bluuebunny/crossref_metadata_2025_split huggingface dataset:
Kovalente Liganden zur Adressierung einer lipophilen Bindetasche in der MAPK p38α
Authors: Bührmann Mike , Hardick Julia , Weisner Jörn , Quambusch Lena , Rauh Daniel 
Published: August 2017

AbstractEin chemisch‐genetischer Ansatz zur kovalenten Adressierung einer einzigartigen lipophilen Bindetasche (LP) in der Mitogen‐aktivierten Proteinkinase p38α, deren physiologische Funktion bis heute nicht völlig verstanden ist, wird vorgestellt. Basierend auf einer Reihe von Kokristallstrukturen wurde eine fokussierte Substanzbibliothek von 2‐Arylchinazolinen entwickelt, die mit Elektrophilen versehen wurden, um p38α‐Mutanten mit artifiziell eingeführten Cysteinen zu generieren. Aufeinander abgestimmte Protein‐Liganden‐Paare wurden über MS‐Analysen identifiziert und mittels MS/MS‐basierten sowie kristallographischen Studien validiert. Einige der kovalenten Liganden, die aus diesem Ansatz hervorgingen, zeigten eine hervorragende Selektivität für jeweils eine einzelne p38α‐Mutante und können zukünftig als Sondenmoleküle zur Aufklärung der LP‐Funktion im Rahmen pharmakologischer Perturbationsexperimente in zellulären Systemen Anwendung finden.
Discovery of a Novel Inhibitor of the Hedgehog Signaling Pathway through Cell‐based Compound Discovery and Target Prediction
Authors: Kremer Lea , Schultz‐Fademrecht Carsten , Baumann Matthias , Habenberger Peter , Choidas Axel , Klebl Bert , Kordes Susanne , Schöler Hans R. , Sterneckert Jared , Ziegler Slava , Schneider Gisbert , Waldmann Herbert 
Published: August 2017

AbstractCell‐based assays enable monitoring of small‐molecule bioactivity in a target‐agnostic manner and help uncover new biological mechanisms. Subsequent identification and validation of the small‐molecule targets, typically employing proteomics techniques, is very challenging and limited, in particular if the targets are membrane proteins. Herein, we demonstrate that the combination of cell‐based bioactive‐compound discovery with cheminformatic target prediction may provide an efficient approach to accelerate the process and render target identification and validation more efficient. Using a cell‐based assay, we identified the pyrazolo‐imidazole smoothib as a new inhibitor of hedgehog (Hh) signaling and an antagonist of the protein smoothened (SMO) with a novel chemotype. Smoothib targets the heptahelical bundle of SMO, prevents its ciliary localization, reduces the expression of Hh target genes, and suppresses the growth of Ptch+/− medulloblastoma cells.
Rational Optimization of Supramolecular Catalysts for the Rhodium‐Catalyzed Asymmetric Hydrogenation Reaction
Authors: Daubignard Julien , Detz Remko J. , Jans Anne C. H. , de Bruin Bas , Reek Joost N. H. 
Published: August 2017

AbstractRational design of catalysts for asymmetric transformations is a longstanding challenge in the field of catalysis. In the current contribution we report a catalyst in which a hydrogen bond between the substrate and the catalyst plays a crucial role in determining the selectivity and the rate of the catalytic hydrogenation reaction, as is evident from a combination of experiments and DFT calculations. Detailed insight allowed in silico mutation of the catalyst such that only this hydrogen bond interaction is stronger, predicting that the new catalyst is faster. Indeed, we experimentally confirmed that optimization of the catalyst can be realized by increasing the hydrogen bond strength of this interaction by going from a urea to phosphine oxide H‐bond acceptor on the ligand.
Fluorescence Electrochemical Microscopy: Capping Agent Effects with Ethidium Bromide/DNA Capped Silver Nanoparticles
Authors: Tanner Eden E. L. , Sokolov Stanislav V. , Young Neil P. , Batchelor‐McAuley Christopher , Compton Richard G. 
Published: August 2017

AbstractFluorescence microscopy and electrochemistry were employed to examine capping agent dynamics in silver nanoparticles capped with DNA intercalated with ethidium bromide, a fluorescent molecule. The capped NPs were studied first electrochemically, demonstrating that the intercalation of the capping agent promotes oxidation of the silver core, occurring at 0.50 V (vs. Ag, compared with 1.15 V for Ag NPs capped in DNA alone). Second, fluorescence electrochemical microscopy revealed that the electron transfer from the nanoparticles is gated by the capping agent, allowing dynamic insights unobservable using electrochemistry alone.
Covalent Lipid Pocket Ligands Targeting p38α MAPK Mutants
Authors: Bührmann Mike , Hardick Julia , Weisner Jörn , Quambusch Lena , Rauh Daniel 
Published: August 2017

AbstractA chemical genetic approach is presented to covalently target a unique lipid binding pocket in the protein kinase p38α, whose function is not yet known. Based on a series of cocrystal structures, a library of 2‐arylquinazolines that were decorated with electrophiles were designed and synthesized to covalently target tailored p38α mutants containing artificially introduced cysteine residues. Matching protein–ligand pairs were identified by MS analysis and further validated by MS/MS studies and protein crystallography. The covalent ligands that emerged from this approach showed excellent selectivity towards a single p38α mutant and will be applicable as suitable probes in future studies of biological systems to dissect the function of the lipid pocket by means of pharmacological perturbations.
Role of the Adsorbed Oxygen Species in the Selective Electrochemical Reduction of CO2 to Alcohols and Carbonyls on Copper Electrodes
Authors: Le Duff Cécile S. , Lawrence Matthew J. , Rodriguez Paramaconi 
Published: August 2017

AbstractThe electrochemical reduction of CO2 into fuels has gained significant attention recently as source of renewable carbon‐based fuels. The unique high selectivity of copper in the electrochemical reduction of CO2 to hydrocarbons has called much interest in discovering its mechanism. In order to provide significant information about the role of oxygen in the electrochemical reduction of CO2 on Cu electrodes, the conditions of the surface structure and the composition of the Cu single crystal electrodes were controlled over time. This was achieved using pulsed voltammetry, since the pulse sequence can be programmed to guarantee reproducible initial conditions for the reaction at every fraction of time and at a given frequency. In contrast to the selectivity of CO2 reduction using cyclic voltammetry and chronoamperometric methods, a large selection of oxygenated hydrocarbons was found under alternating voltage conditions. Product selectivity towards the formation of oxygenated hydrocarbon was associated to the coverage of oxygen species, which is surface‐structure‐ and potential‐dependent.
High‐Fidelity Multistate Switching with Anion–Anion and Acid–Anion Dimers of Organophosphates in Cyanostar Complexes
Authors: Zhao Wei , Qiao Bo , Chen Chun‐Hsing , Flood Amar H. 
Published: August 2017

AbstractThe acid–base switching of complexes formed from anti‐electrostatic anion–anion homodimers of organophosphates and cyanostar macrocycles was investigated for the first time. High‐fidelity 2:2 complexes were selected by using suitably sized organo substituents. Reversible and direct switching occurs with triflic acid and hydroxide base. An unexpected acid⋅⋅⋅anion heterodimer was discovered with weaker picric acid, which helped reveal some of the elementary steps. Switching can also proceed in a cooperative (strong anion then weak acid) or stepwise manner (weak acid then strong anion).
Preparation of metal‐phosphorus hybridized nanomaterials and the action of metal centers on the flame retardancy of epoxy resin
Authors: Liu Lili , Huang Yawen , Yang Yu , Ma Jiajun , Yang Junxiao , Yin Qiang 
Published: August 2017

ABSTRACTThe action of metals on the flame retardancy of thermoplastic has aroused much interest in recent years. However, their action on thermosets is still not clear. In this work, metal‐phosphorus hybridized nanomaterials with different metal centers were prepared via hydrothermal reaction between metal hydroxide/salts with phosphinic/phosphonic acids. The loading of these hybrids in epoxy (EP) resins resulted in great change on fire resistance. Thermogravimetric analysis, solid and gas phase analysis results indicated that the flame retardant action of the hybrids perhaps didn't take place following the conventional models in condensed and gas phase. It was found that the flame retardancy was greatly correlated with the action of metal centers with EP resin, which resulted in the formation of metal‐oxygen bonds and the delayed release of flammable compounds from EP resin. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 45445.
Correlation between gas transport properties and the morphology/dynamics of crystalline fluorinated copolymer membranes
Authors: Nyuui Tatsuki , Matsuba Go , Sato Shuichi , Nagai Kazukiyo , Fujimori Atsuhiro 
Published: August 2017

ABSTRACTThe crystalline structure, dynamics, and gas transport properties (i.e., the gas permeability, gas diffusion coefficient, and gas solubility coefficient) of poly(tetrafluoroethylene‐co‐perfluoroethylvinylether) (PFA) membranes were systematically investigated via differential scanning calorimetry, wide/small/ultra‐small‐angle X‐ray scattering, and quasielastic neutron scattering measurements. We evaluated the gas transport properties using a constant‐volume/variable‐pressure method. The gas permeability and the gas diffusion coefficient decreased with increasing crystallinity of the PFA membranes at crystallinities below 32%. However, in membranes with a crystallinity of 32% or greater, these parameters depended on the characteristics of the gas molecules, such as their kinetic diameter. The so‐called long spacing period and the thickness of the crystalline/amorphous regions increased with crystallinity according to the small/ultra‐small‐angle X‐ray scattering results. Furthermore, the quasielastic neutron scattering measurements indicated that the scattering law was well fitted to a sum of narrow and broad Lorentzian components. In particular, the narrow components, that is, the local motion of amorphous components and side chains, increased with crystallinity. These results suggest that large gas molecules could pass through the PFA membranes, assisted by the motion in the amorphous region. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 45665.
Enhancing crystallization rate and melt strength of PLLA with four‐arm PLLA grafted silica: The effect of molecular weight of the grafting PLLA chains
Authors: Lai Xiang‐Ling , Yang Wei , Wang Zhao , Shi Da‐Wei , Liu Zheng‐Ying , Yang Ming‐Bo 
Published: August 2017

ABSTRACTTo improve the crystallization rate and melt strength of polylactide (PLLA), nano‐size amino silica grafted by four‐arm PLLA (4A‐PLLA) with different molecular weight was synthesized. 1H nuclear magnetic resonance proved that 4A‐PLLA had been grafted onto the surface of SiO2 successfully, and the grafting ratios and the degradation behaviors of the grafted SiO2 nanoparticles (g‐SiO2) were studied. When the grafted silica was introduced into PLLA matrix, the crystallization rate and melt strength of composites were found to be improved and the length of grafted chain played an important role. The extension rheology indicated that long grafted 4A‐PLLA on the surface of SiO2 was more efficient in enhancing the elongational viscosity of PLLA, owing to the stronger interactions between the grafted chains and the matrix. The crystallization behavior of ungrafted silica filled composite was similar to that of neat PLA, while g‐SiO2 played a role of nucleating agent. The crystallinities and the crystallization rates of the composites depended on the content of g‐SiO2 and the grafted chain length of 4A‐PLLA, especially the latter. Longer grafted chain acted as nucleation site in the matrix and significantly improved the crystallization behaviors of PLLA. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 45675.
Particle morphology and morphogenesis of nascent polyethylene produced with a spherical MgCl2‐supported Ziegler–Natta catalyst in slurry process
Authors: Zhang Zhen , Qi Meizhou , Yang Pengjia , Fu Zhisheng , Xu Junting , Fan Zhiqiang 
Published: August 2017

ABSTRACTEthylene polymerizations were conducted in slurry process with a spherical MgCl2‐supported Ziegler–Natta catalyst activated by triethylaluminum, and the morphology of nascent polymer particles was observed by scanning electron microscope. Three kinds of typical microscale morphologies: nodular and rope‐like structures on the external particle surface, and nodular structures in the bulk of the particle were observed. These structures are composed of polyethylene lamellae and amorphous phase filling the space between the lamellae. There is close relation between the polymerization activity and microporosity of the particles. When the activity was higher than 1500 g PE/g Cat, large number of tiny pores appeared in the particles, and rope‐like structures appeared on their surface. Formation of the morphologies can be reasonably explained by models based on multiscale solid structure of the catalyst particle and dynamic interactions among the growing polymer phases. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 45679.
Present Bias and Everyday Self‐Control Failures: A Day Reconstruction Study
Authors: Delaney Liam , Lades Leonhard K. 
Published: August 2017

AbstractEveryday life is full of self‐control problems. The economist's favorite explanation for self‐control problems is present bias. This paper tests whether experimentally elicited present bias predicts self‐control problems in everyday life. We measure present bias by using a standard incentivized delay discounting task and everyday self‐control by using the day reconstruction method (DRM). Because this is the first study to measure everyday self‐control by using the DRM, we also validate the method by showing that its data replicate key results from the seminal Everyday Temptation Study. We find that present bias does not predict everyday self‐control. This points to a distinction between decreasing impatience (as measured in delay discounting tasks) and visceral influences (as occurring in everyday life) as determinants of self‐control problems. We argue that decision making research can benefit from the DRM as a cost‐effective tool that complements lab and field experiments to better understand economic preference measures and their correlates in everyday life decision making. Copyright © 2017 John Wiley & Sons, Ltd.
Kinetics based reaction optimization of enzyme catalyzed reduction of formaldehyde to methanol with synchronous cofactor regeneration
Authors: Marpani Fauziah , Sárossy Zsuzsa , Pinelo Manuel , Meyer Anne S. 
Published: August 2017

AbstractEnzymatic reduction of carbon dioxide (CO2) to methanol (CH3OH) can be accomplished using a designed set‐up of three oxidoreductases utilizing reduced pyridine nucleotide (NADH) as cofactor for the reducing equivalents electron supply. For this enzyme system to function efficiently a balanced regeneration of the reducing equivalents during reaction is required. Herein, we report the optimization of the enzymatic conversion of formaldehyde (CHOH) to CH3OH by alcohol dehydrogenase, the final step of the enzymatic redox reaction of CO2 to CH3OH, with kinetically synchronous enzymatic cofactor regeneration using either glucose dehydrogenase (System I) or xylose dehydrogenase (System II). A mathematical model of the enzyme kinetics was employed to identify the best reaction set‐up for attaining optimal cofactor recycling rate and enzyme utilization efficiency. Targeted process optimization experiments were conducted to verify the kinetically modeled results. Repetitive reaction cycles were shown to enhance the yield of CH3OH, increase the total turnover number (TTN) and the biocatalytic productivity rate (BPR) value for both system I and II whilst minimizing the exposure of the enzymes to high concentrations of CHOH. System II was found to be superior to System I with a yield of 8 mM CH3OH, a TTN of 160 and BPR of 24 μmol CH3OH/U · h during 6 hr of reaction. The study demonstrates that an optimal reaction set‐up could be designed from rational kinetics modeling to maximize the yield of CH3OH, whilst simultaneously optimizing cofactor recycling and enzyme utilization efficiency.
Enhanced diastereoselective synthesis of t‐Butyl 6‐cyano‐(3R,5R)‐dihydroxyhexanoate by using aldo‐keto reductase and glucose dehydrogenase co‐producing engineered Escherichia coli
Authors: Wang Ya‐Jun , Shen Wei , Luo Xi , Liu Zhi‐Qiang , Zheng Yu‐Guo 
Published: August 2017

t‐Butyl 6‐cyano‐(3R,5R)‐dihydroxyhexanoate ((3R,5R)‐2) is a key chiral diol precursor of atorvastatin calcium (Lipitor®). We have constructed a Kluyveromyces lactis aldo‐keto reductase mutant KlAKR‐Y295W/W296L (KlAKRm) by rational design in previous research, which displayed high activity and excellent diastereoselectivity (dep > 99.5%) toward t‐butyl 6‐cyano‐(5R)‐hydroxy‐3‐oxohexanoate ((5R)‐1). To realize in situ cofactor regeneration, a robust KlAKRm and Exiguobacterium sibiricum glucose dehydrogenase (EsGDH) co‐producer E. coli BL 21(DE3) pETDuet‐esgdh (MCS1)/pET‐28b (+)‐klakrm was constructed in this work. Under the optimized conditions, AKR and GDH activities of E. coli BL 21(DE3) pETDuet‐esgdh (MCS1)/pET‐28b (+)‐klakrm peaked at 249.9 U/g DCW (dry cellular weight) and 29100 U/g DCW, respectively. It completely converted (5R)‐1 at substrate loading size of up to 60.0 g/L (5R)‐1 in the absence of exogenous NADH, which was one‐fifth higher than that of the separately prepared KlAKRm and EsGDH under the same conditions. In this manner, a biocatalytic process for (3R,5R)‐2 with productivity of 243.2 kg/m3 d was developed. Compared with the combination of separate expressed KlAKRm with EsGDH, co‐expression of KlAKRm and EsGDH has the advantages of alleviating cell cultivation burden and elevating substrate load. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:1235–1242, 2017
Prognostic role of stereotactic body radiation therapy for elderly patients with advanced and medically inoperable pancreatic cancer
Authors: Zhu Xiaofei , Li Fuqi , Ju Xiaoping , Cao Fei , Cao Yangsen , Fang Fang , Qing Shuiwang , Shen Yuxin , Jia Zhen , Zhang Huojun 
Published: August 2017

AbstractThe role of stereotactic body radiation therapy for the elderly with advanced or medically inoperable pancreatic cancer was still debated. Therefore, we evaluated the value of stereotactic body radiation therapy and its association with survival of those patients. A total of 417 elderly patients were retrospectively reviewed from 2012 to 2015. Overall survival (OS), progression‐free survival (PFS), local recurrence‐free survival (LRFS), distant metastasis‐free survival (DMFS), and toxicities were analyzed. Prescription doses ranged from 30–46.8 Gy in 5–8 fractions. Median age was 73 years old. Median OS, PFS, LRFS, and DMFS were 10, 8, 10, and 9.5 months, respectively. One‐year OS, PFS, LRFS, and DMFS rate were 35.5%, 18.2%, 26.6%, and 27.1%, respectively. Tumor stage and tumor response at 6 months and CA19‐9 levels normalization at 3 months after treatment were independent predictors of OS, PFS, LRFS, and DMFS. Patients with early‐stage cancer, better tumor response, and normalization of CA19‐9 levels had significantly longer OS, PFS, LRFS, and DMFS. Patients with the prodrug of 5‐FU and radiotherapy had longer survival than those with gemcitabine‐based chemotherapy and radiotherapy. Patients who received BED10 ≥ 60 Gy achieved better tumor response compared with those who received BED10 < 60 Gy. Two patients had grade 4 intestinal strictures. No grade 3 or higher hematologic toxicities occurred. Stereotactic body radiation therapy is safe and effective for elderly patients with advanced or medically inoperable pancreatic cancer. Early efficacy could be predictive of prognosis. Higher doses may be associated with efficacy but need further investigation.
Investigation of the Blockage Conditions in a Laminated‐Sheet Microchannel Reactor
Authors: Pan Minqiang , Huang Pingnan , Vafai Kambiz 
Published: August 2017

AbstractThe microchannel reactor is a generally adopted laminated‐sheet structure in which several microchannel sheets with the same or different structures are laminated together and tightened by welding or other connection methods into a single reaction unit. Uniform velocity distribution among the microchannels can improve the heat and mass transfer efficiency. When one or more microchannels are blocked, the uniformity of the velocity distribution is inevitably affected. In this work, the velocity distributions among the microchannels in a single‐sheet and a double‐sheet laminated structure are investigated under different blockage conditions. It is demonstrated in detail that the different blockage conditions in the microchannels and laminated structure display different effects on the velocity value, the shape of the velocity distribution, and the evaluation parameter for uniformity.
Self‐Assembly of Cyclohelicate [M3L3] Triangles Over [M4L4] Squares, Despite Near‐Linear Bis‐terdentate L and Octahedral M
Authors: Hogue Ross W. , Dhers Sébastien , Hellyer Ryan M. , Luo Jingwei , Hanan Garry S. , Larsen David S. , Garden Anna L. , Brooker Sally 
Published: August 2017

AbstractInvited for the cover of this issue is the collaborative team of Anna L. Garden, Sally Brooker and co‐workers at the University of Otago (New Zealand), along with collaborators from Victoria and Montreal (Canada). The image depicts the entropic balancing act between 4 triangles and 3 squares, an argument which must be used with caution. Read the full text of the article at 10.1002/chem.201702153.
Liquid‐liquid equilibrium for the ternary systems water + DMM3 + (p‐xylene, toluene, and n‐heptane) at different temperatures
Authors: Shi Midong , Yu Xuemin , He Gaoyin , Li Qingsong 
Published: August 2017

AbstractIn order to reduce the decomposition of DMM3, the DMM3 aqueous solution was separated by liquid‐liquid extraction. Liquid‐liquid equilibria (LLE) data for three ternary systems of water + DMM3 + p‐xylene, water + DMM3 + toluene, and water + DMM3 + n‐heptane were measured under atmospheric pressure at 303.15 K and 313.15 K. The results indicated that p‐xylene, toluene, and n‐heptane showed excellent extraction ability for separating DMM3 aqueous solution. Moreover, the LLE data were correlated by NRTL and UNIQUAC models with good agreement.
Privacy‐preserving smart data storage for financial industry in cloud computing
Authors: Qiu Meikang , Gai Keke , Zhao Hui , Liu Meiqin 
Published: August 2017

SummaryThe recent booming development of cloud computing has enabled a dramatical revolution for current enterprises to create values. Numerous benefits of utilizing cloud services are enhancing the efficiency of improving or creating new businesses. This trend is also associated with the rapid growth of the wireless networks, such as 5G. However, the great increase of deploying clouds also leads to new concerns in data security. One of the major concerns is private leakage that derives from insiders' malicious operations or attacks. This problem has raised a great restriction for financial firms to execute cloud applications. Focusing on this issue, we propose a new solution, entitled Privacy‐Preserving Smart Storage (PS2) model that targets at solving the privacy leakage problems within the existing threat models. The proposed approach uses a novel distributed data storage method to prevent financial enterprises from insiders' massive data mining‐based attacks.