100 research outputs found

    Auf neue Herausforderungen professionell reagieren : Entwicklung eines Auskunftsdienstkonzeptes f√ľr √∂ffentliche Bibliotheken

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    Gegenstand der hier vorgestellten Arbeit ist die Entwicklung eines schriftlichen Auskunftsdienstkonzeptes f√ľr √Ėffentliche Bibliotheken. Zu Beginn wird ein √úberblick √ľber die Ausgangssituation gegeben und die Funktion solcher Konzepte erl√§utert. Anhand von amerikanischen Beispielen werden m√∂gliche Inhalte dargestellt und eine Einteilung des Konzeptes in Grundelemente vorgenommen. Die Arbeit zeigt mit Hilfe eines Leitfadens wie ein Auskunftsdienstkonzept von der Planung √ľber die Ist-Analyse bis zur Festlegung der Inhalte entwickelt werden kann. Anschlie√üend wird dargelegt, welche Faktoren zur erfolgreichen Umsetzung des Konzeptes geh√∂ren. Ein konkretes Beispiel aus der Praxis liefert die Konzeption f√ľr den Auskunftsdienst der Stadtbibliothek Reutlingen. Es wird √ľberdies aufgezeigt, dass ein derartiges Konzept zur Aufwertung des Auskunftsdienstes beitragen kann

    Highly efficient concentration of lenti- and retroviral vector preparations by membrane adsorbers and ultrafiltration

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    <p>Abstract</p> <p>Background</p> <p>Lentiviral vectors (LVs) can efficiently transduce a broad spectrum of cells and tissues, including dividing and non-dividing cells. So far the most widely used method for concentration of lentiviral particles is ultracentrifugation (UC).</p> <p>An important feature of vectors derived from lentiviruses and prototypic gamma-retroviruses is that the host range can be altered by pseudotypisation. The most commonly used envelope protein for pseudotyping is the glycoprotein of the Vesicular Stomatitis Virus (VSV.G), which is also essential for successful concentration using UC.</p> <p>Results</p> <p>Here, we describe a purification method that is based on membrane adsorbers (MAs). Viral particles are efficiently retained by the anionic exchange MAs and can be eluted with a high-salt buffer. Buffer exchange and concentration is then performed by utilizing ultrafiltration (UF) units of distinct molecular weight cut off (MWCO). With this combined approach similar biological titers as UC can be achieved (2 to 5 √ó 10<sup>9 </sup>infectious particles (IP)/ml). Lentiviral particles from small starting volumes (e.g. 40 ml) as well as large volumes (up to 1,000 ml) cell culture supernatant (SN) can be purified. Apart from LVs, vectors derived from oncoretroviruses can be efficiently concentrated as well. Importantly, the use of the system is not confined to VSV.G pseudotyped lenti- and retroviral particles and other pseudotypes can also be purified.</p> <p>Conclusions</p> <p>Taken together the method presented here offers an efficient alternative for the concentration of lenti- as well as retroviral vectors with different pseudotypes that needs no expensive equipment, is easy to handle and can be used to purify large quantities of viral vectors within a short time.</p

    Deletion of the Ca2+-activated potassium (BK) alpha-subunit but not the BK-beta-1-subunit leads to progressive hearing loss

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    The large conductance voltage- and Ca2+-activated potassium (BK) channel has been suggested to play an important role in the signal transduction process of cochlear inner hair cells. BK channels have been shown to be composed of the pore-forming alpha-subunit coexpressed with the auxiliary beta-1-subunit. Analyzing the hearing function and cochlear phenotype of BK channel alpha-(BKalpha‚Äď/‚Äď) and beta-1-subunit (BKbeta-1‚Äď/‚Äď) knockout mice, we demonstrate normal hearing function and cochlear structure of BKbeta-1‚Äď/‚Äď mice. During the first 4 postnatal weeks also, BKalpha‚Äď/‚Äď mice most surprisingly did not show any obvious hearing deficits. High-frequency hearing loss developed in BKalpha‚Äď/‚Äď mice only from ca. 8 weeks postnatally onward and was accompanied by a lack of distortion product otoacoustic emissions, suggesting outer hair cell (OHC) dysfunction. Hearing loss was linked to a loss of the KCNQ4 potassium channel in membranes of OHCs in the basal and midbasal cochlear turn, preceding hair cell degeneration and leading to a similar phenotype as elicited by pharmacologic blockade of KCNQ4 channels. Although the actual link between BK gene deletion, loss of KCNQ4 in OHCs, and OHC degeneration requires further investigation, data already suggest human BK-coding slo1 gene mutation as a susceptibility factor for progressive deafness, similar to KCNQ4 potassium channel mutations. ¬© 2004, The National Academy of Sciences. Freely available online through the PNAS open access option

    Cognitive behavioural therapy versus supportive therapy for persistent positive symptoms in psychotic disorders: The POSITIVE Study, a multicenter, prospective, single-blind, randomised controlled clinical trial

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    Background: It has been demonstrated that cognitive behavioural therapy (CBT) has a moderate effect on symptom reduction and on general well being of patients suffering from psychosis. However, questions regarding the specific efficacy of CBT, the treatment safety, the cost-effectiveness, and the moderators and mediators of treatment effects are still a major issue. The major objective of this trial is to investigate whether CBT is specifically efficacious in reducing positive symptoms when compared with non-specific supportive therapy (ST) which does not implement CBT-techniques but provides comparable therapeutic attention. Methods: The POSITIVE study is a multicenter, prospective, single-blind, parallel group, randomised clinical trial, comparing CBT and ST with respect to the efficacy in reducing positive symptoms in psychotic disorders. CBT as well as ST consist of 20 sessions altogether, 165 participants receiving CBT and 165 participants receiving ST. Major methodological aspects of the study are systematic recruitment, explicit inclusion criteria, reliability checks of assessments with control for rater shift, analysis by intention to treat, data management using remote data entry, measures of quality assurance (e.g. on-site monitoring with source data verification, regular query process), advanced statistical analysis, manualized treatment, checks of adherence and competence of therapists. Research relating the psychotherapy process with outcome, neurobiological research addressing basic questions of delusion formation using fMRI and neuropsychological assessment and treatment research investigating adaptations of CBT for adolescents is combined in this network. Problems of transfer into routine clinical care will be identified and addressed by a project focusing on cost efficiency. Discussion: This clinical trial is part of efforts to intensify psychotherapy research in the field of psychosis in Germany, to contribute to the international discussion on psychotherapy in psychotic disorders, and to help implement psychotherapy in routine care. Furthermore, the study will allow drawing conclusions about the mediators of treatment effects of CBT of psychotic disorders. Trial Registration Current Controlled Trials ISRCTN2924287

    Altered Error Processing following Vascular Thalamic Damage: Evidence from an Antisaccade Task

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    Event-related potentials (ERP) research has identified a negative deflection within about 100 to 150 ms after an erroneous response ‚Äď the error-related negativity (ERN) - as a correlate of awareness-independent error processing. The short latency suggests an internal error monitoring system acting rapidly based on central information such as an efference copy signal. Studies on monkeys and humans have identified the thalamus as an important relay station for efference copy signals of ongoing saccades. The present study investigated error processing on an antisaccade task with ERPs in six patients with focal vascular damage to the thalamus and 28 control subjects. ERN amplitudes were significantly reduced in the patients, with the strongest ERN attenuation being observed in two patients with right mediodorsal and ventrolateral and bilateral ventrolateral damage, respectively. Although the number of errors was significantly higher in the thalamic lesion patients, the degree of ERN attenuation did not correlate with the error rate in the patients. The present data underline the role of the thalamus for the online monitoring of saccadic eye movements, albeit not providing unequivocal evidence in favour of an exclusive role of a particular thalamic site being involved in performance monitoring. By relaying saccade-related efference copy signals, the thalamus appears to enable fast error processing. Furthermore early error processing based on internal information may contribute to error awareness which was reduced in the patients

    New genetic loci link adipose and insulin biology to body fat distribution.

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    Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

    Diacylglycerol triggers Rim101 pathway dependent necrosis in yeast: a model for lipotoxicity

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    The loss of lipid homeostasis can lead to lipid overload and is associated with a variety of disease states. However, little is known as to how the disruption of lipid regulation or lipid overload affects cell survival. In this study we investigated how excess diacylglycerol (DG), a cardinal metabolite suspected to mediate lipotoxicity, compromises the survival of yeast cells. We reveal that increased DG achieved by either genetic manipulation or pharmacological administration of 1,2-dioctanoyl-sn-glycerol (DOG) triggers necrotic cell death. The toxic effects of DG are linked to glucose metabolism and require a functional Rim101 signaling cascade involving the Rim21 dependent sensing complex and activation of a calpain-like protease. The Rim101 cascade is an established pathway that triggers a transcriptional response to alkaline or lipid stress. We propose that the Rim101 pathway senses DG-induced lipid perturbation and conducts a signaling response that either facilitates cellular adaptation or triggers lipotoxic cell death. Using established models of lipotoxicity i.e. high fat diet in Drosophila and palmitic acid administration in cultured human endothelial cells, we present evidence that the core mechanism underlying this calpain-dependent lipotoxic cell death pathway is phylogenetically conserved

    Investigation of the electrochemical features of carbon-coated TiO2 anode for application in lithium-ion battery using high voltage LiNi0.5Mn1.5O4 spinel cathode

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    In this paper we propose a carbon-coated, nano-sized TiO2 anode for application in lithium-ion batteries. The lithiation-delithiation process characteristic of this mixed anatase/rutile material has been investigated in detail, in order to define the optimal operating voltage range and to further enhance the electrode cycle life. Ex-situ x-ray diffraction measurements demonstrate that the rutile phase becomes electrochemically inactive toward lithium intercalation after the first cycle and remains inactive by cycles. The TiO2 electrochemical behavior is studied by means of various techniques, including galvanostatic cycling and potentiodynamic cycling with galvanostatic acceleration. We show that the combination of the TiO2 anode with a high-voltage, LiNi0.5Mn1.5O4 spinel cathode results in an advanced li-ion battery able to exchange reversibly a capacity higher than 100 mAh/g for over 70 cycles at the high rate of 1C. Considering an average working voltage of about 2.9 V, the theoretical energy content of the cell here disclosed is about 300 Wh kg-1. Taking into account the energy content and high safety level of the full cell, due to the use of a TiO2-based electrode, by operating at a voltage value well far from the one associated to the common electrolyte decomposition, i.e. about 1.7 V, we may propose the anode here studied as suitable material for advanced energy storage systems

    Drosophila Cyclin G Is a Regulator of the Notch Signalling Pathway during Wing Development.

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    Notch signalling regulates a multitude of differentiation processes during Drosophila development. For example, Notch activity is required for proper wing vein differentiation which is hampered in mutants of either the receptor Notch, the ligand Delta or the antagonist Hairless. Moreover, the Notch pathway is involved in several aspects of Drosophila oogenesis as well. We have identified Drosophila Cyclin G (CycG) as a molecular interaction partner of Hairless, the major antagonist in the Notch signalling pathway, in vitro and in vivo. Loss of CycG was shown before to cause female sterility and to disturb the architecture of the egg shell. Nevertheless, Notch dependent processes during oogenesis appeared largely unaffected in cycG mutant egg chambers. Loss of CycG modified the dominant wing phenotypes of Notch, Delta and Hairless mutants. Whereas the Notch loss of function phenotype was ameliorated by a loss of CycG, the phenotypes of either Notch gain of function or of Delta or Hairless loss of function were enhanced. In contrast, loss of CycG had only a minor effect on the wing vein phenotype of mutants affecting the EGFR signalling pathway emphasizing the specificity of the interaction of CycG and Notch pathway members
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