bluuebunny/crossref_metadata_2025 huggingface dataset:
Phenotypic Screening to Identify Small‐Molecule Enhancers for Glucose Uptake: Target Identification and Rational Optimization of Their Efficacy
Authors: Koh Minseob , Park Jongmin , Koo Ja Young , Lim Donghyun , Cha Mi Young , Jo Ala , Choi Jang Hyun , Park Seung Bum
Published: April 2014

Small‐molecule glucose uptake enhancers targeted to myotubes and adipocytes were developed through a phenotypic screening linked with target identification and rational optimization. The target protein of glucose‐uptake enhancers was identified as a nuclear receptor PPARγ (peroxisome proliferator‐activated receptor gamma). Subsequent optimization of initial hits generated lead compounds with high potency for PPARγ transactivation and cellular glucose uptake. Finally, we confirmed that the chirality of optimized ligands differentiates their PPARγ transcriptional activity, binding affinity, and inhibitory activity toward Cdk5 (cyclin‐dependent kinase 5)‐mediated phosphorylation of PPARγ at Ser273. Using phenotype‐based lead discovery along with early‐stage target identification, this study has identified a new small‐molecule enhancer of glucose uptake that targets PPARγ.
Interpenetration as a Mechanism for Negative Thermal Expansion in the Metal–Organic Framework Cu3(btb)2 (MOF‐14)
Authors: Wu Yue , Peterson Vanessa K. , Luks Emily , Darwish Tamim A. , Kepert Cameron J.
Published: April 2014

Metal–organic framework materials (MOFs) have recently been shown in some cases to exhibit strong negative thermal expansion (NTE) behavior, while framework interpenetration has been found to reduce NTE in many materials. Using powder and single‐crystal diffraction methods we investigate the thermal expansion behavior of interpenetrated Cu3(btb)2 (MOF‐14) and find that it exhibits an anomalously large NTE effect. Temperature‐dependent structural analysis shows that, contrary to other interpenetrated materials, in MOF‐14 the large positive thermal expansion of weak interactions that hold the interpenetrating networks together results in a low‐energy contractive distortion of the overall framework structure, demonstrating a new mechanism for NTE.
Stitching 2D Polymeric Layers into Flexible Interpenetrated Metal–Organic Frameworks within Single Crystals
Authors: Zhang Zi‐Xuan , Ding Ni‐Ni , Zhang Wen‐Hua , Chen Jin‐Xiang , Young David J. , Hor T. S. Andy
Published: April 2014

A 2D coordination polymer prepared with bulky diethylformamide solvates exhibits channels which allow dipyridyl bridging ligands to diffuse into the crystal lattice. The absorbed dipyridyls thread through the pores of one layer and substitute the surface diethylformamide molecules on the neighboring layers to stitch alternate layers to form flexible interpenetrated metal–orgaic frameworks. The threading process also results in exchange of the bulky diethylformamide solvates for aqua to minimize congestion and, more strikingly, forces the slippage of two‐dimensional layers, while still maintaining crystallinity.
Dioxygen‐Triggered Transannular Dearomatization of Benzo[5]helicene Diols: Highly Efficient Synthesis of Chiral π‐Extended Diones
Authors: Shen Yun , Lu Hai‐Yan , Chen Chuan‐Feng
Published: April 2014

Oxidative dearomatization is a powerful strategy in organic synthesis. However, reports on using dioxygen as the oxidant, as it is environmentally friendly, readily available (air), and easy to handle, are rather limited. Helicene diols can undergo transannular dearomatization triggered by dioxygen to give diones in quantitative yields within several minutes. By virtue of this, the chirality is successfully transferred from helicity to central chirality to form distorted π‐extended diones having two all‐carbon quaternary stereocenters. The optical resolution was achieved by column chromatography, and the structures and the absolute configurations of the chiral diones were determined by X‐ray analysis.
Fabrication of Multiresponsive Bioactive Nanocapsules through Orthogonal Self‐Assembly
Authors: Yeh Yi‐Cheun , Tang Rui , Mout Rubul , Jeong Youngdo , Rotello Vincent M.
Published: April 2014

Multifunctional self‐assembled systems present platforms for fundamental research and practical applications as they provide tunability of structure, functionality, and stimuli responsiveness. Pragmatic structures for biological applications have multiple design requirements, including control of size, stability, and environmental response. Here we present the fabrication of multifunctional nanoparticle‐stabilized capsules (NPSCs) by using a set of orthogonal supramolecular interactions. In these capsules, fluorescent proteins are attached to quantum dots through polyhistidine coordination. These anionic assemblies interact laterally with cationic gold nanoparticles that are anchored to the fatty acid core through guanidinium–carboxylate interactions. The lipophilic core then provides a reservoir for hydrophobic endosome‐disrupting agents, thereby generating a system featuring stimuli‐responsive release of a payload into the cytosol with fluorescence monitoring.
A Collection of Fullerenes for Synthetic Access Toward Oriented Charge‐Transfer Cascades in Triple‐Channel Photosystems
Authors: Bolag Altan , López‐Andarias Javier , Lascano Santiago , Soleimanpour Saeideh , Atienza Carmen , Sakai Naomi , Martín Nazario , Matile Stefan
Published: April 2014

The development of synthetic methods to build complex functional systems is a central and current challenge in organic chemistry. This goal is important because supramolecular architectures of highest sophistication account for function in nature, and synthetic organic chemistry, contrary to high standards with small molecules, fails to deliver functional systems of similar complexity. In this report, we introduce a collection of fullerenes that is compatible with the construction of multicomponent charge‐transfer cascades and can be placed in triple‐channel architectures next to stacks of oligothiophenes and naphthalenediimides. For the creation of this collection, modern fullerene chemistry—methanofullerenes and 1,4‐diarylfullerenes—is combined with classical Nierengarten–Diederich–Bingel approaches.
Gold(I) as an Artificial Cyclase: Short Stereodivergent Syntheses of (−)‐Epiglobulol and (−)‐4β,7α‐ and (−)‐4α,7α‐Aromadendranediols
Authors: Carreras Javier , Livendahl Madeleine , McGonigal Paul R. , Echavarren Antonio M.
Published: April 2014

Three natural aromadendrane sesquiterpenes, (−)‐epiglobulol, (−)‐4β,7α‐aromadendranediol, and (−)‐4α,7α‐aromadendranediol, have been synthesized in only seven steps in 12, 15, and 17 % overall yields, respectively, from (E,E)‐farnesol by a stereodivergent gold(I)‐catalyzed cascade reaction which forms the tricyclic aromadendrane core in a single step. These are the shortest total syntheses of these natural compounds.
Well‐Defined Four‐Coordinate Iron(II) Complexes For Intramolecular Hydroamination of Primary Aliphatic Alkenylamines
Authors: Bernoud Elise , Oulié Pascal , Guillot Régis , Mellah Mohamed , Hannedouche Jérôme
Published: April 2014

Despite the growing interest in iron catalysis and hydroamination reactions, iron‐catalyzed hydroamination of unprotected primary aliphatic amines and unactivated alkenes has not been reported to date. Herein, a novel well‐defined four‐coordinate β‐diketiminatoiron(II) alkyl complex is shown to be an excellent precatalyst for the highly selective cyclohydroamination of primary aliphatic alkenylamines at mild temperatures (70–90 °C). Both empirical kinetic analyses and the reactivity of an isolated iron(II) amidoalkene dimer, [LFe(NHCH2CPh2CH2CHCH2)]2 favor a stepwise σ‐insertive mechanism that entails migratory insertion of the pendant alkene into an iron–amido bond associated with a rate‐determining aminolysis step.
Crystal‐Plane‐Controlled Selectivity of Cu2O Catalysts in Propylene Oxidation with Molecular Oxygen
Authors: Hua Qing , Cao Tian , Gu Xiang‐Kui , Lu Jiqing , Jiang Zhiquan , Pan Xiaorong , Luo Liangfeng , Li Wei‐Xue , Huang Weixin
Published: April 2014

The selective oxidation of propylene with O2 to propylene oxide and acrolein is of great interest and importance. We report the crystal‐plane‐controlled selectivity of uniform capping‐ligand‐free Cu2O octahedra, cubes, and rhombic dodecahedra in catalyzing propylene oxidation with O2: Cu2O octahedra exposing {111} crystal planes are most selective for acrolein; Cu2O cubes exposing {100} crystal planes are most selective for CO2; Cu2O rhombic dodecahedra exposing {110} crystal planes are most selective for propylene oxide. One‐coordinated Cu on Cu2O(111), three‐coordinated O on Cu2O(110), and two‐coordinated O on Cu2O(100) were identified as the catalytically active sites for the production of acrolein, propylene oxide, and CO2, respectively. These results reveal that crystal‐plane engineering of oxide catalysts could be a useful strategy for developing selective catalysts and for gaining fundamental understanding of complex heterogeneous catalytic reactions at the molecular level.
Identification and X‐ray Co‐crystal Structure of a Small‐Molecule Activator of LFA‐1‐ICAM‐1 Binding
Authors: Hintersteiner Martin , Kallen Jörg , Schmied Mario , Graf Christine , Jung Thomas , Mudd Gemma , Shave Steven , Gstach Hubert , Auer Manfred
Published: April 2014

Stabilization of protein–protein interactions by small molecules is a concept with few examples reported to date. Herein we describe the identification and X‐ray co‐crystal structure determination of IBE‐667, an ICAM‐1 binding enhancer for LFA‐1. IBE‐667 was designed based on the SAR information obtained from an on‐bead screen of tagged one‐bead one‐compound combinatorial libraries by confocal nanoscanning and bead picking (CONA). Cellular assays demonstrate the activity of IBE‐667 in promoting the binding of LFA‐1 on activated immune cells to ICAM‐1.
Unprecedented Iron‐Catalyzed Ester Hydrogenation. Mild, Selective, and Efficient Hydrogenation of Trifluoroacetic Esters to Alcohols Catalyzed by an Iron Pincer Complex
Authors: Zell Thomas , Ben‐David Yehoshoa , Milstein David
Published: April 2014

The synthetically important, environmentally benign hydrogenation of esters to alcohols has been accomplished in recent years only with precious‐metal‐based catalysts. Here we present the first iron‐catalyzed hydrogenation of esters to the corresponding alcohols, proceeding selectively and efficiently in the presence of an iron pincer catalyst under remarkably mild conditions.
Effects of epoxidized natural rubber (ENR‐50) and processing parameters on the properties of NR/EPDM blends using response surface methodology
Authors: Mohamad Noraiham , Yaakub Juliana , Abd Razak Jeefferie , Yaakob Mohd Yuhazri , Shueb Mohammed Iqbal , Muchtar Andanastuti
Published: April 2014

The effects of epoxidized natural rubber (ENR‐50) and processing parameters on the properties of natural rubber/ethylene–propylene–diene rubber (NR/EPDM; 70 : 30 phr) blends were studied. The compounds were prepared by melt compounding method. Using response surface methodology of two‐level full factorial, the effects of ENR‐50 contents (−1 : 5 phr; +1 : 10 phr), mixing temperature (−1 : 50°C; +1 : 110°C), rotor speed (−1 : 40 rpm; +1 : 80 rpm), and mixing time (−1 : 5 min; +1 : 9 min) in NR/EPDM blends were evaluated. Cure characteristics and tensile properties were selected as the responses. The significance of factors and its interaction was analyzed using ANOVA and the model's ability to represent the system was confirmed using the constant of determination, R2 with values above 0.90. It was found that the presence of ENR‐50 has the predominant role on the properties of NR/EPDM blends. The addition of ENR‐50 significantly improved cure characteristics and tensile strength up to 5.12% and 6.48% compared to neat NR/EPDM blends, respectively. These findings were further supported by swell measurement, differential scanning calorimetry, and scanning electron microscopy. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40713.
Incidence of Total Knee and Hip Replacement for Osteoarthritis in Relation to Circulating Sex Steroid Hormone Concentrations in Women
Authors: Hussain Sultana Monira , Cicuttini Flavia M. , Bell Robin J. , Robinson Penelope J. , Davis Susan R. , Giles Graham G. , Graves Stephen , Milne Roger L. , Wang Yuanyuan
Published: April 2014

Objective

The increased prevalence of osteoarthritis (OA) in postmenopausal women suggests that changes in either circulating sex steroid concentrations or the tissue response to sex steroids may have a role in the pathogenesis of OA. The aim of this study was to examine whether circulating sex steroid concentrations are associated with the incidence of total knee and total hip replacement for OA.

Methods

Study subjects (n = 2,621; all women) were recruited in 1990–1994 from the Melbourne Collaborative Cohort Study (MCCS). Circulating sex steroid concentrations were measured in blood samples obtained from the women at the time of recruitment. The incidence of total knee and total hip replacement for OA during 2001–2011 was determined by linking the MCCS records to the Australian Orthopaedic Association National Joint Replacement Registry.

Results

During the followup period, 115 women had undergone total knee replacement and 99 had undergone total hip replacement for OA. Greater log‐transformed concentrations of estradiol were associated with a lower incidence of knee replacement (hazard ratio [HR] 0.70, 95% confidence interval [95% CI] 0.50–0.96), and greater log‐transformed concentrations of androstenedione were associated with a lower incidence of hip replacement (HR 0.70, 95% CI 0.52–0.93). In contrast, greater log‐transformed concentrations of sex hormone binding globulin (SHBG) were associated with a higher incidence of hip replacement (HR 1.70, 95% CI 1.05–2.77).

Conclusion

A lower estradiol concentration is a risk factor for knee OA, while a lower androstenedione concentration and higher SHBG concentration are risk factors for hip OA in women. These findings suggest that circulating sex steroids have a role in the pathogenesis of OA, and that modifying these steroid concentrations may provide a potential strategy for the prevention and treatment of knee and hip OA.
Structural Optimization of Interpenetrated Pillared‐Layer Coordination Polymers for Ethylene/Ethane Separation
Authors: Kishida Keisuke , Horike Satoshi , Watanabe Yoshihiro , Tahara Mina , Inubushi Yasutaka , Kitagawa Susumu
Published: April 2014

With the goal of achieving effective ethylene/ethane separation, we evaluated the gas sorption properties of four pillared‐layer‐type porous coordination polymers with double interpenetration, [Zn2(tp)2(bpy)]n (1), [Zn2(fm)2(bpe)]n (2), [Zn2(fm)2(bpa)]n (3), and [Zn2(fm)2(bpy)]n (4) (tp=terephthalate, bpy=4,4′‐bipyridyl, fm=fumarate, bpe=1,2‐di(4‐pyridyl)ethylene and bpa=1,2‐di(4‐pyridyl)ethane). It was found that 4, which contains the narrowest pores of all of these compounds, exhibited ethylene‐selective sorption profiles. The ethylene selectivity of 4 was estimated to be 4.6 at 298 K based on breakthrough experiments using ethylene/ethane gas mixtures. In addition, 4 exhibited a good regeneration ability compared with a conventional porous material.
FRET‐Based Mitochondria‐Targetable Dual‐Excitation Ratiometric Fluorescent Probe for Monitoring Hydrogen Sulfide in Living Cells
Authors: Yuan Lin , Zuo Qing‐Ping
Published: April 2014

Hydrogen sulfide (H2S) is connected with various physiological and pathological functions. However, understanding the important functions of H2S remains challenging, in part because of the lack of tools for detecting endogenous H2S. Herein, compounds Ratio‐H2S 1/2 are the first FRET‐based mitochondrial‐targetable dual‐excitation ratiometric fluorescent probes for H2S on the basis of H2S‐promoted thiolysis of dinitrophenyl ether. With the enhancement of H2S concentration, the excitation peak at λ≈402 nm of the phenolate form of the hydroxycoumarin unit drastically increases, whereas the excitation band centered at λ≈570 nm from rhodamine stays constant and can serve as a reference signal. Thus, the ratios of fluorescence intensities at λ=402 and 570 nm (I402/I570) exhibit a drastic change from 0.048 in the absence of H2S to 0.36 in the presence of 180 μM H2S; this is a 7.5‐fold variation in the excitation ratios. The favorable properties of the probe include the donor and acceptor excitation bands, which exhibit large excitation separations (up to 168 nm separation) and comparable excitation intensities, high sensitivity and selectivity, and function well at physiological pH. In addition, it is demonstrated that the probe can localize in the mitochondria and determine H2S in living cells. It is expected that this strategy will lead to the development of a wide range of mitochondria‐targetable dual‐excitation ratiometric probes for other analytes with outstanding spectral features, including large separations between the excitation wavelengths and comparable excitation intensities.
Integriertes Entwerfen im digitalen Prozess
Authors: Knippers Jan
Published: April 2014

Computerbasierte Planungs‐, Simulations‐ und Fertigungsverfahren sind seit Jahrzehnten unverzichtbare Hilfsmittel beim Planen und Bauen. Gegenwärtige Entwicklungen zielen auf die Verknüpfung von bisher isolierten Softwarekomponenten zum einen auf die horizontale Integration von verschiedenen Informationen der Planungsbeteiligten in Gebäudedatenmodellen (Building Information Modeling, kurz: BIM) und zum anderen vertikal entlang der gesamten Prozesskette vom frühen Entwurf bis zur Ausführung auf der Baustelle und der Bewirtschaftung der Gebäude. Ziel ist dabei die Steigerung der Effizienz und der Sicherheit von Planungs‐ und Bauabläufen. Darüber hinaus hat dies aber auch tief greifende Auswirkungen auf die Planungskultur: Es verändert sich nicht nur die interdisziplinäre Kommunikation zwischen den Beteiligten, sondern auch die Rolle und die Aufgaben von Architekten und Ingenieuren im Prozess des Planens und Bauens.

Integrative design in the digital process

Computational design, simulation and fabrication methods have been an indispensable means of design and construction for decades. Recent efforts are focused on linking previously isolated components: on the one hand, horizontally through the integration of different information of the various parties involved in consistent data models (Building Information Modeling, short: BIM), on the other hand, vertically along the entire process chain, from the early stages of design to the installation on site and management of the facilities. The aim is to strengthen the efficiency and reliability of design and construction processes. In addition this will lead to a profound change in the culture of design that will not only affect the interdisciplinary communication, but also the role of architects and engineers in the entire process of design and construction.
Ermüdungsversuche an Stahlbetonfertigteilen für Lärmschutzwände an Eisenbahn‐Hochgeschwindigkeitsstrecken
Authors: Keuser Manfred , Hiller Eugen , Lenner Roman
Published: April 2014

Angesichts der dichten Besiedlung kommt dem Schallschutz an Verkehrswegen in Deutschland eine große Bedeutung zu. Insbesondere an Eisenbahnstrecken kommen Lärmschutzwände aus Stahlbetonfertigteilen zum Einsatz. Bei Hochgeschwindigkeitsverkehr führt die Belastung aus Zugvorbeifahrt zu Schwingungen der Wände, sodass die Ermüdungsfestigkeit nachgewiesen werden muss. Im Labor des Instituts für Konstruktiven Ingenieurbau der Universität der Bundeswehr wurden hierzu in den vergangenen Jahren zahlreiche Versuche mit zyklischer Belastung durchgeführt. Dabei wurde dem Auflagerbereich, angesichts der sehr kleinen Auflagerbreite, besondere Beachtung geschenkt.

Reinforced Concrete Precast Panels as Noise Protection along High Speed Rail Tracks

The noise protection along traffic routes has large importance in Germany due to the high density of population. Reinforced concrete panels as noise protection walls are often used especially along railroad tracks. The loading due to high‐speed trains induces oscillation of the walls and the fatigue, therefore, has to be investigated. During the last years, the Laboratory of the Institute of Structural Engineering at the University of the German Armed Forces in Munich performed a large number of tests involving cyclical loading. The particular area of interest was the relatively narrow support.
Die zerstörungsfreie Untersuchung von Durchstanzbewehrung in Flachdecken
Authors: Hugenschmidt Johannes , Fischer Andreas , Schiavi Lucio
Published: April 2014

Mittels Radaruntersuchungen werden Betondeckenbereiche einer Fläche von 2 × 0,9 m2 in Stützennähe in ausgewählten Einstellhallen zerstörungsfrei mit dem Ziel untersucht, typische Bewehrungselemente zur Erhöhung des Durchstanzwiderstands zu erkennen. Im Untersuchungsergebnis zeigte sich, dass diese Elemente, wie z.B. Bewehrungsstäbe, Stahlpilze oder Dübelleisten, mit hoher Wahrscheinlichkeit identifiziert werden können. Die Messdaten liefern für die meisten untersuchten Elementtypen spezifische, reproduzierbare Datenmuster. Mithilfe von Radaruntersuchungen ist es deshalb möglich, auf nicht dokumentierte Bewehrungselemente im Bauwerk zu schließen. Die Bauingenieure können so den Durchstanzwiderstand von Flachdecken im Bereich ihrer Stützen besser beurteilen. Das eröffnet Prüfmöglichkeiten zur Durchstanzproblematik in Bezug auf die Einhaltung technisch verbindlicher Normen sowie zur Untersuchung von Bauschäden oder deren Prophylaxe.

Non‐destructive inspection of punching shear reinforcement in concrete flat slabs

In selected car parks, ground penetrating radar (GPR) surveys were carried out on ceiling areas in the vicinity of piles. The areas inspected were 0.9 m × 2.0 m each. The aim of the surveys was the detection Punching shear reinforcement (PSR). It was shown that several types of PSR can be detected reliably. The acquired GPR data show distinctive reflection patterns for most types of PSR. It is therefore possible to detect punching shear reinforcement in cases where appropriate documentation of the construction details is missing. Thus, GPR surveys can provide information relevant for the engineer for assessing the safety of buildings. This facilitates testing options related to the punching problem. Objects can be tested for compliance with existing standards, for the evaluation of structural damage or for prevention.
Schrägseilbedämpfung mit echtzeitgeregelten MR‐Dämpfern
Authors: Weber Felix , Distl Hans
Published: April 2014

Schrägseile neigen wegen ihrer kleinen Dämpfung von 0,1%–0,15% zu windinduzierten Schwingungen. Da sich Windbedingungen ändern, sind sowohl Schwingamplitude als auch Schwingfrequenz unbekannt. Daher muss ein Seildämpfungssystem die Seile unabhängig von deren Amplitude und Frequenz gleich effizient bedämpfen. Dieser Aufsatz zeigt, wie diese Anforderung mittels echtzeitgeregelter magnetorheologischer Dämpfer erfüllt werden kann. Die Effizienz des adaptiven Seildämpfungssystems ist experimentell validiert und dessen Umsetzung auf den weltgrößten Schrägseilbrücken, der Sutong‐Brücke in China und der Russky‐Brücke in Russland, beschrieben.

Stay Cable Damping by Real‐Time Controlled MR Dampers

Stay cables are prone to wind‐induced vibrations due to their low inherent damping of 0,1%–0,15%. Since wind conditions vary over time, vibration amplitudes and frequencies are unknown. Consequently, cable damping systems must generate amplitude and frequency independent cable damping. It is described how this requirement can be fulfilled by real‐time controlled magnetorheological dampers. The efficiency of the adaptive cable damping system is experimentally validated and its implementation on the world largest stay cable bridges, the Sutong Bridge in China and the Russky Bridge in Russia, is described.
Research experiences and mentoring practices in selected east asian graduate programs: Predictors of research productivity among doctoral students in molecular biology
Authors: Ynalvez Ruby , Garza‐Gongora Claudia , Ynalvez Marcus Antonius , Hara Noriko
Published: April 2014

Although doctoral mentors recognize the benefits of providing quality advisement and close guidance, those of sharing project management responsibilities with mentees are still not well recognized. We observed that mentees, who have the opportunity to co‐manage projects, generate more written output. Here we examine the link between research productivity, doctoral mentoring practices (DMP), and doctoral research experiences (DRE) of mentees in programs in the non‐West. Inspired by previous findings that early career productivity is a strong predictor of later productivity, we examine the research productivity of 210 molecular biology doctoral students in selected programs in Japan, Singapore, and Taiwan. Using principal component (PC) analysis, we derive two sets of PCs: one set from 15 DMP and another set from 16 DRE items. We model research productivity using Poisson and negative‐binomial regression models with these sets as predictors. Our findings suggest a need to re‐think extant practices and to allocate resources toward professional career development in training future scientists. We contend that doctoral science training must not only be an occasion for future scientists to learn scientific and technical skills, but it must also be the opportunity to experience, to acquire, and to hone research management skills. © 2014 by The International Union of Biochemistry and Molecular Biology, 42(4):305–322, 2014.
Enhancing the Efficiency and Regioselectivity of P450 Oxidation Catalysts by Unnatural Amino Acid Mutagenesis
Authors: Kolev Joshua N. , Zaengle Jacqueline M. , Ravikumar Rajesh , Fasan Rudi
Published: April 2014

The development of effective strategies for modulating the reactivity and selectivity of cytochrome P450 enzymes represents a key step toward expediting the use of these biocatalysts for synthetic applications. We have investigated the potential of unnatural amino acid mutagenesis to aid efforts in this direction. Four unnatural amino acids with diverse aromatic side chains were incorporated at 11 active‐site positions of a substrate‐promiscuous CYP102A1 variant. The resulting “uP450s” were then tested for their catalytic activity and regioselectivity in the oxidation of two representative substrates: a small‐molecule drug and a natural product. Large shifts in regioselectivity resulted from these single mutations, and in particular, for para‐acetyl‐Phe substitutions at positions close to the heme cofactor. Screening this mini library of uP450s enabled us to identify P450 catalysts for the selective hydroxylation of four aliphatic positions in the target substrates, including a C(sp3)H site not oxidized by the parent enzyme. Furthermore, we discovered a general activity‐enhancing effect of active‐site substitutions involving the unnatural amino acid para‐amino‐Phe, which resulted in P450 catalysts capable of supporting the highest total turnover number reported to date on a complex molecule (34 650). The functional changes induced by the unnatural amino acids could not be reproduced by any of the 20 natural amino acids. This study thus demonstrates that unnatural amino acid mutagenesis constitutes a promising new strategy for improving the catalytic activity and regioselectivity of P450 oxidation catalysts.
Converting Aspartase into a β‐Amino Acid Lyase by Cluster Screening
Authors: Vogel Andreas , Schmiedel Ramona , Hofmann Ute , Gruber Karl , Zangger Klaus
Published: April 2014

Aspartase, despite being one of the most specific enzymes known, shows potential for application in β‐amino acid synthesis. The substrate binding pocket of AspB from Bacillus sp. YM55‐1 was reshaped by enzyme engineering to accommodate crotonic acid. The mutant enzyme BSASP‐C6 yielded enantiopure (R)‐3‐aminobutyrate from crotonic acid and ammonia. To obtain this mutant, a high‐throughput screening in combination with a focused permutational library was decisive for the success in this project. We achieved this by simultaneous randomisation of four residues within the substrate binding pocket and cluster screening in mixed population. Screening of 300 000 clones was necessary to find the BSASP‐C6 mutant which has β‐amino acid lyase activity. This exemplifies the need for efficient search and screening strategies in creating novel enzyme activities. The BSAPS‐C6 enzyme developed here surpasses the natural substrate functionality of aspartase and thus represents the proof‐of‐concept of application of this novel synthetic route to a broader set of β‐amino acids.
Dynamic Molecular Graphs: “Hopping” Structures
Authors: Cortés‐Guzmán Fernando , Rocha‐Rinza Tomas , Guevara‐Vela José Manuel , Cuevas Gabriel , Gómez Rosa María
Published: April 2014

This work aims to contribute to the discussion about the suitability of bond paths and bond‐critical points as indicators of chemical bonding defined within the theoretical framework of the quantum theory of atoms in molecules. For this purpose, we consider the temporal evolution of the molecular structure of [Fe{C(CH2)3}(CO)3] throughout Born–Oppenheimer molecular dynamics (BOMD), which illustrates the changing behaviour of the molecular graph (MG) of an electronic system. Several MGs with significant lifespans are observed across the BOMD simulations. The bond paths between the trimethylenemethane and the metallic core are uninterruptedly formed and broken. This situation is reminiscent of a “hopping” ligand over the iron atom. The molecular graph wherein the bonding between trimethylenemethane and the iron atom takes place only by means of the tertiary carbon atom has the longest lifespan of all the considered structures, which is consistent with the MG found by X‐ray diffraction experiments and quantum chemical calculations. In contrast, the η4complex predicted by molecular‐orbital theory has an extremely brief lifetime. The lifespan of different molecular structures is related to bond descriptors on the basis of the topology of the electron density such as the ellipticities at the FeCH2bond‐critical points and electron delocalisation indices. This work also proposes the concept of a dynamic molecular graph composed of the different structures found throughout the BOMD trajectories in analogy to a resonance hybrid of Lewis structures. It is our hope that the notion of dynamic molecular graphs will prove useful in the discussion of electronic systems, in particular for those in which analysis on the basis of static structures leads to controversial conclusions.
Photo‐ and Electrocatalytic H2 Production by New First‐Row Transition‐Metal Complexes Based on an Aminopyridine Pentadentate Ligand
Authors: Call Arnau , Codolà Zoel , Acuña‐Parés Ferran , Lloret‐Fillol Julio
Published: April 2014

The synthesis and characterisation of the pentadentate ligand 1,4‐di(picolyl)‐7‐(p‐toluenesulfonyl)‐1,4,7‐triazacyclononane (Py2Tstacn) and their metal complexes of general formula [M(CF3SO3)(Py2Tstacn)][CF3SO3], (M=Fe (1Fe), Co (1Co) and Ni (1Ni)) are reported. Complex 1Co presents excellent H2 photoproduction catalytic activity when using [Ir(ppy)2(bpy)]PF6 (PSIr) as photosensitiser (PS) and Et3N as electron donor, but 1Ni and 1Fe result in a low activity and a complete lack of it, respectively. On the other hand, all three complexes have excellent electrocatalytic proton reduction activity in acetonitrile, when using trifluoroacetic acid (TFA) as a proton source with moderate overpotentials for 1Co (0.59 V vs. SCE) and 1Ni (0.56 V vs. SCE) and higher for 1Fe (0.87 V vs. SCE). Under conditions of CH3CN/H2O/Et3N (3:7:0.2), 1Co (5 μM), with PSIr (100 μM) and irradiating at 447 nm gives a turnover number (TON) of 690 (n/n) and initial turnover frequency (TOF) (TON×t−1) of 703 h−1 for H2 production. It should be noted that 1Co retains 25 % of the catalytic activity for photoproduction of H2 in the presence of O2. The inexistence of a lag time for H2 evolution and the absence of nanoparticles during the first 30 min of the reaction suggest that the main catalytic activity observed is derived from a molecular system. Kinetic studies show that the reaction is −0.7 order in catalyst, and time‐dependent diffraction light scattering (DLS) experiments indicate formation of metal aggregates and then nanoparticles, leading to catalyst deactivation. By a combination of experimental and computational studies we found that the lack of activity in photochemical water reduction by 1Fe can be attributed to the 1FeII/I redox couple, which is significantly lower than the PSIrIII/II, while for 1Ni the pKa value (−0.4) is too small in comparison with the pH (11.9) imposed by the use of Et3N as electron donor.
Sensing of Phosphates by Using Luminescent EuIII and TbIII Complexes: Application to the Microalgal Cell Chlorella vulgaris
Authors: Nadella Sandeep , Sahoo Jashobanta , Subramanian Palani S. , Sahu Abhishek , Mishra Sandhya , Albrecht Markus
Published: April 2014

Phenanthroline‐based chiral ligands L1 and L2 as well as the corresponding EuIII and TbIII complexes were synthesized and characterized. The coordination compounds show red and green emission, which was explored for the sensing of a series of anions such as F−, Cl−, Br−, I−, NO3−, NO2−, HPO42−, HSO4−, CH3COO−, and HCO3−. Among the anions, HPO42− exhibited a strong response in the emission property of both europium(III) and terbium(III) complexes. The complexes showed interactions with the nucleoside phosphates adenosine triphosphate (ATP), adenosine diphosphate (ADP), and adenosine monophosphate (AMP). Owing to this recognition, these complexes have been applied as staining agents in the microalgal cell Chlorella vulgaris. The stained microalgal cells were monitored through fluorescence microscopy and scanning electron microscopy. Initially, the complexes bind to the outer cell wall and then enter the cell wall through holes in which they probably bind to phospholipids. This leads to a quenching of the luminescence properties.
Nucleic Acid Based Logical Systems
Authors: Han Da , Kang Huaizhi , Zhang Tao , Wu Cuichen , Zhou Cuisong , You Mingxu , Chen Zhuo , Zhang Xiaobing , Tan Weihong
Published: April 2014

Researchers increasingly visualize a significant role for artificial biochemical logical systems in biological engineering, much like digital logic circuits in electrical engineering. Those logical systems could be utilized as a type of servomechanism to control nanodevices in vitro, monitor chemical reactions in situ, or regulate gene expression in vivo. Nucleic acids (NA), as carriers of genetic information with well‐regulated and predictable structures, are promising materials for the design and engineering of biochemical circuits. A number of logical devices based on nucleic acids (NA) have been designed to handle various processes for technological or biotechnological purposes. This article focuses on the most recent and important developments in NA‐based logical devices and their evolution from in vitro, through cellular, even towards in vivo biological applications.
Simultaneous Carbon Coating and Lithiation of Oxides by Contact Reaction
Authors: Wächter Florian , Krumeich Frank , Nesper Reinhard
Published: April 2014

Chemical lithiation and carbon coating of cathode materials can lead to strongly improved electrochemical properties, especially if the active materials have low electronic conductivity. This behavior is quite often the case for new high‐capacity materials. A novel synthesis method is presented in which the two processes are performed simultaneously by employing Li2C2 as both the carbon and the lithium source. In this contact reaction, the acetylide anion C22− is oxidized to carbon and deposited directly on the surface of the active material, while lithium is reductively inserted into the oxidant. Two different synthesis routes are demonstrated: a tribochemical approach at room temperature and heat treatments between 150 and 600 °C. The applicability of these new carbon‐coating methods are demonstrated on various crystalline and amorphous LixV2O5 phases. The composites obtained were characterized by powder X‐ray diffraction, transmission electron microscopy, and Raman spectroscopy. In addition, electrochemical data confirm the chemical lithiation and show that lithiated LixV2O5 with specific phases can be prepared selectively.
Mechanopolymerchemie
Authors: Schulz‐Senft Mathias , Lipfert Matthias , Staubitz Anne
Published: April 2014

Chemischen Reaktionen kann auf verschiedenen Wegen Energie zugeführt werden, doch mechanische Energie blieb bisher ein Randphänomen. Ein selektiver Bindungsbruch in kleinen Molekülen benötigt große mechanische Kräfte, die sich nicht einfach auf einzelne Bindungen übertragen lassen. Da mechanische Arbeit das Produkt aus Kraft und Weg ist, ergeben sich für kurze Wege (im Bereich von Bindungslängen) große Kräfte für eine Bindungsspaltung. Makromoleküle sind jedoch länger und durch den größeren Weg sind die benötigten Kräfte für eine Bindungsspaltung geringer. Es wurden Bindungsspaltungen, Cycloreversionen und Isomerisierungen unter Einfluss mechanischer Energie beobachtet. Weiterhin kann mechanische Energie auch andere Reaktionsmechanismen hervorrufen als thermische oder Photoenergie. Praktische Anwendungen in diesem jungen Forschungsfeld entstehen noch und reichen derzeit von besserem Verständnis der Polymerzersetzung durch mechanische Kräfte zur Entwicklung von Dehnungssensoren mit mechanochromen Polymeren.
Cardiac Transplantation in African Americans: A Single‐Center Experience
Authors: Suryanarayana Prakash Goutham , Copeland Hannah , Friedman Mark , Copeland Jack G.
Published: April 2014

Background

In view of limited data on the subject of graft and patient survival differences between African American (AA) and non‐AA heart transplant recipients, we reviewed our experience.

Hypothesis

There is a higher mortality among AA recipients compared with non‐AA recipients after cardiac transplantation.

Methods

The study included all AA patients who have received a heart transplant in our center since 1983. Stepwise Cox regression was used for covariates affecting the survival. The χ2 test was employed to identify the effects of a mechanical assist device and pretransplant creatinine (Cr) on the outcomes in AA and non‐AA patients. Kaplan‐Meier curves were used to examine survival.

Results

The average survival among AA recipients was 5.4 years, compared with 12 years for the non‐AA recipients, with 1‐, 5‐, and 10‐year survival rates of 80%, 55%, and 25%, respectively. This was found to be statistically inferior to the survival probabilities of 92%, 78%, and 58% for the non‐AA group (P < 0.005). Based on stepwise Cox regression, the variables such as ethnicity (P < 0.05), pretransplant Cr (P < 0.05), presence of a mechanical assist device (P < 0.005), and United Network for Organ Sharing (UNOS) status at transplant (P < 0.05) independently predicted the outcomes. Kaplan‐Meier analysis of pretransplant Cr level and survival showed that the AA group did significantly worse for all Cr classes.

Conclusions

There is a statistically significant difference in outcomes between AA and non‐AA patients after cardiac transplantation. African American patients have decreased survival over a period of time. Pretransplant Cr, ethnicity, presence of a mechanical assist device, and UNOS status at transplantation are independent predictors of outcomes.
Discovery, Synthesis and Characterization of a Highly Muscarinic Acetylcholine Receptor (mAChR)‐Selective M5‐Orthosteric Antagonist, VU0488130 (ML381): A Novel Molecular Probe
Authors: Gentry Patrick R. , Kokubo Masaya , Bridges Thomas M. , Cho Hyekyung P. , Smith Emery , Chase Peter , Hodder Peter S. , Utley Thomas J. , Rajapakse Anuruddha , Byers Frank , Niswender Colleen M. , Morrison Ryan D. , Daniels J. Scott , Wood Michael R. , Conn P. Jeffrey , Lindsley Craig W.
Published: April 2014

Of the five G‐protein‐coupled muscarinic acetylcholine receptors (mAChRs; M1–M5), M5 is the least explored and understood due to a lack of mAChR subtype‐selective ligands. We recently performed a high‐throughput functional screen and identified a number of weak antagonist hits that are selective for the M5 receptor. Here, we report an iterative parallel synthesis and detailed molecular pharmacologic profiling effort that led to the discovery of the first highly selective, central nervous system (CNS)‐penetrant M5‐orthosteric antagonist, with sub‐micromolar potency (hM5 IC50=450 nM, hM5 Ki=340 nM, M1–M4 IC50 >30 μM), enantiospecific inhibition, and an acceptable drug metabolism and pharmacokinetics (DMPK) profile for in vitro and electrophysiology studies. This compound will be a powerful tool and molecular probe for the further investigation into the role of M5 in addiction and other diseases.
Well‐posedness of Compressible Euler Equations in a Physical Vacuum
Authors: Jang Juhi , Masmoudi Nader
Published: April 2014

An important problem in gas and fluid dynamics is to understand the behavior of vacuum states, namely the behavior of the system in the presence of a vacuum. In particular, physical vacuum, in which the boundary moves with a nontrivial finite normal acceleration, naturally arises in the study of the motion of gaseous stars or shallow water. Despite its importance, there are only a few mathematical results available near a vacuum. The main difficulty lies in the fact that the physical systems become degenerate along the vacuum boundary. In this paper, we establish the local‐in‐time well‐posedness of three‐dimensional compressible Euler equations for polytropic gases with a physical vacuum by considering the problem as a free boundary problem. © 2015 Wiley Periodicals, Inc.
Atomic and Electronic Structures of Interfaces in Dye‐Sensitized, Nanostructured Solar Cells
Authors: Johansson Erik M. J. , Lindblad Rebecka , Siegbahn Hans , Hagfeldt Anders , Rensmo Håkan
Published: April 2014

Key processes in nanostructured dye‐sensitized solar cells occur at material interfaces containing, for example, oxides, dye molecules, and hole conductors. A detailed understanding of interfacial properties is therefore important for new developments and device optimization. The implementation of X‐ray‐based spectroscopic methods for atomic‐level understanding of such properties is reviewed. Specifically, the use of the chemical and element sensitivity of photoelectron spectroscopy, hard X‐ray photoelectron spectroscopy, and resonant photoelectron spectroscopy for investigating interfacial molecular and electronic properties are described; examples include energy matching, binding configurations, and molecular orbital composition. Finally, results from the complete oxide/dye/hole‐conductor systems are shown and demonstrate how the assembly itself can affect the molecular and electronic structure of the materials.
Silica Mineralization by a Peptide Template Having a High Charge Relay Effect
Authors: Murai Kazuki , Higuchi Masahiro , Kuno Tatsuya , Kato Katsuya
Published: April 2014

The influence of the charge relay effects of peptide organic templates on silica mineralization has been investigated. β‐Sheet‐type peptide showed higher catalytic activity towards the condensation of trimethylsilanol than random‐coil peptides. The higher activity of the β‐sheet peptide was attributed to an effective charge relay effect between the His and Glu residues of the β‐sheet assembly. Furthermore, the silica mineralized on the VHVEVS peptide template formed a flat surface, which was affected by the peptide morphology. This result implied that the growth of the silica occurred at the surface of the peptide template in a manner very similar to that of the enzyme reaction. Thus, by using a specific structural design strategy, this process could be used for the preparation of specific silica particles.
Lignol Cleavage by Pd/C Under Mild Conditions and Without Hydrogen: A Role for Benzylic CH Activation?
Authors: Zhou Xiaoyuan , Mitra Joyee , Rauchfuss Thomas B.
Published: April 2014

The cleavage of CO bonds in lignin model compounds without hydrogen was developed using the commercially available Pd/C. Hydrogen donor solvents are helpful for this reaction through transfer hydrogenation, but not necessary. A redox neutral process that utilizes the internal hydrogen source for the cleavage is also possible. An initial mechanistic study indicates that the β‐benzylic‐H atom in the substrate plays a critical role and that the present system undergoes a process different from previous reports.
Ionic Liquid Promoted Synthesis of Conjugated Carbon Nitride Photocatalysts from Urea
Authors: Lin Zhenzhen , Wang Xinchen
Published: April 2014

To allow for simultaneous textural engineering and doping of carbon nitride materials with heteroatoms, urea has been polymerized with an ionic liquid. The role of urea is to create a delamination effect during carbon nitride synthesis, whereas ionic liquid functions as texture modifier as well as B/F dopant source. This will result in the rational fabrication of boron‐ and fluorine‐containing 2D carbon nitride nanosheets with enhanced optical harvesting and charge separation capabilities for hydrogen evolution catalysis using visible light. We believe that the innovative modification strategy developed herein can be coupled with the already known modification tools of 2D carbon nitride, thus further developing a new family of light‐harvesting 2D platforms for the efficient and sustained utilization of solar radiation for a variety of advanced applications, including CO2 photofixation, organic photosynthesis, and pollutant controls.
The frequency of herpes simplex virus changes in anal Pap smear and its association with squamous intraepithelial lesions in high‐risk male patients
Authors: Greebon Leslie J. , Avery Diane L. , Prihoda Thomas J. , Valente Philip T. , Policarpio‐Nicolas Maria Luisa C.
Published: April 2014

While there are studies postulating a model of synergism between human papillomavirus (HPV) and herpes simplex virus (HSV) in cervical carcinogenesis, the frequency of anal herpes as well as its association with anal squamous intraepithelial lesions (ASILs) has been understudied in men. This study evaluates the frequency of HSV changes in anal Pap smears and its association with ASILs in a high‐risk population. A computerized search for specimens associated with anal cytology that had positive findings of HSV was performed. The electronic medical records were examined for past diagnosis of herpes, HSV serology prior to or after cytology, and if the patient received treatment after cytologic diagnosis of HSV. Of the 470 anal Pap smears (Thin‐prep) examined, seven had cellular changes consistent with HSV infection. All patients were asymptomatic human immunodeficiency virus (HIV) positive males with no prior HSV serology tests. Two patients had prior diagnoses of HSV infection. Cytologic abnormalities were identified in 86% ranging from atypical squamous cells of undetermined significance to high grade squamous intraepithelial lesion. Three patients were treated after the HSV cytologic diagnosis. The frequency of HSV changes in anal Pap smear is low (1.48%), but the presence of concomitant cytologic abnormalities is high (86%). While our findings suggest the possible role of HSV as a HPV co‐factor in ASILs, larger studies are needed to support this. Identification of HSV infection on anal Pap smear is important for institution of patient treatment and subsequent reduction of transmission. Diagn. Cytopathol. 2014;42:487–490. © 2013 Wiley Periodicals, Inc.