bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alcohol involvement among young female drivers in US fatal crashes: unfavourable trends
Authors: Tsai Virginia W , Anderson Craig L , Vaca Federico E 
Published: February 2010

ObjectiveYoung men have greater representation in fatal alcohol-related crashes. Recent studies of young women and risky behaviours have raised concerns about the implications this may have for alcohol-related fatal crashes. The objective of this study was to investigate the representation of young female drivers in US alcohol-involved fatal crashes (1995–2007) and to identify trends heralding future negative changes in crash profiles for young female drivers.DesignFatal crash data were obtained from the US National Highway Traffic Safety Administration Fatal Analysis Reporting System (FARS). Five age groups were analysed. The FARS multiple imputation dataset was used to estimate the proportion of drivers with blood alcohol, and variance estimates were corrected for the procedure. Linear regression was used to measure trends (1995–2007).Results179 891 fatal crashes in all age groups occurred over the study period. The rate of involvement in fatal crashes for young drivers with positive blood alcohol concentrations (BAC) decreased for men and women aged 16 years but increased for women age 19–24 years. Young female drivers had a greater increase than young men in the proportion of alcohol-involved fatal crashes (3.1%, 95% CI 1.9 to 4.3% vs 1.2%, 95% CI 0.2 to 2.1%, p=0.02). Most of the increase occurred in drivers with BAC ≥0.15 g/dl. Drivers with higher BAC had markedly lower safety restraint use. Over time restraint use increased in all BAC groups studied.ConclusionAlcohol-involved fatal crash rates in young female drivers aged 19–24 years have increased. However, male drivers continue to surpass women in the number of alcohol-involved fatal crashes. Restraint use decreases markedly with increasing BAC.
Improved Terrestrial Hydrologic Representation in Mesoscale Land Surface Models
Authors: Choi Hyun I. , Liang Xin-Zhong 
Published: February 2010

Abstract
This study addresses several deficiencies in the existing formulations for terrestrial hydrologic processes in the Common Land Model (CLM) and presents improved solutions, focusing on runoff prediction. In particular, this paper has 1) incorporated a realistic geographic distribution of bedrock depth to improve estimates of the actual soil water capacity; 2) replaced an equilibrium approximation with a dynamic prediction of the water table to produce more reasonable variations of the saturated zone depth; 3) used an exponential decay function with soil depth for the saturated hydraulic conductivity to consider the effect of macropores near the ground surface; 4) formulated an effective hydraulic conductivity of the liquid part at the frozen soil interface and imposed a maximum surface infiltration limit to eliminate numerically generated negative or excessive soil moisture solution; and 5) examined an additional contribution to subsurface runoff from saturation lateral runoff or baseflow controlled by topography. To assess the performance of these modifications, runoff results from a set of offline simulations are validated at a catchment-scaled study domain around the Ohio Valley region. Together, these new schemes enable the CLM to capture well the major characteristics of the observed total runoff variations. The improvement is especially significant at peak discharges under high flow conditions.
Digital gene expression analysis of two life cycle stages of the human-infective parasite, Trypanosoma brucei gambiense reveals differentially expressed clusters of co-regulated genes
Authors: Veitch Nicola J , Johnson Paul CD , Trivedi Urmi , Terry Sandra , Wildridge David , MacLeod Annette 
Published: February 2010

Abstract

Background
The evolutionarily ancient parasite, Trypanosoma brucei, is unusual in that the majority of its genes are regulated post-transcriptionally, leading to the suggestion that transcript abundance of most genes does not vary significantly between different life cycle stages despite the fact that the parasite undergoes substantial cellular remodelling and metabolic changes throughout its complex life cycle. To investigate this in the clinically relevant sub-species, Trypanosoma brucei gambiense, which is the causative agent of the fatal human disease African sleeping sickness, we have compared the transcriptome of two different life cycle stages, the potentially human-infective bloodstream forms with the non-human-infective procyclic stage using digital gene expression (DGE) analysis.

Results
Over eleven million unique tags were generated, producing expression data for 7360 genes, covering 81% of the genes in the genome. Compared to microarray analysis of the related T. b. brucei parasite, approximately 10 times more genes with a 2.5-fold change in expression levels were detected. The transcriptome analysis revealed the existence of several differentially expressed gene clusters within the genome, indicating that contiguous genes, presumably from the same polycistronic unit, are co-regulated either at the level of transcription or transcript stability.

Conclusions
DGE analysis is extremely sensitive for detecting gene expression differences, revealing firstly that a far greater number of genes are stage-regulated than had previously been identified and secondly and more importantly, this analysis has revealed the existence of several differentially expressed clusters of genes present on what appears to be the same polycistronic units, a phenomenon which had not previously been observed in microarray studies. These differentially regulated clusters of genes are in addition to the previously identified RNA polymerase I polycistronic units of variant surface glycoproteins and procyclin expression sites, which encode the major surface proteins of the parasite. This raises a number of questions regarding the function and regulation of the gene clusters that clearly warrant further study.
Comparative gene expression profiling between human cultured myotubes and skeletal muscle tissue
Authors: Raymond Frederic , Métairon Sylviane , Kussmann Martin , Colomer Jaume , Nascimento Andres , Mormeneo Emma , García-Martínez Cèlia , Gómez-Foix Anna M 
Published: February 2010

Abstract

Background
A high-sensitivity DNA microarray platform requiring nanograms of RNA input facilitates the application of transcriptome analysis to individual skeletal muscle (SM) tissue samples. Culturing myotubes from SM-biopsies enables investigating transcriptional defects and assaying therapeutic strategies. This study compares the transcriptome of aneurally cultured human SM cells versus that of tissue biopsies.

Results
We used the Illumina expression BeadChips to determine the transcriptomic differences between tissue and cultured SM samples from five individuals. Changes in the expression of several genes were confirmed by QuantiGene Plex assay or reverse transcription real-time PCR. In cultured myotubes compared to the tissue, 1216 genes were regulated: 583 down and 633 up. Gene ontology analysis showed that downregulated genes were mainly associated with cytoplasm, particularly mitochondria, and involved in metabolism and the muscle-system/contraction process. Upregulated genes were predominantly related to cytoplasm, endoplasmic reticulum, and extracellular matrix. The most significantly regulated pathway was mitochondrial dysfunction. Apoptosis genes were also modulated. Among the most downregulated genes detected in this study were genes encoding metabolic proteins AMPD1, PYGM, CPT1B and UCP3, muscle-system proteins TMOD4, MYBPC1, MYOZ1 and XIRP2, the proteolytic CAPN3 and the myogenic regulator MYF6. Coordinated reduced expression of five members of the GIMAP gene family, which form a cluster on chromosome 7, was shown, and the GIMAP4-reduction was validated. Within the most upregulated group were genes encoding senescence/apoptosis-related proteins CDKN1A and KIAA1199 and potential regulatory factors HIF1A, TOP2A and CCDC80.

Conclusions
Cultured muscle cells display reductive metabolic and muscle-system transcriptome adaptations as observed in muscle atrophy and they activate tissue-remodeling and senescence/apoptosis processes.
Mechanistic insights from a quantitative analysis of pollen tube guidance
Authors: Stewman Shannon F , Jones-Rhoades Matthew , Bhimalapuram Prabhakar , Tchernookov Martin , Preuss Daphne , Dinner Aaron R 
Published: February 2010

Abstract

Background
Plant biologists have long speculated about the mechanisms that guide pollen tubes to ovules. Although there is now evidence that ovules emit a diffusible attractant, little is known about how this attractant mediates interactions between the pollen tube and the ovules.

Results
We employ a semi-in vitro assay, in which ovules dissected from Arabidopsis thaliana are arranged around a cut style on artificial medium, to elucidate how ovules release the attractant and how pollen tubes respond to it. Analysis of microscopy images of the semi-in vitro system shows that pollen tubes are more attracted to ovules that are incubated on the medium for longer times before pollen tubes emerge from the cut style. The responses of tubes are consistent with their sensing a gradient of an attractant at 100-150 μm, farther than previously reported. Our microscopy images also show that pollen tubes slow their growth near the micropyles of functional ovules with a spatial range that depends on ovule incubation time.

Conclusions
We propose a stochastic model that captures these dynamics. In the model, a pollen tube senses a difference in the fraction of receptors bound to an attractant and changes its direction of growth in response; the attractant is continuously released from ovules and spreads isotropically on the medium. The model suggests that the observed slowing greatly enhances the ability of pollen tubes to successfully target ovules. The relation of the results to guidance in vivo is discussed.
STIL, a peculiar molecule from styles, specifically dephosphorylates the pollen receptor kinase LePRK2 and stimulates pollen tube growth in vitro
Authors: Wengier Diego L , Mazzella María A , Salem Tamara M , McCormick Sheila , Muschietti Jorge P 
Published: February 2010

Abstract

Background
LePRK1 and LePRK2 are two pollen receptor kinases localized to the plasma membrane, where they are present in a high molecular weight complex (LePRK complex). LePRK2 is phosphorylated in mature and germinated pollen, but is dephosphorylated when pollen membranes are incubated with tomato or tobacco style extracts.

Results
Here we show that LePRK2 dephosphorylation is mediated by a heat-, acid-, base-, DTT- and protease-resistant component from tobacco styles. Using LePRK2 phosphorylation as a tracking assay for purification, style exudates were subjected to chloroform extraction, anionic exchange, and C18 reverse-phase chromatography columns. We finally obtained a single ~3,550 Da compound (as determined by UV-MALDI-TOF MS) that we named STIL (for Style Interactor for LePRKs). STIL increased pollen tube lengths of in vitro germinated pollen in a dose-dependent manner.

Conclusion
We propose that the LePRK complex perceives STIL, resulting in LePRK2 dephosphorylation and an increase in pollen tube growth.
Genetic diversity of NS5A protein from hepatitis C virus genotype 3a and its relationship to therapy response
Authors: Bittar Cíntia , Jardim Ana Carolina G , Yamasaki Lilian HT , de Queiróz Artur TL , Carareto Claudia MA , Pinho João Renato R , de Carvalho-Mello Isabel Maria VG , Rahal Paula 
Published: February 2010

Abstract

Background
The quasispecies nature of HCV may have important implications for viral persistence, pathogenicity and resistance to antiviral agents. The variability of one of the viral proteins, NS5A, is believed to be related to the response to IFN therapy, the standard treatment for infection. In this study we analyzed the quasispecies composition of NS5A protein in patients infected with HCV genotype 3a, before IFN therapy.

Methods
Viral RNA was isolated from samples of 12 patients: four sustained virological responders (SVR), four non-responders (NR), and four end-of-treatment responders (ETR). cDNA was synthesized, the NS5A region was amplified and the fragments obtained were cloned. Fifteen clones from each patient were sequenced with eight primers, generating 179 contigs.

Results
Higher values for substitution (either synonymous or non-synonymous) and for distance were found in the SVR group. However, the NR group showed relatively more non-synonymous mutations than the other groups, owing to the higher values of dN/dS in complete NS5A and most specific regions. Overall, NS5A protein is undergoing purifying selection, since all dN/dS ratios values are below 0.5.

Conclusions
Our study provides an overview of the genetic variability of complete NS5A protein in HCV genotype 3a.
Activated CD4+T cells enhance radiation effect through the cooperation of interferon-γ and TNF-α
Authors: Wang Yixiang , Radfar Soroosh , Khong Hung T 
Published: February 2010

AbstractBackgroundApproaches that enhance radiation effect may lead to improved clinical outcome and decrease toxicity. Here we investigated whether activated CD4+ T cells (aCD4) can serve as an effective radiosensitizer.MethodsCD4+ T cells were activated with anti-CD3 and anti-CD28 mAbs. Hela cells were presensitized with aCD4 or conditioned supernatant (aCD4S) or recombinant cytokines for 2 days, followed γ-irradiation. The treated cells were cultured for an additional 2 to 5 days for cell proliferation, cell cycle, and western blot assays. For confirmation, other cancer cell lines were also used.ResultsPresensitization of tumor cells with aCD4 greatly increased tumor cell growth inhibition. Soluble factors secreted from activated CD4+T cells were primarily responsible for the observed effect. IFN-γ seemed to play a major role. TNF-α, though inactive by itself, significantly augmented the radiosensitizing activity of IFN-γ. aCD4S, but not IFN-γ or IFN-γ/TNF-α combination, was found to enhance the γ-irradiation-induced G2/M phase arrest. Bax expression was highly upregulated in Hela cells presensitized with aCD4S followed by γ-irradiation. The radio-sensitizing activity of aCD4 is not uniquely observed with Hela cell line, but also seen with other cancer cell lines of various histology.ConclusionsOur findings suggest possible molecular and cellular mechanisms that may help explain the radio-sensitization effect of activated lymphocytes, and may provide an improved strategy in the treatment of cancer with radiotherapy.
Towards treatment planning and treatment of deep-seated solid tumors by electrochemotherapy
Authors: Miklavcic Damijan , Snoj Marko , Zupanic Anze , Kos Bor , Cemazar Maja , Kropivnik Mateja , Bracko Matej , Pecnik Tjasa , Gadzijev Eldar , Sersa Gregor 
Published: February 2010

Abstract

Background
Electrochemotherapy treats tumors by combining specific chemotherapeutic drugs with an intracellular target and electric pulses, which increases drug uptake into the tumor cells. Electrochemotherapy has been successfully used for treatment of easily accessible superficial tumor nodules. In this paper, we present the first case of deep-seated tumor electrochemotherapy based on numerical treatment planning.

Methods
The aim of our study was to treat a melanoma metastasis in the thigh of a patient. Treatment planning for electrode positioning and electrical pulse parameters was performed for two different electrode configurations: one with four and another with five long needle electrodes. During the procedure, the four electrode treatment plan was adopted and the patient was treated accordingly by electrochemotherapy with bleomycin. The response to treatment was clinically and radiographically evaluated. Due to a partial response of the treated tumor, the metastasis was surgically removed after 2 months and pathological analysis was performed.

Results
A partial response of the tumor to electrochemotherapy was obtained. Histologically, the metastasis showed partial necrosis due to electrochemotherapy, estimated to represent 40-50% of the tumor. Based on the data obtained, we re-evaluated the electrical treatment parameters in order to correlate the treatment plan with the clinical response. Electrode positions in the numerical model were updated according to the actual positions during treatment. We compared the maximum value of the measured electric current with the current predicted by the model and good agreement was obtained. Finally, tumor coverage with an electric field above the reversible threshold was recalculated and determined to be approximately 94%. Therefore, according to the calculations, a small volume of tumor cells remained viable after electrochemotherapy, and these were sufficient for tumor regrowth.

Conclusions
In this, the first reported clinical case, deep-seated melanoma metastasis in the thigh of the patient was treated by electrochemotherapy, according to a treatment plan obtained by numerical modeling and optimization. Although only a partial response was obtained, the presented work demonstrates that treatment of deep-seated tumor nodules by electrochemotherapy is feasible and sets the ground for numerical treatment planning-based electrochemotherapy.

Trial registration
EudraCT:2008-008290-54
Expression of the leukemic prognostic marker CD7 is linked to epigenetic modifications in chronic myeloid leukemia
Authors: Rogers Sally L , Zhao Yun , Jiang Xiaoyan , Eaves Connie J , Mager Dixie L , Rouhi Arefeh 
Published: February 2010

AbstractBackgroundExpression levels of the cell surface glycoprotein, CD7, and the serine protease, elastase 2 (ELA2), in the leukemic cells of patients with chronic myeloid leukemia (CML) have been associated with clinical outcome. However, little is known about the mechanisms that underlie the variable expression of these genes in the leukemic cells.ResultsTo address this question, we compared the level of their expression with the DNA methylation and histone acetylation status of 5' sequences of both genes in leukemic cell lines and primitive (lin-CD34+) leukemic cells from chronic phase CML patients. DNA methylation of theELA2gene promoter did not correlate with its expression pattern in lin-CD34+cells from chronic phase CML patient samples even though there was clear differential DNA methylation of this locus inELA2-expressing and non-expressing cell lines. In contrast, we found a strong relation between CD7 expression and transcription-permissive chromatin modifications, both at the level of DNA methylation and histone acetylation with evidence of hypomethylation of theCD7promoter region in the lin-CD34+cells from CML patients with high CD7 expression.ConclusionThese findings indicate a link between epigenetic modifications and CD7 expression in primitive CML cells.
Phase I Pharmacokinetic and Pharmacodynamic Study of 17-dimethylaminoethylamino-17-demethoxygeldanamycin, an Inhibitor of Heat-Shock Protein 90, in Patients With Advanced Solid Tumors
Authors: Ramanathan Ramesh K. , Egorin Merrill J. , Erlichman Charles , Remick Scot C. , Ramalingam Suresh S. , Naret Cynthia , Holleran Julianne L. , TenEyck Cynthia J. , Ivy S. Percy , Belani Chandra P. 
Published: February 2010

Purpose To define the maximum tolerated dose, toxicities, pharmacokinetics, and pharmacodynamics of 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17DMAG). Methods 17DMAG was given intravenously over 1 hour daily for 5 days (schedule A) or daily for 3 days (schedule B) every 3 weeks. Plasma 17DMAG concentrations were measured by liquid chromatography/mass spectrometry. Heat-shock proteins (HSPs) and client proteins were evaluated at baseline and after treatment on day 1 in peripheral blood mononuclear cells (PBMCs) and in pre- and post-treatment (24 hours) biopsies done during cycle 1 at the recommended phase II dose (n = 7). Results Fifty-six patients were entered: 26 on schedule A; 30 on schedule B. The recommended phase II doses for schedules A and B were 16 mg/m2 and 25 mg/m2, respectively. Grade 3/4 toxicities included liver function test elevation (14%), pneumonitis (9%), diarrhea (4%), nausea (4%), fatigue (4%) and thrombocytopenia (4%). There were no objective responses. Four patients had stable disease. 17DMAG half-life was 24 ± 15 hours. 17DMAG area under the curve (range, 0.7 to 14.7 mg/mL × h) increased linearly with dose. The median HSP90, HSP70, and integrin-linked kinase levels were 87.5% (n = 14), 124% (n = 20), and 99.5% (n = 20) of baseline. Changes in HSPs and client proteins in tumor biopsies were not consistent between baseline and 24 hours nor did they change in the same direction as those in PBMCs collected at the time of biopsy. Conclusion The recommended phase II doses of 17DMAG (16 mg/m2 × 5 days or 25 mg/m2 × 3 days, every 3 weeks) are well tolerated and suitable for further evaluation.
HIV As a Risk Factor for Lung Cancer in Women: Data From the Women's Interagency HIV Study
Authors: Levine Alexandra M. , Seaberg Eric C. , Hessol Nancy A. , Preston-Martin Susan , Silver Sylvia , Cohen Mardge H. , Anastos Kathryn , Minkoff Howard , Orenstein Jan , Dominguez Geraldina , Watts D. Heather 
Published: February 2010

Purpose Prior reports of an increased risk of lung cancer in HIV-infected individuals have not always included control groups, nor considered other risk factors such as tobacco exposure. We sought to determine the role of HIV infection and highly active antiretroviral therapy (HAART) on lung cancer incidence in 2,651 HIV-infected and 898 HIV-uninfected women from the Women's Interagency HIV Study (WIHS). Methods A prospective study of the incidence rates of lung cancer was conducted, with cases identified through medical records, death certificates, and state cancer registries. Standardized incidence ratios (SIRs) were calculated to compare lung cancer incidence among HIV-infected and uninfected WIHS participants, with population-based expectations using the Surveillance, Epidemiology, and End Results registry. Behavioral characteristics in the WIHS were compared to US women by age and race adjusting the population-based data from the National Health and Nutritional Examination Survey (NHANES) III. Results Incidence rates of lung cancer were similar among HIV-infected and uninfected WIHS women. Lung cancer SIRs were increased in both HIV-infected and -uninfected women compared with population expectations, but did not differ by HIV status. Among HIV-infected women, lung cancer incidence rates were similar in pre-HAART and HAART eras. All WIHS women with lung cancer were smokers; the risk of lung cancer increased with cumulative tobacco exposure. WIHS women were statistically more likely to smoke than US women studied in NHANES III. Conclusion HIV infection is strongly associated with smoking behaviors that increase lung cancer risk. The role of HIV itself remains to be clarified.