bluuebunny/crossref_metadata_2025_split huggingface dataset:
GIM3E: condition-specific models of cellular metabolism developed from metabolomics and expression data
Authors: Schmidt Brian J. , Ebrahim Ali , Metz Thomas O. , Adkins Joshua N. , Palsson Bernhard Ø. , Hyduke Daniel R. 
Published: August 2013

Abstract
Motivation: Genome-scale metabolic models have been used extensively to investigate alterations in cellular metabolism. The accuracy of these models to represent cellular metabolism in specific conditions has been improved by constraining the model with omics data sources. However, few practical methods for integrating metabolomics data with other omics data sources into genome-scale models of metabolism have been developed.
Results: GIM3E (Gene Inactivation Moderated by Metabolism, Metabolomics and Expression) is an algorithm that enables the development of condition-specific models based on an objective function, transcriptomics and cellular metabolomics data. GIM3E establishes metabolite use requirements with metabolomics data, uses model-paired transcriptomics data to find experimentally supported solutions and provides calculations of the turnover (production/consumption) flux of metabolites. GIM3E was used to investigate the effects of integrating additional omics datasets to create increasingly constrained solution spaces of Salmonella Typhimurium metabolism during growth in both rich and virulence media. This integration proved to be informative and resulted in a requirement of additional active reactions (12 in each case) or metabolites (26 or 29, respectively). The addition of constraints from transcriptomics also impacted the allowed solution space, and the cellular metabolites with turnover fluxes that were necessarily altered by the change in conditions increased from 118 to 271 of 1397.
Availability: GIM3E has been implemented in Python and requires a COBRApy 0.2.x. The algorithm and sample data described here are freely available at: http://opencobra.sourceforge.net/
Contacts: brianjamesschmidt@gmail.com or hyduke@usu.edu
Supplementary information: Supplementary information is available at Bioinformatics online.
RNAfbinv: an interactive Java application for fragment-based design of RNA sequences
Authors: Weinbrand Lina , Avihoo Assaf , Barash Danny 
Published: August 2013

Abstract
Summary: In RNA design problems, it is plausible to assume that the user would be interested in preserving a particular RNA secondary structure motif, or fragment, for biological reasons. The preservation could be in structure or sequence, or both. Thus, the inverse RNA folding problem could benefit from considering fragment constraints.
We have developed a new interactive Java application called RNA fragment-based inverse that allows users to insert an RNA secondary structure in dot-bracket notation. It then performs sequence design that conforms to the shape of the input secondary structure, the specified thermodynamic stability, the specified mutational robustness and the user-selected fragment after shape decomposition. In this shape-based design approach, specific RNA structural motifs with known biological functions are strictly enforced, while others can possess more flexibility in their structure in favor of preserving physical attributes and additional constraints.
Availability: RNAfbinv is freely available for download on the web at http://www.cs.bgu.ac.il/∼RNAexinv/RNAfbinv. The site contains a help file with an explanation regarding the exact use.
Contact: dbarash@cs.bgu.ac.il
catRAPID omics: a web server for large-scale prediction of protein–RNA interactions
Authors: Agostini Federico , Zanzoni Andreas , Klus Petr , Marchese Domenica , Cirillo Davide , Tartaglia Gian Gaetano 
Published: August 2013

Abstract
Summary: Here we introduce catRAPID omics, a server for large-scale calculations of protein–RNA interactions. Our web server allows (i) predictions at proteomic and transcriptomic level; (ii) use of protein and RNA sequences without size restriction; (iii) analysis of nucleic acid binding regions in proteins; and (iv) detection of RNA motifs involved in protein recognition.
Results: We developed a web server to allow fast calculation of ribonucleoprotein associations in Caenorhabditis elegans, Danio rerio, Drosophila melanogaster, Homo sapiens, Mus musculus, Rattus norvegicus, Saccharomyces cerevisiae and Xenopus tropicalis (custom libraries can be also generated). The catRAPID omics was benchmarked on the recently published RNA interactomes of Serine/arginine-rich splicing factor 1 (SRSF1), Histone-lysine N-methyltransferase EZH2 (EZH2), TAR DNA-binding protein 43 (TDP43) and RNA-binding protein FUS (FUS) as well as on the protein interactomes of U1/U2 small nucleolar RNAs, X inactive specific transcript (Xist) repeat A region (RepA) and Crumbs homolog 3 (CRB3) 3′-untranslated region RNAs. Our predictions are highly significant (P &lt; 0.05) and will help the experimentalist to identify candidates for further validation.
Availability: catRAPID omics can be freely accessed on the Web at http://s.tartaglialab.com/catrapid/omics. Documentation, tutorial and FAQs are available at http://s.tartaglialab.com/page/catrapid_group.
Contact: gian.tartaglia@crg.eu
An O2If* star found in isolation in the backyard of NGC 3603
Authors: Roman-Lopes A. 
Published: August 2013

AbstractIn this Letter, we communicate the identification of a new Galactic O2If* star (MTT 68) isolated at a projected linear distance of 3 pc from the centre of the starburst cluster NGC 3603. From its optical photometry, I computed a bolometric luminosity MBol = −10.7, which corresponds to a total stellar luminosity of 1.5 × 106 L⊙. It was found to be an interesting similarity between MTT 68 and the well-known multiple system HD 93129. From Hubble Space Telescope (HST)F656N images of the NGC 3603 field, it was found that MTT 68 is actually a visual binary system with an angular separation of 0.38 arcsec, which corresponds to a projected (minimum) linear distance of rA−B = 1.4 × 10−2 pc. This value is similar to that for the HD 93129A (O2If*) and HD 93129B (O3.5) pair, rA−B = 3.0 × 10−2 pc. On the other hand, HD 93129A has a third closer companion named HD 93129Ab (O3.5) at only 0.053 arcsec, and taking into account that the X-ray to total stellar luminosity ratio for the MTT 68 system (LX/LBol ∼1 × 10−5) is about two orders of magnitude above the canonical value expected for single stars, I suspect that the MTT 68 system probably hosts another massive companion possibly to close to be properly resolved by the HST archive images.
Using Exome Data to Identify Malignant Hyperthermia Susceptibility Mutations
Authors: Gonsalves Stephen G. , Ng David , Johnston Jennifer J. , Teer Jamie K. , Stenson Peter D. , Cooper David N. , Mullikin James C. , Biesecker Leslie G. 
Published: August 2013

Abstract

Background:
Malignant hyperthermia susceptibility (MHS) is a life-threatening, inherited disorder of muscle calcium metabolism, triggered by anesthetics and depolarizing muscle relaxants. An unselected cohort was screened for MHS mutations using exome sequencing. The aim of this study was to pilot a strategy for the RYR1 and CACNA1S genes.

Methods:
Exome sequencing was performed on 870 volunteers not ascertained for MHS. Variants in RYR1 and CACNA1S were annotated using an algorithm that filtered results based on mutation type, frequency, and information in mutation databases. Variants were scored on a six-point pathogenicity scale. Medical histories and pedigrees were reviewed for malignant hyperthermia and related disorders.

Results:
The authors identified 70 RYR1 and 53 CACNA1S variants among 870 exomes. Sixty-three RYR1 and 41 CACNA1S variants passed the quality and frequency metrics but the authors excluded synonymous variants. In RYR1, the authors identified 65 missense mutations, one nonsense, two that affected splicing, and one non–frameshift indel. In CACNA1S, 48 missense, one frameshift deletion, one splicing, and one non–frameshift indel were identified. RYR1 variants predicted to be pathogenic for MHS were found in three participants without medical or family histories of MHS. Numerous variants, previously described as pathogenic in mutation databases, were reclassified by the authors as being of unknown pathogenicity.

Conclusions:
Exome sequencing can identify asymptomatic patients at risk for MHS, although the interpretation of exome variants can be challenging. The use of exome sequencing in unselected cohorts is an important tool to understand the prevalence and penetrance of MHS, a critical challenge for the field.
Systematic studies of modified vocalization: the effect of speech rate on speech production measures during metronome‐paced speech in persons who stutter
Authors: Davidow Jason H. 
Published: August 2013

AbstractBackgroundMetronome‐paced speech results in the elimination, or substantial reduction, of stuttering moments. The cause of fluency during this fluency‐inducing condition is unknown. Several investigations have reported changes in speech pattern characteristics from a control condition to a metronome‐paced speech condition, but failure to control speech rate between conditions limits our ability to determine if the changes were necessary for fluency.AimsThis study examined the effect of speech rate on several speech production variables during one‐syllable‐per‐beat metronomic speech in order to determine changes that may be important for fluency during this fluency‐inducing condition.Methods & ProceduresThirteen persons who stutter (PWS), aged 18–62 years, completed a series of speaking tasks. Several speech production variables were compared between conditions produced at different metronome beat rates, and between a control condition and a metronome‐paced speech condition produced at a rate equal to the control condition.Outcomes & ResultsVowel duration, voice onset time, pressure rise time and phonated intervals were significantly impacted by metronome beat rate. Voice onset time and the percentage of short (30–100 ms) phonated intervals significantly decreased from the control condition to the equivalent rate metronome‐paced speech condition.Conclusions & ImplicationsA reduction in the percentage of short phonated intervals may be important for fluency during syllable‐based metronome‐paced speech for PWS. Future studies should continue examining the necessity of this reduction. In addition, speech rate must be controlled in future fluency‐inducing condition studies, including neuroimaging investigations, in order for this research to make a substantial contribution to finding the fluency‐inducing mechanism of fluency‐inducing conditions.
17β‐Oestradiol Protects Primary‐Cultured Rat Cortical Neurons from Ketamine‐Induced Apoptosis by Activating PI3K/Akt/Bcl‐2 Signalling
Authors: Li Jianli , Wu Honghai , Xue Gai , Wang Pei , Hou Yanning 
Published: August 2013

AbstractNumerous studies in rodents have indicated that exposure to ketamine during the period when synaptogenesis is highly active induces neurodegeneration. Thus, there is a growing need to develop strategies to prevent ketamine‐induced brain injury in the developing brain. Oestradiol is a neuroactive steroid that prevents neuronal cell death in different experimental models by activating cell survival signals and inhibiting apoptotic signals. The main goal of this study was to investigate the neuroprotective effects of 17β‐oestradiol against ketamine‐induced apoptotic neurodegeneration in primary‐cultured cortical neurons. The data revealed that 17β‐oestradiol (0.1 μM) in combination with ketamine (100 μM) increased cell viability in the MTT assay and reduced the number of apoptotic cells detected by TUNEL and Hoechst 33258 staining. To elucidate a possible mechanism by which 17β‐oestradiol exerts its neuroprotective effect, we investigated the PI3K pathway using an inhibitor of PI3K, LY294002. The protective effects of 17β‐oestradiol were abrogated by LY294002. Furthermore, we found that 17β‐oestradiol not only induced phosphorylation of the PI3K substrate Akt, but also increased the expression of Bcl‐2, which down‐regulated ketamine‐induced caspase‐3 activity and inhibited neuronal apoptosis. These data demonstrate that 17β‐oestradiol exerts a neuroprotective effect against ketamine‐induced neuronal apoptosis by activating the PI3K/Akt/Bcl‐2 signalling pathway. Therefore, 17β‐oestradiol appears to be a promising agent in preventing or reversing ketamine's toxic effects on neurons at an early developmental stage.
A phase III randomized trial comparing glucocorticoid monotherapy versus glucocorticoid and rituximab in patients with autoimmune haemolytic anaemia
Authors: Birgens Henrik , Frederiksen Henrik , Hasselbalch Hans C. , Rasmussen Inge H. , Nielsen Ove J. , Kjeldsen Lars , Larsen Herdis , Mourits‐Andersen Torben , Plesner Torben , Rønnov‐Jessen Dorthe , Vestergaard Hanne , Klausen Tobias W. , Schöllkopf Claudia 
Published: August 2013

SummaryThe impact of first‐line treatment with the anti‐CD 20 chimeric monoclonal antibody rituximab in patients with warm‐antibody reactive autoimmune haemolytic anaemia (WAIHA) is unknown. We report the first randomized study of 64 patients with newly diagnosed WAIHA who received prednisolone and rituximab combined (N = 32) or prednisolone monotherapy (N = 32). After 12 months, a satisfactory response was observed in 75% of the patients treated with rituximab and prednisolone but in a significantly smaller proportion (36%) of those given prednisolone alone (P = 0·003). Furthermore, relapse‐free survival was significantly better after the combined therapy than after prednisolone monotherapy (P = 0·02). After 36 months, about 70% of the patients were still in remission in the rituximab‐prednisolone group, whereas only about 45% were still in complete or partial remission in the prednisolone group. There was no significant difference between the two groups regarding adverse reactions to the studied medications. Likewise, serious adverse events were equally distributed, and no allergic reactions to rituximab were recorded. In conclusion, our data show that using rituximab and prednisolone combined rather than prednisolone alone as first‐line treatment in WAIHA increases both the rate and the duration of the response.
EMPLOYMENT EFFECTS OF HEALTH SHOCKS: THE ROLE OF FRINGE BENEFITS
Authors: Zimmer David M. 
Published: August 2013

ABSTRACTThis paper examines whether health shocks influence labour supply. Estimates rely on detailed health measures that not only are more homogeneous than commonly‐used self‐reported health measures, but they also can be interpreted as plausibly exogenous with respect to labour supply. Further, this paper investigates the unique role that certain fringe benefits, namely health insurance and paid sick leave, play in the link between health shocks and subsequent employment activity. Results show that, compared to commonly‐used self‐reported measures of health, health problems defined by the US government as ‘priority’ conditions correlate with smaller labour supply shifts, but non‐work‐related injuries lead to larger shifts. Second, the arrival of a health shock appears to reduce the probability of remaining employed full time, while also increasing the likelihood of quitting work. Relatively few full‐time workers who acquire health problems switch to part‐time employment. Third, in the event of a health shock, sick leave appears to facilitate reductions in employment activities, while employer‐provided insurance appears to hinder such adjustments.
DYNAMICS OF PRODUCTIVITY AND COST OF LABOUR IN ITALIAN MANUFACTURING FIRMS
Authors: Bottazzi Giulio , Grazzi Marco 
Published: August 2013

ABSTRACTThis paper studies the impact of size on labour cost and productivity for Italian manufacturing firms. The distributions of both labour cost and productivity display a wide support, even when disaggregated by sector of industrial activity. Further, both labour cost and productivity, when considered alone, are growing with the size of the firm. We investigate this relationship on a new set of data and we are able to show that once productivity differences among firms have been accounted for, size still retains a positive effect on cost of labour in most of the sectors considered.
Therapeutic Time Window and Dose Dependence of Xenon Delivered via Echogenic Liposomes for Neuroprotection in Stroke
Authors: Peng Tao , Britton George L. , Kim Hyunggun , Cattano Davide , Aronowski Jaroslaw , Grotta James , McPherson David D. , Huang Shao‐Ling 
Published: August 2013

SummaryAimsNeurologic impairment following ischemic injury complicates the quality of life for stroke survivors. Xenon (Xe) has favorable neuroprotective properties to modify stroke. Xe delivery is hampered by a lack of suitable administration strategies. We have developed Xe‐containing echogenic liposomes (Xe‐ELIP) for systemic Xe delivery. We investigated the time window for Xe‐ELIP therapeutic effect and the most efficacious dose for neuroprotection. Molecular mechanisms for Xe neuroprotection were investigated.MethodsXenon‐containing echogenic liposomes were created by a previously developed pressurization‐freezing method. Following right middle cerebral artery occlusion (2 h), animals were treated with Xe‐ELIP at 2, 3, or 5 h to determine time window of therapeutic effect. The neuroprotectant dosage for optimal effect was evaluated 3 h after stroke onset. Expression of brain‐derived neurotrophic factor (BDNF), protein kinase B (Akt), and mitogen‐activated protein kinases (MAPK) was determined.ResultsXenon‐containing echogenic liposomes administration for up to 5 h after stroke onset reduced infract size. Treatment groups given 7 and 14 mg/kg of Xe‐ELIP reduced infarct size. Behavioral outcomes corresponded to changes in infarct volume. Xe‐ELIP treatment reduced ischemic neuronal cell death via activation of both MAPK and Akt. Elevated BDNF expression was shown following Xe‐ELIP delivery.ConclusionThis study demonstrates the therapeutic efficacy of Xe‐ELIP administered within 5 h after stroke onset with an optimal dosage range of 7–14 mg/kg for maximal neuroprotection.
Moderate Hypothermia Inhibits Brain Inflammation and Attenuates Stroke‐Induced Immunodepression in Rats
Authors: Gu Li‐Juan , Xiong Xiao‐Xing , Ito Takashi , Lee Jessica , Xu Bao‐Hui , Krams Sheri , Steinberg Gary K. , Zhao Heng 
Published: August 2013

SummaryAimsStroke causes both brain inflammation and immunodepression. Mild‐to‐moderate hypothermia is known to attenuate brain inflammation, but its role in stroke‐induced immunodepression (SIID) of the peripheral immune system remains unknown. This study investigated the effects in rats of moderate intra‐ischemic hypothermia on SIID and brain inflammation.MethodsStroke was induced in rats by permanent distal middle cerebral artery occlusion combined with transient bilateral common carotid artery occlusion, while body temperature was reduced to 30°C. Real‐time PCR, flow cytometry, in vitro T‐cell proliferation assays, in vivo delayed‐type hypersensitivity (DTH) reaction and confocal microscopy were used to study SIID and brain inflammation.ResultsBrief intra‐ischemic hypothermia helped maintain certain leukocytes in the peripheral blood and spleen and enhanced T‐cell proliferation in vitro and delayed‐type hypersensitivity in vivo, suggesting that hypothermia reduces SIID. In contrast, in the brain, brief intra‐Ischemic hypothermia inhibited mRNA expression of anti‐inflammatory cytokine IL‐10 and proinflammatory mediators INF‐γ, TNF‐α, IL‐2, IL‐1β and MIP‐2. Brief intra‐Ischemic hypothermia also attenuated the infiltration of lymphocytes, neutrophils (MPO+ cells) and macrophages (CD68+ cells) into the ischemic brain, suggesting that hypothermia inhibited brain inflammation.ConclusionsBrief intra‐ischemic hypothermia attenuated SIID and protected against acute brain inflammation.
Change in Plasma Levels of Amino Acid Neurotransmitters and its Correlation with Clinical Heterogeneity in Early Parkinson's Disease Patients
Authors: Yuan Yong‐Sheng , Zhou Xian‐Ju , Tong Qing , Zhang Lei , Zhang Lian , Qi Zhi‐Qiang , Ge Song , Zhang Ke‐Zhong 
Published: August 2013

SummaryBackgroundThe correlation between plasma amino acid (AA) neurotransmitters and clinical heterogeneity in early patients with Parkinson's disease (PD) is still poorly understood.AimsTo examine the plasma levels of AA neurotransmitters in early patients with PD and to evaluate their correlation with PD subtypes.MethodsBased on the predominant symptoms, fifty‐one patients with PD were enrolled and divided into four subgroups: (1) akinetic‐rigid type (ART), (2) tremor‐dominant type (TDT), (3) postural instability/gait difficulty type (PIGD), and (4) mixed type (MT). Plasma levels of AA were measured by HPLC‐RF, and their potential diagnostic practicality and their association with PD subtypes were evaluated by the receiver operating characteristic (ROC) and correlation analysis, respectively.ResultsPatients with PD exhibited markedly lower levels of Asp, Glu, Tau, L‐ser, and lower values of Glu/GABA ratio than healthy controls. The ROC analysis revealed their high sensitivity (77.1–87.5%) and specificity (58.8–88.2%). Furthermore, the glutamic acid (Glu), γ‐aminobutyric acid (GABA) level in the PIGD subtype was increased as compared with other subtypes and was negatively correlated with the ART/PIGD ratio.ConclusionThe decrease in plasma Asp, Glu, Tau, L‐ser levels, and the value of Glu/GABA ratio may be helpful for early PD diagnosis. The elevated GABA level may be the biochemical basis for the specific symptoms of PIGD PD.
White matter maturation supports the development of reasoning ability through its influence on processing speed
Authors: Ferrer Emilio , Whitaker Kirstie J. , Steele Joel S. , Green Chloe T. , Wendelken Carter , Bunge Silvia A. 
Published: August 2013

AbstractThe structure of the human brain changes in several ways throughout childhood and adolescence. Perhaps the most salient of these changes is the strengthening of white matter tracts that enable distal brain regions to communicate with one another more quickly and efficiently. Here, we sought to understand whether and how white matter changes contribute to improved reasoning ability over development. In particular, we sought to understand whether previously reported relationships between white matter microstructure and reasoning are mediated by processing speed. To this end, we analyzed diffusion tensor imaging data as well as data from standard psychometric tests of cognitive abilities from 103 individuals between the ages of 6 and 18. We used structural equation modeling to investigate the network of relationships between brain and behavior variables. Our analyses provide support for the hypothesis that white matter maturation (as indexed either by microstructural organization or volume) supports improved processing speed, which, in turn, supports improved reasoning ability.
Evaluation of thermal stress in hydroxyapatite film fabricated by powder jet deposition
Authors: Akatsuka Ryo , Matsumura Ken , Noji Miyoko , Kuriyagawa Tsunemoto , Sasaki Keiichi 
Published: August 2013

This study aimed to create a thick hydroxyapatite (HA) film on the surface of a human tooth via a powder jet deposition (PJD) device for dental handpieces, and to examine the microstructural and mechanical properties of the HA film. In particular, the effects of thermal stress on this film were evaluated. The HA film was created by blasting 3.18‐μm HA particles, calcinated at 1,200°C, onto the enamel substrate at room temperature and atmospheric pressure. An HA film with an area of 3 mm × 3 mm was prepared and polished. The following HA film parameters were evaluated from the three‐dimensional surface profile: surface roughness, Vickers hardness, and bonding strength before and after artificial aging induced by 500 cycles of thermal cycling (5–55°C). The HA particles in the deposited film were densely packed, and the surface of the HA film was unchanged after thermal cycling. There were also no significant differences in the hardness and the bonding strength of the HA film before and after thermal cycling. The HA film created in this study demonstrated excellent microstructural and mechanical properties, even after the application of thermal stress.