bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reduced integration and differentiation of the imitation network in autism: A combined functional connectivity magnetic resonance imaging and diffusion‐weighted imaging study
Authors: Fishman Inna , Datko Michael , Cabrera Yuliana , Carper Ruth A. , Müller Ralph‐Axel 
Published: September 2015

ObjectiveConverging evidence indicates that brain abnormalities in autism spectrum disorder (ASD) involve atypical network connectivity, but few studies have integrated functional with structural connectivity measures. This multimodal investigation examined functional and structural connectivity of the imitation network in children and adolescents with ASD, and its links with clinical symptoms.MethodsResting state functional magnetic resonance imaging and diffusion‐weighted imaging were performed in 35 participants with ASD and 35 typically developing controls, aged 8 to 17 years, matched for age, gender, intelligence quotient, and head motion.ResultsWithin‐network analyses revealed overall reduced functional connectivity (FC) between distributed imitation regions in the ASD group. Whole brain analyses showed that underconnectivity in ASD occurred exclusively in regions belonging to the imitation network, whereas overconnectivity was observed between imitation nodes and extraneous regions. Structurally, reduced fractional anisotropy and increased mean diffusivity were found in white matter tracts directly connecting key imitation regions with atypical FC in ASD. These differences in microstructural organization of white matter correlated with weaker FC and greater ASD symptomatology.InterpretationFindings demonstrate atypical connectivity of the brain network supporting imitation in ASD, characterized by a highly specific pattern. This pattern of underconnectivity within, but overconnectivity outside the functional network is in contrast with typical development and suggests reduced network integration and differentiation in ASD. Our findings also indicate that atypical connectivity of the imitation network may contribute to ASD clinical symptoms, highlighting the role of this fundamental social cognition ability in the pathophysiology of ASD. Ann Neurol 2015;78:958–969
Simvastatin and vitamin D for migraine prevention: A randomized, controlled trial
Authors: Buettner Catherine , Nir Rony‐Reuven , Bertisch Suzanne M. , Bernstein Carolyn , Schain Aaron , Mittleman Murray A. , Burstein Rami 
Published: September 2015

ObjectiveThe aim of this work was to assess efficacy and tolerability of simvastatin plus vitamin D for migraine prevention in adults with episodic migraine.MethodsWe performed a randomized, double‐blind, placebo‐controlled trial with a 12‐week baseline period and 24‐week intervention period in 57 adults with episodic migraine. Participants were randomly assigned to simvastatin 20 mg tablets twice‐daily plus vitamin D3 1,000 international units capsules twice‐daily or matching placebo tablets and capsules.ResultsCompared to placebo, participants using simvastatin plus vitamin D3 demonstrated a greater decrease in number of migraine days from the baseline period to intervention weeks 1 to 12: a change of –8.0 (interquartile range [IQR]: −15.0 to −2.0) days in the active treatment group versus +1.0 (IQR: −1.0 to + 6.0) days in the placebo group, p < 0.001; and to intervention weeks 13 to 24: a change of −9.0 (IQR: −13 to −5) days in the active group versus +3.0 (IQR: −1.0 to + 5.0) days in the placebo group, p < 0.001. In the active treatment group, 8 patients (25%) experienced 50% reduction in the number of migraine days at 12 weeks and 9 (29%) at 24 weeks postrandomization. In comparison, only 1 patient (3%) in the placebo group (p = 0.03) experienced such a reduction. Adverse events were similar in both active treatment and placebo groups.InterpretationThe results demonstrate that simvastatin plus vitamin D is effective for prevention of headache in adults with episodic migraine. Given statins' ability to repair endothelial dysfunction, this economical approach may also reduce the increased risk for vascular diseases among migraineurs. Ann Neurol 2015;78:970–981
TPM3 deletions cause a hypercontractile congenital muscle stiffness phenotype
Authors: Donkervoort Sandra , Papadaki Maria , de Winter Josine M. , Neu Matthew B. , Kirschner Janbernd , Bolduc Véronique , Yang Michele L. , Gibbons Melissa A. , Hu Ying , Dastgir Jahannaz , Leach Meganne E. , Rutkowski Anne , Foley A. Reghan , Krüger Marcus , Wartchow Eric P. , McNamara Elyshia , Ong Royston , Nowak Kristen J. , Laing Nigel G. , Clarke Nigel F. , Ottenheijm Coen A. C. , Marston Steven B. , Bönnemann Carsten G. 
Published: September 2015

ObjectiveMutations in TPM3, encoding Tpm3.12, cause a clinically and histopathologically diverse group of myopathies characterized by muscle weakness. We report two patients with novel de novo Tpm3.12 single glutamic acid deletions at positions ΔE218 and ΔE224, resulting in a significant hypercontractile phenotype with congenital muscle stiffness, rather than weakness, and respiratory failure in one patient.MethodsThe effect of the Tpm3.12 deletions on the contractile properties in dissected patient myofibers was measured. We used quantitative in vitro motility assay to measure Ca2+ sensitivity of thin filaments reconstituted with recombinant Tpm3.12 ΔE218 and ΔE224.ResultsContractility studies on permeabilized myofibers demonstrated reduced maximal active tension from both patients with increased Ca2+ sensitivity and altered cross‐bridge cycling kinetics in ΔE224 fibers. In vitro motility studies showed a two‐fold increase in Ca2+ sensitivity of the fraction of filaments motile and the filament sliding velocity concentrations for both mutations.InterpretationThese data indicate that Tpm3.12 deletions ΔE218 and ΔE224 result in increased Ca2+ sensitivity of the troponin–tropomyosin complex, resulting in abnormally active interaction of the actin and myosin complex. Both mutations are located in the charged motifs of the actin‐binding residues of tropomyosin 3, thus disrupting the electrostatic interactions that facilitate accurate tropomyosin binding with actin necessary to prevent the on‐state. The mutations destabilize the off‐state and result in excessively sensitized excitation–contraction coupling of the contractile apparatus. This work expands the phenotypic spectrum of TPM3‐related disease and provides insights into the pathophysiological mechanisms of the actin–tropomyosin complex. Ann Neurol 2015;78:982–994
Describing many‐body bosonic waveguide scattering with the truncated Wigner method
Authors: Dujardin Julien , Engl Thomas , Urbina Juan Diego , Schlagheck Peter 
Published: September 2015

We consider quasi‐stationary scattering of interacting bosonic matter waves in one‐dimensional waveguides, as they arise in guided atom lasers. We show how the truncated Wigner (tW) method, which corresponds to the semiclassical description of the bosonic many‐body system on the level of the diagonal approximation, can be utilized in order to describe such many‐body bosonic scattering processes. Special emphasis is put on the discretization of space at the exact quantum level, in order to properly implement the semiclassical approximation and the tW method, as well as on the discussion of the results to be obtained in the continuous limit.
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Organized Aggregation of Porphyrins in Lipid Bilayers for Third Harmonic Generation Microscopy
Authors: Cui Liyang , Tokarz Danielle , Cisek Richard , Ng Kenneth K. , Wang Fan , Chen Juan , Barzda Virginijus , Zheng Gang 
Published: September 2015

AbstractNonlinear optical microscopy has become a powerful tool for high‐resolution imaging of cellular and subcellular composition, morphology, and interactions because of its high spatial resolution, deep penetration, and low photo‐damage to tissue. Developing specific harmonic probes is essential for exploiting nonlinear microscopic imaging for biomedical applications. We report an organized aggregate of porphyrins (OAP) that formed within lipidic nanoparticles showing fingerprint spectroscopic properties, structure‐associated second harmonic generation, and superradiant third harmonic generation. The OAP facilitated harmonic microscopic imaging of living cells with significantly enhanced contrast. The structure‐dependent switch between harmonic (OAP‐intact) and fluorescence (OAP‐disrupted) generation enabled real‐time multi‐modality imaging of the cellular fate of nanoparticles. Robustly produced under various conditions and easily incorporated into pre‐formed lipid nanovesicles, OAP provides a biocompatible nanoplatform for harmonic imaging.
Electron–Proton Decoupling in Excited‐State Hydrogen Atom Transfer in the Gas Phase
Authors: Miyazaki Mitsuhiko , Ohara Ryuhei , Daigoku Kota , Hashimoto Kenro , Woodward Jonathan R. , Dedonder Claude , Jouvet Christophe , Fujii Masaaki 
Published: September 2015

AbstractHydrogen‐release by photoexcitation, excited‐state‐hydrogen‐transfer (ESHT), is one of the important photochemical processes that occur in aromatic acids and is responsible for photoprotection of biomolecules. The mechanism is described by conversion of the initial state to a charge‐separated state along the O(N)‐H bond elongation, leading to dissociation. Thus ESHT is not a simple H‐atom transfer in which a proton and a 1s electron move together. Here we show that the electron‐transfer and the proton‐motion are decoupled in gas‐phase ESHT. We monitor electron and proton transfer independently by picosecond time‐resolved near‐infrared and infrared spectroscopy for isolated phenol–(ammonia)5, a benchmark molecular cluster. Electron transfer from phenol to ammonia occurred in less than 3 picoseconds, while the overall H‐atom transfer took 15 picoseconds. The observed electron‐proton decoupling will allow for a deeper understanding and control of of photochemistry in biomolecules.
Redox Modulation of PTEN Phosphatase Activity by Hydrogen Peroxide and Bisperoxidovanadium Complexes
Authors: Lee Chang‐Uk , Hahne Gernot , Hanske Jonas , Bange Tanja , Bier David , Rademacher Christoph , Hennig Sven , Grossmann Tom N. 
Published: September 2015

AbstractPTEN is a dual‐specificity protein tyrosine phosphatase. As one of the central tumor suppressors, a thorough regulation of its activity is essential for proper cellular homeostasis. The precise implications of PTEN inhibition by reactive oxygen species (e.g. H2O2) and the subsequent structural consequences remain elusive. To study the effects of PTEN inhibition, bisperoxidovanadium (bpV) complexes serve as important tools with the potential for the treatment of nerve injury or cardiac ischemia. However, their mode of action is unknown, hampering further optimization and preventing therapeutic applications. Based on protein crystallography, mass spectrometry, and NMR spectroscopy, we elucidate the molecular basis of PTEN inhibition by H2O2 and bpV complexes. We show that both molecules inhibit PTEN via oxidative mechanisms resulting in the formation of the same intramolecular disulfide, therefore enabling the reactivation of PTEN under reductive conditions.
Printability of elastomer latex for additive manufacturing or 3D printing
Authors: Lukić Maria , Clarke Jane , Tuck Christopher , Whittow William , Wells Garry 
Published: September 2015

ABSTRACTAdditive manufacturing, sometimes referred to as 3D printing is a new, rapidly developing technology which has the potential to revolutionize fabrication of certain high value, complex products. Until now conventional elastomers have not been widely used in the additive manufacturing process. The goal of our work was to determine the feasibility of additive manufacturing using ink jet printing of elastomeric latex materials. Particle size, viscosity, and surface tension were measured for five different latex materials—poly(2‐chloro‐1,3‐butadiene), carboxylated styrene‐butadiene rubber, carboxylated butadiene‐acrylonitrile copolymer, natural rubber, and prevulcanized natural rubber. The XSBR latex was predicted as the one most likely to be printable. Printing trials carried out with the XSBR as the ink proved it to be printable, although technical problems of agglomeration and print head clogging need to be addressed and both the material and process need to be optimized for consistent printing to be achieved. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 42931.
Multicomponent One‐pot Reactions Towards the Synthesis of Stereoisomers of Dipicolylamine Complexes
Authors: Raje Sakthi , Gurusamy Sureshbabu , Koner Abhishek , Mehrotra Sonam , Jennifer Samson Jegan , Vasudev Prema G. , Butcher Ray J. , Angamuthu Raja 
Published: September 2015

AbstractReported are multi‐component one‐pot syntheses of chiral complexes [M(LROR′)Cl2] or [M(LRSR′)Cl2] from the mixture of an N‐substituted ethylenediamine, pyridine‐2‐carboxaldehyde, a primary alcohol or thiol and MCl2 utilizing in‐situ formed cyclized Schiff bases where a C−O bond, two stereocenters, and three C−N bonds are formed (M=Zn, Cu, Ni, Cd; R=Et, Ph; R′=Me, Et, nPr, nBu). Tridentate ligands LROR′ and LRSR′ comprise two chiral centers and a hemiaminal ether or hemiaminal thioether moiety on the dipicolylamine skeleton. Syn‐[Zn(LPhOMe)Cl2] precipitates out readily from the reaction mixture as a major product whereas anti‐[Zn(LPhOMe)Cl2] stays in solution as minor product. Both syn‐[Zn(LPhOMe)Cl2] and anti‐[Zn(LPhOMe)Cl2] were characterized using NMR spectroscopy and mass spectrometry. Solid‐state structures revealed that syn‐[Zn(LPhOMe)Cl2] adopted a square pyramidal geometry while anti‐[Zn(LPhOMe)Cl2] possesses a trigonal bipyramidal geometry around the Zn centers. The scope of this method was shown to be wide by varying the components of the dynamic coordination assembly, and the structures of the complexes isolated were confirmed by NMR spectroscopy, mass spectrometry, and X‐ray crystallography. Syn complexes were isolated as major products with ZnII and CuII, and anti complexes were found to be major products with NiII and CdII. Hemiaminals and hemiaminal ethers are known to be unstable and are seldom observed as part of cyclic organic compounds or as coordinated ligands assembled around metals. It is now shown, with the support of experimental results, that linear hemiaminal ethers or thioethers can be assembled without the assistance of Lewis acidic metals in the multi‐component assembly, and a possible pathway of the formation of hemiaminal ethers has been proposed.
Nonidentical twins: Comparison of frequentist and Bayesian lasso for Cox models
Authors: Zucknick Manuela , Saadati Maral , Benner Axel 
Published: September 2015

One important task in translational cancer research is the search for new prognostic biomarkers to improve survival prognosis for patients. The use of high‐throughput technologies allows simultaneous measurement of genome‐wide gene expression or other genomic data for all patients in a clinical trial. Penalized likelihood methods such as lasso regression can be applied to such high‐dimensional data, where the number of (genomic) covariables is usually much larger than the sample size. There is a connection between the lasso and the Bayesian regression model with independent Laplace priors on the regression parameters, and understanding this connection has been useful for understanding the properties of lasso estimates in linear models (e.g. Park and Casella,). In this paper, we study the lasso in the frequentist and Bayesian frameworks in the context of Cox models. For the Bayesian lasso we extend the approach by Lee et al. (). In particular, we impose the lasso penalty only on the genome features, but not on relevant clinical covariates, to allow the mandatory inclusion of important established factors. We investigate the models in high‐ and low‐dimensional simulation settings and in an application to chronic lymphocytic leukemia.
Simulation and prediction of protein production in fed‐batch E. coli cultures: An engineering approach
Authors: Calleja Daniel , Kavanagh John , de Mas Carles , López‐Santín Josep 
Published: September 2015

ABSTRACTAn overall model describing the dynamic behavior of fed‐batch E. coli processes for protein production has been built, calibrated and validated. Using a macroscopic approach, the model consists of three interconnected blocks allowing simulation of biomass, inducer and protein concentration profiles with time. The model incorporates calculation of the extra and intracellular inducer concentration, as well as repressor–inducer dynamics leading to a successful prediction of the product concentration. The parameters of the model were estimated using experimental data of a rhamnulose‐1‐phosphate aldolase‐producer strain, grown under a wide range of experimental conditions. After validation, the model has successfully predicted the behavior of different strains producing two different proteins: fructose‐6‐phosphate aldolase and ω‐transaminase. In summary, the presented approach represents a powerful tool for E. coli production process simulation and control. Biotechnol. Bioeng. 2016;113: 772–782. © 2015 Wiley Periodicals, Inc.
Sphingolipids contribute to acetic acid resistance in Zygosaccharomyces bailii
Authors: Lindahl Lina , Genheden Samuel , Eriksson Leif A. , Olsson Lisbeth , Bettiga Maurizio 
Published: September 2015

ABSTRACTLignocellulosic raw material plays a crucial role in the development of sustainable processes for the production of fuels and chemicals. Weak acids such as acetic acid and formic acid are troublesome inhibitors restricting efficient microbial conversion of the biomass to desired products. To improve our understanding of weak acid inhibition and to identify engineering strategies to reduce acetic acid toxicity, the highly acetic‐acid‐tolerant yeast Zygosaccharomyces bailii was studied. The impact of acetic acid membrane permeability on acetic acid tolerance in Z. bailii was investigated with particular focus on how the previously demonstrated high sphingolipid content in the plasma membrane influences acetic acid tolerance and membrane permeability. Through molecular dynamics simulations, we concluded that membranes with a high content of sphingolipids are thicker and more dense, increasing the free energy barrier for the permeation of acetic acid through the membrane. Z. bailii cultured with the drug myriocin, known to decrease cellular sphingo­lipid levels, exhibited significant growth inhibition in the presence of acetic acid, while growth in medium without acetic acid was unaffected by the myriocin addition. Furthermore, following an acetic acid pulse, the intracellular pH decreased more in myriocin‐treated cells than in control cells. This indicates a higher inflow rate of acetic acid and confirms that the reduction in growth of cells cultured with myriocin in the medium with acetic acid was due to an increase in membrane permeability, thereby demonstrating the importance of a high fraction of sphingolipids in the membrane of Z. bailii to facilitate acetic acid resistance; a property potentially transferable to desired production organisms suffering from weak acid stress. Biotechnol. Bioeng. 2016;113: 744–753. © 2015 The Authors. Biotechnology and Bioengineering Published by Wiley Periodicals, Inc.
Metabolic routes along digestive system of licorice: multicomponent sequential metabolism method in rat
Authors: Zhang Lei , Zhao Haiyu , Liu Yang , Dong Honghuan , Lv Beiran , Fang Min , Zhao Huihui 
Published: September 2015

AbstractThis study was conducted to establish the multicomponent sequential metabolism (MSM) method based on comparative analysis along the digestive system following oral administration of licorice (Glycyrrhiza uralensis Fisch., leguminosae), a traditional Chinese medicine widely used for harmonizing other ingredients in a formulae. The licorice water extract (LWE) dissolved in Krebs–Ringer buffer solution (1 g/mL) was used to carry out the experiments and the comparative analysis was performed using HPLC and LC‐MS/MS methods. In vitro incubation, in situ closed‐loop and in vivo blood sampling were used to measure the LWE metabolic profile along the digestive system. The incubation experiment showed that the LWE was basically stable in digestive juice. A comparative analysis presented the metabolic profile of each prototype and its corresponding metabolites then. Liver was the major metabolic organ for LWE, and the metabolism by the intestinal flora and gut wall was also an important part of the process. The MSM method was practical and could be a potential method to describe the metabolic routes of multiple components before absorption into the systemic blood stream. Copyright © 2015 John Wiley & Sons, Ltd.
Harnessing Enzymatic Promiscuity in Myxochelin Biosynthesis for the Production of 5‐Lipoxygenase Inhibitors
Authors: Korp Juliane , König Stefanie , Schieferdecker Sebastian , Dahse Hans‐Martin , König Gabriele M. , Werz Oliver , Nett Markus 
Published: September 2015

AbstractThe siderophore myxochelin A is a potent inhibitor of human 5‐lipoxygenase (5‐LO). To clarify whether the iron‐chelating properties of myxochelin A are responsible for this activity, several analogues of this compound were generated in the native producerPyxidicoccus fallaxby precursor‐directed biosynthesis. Testing in a cell‐free assay unveiled three derivatives with bioactivity comparable with that of myxochelin A. Furthermore, it became evident that inhibition of 5‐LO by myxochelins does not correlate with their iron affinities.
Eculizumab as a bridge to immunosuppressive therapy in severe cold agglutinin disease of anti‐Pr specificity
Authors: Shapiro Roman , Chin‐Yee Ian , Lam Selay 
Published: September 2015

Key Clinical MessageSevere cold agglutinin disease with hemodynamic compromise requires rapid stabilization of the autoimmune hemolytic anemia as a bridge to the immunosuppressive effect of rituximab. Herein, we describe eculizumab treatment of severe complement‐mediated hemolysis in a patient whose hemodynamic status deteriorated in spite of supportive blood transfusions and therapeutic plasma exchange.
Turn‐On Ratiometric Fluorescent Probe for Selective Discrimination of Cr3+ from Fe3+ in Aqueous Media for Living Cell Imaging
Authors: Rasheed Lubna , Yousuf Muhammad , Youn Il Seung , Yoon Taeseung , Kim Kwang‐Youn , Seo Young‐Kyo , Shi Genggongwo , Saleh Muhammad , Hur Jin‐Hoe , Kim Kwang S. 
Published: September 2015

AbstractPyrene‐based turn‐on ratiometric fluorescent probe 1 demonstrates high sensitivity and exceptional selectivity toward Cr3+ in the presence of other metals, including Fe3+ in aqueous media. Interaction of Cr3+ with probe 1 brings pyrene moieties close enough to have better aligned π–π stacking, thus enhancing the excimer peak many fold. On the other hand, the interaction of Fe3+ with probe 1 brings forth a negligible difference in stacking, resulting in an insignificant change in fluorescence intensity. Exceptional selectivity of probe 1 with Cr3+ over Fe3+ and other metals has been confirmed by theoretical studies in addition to experimental results. Imaging of HeLa cells observed by confocal fluorescence microscopy reveals that probe 1 can be used to monitor Cr3+ in live cells to map its subcellular distribution.