bluuebunny/crossref_metadata_2025_split huggingface dataset:
3‐Phenylpropanoic Acid‐Based Phosphotyrosine (pTyr) Mimetics: Hit Evolution to a Novel Orally Active Protein Tyrosine Phosphatase 1B (PTP1B) Inhibitor
Authors: Tang Yan‐Bo , Liu Jun‐Zheng , Zhang Shu‐En , Du Xin , Nie Feilin , Tian Jin‐Ying , Ye Fei , Huang Kai , Hu Jin‐Ping , Li Yan , Xiao Zhiyan 
Published: March 2014

AbstractProtein tyrosine phosphatase 1B (PTP1B) is a promising therapeutic target for type 2 diabetes. Herein, we report the evolution of a previously identified 3‐phenylpropanoic acid‐based PTP1B inhibitor to an orally active lead compound. A series of 3‐phenylpropanoic acid‐based PTP1B inhibitors were synthesized, and three of them, 3‐(4‐(9H‐carbazol‐9‐yl)phenyl)‐5‐(3,5‐di‐tert‐butyl‐4‐methoxyphenyl)‐5‐oxopentanoic acid (9), 3‐(4‐(9H‐carbazol‐9‐yl)phenyl)‐5‐(4′‐bromo‐[1,1′‐biphenyl]‐4‐yl)‐5‐oxopentanoic acid (10) and 3‐(4‐(9H‐carbazol‐9‐yl)‐2‐fluorophenyl)‐5‐(4‐cyclohexylphenyl)‐5‐oxopentanoic acid (16), showed IC50 values at sub‐micromolar level. Further in vivo evaluation indicated the sodium salt of 9 not only exhibited significant insulin‐sensitizing and hypoglycemia effects, but also decreased the serum levels of triglyceride and total cholesterol in high‐fat‐diet‐induced insulin resistance model mice. Preliminary in vivo pharmacokinetic studies on the sodium salt of 9 revealed its pharmacokinetic profile after oral administration in rats. These results provide proof‐of‐concept for the dual effects of PTP1B inhibitors on both glucose and lipid metabolisms.
Computational Insight into p21‐Activated Kinase 4 Inhibition: A Combined Ligand‐ and Structure‐Based Approach
Authors: Li Rui‐Juan , Wang Jian , Xu Zhen , Huang Wan‐Xu , Li Jia , Jin Sheng‐Fei , Zhao Dong‐Mei , Cheng Mao‐Sheng 
Published: March 2014

Abstractp21‐Activated kinase 4 (PAK4) is a serine/threonine protein kinase that plays important roles in a wide variety of human diseases including cancer. Targeting this kinase with specific inhibitors is of great interest in the treatment of cancer. In this study, PAK4 and its interaction with ATP‐competitive inhibitors was investigated by a combined ligand‐ and structure‐based approach. First, a ligand‐based pharmacophore model was generated, consisting of five chemical features: a positive ionizable center, two hydrophobic groups, a hydrogen bond donor, and a hydrogen bond acceptor, which is consistent with available SAR information. The characteristics of the active site were then described as a topological region and used in docking of nine selected inhibitors. Combination of the pharmacophore model and results from the docking studies allowed us to weigh the various pharmacophore features and to identify the positive ionizable center as a spacer rather than an essential point. This research led to the proposal of an interaction model inside the PAK4 active site and provided guidance for the design of more potent PAK4 inhibitors.
Lateral habenula and the rostromedial tegmental nucleus innervate neurochemically distinct subdivisions of the dorsal raphe nucleus in the rat
Authors: Sego Chemutai , Gonçalves Luciano , Lima Leandro , Furigo Isadora C. , Donato Jose , Metzger Martin 
Published: March 2014

ABSTRACTThe lateral habenula (LHb) is an epithalamic structure differentiated in a medial (LHbM) and a lateral division (LHbL). Together with the rostromedial tegmental nucleus (RMTg), the LHb has been implicated in the processing of aversive stimuli and inhibitory control of monoamine nuclei. The inhibitory LHb influence on midbrain dopamine neurons has been shown to be mainly mediated by the RMTg, a mostly GABAergic nucleus that receives a dominant input from the LHbL. Interestingly, the RMTg also projects to the dorsal raphe nucleus (DR), which also receives direct LHb projections. To compare the organization and transmitter phenotype of LHb projections to the DR, direct and indirect via the RMTg, we first placed injections of the anterograde tracer Phaseolus vulgaris leucoagglutinin into the LHb or the RMTg. We then confirmed our findings by retrograde tracing and investigated a possible GABAergic phenotype of DR‐projecting RMTg neurons by combining retrograde tracing with in situ hybridization for GAD67. We found only moderate direct LHb projections to the DR, which mainly emerged from the LHbM and were predominantly directed to the serotonin‐rich caudal DR. In contrast, RMTg projections to the DR were more robust, emerged from RMTg neurons enriched in GAD67 mRNA, and were focally directed to a distinctive DR subdivision immunohistochemically characterized as poor in serotonin and enriched in presumptive glutamatergic neurons. Thus, besides its well‐acknowledged role as a GABAergic control center for the ventral tegmental area (VTA)–nigra complex, our findings indicate that the RMTg is also a major GABAergic relay between the LHb and the DR. J. Comp. Neurol. 522:1454–1484, 2014. © 2013 Wiley Periodicals, Inc.
A residual modified transformation formula from munsell to sRGB color system
Authors: Hsiao Shih‐Wen , Tsai Cheng‐Ju 
Published: March 2014

AbstractA residual modified transformation formula from Munsell to sRGB color system is presented in this article. The development of the transformation formula is based on the 1625 Munsell color chips in the Munsell Renotation Data that could be displayed on the sRGB monitor. The developed transformation formula consists of two models, one is named as the corresponding matrix model and the other is the residual modified model. The corresponding matrix model was obtained using numerical analysis methods to map each chip color attribute values from Munsell to sRGB and then its corresponding matrix for each Hue was constructed. The residual modified model was obtained using the discrete cosine transform to construct a residual modified function, which was used to modify the transformation error of each chip after applying the corresponding matrix model. The transformed accuracy rate for the corresponding matrix model is 88.4% and for the residual modified model can be enhanced to 96.6% for all of the chips. The developed transformation formula can be applied to research in which Munsell colors are presented on the sRGB monitor. With the aid of these formulas, designers can show the advanced real‐time results on a sRGB monitor for the product's color planning based on Munsell color system. Therefore, this research has a great contribution on the practical application for color planning in product design. © 2014 Wiley Periodicals, Inc. Col Res Appl, 40, 243–255, 2015
Perovskite Solar Cells Based on Nanocolumnar Plasma‐Deposited ZnO Thin Films
Authors: Ramos F. Javier , López‐Santos Maria C. , Guillén Elena , Nazeeruddin Mohammad Khaja , Grätzel Michael , Gonzalez‐Elipe Agustin R. , Ahmad Shahzada 
Published: March 2014

AbstractZnO thin films having a nanocolumnar microstructure are grown by plasma‐enhanced chemical vapor deposition at 423 K on pre‐treated fluorine‐doped tin oxide (FTO) substrates. The films consist of c‐axis‐oriented wurtzite ZnO nanocolumns with well‐defined microstructure and crystallinity. By sensitizing CH3NH3PbI3 on these photoanodes a power conversion of 4.8 % is obtained for solid‐state solar cells. Poly(triarylamine) is found to be less effective when used as the hole‐transport material, compared to 2,2′,7,7′‐tetrakis(N,N‐di‐p‐methoxyphenylamine)‐9,9′‐spirobifluorene (spiro‐OMeTAD), while the higher annealing temperature of the perovskite leads to a better infiltration in the nanocolumnar structure and an enhancement of the cell efficiency.
One‐Dimensional [Ni(O2CR)2(NN)x] Polymers: Structural, Magnetic, and Density Functional Theory Studies
Authors: Cortijo Miguel , Herrero Santiago , Jerez Belén , Jiménez‐Aparicio Reyes , Perles Josefina , Priego José L. , Torroba Javier , Tortajada José 
Published: March 2014

AbstractFive nickel complexes, [Ni2(3,4,5‐tmb)4(4,4′‐bpy)] (1), [Ni2(2‐ntc)4(4,4′‐bpy)] (2), [Ni(9‐atc)2(4,4′‐bpy)] (3), [Ni(3,4,5‐tmb)2(t‐bpee)] (4), and [Ni2(2‐ntc)4(t‐bpee)2] (5) (3,4,5‐tmb=3,4,5‐trimethoxybenzoate; 2‐ntc=2‐naphthalenecarboxylate; 9‐atc=9‐anthracenecarboxylate; 4,4′‐bpy=4,4′‐bipyridine; t‐bpee=trans‐1,2‐bis(4‐pyridyl)ethylene), are prepared. They are characterized by elemental analysis, IR spectroscopy, thermogravimetric analysis, and single‐crystal and powder X‐ray diffraction. 1 and 2 form linear chains of paddlewheel units joined by 4,4′‐bpy ligands; 3 and 4 display zigzag chains formed by cis‐bis(chelate) Ni(O2CR)2 units joined by 4,4′‐bpy and t‐bpee, respectively; and the structure of 5 consists of double chains. The magnetic behavior of the compounds is also studied, and DFT calculations using the broken‐symmetry approximation are performed to gain a better understanding of the strong antiferromagnetism found in 1.
Biphasic Catalytic Conversion of Fructose by Continuous Hydrogenation of HMF over a Hydrophobic Ruthenium Catalyst
Authors: Yang Yanliang , Du Zhongtian , Ma Jiping , Lu Fang , Zhang Junjie , Xu Jie 
Published: March 2014

AbstractThe production of chemicals directly from sugars is an important step in biomass conversion. Herein, tetrahydro‐2,5‐furandimethanol (THFDM), obtained from fructose, is formed by using a combination of acid and hydrophobic Ru/SiO2 in a water/cyclohexane biphasic system. Two key factors enable the high selectivity towards THFDM: modifying the hydrogenation catalyst so that it has hydrophobic properties, and the continuous hydrogenation of generated 5‐(hydroxymethyl)furfural in the cyclohexane phase. Moreover, the selectivity towards THFDM is found to depend strongly on the acid catalyst used.
Early gestational weight gains within current recommendations result in increased risk of gestational diabetes mellitus among Korean women
Authors: Park Sunmin , Kim Min‐Hyoung , Kim Sung‐Hoon 
Published: March 2014

AbstractBackgroundWe prospectively assessed whether maternal weight gain at 24–28 weeks of gestation (MWG24) influences the risk of developing gestational complications, such as gestational diabetes mellitus (GDM) and other adverse pregnancy outcomes, in pregnant Korean women.MethodsMaternal weight gain from self‐reported pre‐pregnancy weight until 24–28 weeks of gestation was measured in 731 pregnant women, and an expected MWG24 was determined using the Institute of Medicine 2009 guidelines. Glucose tolerance, insulin resistance, insulin secretory capacity, anthropometric measurements, lipid profiles, nutrient intakes and pregnancy outcomes were evaluated at 24–28 weeks of gestation. The adjusted odds ratios (ORs) for GDM, large‐for‐gestational‐age infants, small‐for‐gestational‐age infants and preterm delivery were determined according to maternal weight gain by logistic regression analysis after adjusting for covariates.ResultsCompared with a normal MWG24, an inadequate MWG24 reduced the OR (0.565) for GDM, but an excessive MWG24 did not affect the OR (0.854). However, ORs for preterm delivery were significantly higher in both inadequate and excessive MWG24 groups in comparison with the normal MWG24. There were no other adverse pregnancy outcomes due to the inadequate MWG24. MWG24 was not associated with a significant increase in ORs for delivering large‐for‐gestational‐age or small‐for‐gestational‐age infants or delivery by caesarean section. Although energy intake was less than the estimated energy requirement in all groups, MWG24 was linearly associated with energy intake such that energy balance was positive in the excessive MWG24 group.ConclusionsThis study suggests that both target weight gain and energy intake recommendations for early pregnancy may not be optimal for Korean women and that race‐specific recommendations are needed to decrease the risk of GDM without increasing adverse pregnancy outcomes. Copyright © 2014 John Wiley & Sons, Ltd.
Defining conservation units in a stocking‐induced genetic melting pot: unraveling native and multiple exotic genetic imprints of recent and historical secondary contact inAdriatic grayling
Authors: Meraner Andreas , Cornetti Luca , Gandolfi Andrea 
Published: March 2014

AbstractThe definition of conservation units is crucial for the sustainable management of endangered species, though particularly challenging when recent and past anthropogenic and natural gene flow might have played a role. The conservation of the European grayling,Thymallus thymallus, is particularly complex in its southern distribution area, where the Adriatic evolutionary lineage is endangered by a long history of anthropogenic disturbance, intensive stocking and potentially widespread genetic introgression. We provide mtDNAsequence and microsatellite data of 683 grayling from 30 sites of Adriatic as well as Danubian and Atlantic origin. We apply Bayesian clustering and Approximate Bayesian Computation (ABC) to detect microgeographic population structure and to infer the demographic history of the Adriatic populations, to define appropriate conservation units. Varying frequencies of indigenous genetic signatures of the Adriatic grayling were revealed, spanning from marginal genetic introgression to the collapse of native gene pools. Genetic introgression involved multiple exotic source populations of Danubian and Atlantic origin, thus evidencing the negative impact of few decades of stocking. Within the Adige River system, a contact zone of western Adriatic and eastern Danubian populations was detected, withABCanalyses suggesting a historical anthropogenic origin of eastern Adige populations, most likely founded by medieval translocations. Substantial river‐specific population substructure within the Adriatic grayling Evolutionary Significant Unit points to the definition of different conservation units. We finally propose a catalog of management measures, including the legal prohibition of stocking exotic grayling and the use of molecular markers in supportive‐ and captive‐breeding programs.
Metal‐Catalyzed and Metal‐Free Alkyne Hydrothiolation: Synthetic Aspects and Application Trends
Authors: Dondoni Alessandro , Marra Alberto 
Published: March 2014

AbstractAlkyne hydrothiolation – that is, the addition of the SH bond of a thiol across the carbon‐carbon triple bond of an unactivated alkyne – belongs to the ample class of hydrofunctionalization reactions whose main feature is their occurrence with total atom economy. Hence this reaction is emerging as a valuable tool for the preparation of sulfur‐containing compounds such as vinyl thioethers, which are of interest for their own biological properties and for their use as intermediates in total synthesis. Thus, the first part of this review deals with the various efforts directed towards the preparation of vinyl thioethers in a regio‐ and diastereoselective manner by metal‐catalyzed approaches in recent years. The number of methods employed, with use of a variety of catalysts and reaction conditions, allow the synthesis of vinyl thioethers to be carried out with high efficiency and selectivity. The second part of the article is based on the use of the photoinduced free‐radical approach to hydrothiolation, which allows the introduction of two thiol fragments across the carbon‐carbon triple bond, thereby leading to the formation of dithioethers. This approach turned out to be especially useful as a ligation tool for the installation of densely functionalized arrays on various scaffolds and complex biomolecular systems. Concluding remarks emphasize the role of the photoinduced free‐radical strategy as a complementary tool to copper‐catalyzed azide‐alkyne cycloaddition.
CdSe Quantum Dots Based Electrochemiluminescence Immunosensor with Simple Structure for Ultrasensitive Detection of Salbutamol
Authors: Zhang Jing , Cai Fudong , Deng Anping , Li Jianguo 
Published: March 2014

AbstractA rapid and ultrasensitive electrochemiluminescence (ECL) competitive immunoassay based on CdSe quantum dots (QDs) and the shorter chain as possible (cysteamine and glutaraldehyde) has been designed for the detection of salbutamol (SAL). Cysteamine and glutaraldehyde made coating antigen immobilize well on the gold electrode surface through the reaction between functional groups, which brought about the simplicity of the immunosensor to some extent. Transmission electron microscopy image, dynamic light scattering, photoluminescence, ultraviolet‐visible absorption and electrochemical impedance spectra were used to characterize the prepared CdSe QDs and the cysteamine/glutaraldehyde/Ovalbumin‐SAL/anti‐SAL‐QDs immunosensor. In the air‐saturated PBS buffer containing 0.1 M K2S2O8 and 0.1 M KCl (pH 9.0), a strong ECL emission of QDs can be observed which depended linearly on the logarithm of the salbutamol concentration with a wide range from 0.05 ng mL−1 to 100 ng mL−1, and a detection limit of 0.0056 ng mL−1. The sensitivity, repeatability, and specificity of the ECL immunosensor have been evaluated. The sensor has been applied to real samples with satisfactory results. This work will open new ways of detecting food additive residue based on QDs ECL in immunoassays.
Experimental and Theoretical Study of the Energy Savings from Wet Ethanol Production and Utilization
Authors: López‐Plaza Emilio Luis , Hernández Salvador , Barroso‐Muñoz Fabricio Omar , Segovia‐Hernández Juan Gabriel , Aceves Salvador M. , Martínez‐Frías Joel , Saxena Samveg , Dibble Robert 
Published: March 2014

AbstractAs a result of the energy crisis in recent decades, biofuels have gained importance as an option to diminish the oil dependence of automotive industry. Ethanol is one of these biofuels for which demand around the world has increased in recent years. However, to be used as a fuel, the ethanol must be dehydrated to avoid problems in actual engines, and this step has a high energy cost. To overcome this drawback, some studies have demonstrated the use of wet ethanol in homogeneous charge compression ignition (HCCI) engines. In this work, the production of wet ethanol, using conventional distillation, was studied using rigorous simulation studies and experimental tests in a distillation column. The simulation analysis and experimental validation of the energy requirements to obtain wet ethanol were achieved. The results showed that wet ethanol can be produced by using a distillation column with a small number of stages and low reflux ratios, which results in energy savings. Also, the results indicated that for low purities of the distilled ethanol (wet ethanol), the ratios between the energy required during the distillation process and the energy produced by ethanol during the combustion were low. This result implies that the use of wet ethanol can be considered as realistic option in HCCI engines.
Non‐stationary conditional extremes of northern North Sea storm characteristics
Authors: Jonathan P. , Ewans K. , Randell D. 
Published: March 2014

AbstractCharacterising the joint structure of extremes of environmental variables is important for improved understanding of those environments. Yet, many applications of multivariate extreme value analysis adopt models that assume a particular form of extremal dependence between variables without justification, or restrict attention to regions in which all variables are extreme. The conditional extremes model of Heffernan and Tawn provides one approach to avoiding these particular restrictions.Extremal marginal and dependence characteristics of environmental variables typically vary with covariates. Reliable descriptions of extreme environments should also therefore characterise any non‐stationarity. A recent article by the current authors extends the conditional extremes model of Heffernan and Tawn to include covariate effects, using Fourier representations of model parameters for single periodic covariates.Here, we further extend our recent work, introducing a general purpose spline representation for model parameters as functions of multidimensional covariates, common to all inference steps. We use a non‐crossing quantile regression to estimate appropriate non‐stationary marginal quantiles simultaneously as functions of covariate; these are necessary as thresholds for extreme value modelling and for standardisation of marginal distributions prior to application of the conditional extremes model. Then, we perform marginal extreme value and conditional extremes modelling within a roughness‐penalised likelihood framework, with cross‐validation to estimate suitable model parameter roughness. Finally, we use a bootstrap re‐sampling procedure, encompassing all inference steps, to quantify uncertainties in, and dependence structure of, parameter estimates and estimates of conditional extremes of one variate given large values of another.We validate the approach using simulations from known joint distributions, the extremal dependence structures of which change with covariate. We apply the approach to joint modelling of storm peak significant wave height and associated storm peak period for extra‐tropical storms at a northern North Sea location, with storm direction as covariate. We evaluate the impact of incorporating directional effects on estimates for conditional return values. Copyright © 2014 John Wiley & Sons, Ltd.
How do sediment yields from post‐wildfire debris‐laden flows depend on terrain slope, soil burn severity class, and drainage basin area? Insights from airborne‐LiDAR change detection
Authors: Pelletier Jon D. , Orem Caitlin A. 
Published: March 2014

ABSTRACTWe derived a high‐resolution, spatially continuous map of erosion and deposition associated with the debris‐laden flows triggered by the 2011 Las Conchas wildfire and subsequent rainstorms over a 197 km2 area in New Mexico, USA. This map was produced using airborne‐LiDAR‐derived bare‐earth digital elevation models (DEMs) acquired approximately one year before and one year after the wildfire. Differencing of the pre‐wildfire and post‐wildfire‐and‐rainstorm bare‐earth DEMs yielded a DEM‐of‐difference (DoD) map that quantifies the magnitude of ground‐surface elevation changes due to erosion/deposition within each 1 m2 pixel. We applied a 0.3 m threshold filter to our DoD to remove changes that could have been due to artifacts and/or imperfect georeferencing. The 0.3 m value for the threshold filter was chosen based on the stated accuracy of the LiDAR as well as a comparison of areas of significant topographic change mapped in aerial photographs with those predicted using a range of candidate threshold values for the DoD filter. We developed an automated procedure that accepts the DoD map as input and computes, for every pixel in the DEM, the net sediment volume exported through each pixel by colluvial and/or fluvial processes using a digital routing algorithm. An analysis of the resulting sediment volume map for the Las Conchas fire demonstrates that sediment volume is proportional to upstream contributing area. After normalized by contributing area, the average sediment yield (defined as the sediment volume divided by the contributing area) increases as a power‐law functions of the average terrain slope and soil burn severity class (SBSC) with exponents equal to approximately 1.5. Our analysis quantifies the relationships among sediment yield, average terrain slope, and average soil burn severity class at the watershed scale and should prove useful for predicting the geomorphic response of wildfire‐affected drainage basins. Copyright © 2014 John Wiley & Sons, Ltd.