bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vesicular Stomatitis Virus Genomic RNA PersistsIn Vivoin the Absence of Viral Replication
Authors: Simon Ian D. , van Rooijen Nico , Rose John K. 
Published: December 2009

ABSTRACTOur previous studies using intranasal inoculation of mice with vesicular stomatitis virus (VSV) vaccine vectors showed persistence of vector genomic RNA (gRNA) for at least 60 days in lymph nodes in the absence of detectable infectious virus. Here we show high-level concentration of virus and gRNA in lymph nodes after intramuscular inoculation of mice with attenuated or single-cycle VSV vectors as well as long-term persistence of gRNA in the lymph nodes. To determine if the persistence of gRNA was due to ongoing viral replication, we developed a tagged-primer approach that was critical for detection of VSV mRNA specifically. Our results show that VSV gRNA persists long-term in the lymph nodes while VSV mRNA is present only transiently. Because VSV transcription is required for replication, our results indicate that persistence of gRNA does not result from continuing viral replication. We also performed macrophage depletion studies that are consistent with initial trapping of VSV gRNA largely in lymph node macrophages and subsequent persistence elsewhere in the lymph node.
Discovery of 2-Aminothiazoles as Potent Antiprion Compounds
Authors: Ghaemmaghami Sina , May Barnaby C. H. , Renslo Adam R. , Prusiner Stanley B. 
Published: December 2009

ABSTRACT

Prion diseases are fatal, untreatable neurodegenerative diseases caused by the accumulation of the misfolded, infectious isoform of the prion protein (PrP), termed PrP
Sc
. In an effort to identify novel inhibitors of prion formation, we utilized a high-throughput enzyme-linked immunosorbent assay (ELISA) to evaluate PrP
Sc
reduction in prion-infected neuroblastoma cell lines (ScN2a). We screened a library of ∼10,000 diverse small molecules in 96-well format and identified 121 compounds that reduced PrP
Sc
levels at a concentration of 5 μM. Four chemical scaffolds were identified as potential candidates for chemical optimization based on the presence of preliminary structure-activity relationships (SAR) derived from the primary screening data. A follow-up analysis of a group of commercially available 2-aminothiazoles showed this class as generally active in ScN2a cells. Our results establish 2-aminothiazoles as promising candidates for efficacy studies of animals and validate our drug discovery platform as a viable strategy for the identification of novel lead compounds with antiprion properties.
Der Streit um den ,,nordischen Gedanken“ in der völkischen Bewegung
Authors: Breuer Stefan 
Published: December 2009

AbstractThis essay analyzes the tensions that the rise of “Nordic racism” associated with Hans F. K. Günther triggered within the völkisch movement in the 1920s. Using the examples of the “Deutschbund,” the völkisch wing of the German youth movement “Bündische Jugend” and the German Aristocrats' Association “Deutsche Adelsgenossenschaft,” this essay shows that the reception of the Nordic idea was partially based on misunderstandings and distortions but was also met with open disagreement.
Performance analysis of data scheduling algorithms for multi‐item requests in multi‐channel broadcast environments
Authors: Liu Kai , Lee Victor C. S. 
Published: December 2009

AbstractNowadays querying multiple‐dependent data items in a request is common in many advanced mobile applications, such as traffic information enquiry services. In addition, multi‐channel architectures are widely deployed in many data dissemination systems. In this paper, we extend a number of data productivity‐based scheduling algorithms and evaluate their performance in scheduling multi‐item requests in multi‐channel broadcast environments. We observe from the experimental results two performance problems that render these algorithms ineffective. Lastly, we discuss possible causes of these problems to give insights in the design of a better solution. Copyright © 2009 John Wiley & Sons, Ltd.
Quetiapine: a new option in bipolar depression
Authors: Palazidou Eleni 
Published: December 2009

AbstractBipolar disorder is a condition characterised by periods of depression, mania or depressive and manic symptoms appearing together. Depression is the predominant symptom and is often responsible for poor quality of life. The condition is treatable, but poor compliance is a major problem. Pharmacological treatments include lithium (although it has poor efficacy in depression), valproate and olanzapine (which can cause metabolic syndrome). In this article, Dr Palazidou considers quetiapine, a second‐generation antipsychotic agent, for the treatment of bipolar depression and mania, as well as mixed affective states in bipolar I disorder. Copyright © 2009 John Wiley & Sons, Ltd.
Estimating time to steady state using the effective rate of drug accumulation
Authors: Panebianco Deborah L. , Maes Andrea 
Published: December 2009

AbstractUnless all of a drug is eliminated during each dosing interval, the plasma concentrations within a dosing interval will increase until the time course of change in plasma concentrations becomes invariant from one dosing interval to the next, resulting in steady state. A simple method for estimating drug concentration time to steady state based on multiple dose area under the plasma concentration–time curve and effective rate of drug accumulation is presented. Several point estimates and confidence intervals for time to 90% of steady state are compared, and a recommendation is made on how to summarize and present the results. Copyright © 2009 John Wiley & Sons, Ltd.
Robust identification/invalidation in an LPV framework
Authors: Bianchi Fernando D. , Sánchez‐Peña Ricardo S. 
Published: December 2009

AbstractA robust linear parameter varying (LPV) identification/invalidation method is presented. Starting from a given initial model, the proposed method modifies it and produces an LPV model consistent with the assumed uncertainty/noise bounds and the experimental information. This procedure may complement existingnominalLPV identification algorithms, by adding the uncertainty and noise bounds which produces a set of models consistent with the experimental evidence. Unlike standard invalidation results, the proposed method allows the computation of the necessary changes to the initial model in order to place it within the consistency set. Similar to previous LPV identification procedures, the initial parameter dependency is fixed in advance, but here a methodology to modify this dependency is presented. In addition, all calculations are made on state‐space matrices which simplifies further controller design computations. The application of the proposed method to the identification of nonlinear systems is also discussed. Copyright © 2009 John Wiley & Sons, Ltd.
Attacking the kad network—real world evaluation and high fidelity simulation using DVN
Authors: Wang Peng , Tyra James , Chan‐Tin Eric , Malchow Tyson , Kune Denis Foo , Hopper Nicholas , Kim Yongdae 
Published: December 2009

AbstractThe Kad network, an implementation of the Kademlia DHT protocol, supports the popular eDonkey peer‐to‐peer file sharing network and has over 1 million concurrent nodes. We describe several attacks that exploit critical design weaknesses in Kad to allow an attacker with modest resources to cause a significant fraction of all searches to fail. We measure the cost and effectiveness of these attacks against a set of 16 000 nodes connected to the operational Kad network. Using our large‐scale simulator, DVN, we successfully scaled up to a 200 000 node experiment. We also measure the cost of previously proposed, generic DHT attacks against the Kad network and find that our attacks are much more cost effective. Finally, we introduce and evaluate simple mechanisms to significantly increase the cost of these attacks. Copyright © 2010 John Wiley & Sons, Ltd.
Joseph Smith and the Bible
Authors: Jackson Kent P. 
Published: December 2009

AbstractWith regard to sacred books, Joseph Smith, the founder of Mormonism (1805 – 1844), is best known for his publication of the Book of Mormon, as a history comparable to the Bible, and for other texts he put forth as divine revelations. These volumes established the unique beliefs of Mormonism and set it apart from other religions. What is less well known and often overlooked by historians is the fact that virtually every aspect of Joseph Smith's career involved the Bible, which was central to his theology and to the religious system that he established – but always in ways unique to him. Priesthoods of Aaron and Melchizedek, the building of temples and the establishment of communities in promised lands are all themes for which he invoked biblical precedents. He also produced, but never published in his lifetime, a revision of the Bible itself, the result of three years of adding to and editing the text. In addition, as he taught doctrine in his correspondence, newspaper editorials and sermons, he drew his texts and illustrations from the Bible and virtually never from the Book of Mormon or his own revelations. This article explores the role of the Bible in each of these enterprises and examines the ways Joseph Smith used it in the establishment of Mormon beliefs. The article proposes that, in his extensive use of the Bible, he was making a statement regarding his prophetic authority and his relationship to prophets and scriptures of the past.
Microtoming coupled to microarray analysis to evaluate the spatial metabolic status of Geobacter sulfurreducens biofilms
Authors: Franks Ashley E , Nevin Kelly P , Glaven Richard H , Lovley Derek R 
Published: December 2009

Abstract
Further insight into the metabolic status of cells within anode biofilms is essential for understanding the functioning of microbial fuel cells and developing strategies to optimize their power output. Cells throughout anode biofilms of Geobacter sulfurreducens reduced the metabolic stains: 5-cyano-2,3-ditolyl tetrazolium chloride and Redox Green, suggesting metabolic activity throughout the biofilm. To compare the metabolic status of cells growing close to the anode versus cells in the outer portion of the anode biofilm, anode biofilms were encased in resin and sectioned into inner (0–20 μm from anode surface) and outer (30–60 μm) fractions. Transcriptional analysis revealed that, at a twofold threshold, 146 genes had significant (P&lt;0.05) differences in transcript abundance between the inner and outer biofilm sections. Only 1 gene, GSU0093, a hypothetical ATP-binding cassette transporter, had significantly higher transcript abundances in the outer biofilm. Genes with lower transcript abundance in the outer biofilm included genes for ribosomal proteins and NADH dehydrogenase, suggesting lower metabolic rates. However, differences in transcript abundance were relatively low (&lt;threefold) and the expression of genes for the tricarboxylic acid cycle enzymes was not significantly lower. Lower expression of genes involved in stress responses in the outer biofilm may reflect the development of low pH near the surface of the anode. The results of this study suggest that cells throughout the biofilm are metabolically active and can potentially contribute to current production. The microtoming/microarray strategy described here may be useful for evaluating gene expression with depth in a diversity of microbial biofilms.
Influence of feedback on the stochastic evolution of simple climate systems
Authors: Mahadevan L. , Deutch J. M. 
Published: December 2009

We consider the dynamical evolution of a simple climate system that describes the average temperature of the Earth’s atmosphere owing to radiative forcing and coupling to a positive feedback variable such as the concentration of greenhouse gases in the presence of fluctuations. Analysing the resulting stochastic dynamical system shows that, if the temperature relaxes rapidly relative to the concentration, the time-dependent and stationary probability density functions (pdfs) for the temperature rise possess a fat tail. In contrast, if the feedback variable relaxes rapidly relative to the temperature, the pdf has no fat tail, and, instead, the system shows critical slowing down as the singular limit of positive feedback is approached. However, if there is uncertainty in the feedback variable itself, a fat tail can reappear. Our analysis may be generalized to more complex models with similar qualitative results. Our results have policy implications: although fat tails imply that the expectation of plausible damage functions is infinite, the pdfs permit an examination of the trade-off between reducing emissions and reducing the positive feedback gain.
l‐DOPA‐induced dopamine efflux in the striatum and the substantia nigra in a rat model of Parkinson’s disease: temporal and quantitative relationship to the expression of dyskinesia
Authors: Lindgren Hanna S. , Andersson Daniel R. , Lagerkvist Sören , Nissbrandt Hans , Cenci M. Angela 
Published: December 2009

J. Neurochem. (2010) 112, 1465–1476.Abstract l‐DOPA‐induced dyskinesia in Parkinson’s disease is associated with large increases in brain dopamine (DA) levels following drug dosing, but the precise significance of this phenomenon is not understood. Here we compare DA efflux and metabolism in the striatum and the substantia nigra in dyskinetic and non‐dyskinetic animals following a standard dose of l‐DOPA. Rats with 6‐hydroxydopamine lesions were treated chronically with l‐DOPA, monitored on the abnormal involuntary movements scale, and then subjected to intracerebral microdialysis under freely‐moving conditions. Following s.c. l‐DOPA injection, peak extracellular DA levels in both striatum and substantia nigra were about twice as large in dyskinetic animals compared to non‐dyskinetic rats. This effect was not attributable to differences in DOPA levels or DA metabolism. The larger DA efflux in dyskinetic animals was blunted by 5‐HT1A/5‐HT1B receptor agonists and tetrodotoxin infusion, reflecting release from serotonin neurons. Striatal levels of serotonin and its main metabolite, 5‐hydroxyindolacetic acid were indeed elevated in dyskinetic animals compared to non‐dyskinetic rats, indicating a larger serotonergic innervation density in the former group. High DA release was, however, not sufficient to explain dyskinesia. The ‘abnormal involuntary movements output’ per unit concentration of striatal extracellular DA was indeed much larger in dyskinetic animals compared to non‐dyskinetic cases at most time points examined. The present results indicate that both a high DA release post‐l‐DOPA administration and an increased responsiveness to DA must coexist for a full expression of dyskinesia.
The endogenous cannabinoid, anandamide, inhibits dopamine transporter function by a receptor‐independent mechanism
Authors: Oz Murat , Jaligam Vanaja , Galadari Sehamuddin , Petroianu George , Shuba Yaroslav M. , Shippenberg Toni S. 
Published: December 2009

J. Neurochem.(2010)112, 1454–1464.AbstractThe endocannabinoid, anandamide (AEA), modulates the activity of the dopamine transporter (DAT) in heterologous cells and synaptosomal preparations. The cellular mechanisms mediating this effect are unknown. The present studies employed live cell imaging techniques and the fluorescent, high affinity DAT substrate, 4‐(4‐(dimethylamino)‐styryl)‐N‐methylpyridinium (ASP+), to address this issue. AEA addition to EM4 cells expressing yellow fluorescent protein‐tagged human DAT (hDAT) produced a concentration‐dependent inhibition of ASP+accumulation (IC50: 3.2 ± 0.8 μM). This effect occurred within 1 min after AEA addition and persisted for 10 min thereafter. Pertussis toxin did not attenuate the effects of AEA suggesting a mechanism independent of Gi/Gocoupled receptors. The amidohydrolase inhibitor, phenylmethylsulfonyl fluoride (0.2 mM), failed to alter the AEA‐evoked inhibition of ASP+accumulation. Methanandamide (10 μM), a metabolically stable analogue of AEA inhibited accumulation but arachidonic acid (10 μM) was without effect suggesting that the effects of AEA are not mediated by its metabolic products. The extent of AEA inhibition of ASP+accumulation was not altered in cells pre‐treated with 1 μM URB597, a specific and potent fatty acid amide hydrolase inhibitor, and the cyclooxygenase inhibitor, indomethacin (5 μM) Live cell imaging revealed a significant redistribution of hDAT from the membrane to the cytosol in response to AEA treatment (10 μM; 10 min). Similarly biotinylation experiments revealed that the decrease in DAT function was associated with a reduction in hDAT cell surface expression. These results demonstrate that AEA modulates DAT function via a cannabinoid receptor‐independent mechanism and suggest that AEA may produces this effect, in part, by modulating DAT trafficking.
Polymorphisms Associated with Resistance and Cross-Resistance to Aminoglycosides and Capreomycin in
Mycobacterium tuberculosis
Isolates from South Korean Patients with Drug-Resistant Tuberculosis
Authors: Via Laura E. , Cho Sang-Nae , Hwang Soohee , Bang Hyeeun , Park Seung Kyu , Kang Hyung Seok , Jeon Doosoo , Min Seon Yeong , Oh Taegwon , Kim Yeun , Kim Young Mi , Rajan Vignesh , Wong Sharon Y. , Shamputa Isdore Chola , Carroll Matthew , Goldfeder Lisa , Lee Song A. , Holland Steven M. , Eum Seokyong , Lee Hyeyoung , Barry Clifton E. 
Published: December 2009

ABSTRACT

The aminoglycosides streptomycin, amikacin, and kanamycin and the cyclic polypeptide capreomycin are all widely used in second-line therapy for patients who develop multidrug-resistant tuberculosis. We have characterized a set of 106 clinical isolates of
Mycobacterium tuberculosis
using phenotypic drug susceptibility testing (DST) to determine the extent of resistance to each agent and cross-resistance between agents. These results were compared with polymorphisms in the DNA sequences of ribosome-associated genes previously implicated in resistance and with the clinical outcomes of subjects from whom these isolates were obtained. Thirty-six (34%) of these isolates displayed resistance to one or more of these agents, and the majority of these (20 of 36) showed cross-resistance to one or more agents. Most (33 of 36) of the resistant isolates showed polymorphisms in the 16S ribosome components RpsL and
rrs
. Three resistant strains (3 of 36) were identified that had no known polymorphisms in ribosomal constituents. For kanamycin and streptomycin, molecular DST significantly outperformed phenotypic DST using the absolute concentration method for predicting 4-month sputum conversion (likelihood ratios of 4.0 and 2.0, respectively) and was equivalent to phenotypic DST using the National Committee for Clinical Laboratory Standards (NCCLS)-approved agar proportion method for estimating MIC (likelihood ratio, 4.0). These results offer insight into mechanisms of resistance and cross-resistance among these agents and suggest that the development of rapid molecular tests to distinguish polymorphisms would significantly enhance clinical utility of this important class of second-line antituberculosis drugs.
Broad-SpectrumIn VitroActivity andIn VivoEfficacy of the Antiviral Protein Griffithsin against Emerging Viruses of the FamilyCoronaviridae
Authors: O'Keefe Barry R. , Giomarelli Barbara , Barnard Dale L. , Shenoy Shilpa R. , Chan Paul K. S. , McMahon James B. , Palmer Kenneth E. , Barnett Brian W. , Meyerholz David K. , Wohlford-Lenane Christine L. , McCray Paul B. 
Published: December 2009

ABSTRACTViruses of the familyCoronaviridaehave recently emerged through zoonotic transmission to become serious human pathogens. The pathogenic agent responsible for severe acute respiratory syndrome (SARS), the SARS coronavirus (SARS-CoV), is a member of this large family of positive-strand RNA viruses that cause a spectrum of disease in humans, other mammals, and birds. Since the publicized outbreaks of SARS in China and Canada in 2002-2003, significant efforts successfully identified the causative agent, host cell receptor(s), and many of the pathogenic mechanisms underlying SARS. With this greater understanding of SARS-CoV biology, many researchers have sought to identify agents for the treatment of SARS. Here we report the utility of the potent antiviral protein griffithsin (GRFT) in the prevention of SARS-CoV infection bothin vitroandin vivo. We also show that GRFT specifically binds to the SARS-CoV spike glycoprotein and inhibits viral entry. In addition, we report the activity of GRFT against a variety of additional coronaviruses that infect humans, other mammals, and birds. Finally, we show that GRFT treatment has a positive effect on morbidity and mortality in a lethal infection model using a mouse-adapted SARS-CoV and also specifically inhibits deleterious aspects of the host immunological response to SARS infection in mammals.
The effects of age on skeletal muscle and the phosphocreatine energy system: can creatine supplementation help older adults
Authors: Dalbo Vincent J , Roberts Michael D , Lockwood Chris M , Tucker Patrick S , Kreider Richard B , Kerksick Chad M 
Published: December 2009

Abstract
Creatine supplementation has been found to significantly increase muscle strength and hypertrophy in young adults (≤ 35 yr) particularly when consumed in conjunction with a resistance training regime. Literature examining the efficacy of creatine supplementation in older adults (55-82 yr) suggests creatine to promote muscle strength and hypertrophy to a greater extent than resistance training alone. The following is a review of literature reporting on the effects of creatine supplementation on intramuscular high energy phosphates, skeletal muscle morphology and quality of life in older adults. Results suggest creatine supplementation to be a safe, inexpensive and effective nutritional intervention, particularly when consumed in conjunction with a resistance training regime, for slowing the rate of muscle wasting that is associated with aging. Physicians should strongly consider advising older adults to supplement with creatine and to begin a resistance training regime in an effort to enhance skeletal muscle strength and hypertrophy, resulting in enhanced quality of life.
Validation of a Chinese version of disease specific quality of life scale (HFS-36) for hemifacial spasm in Taiwan
Authors: Huang Yen-Chu , Fan Jun-Yu , Ro Long-Sun , Lyu Rong-Kuo , Chang Hong-Shiu , Chen Sien-Tsong , Hsu Wen-Chuin , Chen Chiung-Mei , Wu Yih-Ru 
Published: December 2009

Abstract

Background and object
There was no Chinese questionnaire to evaluate the health-related quality of life (HRQoL) in patients with hemifacial spasm (HFS). In this study, we aimed to validate a new disease-specific HRQoL scale for HFS (HFS-36) in Chinese version, and compared it to SF-36, a generic HRQoL scale.

Patients and Methods
The HFS-36 Chinese version was modified from English version of HFS-30, including subscales of mobility, activities of daily living (ADL), emotional well-being, stigma, social support, cognition, bodily discomfort, and communication. All the items were scored on the 5-point scales, ranging from 0(never) to 4(always). Patients with HFS were asked to answer HFS-36 and SF-36 questionnaires on the same day before and 6-8 weeks after Botulinum toxin (BTX) injections, respectively. The reliability and validity of HFS-36 scale were evaluated statistically.

Results
Totally, 103 patients (68 females; 35 males) were recruited in this study, with a mean age of 57.6 ± 11.5 years and a mean duration of HFS for 7.6 ± 5.8 years. The intra-class correlation (ICC) and Cronbach's α were over 0.7 in the majority of items. HFS-36 showed a good correlation to HFS severity before BTX treatment and a significant improvement of subscale scoring after BTX treatment. HFS-36 also had a significant correlation to the mental health of SF-36.

Conclusions
The Chinese version of HFS-36 demonstrated a good reliability and validity in subscales of motility, ADL, emotion well-being, stigma and bodily discomfort. The HRQoL was significantly improved after BTX treatment assessed by HFS-36 or SF-36. Compared to SF-36, HFS-36 scale was more sensitive and specific to evaluate the HRQoL in HFS.