bluuebunny/crossref_metadata_2025_split huggingface dataset:
LEGO‐Inspired Drug Design: Unveiling a Class of Benzo[d]thiazoles Containing a 3,4‐Dihydroxyphenyl Moiety as Plasma Membrane H+‐ATPase Inhibitors
Authors: Tung Truong‐Thanh , Dao Trong T. , Junyent Marta G. , Palmgren Michael , Günther‐Pomorski Thomas , Fuglsang Anja T. , Christensen Søren B. , Nielsen John 
Published: November 2017

AbstractThe fungal plasma membrane H+‐ATPase (Pma1p) is a potential target for the discovery of new antifungal agents. Surprisingly, no structure–activity relationship studies for small molecules targeting Pma1p have been reported. Herein, we disclose a LEGO‐inspired fragment assembly strategy for the design, synthesis, and discovery of benzo[d]thiazoles containing a 3,4‐dihydroxyphenyl moiety as potential Pma1p inhibitors. A series of 2‐(benzo[d]thiazol‐2‐ylthio)‐1‐(3,4‐dihydroxyphenyl)ethanones was found to inhibit Pma1p, with the most potent IC50 value of 8 μm in an in vitro plasma membrane H+‐ATPase assay. These compounds were also found to strongly inhibit the action of proton pumping when Pma1p was reconstituted into liposomes. 1‐(3,4‐Dihydroxyphenyl)‐2‐((6‐(trifluoromethyl)benzo[d]thiazol‐2‐yl)thio)ethan‐1‐one (compound 38) showed inhibitory activities on the growth of Candida albicans and Saccharomyces cerevisiae, which could be correlated and substantiated with the ability to inhibit Pma1p in vitro.
Anchoring a Sulfonate Group to an Electron‐Transporting Molecule by an Alkyl Chain and Its Use as the Counter Anion in a Phosphorescent Cationic Iridium Complex
Authors: Wang Pei , Luo Ningzi , Song Xiangzhi , He Lei 
Published: November 2017

AbstractAn electron‐transporting anion prepared by anchoring a sulfonate group onto an electron‐transporting molecule through a flexible alkyl chain and its use as the counter anion in a cationic iridium complex is reported. The flexible alkyl chain improves the solubility of the bulky anion in water or in polar organic solvents. The anion exhibits similar photophysical and electrochemical properties to the parent electron‐transporting molecule. Within the complex, the anion does not disturb the phosphorescence of the cation in the solid film. Solution‐processed small‐molecule organic light‐emitting diodes (OLEDs) using the complex as the dopant show superior performances over the reference device using the conventional complex with a PF6− counter anion. It is revealed that anchoring anionic groups to optoelectronically active molecules with flexible alkyl chains is a feasible approach to develop optoelectronically active anions for assembling ion pairs with advanced optoelectronic properties.
CRISPR/Cas9‐Based Safe‐Harbor Gene Editing in Rhesus iPSCs
Authors: Yada Ravi Chandra , Ostrominski John W. , Tunc Ilker , Hong So Gun , Zou Jizhong , Dunbar Cynthia E. 
Published: November 2017

AbstractNHP iPSCs provide a unique opportunity to test safety and efficacy of iPSC‐derived therapies in clinically relevant NHP models. To monitor these cells in vivo, there is a need for safe and efficient labeling methods. Gene insertion into genomic safe harbors (GSHs) supports reliable transgene expression while minimizing the risk the modification poses to the host genome or target cell. Specifically, this protocol demonstrates targeting of the adeno‐associated virus site 1 (AAVS1), one of the most widely used GSH loci in the human genome, with CRISPR/Cas9, allowing targeted marker or therapeutic gene insertion in rhesus macaque induced pluripotent stem cells (RhiPSCs). Furthermore, detailed instructions for screening targeted clones and a tool for assessing potential off‐target nuclease activity are provided. © 2017 by John Wiley & Sons, Inc.
Tetramer bis‐(8‐hydroxyquinoline) Zinc Crystals Prepared by Physical Vapor Deposition Method
Authors: Wei Zhixian , Song Hui , Dai Chenghu , Chen Zhen , Yan Xueyu , Ji Ziwu , Pang Zhiyong , Han Shenghao 
Published: November 2017

AbstractHigh quality single crystals of bis‐(8‐hydroxyquinoline) zinc (ZnQ2), a π‐conjugated molecular semiconductor with high thermal stability, good electron transport ability and excellent electroluminescence properties, were prepared by physical vapor deposition (PVD) method in a double zone tube furnace. X‐ray single crystal diffraction (XSCD) indicates that the sample was ZnO2 tetramer, (ZnQ2)4, with the triclinic unit cell parameters: a = 10.8537(15) Å, b = 11.8814(16) Å, c = 13.0532(18) Å, α = 74.119(2)°, β = 73.449(2)°, γ = 70.999(2)°, volume = 1494.9(4) Å3 and Z = 1. The crystallization mechanism analysis suggests a classical crystal growth process at low temperatures (300 and 320 °C) and an existence of non‐classical particle‐attachment crystal growth pathway at high temperature (340 °C). The (ZnQ2)4 crystals also show enhanced photoluminescence (PL) intensities and narrower full width at half maximum (FWHM) compared with that of the ZnQ2 thin film.
The CEO as a key microfoundation of global strategy: Task demands, CEO origin, and the CEO's international background
Authors: Kunisch Sven , Menz Markus , Cannella Albert A. 
Published: November 2017

Research SummaryWe explore the selection of new CEOs with international backgrounds as a key microfoundation of global strategy. Building on executive succession, upper echelons, and international business research, we argue that firms choose CEOs with international backgrounds to match their task demands. We further argue that depending on the CEO's origin from inside or outside the firm, different task demands matter. Specifically, we propose that the relationship between internal (firm‐level) task demands and the new CEO's international background is more pronounced for inside successions, whereas the relationship between external (industry‐level) task demands and the new CEO's international background is more pronounced for outside successions. An analysis of a sample of 363 CEO successions in S&P 500 firms supports our reasoning.Managerial SummaryChoosing a CEO with the “right” experience is a crucial concern for many large firms. While firms increasing seem to select new CEOs with international backgrounds, not all firms do so. In this article, we explore several factors that might influence this choice. Our results reveal that the predecessor's international background, the firm's level of internationalization, and the level of internationalization of the firm's industry influence whether a CEO with an international background is selected. Moreover, while for inside successions, the firm's level of internationalization is particularly important, for outside successions, the level of internationalization of the firm's industry is particularly important. Our findings inform those who search, select, and appoint new CEOs, including boards of directors and (executive search) consultants.
Association between structural brain network efficiency and intelligence increases during adolescence
Authors: Koenis Marinka M.G. , Brouwer Rachel M. , Swagerman Suzanne C. , van Soelen Inge L.C. , Boomsma Dorret I. , Hulshoff Pol Hilleke E. 
Published: November 2017

AbstractAdolescence represents an important period during which considerable changes in the brain take place, including increases in integrity of white matter bundles, and increasing efficiency of the structural brain network. A more efficient structural brain network has been associated with higher intelligence. Whether development of structural network efficiency is related to intelligence, and if so to which extent genetic and environmental influences are implicated in their association, is not known. In a longitudinal study, we mapped FA‐weighted efficiency of the structural brain network in 310 twins and their older siblings at an average age of 10, 13, and 18 years. Age‐trajectories of global and local FA‐weighted efficiency were related to intelligence. Contributions of genes and environment were estimated using structural equation modeling. Efficiency of brain networks changed in a non‐linear fashion from childhood to early adulthood, increasing between 10 and 13 years, and leveling off between 13 and 18 years. Adolescents with higher intelligence had higher global and local network efficiency. The dependency of FA‐weighted global efficiency on IQ increased during adolescence (rph=0.007 at age 10; 0.23 at age 18). Global efficiency was significantly heritable during adolescence (47% at age 18). The genetic correlation between intelligence and global and local efficiency increased with age; genes explained up to 87% of the observed correlation at age 18. In conclusion, the brain's structural network differentiates depending on IQ during adolescence, and is under increasing influence of genes that are also associated with intelligence as it develops from late childhood to adulthood.
Preventive effects of tonsil‐derived mesenchymal stem cells on osteoradionecrosis in a rat model
Authors: Park Hae Sang , Lee Jihae , Kim Jin‐Woo , Kim Ha Young , Jung Soo Yeon , Lee Sung Min , Park Chan Hum , Kim Han Su 
Published: November 2017

AbstractBackgroundThe purpose of this study was to investigate the effects of tonsil‐derived mesenchymal stem cells (MSCs) on osteoradionecrosis (ORN).MethodWe generated a mandibular ORN rat model using a combination of 20‐Gy single‐dose irradiation and tooth extraction. Study groups were negative control (tooth extraction only), ORN group (irradiation, tooth extraction), Matrigel‐1 group (Matrigel; BD Biosciences, San Jose, CA; irradiation, Matrigel application immediately after tooth extraction), tonsil‐derived MSC‐1 group (irradiation, tonsil‐derived MSC application immediately after tooth extraction), Matrigel‐4 group (irradiation, Matrigel application 4 weeks after tooth extraction), and tonsil‐derived MSC‐4 group (irradiation, tonsil‐derived MSC application 4 weeks after tooth extraction).ResultBone mineral density was significantly lower in the ORN group than in the negative control group. The tonsil‐derived MSC‐1 group showed significantly higher bone mineral density than did the ORN and tonsil‐derived MSC‐4 groups.ConclusionA single 20‐Gy dose of irradiation combined with tooth extraction successfully generated ORN in the rat model. The tonsil‐derived MSCs can be effective for bone regeneration in ORN, particularly when applied immediately after dentoalveolar trauma or surgery.
Complications of double free flap and free flap combined with locoregional flap in head and neck reconstruction: A systematic review
Authors: Chen Collin L. , Zenga Joseph , Roland Lauren T. , Pipkorn Patrik 
Published: November 2017

AbstractBackgroundThe purpose of this clinical review was to assess the feasibility of reconstructing complex head and neck defects with 2 or more free flaps simultaneously.MethodsA total of 38 articles were reviewed. The patient population included those who received 2 or more free flaps or a single free flap plus a locoregional flap. The primary outcome assessed was rate of complications.ResultsAmong double flaps, the minor complication rate was 6.96% and the major complication rate was 20.0%. In comparison, the free flap plus locoregional flap group had higher rates of minor and major complications of 30.4% and 29.5%, respectively. The median operating time was 660 minutes for double flaps and 602 minutes for free flap plus locoregional flap (P = .828).ConclusionCompared to the single free flap plus locoregional flap, double free flaps are relatively reliable without increasing surgical complications or decreasing flap survival, while only modestly increasing operating times.
Infiltration into frozen soil: From core‐scale dynamics to hillslope‐scale connectivity
Authors: Appels Willemijn M. , Coles Anna E. , McDonnell Jeffrey J. 
Published: November 2017

AbstractInfiltration into frozen soil is a key hydrological process in cold regions. Although the mechanisms behind point‐scale infiltration into frozen soil are relatively well understood, questions remain about upscaling point‐scale results to estimate hillslope‐scale run‐off generation. Here, we tackle this question by combining laboratory, field, and modelling experiments. Six large (0.30‐m diameter by 0.35‐m deep) soil cores were extracted from an experimental hillslope on the Canadian Prairies. In the laboratory, we measured run‐off and infiltration rates of the cores for two antecedent moisture conditions under snowmelt rates and diurnal freeze–thaw conditions observed on the same hillslope. We combined the infiltration data with spatially variable data from the hillslope, to parameterise a surface run‐off redistribution model. We used the model to determine how spatial patterns of soil water content, snowpack water equivalent (SWE), and snowmelt rates affect the spatial variability of infiltration and hydrological connectivity over frozen soil. Our experiments showed that antecedent moisture conditions of the frozen soil affected infiltration rates by limiting the initial soil storage capacity and infiltration front penetration depth. However, shallow depths of infiltration and refreezing created saturated conditions at the surface for dry and wet antecedent conditions, resulting in similar final infiltration rates (0.3 mm hr−1). On the hillslope‐scale, the spatial variability of snowmelt rates controlled the development of hydrological connectivity during the 2014 spring melt, whereas SWE and antecedent soil moisture were unimportant. Geostatistical analysis showed that this was because SWE variability and antecedent moisture variability occurred at distances shorter than that of topographic variability, whereas melt variability occurred at distances longer than that of topographic variability. The importance of spatial controls will shift for differing locations and winter conditions. Overall, our results suggest that run‐off connectivity is determined by (a) a pre‐fill phase, during which a thin surface soil layer wets up, refreezes, and saturates, before infiltration excess run‐off is generated and (b) a subsequent fill‐and‐spill phase on the surface that drives hillslope‐scale run‐off.
Delivery outcomes of large‐for‐gestational‐age newborns stratified by the presence or absence of gestational diabetes mellitus
Authors: Rosen Hadar , Shmueli Anat , Ashwal Eran , Hiersch Liran , Yogev Yariv , Aviram Amir 
Published: November 2017

AbstractObjectiveTo evaluate separate and combined contributions of gestational diabetes mellitus (GDM) and large‐for‐gestational age (LGA) on delivery outcomes.MethodsIn a retrospective cohort study of term singleton deliveries between 2007 and 2014 in Tel Aviv, Israel, outcomes were compared between non‐GDM/AGA pregnancies (reference) and three study groups: non‐GDM/LGA, GDM/appropriate for gestational age (AGA) and GDM/LGA.ResultsOverall, there were 62 102 deliveries, of which 53 201 (85.7%) were eligible for inclusion. Of these, 43 775 (82.3%) were non‐GDM/AGA, 6441 (12.1%) non‐GDM/LGA, 2351 (4.4%) GDM/AGA, and 634 (1.2%) GDM/LGA. Compared with the reference group, the study groups had higher mean maternal age and higher rates of previous cesarean delivery, polyhydramnios, induction of labor, and cesarean delivery. Considering only women attempting vaginal delivery, the three groups were independently associated with adverse outcomes including cesarean delivery (adjusted odds ratio [aOR], 1.5, 1.6, and 2.6 for non‐GDM/LGA, GDM/AGA, and GDM/LGA, respectively), mainly for prolonged first stage of labor, and hypoglycemia (aOR, 1.9, 2.5, and 4.6, respectively). LGA with and without GDM was associated with shoulder dystocia (aOR, 14.5 and 6.9, respectively), prolonged second stage, and jaundice.ConclusionGDM and LGA share similarities in pregnancy complications. The presence of both has a cumulative impact.
A polyelectrolyte multilayer platform for investigating growth factor delivery modes in human liver cultures
Authors: Lin Christine , Romero Raimundo , Sorokina Lioudmila V. , Ballinger Kimberly R. , Place Laura W. , Kipper Matt J. , Khetani Salman R. 
Published: November 2017

AbstractPolyelectrolyte multilayers (PEMs) of chitosan and heparin are useful for mimicking growth factor (GF) binding to extracellular matrix (ECM) as in vivo. Here, we developed a PEM platform for delivering bound/adsorbed GFs to monocultures of primary human hepatocytes (PHHs) and PHH/non‐parenchymal cell (NPC) co‐cultures, which are useful for drug development and regenerative medicine. The effects of ECM protein coating (collagen I, fibronectin, and Matrigel®) and terminal PEM layer on PHH attachment/functions were determined. Then, heparin‐terminated/fibronectin‐coated PEMs were used to deliver varying concentrations of an adsorbed model GF, transforming growth factor β (TGFβ), to PHH monocultures while using soluble TGFβ delivery via culture medium as the conventional control. Soluble TGFβ delivery caused a severe, monotonic, and sustained downregulation of all PHH functions measured (albumin and urea secretions, cytochrome‐P450 2A6 and 3A4 enzyme activities), whereas adsorbed TGFβ delivery caused transient upregulation of 3 out of 4 functions. Finally, functionally stable co‐cultures of PHHs and 3T3‐J2 murine embryonic fibroblasts were created on the heparin‐terminated/fibronectin‐coated PEMs modified with adsorbed TGFβ to elucidate similarities and differences in functional response relative to the monocultures. In conclusion, chitosan‐heparin PEMs constitute a robust platform for investigating the effects of GF delivery modes on PHH monocultures and PHH/NPC co‐cultures. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 971–984, 2018.
Validation of the distress tolerance scale‐short form in obsessive compulsive disorder
Authors: Garner Lauryn E. , Van Kirk Nathaniel , Tifft Eric D. , Krompinger Jason W. , Mathes Brittany M. , Fraire Maria , Falkenstein Martha J. , Brennan Brian P. , Crosby Jesse M. , Elias Jason A. 
Published: November 2017

AbstractObjectiveThis study aimed to develop and validate the Distress Tolerance Scale‐Short Form (DTS‐SF), a modification of the original Distress Tolerance Scale, in a severe/complex sample of individuals with obsessive compulsive disorder (OCD). Currently, there are multiple self‐report measurements of distress tolerance (DT), highlighting the need for a more refined measure.MethodParticipants included 222 individuals with a primary diagnosis of OCD (57% male, average age = 31) seeking intensive/residential treatment. Participants completed surveys at admission, discharge, and each week.ResultsAn exploratory factor analysis revealed a one‐factor solution representing overall DT ability. The DTS‐SF was found to be sensitive to treatment effects. Appropriate associations between the DTS‐SF and other measures were also found, with lower DT associated with greater OCD and depression severity and lower reported quality of life.ConclusionThe DTS‐SF was found to be a valid and reliable measure with high clinical utility for quickly and accurately measuring DT.
Engineering Students' Epistemic Cognition in the Context of Problem Solving
Authors: Faber Courtney , Benson Lisa C. 
Published: November 2017

AbstractBackgroundStudents' beliefs about knowledge (epistemic beliefs) and their motivations toward processing information (epistemic motivation) have been suggested as influencing aspects of learning.PurposeThis study investigated the relationship between engineering students' approach to solving an open‐ended homework problem and their epistemic motivation, engineering epistemic beliefs, and epistemic cognition.MethodsThe initial quantitative phase of this sequential explanatory mixed methods study employed a k‐means cluster analysis to identify homogenous subgroups of biomedical engineering students based on their epistemic beliefs and epistemic motivation measured using a survey (n= 50). Eighteen of these students were interviewed to explore their epistemic cognitions when solving an open‐ended homework problem. Transcripts were analyzed and results were overlaid with the clusters to investigate relationships between students' approaches to problem solving and their epistemic beliefs, motivation, and cognition.ResultsThree clusters of students were identified based on three constructs of epistemic beliefs and epistemic motivation: source of engineering knowledge, certainty of engineering knowledge, and closed‐mindedness. Students in the same cluster activated similar components of epistemic cognition, such as their desired outcomes for solving the problem. Additionally, we identified that the instructor's description of the problem and how the assignment was structured influenced how students approached solving the problem.ConclusionsComparison of clusters revealed that having more constructivist epistemic beliefs does not guarantee that students will set epistemic aims or make epistemic gains. Additionally, students' approaches to solving the open‐ended problem were influenced by their lack of desire to consider other ideas. The outcomes of this study provide a more complete understanding of students' epistemic cognitions and beliefs related to problem solving in the classroom.
On unavoidable‐induced subgraphs in large prime graphs
Authors: Malliaris M. , Terry C. 
Published: November 2017

AbstractChudnovsky, Kim, Oum, and Seymour recently established that any prime graph contains one of a short list of induced prime subgraphs [1]. In the present article, we reprove their theorem using many of the same ideas, but with the key model‐theoretic ingredient of first determining the so‐called amount of stability of the graph. This approach changes the applicable Ramsey theorem, improves the bounds and offers a different structural perspective on the graphs in question. Complementing this, we give an infinitary proof that implies the finite result.
Preparation and comparative evaluation of 99mTc‐HYNIC‐cNGR and 99mTc‐HYNIC‐PEG2‐cNGR as tumor‐targeting molecular imaging probes
Authors: Vats Kusum , Satpati Drishty , Sharma Rohit , Kumar Chandan , Sarma Haladhar Dev , Banerjee Sharmila 
Published: November 2017

The tripeptide sequence asparagine‐glycine‐arginine (NGR) specifically recognizes aminopeptidase N (APN or CD13) receptors highly expressed on tumor cells and vasculature. Thus, NGR peptides can precisely deliver therapeutic and diagnostic compounds to CD13 expressing cancer sites. In this regard, 2 NGR peptide ligands, HYNIC‐c(NGR) and HYNIC‐PEG2‐c(NGR), were synthesized, radiolabeled with 99mTc, and evaluated in CD13‐positive human fibrosarcoma HT‐1080 tumor xenografts. The radiotracers, 99mTc‐HYNIC‐c(NGR) and 99mTc‐HYNIC‐PEG2‐c(NGR), could be prepared in approximately 95% radiochemical purity and exhibited excellent in vitro and in vivo stability. The radiotracers were hydrophilic in nature with log P values being −2.33 ± 0.05 and −2.61 ± 0.08. The uptake of 2 radiotracers 99mTc‐HYNIC‐c(NGR) and 99mTc‐HYNIC‐PEG2‐c(NGR) was similar in nude mice bearing human fibrosarcoma HT‐1080 tumor xenografts, which was significantly reduced (P < .05) during blocking studies. The 2 radiotracers being hydrophilic cleared rapidly from blood, liver, and intestine and were excreted through renal pathway. The pharmacokinetics of 99mTc‐labeled HYNIC peptide could not be modulated through introduction of PEG2 unit, thus posing a challenge for studies with other linkers towards enhanced tumor uptake and retention.