bluuebunny/crossref_metadata_2025_split huggingface dataset:
Eine strukturelle Evaluierung medizinalchemischer Strategien gegen Wirkstoffresistenzen
Authors: Agnello Stefano , Brand Michael , Chellat Mathieu F. , Gazzola Silvia , Riedl Rainer 
Published: May 2018

AbstractDas natürliche Phänomen der Wirkstoffresistenz stellt eine universelle Beeinträchtigung des Nutzens von pharmazeutischen Wirkstoffen in vielen klinischen Indikationen dar. Antibakterielle und antifungale Wirkstoffe sind dabei ebenso betroffen wie Wirkstoffe zur Behandlung von Krebs, Virusinfektionen oder durch Parasiten hervorgerufene Erkrankungen. Trotz der unterschiedlichen biologischen Zielstrukturen und Organismen, die bei der Entwicklung von Wirkstoffresistenzen involviert sind, konnten grundlegende molekulare Prozesse identifiziert werden, die zum Verständnis des Auftretens von Resistenzen beitragen und die Bekämpfung dieser nachteiligen Mechanismen erlauben. Strukturelle Informationen über die Prinzipien von Wirkstoffresistenzen sind heute vielfältig vorhanden, sodass neue Wirkstoffe entwickelt werden können, die weniger anfällig gegenüber einer Resistenzbildung sein werden. Dieser wissensbasierte Ansatz ist eine Grundlage für den Kampf gegen das unvermeidbare Auftreten von Wirkstoffresistenzen.
A Modified System for the Synthesis of Enantioenriched N‐Arylamines through Copper‐Catalyzed Hydroamination
Authors: Ichikawa Saki , Zhu Shaolin , Buchwald Stephen L. 
Published: May 2018

AbstractDespite significant recent progress in copper‐catalyzed enantioselective hydroamination chemistry, the synthesis of chiral N‐arylamines, which are frequently found in natural products and pharmaceuticals, has not been realized. Initial experiments with N‐arylhydroxylamine ester electrophiles were unsuccessful and, instead, their reduction in the presence of copper hydride (CuH) catalysts was observed. Herein, we report key modifications to our previously reported hydroamination methods that lead to broadly applicable conditions for the enantioselective net addition of secondary anilines across the double bond of styrenes, 1,1‐disubstituted olefins, and terminal alkenes. NMR studies suggest that suppression of the undesired reduction pathway is the basis for the dramatic improvements in yield under the reported method.
An Unusual Phase Transition Driven by Vibrational Entropy Changes in a Hybrid Organic–Inorganic Perovskite
Authors: Wei Wenjuan , Li Wei , Butler Keith T. , Feng Guoqiang , Howard Christopher J. , Carpenter Michael A. , Lu Peixiang , Walsh Aron , Cheetham Anthony K. 
Published: May 2018

AbstractThe driving forces for the phase transitions of ABX3 hybrid organic–inorganic perovskites have been limited to the octahedral tilting, order–disorder, and displacement. Now, a complex structural phase transition has been explored in a HOIP, [CH3NH3][Mn(N3)3], based on structural characterizations and ab initio lattice dynamics calculations. This unusual first‐order phase transition between two ordered phases at about 265 K is primarily driven by changes in the collective atomic vibrations of the whole lattice, along with concurrent molecular displacements and an unusual octahedral tilting. A significant entropy difference (4.35 J K−1 mol−1) is observed between the low‐ and high‐temperature structures induced by such atomic vibrations, which plays a main role in driving the transition. This finding offers an alternative pathway for designing new ferroic phase transitions and related physical properties in HOIPs and other hybrid crystals.
Copper‐Catalyzed Borocarbonylative Coupling of Internal Alkynes with Unactivated Alkyl Halides: Modular Synthesis of Tetrasubstituted β‐Borylenones
Authors: Cheng Li‐Jie , Mankad Neal P. 
Published: May 2018

AbstractReported is a general procedure to synthesize tetrasubstituted enones, which are borylated in the β‐position, using a copper‐catalyzed four‐component coupling reaction of simple chemical feedstocks: internal alkynes, alkyl halides, bis(pinacolato)diboron (B2pin2), and CO. A broad scope of highly functionalized β‐borylated enones, a largely unknown class of organic compounds, can be accessed efficiently using this method. The synthesis of all‐carbon tetrasubstituted enones was realized by employing the β‐borylated enone unit, without purification, in a Suzuki–Miyaura coupling. The utility of the method was further demonstrated by various transformations, including halogenation, oxidation, and protodeboration, of the corresponding reduced oxaborole species to provide densely substituted allylic alcohol and ketone products.
High‐Internal‐Phase Pickering Emulsions Stabilized Solely by Peanut‐Protein‐Isolate Microgel Particles with Multiple Potential Applications
Authors: Jiao Bo , Shi Aimin , Wang Qiang , Binks Bernard P. 
Published: May 2018

AbstractHigh‐internal‐phase Pickering emulsions have various applications in materials science. However, the biocompatibility and biodegradability of inorganic or synthetic stabilizers limit their applications. Herein, we describe high‐internal‐phase Pickering emulsions with 87 % edible oil or 88 % n‐hexane in water stabilized by peanut‐protein‐isolate microgel particles. These dispersed phase fractions are the highest in all known food‐grade Pickering emulsions. The protein‐based microgel particles are in different aggregate states depending on the pH value. The emulsions can be utilized for multiple potential applications simply by changing the internal‐phase composition. A substitute for partially hydrogenated vegetable oils is obtained when the internal phase is an edible oil. If the internal phase is n‐hexane, the emulsion can be used as a template to produce porous materials, which are advantageous for tissue engineering.
A Structural View on Medicinal Chemistry Strategies against Drug Resistance
Authors: Agnello Stefano , Brand Michael , Chellat Mathieu F. , Gazzola Silvia , Riedl Rainer 
Published: May 2018

AbstractThe natural phenomenon of drug resistance is a widespread issue that hampers the performance of drugs in many major clinical indications. Antibacterial and antifungal drugs are affected, as well as compounds for the treatment of cancer, viral infections, or parasitic diseases. Despite the very diverse set of biological targets and organisms involved in the development of drug resistance, the underlying molecular mechanisms have been identified to understand the emergence of resistance and to overcome this detrimental process. Detailed structural information on the root causes for drug resistance is nowadays frequently available, so next‐generation drugs can be designed that are anticipated to suffer less from resistance. This knowledge‐based approach is essential for fighting the inevitable occurrence of drug resistance.
The Scaffold Design of Trivalent Chelator Heads Dictates Affinity and Stability for Labeling His‐tagged Proteins in vitro and in Cells
Authors: Gatterdam Karl , Joest Eike F. , Gatterdam Volker , Tampé Robert 
Published: May 2018

AbstractSmall chemical/biological interaction pairs are at the forefront in tracing protein function and interaction at high signal‐to‐background ratios in cellular pathways. However, the optimal design of scaffold, linker, and chelator head still deserve systematic investigation to achieve the highest affinity and kinetic stability for in vitro and especially cellular applications. We report on a library of N‐nitrilotriacetic acid (NTA)‐based multivalent chelator heads (MCHs) built on linear, cyclic, and dendritic scaffolds and compare these with regard to their binding affinity and stability for the labeling of cellular His‐tagged proteins. Furthermore, we describe a new approach for tracing cellular target proteins at picomolar probe concentrations in cells. Finally, we outline fundamental differences between the MCH scaffolds and define a cyclic trisNTA chelator that displays the highest affinity and kinetic stability of all reported reversible, low‐molecular‐weight interaction pairs.
Towards Macroscopic Crystalline 2D Polymers
Authors: Feng Xinliang , Schlüter A. Dieter 
Published: May 2018

AbstractPeriodic and nanoporous monolayer polymers, the structures of which can be viewed as molecular fishing nets, have been classified as 2D polymers. They have been previously synthesized under mild photoirradiation conditions in the interior of layered single crystals of well‐designed monomers, followed by a liquid‐phase exfoliation. While these mild conditions allow for full structure control, the size of 2D polymers obtained cannot exceed that of the crystals from which they are prepared. In this Review, we discuss different concepts currently pursued to prepare macroscopically sized 2D polymers, focusing on syntheses at the air–water and liquid–liquid interfaces. While these interfaces are larger reaction loci than single crystals, sheet‐like polymers obtained at them pose complex and time‐consuming analytical challenges. Some of these challenges are concretely discussed and indicators are provided for identifying the promising cases, enabling to concentrate on them in the future research. Additionally, this Review discusses three representative examples of 2D polymers to provide a state‐of‐the‐art picture of this emerging field of polymer and materials science. Finally, we sketch the range of applications, such as nanomembranes, electronics, optoelectronics, and electrocatalysts for water splitting, that are relevant for these novel organic 2D materials.
The Remarkable Effect of Halogen Substitution on the Membrane Transport of Fluorescent Molecules in Living Cells
Authors: Ungati Harinarayana , Govindaraj Vijayakumar , Mugesh Govindasamy 
Published: May 2018

AbstractSmall‐molecule‐based fluorescent probes have become important tools in biology for sensing and imaging applications. However, the biological applications of many of the fluorescent molecules are hampered by low cellular uptake and high toxicity. In this paper, we show for the first time that the introduction of halogen atoms enhances the cellular uptake of fluorescent molecules and the nature of halogen atoms plays a crucial role in the plasma membrane transport in mammalian cells. The remarkably higher uptake of iodinated compounds compared to that of their chloro or bromo analogues suggests that the strong halogen bonding ability of iodine atoms may play an important role in the membrane transport. This study provides a novel strategy for the transport of fluorescent molecules across the plasma membrane in living cells.
In Situ Cyclization of Native Proteins: Structure‐Based Design of a Bicyclic Enzyme
Authors: Pelay‐Gimeno Marta , Bange Tanja , Hennig Sven , Grossmann Tom N. 
Published: May 2018

AbstractIncreased tolerance of enzymes towards thermal and chemical stress is required for many applications and can be achieved by macrocyclization of the enzyme resulting in the stabilizing of its tertiary structure. Thus far, macrocyclization approaches utilize a very limited structural diversity, which complicates the design process. Herein, we report an approach that enables cyclization through the installation of modular crosslinks into native proteins composed entirely of proteinogenic amino acids. Our stabilization procedure involves the introduction of three surface‐exposed cysteine residues, which are reacted with a triselectrophile, resulting in the in situ cyclization of the protein (INCYPRO). A bicyclic version of sortase A was designed that exhibits increased tolerance towards thermal as well as chemical denaturation, and proved to be efficient in protein labeling under denaturing conditions. In addition, we applied INCYPRO to the KIX domain, resulting in up to 24 °C increased thermal stability.
High‐Frequency Fe–H Vibrations in a Bridging Hydride Complex Characterized by NRVS and DFT
Authors: Pelmenschikov Vladimir , Gee Leland B. , Wang Hongxin , MacLeod K. Cory , McWilliams Sean F. , Skubi Kazimer L. , Cramer Stephen P. , Holland Patrick L. 
Published: May 2018

AbstractHigh‐spin iron species with bridging hydrides have been detected in species trapped during nitrogenase catalysis, but there are few general methods of evaluating Fe−H bonds in high‐spin multinuclear iron systems. An 57Fe nuclear resonance vibrational spectroscopy (NRVS) study on an Fe(μ‐H)2Fe model complex reveals Fe−H stretching vibrations for bridging hydrides at frequencies greater than 1200 cm−1. These isotope‐sensitive vibrational bands are not evident in infrared (IR) spectra, showing the power of NRVS for identifying hydrides in this high‐spin iron system. Complementary density functional theory (DFT) calculations elucidate the normal modes of the rhomboidal iron hydride core.
Adsorption characteristics and kinetics of synthesized anionic surfactant and polymeric surfactant on sand surface for application in enhanced oil recovery
Authors: Saxena Neha , Kumar Sudhir , Mandal Ajay 
Published: May 2018

AbstractThe adsorption behaviour of aqueous solutions of anionic surfactant and polymeric surfactant derived from Jatropha oil onto sand surface was investigated in connection of their application in enhanced oil recovery. The loss of surfactant by adsorption on reservoir rock must be premeditated for proper design of injected surfactant slugs in a chemical enhanced oil recovery. The sand particles used in the present study as representative of reservoir rock were characterized by Fourier transform infrared and energy‐dispersive X‐ray analyses. Adsorption properties were studied as a function of time and concentration for both surfactant and polymeric surfactant. The equilibrium adsorption data were fitted with the Langmuir, Freundlich, Temkin, and Redlich–Peterson isotherm models. Thermodynamic studies revealed that the adsorption of surfactant and polymeric surfactant were spontaneous in sand–aqueous system. The kinetics of adsorption was explained using different equations, namely, the Lagergren first‐order equation, the pseudo second‐order equation, and the intraparticle diffusion equation. The kinetic parameters in each model were identified and measured in order to explain adsorption dynamics.
Numerical study of phase split characteristics of slug flow at a branching micro‐T‐junction
Authors: Dong Jianxin , Zhang Xubin , Wang Fumin , Lv Guojun , Wu Botao , Cai Wangfeng 
Published: May 2018

AbstractThe phase split behavior of air–water slug flow at branching micro‐T‐junctions was studied by the volume of fluid model. The effects of velocity, surface tension, and viscosity on phase split results have been tested by slug units of fixed length. The split of a gas bubble at the T‐junction shows obstructing and nonobstructing modes. Through comparison, we found that the appearance of tunnels changes the driving force of bubble breakup from upstream pressure to viscous shearing force. Split features are influenced by the length of slug unit and the flow ratio in the obstructing mode. Nevertheless, the viscous force and surface tension should not be slighted for nonobstructing mode. Moreover, tendency of the flow maldistribution of nonobstructing mode is more pronounced with higher velocity and smaller surface tension. The liquid slug length has a negligible effect on the split results of gas phase. Thus, the results of two‐phase split could be obtained from the gas split ratio solely. Pattern diagram for the transition between the 2 modes was proposed. Eventually, the importance of the length information of slug unit was also verified by the predictive model of phase split that formulated with the regression analysis of numerical data.
DinCH and ESBO actual migration from PVC infusion tubings used in an oncopediatric unit
Authors: Tortolano Lionel , Matmati Houssem , Bourhis Matthieu , Manerlax Katia , Lemare François , Saunier Johanna , Yagoubi Najet 
Published: May 2018

ABSTRACTPlasticizer leaching from poly(vinyl chloride) (PVC) tubing is a well‐studied phenomenon and is a real issue in medical care today. The present study focuses on the release of two plasticizers 1,2‐cyclohexane dicarboxylic acid diisononyl ester (DINCH) (primary) and epoxidized soy bean oil (ESBO) (secondary) from PVC extension tubings used in an oncopediatric unit. The release of plasticizers is calculated by comparison to unused tubings with the same batch number. Both the DINCH and ESBO ratio diminishes in used versus new extension tubings. The loss of plasticizers has not been related to the presence of a specific drug. Our results confirm the leaching of classic plasticizers like the DINCH and of secondary plasticizers like the ESBO from tubings in real life. It confirms too the existence of a complex phenomenon in which exchanges between drugs, lipids, PVC matrices, and the administration sequences can change the global release of plasticizers. Considering all the variables involved in real‐life data, the in vitro testing appears to be the most efficient way to confirm these observations. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 46649.
Degradation and residues of indoxacarb enantiomers in rice plants, rice hulls and brown rice using enriched S‐indoxacarb formulation and enantiopure formulation
Authors: Shi Lihong , Gui Ting , Zhao Shan , Xu Jin , Wang Fei , Sui Changling , Zhang Yuping , Hu Deyu 
Published: May 2018

AbstractA chiral liquid chromatography–tandem high resolution mass spectroscopic method was developed for the analysis of indoxacarb enantiomers in rice plants, rice hulls and brown rice. Chiral separation of two enantiomers was carried out on a Superchiral S‐OD column maintained at 20°C and eluted with 0.3 mL/min methanol. Samples were extracted by acetonitrile solution with ultrasound and cleansed by dispersive solid‐phase extraction of 50 mg of primary secondary amine and 50 mg of C18. This method was successfully used to study the degradation and residues of two enantiomers with enriched S‐indoxacarb (2.33S/1R) and pure S‐indoxacarb in rice plants. The half‐lives of R‐indoxacarb and S‐indoxacarb were 4.20–4.33 and 3.45–3.57 days in rice plants during the degradation of enriched S‐indoxacarb in Guizhou and Hunan, respectively, whereas the half‐lives of pure S‐indoxacarb were 2.68 and 3.69 days in Guizhou and Hunan, respectively. The results indicated that preferential S‐indoxacarb degradation occurred and that enantiomeric transformation was absent in the total experiment periods of pure S‐indoxacarb in rice plants. The final residue concentrations of indoxacarb enantiomers in brown rice were significantly less than those in rice plants and rice hulls in the same rice field after applying indoxacarb SC and indoxacarb EC.
How industry peers improve your sustainable development? The role of listed firms in environmental strategies
Authors: Yang Xue , Wang Yuandi , Hu Die , Gao Yongqiang 
Published: May 2018

AbstractFactors driving firms to become more sustainable have been widely investigated in the literature on environmental strategy, but some important horizontal factors are still missing, such as influence from peers in the same industry. Drawing on signaling theory and expectancy theory, we complement existing studies by highlighting the role of listed firms in raising other firms' awareness and motivation of adopting environmental strategies, while taking the moderating capability factor into account. By setting our study in the context of listed and nonlisted private‐owned enterprises in China, the empirical analysis of 1,391 nonlisted firms indicates that the number of listed firms in an industry has positive effects on both reactive and proactive environmental strategies of nonlisted firms. The superior performance of these listed peers motivates nonlisted firms to adopt a proactive environmental strategy but constraints the reactive one. These effects are further strengthened by the relative scale of a nonlisted firm.
Pathway analysis of genetic variants in folate‐mediated one‐carbon metabolism‐related genes and survival in a prospectively followed cohort of colorectal cancer patients
Authors: Ose Jennifer , Botma Akke , Balavarca Yesilda , Buck Katharina , Scherer Dominique , Habermann Nina , Beyerle Jolantha , Pfütze Katrin , Seibold Petra , Kap Elisabeth J. , Benner Axel , Jansen Lina , Butterbach Katja , Hoffmeister Michael , Brenner Hermann , Ulrich Alexis , Schneider Martin , Chang‐Claude Jenny , Burwinkel Barbara , Ulrich Cornelia M. 
Published: May 2018

AbstractFolate‐mediated one‐carbon metabolism (FOCM) is a key pathway essential for nucleotide synthesis, DNA methylation, and repair. This pathway is a critical target for 5‐fluorouracil (5‐FU), which is predominantly used for colorectal cancer (CRC) treatment. A comprehensive assessment of polymorphisms in FOCM‐related genes and their association with prognosis has not yet been performed. Within 1,739 CRC cases aged ≥30 years diagnosed from 2003 to 2007 (DACHS study), we investigated 397 single nucleotide polymorphisms (SNPs) and 50 candidates in 48 FOCM‐related genes for associations with overall‐ (OS) and disease‐free survival (DFS) using multiple Cox regression (adjusted for age, sex, stage, grade, BMI, and alcohol). We investigated effect modification by 5‐FU‐based chemotherapy and assessed pathway‐specific effects. Correction for multiple testing was performed using false discovery rates (FDR). After a median follow‐up time of 5.0 years, 585 patients were deceased. For one candidate SNP in MTHFR and two in TYMS, we observed significant inverse associations with OS (MTHFR: rs1801133, C677T: HRhet = 0.81, 95% CI: 0.67–0.97; TYMS: rs1001761: HRhet = 0.82, 95% CI: 0.68–0.99 and rs2847149: HRhet = 0.82, 95% CI: 0.68–0.99). After FDR correction, one polymorphism in paraoxonase 1 (PON1; rs3917538) was significantly associated with OS (HRhet = 1.28, 95% CI: 1.07–1.53; HRhzv = 2.02, 95% CI:1.46–2.80; HRlogAdd = 1.31, pFDR = 0.01). Adjusted pathway analyses showed significant associations for pyrimidine biosynthesis (P = 0.04) and fluorouracil drug metabolism (P < 0.01) with significant gene–chemotherapy interactions, including PON1 rs3917538. This study supports the concept that FOCM‐related genes could be associated with CRC survival and may modify effects of 5‐FU‐based chemotherapy in genes in pyrimidine and fluorouracil metabolism, which are relevant targets for therapeutic response and prognosis in CRC. These results require confirmation in additional clinical studies.
SNAI2 and TWIST1 in lymph node progression in early stages of NSCLC patients
Authors: Emprou Camille , Le Van Quyen Pauline , Jégu Jérémie , Prim Nathalie , Weingertner Noëlle , Guérin Eric , Pencreach Erwan , Legrain Michèle , Voegeli Anne‐Claire , Leduc Charlotte , Mennecier Bertrand , Falcoz Pierre‐Emmanuel , Olland Anne , Santelmo Nicolas , Quoix Elisabeth , Massard Gilbert , Guenot Dominique , Chenard Marie‐Pierre , Beau‐Faller Michèle 
Published: May 2018

AbstractLymph node metastasis is an important prognosis factor in non‐small cell lung cancer (NSCLC) patients. The aim of this study was to investigate the role of epithelial to mesenchymal transition (EMT) in lymph node progression in the early stages of NSCLC. We studied a retrospective cohort of 160 consecutive surgically treated NSCLC patients with available frozen tumor samples for expression of EMT markers (CDH1, CTNNB1, CDH2, and VIMENTIN), inducers (TGFB1, c‐MET, and CAIX), and transcription factors (EMT‐TF: SNAI1, SNAI2, ZEB1, TWIST1, and TWIST2). Partial EMT was more frequent in N1‐2 (N+) vs N0 patients (P < .01). TGFB1 (P = .02) as well as SNAI2 (P < .01) and TWIST1 (P = .04) were the most differentially expressed genes in N+ tumors. In this group, ZEB1 was correlated with all EMT inducers and other EMT‐TFs were overexpressed depending on the inducers. CAIX was an independent prognostic factor for overall survival (IC 95% HR: 1.10‐5.14, P = .03). Partial EMT is involved in lymph node progression of NSCLC patients and depends on the TGFβ pathway. EMT‐TFs are differentially expressed depending on EMT inducers. CAIX might be a relevant prognostic marker in early stage NSCLC.