bluuebunny/crossref_metadata_2025_split huggingface dataset:
An Efficient Robotic Tendon for Gait Assistance
Authors: Hollander Kevin W. , Ilg Robert , Sugar Thomas G. , Herring Donald 
Published: September 2006

AbstractA robotic tendon is a spring based, linear actuator in which the stiffness of the spring is crucial for its successful use in a lightweight, energy efficient, powered ankle orthosis. Like its human analog, the robotic tendon uses its inherent elastic nature to reduce both peak power and energy requirements for its motor. In the ideal example, peak power required of the motor for ankle gait is reduced from 250 W to just 77 W. In addition, ideal energy requirements are reduced from nearly 36 J to just 21 J. Using this approach, an initial prototype has provided 100% of the power and energy necessary for ankle gait in a compact 0.95kg package, seven times less than an equivalent motor/gearbox system.
Sex differences in baseline neuropsychological function and concussion symptoms of collegiate athletes
Authors: Covassin T , Swanik C B , Sachs M , Kendrick Z , Schatz P , Zillmer E , Kaminaris C 
Published: September 2006

Objective:To investigate sex differences in baseline neuropsychological function and concussion symptoms between male and female collegiate athletes.Methods:A post-test only design was used to examine baseline neuropsychological test scores and concussion symptoms. A total of 1209 NCAA Division I collegiate athletes from five northeastern universities in the USA completed a baseline ImPACT test. ImPACT, a computerised neuropsychological test battery, was administered during an athlete’s pre-season.Results:Female athletes performed significantly better than male athletes on baseline verbal memory scores (p = 0.001), while male athletes performed significantly better than female athletes on baseline visual memory scores (p = 0.001). Female athletes endorsed a significant number of mild baseline symptoms as compared to male athletes.Conclusions:Male and female athletes exhibit differences on baseline neuropsychological test performance and concussion symptoms.
Heat-related and cold-related deaths in England and Wales: who is at risk?
Authors: Hajat S , Kovats R S , Lachowycz K 
Published: September 2006

Background:Despite the high burden from exposure to both hot and cold weather each year in England and Wales, there has been relatively little investigation on who is most at risk, resulting in uncertainties in informing government interventions.Objective:To determine the subgroups of the population that are most vulnerable to heat-related and cold-related mortality.Methods:Ecological time-series study of daily mortality in all regions of England and Wales between 1993 and 2003, with postcode linkage of individual deaths to a UK database of all care and nursing homes, and 2001 UK census small-area indicators.Results:A risk of mortality was observed for both heat and cold exposure in all regions, with the strongest heat effects in London and strongest cold effects in the Eastern region. For all regions, a mean relative risk of 1.03 (95% confidence interval (CI) 1.02 to 1.03) was estimated per degree increase above the heat threshold, defined as the 95th centile of the temperature distribution in each region, and 1.06 (95% CI 1.05 to 1.06) per degree decrease below the cold threshold (set at the 5th centile). Elderly people, particularly those in nursing and care homes, were most vulnerable. The greatest risk of heat mortality was observed for respiratory and external causes, and in women, which remained after control for age. Vulnerability to either heat or cold was not modified by deprivation, except in rural populations where cold effects were slightly stronger in more deprived areas.Conclusions:Interventions to reduce vulnerability to both hot and cold weather should target all elderly people. Specific interventions should also be developed for people in nursing and care homes as heat illness is easily preventable.
Differential changes in β-adrenoceptor signal transduction in left and right ventricles of infarcted ratsThis paper is one of a selection of papers published in this Special issue, entitled Second Messengers and Phosphoproteins—12th International Conference.
Authors: Sethi Rajat , Saini Harjot K. , Wang Xi , Elimban Vijayan , Babick Andrea , Dhalla Naranjan S. 
Published: September 2006

Although different experimental and clinical studies have revealed varying degrees of defects in β-adrenoceptors (β-ARs) during the development of heart failure, the mechanisms for differences in β-AR signal transduction between the left (LV) and right ventricle (RV) are not understood. Because biochemical alterations in the myocardium depend on the stage of heart disease, this study was undertaken to assess the status of β-ARs in the LV and RV at different stages of heart failure. Myocardial infarction was induced in rats by occluding the left coronary artery for 8 and 24 weeks. The β-AR signal transduction was monitored by measuring β1-AR density, the isoproterenol-induced positive inotropic effect, the increase in [Ca2+]i in cardiomyocytes, and the activation of adenylyl cyclase. The β-AR signal transduction parameters in the 8- and 24-week failing LV were depressed, whereas the RV showed upregulation at 8 weeks and downregulation at 24 weeks of these mechanisms. These results suggest that β-AR-mediated signal transduction in the LV and RV are differentially regulated and are dependent upon the stage of development of congestive heart failure due to myocardial infarction.
EFFECT OF THICKNESS OF LIQUID CRYSTALLINE LAYER ON THE THERMOTROPIC AND THERMODYNAMICAL PROPERTIES OF NEMATIC-ISOTROPIC LIQUID AND ISTROPIC LIQUID-NEMATIC PHASE TRANSITIONS
Authors: POLAT ÖMER , NESRULLAJEV ARIF , OKTIK ŞENER 
Published: September 2006

In this work, effect of thickness of the liquid crystalline layer on the morphologic, thermotropic and thermodynamical properties of the nematic–isotropic liquid and isotropic liquid–nematic phase transitions in Shiff based liquid crystals has been investigated. The shift of temperatures of the nematic–isotropic liquid and isotropic liquid–nematic phase transitions to the lower temperatures and the widening of linear and temperature widths of the heterophase regions of these phase transitions by the increase in the thickness of liquid crystalline layer have been found. The effect of thickness of liquid crystalline layer on morphologic, thermotropic and thermodynamical properties of liquid crystals under investigations is connected with change of interaction energy between liquid crystalline molecules and reference surfaces.
A Simulation Model to Estimate the Cost and Effectiveness of Alternative Dialysis Initiation Strategies
Authors: Lee Chris P. , Chertow Glenn M. , Zenios Stefanos A. 
Published: September 2006

Background. Patients with end-stage renal disease (ESRD) require dialysis to maintain survival. The optimal timing of dialysis initiation in terms of cost-effectiveness has not been established. Methods . We developed a simulation model of individuals progressing towards ESRD and requiring dialysis. It can be used to analyze dialysis strategies and scenarios. It was embedded in an optimization frame worked to derive improved strategies. Results. Actual (historical) and simulated survival curves and hospitalization rates were virtually indistinguishable. The model overestimated transplantation costs (10%) but it was related to confounding by Medicare coverage. To assess the model's robustness, we examined several dialysis strategies while input parameters were perturbed. Under all 38 scenarios, relative rankings remained unchanged. An improved policy for a hypothetical patient was derived using an optimization algorithm. Conclusion. The model produces reliable results and is robust. It enables the cost-effetiveness analysis of dialysis strategies.
An Iterative Bayesian Approach to Health Technology Assessment: Application to a Policy of Preoperative Optimization for Patients Undergoing Major Elective Surgery
Authors: Fenwick Elisabeth , Palmer Steve , Claxton Karl , Sculpher Mark , Abrams Keith , Sutton Alex 
Published: September 2006

Purpose. This article presents an iterative framework for managing the dynamic process of health technology assessment. The framework uses Bayesian statistical decision theory and value of information (VOI) analysis to inform decision making regarding appropriate patient management and to direct future research effort over the lifetime of a technology. Within the article, the framework is applied to a policy decision regarding preoperative patient management before major elective surgery, for which trial data are available. Method. The evidence available prior to the trial is used to determine the appropriate method of patient management and to ascertain whether, at the time of commissioning, the trial was potentially worthwhile. The prior information is then updated with the trial data via a Bayesian analysis using informative priors. This post trial information set is then used to reassess the appropriate method for patient management and to determine whether there is a requirement for any further research. Results. Prior to the trial, preoperative optimization with dopexamine is identified as the appropriate method of patient management. The results of the VOI analysis suggest that a short-term trial was potentially worthwhile (population expected value of perfect information [EVPI] = £48 million). Following the trial, the uncertainty surrounding the choice of appropriate patient management and the potential worth of further research had increased (population EVPI = £67 million). Conclusions. The article demonstrates the value and practicality of applying the iterative framework to the dynamic process of health technology assessment. It is only by formally incorporating all of the information available to decision makers, through informed priors, that the appropriate decisions can be made.
IRAG mediates NO/cGMP-dependent inhibition of platelet aggregation and thrombus formation
Authors: Antl Melanie , von Brühl Marie-Luise , Eiglsperger Christina , Werner Matthias , Konrad Ildiko , Kocher Thomas , Wilm Matthias , Hofmann Franz , Massberg Steffen , Schlossmann Jens 
Published: September 2006

AbstractDefective regulation of platelet activation/aggregation is a predominant cause for arterial thrombosis, the major complication of atherosclerosis triggering myocardial infarction and stroke. A central regulatory pathway conveying inhibition of platelet activation/aggregation is nitric oxide (NO)/cyclic GMP (cGMP) signaling by cGMP-dependent protein kinase I (cGKI). However, the regulatory cascade downstream of cGKI mediating platelet inhibition is still unclear. Here, we show that the inositol-1,4,5-trisphosphate receptor–associated cGMP kinase substrate (IRAG) is abundantly expressed in platelets and assembled in a macrocomplex together with cGKIβ and the inositol-1,4,5-trisphosphate receptor type I (InsP3RI). cGKI phosphorylates IRAG at Ser664 and Ser677 in intact platelets. Targeted deletion of the IRAG-InsP3RI interaction in IRAGΔ12/Δ12 mutant mice leads to a loss of NO/cGMP-dependent inhibition of fibrinogen-receptor activation and platelet aggregation. Intracellular calcium transients were not affected by DEA/NO or cGMP in mutant platelets. Furthermore, intravital microscopy shows that NO fails to prevent arterial thrombosis of the injured carotid artery in IRAGΔ12/Δ12 mutants. These findings reveal that interaction between IRAG and InsP3RI has a central role in NO/cGMP-dependent inhibition of platelet aggregation and in vivo thrombosis.
Aberrant transcriptional regulation of the MLL fusion partner EEN by AML1-ETO and its implication in leukemogenesis
Authors: Ma Li-Heng , Liu Han , Xiong Hui , Chen Bing , Zhang Xiao-Wei , Wang Yue-Ying , Le Huang-Ying , Huang Qiu-Hua , Zhang Qing-Hua , Li Bo-Liang , Chen Zhu , Chen Sai-Juan 
Published: September 2006

AbstractThe EEN (extra eleven nineteen) gene, located on chromosome 19p13, was cloned as a fusion with MLL from a patient with acute myeloid leukemia (AML) with translocation t(11;19)(q23;p13). In this study, we characterized the genomic structure of the EEN gene, including its 5′ regulatory region and transcription start site (TSS). We found that Sp1 could bind to the guanine-cytosine (GC)–stretch of the EEN promoter and was critical for the normal EEN expression, whereas the leukemia-associated fusion protein AML1-ETO could aberrantly transactivate the EEN gene through an AML1 binding site. Of note, overexpressed EEN showed oncogenic properties, such as transforming potential in NIH3T3 cells, stimulating cell proliferation, and increasing the activity of transcriptional factor AP-1. Retroviral transduction of EEN increased self-renewal and proliferation of murine hematopoietic progenitor cells. Moreover, Kasumi-1 and HL60-cell growth was inhibited with down-regulation of EEN by RNAi. These findings demonstrate that EEN might be a common target in 2 major types of AML associated with MLL or AML1 translocations, and overexpression of EEN may play an essential role in leukemogenesis.
Successful bone marrow transplantation for IPEX syndrome after reduced-intensity conditioning
Authors: Rao Aarati , Kamani Naynesh , Filipovich Alexandra , Lee Susan Molleran , Davies Stella M. , Dalal Jignesh , Shenoy Shalini 
Published: September 2006

Abstract
Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a rare, fatal autoimmune disorder caused by mutations in the FOXP3 gene leading to the disruption of signaling pathways involved in regulatory T-lymphocyte function. Lifelong multiagent immunosuppression is necessary to control debilitating autoimmune manifestations such as colitis and food allergies. Allogeneic hematopoietic stem cell transplantation (HSCT) can restore T-cell regulatory function but has been previously associated with poor outcome. We describe successful HSCT in 4 patients with IPEX syndrome using a novel reduced-intensity conditioning regimen that resulted in stable donor engraftment, reconstitution of FOXP3+ T regulatory CD4+ cells, and amelioration of gastrointestinal symptoms.
Phenotypic heterogeneity is an evolutionarily conserved feature of the endothelium
Authors: Yano Kiichiro , Gale Daniel , Massberg Steffen , Cheruvu Pavan K. , Monahan-Earley Rita , Morgan Ellen S. , Haig David , von Andrian Ulrich H. , Dvorak Ann M. , Aird William C. 
Published: September 2006

Abstract
Mammalian endothelial cells (ECs) display marked phenotypic heterogeneity. Little is known about the evolutionary mechanisms underlying EC heterogeneity. The last common ancestor of hagfish and gnathostomes was also the last common ancestor of all extant vertebrates, which lived some time more than 500 million years ago. Features of ECs that are shared between hagfish and gnathostomes can be inferred to have already been present in this ancestral vertebrate. The goal of this study was to determine whether the hagfish endothelium displays phenotypic heterogeneity. Electron microscopy of the aorta, dermis, heart, and liver revealed ultrastructural heterogeneity of the endothelium. Immunofluorescent studies demonstrated marked differences in lectin binding between vascular beds. Intravital microscopy of the dermis revealed histamine-induced adhesion of leukocytes in capillaries and postcapillary venules, but no such adhesion in arterioles. Together, these data suggest that structural, molecular, and functional heterogeneity of the endothelium evolved as an early feature of this cell lineage.
IgA Fc receptor I signals apoptosis through the FcRγ ITAM and affects tumor growth
Authors: Kanamaru Yutaka , Tamouza Houda , Pfirsch Séverine , El Mehdi Delphine , Guérin-Marchand Claudine , Pretolani Marina , Blank Ulrich , Monteiro Renato C. 
Published: September 2006

AbstractThe IgA Fc receptor (FcαRI) has dual proinflammatory and anti-inflammatory functions that are transmitted through the immunoreceptor tyrosine-based activation motifs (ITAMs) of the associated FcRγ subunit. Whereas the involvement of FcαRI in inflammation is well documented, little is known of its anti-inflammatory mechanisms. Here we show that monomeric targeting of FcαRI by anti-FcαRI Fab or serum IgA triggers apoptosis in human monocytes, monocytic cell lines, and FcαRI+ transfectants. However, the physiologic ligand IgA induced apoptosis only when cells were cultured in low serum conditions, indicating differences with induction of anti-inflammatory signaling. Apoptosis signaling required the FcRγ ITAM, as cells transfected with FcαRI or with a chimeric FcαRI-FcRγ responded to death-activating signals, whereas cells expressing a mutated FcαRIR209L unable to associate with FcRγ, or an ITAM-mutated chimeric FcαRI-FcRγ, did not respond. FcαRI-mediated apoptosis signals were blocked by treatment with the pan-caspase inhibitor zVAD-fmk, involved proteolysis of procaspase-3, and correlated negatively with SHP-1 concentration. Anti-FcαRI Fab treatment of nude mice injected subcutaneously with FcαRI+ mast-cell transfectants prevented tumor development and halted the growth of established tumors. These findings demonstrate that, on monomeric targeting, FcαRI functions as an FcRγ ITAM-dependent apoptotic module that may be fundamental for controlling inflammation and tumor growth.
Human T-cell leukemia virus type-1 Tax oncoprotein regulates G-protein signaling
Authors: Twizere Jean-Claude , Springael Jean-Yves , Boxus Mathieu , Burny Arsène , Dequiedt Franck , Dewulf Jean-François , Duchateau Julie , Portetelle Daniel , Urbain Patrice , Lint Carine Van , Green Patrick L. , Mahieux Renaud , Parmentier Marc , Willems Luc , Kettmann Richard 
Published: September 2006

AbstractHuman T-cell leukemia virus type-1 (HTLV-1) is associated with adult T-cell leukemia (ATL) and neurological syndromes. HTLV-1 encodes the oncoprotein Tax-1, which modulates viral and cellular gene expression leading to T-cell transformation. Guanine nucleotide–binding proteins (G proteins) and G protein–coupled receptors (GPCRs) constitute the largest family of membrane proteins known and are involved in the regulation of most biological functions. Here, we report an interaction between HTLV-1 Tax oncoprotein and the G-protein β subunit. Interestingly, though the G-protein β subunit inhibits Tax-mediated viral transcription, Tax-1 perturbs G-protein β subcellular localization. Functional evidence for these observations was obtained using conditional Tax-1–expressing transformed T-lymphocytes, where Tax expression correlated with activation of the SDF-1/CXCR4 axis. Our data indicated that HTLV-1 developed a strategy based on the activation of the SDF-1/CXCR4 axis in the infected cell; this could have tremendous implications for new therapeutic strategies.
Expression of Livin, an antiapoptotic protein, is an independent favorable prognostic factor in childhood acute lymphoblastic leukemia
Authors: Choi Jaewon , Hwang Yu Kyeong , Sung Ki Woong , Lee Soo Hyun , Yoo Keon Hee , Jung Hye Lim , Koo Hong Hoe , Kim Hee-Jin , Kang Hyong Jin , Shin Hee Young , Ahn Hyo Seop 
Published: September 2006

Abstract
Livin, a member of the inhibitor of apoptosis proteins, has been considered to be a poor prognostic marker in malignancies. However, little is known about the clinical relevance of Livin expression in childhood acute lymphoblastic leukemia (ALL). In this study, the expression of Livin was analyzed in 222 patients with childhood ALL using quantitative reverse transcriptase–polymerase chain reaction (RT-PCR) to investigate a possible association with the clinical features at diagnosis and treatment outcomes. Both Livin expression rates and expression levels were higher in patients with favorable prognostic factors. The expression rate was also higher in patients with a favorable day 7 bone marrow response to induction chemotherapy (P < .001). The Livin expression was related to the absence of relapse (P < .001). Similarly, the relapse-free survival rate (± 95% CI) was higher in patients with Livin expression than in patients without Livin expression (97.9% ± 4.0% versus 64.9% ± 11.8%, P < .001). Multivariate analysis for relapse-free survival demonstrated that Livin expression was an independent favorable prognostic factor in childhood ALL (P = .049). This study suggests that Livin expression is a novel prognostic marker in childhood ALL and thus needs to be incorporated into the patient stratification and treatment protocols.
Human RPS19, the gene mutated in Diamond-Blackfan anemia, encodes a ribosomal protein required for the maturation of 40S ribosomal subunits
Authors: Flygare Johan , Aspesi Anna , Bailey Joshua C. , Miyake Koichi , Caffrey Jacqueline M. , Karlsson Stefan , Ellis Steven R. 
Published: September 2006

Abstract
Diamond-Blackfan anemia (DBA) typically presents with red blood cell aplasia that usually manifests in the first year of life. The only gene currently known to be mutated in DBA encodes ribosomal protein S19 (RPS19). Previous studies have shown that the yeast RPS19 protein is required for a specific step in the maturation of 40S ribosomal subunits. Our objective here was to determine whether the human RPS19 protein functions at a similar step in 40S subunit maturation. Studies where RPS19 expression is reduced by siRNA in the hematopoietic cell line, TF-1, show that human RPS19 is also required for a specific step in the maturation of 40S ribosomal subunits. This maturation defect can be monitored by studying rRNA-processing intermediates along the ribosome synthesis pathway. Analysis of these intermediates in CD34− cells from the bone marrow of patients with DBA harboring mutations in RPS19 revealed a pre-rRNA–processing defect similar to that observed in TF-1 cells where RPS19 expression was reduced. This defect was observed to a lesser extent in CD34+ cells from patients with DBA who have mutations in RPS19.
In silico and in vivo splicing analysis of MLH1 and MSH2 missense mutations shows exon- and tissue-specific effects
Authors: Lastella Patrizia , Surdo Nicoletta Concetta , Resta Nicoletta , Guanti Ginevra , Stella Alessandro 
Published: September 2006

Abstract

Background
Abnormalities of pre-mRNA splicing are increasingly recognized as an important mechanism through which gene mutations cause disease. However, apart from the mutations in the donor and acceptor sites, the effects on splicing of other sequence variations are difficult to predict. Loosely defined exonic and intronic sequences have been shown to affect splicing efficiency by means of silencing and enhancement mechanisms. Thus, nucleotide substitutions in these sequences can induce aberrant splicing. Web-based resources have recently been developed to facilitate the identification of nucleotide changes that could alter splicing. However, computer predictions do not always correlate with in vivo splicing defects. The issue of unclassified variants in cancer predisposing genes is very important both for the correct ascertainment of cancer risk and for the understanding of the basic mechanisms of cancer gene function and regulation. Therefore we aimed to verify how predictions that can be drawn from in silico analysis correlate with results obtained in an in vivo splicing assay.

Results
We analysed 99 hMLH1 and hMSH2 missense mutations with six different algorithms. Transfection of three different cell lines with 20 missense mutations, showed that a minority of them lead to defective splicing. Moreover, we observed that some exons and some mutations show cell-specific differences in the frequency of exon inclusion.

Conclusion
Our results suggest that the available algorithms, while potentially helpful in identifying splicing modulators especially when they are located in weakly defined exons, do not always correspond to an obvious modification of the splicing pattern. Thus caution must be used in assessing the pathogenicity of a missense or silent mutation with prediction programs. The variations observed in the splicing proficiency in three different cell lines suggest that nucleotide changes may dictate alternative splice site selection in a tissue-specific manner contributing to the widely observed phenotypic variability in inherited cancers.