bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tetraethylammonium Bromide‐Catalyzed Oxidative Thioesterification of Aldehydes and Alcohols
Authors: Zhu Xuebin , Shi Yan , Mao Haibin , Cheng Yixiang , Zhu Chengjian 
Published: November 2013

AbstractA metal‐free, tetraethylammonium bromide‐catalyzed oxidative coupling of aldehydes or alcohols with thiophenols or disulfides has been developed. This protocol affords an efficient and inexpensive approach to the synthesis of a wide range of thioesters in high yields.magnified image
Iron Chloride‐Catalyzed Three‐Component Domino Sequences: Syntheses of Functionalized α‐Oxy‐N‐acylhemiaminals and α‐Oxyimides
Authors: Drouet Fleur , Zhu Jieping , Masson Géraldine 
Published: November 2013

AbstractThe iron(III) chloride‐multicatalyzed dioxygenation of enamides with TEMPO in the presence of alcohols has been developed. This multicomponent domino process affords efficient new strategies for the synthesis of α‐oxy‐N‐acylhemiaminals or α‐oxyimides in good to excellent yields under mild conditions.magnified image
Transport characteristics and transporter‐based drug–drug interactions of TM‐25659, a novel TAZ modulator
Authors: Choi Min‐Koo , Kwon Mihwa , Ahn Jin Hee , Kim Nak Jung , Bae Myung‐Ae , Song Im‐Sook 
Published: November 2013

ABSTRACTThe in vitro metabolic stability and transport mechanism of TM‐25659, a novel TAZ modulator, was investigated in human hepatocytes and human liver microsomes (HLMs) based on the preferred hepatobiliary elimination in rats. In addition, the in vitro transport mechanism and transporter‐mediated drug–drug interactions were evaluated using oocytes and MDCKII cells overexpressing clinically important drug transporters. After a 1 h incubation in HLMs, 92.9 ± 9.5% and 95.5 ± 11.6% of the initial TM‐25659 remained in the presence of NADPH and UDPGA, respectively. Uptake of TM‐25659 readily accumulated in human hepatocytes at 37 ºC (i.e. 6.7‐fold greater than that at 4 ºC), in which drug transporters such as OATP1B1 and OATP1B3 were involved. TM‐25659 had a significantly greater basal to apical transport rate (5.9‐fold) than apical to basal transport rate in the Caco‐2 cell monolayer, suggesting the involvement of an efflux transport system. Further studies using inhibitors of efflux transporters and overexpressing cells revealed that MRP2 was involved in the transport of TM‐25659. These results, taken together, suggested that TM‐25659 can be actively influxed into hepatocytes and undergo biliary excretion without substantial metabolism. Additionally, TM‐25659 inhibited the transport activities of OATP1B1 and OATP1B3 with IC50 values of 36.3 and 25.9 μm, respectively. TM‐25659 (100 μm) increased the accumulation of the probe substrate by 160% and 213%, respectively, through the inhibition of efflux function of P‐gp and MRP2. In conclusion, OATP1B1, OATP1B3, P‐gp and MRP2 might be major transporters responsible for the pharmacokinetics and drug–drug interaction of TM‐25659, although their contribution to in vivo pharmacokinetics needs to be further investigated. Copyright © 2013 John Wiley & Sons, Ltd.
Real‐time monitoring and control of soluble signaling factors enables enhanced progenitor cell outputs from human cord blood stem cell cultures
Authors: Csaszar Elizabeth , Chen Kun , Caldwell Julia , Chan Warren , Zandstra Peter W. 
Published: November 2013

ABSTRACTMonitoring and control of primary cell cultures is challenging as they are heterogenous and dynamically complex systems. Feedback signaling proteins produced from off‐target cell populations can accumulate, inhibiting the production of the desired cell populations. Although culture strategies have been developed to reduce feedback inhibition, they are typically optimized for a narrow range of process parameters and do not allow for a dynamically regulated response. Here we describe the development of a microbead‐based process control system for the monitoring and control of endogenously produced signaling factors. This system uses quantum dot barcoded microbeads to assay endogenously produced signaling proteins in the culture media, allowing for the dynamic manipulation of protein concentrations. This monitoring system was incorporated into a fed‐batch bioreactor to regulate the accumulation of TGF‐β1 in an umbilical cord blood cell expansion system. By maintaining the concentration of TGF‐β1 below an upper threshold throughout the culture, we demonstrate enhanced ex vivo expansion of hematopoietic progenitor cells at higher input cell densities and over longer culture periods. This study demonstrates the potential of a fully automated and integrated real‐time control strategy in stem cell culture systems, and provides a powerful strategy to achieve highly regulated and intensified in vitro cell manufacturing systems. Biotechnol. Bioeng. 2014;111: 1258–1264. © 2013 The Authors Biotechnology and Bioengineering Published by Wiley Periodicals, Inc.
Variations of coronary hemodynamic responses to intravenous adenosine infusion: Implications for fractional flow reserve measurements
Authors: Seto Arnold H. , Tehrani David M. , Bharmal Murtaza I. , Kern Morton J. 
Published: November 2013

BackgroundContinuous intravenous adenosine infusion reportedly produces stable and maximal hyperemia to allow for fractional flow reserve (FFR) measurement; however, several observers have noted variation of the coronary/aortic (Pd/Pa) pressure ratio during the course of an adenosine infusion.MethodsPd/Pa pressure recordings during continuous peripheral intravenous adenosine infusion were examined in 51 patients (68 measurements) with data collected for at least 150 sec and for at least 30 sec after the lowest Pd/Pa reading. The lowest recorded Pd/Pa ratio was used as the true FFR value at maximal hyperemia. The highest subsequent Pd/Pa during the remaining period of adenosine infusion was recorded. A separate cohort of 12 patients had Pd/Pa values measured with both peripheral and central infusion.ResultsThe average FFR value was 0.82 ± 0.10 and was recorded 99 ± 33 sec into the infusion. The Pd/Pa value showed a subsequent average increase of 0.08 ± 0.07 at 135 ± 32 sec. From the lowest measurement, Pd/Pa changed from a ratio ≤0.80 to >0.80 in 28% of recordings. In the cohort with matched recordings, central infusion reduced the severity (mean change of 0.08 vs. 0.11, P = 0.09) but not the incidence of Pd/Pa variability compared with peripheral infusion.ConclusionInstability of Pd/Pa measurements is common over the course of a continuous intravenous adenosine infusion. FFR remains valid as the lowest value of Pd/Pa observed, however, Pd/Pa variability may subsequently occur and complicate pullback measurements for serial or multiple lesions. © 2013 Wiley Periodicals, Inc.
Inhibition of Hypoxia‐Induced Gene Transcription by Substituted Pyrazolyl Oxadiazoles: Initial Lead Generation and Structure–Activity Relationships
Authors: Härter Michael , Thierauch Karl‐Heinz , Boyer Stephen , Bhargava Ajay , Ellinghaus Peter , Beck Hartmut , Greschat‐Schade Susanne , Hess‐Stumpp Holger , Unterschemmann Kerstin 
Published: November 2013

AbstractThe transcription factors hypoxia‐inducible factor‐1 and ‐2 (HIF‐1 and HIF‐2) orchestrate a multitude of processes that allow tumor cells to survive under conditions of low oxygen and nutrients, and that lead to resistance to some apoptotic pathways and facilitate invasion and metastasis. Therefore, inhibition of transactivation by HIF has become an attractive target in cancer research. Herein we present the results of a cell‐based screening approach that led to the discovery of substituted 1H‐pyrazole‐3‐carboxamides. Chemical optimization of the hit class with respect to potency and metabolic stability is described; it resulted in novel 5‐(1H‐pyrazol‐3‐yl)‐1,2,4‐oxadiazoles that inhibit the hypoxia‐induced accumulation of HIF‐1α and HIF‐2α. The HIF inhibitory potency in the screening cell system was improved from IC50 190 to 0.7 nM, and significant parts of the SAR are disclosed. For a key compound, the ability to suppress the hypoxia‐induced expression of HIF target genes was studied in A549 human lung adenocarcinoma cells. The same compound shows a favorable pharmacokinetic profile in rats after i.v. and p.o. administration.
The Fight against the Influenza A Virus H1N1: Synthesis, Molecular Modeling, and Biological Evaluation of Benzofurazan Derivatives as Viral RNA Polymerase Inhibitors
Authors: Pagano Mafalda , Castagnolo Daniele , Bernardini Martina , Fallacara Anna Lucia , Laurenzana Ilaria , Deodato Davide , Kessler Ulrich , Pilger Beatrice , Stergiou Lilli , Strunze Stephan , Tintori Cristina , Botta Maurizio 
Published: November 2013

AbstractThe influenza RNA polymerase complex, which consists of the three subunits PA, PB1, and PB2, is a promising target for the development of new antiviral drugs. A large library of benzofurazan compounds was synthesized and assayed against influenza virus A/WSN/33 (H1N1). Most of the new derivatives were found to act by inhibiting the viral RNA polymerase complex through disruption of the complex formed between subunits PA and PB1. Docking studies were also performed to elucidate the binding mode of benzofurazans within the PB1 binding site in PA and to identify amino acids involved in their mechanism of action. The predicted binding pose is fully consistent with the biological data and lays the foundation for the rational development of more effective PA–PB1 inhibitors.
Steady‐state pharmacokinetics of sirolimus in stable adult Chinese renal transplant patients
Authors: Wang Huifen Faye , Qiu Feng , Wu Xiongfe , Fang Juanzhi , Crownover Penelope , Korth‐Bradley Joan , Schulman Seth 
Published: November 2013

AbstractThis open‐label, nonrandomized study was conducted to evaluate the steady‐state pharmacokinetics of sirolimus in 24 stable Chinese renal transplant patients receiving daily oral maintenance doses of sirolimus (1–4 mg). Repeated trough and serial whole blood sirolimus concentrations over a 24‐hour dosing interval were collected and assayed using high‐performance liquid chromatography with tandem mass spectrometry (HPLC/MS/MS). Non‐compartmental analysis (NCA) was employed to calculate sirolimus pharmacokinetic parameters. Cytochrome P450 (CYP) 3A5 genotyping was performed. Cyclosporine (CsA) levels were determined for patients who took concomitant CsA. Mean (±SD) sirolimus maximum concentration (Cmax), area under the concentration–time curve within a dosing interval of τ (AUCτ), oral clearance (CL/F), and trough concentration (Ctrough) at steady state were: 14.1 ± 13.4 ng/mL, 199 ± 210 ng · h/mL, 10.1 ± 4.4 L/h, and 5.9 ± 6.3 ng/mL, respectively. Median tmax (range) was 2.49 hours (1–12 hours). A strong correlation was observed between Ctrough and AUCτ. Pharmacokinetics of sirolimus in patients with and without concomitant CsA were comparable. Allele frequency of CYP3A5*3 was 70.9% and a trend of higher oral clearance was observed in CYP3A5 expressers compared with non‐expressers although the number of subjects in each genotype was small.
The role of collegial alliance in family‐based treatment of adolescent anorexia nervosa: A pilot study
Authors: Murray Stuart B. , Griffiths Scott , Le Grange Daniel 
Published: November 2013

ABSTRACTObjectiveIn keeping with broader efforts to identify mediators and moderators of treatment outcome in anorexia nervosa, this pilot study investigated the association between collegial alliance, which refers to the perceived alliance between case‐involved professionals, and treatment outcomes in adolescent patients undergoing family‐based treatment (FBT) for anorexia nervosa.MethodThe self‐reported collegial alliance scores of five FBT practitioners were collected, alongside weight‐ and cognitive‐related outcomes for 29 consecutive cases of adolescent anorexia nervosa under their care.ResultsCollegial alliance discriminated between patients who dropped out of treatment and patients who completed treatment,t(27) = 3.68,p = .001,η2 = .33. Furthermore, there was a strong negative correlation between collegial alliance scores early on in treatment and disordered eating symptoms later in treatment,r(23) = −.67,p < .001. Moderate but non‐significant associations were observed between early collegial alliance and patient's percentage of expected body weight later in treatment,r(23) = .32,p = .13.DiscussionThese findings have important implications for the augmentation of FBT, suggesting that unity amongst clinicians promotes positive treatment outcomes, particularly with regard to disordered eating symptomatology. © 2013 Wiley Periodicals, Inc. (Int J Eat Disord 2014; 47:418–421)
Hydraulic redistribution by plants and nutrient stoichiometry: Shifts under global change
Authors: Sardans Jordi , Peñuelas Josep 
Published: November 2013

ABSTRACTHydraulic lift, water movement from deep to upper soil layers by roots, is a widespread process in temperate and semi‐arid environments. It can contribute 17–81% of total water transpired and favour the uptake of nutrients available mainly from soil organic matter decomposition (e.g. N). Downward siphoning, water movement from upper to deep soil layers, can represent 10–60% of total transpired water, favouring the uptake of nutrients supplied mainly from the leaching of bedrock minerals (e.g. P and K). These vertical water movements also can affect the N : P ratio of runoff waters when, in the case of hydraulic lift, they open the possibility for a given pulse of water to circulate multiple times across the N‐rich upper soil layers. Plants, thus, affect the stoichiometry of nutrients in soils and groundwater not only through the physical protection of the soil and through the water uptake but also through water redistribution. Soil water redistribution can also play an outstanding role in the ecosystem responses to global change drivers. The increase in soil patchiness in current and future arid lands modifies runoff fluxes, hydraulic lift and downward siphoning, allowing plants to dispose of higher water and nutrient availabilities. The higher use of hydraulic lift and/or downward siphoning by alien species is a possible cause of alien plant success. Further mechanistic and quantitative research is thus warranted to discern the plant role in water and nutrient cycling and in the responses to global change. Copyright © 2014 John Wiley & Sons, Ltd.
An Expert Solution to Assess an Industrially Situated, Computer‐Enabled Design Project
Authors: Sherrett Benjamin U. , Nefcy Erick J. , Gummer Edith S. , Koretsky Milo D. 
Published: November 2013

AbstractBackgroundProcess development is a common and critical task for industrial chemical engineers; however, it is difficult to create activities to give students such practice in their university education. Using a computer‐based simulation, we have created an authentic, industrially situated process development task that students can complete by applying their foundational knowledge and skills. We present a case study of an expert's solution to this task, which is compared with those of higher‐ and lower‐performing student teams.PurposeThe expert study sought to characterize modeling approaches to this task and to develop a set of target competencies to evaluate evidence of student learning as a guide to assessment.Design/MethodThis comparative case study used ethnographic methodology to capture descriptions of the models and strategies that an expert and two advanced undergraduate student teams employed.ResultsWe categorized the expert solution into steps of information gathering, problem formulation, and iterative modeling and experimentation. We identified fourteen expert competencies and used them to assess two sample student solutions. Each student solution contained some expert competencies; a higher number of expert competencies are evident in the student team that had been previously identified as higher performing.ConclusionsThe framework demonstrates constructive alignment of an authentic project task with evidence of student learning to evaluate the competencies students develop. This model example can be extended to other computer‐enabled learning environments and, more generally, to capstone projects and other types of open‐ended project work.
Biembedding a Steiner Triple System With a Hamilton Cycle Decomposition of a Complete Graph
Authors: McCourt Thomas A. 
Published: November 2013

AbstractWe construct a face two‐colourable, blue and green say, embedding of the complete graph in a nonorientable surface in which there are blue faces each of which have a hamilton cycle as their facial walk and green faces each of which have a triangle as their facial walk; equivalently a biembedding of a Steiner triple system of order n with a hamilton cycle decomposition of , for all and . Using a variant of this construction, we establish the minimum genus of nonorientable embeddings of the graph , for where and .
Does histology predict outcome for malignant vascular tumors of the liver?
Authors: Groeschl Ryan T. , Miura John T. , Oshima Kiyoko , Gamblin T. Clark , Turaga Kiran K. 
Published: November 2013

Background and ObjectivesMalignant vascular tumors (MVT) of the liver are uncommon and poorly understood. We hypothesized that tumor histology is a predominant factor associated with survival in these tumors.MethodsPatients with malignant histopathologic diagnoses of hepatic angiosarcoma (AS), hemangioendothelioma (HE) and its epithelioid variant (EHE), or hemangiopericytoma (HP) were identified using the SEER database (1973–2007). Overall survival (OS) was studied with Kaplan–Meier curves.ResultsWe included 297 patients with MVT (207 AS, 28 HE, 56 EHE, 6 HP). All tumors demonstrated metastatic potential, although EHE and AS had the highest rate of regional or distant metastases (75% each). Patients with AS had the shortest median OS (1 month), however, those undergoing surgery had improved survival (6 months). Three patients with AS underwent liver transplant and lived for 11, 21, and 91 months each. Patients with EHE had the longest overall median survival of 75 months (30–183,P < 0.001). Surgical resection and transplant did not demonstrate an improvement in OS of patients with EHE in multivariable models.ConclusionsHistology is an important factor in determining survival for patients with hepatic MVT. Patients with EHE have the longest OS, whereas patients with AS have shorter survival but may benefit from surgery.J. Surg. Oncol. 2014 109:483–486. © 2013 Wiley Periodicals, Inc.
Cost‐utility analysis of bilateral cochlear implantation in adults: A health economic assessment from the perspective of a publicly funded program
Authors: Chen Joseph M. , Amoodi Hossam , Mittmann Nicole 
Published: November 2013

Objectives/HypothesisTo determine the cost‐effectiveness of bilateral cochlear implantation (CI) in deaf adults.Study DesignCost–utility analysis.MethodsNinety patients and 52 health professionals served as proxies to estimate the benefit of bilateral cochlear implantation, utilizing the Health Utility Index. Three scenarios were created to reflect 1) deafness without intervention, 2) unilateral CI, and 3) bilateral CI. Cost evaluation reflected the burden on a publicly funded healthcare system. The base case included 25 years of service provision, processor upgrades every 5 years, 50% price reduction for second side, and 15% failure rate. Discounting and sensitivity analyses were applied.ResultsCosts were $63,632 (unilateral CI), $111,764 (bilateral CI), and $48,132 (incremental cost of second CI). The health preference gained from no intervention to unilateral CI, and to bilateral CI were 0.270 and 0.305. Incremental utility gained by the second implant was 11.5% of total. The incremental cost‐utility ratio (ICUR) was $14,658/quality‐adjusted life year (QALY) for bilateral CI compared to no intervention. It was stable regardless of discounting or sensitivity analyses. ICUR was $55,020/QALY from unilateral to bilateral CI with higher uncertainties. It improved with differential discounting, further second‐side price reduction, and reduced frequency of processor upgrades. ICUR worsened with reduced length of use and higher failure rates.ConclusionsSequential bilateral CI was cost‐effective when compared to no intervention, although gains were made mostly by the first implant. Cost‐effectiveness compared to unilateral implantation was borderline but improved through base case variations to reflect long‐term gains or cost‐saving measures.Level of Evidence2C Laryngoscope, 124:1452–1458, 2014
A Neutral Supramolecular Hyperbranched Polymer Fabricated from an AB2‐Type Copillar[5]arene
Authors: Wang Xiaoyang , Deng Hongmei , Li Jian , Zheng Kai , Jia Xueshun , Li Chunju 
Published: November 2013

A heterotritopic copillar[5]arene monomer by introducing effective neutral guest moieties (methylene chains end‐capped with cyano and triazole groups) to a pillar[5]arene macrocycle is prepared. This well‐designed AB2‐type copillar[5]arene contains strong host–guest recognition motifs that are connected with relatively flexible and long linkers, thus efficiently assembles to form supramole­cular hyperbranched polymer (SHP) in chloroform solution, which is characterized by various techniques including 1H NMR, DOSY, viscosity, DLS, and TEM. Particularly, this supramolecular polymer can be effectively depolymerized by adding a competitive butanedinitrile guest.
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Hip strength: Ankle proprioceptive threshold ratio predicts falls and injury in diabetic neuropathy
Authors: Richardson James K. , Demott Trina , Allet Lara , Kim Hogene , Ashton‐miller James A. 
Published: November 2013

ABSTRACTIntroduction: We determined lower limb neuromuscular capacities associated with falls and fall‐related injuries in older people with declining peripheral nerve function. Methods: Thirty‐two subjects (67.4 ± 13.4 years; 19 with type 2 diabetes), representing a spectrum of peripheral neurologic function, were evaluated with frontal plane proprioceptive thresholds at the ankle, frontal plane motor function at the ankle and hip, and prospective follow‐up for 1 year. Results: Falls and fall‐related injuries were reported by 20 (62.5%) and 14 (43.8%) subjects, respectively. The ratio of hip adductor rate of torque development to ankle proprioceptive threshold (HipSTR/AnkPRO) predicted falls (pseudo‐R2 = .726) and injury (pseudo‐R2 = .382). No other variable maintained significance in the presence of HipSTR/AnkPRO. Conclusions: Fall and injury risk in the population studied is related inversely to HipSTR/AnkPRO. Increasing rapidly available hip strength in patients with neuropathic ankle sensory impairment may decrease risk of falls and related injuries. Muscle Nerve 50: 437–442, 2014