bluuebunny/crossref_metadata_2025_split huggingface dataset:
Catalytic Asymmetric Mannich‐Type Reaction of N‐Alkylidene‐α‐Aminoacetonitrile with Ketimines
Authors: Lin Shaoquan , Kawato Yuji , Kumagai Naoya , Shibasaki Masakatsu 
Published: March 2015

AbstractOptically active vicinal diamines are versatile chiral building blocks in organic synthesis. A soft Lewis acid/hard Brønsted base cooperative catalyst allows for an efficient stereoselective coupling of N‐alkylidene‐α‐aminoacetonitrile and ketimines to access this class of compounds bearing consecutive tetra‐ and trisubstituted stereogenic centers. The strategic use of a soft Lewis basic thiophosphinoyl group for ketimines is the key to promoting the reaction, and aliphatic ketimines serve as suitable substrates with as little as 3 mol % catalyst loading.
Ruthenium(II)‐katalysierte C‐H‐Aktivierung/Alkinanellierung durch schwache Koordination mit O2 als einzigem Oxidationsmittel
Authors: Warratz Svenja , Kornhaaß Christoph , Cajaraville Ana , Niepötter Benedikt , Stalke Dietmar , Ackermann Lutz 
Published: March 2015

AbstractAerobe oxidative C‐H‐Funktionalisierungen von schwach koordinierenden Benzoesäuren wurden mit vielseitig anwendbaren Ruthenium(II)‐biscarboxylat‐Komplexen unter Sauerstoffatmosphäre oder Luft ermöglicht. Mechanistische Studien führten zur Identifizierung der Schlüsselfaktoren der Oxidation von Ruthenium(0)‐Komplexen.
Nickel‐Catalyzed Asymmetric Transfer Hydrogenation of Hydrazones and Other Ketimines
Authors: Xu Haiyan , Yang Peng , Chuanprasit Pratanphorn , Hirao Hajime , Zhou Jianrong (Steve) 
Published: March 2015

AbstractWe report the use of nickel catalysts for the catalytic transfer hydrogenation of hydrazones and other ketimines with formic acid. Strongly donating bisphosphines must be used to support the catalysts. As in enzymatic catalysis, attractive weak interactions may be important for stereochemical control by the nickel/binapine catalyst.
Electron Flow in Reaction Mechanisms—Revealed from First Principles
Authors: Knizia Gerald , Klein Johannes E. M. N. 
Published: March 2015

AbstractThe “curly arrow” of Robinson and Ingold is the primary tool for describing and rationalizing reaction mechanisms. Despite this approach’s ubiquity and stellar success, its physical basis has never been clarified and a direct connection to quantum chemistry has never been found. Here we report that the bond rearrangements expressed by curly arrows can be directly observed in ab initio computations, as transformations of intrinsic bond orbitals (IBOs) along the reaction coordinate. Our results clarify that curly arrows are rooted in physical reality—a notion which has been challenged before—and show how quantum chemistry can directly establish reaction mechanisms in intuitive terms and unprecedented detail.
Covalent and Stable CuAAC Modification of Silicon Surfaces for Control of Cell Adhesion
Authors: Vutti Surendra , Buch‐Månson Nina , Schoffelen Sanne , Bovet Nicolas , Martinez Karen L. , Meldal Morten 
Published: March 2015

AbstractStable primary functionalization of metal surfaces plays a significant role in reliable secondary attachment of complex functional molecules used for the interfacing of metal objects and nanomaterials with biological systems. In principle, this can be achieved through chemical reactions either in the vapor or liquid phase. In this work, we compared these two methods for oxidized silicon surfaces and thoroughly characterized the functionalization steps by tagging and fluorescence imaging. We demonstrate that the vapor‐phase functionalization only provided transient surface modification that was lost on extensive washing. For stable surface modification, a liquid‐phase method was developed. In this method, silicon wafers were decorated with azides, either by silanization with (3‐azidopropyl)triethoxysilane or by conversion of the amine groups of an aminopropylated surface by means of the azido‐transfer reaction. Subsequently, D‐amino acid adhesion peptides could be immobilized on the surface by use of CuI‐catalyzed click chemistry. This enabled the study of cell adhesion to the metal surface. In contrast to unmodified surfaces, the peptide‐modified surfaces were able to maintain cell adhesion during significant flow velocities in a microflow reactor.
Structures of the Apo and FAD‐Bound Forms of 2‐Hydroxybiphenyl 3‐monooxygenase (HbpA) Locate Activity Hotspots Identified by Using Directed Evolution
Authors: Jensen Chantel N. , Mielke Tamara , Farrugia Joseph E. , Frank Annika , Man Henry , Hart Sam , Turkenburg Johan P. , Grogan Gideon 
Published: March 2015

AbstractThe FAD‐dependent monooxygenase HbpA from Pseudomonas azelaica HBP1 catalyses the hydroxylation of 2‐hydroxybiphenyl (2HBP) to 2,3‐dihydroxybiphenyl (23DHBP). HbpA has been used extensively as a model for studying flavoprotein hydroxylases under process conditions, and has also been subjected to directed‐evolution experiments that altered its catalytic properties. The structure of HbpA has been determined in its apo and FAD‐complex forms to resolutions of 2.76 and 2.03 Å, respectively. Comparisons of the HbpA structure with those of homologues, in conjunction with a model of the reaction product in the active site, reveal His48 as the most likely acid/base residue to be involved in the hydroxylation mechanism. Mutation of His48 to Ala resulted in an inactive enzyme. The structures of HbpA also provide evidence that mutants achieved by directed evolution that altered activity are comparatively remote from the substrate‐binding site.
Improving Cell‐Free Protein Synthesis through Genome Engineering of Escherichia coli Lacking Release Factor 1
Authors: Hong Seok Hoon , Kwon Yong‐Chan , Martin Rey W. , Des Soye Benjamin J. , de Paz Alexandra M. , Swonger Kirsten N. , Ntai Ioanna , Kelleher Neil L. , Jewett Michael C. 
Published: March 2015

AbstractSite‐specific incorporation of non‐standard amino acids (NSAAs) into proteins opens the way to novel biological insights and applications in biotechnology. Here, we describe the development of a high yielding cell‐free protein synthesis (CFPS) platform for NSAA incorporation from crude extracts of genomically recoded Escherichia coli lacking release factor 1. We used genome engineering to construct synthetic organisms that, upon cell lysis, lead to improved extract performance. We targeted five potential negative effectors to be disabled: the nuclease genes rna, rnb, csdA, mazF, and endA. Using our most productive extract from strain MCJ.559 (csdA− endA−), we synthesized 550±40 μg mL−1 of modified superfolder green fluorescent protein containing p‐acetyl‐L‐phenylalanine. This yield was increased to ∼1300 μg mL−1 when using a semicontinuous method. Our work has implications for using whole genome editing for CFPS strain development, expanding the chemistry of biological systems, and cell‐free synthetic biology.
Comparison of the Electronic and Vibrational Optical Activity of a Europium(III) Complex
Authors: Wu Tao , Hudecová Jana , You Xiao‐Zeng , Urbanová Marie , Bouř Petr 
Published: March 2015

AbstractThe geometry and the electronic structure of chiral lanthanide(III) complexes are traditionally probed by electronic methods, such as circularly polarised luminescence (CPL) and electronic circular dichroism (ECD) spectroscopy. The vibrational phenomena are much weaker. In the present study, however, significant enhancements of vibrational circular dichroism (VCD) and Raman optical activity (ROA) spectral intensities were observed during the formation of a chiral bipyridine–EuIII complex. The ten‐fold enhancement of the vibrational absorption and VCD intensities was explained by a charge‐transfer process and the dominant effect of the nitrate ion on the spectra. A much larger enhancement of the ROA and Raman intensities and a hundred‐fold increase of the circular intensity difference (CID) ratio were explained by the resonance of the λ=532 nm laser light with the 7F0 → 5D0 transitions. This phenomenon is combined with a chirality transfer, and mixing of the Raman and luminescence effects involving low‐energy 7F states of europium. The results thus indicate that the vibrational optical activity (VOA) may be a very sensitive tool for chirality detection and probing of the electronic structure of EuIII and other coordination compounds.
Guanidine‐Based Polymer Brushes Grafted onto Silica Nanoparticles as Efficient Artificial Phosphodiesterases
Authors: Savelli Claudia , Salvio Riccardo 
Published: March 2015

AbstractPolymer brushes grafted to the surface of silica nanoparticles were fabricated by atom‐transfer radical polymerization (ATRP) and investigated as catalysts in the cleavage of phosphodiesters. The surfaces of silica nanoparticles were functionalized with an ATRP initiator. Surface‐initiated ATRP reactions, in varying proportions, of a methacrylate moiety functionalized with a phenylguanidine moiety and an inert hydrophilic methacrylate species afforded hybrid nanoparticles that were characterized with potentiometric titrations, thermogravimetric analysis, and SEM. The activity of the hybrid nanoparticles was tested in the transesterification of the RNA model compound 2‐hydroxypropyl para‐nitrophenylphosphate (HPNP) and diribonucleoside monophosphates. A high catalytic efficiency and a remarkable effective molarity, thus overcoming the effective molarities previously observed for comparable systems, indicate the existence of an effective cooperation of the guanidine/guanidinium units and a high level of preorganization in the nanostructure. The investigated system also exhibits a marked and unprecedented selectivity for the diribonucleoside sequence CpA. The results presented open up the way for a novel and straightforward strategy for the preparation of supramolecular catalysts.
Prognostic Implications of Low Level Cardiac Troponin Elevation Using High‐Sensitivity Cardiac Troponin T
Authors: Grinstein Jonathan , Bonaca Marc P. , Jarolim Petr , Conrad Michael J. , Bohula‐May Erin , Deenadayalu Naveen , Braunwald Eugene , Giugliano Robert P. , Newby L. Kristin , Sabatine Marc S. , Morrow David A. 
Published: March 2015

ABSTRACTBackgroundHigh‐sensitivity cardiac troponin T (hsTnT) is used in many countries, but is not available in the United States. Prior evidence has been viewed as inconclusive as to whether low cardiac troponin T (cTnT) concentrations detected with hsTnT are prognostically meaningful compared with fourth‐generation cTnT.HypothesisThe aim of this study was to assess the prognostic performance of low‐level cTnT elevations using the hsTnT assay compared with the assay (fourth‐generation) currently available in the United States.MethodsWe measured serum cTnT in 4160 patients with non–ST‐elevation acute coronary syndrome using both the hsTnT and fourth‐generation assays. Patients were stratified at the 99th percentile cut point for each assay.ResultsPatients with baseline hsTnT ≥14 ng/L (n = 3697) vs <14 ng/L were at higher 30‐day risk of cardiovascular death (CVD) or myocardial infarction (MI) (9.1% vs 1.9%, P < 0.0001). After adjusting for all other elements of the Thrombolysis In Myocardial Infarction risk score, hsTnT ≥14 carried a 5.2‐fold higher risk of CVD/MI (95% confidence interval [CI]: 2.6‐10.1, P < 0.0001). Low levels of hsTnT (14–50 ng/L) also revealed increased risk (CVD/MI: 6.4%, P = 0.002). Importantly, patients with negative fourth‐generation cTnT but positive hsTnT were at 4.5‐times higher risk of CVD/MI (95% CI: 1.9‐11.0, P = 0.0008) than patients with negative hsTnT. In contrast, patients with a negative hsTnT but positive fourth‐generation cTnT result had a lower rate of CVD/MI than with a positive hsTnT (1.3% vs 8.2%, P = 0.0005).ConclusionsLow‐level increases in cTnT detected using the hsTnT assay identified patients at a meaningfully higher risk and who might otherwise be missed, and improves upon risk stratification using the cTnT assay currently available in the United States.
Pharmacophore‐Based Design of Novel Oxadiazoles as Selective Sphingosine‐1‐phosphate (S1P) Receptor Agonists with in vivo Efficacy
Authors: Quattropani Anna , Sauer Wolfgang H. B. , Crosignani Stefano , Dorbais Jerome , Gerber Patrick , Gonzalez Jerome , Marin Delphine , Muzerelle Mathilde , Beltran Fanny , Nichols Anthony , Georgi Katrin , Schneider Manfred , Vitte Pierre‐Alain , Eligert Valerie , Novo‐Perez Laurence , Hantson Jennifer , Nock Sebastien , Carboni Susanna , de Souza Adriano Luis Soares , Arrighi Jean‐François , Boschert Ursula , Bombrun Agnes 
Published: March 2015

AbstractSphingosine‐1‐phosphate (S1P) receptor agonists have shown promise as therapeutic agents for multiple sclerosis (MS) due to their regulatory roles within the immune, central nervous system, and cardiovascular system. Here, the design and optimization of novel [1,2,4]oxadiazole derivatives as selective S1P receptor agonists are described. The structure–activity relationship exploration was carried out on the three dominant segments of the series: modification of the polar head group (P), replacement of the oxadiazole linker (L) with different five‐membered heterocycles, and the use of diverse 2,2′‐disubstituted biphenyl moieties as the hydrophobic tail (H). All three segments have a significant impact on potency, S1P receptor subtype selectivity, physicochemical properties, and in vitro absorption, distribution, metabolism, excretion and toxicity (ADMET) profile of the compounds. From these optimization studies, a selective S1P1 agonist, N‐methyl‐N‐(4‐{5‐[2‐methyl‐2′‐(trifluoromethyl)biphenyl‐4‐yl]‐1,2,4‐oxadiazol‐3‐yl}benzyl)glycine (45), and a dual S1P1,5 agonist, N‐methyl‐N‐(3‐{5‐[2′‐methyl‐2‐(trifluoromethyl)biphenyl‐4‐yl]‐1,2,4‐oxadiazol‐3‐yl}benzyl)glycine (49), emerged as frontrunners. These compounds distribute predominantly in lymph nodes and brain over plasma and induce long lasting decreases in lymphocyte count after oral administration. When evaluated head‐to‐head in an experimental autoimmune encephalomyelitis mouse model, together with the marketed drug fingolimod, a pan‐S1P receptor agonist, S1P1,5 agonist 49 demonstrated comparable efficacy while S1P1‐selective agonist 45 was less potent. Compound 49 is not a prodrug, and its improved property profile should translate into a safer treatment of relapsing forms of MS.
Preference index for Japanese complexion under illuminations
Authors: Yano Tadashi , Hashimoto Kenjiro 
Published: March 2015

AbstractThis article proposes a useful evaluation method based on preferred complexion as one of color‐rendering methods of light sources. A relational equation between subjective evaluation values of preferred Japanese complexion under various illuminations and the D65 corresponding colors by adopting CIE94 chromatic adaptation transform on the CIE 1976 u′v′ chromaticity diagram was derived by using multiple regression. Then, preference index of skin color or PS was developed in order to evaluate quantitatively the degrees of preferred complexion from the equation. Furthermore, a new index PS(ac,bc) was derived by using CAM02 color appearance model instead of the CIE94. Each relationship of Ra, R15, CQS, MCRI, FCI, CCRI, and HCR to PS was examined. Then, the PS was found as an independent index which was quite different from the other indices when the PS was more than or equal to 80. Therefore, it is useful to develop and evaluate light sources to realize more comfortable lighting environments by applying the concept of the PS. © 2015 Wiley Periodicals, Inc. Col Res Appl, 41, 143–153, 2016
Evaluation of opicapone on cardiac repolarization in a thorough QT/QTc study
Authors: Pinto Roberto , l'Hostis Philippe , Patat Alain , Homery Marie‐Claude , Falcão Amílcar , Nunes Teresa , Rocha José‐Francisco , Soares‐da‐Silva Patrício 
Published: March 2015

AbstractOpicapone, a novel third‐generation catechol‐O‐methyltransferase inhibitor for use as adjunctive therapy in levodopa‐treated Parkinson's disease patients, was investigated on cardiac repolarization in healthy adult volunteers. This was a single‐center, randomized, double‐blind, placebo‐controlled, open‐label active‐controlled, 4‐period crossover study conducted in 64 subjects. In each period, subjects received a single oral dose of 50 mg opicapone, 800 mg opicapone, placebo, or 400 mg moxifloxacin and 24‐hour 12‐lead Holter monitoring was performed on day ‐1 (baseline) and after each single dose. After a single oral administrations of 50 and 800 mg opicapone, opicapone was the major entity in the circulation, with a median tmax of 1.5–2.0 hours. Opicapone was rapidly eliminated, with an elimination half‐life of 1–2 hours. There was no clinically relevant effect of 50 and 800 mg opicapone versus placebo on cardiac depolarization or repolarization. All upper bounds of the 1‐sided 95% confidence interval (CI) were below 10 milliseconds, confirming that opicapone has no QT‐prolonging effect. Moxifloxacin caused an increase in the QTcI, with a lower bound of the 2‐sided 95% CI always higher than 5 milliseconds, around the tmax of peak concentration, demonstrating assay sensitivity. In conclusion, administration of opicapone at therapeutic (50 mg) and supratherapeutic (800 mg) doses did not induce a clinically significant prolongation of the QTc interval.
Toward the Prediction of Activity in the Ethylene Polymerisation of ansa‐Bis(indenyl) Zirconocenes: Effect of the Stereochemistry and Hydrogenation of the Indenyl Moiety
Authors: Bravo Iván , Alonso‐Moreno Carlos , Carrillo‐Hermosilla Fernando , López‐Solera Isabel , Antiñolo Antonio , Albaladejo José 
Published: March 2015

AbstractA combined experimental and quantum chemical study has been performed on rac‐ and meso‐[Zr{1‐Me2Si(3‐η5‐C9H5Et)2}Cl2] (rac‐ and meso‐1) and their hydrogenated forms (rac‐ and meso‐2) to understand ligand effects and guide ligand design for more active ansa‐bis(indenyl) zirconocenes for the polymerisation of ethylene. The rac‐ansa‐zirconocene rac‐[Zr(1‐Me2Si{3‐Et‐(η5‐C9H9)}2)Cl2] (rac‐2) has been prepared and fully characterised by NMR spectroscopy and elemental analysis. The molecular structure of rac‐2 has also been determined by single‐crystal XRD. The behaviour of the catalysts was analysed in the polymerisation of ethylene and higher activities were obtained for rac‐1 and its hydrogenated form rac‐2. The influence of the stereochemistry and hydrogenation of the indenyl ligand on the experimental activities has been evaluated by computational studies. The differences along the reaction pathway are dominated by changes in the relative stabilities of the catalytic intermediates. A hybrid density functional B3LYP study, in the presence of toluene as the solvent, indicates that the rac forms give rise to more active species than their meso counterparts. The hydrogenation of the rac forms is a very promising approach to increase activities in polymerisation, in contrast to the meso forms. Finally, the global mechanism rate constants for the polymerisation reaction for each metallocene were calculated by using the thermodynamic formulation of transition‐state theory to complement the computational study.
Mesenchymal Deletion of Histone Demethylase NO66 in Mice Promotes Bone Formation
Authors: Chen Qin , Sinha Krishna , Deng Jian Min , Yasuda Hideyo , Krahe Ralf , Behringer Richard R , de Crombrugghe Benoit 
Published: March 2015

ABSTRACT

Our previous studies indicated that the Jumonji C (JmjC)-domain-containing NO66 is a histone demethylase with specificity for methylated histone H3K4 and H3K36. NO66 binds to the transcription factor Osterix (Osx) and inhibits its transcriptional activity in promoter assays. However, the physiological role of NO66 in formation of mammalian bones is unknown. Here, using a genetically engineered mouse model, we show that during early skeletal development, Prx1-Cre–dependent mesenchymal deletion of NO66 promotes osteogenesis and formation of both endochondral as well as intramembranous skeletal elements, leading to a larger skeleton and a high bone mass phenotype in adult mice. The excess bone formation in mice where NO66 was deleted in cells of mesenchymal origin is associated with an increase in the number of preosteoblasts and osteoblasts. Further analysis revealed that in the embryonic limbs and adult calvaria of mice with deletion of NO66 in cells of mesenchymal origin, expression of several genes including bone morphogenetic protein 2 (Bmp2), insulin-like growth factor 1 (Igf1), and osteoclast inhibitor osteoprotegerin was increased, concurrent with an increase in expression of bone formation markers such as osterix (Osx), type I collagen, and bone sialoprotein (Bsp). Taken together, our results provide the first in vivo evidence that NO66 histone demethylase plays an important role in mammalian osteogenesis during early development as well as in adult bone homeostasis. We postulate that NO66 regulates bone formation, at least in part, via regulating the number of bone-forming cells and expression of multiple genes that are critical for these processes. © 2015 American Society for Bone and Mineral Research.
An ATF4‐Signal‐Modulating Machine Other Than GADD34 Acts in ATF4‐to‐CHOP Signaling to Block CHOP Expression in ER‐Stress‐Related Autophagy
Authors: Iwasaki Noboru , Sugiyama Yoshiki , Miyazaki Shuichi , Nakagawa Hiroshi , Nishimura Kazuhiko , Matsuo Saburo 
Published: March 2015

ABSTRACTCells respond to ER‐stress via ER‐stress sensors, leading to the UPR and subsequent apoptosis; however, occasionally, they activate autophagy without subsequent apoptosis in response to ER‐stress. We previously showed that the induction of apoptosis by ER‐stress was related to the presence or absence of CHOP expression; nevertheless, how ATF4 expression is elicited without downstream CHOP expression is unknown. We studied the role of GADD34 on the induction of autophagy and/or apoptosis by NaF‐ or tunicamycin‐induced ER‐stress in HepG2 cells transfected with GADD34 siRNA. Although NaF and tunicamycin both induced PERK activation followed by eIF2α phosphorylation and ATF4 expression, CHOP expression was only induced by tunicamycin. Concomitant with the signaling change, autophagy was activated both by NaF and tunicamycin, and apoptosis was induced only by tunicamycin. After 4 h, GADD34 mRNA expression was also increased by NaF and tunicamycin. Suppression of GADD34 by GADD34 siRNA increased ATF4 expression in both NaF‐ and tunicamycin‐treated cells. The GADD34 siRNA increased CHOP expression, which corresponded to increased ATF4 in tunicamycin‐treated cells; however, the increased ATF4 did not induce CHOP expression in NaF‐treated cells. In concert with signal changes, siRNA treatment additively increased the autophagic activity of both NaF‐ and tunicamycin‐treated cells; however, apoptosis was produced and accelerated only for tunicamycin‐treated cells. These findings indicate that GADD34 expression induced by ER‐stress delays CHOP expression and retards apoptotic cell death, and that an ATF4‐signal‐modulating machine other than GADD34 acts on ATF4‐to‐CHOP signaling to block ATF4‐induced CHOP expression in ER‐stress related autophagy. J. Cell. Biochem. 116: 1300–1309, 2015. © 2014 Wiley Periodicals, Inc.
Calibration of the limiting current of oxygen sensors by the Fermi–Dirac distribution
Authors: Changshi Liu , Feng Li 
Published: March 2015

AbstractBased on Fermi–Dirac distribution, a physical model describing the current–voltage characteristics of limiting‐current oxygen sensors is presented. The model focuses on the prediction of the current via voltage by using an analytically invertible method. The response of oxygen concentration to limiting current is explained theoretically via a function. The simulations agree very well with the observed curves (either current versus voltage or oxygen concentration versus limiting current). Consequently, the oxygen concentration can be predicted from limiting current by using only one function. Copyright © 2015 John Wiley & Sons, Ltd.