bluuebunny/crossref_metadata_2025_split huggingface dataset:
Akt Inhibitor Akt-IV Blocks Virus Replication through an Akt-Independent Mechanism
Authors: Dunn Ewan F. , Fearns Rachel , Connor John H. 
Published: September 2009

ABSTRACTMany viruses activate the phosphatidylinositol 3′-kinase (PI3k)/Akt intracellular signaling pathway to promote viral replication. We have analyzed whether a rapidly replicating rhabdovirus, vesicular stomatitis virus (VSV), requires the PI3k/Akt signaling pathway for its replication. Through the use of chemical inhibitors of PI3k and Akt, we show that VSV replication and cytopathic effects do not require activation of these kinases. Inhibitors that block the activating phosphorylations of Akt at threonine 308 (Thr308) and serine 473 (Ser473) did not inhibit VSV protein expression or the induction of the cytopathic effects of VSV. One compound, Akt inhibitor Akt-IV, inhibited the replication of VSV, respiratory syncytial virus, and vaccinia virus but increased the phosphorylation of Akt at positions Thr308 and Ser473 and did not inhibit Akt kinase activity in vitro. Together, our data suggest that the PI3k/Akt pathway is of limited relevance to the replication of VSV but that Akt inhibitor Akt-IV is a novel broad-spectrum antiviral compound with a mechanism differing from that of its previously reported effect on the PI3k/Akt pathway. Identification of other targets for this compound may define a new approach for blocking virus replication.
The Roles of Chemokines in Rabies Virus Infection: Overexpression May Not Always Be Beneficial
Authors: Zhao Ling , Toriumi Harufusa , Kuang Yi , Chen Huanchun , Fu Zhen F. 
Published: September 2009

ABSTRACT
It was found previously that induction of innate immunity, particularly chemokines, is an important mechanism of rabies virus (RABV) attenuation. To evaluate the effect of overexpression of chemokines on RABV infection, chemokines macrophage inflammatory protein 1α (MIP-1α), RANTES, and IP-10 were individually cloned into the genome of attenuated RABV strain HEP-Flury. These recombinant RABVs were characterized in vitro for growth properties and expression of chemokines. It was found that all the recombinant viruses grew as well as the parent virus, and each of the viruses expressed the intended chemokine in a dose-dependent manner. When these viruses were evaluated for pathogenicity in the mouse model, it was found that overexpression of MIP-1α further decreased RABV pathogenicity by inducing a transient innate immune response. In contrast, overexpression of RANTES or IP-10 increased RABV pathogenicity by causing neurological diseases, which is due to persistent and high-level expression of chemokines, excessive infiltration and accumulation of inflammatory cells in the central nervous system, and severe enhancement of blood-brain barrier permeability. These studies indicate that overexpression of chemokines, although important in controlling virus infection, may not always be beneficial to the host.
Tryptophan Residues in the Portal Protein of Herpes Simplex Virus 1 Critical to the Interaction with Scaffold Proteins and Incorporation of the Portal into Capsids
Authors: Yang Kui , Baines Joel D. 
Published: September 2009

ABSTRACT

Incorporation of the herpes simplex virus 1 (HSV-1) portal vertex into the capsid requires interaction with a 12-amino-acid hydrophobic domain within capsid scaffold proteins. The goal of this work was to identify domains and residues in the U
L
6-encoded portal protein pU
L
6 critical to the interaction with scaffold proteins. We show that whereas the wild-type portal and scaffold proteins readily coimmunoprecipitated with one another in the absence of other viral proteins, truncation beyond the first 18 or last 36 amino acids of the portal protein precluded this coimmunoprecipitation. The coimmunoprecipitation was also precluded by mutation of conserved tryptophan (W) residues to alanine (A) at positions 27, 90, 127, 163, 241, 262, 532, and 596 of U
L
6. All of these W-to-A mutations precluded the rescue of a viral deletion mutant lacking U
L
6, except W163A, which supported replication poorly, and W596A, which fully rescued replication. A recombinant virus bearing the W596A mutation replicated and packaged DNA normally, and scaffold proteins readily coimmunoprecipitated with portal protein from lysates of infected cells. Thus, viral functions compensated for the W596A mutation's detrimental effects on the portal-scaffold interaction seen during transient expression of portal and scaffold proteins. In contrast, the W27A mutation precluded portal-scaffold interactions in infected cell lysates, reduced the solubility of pU
L
6, decreased incorporation of the portal into capsids, and abrogated viral-DNA cleavage and packaging.
Cleavage of IPS-1 in Cells Infected with Human Rhinovirus
Authors: Drahos Jennifer , Racaniello Vincent R. 
Published: September 2009

ABSTRACT

Rhinoviruses are prevalent human pathogens that are associated with life-threatening acute asthma exacerbations. The innate immune response to rhinovirus infection, which may play an important role in virus-induced asthma induction, has not been comprehensively investigated. We examined the innate immune response in cells infected with human rhinovirus 1a (HRV1a). Beta interferon (IFN-β) mRNA was induced in HRV1a-infected cells at levels significantly lower than in cells infected with Sendai virus. To understand the basis for this observation, we determined whether components of the pathway leading to IFN-β induction were altered during infection. Dimerization of the transcription factor IRF-3, which is required for synthesis of IFN-β mRNA, is not observed in cells infected with HRV1a. Beginning at 7 h postinfection, IPS-1, a protein that is essential for cytosolic sensing of viral RNA, is degraded in HRV1a-infected cells. Induction of apoptosis by puromycin led to the cleavage of IPS-1, but treatment of HRV1a-infected cells with the pan-caspase inhibitor, zVAD, did not block cleavage of IPS-1. IPS-1 is cleaved in vitro by caspase-3 and by the picornaviral proteinases 2A
pro
and 3C
pro
. Expression of HRV1a and polioviral 2A
pro
and 3C
pro
led to degradation of IPS-1 in cells. These results suggest that IPS-1 is cleaved during HRV1a infection by three different proteases. Cleavage of IPS-1 may be a mechanism for evasion of the type I IFN response, leading to a more robust infection.
Role of RNA Structures in Genome Terminal Sequences of the Hepatitis C Virus for Replication and Assembly
Authors: Friebe Peter , Bartenschlager Ralf 
Published: September 2009

ABSTRACT

Hepatitis C virus (HCV) is a positive-strand RNA virus replicating its genome via a negative-strand [(−)] intermediate. Little is known about replication signals residing in the 3′ end of HCV (−) RNA. Recent studies identified seven stem-loop structures (SL-I′, -IIz′, -IIy′, -IIIa′, -IIIb′, -IIIcdef′, and -IV′) in this region. In the present study, we mapped the minimal region required for RNA replication to SL-I′ and -IIz′, functionally confirmed the SL-IIz′ structure, and identified SL-IIIa′ to -IV′ as auxiliary replication elements. In addition, we show that the 5′ nontranslated region of the genome most likely does not contain
cis
-acting RNA structures required for RNA packaging into infectious virions.
Antagonism to and Intracellular Sequestration of Human Tetherin by the Human Immunodeficiency Virus Type 2 Envelope Glycoprotein
Authors: Le Tortorec Anna , Neil Stuart J. D. 
Published: September 2009

ABSTRACTTetherin (CD317/BST-2), an interferon-induced membrane protein, restricts the release of nascent retroviral particles from infected cell surfaces. While human immunodeficiency virus type 1 (HIV-1) encodes the accessory genevputo overcome the action of tetherin, the lineage of primate lentiviruses that gave rise to HIV-2 does not. It has been previously reported that the HIV-2 envelope glycoprotein has a Vpu-like function in promoting virus release. Here we demonstrate that the HIV-2 Rod envelope glycoprotein (HIV-2 Rod Env) is a tetherin antagonist. Expression of HIV-2 Rod Env, but not that of HIV-1 or the closely related simian immunodeficiency virus (SIV) SIVmac1A11, counteracts tetherin-mediated restriction of Vpu-defective HIV-1 in a cell-type-specific manner. This correlates with the ability of the HIV-2 Rod Env to mediate cell surface downregulation of tetherin. Antagonism requires an endocytic motif conserved across HIV/SIV lineages in the gp41 cytoplasmic tail, but specificity for tetherin is governed by extracellular determinants in the mature Env protein. Coimmunoprecipitation studies suggest an interaction between HIV-2 Rod Env and tetherin, but unlike studies with Vpu, we found no evidence of tetherin degradation. In the presence of HIV-2 Rod Env, tetherin localization is restricted to thetrans-Golgi network, suggesting Env-mediated effects on tetherin trafficking sequester it from virus assembly sites on the plasma membrane. Finally, we recapitulated these observations in HIV-2-infected CD4+T-cell lines, demonstrating that tetherin antagonism and sequestration occur at physiological levels of Env expression during virus replication.
Occupational asthma and allergy in snow crab processing in Newfoundland and Labrador
Authors: Gautrin D , Cartier A , Howse D , Horth-Susin L , Jong M , Swanson M , Lehrer S , Fox G , Neis B 
Published: September 2009

Background:Risk factors and prevalence of occupational asthma (OA) and occupational allergy (OAl) in the snow crab-processing industry have been poorly studied.Objective:To estimate the prevalence of OA and OAl in snow crab-processing workers and determine their relationship with exposure to snow crab allergens and other potential risk factors.Methods:A total of 215 workers (120 female/95 male) were recruited from four plants in Newfoundland and Labrador, Canada in 2001–2002. Results from questionnaires, skin-prick tests to snow crab meat and cooking water, specific IgEs against the latter, spirometry and peak flow monitoring were used to develop a diagnostic algorithm. An index based on work history and exposure measurements of snow crab aeroallergens was developed to estimate the cumulative exposure for each worker.Results:The prevalences of almost certain or highly probable OA and OAl were 15.8% and 14.9%, respectively. A high cumulative exposure to crab allergens, in jobs mostly held by women, was associated with OA (odds ratio (OR) = 14.0, 95% CI 3.0 to 65.8) (highest vs lowest Cumulative Exposure Index) and with OAl (OR = 7.1, 95% CI 1.9 to 29.0); job held when symptoms started (cleaning, packing, freezing) also predicted OA (OR = 3.9, 95% CI 1.6 to 8.7) and OAl (OR = 3.2, 95% CI 1.4 to 7.5). Atopy (OR = 2.8, 95% CI 1.2 to 6.8), female gender (OR = 10.7, 95% CI 3.6 to 32.1) and smoking were significant determinants for OA (OR = 3.1, 95% CI 1.3 to 7.4).Conclusions:The prevalences of OA and OAl are high in snow crab-processing workers of Canada’s East Coast. Cumulative exposure to snow crab allergens was related to the prevalences of OA and OAl in a dose–response manner taking into account atopy, gender and smoking.
Cause-specific mortality of Dutch chlorophenoxy herbicide manufacturing workers
Authors: Boers D , Portengen L , Bueno-de-Mesquita H Bas , Heederik D , Vermeulen R 
Published: September 2009

Objective:A retrospective cohort study was conducted in two chlorophenoxy herbicide manufacturing factories, producing mainly 2,4,5-trichlorophenoxyacetic acid (factory A) and 4-chloro-2-methylphenoxyacetic acid, 4-chloro-2-methylphenoxy propanoic acid and 2,4-dichlorophenoxyacetic acid (factory B). Previously, we have shown elevated risks for mortality and cancer mortality in this cohort. The purpose of the current, third follow-up, is to provide an updated assessment of cause-specific mortality for both factories.Methods:The study population was defined as all persons working in one of the two factories during 1955–1985 for factory A, or during 1965–1986 for factory B. Analyses were performed using Cox proportional hazard models, using attained age as the timescale. Exposure to phenoxy herbicides and dioxins was expected to be different for factory A and factory B and the factories were therefore analysed separately.Results:Previously reported increased risks for respiratory cancer, non-Hodgkin’s lymphoma and ischaemic heart disease in factory A could not be confirmed in the present analysis. However, increased risks were observed for all cancers in both factory A (hazard ratio (HR) 1.31; 95% CI 0.86 to 2.01) and factory B (HR 1.54; 95% CI 1.00 to 2.37). Increased risks for urinary cancers (HR 4.2; 95% CI 0.99 to 17.89) and genital cancers (HR 2.93; 95% CI 0.61 to 14.15) were observed in factory A, consistent with earlier reported results in this population. More detailed analyses showed that this increased risk for urinary and genital cancers in exposed workers was not due to selection of healthy controls and could not be attributed to specific products or departments.Conclusion:The results of this study showed only slight increases in cancer mortality risk. The increased risk for urinary cancers is noteworthy, but could not be linked to a specific exposure and needs to be confirmed in similar cohorts.
A FEATURE-BASED SCHEME FOR DETECTING AND CLASSIFYING VIDEO-SHOT TRANSITIONS BASED ON SPATIO-TEMPORAL ANALYSIS AND FUZZY CLASSIFICATION
Authors: LIN GUO-SHIANG , CHANG MIN-KUAN , CHIU SHIEN-TANG 
Published: September 2009

In this paper, we propose a feature-based scheme for detecting different genres of video shot transitions based on spatio-temporal analysis and model parameter estimation. In feature extraction, the histogram difference and its modified versions are calculated from the effectiveness of detecting cuts and reducing the impact of fleeting lights. We propose a hybrid algorithm composed of adaptive thresholding, parameter calculation, and transition duration refinement to measure model parameters. Some properties of the associated model parameters of each transition are computed as features. A feature measuring the time gap between two consecutive shots is also adopted. After feature extraction, a fuzzy classifier integrates these features to distinguish nontransitions, cuts, and dissolve-type features from one to another. Many test videos having different types of shots are used for performance evaluation. The experimental results demonstrate that the proposed scheme not only detects cuts, dissolves, and fades well, but also accurately locates the duration of each dissolve-type transition. In addition, the proposed scheme outperforms some existing methods in terms of cut and dissolve detection.
Study of a-Si1-XCX: H Thin Films Obtained by PECVD in Temperatures Lower than 250{degree sign}C Aiming Applications in Optics, Thin Films Devices on Polymeric Substrate and MEMS
Authors: Pelegrini Marcus V. , Pereyra Inés 
Published: September 2009

In this work high optical gap amorphous Silicon Carbide films (a-SixCx-1:H) are produced, studied and characterized. The films are grown at low temperature by PECVD technique, looking for applications in optical devices, MEMS and thin film electronic devices on polymeric substrates.	Properties like chemical bonding, refraction index, optical gap, chemical composition and corrosion resistance to KOH solutions are analyzed through FTIR, Optical absorption and RBS measurements and etching tests in KOH. Also MOS capacitors using these films as gate dielectric are fabricated in order to analyze its electrical properties, aiming to verify the influence of the deposition temperature in the SiC structure.
Early Modern Green Sickness and Pre-Freudian Hysteria
Authors: Schleiner Winfried 
Published: September 2009

AbstractIn early modern medicine, both green sickness (or chlorosis) and hysteria were understood to be gendered diseases, diseases of women. Green sickness, a disease of young women, was considered so serious that John Graunt, the father of English statistics, thought that in his time dozens of women died of it in London every year. One of the symptoms of hysteria was that women fell unconscious. The force of etymology and medical tradition was so strong that in one instance the gender of the patient seems to have been changed by the recorder to make the case fit medical theory.
Project-driven Concurrent Product Development
Authors: Duhovnik Jožef , Žargi Urban , Kušar Janez , Starbek Marko 
Published: September 2009

When entering the global market, companies encounter several difficulties, the most severe being long product development times and too high costs of sequential product and process development. In order to overcome this problem, the companies will have to make a shift from sequential product development (which is wasteful regarding time and costs) to a project-driven concurrent product development as soon as possible. The article presents a procedure for project-driven concurrent product development by taking into account three strategic management methods: parallelness, standardization, and integration of product development processes. Also presented are the changes in organizational concept of the company, organization of processes, organization of work and organization of IT, which are required for a transition from sequential to concurrent product development. Finally, an analysis is presented on concurrent product development teams in a company; this analysis is a prerequisite for a transition to a new method of product development.
Stress failure plays a major role in the development of high-altitude pulmonary oedema in rats
Authors: Bai C. , She J. , Goolaerts A. , Song Y. , Shen C. , Shen J. , Hong Q. 
Published: September 2009

Hypoxia and exertion are considered as the two main factors in the development of high-altitude pulmonary oedema (HAPE), however its pathophysiology remains unclear. Therefore, we established a model in which 32 Sprague–Dawley rats were randomly assigned to normoxic rest, hypoxic rest, normoxic exercise and hypoxic exercise.An altitude of 4,700 m was simulated using hypobaric hypoxia, while exercise consisted 48 h walk with 15–20 min breaks every 4 h. Arterial blood gas, bronchoalveolar lavage (BAL), lung wet-to-dry weight (W/D) ratio and histological measurements were conducted on each animal.In rats exercising in hypoxia, BAL protein and lung W/D ratio were significantly increased but no changes in BAL leukotriene B4and immunoglobulin M were observed. In the same group, lung histology showed typical haemorrhagic lung oedema and disruption of both alveolar epithelium and capillary endothelium while hypoxia or exertion alone only induced slight endothelium and epithelium swelling/disruption.Our study established a direct link between histological and physiological evidence of HAPE-like symptoms and we demonstrated that hypoxia and exertion can synergistically induce HAPE-like symptoms in Sprague–Dawley rats without inducing lung inflammation. We therefore propose that alveolar epithelium and capillary endothelium stress failure play a major role in the development of HAPE.
New concepts for expressing forced expiratory volume in 1 s arising from survival analysis
Authors: Miller M. R. , Pedersen O. F. 
Published: September 2009

Spirometric lung function is partly determined by sex, age and height (Ht). Commonly, lung function is expressed as a percentage of the predicted value (PP) in order to account for these effects.Since the PP method retains sex, age and Ht bias, forced expiratory volume in 1 s (FEV1) standardised by powers of Ht and by a new sex-specific lower limit (FEV1quotient (FEV1Q)) were investigated to determine which method best predicted all-cause mortality in >26,967 patients and normal subjects.On multivariate analysis, FEV1Q was the best predictor, with a hazard ratio for the worst decile of 6.9 compared to 4.1 for FEV1PP. On univariate analysis, the hazard ratios were 18.8 compared to 6.1, respectively; FEV1·Ht−3was the next-best predictor of survival. Median survival was calculated for simple cut-off values of FEV1Q and FEV1·Ht−3. These survival curves were accurately fitted (r2 = 1.0) by both FEV1Q and FEV1·Ht−3values expressed polynomially, and so an individual's test result could be used to estimate survival (withsdfor median survival of 0.22 and 0.61 yrs, respectively).It is concluded that lung function impairment should be expressed in a new way, here termed the FEV1Q, or, alternatively, as FEV1·Ht−3, since these indices best relate spirometric lung function to all-cause mortality and survival.
Study of prone positioning to reduce ventilator-associated pneumonia in hypoxaemic patients
Authors: Mounier R. , Adrie C. , Français A. , Garrouste-Orgeas M. , Cheval C. , Allaouchiche B. , Jamali S. , Dinh-Xuan A. T. , Goldgran-Toledano D. , Cohen Y. , Azoulay E. , Timsit J-F. , Ricard J-D. 
Published: September 2009

The aim of the present study was to examine whether prone positioning (PP) affects ventilator associated-pneumonia (VAP) and mortality in patients with acute lung injury/adult respiratory distress syndrome.2,409 prospectively included patients were admitted over 9 yrs (2000–2008) to 12 French intensive care units (ICUs) (OUTCOMEREA). The patients required invasive mechanical ventilation (MV) and had arterial oxygen tension/inspiratory oxygen fraction ratios <300 during the first 48 h. Controls were matched to PP patients on the PP propensity score (±10%), MV duration longer than that in PP patients before the first turn prone, and centre.VAP incidence was similar in the PP and control groups (24versus13 episodes·1,000 patient-days MV−1respectively, p = 0.14). After adjustment, PP did not decrease VAP occurrence (HR 1.64 (95% CI 0.70–3.84); p = 0.25) but significantly delayed hospital mortality (HR 0.56 (95% CI 0.39–0.79); p = 0.001), without decreasing 28-day mortality (37% in both groups).Post hocanalyses indicated that PP did not protect against VAP but, when used for >1 day, might decrease mortality and benefit the sickest patients (Simplified Acute Physiology Score >50).In ICU patients with hypoxaemic acute respiratory failure, PP had no effect on the risk of VAP. PP delayed mortality without decreasing 28-day mortality. PP >1 day might decrease mortality, particularly in the sickest patients.
Prevention of panic attacks and panic disorder in COPD
Authors: Livermore N. , Sharpe L. , McKenzie D. 
Published: September 2009

This study examined whether cognitive behavioural therapy (CBT) could prevent the development or worsening of panic-spectrum psychopathology and anxiety symptoms in chronic obstructive pulmonary disease (COPD).41 patients with COPD, who had undergone pulmonary rehabilitation, were randomised to either a four-session CBT intervention condition (n = 21) or a routine care condition (n = 20). Assessments were at baseline, post-intervention, and at 6-, 12- and 18-month follow-ups. Primary outcomes were the rates of panic attacks, panic disorder and anxiety symptoms. Secondary outcomes were depressive symptoms, catastrophic cognitions about breathing difficulties, disease-specific quality of life and hospital admission rates.There were no significant differences between the groups on outcome measures at baseline. By the 18-month follow-up assessment, 12 (60%) routine care group participants had experienced at least one panic attack in the previous 6 months, with two (17%) of these being diagnosed with panic disorder, while no CBT group participants experienced any panic attacks during the follow-up phase. There were also significant reductions in anxiety symptoms and catastrophic cognitions in the CBT group at all three follow-ups and a lower number of hospital admissions between the 6- and 12-month follow-ups.The study provides evidence that a brief, specifically targeted CBT intervention can treat panic attacks in COPD patients and prevent the development and worsening of panic-spectrum psychopathology and anxiety symptoms.