion (2007) 22, 137—142.
Study of Galactic Sources with H.E.S.S.
2007-03-01

The H.E.S.S. imaging air Cherenkov telescope array has performed a blind survey at energies above 100 GeV of parts of the Galactic plane as well as dedicated (deeper) observations of gamma-ray source candidates. New sources including shell type super-nova remnants, pulsar-wind nebulae, binary systems, cosmic ray illuminated molecular clouds, as well as unidentified sources have been found. In this contribution, a selected overview of the recent results focussing on shell type supernova remnants and pulsar wind nebulae is given.
Expression of 3-hydroxyisobutyrate dehydrogenase among neural cells
2007-03-01

Branched-chain amino acids (BCAA) – isoleucine, leucine and valine – belong to a limited group of substances transported through the blood-brain barrier and serving as substrates for meeting brain energy demands. Previous studies have shown the ubiquitous expression of a branched-chain alpha-keto acid dehydrogenase among neural cells. This enzyme catalyzes the initial and rate-limiting step in the irreversible degradative pathway for the carbon skeleton of valine and the other two BCAA. Unlike the acyl-CoA derivates in the irreversible part of valine catabolism, 3-hydroxyisobutyrate can be released from cells by transport across the mitochondrial and plasma membranes. Therefore, to assess the ability of neural cells to make use of this valine derived carbon skeleton as a metabolic substrate, we have investigated the distribution of the enzyme processing this hydroxyl acid, 3-hydroxyisobutyrate dehydrogenase (3-HIBDH), in cultured neural cells. To achieve this, 3-HIBDH has been purified from rat liver to serve as antigen for the production of an antiserum. Affinity purified antibodies against 3-HIBDH specifically recognized the enzyme in liver and brain homogenates. Immunoblotting demonstrated the ubiquitous expression of 3-HIBDH among cultured macroglial (astroglia, oligodendroglia and ependymocytes) and neuronal cells. Furthermore, immunofluorescence doublelabeling of astroglial cells with antisera against 3-HIBDH and the mitochondrial marker pyruvate dehydrogenase localized 3-HIBDH to mitochondria. The expression of 3HIBDH in neural cells demonstrates their ability to engage in the catabolism of valine imported into the brain for generation of energy. from Annual Meeting of the Study Group Neurochemistry. International Conference of the Gesellschaft fur Biochemie und Molekularbiologie 2006 (GBM 2006): Molecular pathways in health and disease of the nervous system Witten, Germany. 28–30 September 2006
(Mis-)Understanding Education Externalities
2007-03-01

This article critically evaluates the current state of research on education externalities. It occurs that much of the confusion regarding their magnitude results from conceptual misunderstandings pertaining to their nature. The essay distinguishes the concepts education, teaching, and knowledge. Whereas pure teaching yields externalities on the primary and secondary level, only the generation of knowledge may produce the spillovers which are typically linked to the tertiary level. The accumulation of education itself does not have such an effect. Education is argued to be a private good with well defined property rights. Individuals may exploit those and provide the production sector with the efficient amount of human capital. Following this rationale, it is demonstrated that empirical studies, contrasting estimations of private and social returns to education, are unsuitable to substantiate the existence of externalities. As a consequence, subsidies to tertiary programs are called into question.
Natural History of Dengue Virus (DENV)–1 and DENV‐4 Infections: Reanalysis of Classic Studies
2007-03-02

Incubation period was negatively correlated with disease severity, potentially reflecting a dose-response mechanism. The historical data provided useful details concerning serotype differences in the natural history of primary DENV infections.
Regulation of NH4 + Transport by Essential Cross Talk between AMT Monomers through the Carboxyl Tails
2007-03-02

Abstract Ammonium transport across plant plasma membranes is facilitated by AMT/Rh-type ammonium transporters (AMTs), which also have homologs in most organisms. In the roots of the plant Arabidopsis (Arabidopsis thaliana), AMTs have been identified that function directly in the high-affinity NH4 + acquisition from soil. Here, we show that AtAMT1;2 has a distinct role, as it is located in the plasma membrane of the root endodermis. AtAMT1;2 functions as a comparatively low-affinity NH4 + transporter. Mutations at the highly conserved carboxyl terminus (C terminus) of AMTs, including one that mimics phosphorylation at a putative phosphorylation site, impair NH4 + transport activity. Coexpressing these mutants along with wild-type AtAMT1;2 substantially reduced the activity of the wild-type transporter. A molecular model of AtAMT1;2 provides a plausible explanation for the dominant inhibition, as the C terminus of one monomer directly contacts the neighboring subunit. It is suggested that part of the cytoplasmic C terminus of a single monomer can gate the AMT trimer. This regulatory mechanism for rapid and efficient inactivation of NH4 + transporters may apply to several AMT members to prevent excess influx of cytotoxic ammonium.
Deficiency of the autoimmune regulator AIRE in thymomas is insufficient to elicit autoimmune polyendocrinopathy syndrome type 1 (APS‐1)
2007-03-02

Abstract Thymomas are thymic epithelial neoplasms, associated with a variety of autoimmune disorders (especially myasthenia gravis), that apparently result from aberrant intra‐tumourous thymopoiesis and export of inefficiently tolerized T‐cells to the periphery. The autoimmune regulator (AIRE) drives the expression of self‐antigens in the thymic medulla and plays an essential role in ‘central’ tolerance in both humans and mice. However, while inactivating AIRE mutations result in the ‘autoimmune polyendocrinopathy syndrome type 1’ (APS‐1), its major features are not well reproduced in AIRE ‐knock‐out mice. Therefore, alternative human disease scenarios with concomitant AIRE deficiency may be valuable tools to test conclusions drawn from mouse models. Here we show, in a large series, that ∼95% of thymoma patients are ‘chimeric’; expression of AIRE and major AIRE‐related autoantigens (eg insulin) were undetectable in their tumours but maintained in their remnant thymic tissue and lymph nodes. Notably, despite the AIRE‐deficient thymopoiesis in thymomas, disorders and autoantibodies typical of APS‐1 were distinctly uncommon in these patients. The one striking similarity was in the recently observed neutralizing anti‐type I interferon (IFN) antibodies, which are found at diagnosis in 100% of patients with APS‐1 and in ∼60% of patients with thymomas, as we show here. We conclude that APS‐1 type autoantigens must be protected from autoimmunity by mechanisms that do not extend to the muscle autoantigens so frequently targeted in thymoma patients but so rarely recognized in APS‐1. Thus our findings argue strongly for a tolerogenic function of AIRE beyond its role in negative T‐cell selection in human thymopoiesis, and/or for specific autoimmunization against muscle in thymomas. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.
Synthesis of Novel Covalently Linked Dimeric Phthalocyanines
2007-03-02

Abstract We report the syntheses of the dimeric homonuclear Pcs 9a and 9b and of the dimeric heteronuclear Pc 9c , starting from the unsymmetrical phthalocyanines 7a and 7b , each containing a phenolic OH group in one of its substituents. Compounds 9a and 9b were obtained by single‐step alkylations of 7a and 7b with 1,6‐dibromohexane or, in better yields, by coupling of Pcs 7a and 7b with the bromoalkyl‐derivatized Pcs 8a and 8b , while 9c was prepared by treatment of 8a with Pc‐Ni complex 7b . The dimeric Pcs 9a – 9c show strong cofacial intramolecular association in solution. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2007)
Steady-State Techniques for Low Sensitivity and Slowly Relaxing Nuclei
2007-03-02

The sections in this article are 1 Introduction 2 Theoretical Analysis of the Steady-State Free Precession Technique 3 Recording of NMR Spectra with the Steady-State Technique 4 Measuring Techniques for Extremely Long Relaxation Times 5 Investigation of Nuclei with Spin–Spin Coupling 6 Biographical Sketch Related Articles
Expression pattern of the water channel aquaporin‐4 in human gliomas is associated with blood–brain barrier disturbance but not with patient survival
2007-03-04

Abstract Aquaporin‐4 (AQP4), the most prominent CNS water channel, is restricted to the glia limitans and astrocytic endfeet. We previously showed the loss of spatial AQP4 expression in glioblastomas and a redistribution across the cell surface. However, opposing AQP4 functions have been described: protective in vasogenic but detrimental in cytotoxic brain edema. Thus, specific AQP4 induction to prevent or reduce vasogenic edema is suggested. To elucidate the AQP4 role in brain tumors, we investigated 189 WHO grade I–IV gliomas by immunohistochemistry and the prognostic significance for patients' survival. In gliomas, a remarkable de novo AQP4 redistribution was observed in comparison with normal CNS tissue. Surprisingly, the highest membraneous staining levels were seen in pilocytic astrocytomas WHO grade I and grade IV glioblastomas, both significantly higher than in WHO grade II astrocytomas. AQP4 up‐regulation was associated with brain edema formation; however, no association between survival and WHO grade‐dependent AQP4 expression was seen. Hence, AQP4 redistribution may go along with other tumor properties, such as vascular proliferation and resulting blood–brain barrier disturbance, features usually prominent in pilocytic astrocytomas WHO I and glioblastomas WHO grade IV. In summary, our findings question the protective role of AQP4 in vasogenic brain edema. Although AQP4 was associated with brain edema formation, one has to question the suitability of AQP4 induction as a promising approach in vasogenic brain edema prevention and treatment. In addition, our results provide unexpectedly high AQP4 levels in pilocytic astrocytomas and present AQP4 as tumor progression marker in WHO grade II–IV astrocytomas. © 2007 Wiley‐Liss, Inc.