bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimization of Diarylthiazole B‐Raf Inhibitors: Identification of a Compound Endowed with High Oral Antitumor Activity, Mitigated hERG Inhibition, and Low Paradoxical Effect
Authors: Pulici Maurizio , Traquandi Gabriella , Marchionni Chiara , Modugno Michele , Lupi Rosita , Amboldi Nadia , Casale Elena , Colombo Nicoletta , Corti Luca , Fasolini Marina , Gasparri Fabio , Pastori Wilma , Scolaro Alessandra , Donati Daniele , Felder Eduard , Galvani Arturo , Isacchi Antonella , Pesenti Enrico , Ciomei Marina 
Published: November 2014

AbstractAberrant activation of the mitogen‐activated protein kinase (MAPK)‐mediated pathway components, RAF‐MEK‐ERK, is frequently observed in human cancers and clearly contributes to oncogenesis. As part of a project aimed at finding inhibitors of B‐Raf, a key player in the MAPK cascade, we originally identified a thiazole derivative endowed with high potency and selectivity, optimal in vitro ADME properties, and good pharmacokinetic profiles in rodents, but that suffers from elevated hERG inhibitory activity. An optimization program was thus undertaken, focused mainly on the elaboration of the R1 and R2 groups of the scaffold. This effort ultimately led to N‐(4‐{2‐(1‐cyclopropylpiperidin‐4‐yl)‐4‐[3‐(2,5‐difluorobenzenesulfonylamino)‐2‐fluorophenyl]thiazol‐5‐yl}‐pyridin‐2‐yl)acetamide (20), which maintains favorable in vitro and in vivo properties, but lacks hERG liability. Besides exhibiting potent antiproliferative activity against only cell lines bearing B‐Raf V600E or V600D mutations, compound 20 also intriguingly shows a weaker “paradoxical” activation of MEK in non‐mutant B‐Raf cells than other known B‐Raf inhibitors. It also demonstrates very good efficacy in vivo against the A375 xenograft melanoma model (tumor volume inhibition >90 % at 10 mg kg−1); it is therefore a suitable candidate for preclinical development.
A Spray‐Based Technique for the Production of MnS Thin Films
Authors: Amirav Lilac , Lifshitz Efrat 
Published: November 2014

AbstractA spray‐based technique, originally developed for the production of semiconductor nanocrystals, is utilized for the preparation of high‐quality nanocrystalline thin films, as demonstrated with manganese sulfide. The films are formed by the use of pneumatic‐assisted thermospray or pneumatic nebulizers. Our simple, low‐cost, and low‐temperature process results in a dense and phase‐pure grain structure. The concepts and benefits of this technique are described and discussed. The film characteristics show dependence on the experimental parameters, in particular the rate of solvent vaporization. Three alternative film formation mechanisms are suggested for cases with varied experimental conditions.
Computational Insights into the Charge Relaying Properties of β‐Turn Peptides in Protein Charge Transfers
Authors: Zhang Ru , Liu Jinxiang , Yang Hongfang , Wang Shoushan , Zhang Meng , Bu Yuxiang 
Published: November 2014

AbstractDensity functional theory calculations suggest that β‐turn peptide segments can act as a novel dual‐relay elements to facilitate long‐range charge hopping transport in proteins, with the N terminus relaying electron hopping transfer and the C terminus relaying hole hopping migration. The electron‐ or hole‐binding ability of such a β‐turn is subject to the conformations of oligopeptides and lengths of its linking strands. On the one hand, strand extension at the C‐terminal end of a β‐turn considerably enhances the electron‐binding of the β‐turn N terminus, due to its unique electropositivity in the macro‐dipole, but does not enhance hole‐forming of the β‐turn C terminus because of competition from other sites within the β‐strand. On the other hand, strand extension at the N terminal end of the β‐turn greatly enhances hole‐binding of the β‐turn C terminus, due to its distinct electronegativity in the macro‐dipole, but does not considerably enhance electron‐binding ability of the N terminus because of the shared responsibility of other sites in the β‐strand. Thus, in the β‐hairpin structures, electron‐ or hole‐binding abilities of both termini of the β‐turn motif degenerate compared with those of the two hook structures, due to the decreased macro‐dipole polarity caused by the extending the two terminal strands. In general, the high polarity of a macro‐dipole always plays a principal role in determining charge‐relay properties through modifying the components and energies of the highest occupied and lowest unoccupied molecular orbitals of the β‐turn motif, whereas local dipoles with low polarity only play a cooperative assisting role. Further exploration is needed to identify other factors that influence relay properties in these protein motifs.
Bimolecular Crystals with an Intercalated Structure Improve Poly(p‐phenylenevinylene)‐Based Organic Photovoltaic Cells
Authors: Lim Kyung‐Geun , Park Jun‐Mo , Mangold Hannah , Laquai Frédéric , Choi Tae‐Lim , Lee Tae‐Woo 
Published: November 2014

AbstractThe exciton dissociation, recombination, and charge transport of bulk heterojunction organic photovoltaic cells (OPVs) is influenced strongly by the nanomorphology of the blend, such as the grain size and the molecular packing. Although it is well known that polymers based on amorphous poly(p‐phenylenevinylene) (PPV) have a fundamental limit to their efficiency because of low carrier mobility, which leads to increased recombination and unbalanced charge extraction, herein, we demonstrate that the issue can be overcome by forming bimolecular crystals of an amorphous PPV‐based polymer:phenyl‐C61‐butyric acid methyl ester (PCBM) intercalated structure. We used amorphous poly(2,5‐dioctyloxy‐p‐phenylene vinylene‐alt‐2′,5′‐thienylene vinylene) (PPVTV), which has a simple chemical structure. A reasonably high power conversion efficiency (∼3.5 %) was obtained, although the material has an intrinsically amorphous structure and a relatively large band gap (2.0 eV). We demonstrate a correlation between a well‐ordered bimolecular crystal of PPVTV:PCBM and an improved hole mobility of a PPVTV:PCBM film compared to a pristine PPVTV film by using 2 D grazing incidence XRD and space‐charge‐limited current measurements. Furthermore, we show that the bimolecular crystal structure in high‐performance OPVs is related to an optimum molecular packing, which is influenced by the PPVTV:PCBM blending ratio, side‐chain length, and molecular weight of the PPVTV polymer. Improved charge transport in PPVTV:PCBM bimolecular crystals leads to a fast sweep out of charges and thus suppression of nongeminate recombination under the operating conditions.
Kinetic modeling of multi‐component crystallization of industrial‐grade oils and fats
Authors: Hjorth Jeppe L. , Miller Rasmus L. , Woodley John M. , Kiil Søren 
Published: November 2014

Transient crystallization kinetics is investigated for complex, industrial‐grade vegetable oils consisting of more than ten triacylglycerols (TAG). The classical nucleation model has been used to describe primary nucleation, while secondary nucleation has been described by a semi‐empirical approach. Growth is modeled using a modified Burton‐Cabrera‐Frank (BCF) model. Surface tensions and growth constants have been determined using focused‐beam‐reflectance measurements (FBRM). The required adjustable parameters in the model have been fitted to overall crystallization curves obtained by solid‐fat content (SFC) measurements for a given oil at different cooling rates and degrees of dilution. The developed model can accommodate more polymorphs simultaneously and performs well with respect to predicting crystallization onset, rate of crystallization and final SFC value. It can also qualitatively describe how higher cooling rates lead to formation of more meta‐stable crystals and smaller mean‐crystal sizes.Practical applications: The model provides a good starting point for developing more realistic, transient models for TAG crystallization with the ability to accommodate processing conditions and complex chemical compositions. Such a predictive model may provide a powerful tool to screen and optimize oil formulations in industrial processes and allow product developers to evaluate recrystallization events.An advanced transient, mathematical model describing the course of crystallization in natural, multi‐component, multi‐phase vegetable oils and fats has been developed. The model is based on well described nucleation and growth kinetics and accommodates the presence of more polymorphic crystal forms. The result is an industry‐relevant model aiding understanding and predictability of oil and fat crystallization with respect to processing conditions and chemical compositions.
Iron/Caffeine as a Catalytic System for Microwave‐Promoted Benzamide Formation
Authors: Bantreil Xavier , Navals Pauline , Martinez Jean , Lamaty Frédéric 
Published: November 2014

AbstractThe amide bond is an essential unit in many drugs and polymers. The catalyzed oxidation of alcohols and amines is an effective method to form amides with limited undesired waste. Herein, we demonstrate the beneficial effect of microwave activation for this reaction. The benzamides were directly formed from alcohols and amine hydrochloride salts in short reaction times with yields up to 84 % and TOFs (turnover frequencies) up to 33.6 h–1. Among the examined transition metals, only nontoxic and inexpensive FeCl2·4H2O together with caffeine as a stabilizing ligand provided a uniquely efficient catalytic system for the transformation. Natural sources of caffeine were also evaluated under the amidation conditions.
Filtering out repetitive auditory stimuli in fibromyalgia: A study of P50 sensory gating
Authors: Carrillo‐de‐la‐Peña M.T. , Triñanes Y. , González‐Villar A. , Gómez‐Perretta C. , García‐Larrea L. 
Published: November 2014

AbstractBackgroundIt has been suggested that fibromyalgia (FM) patients show increased sensory processing of nociceptive and non‐nociceptive stimuli and also reduced habituation. Although this pattern of increased reactivity has been established for the somatosensory modality, its generalization to other sensory modalities remains controversial.MethodsAuditory evoked potentials were obtained using a paired‐stimuli paradigm from a sample of 52 FM female patients and 55 healthy women matched for age and socio‐economic status. Sensory gating of the P50 component, as indicated by P50 suppression rates to the second identical stimuli, was analysed in relation to clinical indices of FM, including algometry of tender points and a number of self‐reported questionnaires.ResultsSensory gating mechanisms in FM patients proved to be normal, robust and as efficient as those recorded in control subjects. There was no correlation between P50 suppression rates and indices of clinical or experimental (threshold or tolerance) pain. In addition, P50 sensory gating was not related to the other main symptoms of FM, including fatigue, sleep dysfunction or co‐morbid depression, nor to hypersensitivity to noise or headache.ConclusionsThe results indicate that FM patients do not present significant deficits in early sensory gating when processing auditory stimuli, and therefore challenge the ‘generalized hypersensitivity’ hypothesis of FM.
An experimental validation of time domain system identification methods with fusion of heterogeneous data
Authors: Chatzis M.N. , Chatzi E.N. , Smyth A.W. 
Published: November 2014

SummaryRecent events of significant seismic activity (L' Aquila 2009, Christchurch 2011), have highlighted the importance of accurately assessing the properties of structures, for estimating their risk in future earthquakes as well as detecting and quantifying damage following an event. This demand may be fulfilled through implementation of SHM methodologies, which offer a means of assessing structural condition through the use of sensor data. Furthermore, the emergence of various sensor technologies has improved the quality of collected signals and made the idea of fusing heterogeneous data more appealing. Similar steps were achieved in advancing system identification algorithms. Several methods such as the Autoregressive Moving Average, Least Squares Estimation, Eigensystem Realization Algorithm, and Subspace State‐Space System Identification (SSID) perform well in identifying elastic properties. However, the resulting matrices are often not obtained with respect to the physical basis, which is often desirable. Such a representation is obtained by default in Bayesian estimation methods, as the Unscented Kalman Filter and Particle Filters, which have recently been applied in the literature for data fusion problems. In this work, an experimental structure mounted on a shake table is monitored using accelerometers and displacement sensors. A method is developed (T‐SSID) to transform the results of the SSID onto the physical basis. The introduced method and the Unscented Kalman Filter are employed identifying the structural properties and detecting an artificially induced in the original system damage. The performance of various sensor setups, which include fusion of heterogeneous sensors, are investigated to illustrate the performance of both methods, their ability to localize damage, and the benefits of data fusion. Copyright © 2014 John Wiley & Sons, Ltd.
The potential of novel Festulolium (2n = 4x = 28) hybrids as productive, nutrient‐use‐efficient fodder for ruminants
Authors: Humphreys Mike W. , O'Donovan Sally A. , Farrell Markku S. , Gay Alan P. , Kingston‐Smith Alison H. 
Published: November 2014

AbstractThe field performance and potential future use of F1 Lolium multiflorum and Lolium perenne × Festuca arundinacea var. glaucescens and Festuca mairei hybrids (2n = 4x = 28) are described. Foliar trait expression in the hybrids was largely determined by the Lolium rather than their Festuca parent ensuring maintenance of high‐forage quality. All four Festulolium populations comprised high‐yielding genotypes, but the L. multiflorum populations were particularly erect and tall, while the L. perenne populations had significantly higher numbers of tillers and were prostrate. Forage yields of the Festulolium populations assessed in field plot trials were either not significantly different from, or were superior to leading L. multiflorum and L. perenne cultivars used as controls. Endogenous plant proteases contribute to excessive proteolysis in the rumen which causes environmental N pollution. Protein degradation due to plant‐mediated proteolysis was assessed by in vitro exposure of leaves to the environmental conditions of the rumen (39°C, anaerobic) and calculated based on the time taken for protein levels to be reduced to half their original levels (t½). Leaf proteins were significantly more stable in L. multiflorum × F. arundinacea var. glaucescens and L. perenne × F. arundinacea var. glaucescens F1 hybrids (t½ 18–21 h) than in their respective Lolium parental genotypes (t½ 4–5 h), and there was a highly significant genome interaction. The t½ in the majority of the L. multiflorum × F. arundinacea var. glaucescens F1 hybrids studied often exceeded 24 h, whereas t½ of their Lolium and Festuca parents was consistently <14 h. Although inferior to the F1, F. arundinacea var. glaucescens genotypes tested had significantly greater t½ than L. perenne under rumen‐simulated conditions. Significant variation in protein stability was apparent within the F1 and their respective parent species' groups. The initial protein content of the F1 hybrids was lower than their respective parents, but following 24‐h exposure to anoxia at 39°C, the protein content of both parent and hybrid genotypes was similar. The differences in protein stability between parental and hybrid genotypes was due to the greater rate of protein decline observed in the Lolium genotypes. Hence, uptake of these Festulolium hybrids as forage crops has potential to directly mitigate environmental impact of livestock farming without affecting production capacity.
High Polymer Content 2,5‐Pyridine‐Polybenzimidazole Copolymer Membranes with Improved Compressive Properties
Authors: Molleo M. A. , Chen X. , Ploehn H. J. , Benicewicz B. C. 
Published: November 2014

AbstractThree series of polybenzimidazole (PBI) random copolymers (2,5‐pyridine‐r‐meta‐PBI, 2,5‐pyridine‐r‐para‐PBI, and 2,5‐pyridine‐r‐2OH‐PBI) were synthesized and cast into phosphoric acid (PA) doped membranes using the PolyPhosphoric Acid (PPA) Process. Copolymer composition was adjusted using co‐monomers that impart high and low solubility characteristics to simultaneously control overall copolymer solubility and gel membrane stability. Measured under a static compressive force at 180 °C, copolymer membranes generally exhibited decreased creep compliance with increasing polymer content. Within each series of copolymer membranes, increasing polymer contents proportionally reduced the phosphoric acid/polymer repeat unit (PA/PRU) ratios and their respective proton conductivities. Some copolymer membranes exhibited comparable fuel cell performances (up to 0.66 V at 0.2 A cm−2 following break‐in) to para‐PBI (0.68 V at 0.2 A cm−2) and equal to 3,5‐pyridine‐based high solids membranes. Furthermore, 2,5‐pyridine copolymer membranes maintained a consistent fuel cell voltage of >0.6 V at 0.2 A cm−2 for over 8600 h under steady‐state operation conditions. Phosphoric acid loss was monitored during long‐term studies and demonstrated acid losses as low as 5.55 ng cm−2 h−1. The high‐temperature creep resistance and long‐term operational stabilities of the 2,5‐pyridine copolymer membranes suggest that they are excellent candidates for use in extended lifetime electrochemical applications.
Advantages of a combined method of decalcification compared to EDTA
Authors: Castania Vitor Aparecido , Silveira Joáo Walter de Souza da , Issy Ana Carolina , Pitol Dimitrius Leonardo , Castania Mayara Leite , Neto Abel Dorigan , Del Bel Elaine Aparecida , Defino Helton Luiz Aparecido 
Published: November 2014

ABSTRACTDecalcification of mineralized tissues is an essential step during tissue processing in the routine histopathology. The time required for complete decalcification, and the effect of decalcifier on cellular and tissue morphology are important parameters which influence the selection of decalcifying agents. In this study, we compared a decalcifying solution (ETDA) composed of both acid and chelating agents to a classical and well‐known decalcifying agent (EDTA). To this purpose, the optic density of bone radiographs, residual calcium analysis, bone sample weight, and histological and immunohistochemical analysis were performed. Our data suggest that, similarly to EDTA, the ETDA solution completely removes the calcium ions from the samples enabling easy sectioning. However, unlike the EDTA, this agent takes much less time. Furthermore, both agents showed comparable decalcification efficacy, and similarly, they did not produce cellular, tissue or antigenicity impairments. Therefore, ETDA may be a suitable option when it is necessary an association between a rapid and complete removal of calcium minerals, and a suitable preservation of structure and antigenicity of tissues. Microsc. Res. Tech. 78:111–118, 2015. © 2014 Wiley Periodicals, Inc.
Estimation of volume densities of hepatocytic peroxisomes in a model fish: Catalase conventional immunofluorescence versus cytochemistry for electron microscopy
Authors: Madureira Tânia Vieira , Lopes Célia , Malhão Fernanda , Rocha Eduardo 
Published: November 2014

ABSTRACTAccurately accessing changes in the intracellular volumes (or numbers) of peroxisomes within a cell can be a lengthy task, because unbiased estimations can be made only by studies conducted under transmission electron microscopy. Yet, such information is often required, namely for correlations with functional data. The optimization and applicability of a fast and new technical proceeding based on catalase immunofluorescence was implemented herein by using primary hepatocytes from brown trout (Salmo trutta f. fario), exposed during 96 h to two distinct treatments (0.1% ethanol and 50 µM of 17α‐ethynylestradiol). The time and cost efficiency, together with the results obtained by stereological analyses, specifically directed to the volume densities of peroxisomes, and additionally of the nucleus in relation to the hepatocyte, were compared with the well‐established 3,3'‐diaminobenzidine cytochemistry for electron microscopy. With the immuno technique it was possible to correctly distinguish punctate peroxisomal profiles, allowing the selection of the marked organelles for quantification. By both methodologies, a significant reduction in the volume density of the peroxisome within the hepatocyte was obtained after an estrogenic input. The most interesting point here was that the volume density ratios were quite correlated between both techniques. Overall, the immunofluorescence protocol for catalase was evidently faster, cheaper and provided reliable quantitative data that discriminated in the same way the compared groups. After this validation study, we recommend the use of catalase immunofluorescence as the first option for rapid screening of changes of the amount of hepatocytic peroxisomes, using their volume density as an indicator. Microsc. Res. Tech. 78:134–139, 2015. © 2014 Wiley Periodicals, Inc.
Morphology of the lingual surface of South American fur seal (Arctocephalus australis) and sea lion (Otaria flavescens)
Authors: Erdoğan Serkan , Villar Arias Silvia , Pérez William 
Published: November 2014

ABSTRACTIn this study, we aimed to describe the morphological characteristics of the lingual papillae in two species of Otariidae family by stereomicroscopy and scanning electron microscopy. We used tongues of two South American Otariidae species. The tongues were elongated and terminated in bifid apex and there was no median sulcus on the dorsal lingual surface. The most numerous type of lingual papilla was filiform in the South American fur seal (SASL) and entire dorsal lingual surface was covered by these filiform papillae but the dorsal surface of the tongue of the South American sea lion was covered by numerous polygonal projections, which were different in size. Fungiform papillae were detected in only SASL and they randomly distributed on the lingual apex and body, and some fungiform papillae were collected into twosome or threesome groups on the posterior part of the lingual body. Circumvallate papilla was found in the center of the lingual radix of South American sea lion. Thread‐like conical papillae were common for both species and they located on the lingual radix. We determined that lingual surface morphology was completely different in each species, although they were members of the same family, Otariidae. Microsc. Res. Tech. 78:140–147, 2015. © 2014 Wiley Periodicals, Inc.
The Impact of Social Beliefs on Microfinance Performance
Authors: Burzynska Katarzyna , Berggren Olle 
Published: November 2014

AbstractWe apply a panel of 331 microfinance institutions from 37 countries to investigate the relationship between social beliefs and microfinance financial performance over the period of 2003–2011. We find that microfinance institutions in countries with higher levels of trust and more collectivist culture have lower operating and default costs and charge lower interest rates. These results provide the first large cross‐country evidence that social beliefs are important determinants of microfinance performance. Copyright © 2014 John Wiley & Sons, Ltd.