bluuebunny/crossref_metadata_2025_split huggingface dataset:
Drug Side Effect Profiles as Molecular Descriptors for Predictive Modeling of Target Bioactivity
Authors: Baker Nancy C. , Fourches Denis , Tropsha Alexander 
Published: February 2015

AbstractWe have explored the potential of using side effect profiles of drugs to predict their bioactivities at the receptor level. Serotonin 5‐HT6 binding and dopamine antagonism were investigated in separate studies. A set of 5‐HT6 binders and non‐binders was retrieved from the PDSP Ki database, whereas dopamine antagonists were retrieved from the MeSH Pharmaceutical Action file. The side effect data was extracted from ChemoText, a data repository containing MeSH annotations pulled from MEDLINE records. These side effects profiles were treated as molecular descriptors enabling a QSAR‐like approach to build models that could reliably discriminate different classes of molecules, e.g., binders versus non‐binders, and dopamine antagonists versus non‐antagonists. Selected models with the best external prediction performances were applied to a library of ca. 1000 chemicals with known side effects profiles in order to predict their potential 5‐HT6 binding and/or dopamine antagonism. In each case the virtual screening process was able to identify putatively active compounds that through subsequent literature‐based validation were found to be likely or known 5‐HT6 binders or dopamine antagonists. These results demonstrate that side effect profiles can be utilized to predict a drug’s unknown molecular activity, thus representing a valuable opportunity in repositioning the drug for a new indications.
Effect of voluntary physical activity initiated at age 7 months on skeletal hindlimb and cardiac muscle function in mdx mice of both genders
Authors: Ferry Arnaud , Benchaouir Rachid , Joanne Pierre , Peat Rachel A. , Mougenot Nathalie , Agbulut Onnik , Butler‐Browne Gillian 
Published: February 2015

ABSTRACTIntroduction: The effects of voluntary activity initiated in adult mdx (C57BL/10ScSc‐DMDmdx/J) mice on skeletal and cardiac muscle function have not been studied extensively. Methods: We studied the effects of 3 months of voluntary wheel running initiated at age 7 months on hindlimb muscle weakness, increased susceptibility to muscle contraction−induced injury, and left ventricular function in mdx mice. Results: We found that voluntary wheel running did not worsen the deficit in force‐generating capacity and the force drop after lengthening contractions in either mdx mouse gender. It increased the absolute maximal force of skeletal muscle in female mdx mice. Moreover, it did not affect left ventricular function, structural heart dimensions, cardiac gene expression of inflammation, fibrosis, or remodeling markers. Conclusion: These results indicate that voluntary activity initiated at age 7 months had no detrimental effects on skeletal or cardiac muscles in either mdx mouse gender. Muscle Nerve 52: 788–794, 2015
Muscle ultrasound quantifies disease progression over time in infants and young boys with duchenne muscular dystrophy
Authors: Zaidman Craig M. , Malkus Elizabeth C. , Connolly Anne M. 
Published: February 2015

ABSTRACTIntroduction: Quantitative muscle ultrasound (QUS) in boys with Duchenne muscular dystrophy (DMD) shows increased echointensity as muscle is replaced with fat and fibrosis. Studies of quantitative ultrasound in infants/young boys with DMD over time have not been reported. Methods: We used calibrated muscle backscatter (cMB), a reproducible measure of ultrasound echointensity, to quantify muscle pathology in 5 young boys with DMD (ages 0.5–2.8 years) over 17–29 months. We compared the results with repeated assessments of function (n = 4) and with muscle ultrasound images from a cross‐section of 6 male controls (0.6–3.1 years). Results: cMB in boys with DMD increased (worsened) over time (P < 0.001), whereas function improved. After age 2 years, cMB in most (4 of 5) boys with DMD was higher than in any control. Conclusions: QUS measures disease progression in young boys with DMD despite functional improvements. QUS could be employed as an outcome measure for serial assessment of young boys with DMD. Muscle Nerve 52: 334–338, 2015
Morphological changes in the cervical muscles of women with chronic whiplash can be modified with exercise—A pilot study
Authors: O'leary Shaun , Jull Gwendolen , Van Wyk Luke , Pedler Ashley , Elliott James 
Published: February 2015

ABSTRACTIntroduction: In this preliminary study we determined whether MRI markers of cervical muscle degeneration [elevated muscle fatty infiltration (MFI), cross‐sectional area (CSA), and reduced relative muscle CSA (rmCSA)] could be modified with exercise in patients with chronic whiplash. Methods: Five women with chronic whiplash undertook 10 weeks of neck exercise. MRI measures of the cervical multifidus (posterior) and longus capitus/colli (anterior) muscles, neck muscle strength, and self‐reported neck disability were recorded at baseline and at completion of the exercise program. Results: Overall significant increases in CSA and rmCSA were observed for both muscles, but significant reductions in MFI were only evident in the cervical multifidus muscle. These changes coincided with increased muscle strength and reduced neck disability. Conclusions: MRI markers of muscle morphology in individuals with chronic whiplash appear to be modifiable with exercise. Muscle Nerve 52: 772–779, 2015
Ultrasonographic identification of nerve pathology in neuralgic amyotrophy: Enlargement, constriction, fascicular entwinement, and torsion
Authors: Arányi Zsuzsanna , Csillik Anita , Dévay Katalin , Rosero Maja , Barsi Péter , Böhm Josef , Schelle Thomas 
Published: February 2015

ABSTRACTIntroductionThe aim of this study was to characterize the ultrasonographic findings on nerves in neuralgic amyotrophy.MethodsFourteen patients with neuralgic amyotrophy were examined using high‐resolution ultrasound.ResultsFour types of abnormalities were found: (1) focal or diffuse nerve/fascicle enlargement (57%); (2) incomplete nerve constriction (36%); (3) complete nerve constriction with torsion (50%; hourglass‐like appearance); and (4) fascicular entwinement (28%). Torsions were confirmed intraoperatively and were seen on the radial nerve in 85% of patients. A significant correlation was found between no spontaneous recovery of nerve function and constriction/torsion/fascicular entwinement (P = 0.007).ConclusionUltrasonographic nerve pathology in neuralgic amyotrophy varies in order of severity from nerve enlargement to constriction to nerve torsion, with treatment ranging from conservative to surgical. We postulate that the constriction caused by inflammation is the precursor of torsion and that development of nerve torsion is facilitated by the rotational movements of limbs. Muscle Nerve 52: 503–511, 2015
Fibromyalgia‐like symptoms associated with irritable bowel syndrome: A challenging diagnosis of late‐onset Pompe disease
Authors: Gesquière‐Dando Aude , Attarian Shahram , Maues De Paula André , Pouget Jean , Salort‐Campana Emmanuelle 
Published: February 2015

ABSTRACTIntroduction: Late‐onset Pompe disease (LOPD) is a rare autosomal recessive disorder which usually presents as a limb‐girdle myopathy with early respiratory involvement. Methods: We report 2 sisters with an uncommon presentation of LOPD characterized by fibromyalgia‐like pain associated with irritable bowel syndrome. Results: In both sisters, clinical examination was normal and had remained stable for 10 years. The serum creatine kinase level was mildly elevated. Several muscle biopsies showed slight nonspecific myopathic abnormalities. A dried blood spot test indicated acid maltase deficiency. The diagnosis of LOPD was confirmed genetically. Both sisters subsequently developed proximal muscle weakness after pregnancy and started enzyme replacement therapy. Under treatment, gastrointestinal symptoms improved, but pain persisted. Conclusions: Clinicians should be aware of this atypical presentation of LOPD to enable earlier diagnosis and treatment. Muscle Nerve 52: 300–304, 2015
Amelioration of ischemia‐reperfusion–induced muscle injury by the recombinant human MG53 protein
Authors: Zhu Hua , Hou Jincai , Roe Janet L. , Park Ki Ho , Tan Tao , Zheng Yongqiu , Li Lei , Zhang Cuixiang , Liu Jianxun , Liu Zhenguo , MA Jianjie , Walters Thomas J. 
Published: February 2015

ABSTRACTIntroduction: Ischemia‐reperfusion injury (I‐R) in skeletal muscle requires timely treatment. Methods: Rodent models of I‐R injury were used to test the efficacy of recombinant human MG53 (rhMG53) protein for protecting skeletal muscle. Results: In a mouse I‐R injury model, we found that mg53,−/− mice are more susceptible to I‐R injury. rhMG53 applied intravenously to the wild‐type mice protected I‐R injured muscle, as demonstrated by reduced CK release and Evans blue staining. Histochemical studies confirmed beneficial effects of rhMG53. Of interest, rhMG53 did not protect against I‐R injury in rat skeletal muscle. This was likely due to the fact that the plasma level of endogenous MG53 protein is high in rats. Conclusions: Our data suggest that rhMG53 may be a potential therapy for protection against muscle trauma. A mouse model appears to be a better choice than a rat model for evaluating potential treatments for protecting skeletal muscle. Muscle Nerve 52: 852–858, 2015
Layers of Experiments with Adaptive Combined Design
Authors: Kim Sungil , Kim Heeyoung , Lu Jye‐Chyi , Casciato Michael J. , Grover Martha A. , Hess Dennis W. , Lu Richard W. , Wang Xin 
Published: February 2015

AbstractIn the field of nanofabrication, engineers often face unique challenges in resource‐limited experimental budgets, the sensitive nature of process behavior with respect to controllable variables, and highly demanding tolerance requirements. To effectively overcome these challenges, this article proposes a methodology for a sequential design of experiments through batches of experimental runs, aptly named Layers of Experiments with Adaptive Combined Design (LoE/ACD). In higher layers, where process behavior is less understood, experimental regions cover more design space and data points are more spread out. In lower layers, experimental regions are more focused to improve understanding of process sensitivities in a local, data‐rich environment. The experimental design is a combination of a space‐filling and an optimal design with a tuning parameter that is dependent on the amount of information accumulated over the various layers. The proposed LoE/ACD method is applied to optimize a carbon dioxide (epet‐CO2) assisted deposition process for fabricating silver nanoparticles with pressure and temperature variables. © 2015 Wiley Periodicals, Inc. Naval Research Logistics 62: 127–142, 2015
Active Sensing for Monitoring the Properties of Solid Rocket Motor Propellant Grains
Authors: Lopatin Craig , Grinstein Dan 
Published: February 2015

AbstractAging induced changes in the mechanical properties of solid propellant can lead to defects, such as cracks and grain‐liner separations, that limit the service lifetime of solid rocket motors. The use of embedded sensors is one approach that is being explored by various researchers to augment legacy inspection and prediction methods. We present herein an active sensing technique that is particularly suited for monitoring the properties of solid propellant, as it does not introduce electrical wires into the motor. Based on the use of magnetic induction for excitation and an optical fiber Bragg grating sensor to measure deformation, the method can be used to characterize the properties of a material with which it is in contact. In this paper, we first present proof‐of‐principal experiments demonstrating the utility of the method in characterizing the visco‐elastic properties of an adhesive, and in following changes in viscosity of an epoxy resin during cure. We next apply the method to solid propellant, and present data demonstrating that the method can be used to measure a deflection‐load curve of an aluminized HTPB propellant. In addition, we also show that the observed strain rate sensitivity matches that found in the literature and that the method had more than adequate resolution to observe the expected changes in material properties due to aging.
Production of Gene-Corrected Adult Beta Globin Protein in Human Erythrocytes Differentiated from Patient iPSCs After Genome Editing of the Sickle Point Mutation
Authors: Huang Xiaosong , Wang Ying , Yan Wei , Smith Cory , Ye Zhaohui , Wang Jing , Gao Yongxing , Mendelsohn Laurel , Cheng Linzhao 
Published: February 2015

Abstract
Human induced pluripotent stem cells (iPSCs) and genome editing provide a precise way to generate gene-corrected cells for disease modeling and cell therapies. Human iPSCs generated from sickle cell disease (SCD) patients have a homozygous missense point mutation in the HBB gene encoding adult β-globin proteins, and are used as a model system to improve strategies of human gene therapy. We demonstrate that the CRISPR/Cas9 system designer nuclease is much more efficient in stimulating gene targeting of the endogenous HBB locus near the SCD point mutation in human iPSCs than zinc finger nucleases and TALENs. Using a specific guide RNA and Cas9, we readily corrected one allele of the SCD HBB gene in human iPSCs by homologous recombination with a donor DNA template containing the wild-type HBB DNA and a selection cassette that was subsequently removed to avoid possible interference of HBB transcription and translation. We chose targeted iPSC clones that have one corrected and one disrupted SCD allele for erythroid differentiation assays, using an improved xeno-free and feeder-free culture condition we recently established. Erythrocytes from either the corrected or its parental (uncorrected) iPSC line were generated with similar efficiencies. Currently ∼6%–10% of these differentiated erythrocytes indeed lacked nuclei, characteristic of further matured erythrocytes called reticulocytes. We also detected the 16-kDa β-globin protein expressed from the corrected HBB allele in the erythrocytes differentiated from genome-edited iPSCs. Our results represent a significant step toward the clinical applications of genome editing using patient-derived iPSCs to generate disease-free cells for cell and gene therapies. Stem Cells 2015;33:1470–1479
Genome Modification Leads to Phenotype Reversal in Human Myotonic Dystrophy Type 1 Induced Pluripotent Stem Cell-Derived Neural Stem Cells
Authors: Xia Guangbin , Gao Yuanzheng , Jin Shouguang , Subramony S.H. , Terada Naohiro , Ranum Laura P.W. , Swanson Maurice S. , Ashizawa Tetsuo 
Published: February 2015

AbstractMyotonic dystrophy type 1 (DM1) is caused by expanded CTG repeats in the 3'-untranslated region (3′ UTR) of the DMPK gene. Correcting the mutation in DM1 stem cells would be an important step toward autologous stem cell therapy. The objective of this study is to demonstrate in vitro genome editing to prevent production of toxic mutant transcripts and reverse phenotypes in DM1 stem cells. Genome editing was performed in DM1 neural stem cells (NSCs) derived from human DM1 induced pluripotent stem (iPS) cells. An editing cassette containing SV40/bGH polyA signals was integrated upstream of the CTG repeats by TALEN-mediated homologous recombination (HR). The expression of mutant CUG repeats transcript was monitored by nuclear RNA foci, the molecular hallmarks of DM1, using RNA fluorescence in situ hybridization. Alternative splicing of microtubule-associated protein tau (MAPT) and muscleblind-like (MBNL) proteins were analyzed to further monitor the phenotype reversal after genome modification. The cassette was successfully inserted into DMPK intron 9 and this genomic modification led to complete disappearance of nuclear RNA foci. MAPT and MBNL 1, 2 aberrant splicing in DM1 NSCs were reversed to normal pattern in genome-modified NSCs. Genome modification by integration of exogenous polyA signals upstream of the DMPK CTG repeat expansion prevents the production of toxic RNA and leads to phenotype reversal in human DM1 iPS-cells derived stem cells. Our data provide proof-of-principle evidence that genome modification may be used to generate genetically modified progenitor cells as a first step toward autologous cell transfer therapy for DM1. Stem Cells 2015;33:1829–1838
Hypoxic Preconditioning of Mesenchymal Stromal Cells Induces Metabolic Changes, Enhances Survival, and Promotes Cell Retention In Vivo
Authors: Beegle Julie , Lakatos Kinga , Kalomoiris Stefanos , Stewart Heather , Isseroff R. Rivkah , Nolta Jan A. , Fierro Fernando A. 
Published: February 2015

AbstractMesenchymal stem cells/multipotent stromal cells (MSCs) are promising therapeutics for a variety of conditions. However, after transplantation, cell retention remains extremely challenging. Given that many hypoxic signals are transitory and that the therapeutic administration of MSCs is typically into tissues that are normally hypoxic, we studied the effect of hypoxic preconditioning (HP) prior to new exposure to hypoxia. We show that preincubation for 2 days or more in 1% oxygen reduces serum deprivation-mediated cell death, as observed by higher cell numbers and lower incorporation of EthD-III and Annexin V. Consistently, HP-MSCs expressed significantly lower levels of cytochrome c and heme oxygenase 1 as compared to controls. Most importantly, HP-MSCs showed enhanced survival in vivo after intramuscular injection into immune deficient NOD/SCID-IL2Rgamma−/− mice. Interestingly, HP-MSCs consume glucose and secrete lactate at a slower rate than controls, possibly promoting cell survival, as glucose remains available to the cells for longer periods of time. In addition, we compared the metabolome of HP-MSCs to controls, before and after hypoxia and serum deprivation, and identified several possible mediators for HP-mediated cell survival. Overall, our findings suggest that preincubation of MSCs for 2 days or more in hypoxia induces metabolic changes that yield higher retention after transplantation. Stem Cells 2015;33:1818–1828
Experience‐sensitive epigenetic mechanisms, developmental plasticity, and the biological embedding of chronic disease risk
Authors: Cunliffe Vincent T. 
Published: February 2015

A wide range of developmental, nutritional, environmental, and social factors affect the biological activities of epigenetic mechanisms. These factors change spatiotemporal patterns of gene expression in a variety of different ways and bring significant impacts to bear on development, physiology, and disease risk throughout the life course. Abundant evidence demonstrates that behavioral stressors and adverse nutritional conditions are particularly potent inducers of epigenetic changes and enhancers of chronic disease risks. Recent insights from both human clinical studies and research with model organisms further indicate that such experience‐dependent changes to the epigenome can be transmitted through the germline across multiple generations, with important consequences for the heritability of both adaptive and maladaptive phenotypes. Epigenetics research thus offers many possibilities for developing informative biomarkers of acquired chronic disease risk and determining the effectiveness of preventive and therapeutic interventions. Moreover, the experience‐sensitive nature of these disease risks raises important questions about societal and individual responsibilities for the prevention of ill‐health and the promotion of well‐being during development, across the life course and between generations. Better understanding of how epigenetic mechanisms regulate developmental plasticity and mediate the biological embedding of chronic disease risks is therefore likely to shed important new light on the nature of the pathophysiological mechanisms linking social and health inequalities, and will help to inform public policy initiatives in this area. WIREs Syst Biol Med 2015, 7:53–71. doi: 10.1002/wsbm.1291This article is categorized under:

Developmental Biology > Developmental Processes in Health and Disease
Physiology > Physiology of Model Organisms
Biological Mechanisms > Regulatory Biology
Flux Synthesis, Modulated Crystal Structures, and Physical Properties of REMn0.5SeO (RE = La, Ce)
Authors: Peschke Simon , Nitsche Fabian , Johrendt Dirk 
Published: February 2015

AbstractThe selenide oxides REMn0.5SeO (RE = La, Ce) were synthesized by heating RE2O3, RE, Mn, and Se in a NaI/KI flux at 800 °C, and their modulated crystal structures determined by X‐ray single crystal and powder diffraction {P 1 1 2/n(αβ½)0s, Z = 2, LaMn0.5SeO: a = 405.7(1), b = 405.7(1), c = 915.2(1) pm, γ = 90°, q = [1/10, –1/10, ½]; CeMn0.5SeO: a = 402.0(1), b = 401.8(1), c = 910.7(1) pm, γ = 90.000(4)°, q = [0.0789(2), –0.0783(2), ½]}. The structures are related to the ZrCuSiAs‐type structure with ordered vacancies at the manganese sites. The resulting modulations of the checkerboard pattern in the [Mn0.5Se] layers can be approximated by 10a × 10b × 2c and 51a × 51b × 2c supercells in LaMn0.5SeO and CeMn0.5SeO, respectively. Both compounds are insulators. The optical bandgap of LaMn0.5SeO was determined to 2.13 eV from the Kubelka‐Munk function. Magnetic measurements indicate antiferromagnetic ordering of the Mn2+ moments with Néel points well above room temperature, as known from related manganese compounds.
Stability and symmetry breaking in the general three-Higgs-doublet model
Authors: Maniatis M. , Nachtmann O. 
Published: February 2015

Abstract
Stability, electroweak symmetry breaking, and the stationarity equations of the general three-Higgs doublet model (3HDM) where all doublets carry the same hypercharge are discussed in detail. Employing the bilinear formalism the study of the 3HDM potential turns out to be straightforward.
Daily temperature grids for Austria since 1961—concept, creation and applicability
Authors: Hiebl Johann , Frei Christoph 
Published: February 2015

AbstractCurrent interest into past climate change and its potential role for changes in the environment call for spatially distributed climate datasets of high temporal resolution and extending over several decades. To foster such research, we present a new gridded dataset of daily minimum and maximum temperature covering Austria at 1-km resolution and extending back till 1961 at daily time resolution. To account for the complex and highly variable thermal distributions in this high-mountain region, we adapt and employ a recently published interpolation method that estimates nonlinear temperature profiles with altitude and accounts for the non-Euclidean spatial representativity of station measurements. The spatial analysis builds upon 150 station series in and around Austria (homogenised where available), all of which extend over or were gap-filled to cover the entire study period. The restriction to (almost) complete records shall avoid long-term inconsistencies from changes in the station network. Systematic leave-one-out cross-validation reveals interpolation errors (mean absolute error) of about 1 °C. Errors are relatively larger for minimum compared to maximum temperatures, for the interior of the Alps compared to the flatland and for winter compared to summer. Visual comparisons suggest that valley-scale inversions and föhn are more realistically captured in the new compared to existing datasets. The usefulness of the presented dataset (SPARTACUS) is illustrated in preliminary analyses of long-term trends in climate impact indices. These reveal spatially variable and eventually considerable changes in the thermal climate in Austria.