bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distribution of an allele associated with blond hair color across northern island melanesia
Authors: Norton Heather L. , Correa Elena A. , Koki George , Friedlaender Jonathan S. 
Published: January 2014

AbstractPigmentation of the skin, hair, and eyes is a complex trait controlled by multiple genetic loci. Recently a non‐synonymous mutation in the pigmentation candidate gene TYRP1 was shown to be significantly associated with a blond‐hair phenotype in populations from the Solomon Islands. The distribution of this mutation in the islands of Northern Island Melanesia, where the blondism phenotype is also prevalent, was unknown. Here, we present data describing the distribution of this allele in 550 individuals sampled from across this region, and test for associations between genotype at this locus and quantitatively measured skin and hair pigmentation phenotype. We report that the frequency of the 93C allele is notably lower than observed in the Solomons (0.12 vs. 0.26). The allele exhibits significant geographic heterogeneity across the islands sampled (χ2 = 108.4, P < 0.0001). It is observed at its highest frequencies on the islands of New Ireland and New Hanover, while being almost completely absent from the large island of New Britain. Using linear regression with age, sex, and island as covariates we report that, as in the Solomons, the 93C allele is significantly associated with a decrease in hair pigmentation but not skin pigmentation. We discuss the distribution of the 93C allele across the Southwest Pacific in light of its possible place of origin and dispersal. Am J Phys Anthropol 153:653–662, 2014. © 2014 Wiley Periodicals, Inc.
Peierls‐verzerrtes monoklines MnB4mit einer Mn‐Mn‐Bindung
Authors: Knappschneider Arno , Litterscheid Christian , George Nathan C. , Brgoch Jakoah , Wagner Norbert , Beck Johannes , Kurzman Joshua A. , Seshadri Ram , Albert Barbara 
Published: January 2014

AbstractDie Tetraboride von Chrom und Mangan zeigen ein ungewöhnliches Boratomgerüst, das hypothetischem tetragonalen Diamant ähnelt. Es wird angenommen, dass sie sehr hart sind. Jetzt wurden Einkristalle von MnB4erhalten. Die Verbindung kristallisiert im monoklinen Kristallsystem (P21/c) mit einer Struktur, die vier kristallographisch unabhängige Boratom‐Positionen aufweist, was in Übereinstimmung mit den Ergebnissen der11B‐MAS‐NMR‐Spektroskopie steht. Ein unerwartet kurzer Abstand zwischen Mn‐Atomen deutet auf eine Mn‐Mn‐Doppelbindung hin und wird durch Peierls‐Verzerrung verursacht. Die Struktur wurde mit Gruppe‐Untergruppe‐Beziehungen bestimmt. DFT‐Rechnungen lassen auf MnIund Paramagnetismus schließen, letzterer wurde durch magnetische Messungen bestätigt. Die Zustandsdichten zeigen eine Pseudo‐Bandlücke am Fermi‐Niveau; für MnB4wurde halbleitendes Verhalten beobachtet.
Steuerung der intrazellulären Proteinmenge durch niedermolekulare Modulatoren des Ubiquitin‐Proteasom‐Systems
Authors: Buckley Dennis L. , Crews Craig M. 
Published: January 2014

AbstractIm Bereich der chemischen Biologie werden biologische Sonden‐ und Wirkstoffmoleküle klassischerweise genutzt, um die Aktivität von Proteinen (wie Enzymen und Rezeptoren) zu modulieren, die sich verhältnismäßig leicht durch niedermolekulare Verbindungen beeinflussen lassen. Der verbleibende Rest, der die Mehrheit des Proteoms stellt, galt lange Zeit als für Wirkstoffe unzugänglich (“undruggable”). Mithilfe niedermolekularer Modulatoren des Ubiquitin‐Proteasomsystems (UPS) ist es möglich, statt der Proteinaktivität die Proteinmenge zu modulieren, was die Anzahl der zugänglichen Zielmoleküle erhöht. Während ein Angriff auf das Proteasom selbst zu einer globalen Erhöhung der Proteinmenge führen kann, lässt sich durch das Ansteuern anderer Komponenten des UPS (z. B. der E3‐Ubiquitinligasen) in gezielter Weise eine Erhöhung von Proteinmengen erreichen. Als Alternative dazu beginnen sich verschiedene Strategien zur Induktion des Proteinabbaus mittels niedermolekularer “Sonden” abzuzeichnen. Durch die Fähigkeit, den Abbau bestimmter Proteine zu induzieren und/oder zu inhibieren, besitzen niedermolekulare Modulatoren des UPS das Potenzial, den für Wirkstoffe zugänglichen Anteil des Proteoms über klassische Zielstrukturen wie Enzyme und Rezeptoren hinaus in signifikanter Weise zu erweitern.
Single Mutations in Tau Modulate the Populations of Fibril Conformers through Seed Selection
Authors: Meyer Virginia , Dinkel Paul D. , Luo Yin , Yu Xiang , Wei Guanghong , Zheng Jie , Eaton Gareth R. , Ma Buyong , Nussinov Ruth , Eaton Sandra S. , Margittai Martin 
Published: January 2014

AbstractSeeded conversion of tau monomers into fibrils is a central step in the progression of tau pathology in Alzheimer’s disease and other neurodegenerative disorders. Self‐assembly is mediated by the microtubule binding repeats in tau. There are either three or four repeats present depending on the protein isoform. Here, double electron‐electron resonance spectroscopy was used to investigate the conformational ensemble of four‐repeat tau fibrils. Single point mutations at key positions in the protein (ΔK280, P301S, P312I, D314I) markedly change the distribution of fibril conformers after template‐assisted growth, whereas other mutations in the protein (I308M, S320F, G323I, G326I, Q336R) do not. These findings provide unprecedented insights into the seed selection of tau disease mutants and establish conformational compatibility as an important driving force in tau fibril propagation.
Enantiomerenreine [M6L12]‐ oder [M12L24]‐Polyeder aus flexiblen Bis(pyridin)‐Liganden
Authors: Gütz Christoph , Hovorka Rainer , Klein Christoph , Jiang Qian‐Qian , Bannwarth Christoph , Engeser Marianne , Schmuck Carsten , Assenmacher Wilfried , Mader Werner , Topić Filip , Rissanen Kari , Grimme Stefan , Lützen Arne 
Published: January 2014

AbstractDie koordinationsgetriebene Selbstorganisation ist eine der leistungsfähigsten Strategien zum Aufbau nanometergroßer diskreter (supra‐)molekularer Aggregate. Hier berichten wir über die Verwendung von zwei konstitutionsisomeren Bis(pyridin)‐Liganden auf der Basis von BINOL zu diesem Zweck. Je nach Substitutionsmuster des BINOL‐Gerüsts bilden sich bei der Koordination an PdII‐Ionen enantiomerenreine, endo‐ oder exo‐funktionalisierte sechs‐ oder zwölfkernige metallosupramolekulare Polyeder mit einem chiralen Gerüst. Die Aggregate wurden mittels NMR, MS, DLS, TEM und EELS sowie ECD charakterisiert. Die außergewöhnlich hohen molaren Circulardichroismen der Komplexe konnten durch den Vergleich experimenteller ECD‐Daten mit simulierten Daten (vereinfachte Tamm‐Dancoff‐Näherung zur zeitabhängigen DFT) nachvollzogen werden. Hervorzuheben ist ferner, dass die Selbstorganisationsprozesse vollständig selektiv im Sinne einer “narzisstischen” Selbsterkennung ablaufen, obwohl die Liganden ein hohes Maß an Rotationsfreiheit um die zentrale Aryl‐Aryl‐Bindung aufweisen.
Enantiomerically Pure [M6L12] or [M12L24] Polyhedra from Flexible Bis(Pyridine) Ligands
Authors: Gütz Christoph , Hovorka Rainer , Klein Christoph , Jiang Qian‐Qian , Bannwarth Christoph , Engeser Marianne , Schmuck Carsten , Assenmacher Wilfried , Mader Werner , Topić Filip , Rissanen Kari , Grimme Stefan , Lützen Arne 
Published: January 2014

AbstractCoordination‐driven self‐assembly is one of the most powerful strategies to prepare nanometer‐sized discrete (supra)molecular assemblies. Herein, we report on the use of two constitutionally isomeric BINOL‐based bis(pyridine) ligands for this purpose. Upon coordination to PdII ions these self‐assemble into enantiomerically pure endo‐ and exo‐functionalized hexa‐ and dodecanuclear metallosupramolecular spheres with a chiral skeleton depending on the substitution pattern of the BINOL core. These aggregates were characterized by NMR, MS, DLS, TEM, and EELS as well as ECD. Furthermore, experimental ECD data could be compared to those obtained from theoretical simulations using a simplified Tamm–Dancoff approximation to time‐dependent DFT to rationalize the extraordinary high molar circular dichroisms. Despite the rotational freedom around the central aryl–aryl bond of these ligands, the self‐assembly process happens completely selective in a “narcissistic” self‐recognition manner.
Peptide Ligands Stabilized by Small Molecules
Authors: Chen Shiyu , Bertoldo Davide , Angelini Alessandro , Pojer Florence , Heinis Christian 
Published: January 2014

AbstractBicyclic peptides generated through directed evolution by using phage display offer an attractive ligand format for the development of therapeutics. Being nearly 100‐fold smaller than antibodies, they promise advantages such as access to chemical synthesis, efficient diffusion into tissues, and needle‐free application. However, unlike antibodies, they do not have a folded structure in solution and thus bind less well. We developed bicyclic peptides with hydrophilic chemical structures at their center to promote noncovalent intramolecular interactions, thereby stabilizing the peptide conformation. The sequences of the peptides isolated by phage display from large combinatorial libraries were strongly influenced by the type of small molecule used in the screen, thus suggesting that the peptides fold around the small molecules. X‐ray structure analysis revealed that the small molecules indeed formed hydrogen bonds with the peptides. These noncovalent interactions stabilize the peptide–protein complexes and contribute to the high binding affinity.
A B–C Double Bond Unit Coordinated to Platinum: An Alkylideneboryl Ligand that Is Isoelectronic to Neutral Aminoborylene Ligands
Authors: Brand Johannes , Braunschweig Holger , Hupp Florian , Phukan Ashwini K. , Radacki Krzysztof , Sen Sakya S. 
Published: January 2014

AbstractThe reaction of [Pt(PCy3)2] with Br2B‐CH(SiMe3)2 resulted in generation of the first alkylideneboryl complex, trans‐[Br(Cy3P)2Pt{BCH(SiMe3)}], with concomitant elimination of Me3SiBr. The trans bromide ligand of the alkylideneboryl complex was readily substituted by a methyl group upon treatment with methyllithium, leading to another alkylideneboryl complex, trans‐[Me(Cy3P)2Pt{BCH(SiMe3)}]. Various spectrochemical techniques, single‐crystal X‐ray crystallography, and quantum chemical calculations confirmed the formulation of a double bond between the boron and the carbon atom. The theoretical studies also provided evidence for the stronger trans influence of the alkylideneboryl ligand over iminoboryl and oxoboryl ligands.
Total Synthesis of (±)‐Aspidophylline A
Authors: Ren Weiwu , Wang Qian , Zhu Jieping 
Published: January 2014

AbstractA total synthesis of aspidophylline A, a pentacyclic akuammiline‐type monoterpene indole alkaloid, is described. The synthesis features: 1) rapid access to a fully functionalized dihydrocarbazole through the desymmetrization of readily available 2‐allyl‐2‐(o‐nitrophenyl)cyclohexane‐1,3‐dione; 2) an intramolecular azidoalkoxylation of an enecarbamate to install both the furoindoline ring and the azido functionality; and 3) an intramolecular Michael addition for the construction of the 2‐azabicyclo[3.3.1]nonane ring system.
Microneedles from fish scale biopolymer
Authors: Olatunji Ololade , Igwe Chima C. , Ahmed Aroke S. , Alhassan Dewale O. A. , Asieba GGodfrey O. , Diganta Bhusan Das 
Published: January 2014

ABSTRACTThis article reports on microneedles produced from biopolymer films extracted from fish scales of tilapia (Oreochromiss sp.) using micromolding technique. Evaluation of the properties of polypeptide films prepared from the fish scales gave refractive index (1.34), protein concentration (78%), ash content (1.6%) at (22%) moisture content. The microneedles successfully inserted into artificial skin models and imaging using digital camera showed microneedles remained intact when inserted and when removed from the skin model. Microneedles also successfully inserted into porcine skin and were shown to dissolve gradually at 0 s, 60 s, 120 s, and 180 s after insertion. Microneedles containing methylene blue as model drug were also produced and successfully pierced porcine skin. 3D finite element (FEM) simulations were performed using the measured mechanical properties of the biopolymer films (Young's modulus 0.23 N/mm2 and tensile strength 1.8105 N/mm2) to evaluate the stress distribution on various dimensions of the fish scale derived microneedles and hence, their ability to withstand force necessary to pierce the skin without fracture. Results from mechanical analysis using FEM showed that microneedles with tip radius between 10 and 100 μm could withstand up to 0.12 N of force per microneedle without fracture, which is indicated when the stress at the tip of the microneedle exceeds the ultimate stress of the material of fabrication. Using skin insertion tests and finite element simulations, this study provides evidence that microneedles fabricated from fish scale biopolymer can effectively pierce and degrade into skin and therefore are good candidate for transdermal applications. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40377.
Quantitative fluorescent profiling ofVEGFRs reveals tumor cell and endothelial cell heterogeneity in breast cancer xenografts
Authors: Imoukhuede Princess. I. , Popel Aleksander S. 
Published: January 2014

AbstractPlasma membrane‐localized vascular endothelial growth factor receptors (VEGFR) play a critical role in transducingVEGFsignaling toward pro and antiangiogenic outcomes and quantitative characterization of these receptors is critical toward identifying biomarkers for antiangiogenic therapies, understanding mechanisms of action of antiangiogenic drugs, and advancing predictive computational models. While in vitro analysis of cell surface‐VEGFRs has been performed, little is known about the levels of cell surface‐VEGFRon tumor cells. Therefore, we inoculate nude mice with the human triple‐negative breast cancer,MDA‐MB‐231, cell line; isolate human tumor cells and mouse tumor endothelial cells from xenografts; and quantitatively characterize theVEGFRlocalization on these cells. We observe 15,000 surface‐VEGFR1/tumor endothelial cell versus 8200 surface‐VEGFR1/tumor endothelial cell at 3 and 6 weeks of tumor growth, respectively; and we quantify 1200–1700 surface‐VEGFR2/tumor endothelial cell. The tumor cell levels ofVEGFR1 andVEGFR2 are relatively constant between 3 and 6 weeks: 2000–2200 surface‐VEGFR1/tumor cell and ~1000 surface‐VEGFR2/tumor cell. Cell‐by‐cell analysis provides additional insight into tumor heterogeneity by identifying four cellular subpopulations based on size and levels of cell membrane‐localizedVEGFR. Furthermore, when these ex vivo data are compared to in vitro data, we observe little to noVEGFRs onMDA‐MB‐231 cells, and theMDA‐MB‐231VEGFRsurface levels are not regulated by a saturating dose ofVEGF. Overall, the quantification of these dissimilarities for the first time in tumor provides insight into the balance of modulatory (VEGFR1) and proangiogenic (VEGFR2) receptors.
Bone marrow mesenchymal stem cells ameliorate inflammatory factor‐induced dysfunction of INS‐1 cells on chip
Authors: sun Yu , Yao Zhina , lin Peng , hou Xinguo , Chen Li 
Published: January 2014

AbstractUsing a microfluidic chip, we have investigated whether bone marrow mesenchymal stem cells (BM‐MSCs) could ameliorate IL‐1β/IFN‐γ‐induced dysfunction of INS‐1 cells. BM‐MSCs were obtained from diabetes mellitus patients and their cell surface antigen expression profiles were analyzed by flow cytometric. INS‐1 cells were cocultured with BM‐MSCs on a microfluidic chip with persistent perfusion of medium containing 1 ng/mL IL‐1β and 2.5 U/mL IFN‐γ for 72 h. BM‐MSCs could partially rescue INS‐1 cells from cytokine‐induced dysfunction and ameliorate the expression of insulin and PDX‐1 gene in INS‐1 cells. Thus BM‐MSCs can be viewed as a promising stem cell source to depress inflammatory factor‐induced dysfunction of pancreatic β cells in diabetic patients.
Strategic orientation and new product performance: The roles of technological capability
Authors: Hsu Teresa Tiaojung , Tsai Kuen‐Hung , Hsieh Ming‐Hung , Wang Wei‐Yuan 
Published: January 2014

AbstractAlthough prior research has examined the linkage between strategic orientation and new product performance, existing empirical evidence suggests exploration of the effects of a firm's internal factors on this linkage is required. This study aims to fill the marketing literature gap by addressing how technological capability moderates the strategic orientation‐new product performance relationship. This study measures new product performance as a two‐dimensional construct to avoid the oversimplified bias. Research hypotheses are tested using a sample of 121 information system product projects and a hierarchical regression approach is utilized. Results show that (a) technological capability strengthens the market orientation‐performance relationship and (b) technological capability affects the financial performance effects of market and technology orientations via market performance. Copyright © 2014 ASAC. Published by John Wiley & Sons, Ltd.
New Antithrombotics for Secondary Prevention of Acute Coronary Syndrome
Authors: Goto Shinya , Tomita Aiko 
Published: January 2014

AbstractPatients with acute coronary syndrome (ACS) usually receive acetylsalicylic acid plus an adenosine diphosphate (ADP) receptor inhibitor to reduce the long‐term risk of recurrent events. However, patients receiving standard antiplatelet prophylaxis still face a substantial risk of recurrent events. Strategies involving 3 antithrombotic agents with different modes of action have now been tested. In Thrombin Receptor Antagonists for Clinical Event Reduction (TRA‐CER), compared with standard care alone, bleeding complications including intracranial hemorrhage (ICH) were increased with the addition of vorapaxar, without efficacy benefit. In Trial to Assess the Effects of SCH 530348 in Preventing Heart Attack and Stroke in Patients With Atherosclerosis (TRA 2°P–TIMI 50), the addition of vorapaxar reduced recurrent events compared with standard care in stable patients with prior myocardial infarction. This study was terminated early in patients with prior stroke owing to excess ICH, though an increased risk of ICH or fatal bleeding was not detected in patients with prior myocardial infarction. The Apixaban for Prevention of Acute Ischemic and Safety Events 2 (APPRAISE‐2) trial of standard‐dose apixaban added to standard care in patients with ACS was also stopped early owing to excess serious bleeding. However, in Rivaroxaban in Combination With Aspirin Alone or With Aspirin and a Thienopyridine in Patients With Acute Coronary Syndromes (ATLAS ACS 2 TIMI 51), fatal bleeding or fatal ICH did not increase with low‐dose rivaroxaban added to low‐dose acetylsalicylic acid‐based standard care compared with standard care alone. In that trial, a significant reduction of recurrent vascular events was shown with 3 antithrombotic regimens compared with standard care. Therefore, depending on drug dose and patient population, further reductions in recurrent vascular events after ACS may be possible in future clinical practice, with a favorable benefit‐risk profile.
Prehospital Telemedicine Electrocardiogram Triage for a Regional Public Emergency Medical Service: Is It Worth It? A Preliminary Cost Analysis
Authors: Brunetti Natale Daniele , Dellegrottaglie Giulia , Lopriore Claudio , Di Giuseppe Giuseppe , De Gennaro Luisa , Lanzone Saverio , Di Biase Matteo 
Published: January 2014

AbstractBackgroundTelemedicine has been shown to improve quality of health‐care delivery in several fields of medicine; its cost‐effectiveness, however, is still a matter of debate.HypothesisPre‐hospital telemedicine electrocardiogram triage for regional public emergency medical service may reduce costs.MethodsAn economic evaluation (cost analysis) was performed from the perspective of regional health‐care system. Patients enrolled in the study and considered for cost analysis were those who called the local emergency medical service (EMS; dialing 1‐1‐8) during 2012 and underwent prehospital field triage with a telemedicine electrocardiogram (ECG) in the case of suspected acute cardiac disease (acute coronary syndrome, arrhythmia). The prehospital ECGs were read by a remote cardiologist, available 24/7. Cost savings associated with this method were calculated by subtracting the cost of prehospital triage with telemedicine support from the cost of conventional emergency department triage (ECG and consultation by a cardiologist).ResultsDuring 2012, the regional EMS performed 109 750 ECGs by telemedicine support. The associated total cost for the regional health‐care system was €1 833 333, with a €16.70 cost per single ECG/consultation. Given the cost of similar conventional emergency department treatment from a regional rate list of €24.80 to €55.20, the savings was €8.10 to €38.40 per ECG/consultation (total savings, €891 759.50 to €4 219 379.50). The cost for ruling out an acute cardiac disease was €25.30; for a prehospital diagnosis of cardiovascular disease, €49.20. With 629 prehospital diagnoses of ST‐elevation myocardial infarction and reported reductions in mortality thanks to prehospital diagnosis deduced from prior studies, 69 lives per year presumably could be saved, with a cost per quality‐adjusted life year gained of €1927, €990/€ − 2508 after correction for potential savings.ConclusionsPrehospital EMS triage with telemedicine ECG in patients with suspected acute cardiac disease may reduce health‐care costs.
Effects of Cardiac Rehabilitation in Diabetic Patients: Both Cardiac and Noncardiac Factors Determine Improvement in Exercise Capacity
Authors: St. Clair Mitchell , Mehta Hardik , Sacrinty Matthew , Johnson Dominic , Robinson Killian 
Published: January 2014

AbstractBackgroundDiabetic patients have a worse prognosis than nondiabetic patients after myocardial infarction. Although exercise improves risk factors, exercise capacity, and mortality, it is still unclear if these benefits are the same as in nondiabetics. Furthermore, although exercise tolerance is predicted by systolic and diastolic dysfunction in nondiabetics, its role as a predictor of exercise capacity in diabetics remains unclear.HypothesisDiabetics and nondiabetics see a similar improvement in their cardiac risk factors and exercise parameters from exercise‐based cardiac rehabilitation (CR).MethodsA series of 370 diabetics and 942 nondiabetics entered a 36‐session outpatient CR program after interventions for coronary heart disease or after bypass or cardiac valve surgery. The program consisted of physical exercise, lifestyle modification, and pharmacotherapy.ResultsQuality of life, weight, blood pressure, and lipid profiles improved significantly in both groups during the 12‐week program. Baseline metabolic equivalents (METs) were lower in diabetics vs nondiabetics at the start of CR (2.4 vs 2.7, P < 0.001). Although both groups increased their exercise capacity, diabetics had less improvement (change in METs 1.7 vs 2.6, P < 0.001). Significant predictors for improvement after CR included age, sex, and weight, as well as both systolic and diastolic function. After adjustment for these, diabetes remained a significant predictor of reduced improvement in exercise capacity.ConclusionsDiabetics saw a significant benefit in quality of life, weight, exercise tolerance, and cardiac risk factors, but to a lesser extent when compared with nondiabetics. The mechanisms for poorer improvement in diabetics following CR also include noncardiac factors and require further study.