bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heterosubtypic T‐cell responses against avian influenza H5 haemagglutinin are frequently detected in individuals vaccinated against or previously infected with human subtypes of influenza
Authors: Goy Kylie , Von Bibra Sally , Lewis Jenny , Laurie Karen , Barr Ian , Anderson David , Hellard Margaret , Ffrench Rosemary 
Published: July 2008

Background  Cellula r immune responses play a critical role in providing help for the production of neutralizing antibodies to influenza virus, as well as producing anti‐viral cytokines and killing infected cells in the lung. Heterosubtypic T‐cell responses between different subtypes of influenza have been shown to exist in humans and to provide protection against morbidity and mortality associated with H5N1 infection in animal challenge models. Therefore, existing T‐cell responses induced by natural infection or vaccination in humans may provide some degree of protection from infection with H5N1 strains, or may attenuate the severity of disease.Objectives  To investigate heterosubtypic T‐cell responses to avian influenza in humans.Methods  T‐cell responses to an overlapping set of H5 HA peptides and inactivated viruses (H1N1, H3N2 and H5N1) were assessed using IFN‐γ and IL‐2 enzyme‐linked immunospot (ELISpot) assays in a cohort of adults either vaccinated against seasonal influenza in the last 3 years (n = 20) or previously infected (n = 40).Results  T‐cell responses to all three subtypes of virus were found in both infected and vaccinated individuals by IFN‐γ and IL‐2 ELISpot assays. Approximately half of the participants from each group had a positive T‐cell response to the H5 HA peptides in the IFN‐γ or IL‐2 ELISpot assay.Conclusions  Heterosubtypic T‐cell responses to H5 HA occur quite frequently in vaccinated and infected individuals. Further investigation of these responses and what role they may play upon challenge or vaccination against H5N1 may assist in vaccine design for avian influenza.
U.K. HiGEM: The New U.K. High-Resolution Global Environment Model—Model Description and Basic Evaluation
Authors: Shaffrey L. C. , Stevens I. , Norton W. A. , Roberts M. J. , Vidale P. L. , Harle J. D. , Jrrar A. , Stevens D. P. , Woodage M. J. , Demory M. E. , Donners J. , Clark D. B. , Clayton A. , Cole J. W. , Wilson S. S. , Connolley W. M. , Davies T. M. , Iwi A. M. , Johns T. C. , King J. C. , New A. L. , Slingo J. M. , Slingo A. , Steenman-Clark L. , Martin G. M. 
Published: July 2008

AbstractThis article describes the development and evaluation of the U.K.’s new High-Resolution Global Environmental Model (HiGEM), which is based on the latest climate configuration of the Met Office Unified Model, known as the Hadley Centre Global Environmental Model, version 1 (HadGEM1). In HiGEM, the horizontal resolution has been increased to 0.83° latitude × 1.25° longitude for the atmosphere, and 1/3° × 1/3° globally for the ocean. Multidecadal integrations of HiGEM, and the lower-resolution HadGEM, are used to explore the impact of resolution on the fidelity of climate simulations.Generally, SST errors are reduced in HiGEM. Cold SST errors associated with the path of the North Atlantic drift improve, and warm SST errors are reduced in upwelling stratocumulus regions where the simulation of low-level cloud is better at higher resolution. The ocean model in HiGEM allows ocean eddies to be partially resolved, which dramatically improves the representation of sea surface height variability. In the Southern Ocean, most of the heat transports in HiGEM is achieved by resolved eddy motions, which replaces the parameterized eddy heat transport in the lower-resolution model. HiGEM is also able to more realistically simulate small-scale features in the wind stress curl around islands and oceanic SST fronts, which may have implications for oceanic upwelling and ocean biology.Higher resolution in both the atmosphere and the ocean allows coupling to occur on small spatial scales. In particular, the small-scale interaction recently seen in satellite imagery between the atmosphere and tropical instability waves in the tropical Pacific Ocean is realistically captured in HiGEM. Tropical instability waves play a role in improving the simulation of the mean state of the tropical Pacific, which has important implications for climate variability. In particular, all aspects of the simulation of ENSO (spatial patterns, the time scales at which ENSO occurs, and global teleconnections) are much improved in HiGEM.
The MSG Global Instability Indices Product and Its Use as a Nowcasting Tool
Authors: Koenig Marianne , de Coning Estelle 
Published: July 2008

Abstract
The European geostationary Meteosat Second Generation (MSG) satellite offers a variety of channels to use for various purposes, including nowcasting of convection. A number of applications have also been developed to make use of these new capabilities for nowcasting, especially for the detection and prediction of severe weather. The MSG infrared channel selection makes it possible to assess the air stability in preconvective, that is, still cloud-free, conditions. Instability indices are traditionally derived from radiosonde profiles. Such indices typically combine measures of the thermal and moisture properties and often only use a small quantity of vertical profile parameters. MSG-based temperature and moisture retrievals are used for the derivation of stability indices, which are a part of the MSG meteorological products derived centrally at the European Organisation for the Exploitation of Meteorological Satellites (EUMETSAT). Such indices are of an empirical nature, are often only applicable to certain geographic regions, and their thresholds are dependent on seasonal variation, but they can assess the likelihood of convection within the next few hours, thus providing a warning lead of about 6–9 h. Numerous test cases and the more quantitative verification process that was initiated by the South African Weather Service show the generally good warning potential of the derived instability fields. The added capability of a nearly continuous monitoring of the instability fields that is guaranteed by MSG’s 15-min repeat cycle is most valuable, since it provides nowcasters with new information much more regularly than the twice-a-day soundings at only a limited number of radiosonde stations. The current EUMETSAT instability product is aimed at helping forecasters to focus their attention on a certain region, which can then be monitored more closely with other means, like satellite imagery and radar data, over the next few hours.
Eight-week, placebo-controlled, double-blind comparison of the antidepressant efficacy and tolerability of bupropion XR and venlafaxine XR
Authors: Hewett K , Chrzanowski W , Schmitz M , Savela A , Milanova V , Gee M , Krishen A , Millen L , Leary MO , Modell J 
Published: July 2008

Abstract The efficacy, safety and tolerability of bupropion XR and venlafaxine XR was assessed and compared with placebo in adult outpatients with major depressive disorder (MDD). Adults meeting DSM-IV criteria for MDD with a minimum Hamilton Depression Rating Scale (HAMD) 17-Item total score of ≥18 were randomized to eight weeks of double-blind treatment with either bupropion XR (150 mg/day), venlafaxine XR (75 mg/day) or placebo. At the end of the fourth week of treatment, a dosage increase to bupropion XR 300 mg/day or venlafaxine XR 150 mg/day was allowed if, in the opinion of the investigator, response was inadequate. The primary efficacy endpoint was mean change from baseline at week 8 in the Montgomery-Asberg Depression Rating Scale (MADRS) total score last observation carried forward (LOCF). Mean changes from baseline at week 8 (LOCF) in MADRS total score were statistically significant for bupropion XR and venlafaxine XR patients compared to the placebo group: −16.0 for bupropion XR ( P = 0.006 vs placebo), −17.1 for venlafaxine XR ( P < 0.001 vs placebo) and −13.5 for placebo. Secondary outcomes (including CGI-S, HAM-A, MEI, Q-LES-Q-SF, responder and remitter analyses) also improved significantly for both active treatment groups compared with placebo. The most frequently reported adverse events were dry mouth and insomnia for bupropion XR, and nausea, hyperhidrosis, fatigue, and insomnia for venlafaxine XR. In this double-blind, placebo-controlled trial, bupropion XR at doses up to 300 mg/day and venlafaxine XR at doses up to 150 mg/day demonstrated comparable antidepressant efficacy.
Combined functional and molecular analysis of tumor cell signaling defines 2 distinct myeloma subgroups: Akt-dependent and Akt-independent multiple myeloma
Authors: Zöllinger Angela , Stühmer Thorsten , Chatterjee Manik , Gattenlöhner Stefan , Haralambieva Eugenia , Müller-Hermelink Hans-Konrad , Andrulis Mindaugas , Greiner Axel , Wesemeier Carmen , Rath Jörg C. , Einsele Hermann , Bargou Ralf C. 
Published: July 2008

AbstractAlthough the phosphatidylinositide 3-kinase (PI3K)/Akt pathway has been reported to contribute to the malignant growth of multiple myeloma (MM), the true relevance of Akt kinases for this disease is still unclear. In particular, functional analyses in primary tumor cells and genetic target validation experiments are missing. Here, we used combined functional and molecular analyses to determine the importance of Akt activity in a large panel of primary MM samples and in MM cell lines. Akt down-regulation with isoform-specific siRNA constructs or with an Akt1/2-specific pharmacologic inhibitor strongly induced apoptosis in approximately half of the primary MM samples analyzed. Sensitivity to Akt inhibition strongly correlated with the activation status of Akt as determined by immunohistochemistry, phospho-Akt–specific flow cytometry, and Western analysis. Additional blockade of the MAPK and the IL-6R/STAT3 pathways was often not sufficient to decrease the viability of MM cells resilient to Akt inhibition. Taken together, these experiments led to the identification of 2 myeloma subgroups: Akt-dependent and Akt-independent MM.
Brain Derived Neurotrophic Factor (BDNF) Contributes to the Pain Hypersensitivity Following Surgical Incision in the Rats
Authors: Li Chang-Qi , Xu Jun-Mei , Liu Dan , Zhang Jian-Yi , Dai Ru-Ping 
Published: July 2008

Background: The pathogenic role of brain derived neurotrophic factor (BDNF) in the incisional pain is poorly understood. The present study explores the role of the BDNF in the incision-induced pain hypersensitivity. Methods: A longitudinal incision was made in one plantar hind paw of isoflurane-anesthetized rats. Dorsal root ganglias (DRG) and spinal cords were removed at various postoperative times (1–72 h). Expression pattern of BDNF was determined by immunohistochemistry and double-labeling immunofluorescence. Lidocaine-induced blockade of sciatic nerve function was used to determine the importance of afferent nerve activity on BDNF expression in the DRG and spinal cord after incision. BDNF antibody was administered intrathecally (IT) or intraperitoneal (IP) to modulate the spinal BDNF or peripheral BDNF after incision. Results: After hind-paw incision, the BDNF was upregulated in the ipsilateral lumbar DRG and spinal cord whereas thoracic BDNF remained unchanged in response to incision. The upregulated BDNF was mainly expressed in the large-sized neurons in DRG and the neurons and the primary nerve terminals in the spinal cord. Sciatic nerve blockade prevented the increase of BDNF in the DRG and spinal cord. IT injection of BDNF antibody greatly inhibited the mechanical allodynia induced by incision whereas IP administration had only marginal effect. Conclusion: The present study showed that incision induced the segmental upregulation of BDNF in the DRG and spinal cord through somatic afferent nerve transmission, and the upregulated BDNF contributed to the pain hypersensitivity induced by surgical incision.
HPLC with UV or Mass Spectrometric Detection for Quantifying Endogenous Uracil and Dihydrouracil in Human Plasma
Authors: Švobaitė Rūta , Solassol Isabelle , Pinguet Frederic , Ivanauskas Liudas , Brès Janine , Bressolle Françoise M M 
Published: July 2008

Abstract
Background: We developed and compared 2 different methods for quantifying uracil (U) and dihydrouracil (UH2) in BSA and human plasma. Special attention was paid to the selectivity/specificity and the absence of a matrix effect. The UH2/U ratio is intended as a biomarker to identify patients with deficiency in 5-fluorouracil metabolism.
Methods: We quantified U and UH2 with 2 liquid chromatography methods after solid-phase extraction, one with UV detection (LC-UV) and the other with mass spectrometric detection (LC-MS). We selected 2 internal standards to prevent the risk of interferences. Separation was achieved with a Waters Atlantis dC18 column (LC-MS) or a Waters SymmetryShield RP18 column connected with an Atlantis dC18 (LC-UV). Mass spectrometric data were acquired in single-ion monitoring mode.
Results: Assay imprecision in BSA solution was &lt;15% (LC-UV) and &lt;12% (LC-MS); in plasma, assay imprecision was &lt;9.5% and &lt;9.0%, respectively. Recoveries were 88.2%–110% (LC-UV) and 94.8%–107% (LC-MS). Extraction efficiencies were ≥89.0%. In BSA, the lower limits of quantification for U and UH2 were 2.5 μg/L and 6.25 μg/L, respectively, for the LC-UV method and 2.5 μg/L and 3.1 μg/L for LC-MS. The corresponding values in plasma were 11.6 μg/L and 21.5 μg/L, and 4.1 μg/L and 12.1 μg/L.
Conclusions: To estimate endogenous U and UH2 concentrations and their ratio, we recommend the use of a drug-free human plasma pool in which baseline U and UH2 concentrations have previously been measured with the standard-addition method. Our LC-MS method, which has the better test performance and is useful for measuring UH2/U ratios in cancer patients, is preferred when this equipment is available.
The determinants of Lifespan in the Nematode Caenorhabditis Elegans: A Short Primer
Authors: Geanacopoulos Mark 
Published: July 2008

Transparent, easily-maintained, amenable to genetic manipulation, and living for only a few weeks, the nematode Caenorhabditis elegans is a leading animal model for the study of the determinants of lifespan. The original genetic screen for increased longevity identified a mutant, age-1, with a defect in one component of a signal transduction pathway. This pathway functioned as a genetic switch and governed the decision whether to enter a specialized larval form, dauer, that enables the worm to withstand the scarcity of food or other stressful conditions. These age-1 worms had an increased tendency to become dauers, but if they did not adopt the dauer developmental pathway, they lived longer than wild type worms. age-1 and other longevity mutants with dauer phenotypes are vigorous, indicating that they do not suffer from a significant energy deficit, and stress resistant. Mutation of genes encoding mitochondrial components was found to be another means of extending the lifespan of the worm, although the associated phenotypes suggest a deficiency of available energy. While there are now many documented genetic manipulations which can extend the worm's lifespan, it has been difficult to come to definite conclusions as to the mechanism (s) by which lifespan is extended. The most carefully studied mutant strains have complex changes in gene expression and metabolism making it difficult to ascertain what changes are critical. The free radical theory of aging is the dominant biochemical theory of aging, and the phenotypes of the well-characterized longevity mutants worm can be accommodated to it. However discrete interventions to lower reactive oxygen species, or mitigate their effects, have not produced consistent easily-interpretable results in terms of lifespan extension. It has become clear that the insulin-dependent signalling mechanism that regulates lifespan in the worm functions in the context of a complex endocrine system and the hormonal control of aging is an emerging focus of research in worms and higher organisms.
Efficient TiO2 Photocatalysts from Surface Hybridization of TiO2 Particles with Graphite‐like Carbon
Authors: Zhang Li‐Wu , Fu Hong‐Bo , Zhu Yong‐Fa 
Published: July 2008

AbstractSurface hybridization of TiO2 with graphite‐like carbon layers of a few molecular layers thickness yields efficient photocatalysts. Photoelectrochemical measurements confirm an electronic interaction between TiO2 and the graphite‐like carbon. A TiO2 photocatalyst with a carbon shell of three molecular layers thickness (∼1 nm) shows the highest photocatalytic activity which is about two times higher than that of Degussa P25 TiO2 under UV light irradiation. The mechanism of the enhanced photocatalytic activity under UV irradiation is based on the high migration efficiency of photoinduced electrons at the graphite‐like carbon/TiO2 interface, which is due to the electronic interaction between both materials. In addition, a high activity under visible light irradiation is observed after graphite‐like carbon hybridization. TiO2's response is extended into the visible range of the solar spectrum due to the electronic coupling of π states of the graphite‐like carbon and conduction band states of TiO2.
Templateless Synthesis of Polygonal Gold Nanoparticles: An Unsupported and Reusable Catalyst with Superior Activity
Authors: Rashid Md. Harunar , Mandal Tarun K. 
Published: July 2008

AbstractWe report the synthesis of polygonal gold nanoparticles (GNPs) by an in situ reduction technique using ferric ammonium citrate as reducing agent in absence of any surfactant or polymeric template. Transmission electron microscopic analysis and selected area electron diffraction patterns confirmed the formation of well‐crystalline polygonal GNPs grown preferentially along the (111) direction, which is consistent with the results of X‐ray diffractometry analysis. The results of control experiments of HAuCl4 with tri‐ammonium citrate in presence of different externally added metal ions like Fe3+, Ni2+, Cu2+, Zn2+, and Al3+ suggested the ion‐induced growth mechanism in the formation of polygonal GNPs. The purified polygonal GNPs were then successfully used as catalyst in the borohydride reduction of three isomeric nitrophenols and also in the aerobic oxidation of different D‐hexoses (e.g., D‐glucose, D‐mannose, D‐fructose). The catalytic activity of these polygonal GNPs is higher by a factor of 300–1000, depending on the GNP's sample type, in nitrophenol reduction compared to that of spherical GNPs. Similar activity enhancement was also observed in the aerobic oxidation of different D‐hexoses. These polygonal GNPs catalyst are very stable and could be reused several times in the borohydride reduction of nitrophenols without much losing in their virgin catalytic activity.
Genetic evidence implicating multiple genes in the MET receptor tyrosine kinase pathway in autism spectrum disorder
Authors: Campbell Daniel B. , Li Chun , Sutcliffe James S. , Persico Antonio M. , Levitt Pat 
Published: July 2008

AbstractA functional promoter variant of the gene encoding the MET receptor tyrosine kinase alters SP1 and SUB1 transcription factor binding, and is associated with autism spectrum disorder (ASD). Recent analyses of postmortem cerebral cortex from ASD patients revealed altered expression of MET protein and three transcripts encoding proteins that regulate MET signaling, hepatocyte growth factor (HGF), urokinase plasminogen activator receptor (PLAUR) and plasminogen activator inhibitor‐1 (SERPINE1). To address potential risk conferred by multiple genes in the MET signaling pathway, we screened all exons and 5′ promoter regions for variants in the five genes encoding proteins that regulate MET expression and activity. Identified variants were genotyped in 664 families (2,712 individuals including 1,228 with ASD) and 312 unrelated controls. Replicating our initial findings, family‐based association test (FBAT) analyses demonstrated that the MET promoter variant rs1858830 C allele was associated with ASD in 101 new families (P=0.033). Two other genes in the MET signaling pathway also may confer risk. A haplotype of the SERPINE1 gene exhibited significant association. In addition, the PLAUR promoter variant rs344781 T allele was associated with ASD by both FBAT (P=0.006) and case–control analyses (P=0.007). The PLAUR promoter rs344781 relative risk was 1.93 (95% confidence interval [CI]: 1.12–3.31) for genotype TT and 2.42 (95% CI: 1.38–4.25) for genotype CT compared to genotype CC. Gene–gene interaction analyses suggested a significant interaction between MET and PLAUR. These data further support our hypothesis that genetic susceptibility impacting multiple components of the MET signaling pathway contributes to ASD risk.
Development of a fatigue and functional impact scale in anemic cancer patients receiving chemotherapy
Authors: Cella David , Viswanathan Hema N. , Hays Ron D. , Mendoza Tito R. , Stein Kevin D. , Pasta David J. , Foreman Aimee J. , Vadhan‐Raj Saroj , Kallich Joel D. 
Published: July 2008

AbstractBACKGROUND.This study was conducted to develop a brief measure of fatigue and functional impact in cancer patients with anemia.METHODS.Data were obtained from a multisite, phase 2 study of darbepoetin‐α (n = 1558). Eligible patients were ≥18 years with nonmyeloid malignancies and anemia (hemoglobin ≤11 g/dL) who were receiving chemotherapy. Items from the Functional Assessment of Cancer Therapy‐Fatigue (FACT‐F), Brief Fatigue Inventory (BFI), Fatigue Symptom Inventory (FSI), and items adapted from the Medical Outcomes Study SF‐36 physical functioning scale were evaluated for inclusion in the measure. Items were selected by identifying the best predictors of total FACT‐F scores, hemoglobin, and adjusted maximum oxygen uptake (VO2Max) in regression models. Correlations were examined between scale scores and adjusted VO2Max, hemoglobin, performance status, self‐reported energy, and productivity.RESULTS.Data from 401 patients with complete data were used to identify 8 items for the Fatigue and Functional Impact Scale (FFIS), which was then evaluated using 1355 of the 1558 patients. The FFIS had an estimated internal consistency reliability of 0.90. The FFIS had significant correlations with the FACT‐F (r = 0.94), FSI (r = 0.80), and BFI (r = 0.86), from which it was derived. The FFIS also correlated substantially with single‐item measures of energy (r = 0.75) and productivity (r = 0.72).CONCLUSIONS.The FFIS is a reliable, brief, and practical tool that is potentially suitable for identifying fatigue and functional impact in cancer patients. Cancer 2008. © 2008 American Cancer Society.