bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estimates of the impact of a future influenza pandemic in China
Authors: Yu Hongjie , Feng Luzhao , Peng Zhibin , Feng Zijian , Shay David K. , Yang Weizhong 
Published: July 2009

Background  The next influenza pandemic will create a surge in demand for health resources in China, with its current population of >1·3 billion persons and under‐developed medical care and public health system. However, few pandemic impact data are available for China.Objectives  We estimated the effects of a future influenza pandemic in China by examining pandemic scenarios of varying severity and described the time distribution of cases during a first wave.Methods We used a Monte‐Carlo simulation model and death rates, hospitalizations and outpatient visits for 1918‐ and 1968‐like pandemic scenarios and data from the literature or experts’ opinion to estimate four health outcomes: deaths, hospitalizations, outpatient medical visits and clinical illness for which medical care was not sought. For each of the two scenarios we estimated outcomes by week using a normal distribution.Results  We estimated that a 1968 scenario in China would result in 460 000–700 000 deaths, 1·94–2·27 million hospitalizations, 111–117 million outpatient visits and 192–197 million illnesses for which medical care was not sought. Fifty‐two percent of hospitalizations occurred during the two‐peak weeks of the first wave. We estimated that patients at high‐risk of influenza complications (10–17% of the population) would account for 61–75% of all deaths. For a 1918 scenario, we estimated that 4·95–6·95 million deaths, 20·8–22·7 million hospitalizations and 101–108 million outpatient visits could occur.Conclusion  Even a 1968 pandemic scenario will pose substantial challenges for the medical and public health system in China, and planning to manage these challenges is essential.
Defining the Components of the Research Pipeline
Authors: Kleinman Michael S. , Mold James W. 
Published: July 2009

AbstractThe National Institutes of Health (NIH) has proposed that research moves from “bench to bedside” through a Pipeline consisting of distinct research categories bridged by bidirectional translation. The original NIH Pipeline has now been expanded to include practice‐ and community‐based research. We developed operational definitions for the elements along the expanded NIH Pipeline. The proposed definitions were pilot‐tested and refined using the Computer Retrieval of Information on Scientific Projects (CRISP) and the Secure Internet‐Linked Web Technologies (SILK) database containing funding information for individual NIH awards. Using our definitions, two reviewers independently agreed on the categorization of 94% of 866 National Heart, Lung, and Blood Institute (NHLBI)‐funded projects, and 99% of projects could be placed into a single research category.
“Choice” in Filial Care Work: Moving beyond a Dichotomy
Authors: FUNK LAURA M. , KOBAYASHI KAREN M. 
Published: July 2009

Les auteures analysent le concept du «choix» dans le travail des aidants naturels filiaux. Dans la documentation théorique et empirique sur le travail des aidants naturels, une dichotomie entre le «choix» et l'«obligation» est considérée comme une construction sociale. Néanmoins, cette dichotomie ne reflète pas adéquatement les expériences familiales de fourniture de soins; par exemple, le choix et l'obligation ne constituent pas des motivations mutuellement exclusives. Ils sont plutôt «relationnels», «contextuels» et manifestes dans l'interaction entre des macro et des microcontextes. La dichotomie choix‐obligation est également idéologique. Sur le plan de la politique morale, elle fait la promotion du déchargement de la responsabilité des gouvernements sur les familles, elle obscurcit la complexité des relations filiales et peut même promouvoir l'ambivalence psychologique.In this paper, we discuss the concept of “choice” in filial care work. A dichotomy between choice and obligation is constructed in theoretical and empirical literature on filial care work. However, this dichotomy does not adequately reflect family caregiving experiences; for instance, choice and obligation are not mutually exclusive motivations. Rather, choice and obligation are “relational” and “contextual” and manifest in the interaction between macro‐ and micro‐contexts. The choice‐obligation dichotomy is also ideological. At the moral‐political level, it promotes the downloading of responsibility by governments to family, obscures the complexity of filial relationships, and may even promote psychological ambivalence.
Beating Betz: Energy Extraction Limits in a Constrained Flow Field
Authors: Jamieson Peter M. 
Published: July 2009

Abstract
Experiments with diffusers and other flow concentrating devices have shown that the power performance coefficient Cp of an energy extraction device, defined in relation to the area of flow intercepted at the device, may exceed the Betz limit. “Beating Betz,” in that sense, has been long established but no theory has existed to define in a generalized way what ideal limit may apply to Cp in such situations. Recent analysis has resolved this. This indicates that, irrespective of the presence of flow concentration systems or other influences that perturb the flow but do not in themselves extract energy, there is a universal ideal limit of energy extraction. This is found to be 89 of the upstream kinetic energy in the streamtube associated with the energy extraction. Moreover, the familiar Betz equations for power and thrust coefficients can be generalized in a simple way to express this. Although this work has been developed in the context of wind energy, it will be apparent that the results are of general significance for any application of ducted rotors or propellers in a fluid stream.
Atrial fibrillation in endurance-trained athletes: Table 1
Authors: Sorokin A V , Araujo C G S , Zweibel S , Thompson P D 
Published: July 2009

BackgroundEndurance exercise training produces multiple cardiac adaptations including changes in electrophysiological function that may make endurance-trained athletes more vulnerable to atrial fibrillation (AF). This possible association is not recognised by many practising cardiologists and sports physicians. Consequently, we performed a literature review to examine the relationship between atrial fibrillation and endurance exercise training among athletes. PubMed was searched from January 1960 through December 2008 to identify articles examining the relationship between endurance exercise training and AF.ResultsEvidence suggests that athletes are at increased risk for development of AF. Possible factors increasing AF in this population include increased parasympathetic tone, reduced sympathetic tone, increased atrial size and increased inflammation.DiscussionSuggested management of AF in athletes should follow similar principles to those used to manage AF in the general population.
Low-power FinFET circuit synthesis using multiple supply and threshold voltages
Authors: Mishra Prateek , Muttreja Anish , Jha Niraj K. 
Published: July 2009

According to Moore's law, the number of transistors in a chip doubles every 18 months. The increased transistor-count leads to increased power density. Thus, in modern circuits, power efficiency is a central determinant of circuit efficiency. With scaling, leakage power accounts for an increasingly larger portion of the total power consumption in deep submicron technologies (>40%).
FinFET technology has been proposed as a promising alternative to deep submicron bulk CMOS technology, because of its better scalability, short-channel characteristics, and ability to suppress leakage current and mitigate device-to-device variability when compared to bulk CMOS. The subthreshold slope of a FinFET is approximately 60mV which is close to ideal.

In this article, we propose a methodology for low-power FinFET based circuit synthesis. A mechanism called TCMS (Threshold Control through Multiple Supply Voltages) was previously proposed for improving the power efficiency of FinFET based global interconnects. We propose a significant generalization of TCMS to the design of any logic circuit. This scheme represents a significant divergence from the conventional multiple supply voltage schemes considered in the past. It also obviates the need for voltage level-converters. We employ accurate delay and power estimates using table look-up methods based on HSPICE simulations for supply voltage and threshold voltage optimization. Experimental results demonstrate that TCMS can provide power savings of 67.6% and device area savings of 65.2% under relaxed delay constraints. Two other variants of TCMS are also proposed that yield similar benefits. We compare our scheme to extended cluster voltage scaling (ECVS), a popular dual-

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scheme presented in the literature. ECVS makes use of voltage level-converters. Even when it is assumed that these level-converters have zero delay, thus significantly favoring ECVS in time-constrained power optimization, TCMS still outperforms ECVS.
Gα12-Mediated Pathway Promotes Invasiveness of Nasopharyngeal Carcinoma by Modulating Actin Cytoskeleton Reorganization
Authors: Liu Shu-Chen , Jen Yee-Min , Jiang Shih Sheng , Chang Junn-Liang , Hsiung Chao A. , Wang Chih-Hung , Juang Jyh-Lyh 
Published: July 2009

Abstract
The molecular mechanisms behind the aggressiveness of nasopharyngeal carcinoma (NPC), a highly invasive and metastatic head and neck malignancy, have not been made clear. In this study investigating these mechanisms, guanine nucleotide-binding protein α12 subunit (Gα12) signaling was found by microarray analysis to be increased in primary NPC cells and NPC-derived cell lines. Using small interfering RNA to knock down Gα12 in NPC cells resulted in a reduction in cell migration and invasion as well as a reversal in fibroblastoid morphology. Using microarray analysis, we also found a reduction in expression of key actin dynamics regulators and several epithelial-to-mesenchymal transition–related genes in Gα12-depleted NPC cells. Knocking down one of those genes, IQ motif containing GTPase activating protein 1, reduced the migration and formation of adherens junctions and reversed the fibroblastoid morphology of NPC cells, as knocking down Gα12 was found to do. Immunohistochemical analysis found NPC tumors to have significantly greater levels of Gα12 protein than the normal basal epithelial cells. Quantitative real-time PCR analysis revealed a significant correlation between Gα12 mRNA levels and NPC lymph node metastasis. Together, our findings support a model in which activation of Gα12 signaling promotes tumorigenesis and progression of NPC by modulating actin cytoskeleton reorganization and expression of epithelial-to-mesenchymal transition–related genes. [Cancer Res 2009;69(15):6122–30]
Loss of RhoB Expression Promotes Migration and Invasion of Human Bronchial Cells Via Activation of AKT1
Authors: Bousquet Emilie , Mazières Julien , Privat Maud , Rizzati Virginie , Casanova Anne , Ledoux Adeline , Mery Eliane , Couderc Bettina , Favre Gilles , Pradines Anne 
Published: July 2009

Abstract
Lung cancer is the leading cause of cancer-related death worldwide, mainly due to its highly metastatic properties. Previously, we reported an inverse correlation between RhoB expression and the progression of the lung cancer, occurring between preinvasive and invasive tumors. Herein, we mimicked the loss of RhoB observed throughout lung oncogenesis with RNA interference in nontumoral bronchial cell lines and analyzed the consequences on both cell transformation and invasion. Down-regulation of RhoB did not modify the cell growth properties but did promote migration and invasiveness. Furthermore, RhoB depletion was accompanied by modifications of actin and cell adhesion. The specific activation of the Akt1 isoform and Rac1 was found to be critical for this RhoB-mediated regulation of migration. Lastly, we showed that RhoB down-regulation consecutive to K-RasV12 cell transformation is critical for cell motility but not for cell proliferation. We propose that RhoB loss during lung cancer progression relates to the acquisition of invasiveness mediated by the phosphatidylinositol 3-kinase (PI3K)/AKT and Rac1 pathways rather than to tumor initiation. [Cancer Res 2009;69(15):6092–99]
Protein Kinase Cδ Activates RelA/p65 and Nuclear Factor-κB Signaling in Response to Tumor Necrosis Factor-α
Authors: Lu Zheng-Guang , Liu Hanshao , Yamaguchi Tomoko , Miki Yoshio , Yoshida Kiyotsugu 
Published: July 2009

Abstract
Nuclear factor-κB (NF-κB) is tightly modulated by IκB kinases and IκBα in the cytoplasm. On stimulation, NF-κB translocates into the nucleus to initiate transcription; however, regulation of its transcriptional activity remains obscure. Here, we show that protein kinase C (PKC) δ controls the main subunit of NF-κB, RelA/p65. On exposure to tumor necrosis factor-α (TNF-α), the expression of RelA/p65 target genes such as IκBα, RelB, and p100/p52 is up-regulated in a PKCδ-dependent manner. The results also show that PKCδ is targeted to the nucleus and forms a complex with RelA/p65 following TNF-α exposure. Importantly, kinase activity of PKCδ is required for RelA/p65 transactivation. In concert with these results, PKCδ activates RelA/p65 for its occupancy to target-gene promoters, including IκBα and p100/p52. Moreover, functional analyses show that inhibition of PKCδ is associated with substantial attenuation of NF-κB activity in response to TNF-α. These findings provide evidence that PKCδ orchestrates RelA/p65 transactivation, a requisite for NF-κB signaling pathway in the nucleus. [Cancer Res 2009;69(14):5927–35]
Kinome Profiling of Chondrosarcoma Reveals Src-Pathway Activity and Dasatinib as Option for Treatment
Authors: Schrage Yvonne M. , Briaire-de Bruijn Inge H. , de Miranda Noel F.C.C. , van Oosterwijk Jolieke , Taminiau Antonie H.M. , van Wezel Tom , Hogendoorn Pancras C.W. , Bovée Judith V.M.G. 
Published: July 2009

Abstract
Chondrosarcomas are notorious for their resistance to conventional chemotherapy and radiotherapy, indicating there are no curative treatment possibilities for patients with inoperable or metastatic disease. We therefore explored the existence of molecular targets for systemic treatment of chondrosarcoma using kinome profiling. Peptide array was performed for four chondrosarcoma cell lines and nine primary chondrosarcoma cultures with GIST882, MSCs, and colorectal cancer cell lines as controls. Activity of kinases was verified using immunoblot, and active Src- and platelet-derived growth factor receptor (PDGFR) signaling were further explored using imatinib and dasatinib on chondrosarcoma in vitro. The AKT1/GSK3B pathway was clearly active in chondrosarcoma. In addition, the PDGFR pathway and the Src kinase family were active. PDGFR and Src kinases can be inhibited by imatinib and dasatinib, respectively. Although imatinib did not show any effect on chondrosarcoma cell cultures, dasatinib showed a decrease in cell viability at nanomolar concentrations in seven of nine chondrosarcoma cultures. However, inhibition of phosphorylated Src (Y419) was found both in responsive and nonresponsive cells. In conclusion, using kinome profiling, we found the Src pathway to be active in chondrosarcoma. Moreover, we showed in vitro that the inhibitor of the Src pathway, dasatinib, may provide a potential therapeutic benefit for chondrosarcoma patients who are not eligible for surgery. [Cancer Res 2009;69(15):6216–22]
The G Protein–Coupled Receptor 87 Is Necessary for p53-Dependent Cell Survival in Response to Genotoxic Stress
Authors: Zhang Yanhong , Qian Yingjuan , Lu Wenfu , Chen Xinbin 
Published: July 2009

Abstract
p53 regulates an array of target genes, which mediates p53 tumor suppression by inducing cell cycle arrest, apoptosis, and cell survival. G protein–coupled receptors belong to a superfamily of cell surface molecules and are known to regulate cell proliferation, migration, and survival. Here, we found that G protein–coupled receptor 87 (GPR87) was up-regulated by p53 and by DNA damage in a p53-dependent manner. We also found that p53 directly regulated GPR87 potentially via a p53-responsive element in the GPR87 gene. To investigate the role of GPR87 in the p53 pathway, we generated multiple RKO and MCF7 cell lines in that GPR87 can be inducibly overexpressed or knocked down by a tetracycline-inducible system. We found that overexpression of GPR87 had little effect on cell growth. However, GPR87 knockdown sensitized cancer cells to DNA damage–induced growth suppression via enhanced p53 stabilization and activation. Importantly, the prosurvival activity of GPR87 can be reversed by knockdown of p53. Together, our results suggested that GPR87 is essential for p53-dependent cell survival in response to DNA damage. Thus, due to its expression on the cell surface and its role in cell survival, GPR87 may be explored as a novel therapeutic target for cancer treatment and prevention. [Cancer Res 2009;69(15):6049–56]
Autologous Melanoma Vaccine Induces Antitumor and Self-Reactive Immune Responses That Affect Patient Survival and Depend on MHC Class II Expression on Vaccine Cells
Authors: Lotem Michal , Machlenkin Arthur , Hamburger Tamar , Nissan Aviram , Kadouri Luna , Frankenburg Shoshana , Gimmon Zvi , Elias Orit , David Inna Ben , Kuznetz Anna , Shiloni Eitan , Peretz Tamar 
Published: July 2009

AbstractPurpose: Autologous melanoma cells display a broad variety of tumor antigens and were used for treatment of American Joint Committee on Cancer stages III and IV melanoma as an adjuvant or active therapy. Survival data and immune response were evaluated in vaccinated patients.Experimental Design: Forty-seven patients received 2,4-dinitrophenyl–conjugated autologous melanoma vaccine as an adjuvant (23 patients) or therapy (24 patients). CD4 and CD8 T-cell response in blood sampled before vaccination and after five or eight vaccine doses was evaluated against melanoma cells and autologous peripheral blood mononuclear cells using IFNγ enzyme–linked immunospot. Serum levels of antilivin, an inhibitor of apoptosis, and anti-gp100 IgG were determined.Results: The immunologic effect of the vaccine differed between the two groups of patients. In the adjuvant group, there was a significant increase in CD8 melanoma-reactive T cells (P = 0.035) after vaccination and an increase in antimelanoma CD4 T cells correlating with improved overall survival (P = 0.04). In the therapeutic group, there was no objective tumor regression; antimelanoma T-cell reactivity increased by a small amount, stayed the same, or in some cases decreased. In all patients, a significant increase was noted in CD4 T-cell reactivity against autologous peripheral blood mononuclear cells (P = 0.02), which did not affect survival. Increased antilivin IgG was associated with improved survival. Expression of MHC class II on melanoma cells was vital for the immunogenicity of the vaccine.Conclusion: Autologous melanoma cell vaccine is capable of inducing effective antimelanoma CD4 T-cell activity associated with improved survival. Patients with active metastatic disease generally displayed reduced immune response and gained little from active immunization.
The development of a comparison approach for Illumina bead chips unravels unexpected challenges applying newest generation microarrays
Authors: Eggle Daniela , Debey-Pascher Svenja , Beyer Marc , Schultze Joachim L 
Published: July 2009

Abstract

Background
The MAQC project demonstrated that microarrays with comparable content show inter- and intra-platform reproducibility. However, since the content of gene databases still increases, the development of new generations of microarrays covering new content is mandatory. To better understand the potential challenges updated microarray content might pose on clinical and biological projects we developed a methodology consisting of in silico analyses combined with performance analysis using real biological samples.

Results
Here we clearly demonstrate that not only oligonucleotide design but also database content and annotation strongly influence comparability and performance of subsequent generations of microarrays. Additionally, using human blood samples and purified T lymphocyte subsets as two independent examples, we show that a performance analysis using biological samples is crucial for the assessment of consistency and differences.

Conclusion
This study provides an important resource assisting investigators in comparing microarrays of updated content especially when working in a clinical or regulatory setting.
Rooting human parechovirus evolution in time
Authors: Faria Nuno R , de Vries Michel , van Hemert Formijn J , Benschop Kimberley , van der Hoek Lia 
Published: July 2009

Abstract

Background
The Picornaviridae family contains a number of important pathogenic viruses, among which the recently reclassified human parechoviruses (HPeVs). These viruses are widespread and can be grouped in several types. Understanding the evolutionary history of HPeV could answer questions such as how long the circulating lineages last shared a common ancestor and how the evolution of this viral species is shaped by its population dynamics. Using both strict and relaxed clock Bayesian phylogenetics we investigated 1) the substitutions rates of the structural P1 and capsid VP1 regions and 2) evolutionary timescale of currently circulating HPeV lineages.

Results
Our estimates reveal that human parechoviruses exhibit high substitution rates for both structural P1 and capsid VP1 regions, respectively 2.21 × 10-3 (0.48 – 4.21 × 10-3) and 2.79 × 10-3 (2.05 – 3.66 × 10-3) substitutions per site per year. These are within the range estimated for other picornaviruses. By employing a constant population size coalescent prior, the date of the most recent common ancestor was estimated to be at around 1600 (1427–1733). In addition, by looking at the frequency of synonymous and non-synonymous substitutions within the VP1 gene we show that purifying selection constitutes the dominating evolutionary force leading to strong amino acid conservation.

Conclusion
In conclusion, our estimates provide a timescale for the evolution of HPeVs and suggest that genetic diversity of current circulating HPeV types has arisen about 400 years ago.