bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular and clinical features of refractory anemia with ringed sideroblasts associated with marked thrombocytosis
Authors: Malcovati Luca , Della Porta Matteo G. , Pietra Daniela , Boveri Emanuela , Pellagatti Andrea , Gallì Anna , Travaglino Erica , Brisci Angela , Rumi Elisa , Passamonti Francesco , Invernizzi Rosangela , Cremonesi Laura , Boultwood Jacqueline , Wainscoat James S. , Hellström-Lindberg Eva , Cazzola Mario 
Published: August 2009

AbstractWe studied patients with myeloid neoplasm associated with ringed sideroblasts and/or thrombocytosis. The combination of ringed sideroblasts 15% or greater and platelet count of 450 × 109/L or greater was found in 19 subjects fulfilling the diagnostic criteria for refractory anemia with ringed sideroblasts (RARS) associated with marked thrombocytosis (RARS-T), and in 3 patients with primary myelofibrosis. JAK2 and MPL mutations were detected in circulating granulocytes and bone marrow CD34+ cells, but not in T lymphocytes, from 11 of 19 patients with RARS-T. Three patients with RARS, who initially had low to normal platelet counts, progressed to RARS-T, and 2 of them acquired JAK2 (V617F) at this time. In female patients with RARS-T, granulocytes carrying JAK2 (V617F) represented only a fraction of clonal granulocytes as determined by X-chromosome inactivation patterns. RARS and RARS-T patient groups both consistently showed up-regulation of ALAS2 and down-regulation of ABCB7 in CD34+ cells, but several other genes were differentially expressed, including PSIP1 (LEDGF), CXCR4, and CDC2L5. These observations suggest that RARS-T is indeed a myeloid neoplasm with both myelodysplastic and myeloproliferative features at the molecular and clinical levels and that it may develop from RARS through the acquisition of somatic mutations of JAK2, MPL, or other as-yet-unknown genes.
Blocking PD-1 in cancer immunotherapy
Authors: Dotti Gianpietro 
Published: August 2009

Abstract
The PD-1 pathway is emerging as an important tumor-evasion mechanism. In this issue of Blood, 3 independent groups report that PD-1 is highly expressed by tumor-specific cytotoxic T lymphocytes in hematologic and nonhematologic malignancies, and is associated with impaired T-cell function.
A new genetic subgroup of chronic granulomatous disease with autosomal recessive mutations in p40phox and selective defects in neutrophil NADPH oxidase activity
Authors: Matute Juan D. , Arias Andres A. , Wright Nicola A. M. , Wrobel Iwona , Waterhouse Christopher C. M. , Li Xing Jun , Marchal Christophe C. , Stull Natalie D. , Lewis David B. , Steele MacGregor , Kellner James D. , Yu Weiming , Meroueh Samy O. , Nauseef William M. , Dinauer Mary C. 
Published: August 2009

Abstract
Chronic granulomatous disease (CGD), an immunodeficiency with recurrent pyogenic infections and granulomatous inflammation, results from loss of phagocyte superoxide production by recessive mutations in any 1 of 4 genes encoding subunits of the phagocyte NADPH oxidase. These include gp91phox and p22phox, which form the membrane-integrated flavocytochrome b, and cytosolic subunits p47phox and p67phox. A fifth subunit, p40phox, plays an important role in phagocytosis-induced superoxide production via a phox homology (PX) domain that binds to phosphatidylinositol 3-phosphate (PtdIns(3)P). We report the first case of autosomal recessive mutations in NCF4, the gene encoding p40phox, in a boy who presented with granulomatous colitis. His neutrophils showed a substantial defect in intracellular superoxide production during phagocytosis, whereas extracellular release of superoxide elicited by phorbol ester or formyl-methionyl-leucyl-phenylalanine (fMLF) was unaffected. Genetic analysis of NCF4 showed compound heterozygosity for a frameshift mutation with premature stop codon and a missense mutation predicting a R105Q substitution in the PX domain. Parents and a sibling were healthy heterozygous carriers. p40phoxR105Q lacked binding to PtdIns(3)P and failed to reconstitute phagocytosis-induced oxidase activity in p40phox-deficient granulocytes, with premature loss of p40phoxR105Q from phagosomes. Thus, p40phox binding to PtdIns(3)P is essential for phagocytosis-induced oxidant production in human neutrophils and its absence can be associated with disease.
Lipopolysaccharide preconditioning enhances the efficacy of mesenchymal stem cells transplantation in a rat model of acute myocardial infarction
Authors: Yao Yongwei , Zhang Fumin , Wang Liansheng , Zhang Guohui , Wang Zhaojun , Chen Jianmei , Gao Xiang 
Published: August 2009

Abstract

Background
Mesenchymal stem cells (MSCs)-based regenerative therapy is currently regarded as an alternative approach to salvage the acute myocardial infarcted hearts. However, the efficiency of MSCs transplantation is limited by lower survival rate of engrafted MSCs. In previous study, we found that 1.0 μg/ml Lipopolysaccharide (LPS) could protect MSCs against apoptosis induced by oxidative stress and meanwhile enhance the proliferation of MSCs. Therefore, in the present study, we firstly preconditioned MSCs with 1.0 μg/ml LPS, then transplanted MSCs into ischemic myocardium, and observed the survival and cardiac protective capacity of MSCs in a rat model of acute myocardial infarction. Furthermore, we tried to explore the underlying mechanisms and the role of Toll-like receptor-4 (TLR4) in the signal pathway of LPS-induced cardiac protection.

Methods and results
Acute myocardial infarction model was developed by left anterior descending coronary artery ligation. 60 rats were divided into 4 groups randomly and given an intramyocardial injection of one of the following treatments: 30 μl PBS (control group), 3 × 106 wild MSCs/30 μl (wMSCs group), 3 × 106 LPS-preconditioned wild MSCs/30 μl (LPS-wMSCs group), or 3 × 106 LPS-preconditioned TLR4 gene deleted MSCs/30 μl (LPS-tMSCs group). After 3 weeks, LPS-preconditioned wild MSCs transplantation ameliorated cardiac function and reduced fibrosis of infarcted myocardium. Vascular density was markedly increased in LPS-wMSCs group compared with other three groups. Survival rate of engrafted MSCs was elevated and apoptosis of myocardium was reduced in infarcted heart. Expression of vascular endothelial growth factor (VEGF) and phospho-Akt was increased in the infarcted myocardium after transplantation of LPS-preconditioned MSCs.

Conclusion
LPS preconditioning enhanced survival of engrafted MSCs, stimulated expression of VEGF and activated PI3K/Akt pathway. LPS preconditioning before MSCs transplantation resulted in superior therapeutic neovascularization and recovery of cardiac function. LPS preconditioning provided a novel strategy in maximizing biologic and functional properties of MSCs.
Extracting biologically significant patterns from short time series gene expression data
Authors: Tchagang Alain B , Bui Kevin V , McGinnis Thomas , Benos Panayiotis V 
Published: August 2009

Abstract

Background
Time series gene expression data analysis is used widely to study the dynamics of various cell processes. Most of the time series data available today consist of few time points only, thus making the application of standard clustering techniques difficult.

Results
We developed two new algorithms that are capable of extracting biological patterns from short time point series gene expression data. The two algorithms, ASTRO and MiMeSR, are inspired by the rank order preserving framework and the minimum mean squared residue approach, respectively. However, ASTRO and MiMeSR differ from previous approaches in that they take advantage of the relatively few number of time points in order to reduce the problem from NP-hard to linear. Tested on well-defined short time expression data, we found that our approaches are robust to noise, as well as to random patterns, and that they can correctly detect the temporal expression profile of relevant functional categories. Evaluation of our methods was performed using Gene Ontology (GO) annotations and chromatin immunoprecipitation (ChIP-chip) data.

Conclusion
Our approaches generally outperform both standard clustering algorithms and algorithms designed specifically for clustering of short time series gene expression data. Both algorithms are available at http://www.benoslab.pitt.edu/astro/.
Identification of three wheat globulin genes by screening a Triticum aestivum BAC genomic library with cDNA from a diabetes-associated globulin
Authors: Loit Evelin , Melnyk Charles W , MacFarlane Amanda J , Scott Fraser W , Altosaar Illimar 
Published: August 2009

Abstract

Background
Exposure to dietary wheat proteins in genetically susceptible individuals has been associated with increased risk for the development of Type 1 diabetes (T1D). Recently, a wheat protein encoded by cDNA WP5212 has been shown to be antigenic in mice, rats and humans with autoimmune T1D. To investigate the genomic origin of the identified wheat protein cDNA, a hexaploid wheat genomic library from Glenlea cultivar was screened.

Results
Three unique wheat globulin genes, Glo-3A, Glo3-B and Glo-3C, were identified. We describe the genomic structure of these genes and their expression pattern in wheat seeds. The Glo-3A gene shared 99% identity with the cDNA of WP5212 at the nucleotide and deduced amino acid level, indicating that we have identified the gene(s) encoding wheat protein WP5212. Southern analysis revealed the presence of multiple copies of Glo-3-like sequences in all wheat samples, including hexaploid, tetraploid and diploid species wheat seed. Aleurone and embryo tissue specificity of WP5212 gene expression, suggested by promoter region analysis, which demonstrated an absence of endosperm specific cis elements, was confirmed by immunofluorescence microscopy using anti-WP5212 antibodies.

Conclusion
Taken together, the results indicate that a diverse group of globulins exists in wheat, some of which could be associated with the pathogenesis of T1D in some susceptible individuals. These data expand our knowledge of specific wheat globulins and will enable further elucidation of their role in wheat biology and human health.
Factors influencing prescribing behaviour of physicians in Greece and Cyprus: results from a questionnaire based survey
Authors: Theodorou Mamas , Tsiantou Vasiliki , Pavlakis Andreas , Maniadakis Nikos , Fragoulakis Vasilis , Pavi Elpida , Kyriopoulos John 
Published: August 2009

Abstract

Background
Over the past few decades, drug and overall healthcare expenditure have risen rapidly in most countries. The present study investigates the attitudes and the factors which influence physician prescribing decisions and practice in Greece and Cyprus.

Methods
A postal questionnaire was developed by researchers at the Department of Health Economics at the National School of Public Health in Greece, specifically for the purposes of the study. This was then administered to a sample of 1,463 physicians in Greece and 240 physicians in Cyprus, stratified by sex, specialty and geographic region.

Results
The response rate was 82.3% in Greece and 80.4% in Cyprus. There were similarities but also many differences between the countries. Clinical effectiveness is the most important factor considered in drug prescription choice in both countries. Greek physicians were significantly more likely to take additional criteria under consideration, such as the drug form and recommended daily dose and the individual patient preferences. The list of main sources of information for physicians includes: peer-reviewed medical journals, medical textbooks, proceedings of conferences and pharmaceutical sales representatives. Only half of prescribers considered the cost carried by their patients. The majority of doctors in both countries agreed that the effectiveness, safety and efficacy of generic drugs may not be excellent but it is acceptable. However, only Cypriot physicians actually prescribe them. Physicians believe that new drugs are not always better and their higher prices are not necessarily justified. Finally, doctors get information regarding adverse drug reactions primarily from the National Organisation for Medicines. However, it is notable that the majority of them do not inform the authorities on such reactions.

Conclusion
The present study highlights the attitudes and the factors influencing physician behaviour in the two countries and may be used for developing policies to improve their choices and hence to increase clinical and economic effectiveness and efficiency.
Tumor Necrosis Factor-Alpha (TNF-α) Enhances Functional Thermal and Chemical Responses of TRP Cation Channels in Human Synoviocytes
Authors: Kochukov Mikhail Y , McNearney Terry A , Yin Huaizhi , Zhang Liping , Ma Fei , Ponomareva Larissa , Abshire Sarah , Westlund Karin N 
Published: August 2009

Background We have shown functional expression of several TRP channels on human synovial cells, proposing significance in known calcium dependent proliferative and secretory responses in joint inflammation. The present study further characterizes synoviocyte TRP expression and activation responses to thermal and osmotic stimuli after pre-treatment with proinflammatory mediator tumor necrosis factor alpha (TNF-α, EC50 1.3221 × 10−10g/L). Results Fluorescent imaging of Fura-2 loaded human SW982 synoviocytes reveals immediate and delayed cytosolic calcium oscillations elicited by (1) TRPV1 agonists capsaicin and resiniferatoxin (20 – 40% of cells), (2) moderate and noxious temperature change, and (3) osmotic stress TRPV4 activation (11.5% of cells). TNF-alpha pre-treatment (1 ng/ml, 8 – 16 hr) significantly increases (doubles) capsaicin responsive cell numbers and [Ca2+]i spike frequency, as well as enhances average amplitude of temperature induced [Ca2+]i responses. With TNF-alpha pre-treatment for 8, 12, and 16 hr, activation with 36 or 45 degree bath solution induces bimodal [Ca2+]i increase (temperature controlled chamber). Initial temperature induced rapid transient spikes and subsequent slower rise reflect TRPV1 and TRPV4 channel activation, respectively. Only after prolonged TNF-alpha exposure (12 and 16 hr) is recruitment of synoviocytes observed with sensitized TRPV4 responses to hypoosmolarity (3–4 fold increase). TNF-alpha increases TRPV1 (8 hr peak) and TRPV4 (12 hr peak) immunostaining, mRNA and protein expression, with a TRPV1 shift to membrane fractions. Conclusion TNF-α provides differentially enhanced synoviocyte TRPV1 and TRPV4 expression and [Ca2+]i response dependent on the TRP stimulus and time after exposure. Augmented relevance of TRPV1 and TRPV4 as inflammatory conditions persist would provide calcium mediated cell signaling required for pathophysiological responses of synoviocytes in inflammatory pain states.
Altered RNA splicing contributes to skeletal muscle pathology in Kennedy disease knock-in mice
Authors: Yu Zhigang , Wang Adrienne M. , Robins Diane M. , Lieberman Andrew P. 
Published: August 2009

SUMMARY
Here, we used a mouse model of Kennedy disease, a degenerative disorder caused by an expanded CAG repeat in the androgen receptor (AR) gene, to explore pathways leading to cellular dysfunction. We demonstrate that male mice containing a targeted Ar allele with 113 CAG repeats (AR113Q mice) exhibit hormone- and glutamine length-dependent missplicing of Clcn1 RNA in skeletal muscle. Changes in RNA splicing are associated with increased expression of the RNA-binding protein CUGBP1. Furthermore, we show that skeletal muscle denervation in the absence of a repeat expansion leads to increased CUGBP1 expression. However, this induction of CUGBP1 is not sufficient to alter Clcn1 RNA splicing, indicating that changes mediated by both denervation and AR113Q toxicity contribute to altered RNA processing. To test this notion directly, we exogenously expressed the AR in vitro and observed hormone-dependent changes in the splicing of pre-mRNAs from a human cardiac troponin T minigene. These effects were notably similar to changes mediated by RNA with expanded CUG tracts, but not CAG tracts, highlighting unanticipated similarities between CAG and CUG repeat diseases. The expanded glutamine AR also altered hormone-dependent splicing of a calcitonin/calcitonin gene-related peptide minigene, suggesting that toxicity of the mutant protein additionally affects RNA processing pathways that are distinct from those regulated by CUGBP1. Our studies demonstrate the occurrence of hormone-dependent alterations in RNA splicing in Kennedy disease models, and they indicate that these changes are mediated by both the cell-autonomous effects of the expanded glutamine AR protein and by alterations in skeletal muscle that are secondary to denervation.
Photochemistry of anthocyanins and their biological role in plant tissues
Authors: Quina Frank H. , Moreira Paulo F. , Vautier-Giongo Carolina , Rettori Daniel , Rodrigues Rita F. , Freitas Adilson A. , Silva Palmira F. , Maçanita António L. 
Published: August 2009

Abstract
Anthocyanins, the major red, purple, and blue pigments of plants, absorb visible as well as UV radiation and are effective antioxidants and scavengers of active oxygen species. In plant leaves, one of the functional roles proposed for anthocyanins is protection of the photosynthetic apparatus from the effects of excess incident visible or UV-B radiation and photooxidative stress. In essence, a photoprotective role requires that the excited singlet states of both complexed and uncomplexed anthocyanins deactivate back to the ground state so quickly that intersystem crossing, photoreaction, and diffusion-controlled quenching processes cannot compete. Studies of the photochemical properties of synthetic analogs of anthocyanins and of several naturally occurring anthocyanins show that this is indeed the case, uncomplexed anthocyanins decaying back to the ground state via fast (subnanosecond) excited-state proton transfer (ESPT) and anthocyanin-copigment complexes by fast (subpicosecond) charge-transfer-mediated internal conversion.
Local recognition of the line graph of an anisotropic vector space
Authors: Altmann Kristina , Gramlich Ralf 
Published: August 2009

Abstract
Let n ≥ 7 and let V be an (n + 2)-dimensional vector space endowed with an anisotropic sesquilinear form. In this article we characterise the graph whose vertices are the two-dimensional subspaces of V and in which two vertices are adjacent if and only if the corresponding two-dimensional spaces are perpendicular with respect to the sesquilinear form.
A Planar Integral Self-Affine Tile with Cantor Set Intersections with Its Neighbors
Authors: Duan Shu-Juan , Liu Dan , Tang Tai-Man 
Published: August 2009

Abstract
We give an example of a planar self-affine tile that intersects some of its neighbors in the tiling it generates in Cantor sets. The reasoning also shows that it has nontrivial fundamental group. The technique used is to obtain information from a good approximation of the tile, namely, an estimation of its convex hull.
Factor Complexity of Infinite Words Associated with Non-Simple Parry Numbers
Authors: Klouda Karel , Pelantová Edita 
Published: August 2009

Abstract
The factor complexity of the infinite word u

β
canonically associated with a non-simple Parry number β is studied. Our approach is based on the notion of special factors introduced by Berstel and Cassaigne. At first, we give a handy method for determining infinite left special branches; this method is applicable to a broad class of infinite words which are fixed points of a primitive substitution. In the second part of the article, we focus on infinite words u

β
only. To complete the description of their special factors, we define and study (a, b)-maximal left special factors. This enables us to characterize non-simple Parry numbers β for which the word u

β
has affine complexity.
From ecological risk assessments to risk governance: Evaluation of the Norwegian management system for contaminated sediments
Authors: Sparrevik Magnus , Breedveld Gijs D 
Published: August 2009

Abstract
Managing of contaminated sediments is a complex process that will naturally have to balance scientific, political, and economic interests. This study evaluates the Norwegian system for managing contaminated sediments toward a generic system for risk governance encompassing both knowledge, legally prescribed procedures, and social values. The review has been performed examining the management plans for 17 prioritized contaminated fjord systems in Norway. The results indicate a strong focus in the Norwegian management system on ecological risk assessment. This facilitates selection of local sustainable remediation measures, but may also complicate the balance toward other relevant interests in a decision-making process. The Norwegian system lacks management tools to identify and handle ambiguity through concern assessments and stakeholder involvement, and the decision-making process seems to a large extent based on ad hoc decisions, making it difficult to incorporate and document multicriteria evaluations into the management process. To develop a sustainable management system, encompassing environmental, economical, and social interests, a stronger focus on concern assessment and multicriteria evaluations is required. Integr Environ Assess Manag 2010;6:240–248. © 2009 SETAC
The synergy of solar radiation, plant biomass, and humidity as an indicator of ecological functions of the landscape: A case study from Central Europe
Authors: Hesslerová Petra , Pokorný Jan 
Published: August 2009

Abstract
Monitoring the dissipation of the daily pulse of solar energy is one of the ways to assess functionality in landscapes. The temperature of the land cover indicates both balances among fluxes of solar energy (reflection, latent, and sensible heat) and conditions for matter retention in the landscape. Temperature is distributed across landscape depending on the type and structure of land cover, qualitative parameters (contents of chlorophyll and water), and the related process of evapotranspiration. The present study explains a method used for objectively diagnosing the ecological functions of the landscape, drawing theoretically from the Energy-Transport-Reaction model and using Landsat multispectral satellite data. The method is applied to 3 images taken in the northwest of the Czech Republic and in Saxony (Germany), in 1986, 1995, and 2004. Integr Environ Assess Manag 2010;6:249–259. © 2009 SETAC
Production Optimization in Closed-Loop Reservoir Management
Authors: Wang Chunhong , Li Gaoming , Reynolds Albert C. 
Published: August 2009

Summary
In closed-loop reservoir management, one periodically updates reservoir models by integrating production data and then solves an optimal control problem to determine optimum operating conditions to maximize hydrocarbon production or net present value (NPV) for the remaining expected life of the reservoir. The cycle of model updating and production optimization is repeated at specified times. Here, to account for geological uncertainty, we suggest using the ensemble Kalman filter for reservoir model updating and consider three different algorithms for production optimization. Two simple but representative examples indicate that the steepest ascent algorithm is the best of the optimization methods. If the required adjoint software for calculating the gradient of NPV with respect to the controls is not available, we show that iteration using an easily computed stochastic gradient can yield a good estimate of the optimal NPV if properly implemented. For the problem considered, it is shown that NPV is a nonlinear function of the controls, but the final controls from the cases with both known true geology and uncertain geology show "bang-bang" behavior.