bluuebunny/crossref_metadata_2025 huggingface dataset:
Multiparameter Particle Display (MPPD): A Quantitative Screening Method for the Discovery of Highly Specific Aptamers
Authors: Wang Jinpeng , Yu Jingwen , Yang Qin , McDermott John , Scott Alexander , Vukovich Matthew , Lagrois Remy , Gong Qiang , Greenleaf William , Eisenstein Michael , Ferguson B. Scott , Soh H. Tom
Published: December 2016

Aptamers are a promising class of affinity reagents because they are chemically synthesized, thus making them highly reproducible and distributable as sequence information rather than a physical entity. Although many high‐quality aptamers have been previously reported, it is difficult to routinely generate aptamers that possess both high affinity and specificity. One of the reasons is that conventional aptamer selection can only be performed either for affinity (positive selection) or for specificity (negative selection), but not both simultaneously. In this work, we harness the capacity of fluorescence activated cell sorting (FACS) for multicolor sorting to simultaneously screen for affinity and specificity at a throughput of 107 aptamers per hour. As a proof of principle, we generated DNA aptamers that exhibit picomolar to low nanomolar affinity in human serum for three diverse proteins, and show that these aptamers are capable of outperforming high‐quality monoclonal antibodies in a standard ELISA detection assay.
Hybrid Polymer/Garnet Electrolyte with a Small Interfacial Resistance for Lithium‐Ion Batteries
Authors: Li Yutao , Xu Biyi , Xu Henghui , Duan Huanan , Lü Xujie , Xin Sen , Zhou Weidong , Xue Leigang , Fu Gengtao , Manthiram Arumugam , Goodenough John B.
Published: December 2016

Li7La3Zr2O12‐based Li‐rich garnets react with water and carbon dioxide in air to form a Li‐ion insulating Li2CO3 layer on the surface of the garnet particles, which results in a large interfacial resistance for Li‐ion transfer. Here, we introduce LiF to garnet Li6.5La3Zr1.5Ta0.5O12 (LLZT) to increase the stability of the garnet electrolyte against moist air; the garnet LLZT‐2 wt % LiF (LLZT‐2LiF) has less Li2CO3 on the surface and shows a small interfacial resistance with Li metal, a solid polymer electrolyte, and organic‐liquid electrolytes. An all‐solid‐state Li/polymer/LLZT‐2LiF/LiFePO4 battery has a high Coulombic efficiency and long cycle life; a Li‐S cell with the LLZT‐2LiF electrolyte as a separator, which blocks the polysulfide transport towards the Li‐metal, also has high Coulombic efficiency and kept 93 % of its capacity after 100 cycles.
Copper(II)–Thymine Coordination Polymer Nanoribbons as Potential Oligonucleotide Nanocarriers
Authors: Vegas Verónica G. , Lorca Romina , Latorre Ana , Hassanein Khaled , Gómez‐García Carlos J. , Castillo Oscar , Somoza Álvaro , Zamora Félix , Amo‐Ochoa Pilar
Published: December 2016

The direct reaction between copper nitrate, thymine‐1‐acetic acid, and 4,4′‐bipyridine in water leads to the formation of a blue colloid comprising uniform crystalline nanoribbons (length >1 μm; width ca. 150–185 nm; diameter ca. 15–60 nm) of a coordination polymer. The polymer displays a thymine‐based structure freely available for supramolecular interactions. These nanostructures show significant selective interaction with single‐stranded oligonucleotides based on adenine. Remarkably, they present low cell toxicity in three cell lines–despite the copper(II) content–and can be used as nanocarriers of oligonucleotides. These results suggest the potential of these types of nanostructures in several biological applications.
Efficient Synthesis of Trifluoromethyl Amines through a Formal Umpolung Strategy from the Bench‐Stable Precursor (Me4N)SCF3
Authors: Scattolin Thomas , Deckers Kristina , Schoenebeck Franziska
Published: December 2016

Reported herein is the one‐pot synthesis of trifluoromethylated amines at room temperature using the bench‐stable (Me4N)SCF3 reagent and AgF. The method is rapid, operationally simple and highly selective. It proceeds via a formal umpolung reaction of the SCF3 with the amine, giving quantitative formation of thiocarbamoyl fluoride intermediates within minutes that can readily be transformed to N‐CF3. The mildness and high functional group tolerance render the method highly attractive for the late‐stage introduction of trifluoromethyl groups on amines, as demonstrated herein for a range of pharmaceutically relevant drug molecules.
Confinement Alters the Structure and Function of Calmodulin
Authors: Xu Guohua , Cheng Kai , Wu Qiong , Liu Maili , Li Conggang
Published: December 2016

Many cellular reactions involving proteins, including their biosynthesis, misfolding, and transport, occur in confined compartments. Despite its importance, a structural basis of understanding of how confined environments alter protein function is still lacking. Herein, we explore structure–function correlations of calmodulin (CaM), a multidomain protein involved in many calcium‐mediated signaling pathways, in reverse micelles. Confinement dramatically alters CaM structure and function. The protein forms an extended structure in bulk water, but becomes compacted in reverse micelles. In addition, confinement changes the function of CaM. Specifically, the protein binds the MLCK, AcN19, and somatostatin peptides in dilute buffer, but binds only the MLCK and AcN19 peptides in reverse micelles. In summary, we determined a new CaM structure in reverse micelles and demonstrate that confinement can modulate both protein structure and function.
Synthese meta‐funktionalisierter Pyridine über selektive dehydrierende Heterokondensation von β‐ und γ‐Aminoalkoholen
Authors: Hille Toni , Irrgang Torsten , Kempe Rhett
Published: December 2016

Neue Reaktionen, in denen Alkohole in bedeutende Verbindungsklassen umgewandelt werden, gewinnen zunehmend an Bedeutung, da ihre Entwicklung zur Erhaltung unseres fossilen Kohlenstoffmaterials und zur Reduzierung der CO2‐Emissionen beiträgt. Zwei Schlüsselkonzepte für die katalytische Alkoholkonvertierung sind das Borrowing‐Hydrogen‐ oder Hydrogen‐Autotransfer‐Konzept und das Konzept der akzeptorlosen dehydrierenden Kondensation. Hier werden beide Konzepte zur Synthese von meta‐funktionalisierten Pyridinen kombiniert. Zuerst werden Diole und Amine zu β‐Aminoalkoholen verknüpft, die danach mit γ‐Aminoalkoholen eine selektive dehydrierende Heterokondensation durchlaufen können. PN5P‐Pinzettenligand‐stabilisierte Ir‐Katalysatoren vermitteln die Reaktionen am effizientesten. Alle hier beschriebenen Beispiele von 3‐Aminopyridinen wurden erstmals synthetisiert, was den Innovationsgrad der Methode und die Probleme bei der Synthese derartiger meta‐funktionalisierter Pyridine betont.
Dehydrogenation of the NH−NH Bond Triggered by Potassium tert‐Butoxide in Liquid Ammonia
Authors: Wang Lei , Ishida Akiko , Hashidoko Yasuyuki , Hashimoto Makoto
Published: December 2016

A novel strategy for the dehydrogenation of the NH−NH bond is disclosed using potassium tert‐butoxide (tBuOK) in liquid ammonia (NH3) under air at room temperature. Its synthetic value is well demonstrated by the highly efficient synthesis of aromatic azo compounds (up to 100 % yield, 3 min), heterocyclic azo compounds, and dehydrazination of phenylhydrazine. The broad application of this strategy and its benefit to chemical biology is proved by a novel, convenient, one‐pot synthesis of aliphatic diazirines, which are important photoreactive agents for photoaffinity labeling.
Synthesis, Characterization, and Computational Analysis of the Dialanate Dianion, [H3Al‐AlH3]2−: A Valence Isoelectronic Analogue of Ethane
Authors: Bonyhady Simon J. , Holzmann Nicole , Frenking Gernot , Stasch Andreas , Jones Cameron
Published: December 2016

The first example of a well‐defined binary, low‐oxidation‐state aluminum hydride species that is stable at ambient temperature, namely the dianion in [{(DepNacnac)Mg}2(μ‐H)]2[H3Al‐AlH3] (DepNacnac=[(DepNCMe)2CH]−, Dep=2,6‐diethylphenyl), has been prepared via a magnesium(I) reduction of the alanate complex, (DepNacnac)Mg(μ‐H)3AlH(NEt3). An X‐ray crystallographic analysis has shown the compound to be a contact ion complex, which computational studies have revealed to be the source of the stability of the aluminum(II) dianion.
Amidinyl Radical Formation through Anodic N−H Bond Cleavage and Its Application in Aromatic C−H Bond Functionalization
Authors: Zhao Huai‐Bo , Hou Zhong‐Wei , Liu Zhan‐Jiang , Zhou Ze‐Feng , Song Jinshuai , Xu Hai‐Chao
Published: December 2016

We report herein an atom‐economical and sustainable approach to access amidinyl radical intermediates through the anodic cleavage of N−H bonds. The resulting nitrogen‐centered radicals undergo cyclizations with (hetero)arenes, followed by rearomatization, to afford functionalized tetracyclic benzimidazoles in a highly straightforward and efficient manner. This metal‐ and reagent‐free C−H/N−H cross‐coupling reaction exhibits a broad substrate scope and proceeds with high chemoselectivity.
A Unique Blend of 2‐Fluorenyl‐2‐anthracene and 2‐Anthryl‐2‐anthracence Showing White Emission and High Charge Mobility
Authors: Chen Mengyun , Zhao Yang , Yan Lijia , Yang Shuai , Zhu Yanan , Murtaza Imran , He Gufeng , Meng Hong , Huang Wei
Published: December 2016

White‐light‐emitting materials with high mobility are necessary for organic white‐light‐emitting transistors, which can be used for self‐driven OLED displays or OLED lighting. In this study, we combined two materials with similar structures—2‐fluorenyl‐2‐anthracene (FlAnt) with blue emission and 2‐anthryl‐2‐anthracence (2A) with greenish‐yellow emission—to fabricate OLED devices, which showed unusual solid‐state white‐light emission with the CIE coordinates (0.33, 0.34) at 10 V. The similar crystal structures ensured that the OTFTs based on mixed FlAnt and 2A showed high mobility of 1.56 cm2 V−1 s−1. This simple method provides new insight into the design of high‐performance white‐emitting transistor materials and structures.
Development of Chemical Tools to Monitor and Control Isoaspartyl Peptide Methyltransferase Activity
Authors: Kimura Yusuke , Komatsu Toru , Yanagi Kouichi , Hanaoka Kenjiro , Ueno Tasuku , Terai Takuya , Kojima Hirotatsu , Okabe Takayoshi , Nagano Tetsuo , Urano Yasuteru
Published: December 2016

We have established a coupled assay system targeting protein l‐isoaspartyl methyltransferase (PIMT), a key enzyme in the metabolism of isoaspartyl peptides and proteins. The system utilizes a fluorogenic peptide probe containing an isoaspartyl residue at the P1′ position of the caspase‐3 recognition sequence. Following PIMT‐catalyzed methyl transfer reaction, the methylated probe is specifically cleaved by caspase‐3 to give fluorescence activation. High‐throughput screening of our chemical library with this assay system identified PIMT inhibitors that may be useful as leads in the design of chemical probes for controlling PIMT activity.
Synthesis of meta‐Functionalized Pyridines by Selective Dehydrogenative Heterocondensation of β‐ and γ‐Amino Alcohols
Authors: Hille Toni , Irrgang Torsten , Kempe Rhett
Published: December 2016

New reactions that convert alcohols into important classes of compounds are becoming increasingly important as their development contributes to the conservation of our fossil carbon feedstock and the reduction of CO2 emissions. Two key catalytic alcohol conversion concepts are borrowing hydrogen or hydrogen autotransfer and acceptorless dehydrogenative condensation. Herein, we combined both concepts to synthesize meta‐functionalized pyridines. First, diols and amines were linked to β‐amino alcohols, which can then undergo a selective dehydrogenative heterocondensation with γ‐amino alcohols. Iridium catalysts stabilized by PN5P pincer ligands that were developed in our laboratory mediate the reactions most efficiently. All of the 3‐aminopyridines that we describe in this paper have been synthesized for the first time, emphasizing the degree of innovation of this method and the problems associated with the synthesis of such meta‐functionalized pyridines.
Room‐Temperature Arylation of Thiols: Breakthrough with Aryl Chlorides
Authors: Jiang Min , Li Haifang , Yang Haijun , Fu Hua
Published: December 2016

The formation of aryl C−S bonds is an important chemical transformation because aryl sulfides are valuable building blocks for the synthesis of biologically and pharmaceutically active molecules and organic materials. Aryl sulfides have traditionally been synthesized through the transition‐metal‐catalyzed cross‐coupling of aryl halides with thiols. However, the aryl halides used are usually bromides and iodides; readily available, low‐cost aryl chlorides often not reactive enough. Furthermore, the deactivation of transition‐metal catalysts by thiols has forced chemists to use high catalyst loadings, specially designed ligands, high temperatures, and/or strong bases, thus leading to high costs and the incompatibility of some functional groups. Herein, we describe a simple and efficient visible‐light photoredox arylation of thiols with aryl halides at room temperature. More importantly, various aryl chlorides are also effective arylation reagents under the present conditions.
Pedestrian crowd tactical‐level decision making during emergency evacuations
Authors: Haghani Milad , Sarvi Majid
Published: December 2016

This paper investigates pedestrian crowd tactical‐level decision making during emergency evacuations. Of particular interest is crowd exit‐choice behaviour. Two sources of stated choice data are collected and combined. One data set is derived from an experiment linked to a real‐life exit choice experience of participants (in a non‐evacuation setting). We examine aspects that have often been taken for granted in the literature in connection with egress behaviour of crowds during emergencies. We quantify evacuees' trade‐off between “distance”, “density”, “exit visibility” and “directional density” as well as the interactive effect between exit visibility and tendency to follow others. A comprehensive random‐utility analysis is conducted ranging from traditionally practiced models to the state‐of‐the‐practice methods such as random‐coefficient nested logit. Our findings suggest that (i) unless evacuees face certain levels of uncertainty in the escape environment; flows of crowd are unlikely to be followed. Otherwise, most evacuees perceive other individuals as potential sources of congestion and extra delay (generalisation to situations where crowd is completely unfamiliar with the egress geometry, however, may require careful scrutiny). (ii) Evacuees mostly prefer visible exits over the exits whose congestion level is unknown to them (i.e. the tendency to minimise ambiguity). (iii) The presence of attribute uncertainty (e.g. exit visibility) significantly changes the impact of observing decisions of others on each individual choice maker. We also found out that (iv) spatial distribution of exits has a significant influence on evacuees' decisions (presenting itself in the form of violating the IIA assumption). (v) The marginal weights that different individuals place upon attributes of exits are significantly heterogeneous. (vi) There is meaningful correlation between certain utility weights of individual evacuees. These behavioural findings can provide significant behavioural insight essential for safe evacuation planning and accurate forecast of evacuees' behaviour. Copyright © 2016 John Wiley & Sons, Ltd.
Shared molecular networks in orofacial and neural tube development
Authors: Kousa Youssef A. , Mansour Tamer A. , Seada Haitham , Matoo Samaneh , Schutte Brian C.
Published: December 2016

Background

Single genetic variants can affect multiple tissues during development. Thus it is possible that disruption of shared gene regulatory networks might underlie syndromic presentations. In this study, we explore this idea through examination of two critical developmental programs that control orofacial and neural tube development and identify shared regulatory factors and networks. Identification of these networks has the potential to yield additional candidate genes for poorly understood developmental disorders and assist in modeling and perhaps managing risk factors to prevent morbidly and mortality.

Methods

We reviewed the literature to identify genes common between orofacial and neural tube defects and development. We then conducted a bioinformatic analysis to identify shared molecular targets and pathways in the development of these tissues. Finally, we examine publicly available RNA‐Seq data to identify which of these genes are expressed in both tissues during development.

Results

We identify common regulatory factors in orofacial and neural tube development. Pathway enrichment analysis shows that folate, cancer and hedgehog signaling pathways are shared in neural tube and orofacial development. Developing neural tissues differentially express mouse exencephaly and cleft palate genes, whereas developing orofacial tissues were enriched for both clefting and neural tube defect genes.

Conclusion

These data suggest that key developmental factors and pathways are shared between orofacial and neural tube defects. We conclude that it might be most beneficial to focus on common regulatory factors and pathways to better understand pathology and develop preventative measures for these birth defects. Birth Defects Research 109:169–179, 2017. © 2016 Wiley Periodicals, Inc.
The Value Relevance of Environmental Audits: Evidence from Japan
Authors: Lee Ki‐Hoon , Park Bum‐Jin , Song Hakjoon , Yook Keun‐Hyo
Published: December 2016

Environmental audits are implemented internally in order to monitor compliance with environmental laws, regulations and related accounting rules, and to develop recommendations for ways in which to improve environmental accounting processes and performance. In addition, external third‐party assurance on environmental information is used to verify whether firms’ disclosures on environmental information are in compliance with environmental accounting rules and regulations. We examine whether firms’ environmental audits positively affect their market values and whether third‐party assurance strengthens positive effects, using value relevance theory as a theoretical foundation. Our main tests are based on 266 Japanese manufacturing firms’ published environmental reports for the period 2010–2013. We find that the average market value of firms that implement environmental audits is 9 percent greater than those that do not. Further, we find that environmental audits positively affect firm value, largely through interaction with third‐party assurance. Copyright © 2016 John Wiley & Sons, Ltd and ERP Environment
Different Enzymatic Processing of γ‐Phosphoramidate and γ‐Phosphoester‐Modified ATP Analogues
Authors: Ermert Susanne , Hacker Stephan M. , Buntru Alexander , Scheffner Martin , Hauck Christof R. , Marx Andreas
Published: December 2016

Monitoring the activity of ATP‐consuming enzymes provides the basis for elucidating their modes of action and regulation. Although a number of ATP analogues have been developed for this, their scope is restricted because of the limited acceptance by respective enzymes. In order to clarify which kind of phosphate‐modified ATP analogues are accepted by the α‐β‐phosphoanhydride‐cleaving ubiquitin‐activating enzyme 1 (UBA1) and the β‐γ‐phosphoanhydride‐cleaving focal adhesion kinase (FAK), we tested phosphoramidate‐ and phosphoester‐modified ATP analogues. UBA1 and FAK were able to convert phosphoramidate‐modified ATP analogues, even with a bulky modification like biotin. In contrast, a phosphoester‐modified analogue was poorly accepted. These results demonstrate that minor variations in the design of ATP analogues for monitoring ATP utilization have a significant impact on enzymatic acceptance.
Nuclear co‐repressor (NCoR) is required to maintain insulin sensitivity in C2C12 myotubes
Authors: Choudhary Abhijeet K. , Dey Chinmoy S.
Published: December 2016

Nuclear co‐repressor (NCoR) regulates peripheral insulin sensitivity; however, its role in modulating insulin sensitivity in skeletal muscle remains elusive. Present study investigated protein expression and effect of NCoR on insulin sensitivity in murine skeletal muscle cell line C2C12. Myotubes as compared to myoblasts of C2C12 cells were found to be more sensitive in response to insulin as increase in insulin‐stimulated phosphorylation of AKT at serine 473 residue (pAKTS473) was significantly higher in myotubes. Incidentally, reduced protein level of NCoR coincided with differentiation of myoblasts into myotubes of C2C12 cells. However, insulin stimulation per se failed to affect protein level of NCoR either in myoblasts or myotubes of C2C12 cells. To assess the role of NCoR on insulin sensitivity, NCoR was transiently knocked down using siRNA in myotubes of C2C12. In fact, transient silencing of NCoR led to significant reduction in insulin‐stimulated pAKTS473 and impaired glucose uptake. This observation is in contrast to published studies where NCoR has been reported to negatively regulate insulin signaling cascade. Furthermore, transient silencing of NCoR failed to improve insulin sensitivity in chronic hyperinsulinemia‐induced insulin‐resistant model of C2C12 cells. Importantly, inhibition of lysosomal protein degradation pathway using ammonium chloride restored protein level of NCoR but failed to increase glucose uptake in serum‐starved C2C12 myotubes. Collectively, data from present study show differential protein level of NCoR under different cell state (myoblast and myotubes) of C2C12 cells and NCoR proves to be vital for maintaining insulin sensitivity in C2C12 myotubes.
Effect of Shear Rate Distribution on Particle Aggregation in a Stirred Vessel
Authors: Masuda Hayato , Tsuda Kazuto , Matsui Keisuke , Komoda Yoshiyuki , Ohmura Naoto
Published: December 2016

The modeling of particle aggregation under a simple shear flow and the extension of the model to a stirred vessel is described. The model quantitatively demonstrates the change of the number of aggregates with time for each shear rate. This number increased with higher shear rate and, conversely, the aggregate size became small when raising the shear rate. This was because aggregates were broken by the stronger shear force. The number of aggregates for different impellers was determined. The shear rate was back‐calculated from the experimentally obtained aggregate size and the model equation. This shear rate was different from that estimated from the Metzner‐Otto method, consequently, some revisions of the Metzner‐Otto equation might be necessary for its application to particle aggregation.
Mediated Catalytic Voltammetry of Holo and Heme‐Free Human Sulfite Oxidases
Authors: Kalimuthu Palraj , Belaidi Abdel A. , Schwarz Guenter , Bernhardt Paul V.
Published: December 2016

Herein, we report the electrocatalytic voltammetry of holo and heme‐free human sulfite oxidase (HSO) mediated by the synthetic iron complexes 1,2‐bis(1,4,7‐triaza‐1‐cyclononyl)ethane iron(III) bromide, ([Fe(dtne)]Br3.3H2O), potassium ferricyanide (K3[Fe(CN)6]), and ferrocene methanol (FM) at a 5‐(4′‐pyridinyl)‐1,3,4‐oxadiazole‐2‐thiol (Hpyt) modified gold working electrode. Holo HSO contains two electroactive redox cofactors, comprising a mostly negatively charged cyt b5 (heme) domain and a Mo cofactor (Moco) domain (the site of sulfite oxidation), where the surface near the active site is positively charged. We anticipated different catalytic voltammetry based on either repulsive or attractive electrostatic interactions between the holo or heme‐free enzymes and the positively or negatively charged redox mediators. Both holo and heme‐free HSO experimental catalytic voltammetry has been modeled by using electrochemical simulation across a range of sweep rates and concentrations of substrate and both positive and negatively charged electron acceptors ([Fe(dtne)]3+, [Fe(CN)6]3− and FM+), which provides new insights into the kinetics of the HSO catalytic mechanism. These mediator complexes have almost the same redox potential (all lying in the range +415 to +430 mV vs. NHE) and, thus, deliver the same driving force for electron transfer with the Mo cofactor. However, differences in the electrostatic affinities between HSO and the mediator have a significant influence on the electrocatalytic response.
MoS2/Carbon Nanotube Core–Shell Nanocomposites for Enhanced Nonlinear Optical Performance
Authors: Zhang Xiaoyan , Selkirk Andrew , Zhang Saifeng , Huang Jiawei , Li Yuanxin , Xie Yafeng , Dong Ningning , Cui Yun , Zhang Long , Blau Werner J. , Wang Jun
Published: December 2016

Nanocomposites of layered MoS2 and multi‐walled carbon nanotubes (CNTs) with core–shell structure were prepared by a simple solvothermal method. The formation of MoS2 nanosheets on the surface of coaxial CNTs has been confirmed by scanning electron microscopy, transmission electron microscopy, absorption spectrum, Raman spectroscopy, and X‐ray photoelectron spectroscopy. Enhanced third‐order nonlinear optical performances were observed for both femtosecond and nanosecond laser pulses over a broad wavelength range from the visible to the near infrared, compared to those of MoS2 and CNTs alone. The enhancement can be ascribed to the strong coupling effect and the photoinduced charge transfer between MoS2 and CNTs. This work affords an efficient way to fabricate novel CNTs based nanocomposites for enhanced nonlinear light–matter interaction. The versatile nonlinear properties imply a huge potential of the nanocomposites in the development of nanophotonic devices, such as mode‐lockers, optical limiters, or optical switches.
Chemically Reduced Graphene Oxide for the Assessment of Food Quality: How the Electrochemical Platform Should Be Tailored to the Application
Authors: Chng Chu'Er , Ambrosi Adriano , Chua Chun Kiang , Pumera Martin , Bonanni Alessandra
Published: December 2016

Graphene platforms have been drawing considerable attention in electrochemistry for the detection of various electroactive probes. Depending on the chemical composition and properties of the probe, graphene materials with diverse structural features may be required to achieve an optimal electrochemical performance. This work comprises a comparative study on three chemically modified graphenes, obtained from the same starting material and with different oxygen functionalities and structural defects (graphene oxide (GO), chemically reduced graphene oxide (CRGO), and thermally reduced graphene oxide (TRGO)) towards the electrochemical detection of quinine, an important flavoring agent present in tonic‐based beverages. In general, the reduced graphenes, namely CRGO and TRGO, showed enhanced performance in terms of calibration sensitivity and selectivity, due to the improved heterogeneous electron‐transfer rates on their surfaces. In particular, CRGO provided the best overall electrochemical performance, which can be attributed to its higher density of structural defects and reduced amount of oxygen functionalities. For this reason, CRGO was employed for the electrochemical detection of quinine in commercial tonic drink samples, showing high sensitivity and selectivity, and therefore representing a valid low‐cost alternative to more complicated and time consuming traditional analytical methods.
A Bio‐Chemosynthetic Approach to Superparamagnetic Iron Oxide–Ansamitocin Conjugates for Use in Magnetic Drug Targeting
Authors: Wang Liang‐Liang , Balakrishnan Asha , Bigall Nadja‐Carola , Candito David , Miethe Jan Frederick , Seidel Katja , Xie Yu , Ott Michael , Kirschning Andreas
Published: December 2016

A combination of mutasynthesis using a mutant strain of A. pretiosum blocked in the biosynthesis of amino‐hydroxybenzoic acid (AHBA) and semisynthesis relying on a Stille cross‐coupling step provided access to new ansamitocin derivatives of which one was attached by a thermolabile linker to nanostructured iron oxide particles. When exposed to an oscillating electromagnetic field the resulting iron oxide/ansamitocin conjugate 19 heats up in an aqueous suspension and the ansamitocin derivative 16 is released by means of a retro‐Diels–Alder reaction. It exerts strong antiproliferative activity (IC50=4.8 ng mg−1) in mouse fibroblasts. These new types of conjugates have the potential for combating cancer through hyperthermia and chemotherapy using an electromagnetic external trigger.
Computational Prediction and Rationalization, and Experimental Validation of Handedness Induction in Helical Aromatic Oligoamide Foldamers
Authors: Liu Zhiwei , Hu Xiaobo , Abramyan Ara M. , Mészáros Ádám , Csékei Márton , Kotschy András , Huc Ivan , Pophristic Vojislava
Published: December 2016

Metadynamics simulations were used to describe the conformational energy landscapes of several helically folded aromatic quinoline carboxamide oligomers bearing a single chiral group at either the C or N terminus. The calculations allowed the prediction of whether a helix handedness bias occurs under the influence of the chiral group and gave insight into the interactions (sterics, electrostatics, hydrogen bonds) responsible for a particular helix sense preference. In the case of camphanyl‐based and morpholine‐based chiral groups, experimental data confirming the validity of the calculations were already available. New chiral groups with a proline residue were also investigated and were predicted to induce handedness. This prediction was verified experimentally through the synthesis of proline‐containing monomers, their incorporation into an oligoamide sequence by solid phase synthesis and the investigation of handedness induction by NMR spectroscopy and circular dichroism.
The Assembly of an All‐Inorganic Porous Soft Framework from Metal Oxide Molecular Nanowires
Authors: Zhang Zhenxin , Sadakane Masahiro , Noro Shin‐ichiro , Hiyoshi Norihito , Yoshida Akihiro , Hara Michikazu , Ueda Wataru
Published: December 2016

An all‐inorganic soft framework is rare but interesting for both fundamental research and practical applications. Here, an all‐inorganic soft framework based on a transition metal oxide is reported. The periodic connection of a one‐dimensional anionic tungstoselenate molecular wire building block with a CoII ion is used to construct the crystalline material. The crystal structure of the material was determined by high‐angle annular dark‐field scanning transmission electron microscopy combined with several characterization techniques. The soft framework of the material enables water adsorption/desorption with a change in its structure, leading to a high level of water adsorption. The framework of the material is flexible, and the structure of the molecular wire building block is stable during the water adsorption/desorption process.
Three‐Dimensional Metal–Organic Framework as Super Heat‐Resistant Explosive: Potassium 4‐(5‐Amino‐3‐Nitro‐1H‐1,2,4‐Triazol‐1‐Yl)‐3,5‐Dinitropyrazole
Authors: Li Chuan , Zhang Man , Chen Qishan , Li Yingying , Gao Huiqi , Fu Wei , Zhou Zhiming
Published: December 2016

A new super heat‐resistant explosive, potassium 4‐(5‐amino‐3‐nitro‐1H‐1,2,4‐triazol‐1‐yl)‐3,5‐dinitropyrazole (KCPT, 1), featuring a three‐dimensional (3D) energetic metal–organic framework (MOF) was synthesized and fully characterized. The new 3D MOF was found to be extremely heat‐resistant, having a high decomposition temperature of 323 °C. In addition, KCPT exhibits the best calculated detonation performance (vD=8457 m s−1, p=32.5 GPa) among the reported super heat‐resistant explosives or energetic potassium salts while retaining a suitable impact sensitivity of 7.5 J, which makes it one of the most promising heat‐resistant explosives.
Gold(I) Fluorohalides: Theory and Experiment
Authors: Baya Miguel , Pérez‐Bitrián Alberto , Martínez‐Salvador Sonia , Casas José M. , Menjón Babil , Orduna Jesús
Published: December 2016

The anionic trifluoromethylgold(I) derivatives [CF3AuX]−, which have been prepared and isolated as their [PPh4]+ salts in good yield, undergo thermally induced difluorocarbene extrusion in the gas phase, giving rise to the mixed gold(I) fluorohalide complexes [F−Au−X]− (X=Cl, Br, I). These triatomic species have been detected by tandem mass spectrometry (MS2) experiments and their properties have been analyzed by DFT methods. The CF2 extrusion mechanism from the Au−CF3 moiety serves as a model for the CF2 insertion into the Au−F bond, since both reactivity channels are connected by the microreversibility principle.
Using chiral peptide substitutions to probe the structure function relationship of a key residue of Aβ42
Authors: Warner Christopher J.A. , Dutta Subrata , Foley Alejandro R. , Chen Eefei , Kliger David S. , Raskatov Jevgenij A.
Published: December 2016

Amyloid beta‐protein 42 plays an important role in the onset and progression of Alzheimer's disease. Familial mutations have identified the glutamate residue 22 as a hotspot with regard to peptide neurotoxicity. We introduce an approach to study the influence of systematic sidechain modification at this residue, employing chirality as a structural probe. Circular dichroism experiments reveal that charge‐preserving alterations of the amino acid sidechain attenuate the characteristic random coil to β‐sheet transition associated with the wildtype peptide. Removal of the negative charge from residue 22, a trait observed with all known familial mutations at this residue, gives rise to a peptide with limited random coil propensity and high β‐sheet characteristics. Our approach can be extended to other residues of Aβ, as well as further amyloidogenic peptides.
Modelling mitral valvular dynamics–current trend and future directions
Authors: Gao Hao , Qi Nan , Feng Liuyang , Ma Xingshuang , Danton Mark , Berry Colin , Luo Xiaoyu
Published: December 2016

Dysfunction of mitral valve causes morbidity and premature mortality and remains a leading medical problem worldwide. Computational modelling aims to understand the biomechanics of human mitral valve and could lead to the development of new treatment, prevention and diagnosis of mitral valve diseases. Compared with the aortic valve, the mitral valve has been much less studied owing to its highly complex structure and strong interaction with the blood flow and the ventricles. However, the interest in mitral valve modelling is growing, and the sophistication level is increasing with the advanced development of computational technology and imaging tools. This review summarises the state‐of‐the‐art modelling of the mitral valve, including static and dynamics models, models with fluid‐structure interaction, and models with the left ventricle interaction. Challenges and future directions are also discussed.
Supramolecular Nanofibers as Ambient Stable Wide Voltage Window Electrolyte for Micro‐Supercapacitors
Authors: Mogera Umesha , Gedda Murali , George Subi J. , Kulkarni Giridhar U.
Published: December 2016

In this paper, we explore the use of supramolecular nanofibers as an electrolyte for in‐plane micro‐supercapacitors. The supramolecular nanofibers obtained from the self‐assembly of donor–acceptor (D‐A) molecules, coronene tetracarboxylate salt (CS) and dodecyl methyl viologen (DMV), carrying positive and negative ionic charges, respectively, were drop‐coated onto metal gap electrodes using an aqueous dispersion to form the device. Under dry conditions (<35 % relative humidity, RH), the device exhibited a stack capacitance of 160 F cm−3 with energy and power densities comparable to high‐performance micro‐supercapacitors. Although the electrolyte has aqueous origin, in dry conditions, it is capable of operating in a voltage window of 0–3 V. This supramolecular micro‐supercapacitor device (micro‐SS) was fabricated only with metal electrodes without using electrode material in it, thanks to the ability of the nanofiber to provide extended surface area for charge storage. The 1D face‐to‐face arrangement of D‐A molecules seems to provide an efficient pathway for the diffusion of ions across the electrodes. The present study not only provides a new approach to obtain an ambient stable electrolyte with wide operating voltage window but also gives a low‐cost method of fabricating micro‐supercapacitors with reasonably high energy and power densities.
Multiconfigurational Effects in Theoretical Resonance Raman Spectra
Authors: Ma Yingjin , Knecht Stefan , Reiher Markus
Published: December 2016

We analyze resonance Raman spectra of the nucleobase uracil in the short‐time approximation calculated with multiconfigurational methods. We discuss the importance of static electron correlation by means of density‐matrix renormalization group self‐consistent field (DMRG‐SCF) calculations. Our DMRG‐SCF results reveal that a minimal active orbital space that leads to a qualitatively correct description of the resonance Raman spectrum of uracil should encompass parts of the σ/σ* bonding/anti‐bonding orbitals of the pyrimidine ring. We trace these findings back to the considerable entanglement between the σ/σ* bonding/anti‐bonding as well as valence π/π* orbitals in the excited‐state electronic structure of uracil, which indicates non‐negligible non‐dynamical correlation effects that are less pronounced in the electronic ground state.
Exploring Glucocorticoid Receptor Agonists Mechanism of Action Through Mass Cytometry and Radial Visualizations
Authors: Abraham Yann , Gerrits Bertran , Ludwig Marie‐Gabrielle , Rebhan Michael , Gubser Keller Caroline
Published: December 2016

Recent advances in combining flow cytometry and mass spectrometry have led to the development of mass cytometry, allowing for the interrogation of complex cell populations on an unprecedented scale. The volumes and high dimensionality of mass cytometry data pose significant challenges in terms of analysis and visualization. We implement a method called Radviz, where multidimensional single cell data can be visualized as a projection that maintains the original dimensions and data complexity whilst facilitating analysis and visualization. This enables identification of changes in populations, focusing the analysis on the most relevant aspect of large multidimensional datasets. To highlight the potential of Radviz, we profiled peripheral mononuclear blood cells (PBMCs) from three healthy donors and showed donor‐specific differences in the number and composition of cell populations. In a second study, we explored the anti‐inflammatory effects of two glucocorticoid receptor (GR) ligands (cpd6 and cpd11) compared to dexamethasone (Dex) on human primary macrophages. Standard analysis at the population level showed that cpd6 and cpd11 have an overall anti‐inflammatory profile similar to that of Dex. CyTOF profiling and Radviz‐driven analysis at the single cell level confirmed this observation, and identified a concentration‐dependent effect of cpd6 that was not detected at the population level. Altogether, Radviz combines the strengths of a projection method, reducing the dimensionality of datasets, with that of a scatter plot, where the identity of each point can be inferred from the distance to the axis. This enables the visual exploration, analysis, and interpretation of complex, high dimensional data. © 2016 International Clinical Cytometry Society
Mass Cytometry Analytical Approaches Reveal Cytokine‐Induced Changes in Natural Killer Cells
Authors: Vendrame Elena , Fukuyama Julia , Strauss‐Albee Dara M. , Holmes Susan , Blish Catherine A.
Published: December 2016

Background

Natural killer (NK) cells have antiviral and antitumor activity that could be harnessed for the treatment of infections and malignancies. To maintain cell viability and enhance antiviral and antitumor effects, NK cells are frequently treated with cytokines. Here they performed an extensive assessment of the effects of cytokines on the phenotype and function of human NK cells.

Methods

They used cytometry by time‐of‐flight (CyTOF) to evaluate NK cell repertoire changes after stimulation with interleukin (IL)‐2, IL‐15 or a combination of IL‐12/IL‐15/IL‐18. To analyze the high dimensional CyTOF data, they used several statistical and visualization tools, including viSNE (Visualization of t‐Distributed Stochastic Neighbor Embedding), Citrus (Cluster identification, characterization, and regression), correspondence analysis, and the Friedman–Rafsky test.

Results

All three treatments (IL‐2, IL‐15, and IL‐12/IL‐15/IL‐18) increase expression of CD56 and CD69. The effects of treatment with IL‐2 and IL‐15 are nearly indistinguishable and characterized principally by increased expression of surface markers including CD56, NKp30, NKp44, and increased expression of functional markers, such as perforin, granzyme B, and MIP‐1β. The combination of IL‐12/IL‐15/IL‐18 induces a profound shift in the repertoire structure, decreasing expression of CD16, CD57, CD8, NKp30, NKp46, and NKG2D, and dramatically increasing expression of IFN‐γ.

Conclusions

CyTOF provides insights into the effects of cytokines on the phenotype and function of NK cells, which could inform future research efforts and approaches to NK cell immunotherapy. There are several analytical approaches to CyTOF data, and the appropriate method should be carefully selected based on which aspect of the dataset is being explored. © 2016 International Clinical Cytometry Society
From adolescent to elder rats: Motivation for palatable food and cannabinoids receptors
Authors: Amancio‐Belmont Octavio , Romano‐López Antonio , Ruiz‐Contreras Alejandra Evelin , Méndez‐Díaz Mónica , Prospéro‐García Oscar
Published: December 2016

To analyze motivation, food self‐administration and decision‐making were evaluated in adolescent, adult, and aged rats. Subjects were trained to press a lever (fixed ratio, FR1 and FR5) in an operant chamber, to obtain chocolate flavor pellets. They assessed the progressive ratio (PR), extinction, and reinstatement of the behavior. To estimate decision‐making for food, rats were trained in the conditioned place preference (CPP) paradigm: (a) associating one compartment with lab chow (LCh) one day and the other compartment with rice krisspies (RK), the next day. (b) Training similar to (a) but on the day RK was the reinforcer, it was delivered with a progressive delay. In addition, CB1 and CB2 receptor expression in the nucleus accumbens (NAcc) and prefrontal cortex (PFC) was estimated by means of Western blot. Adolescent rats consumed higher amounts of RK/body weight than adult and aged rats during FR1, FR5, and PR. Extinction was more prolonged for adolescent rats than for adult and aged rats. First CPP condition, all three groups of rats preferred the RK‐associated compartment. Second CPP condition, adolescent rats developed equal preference to both compartments, while adult and aged rats preferred the RK‐associated compartment. Rats per group ate a similar amount of either reinforcer. Adolescent rats exhibited low expression of CB1R in the NAcc and low expression of both CB1R and CB2R in the PFC compared with adult and aged rats. Adolescent rats display higher motivation for palatable food and an indiscriminate seeking behavior suggesting involvement of both homeostatic and hedonic systems in their decision‐making processes. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 917–927, 2017
Identification of novel disulfide adducts between the thiol containing leaving group of the nerve agent VX and cysteine containing tripeptides derived from human serum albumin
Authors: Kranawetvogl Andreas , Küppers Jim , Gütschow Michael , Worek Franz , Thiermann Horst , Elsinghorst Paul W. , John Harald
Published: December 2016

Chemical warfare agents represent a continuous and considerable threat to military personnel and the civilian population. Such compounds are prohibited by the Chemical Weapons Convention, to which adherence by the member states is strictly controlled. Therefore, reliable analytical methods for verification of an alleged use of banned substances are required. Accordingly, current research focuses on long‐term biomarkers derived from covalent adducts with biomolecules such as proteins. Recently, we have introduced a microbore liquid chromatography/electrospray ionization high‐resolution tandem mass spectrometry method allowing for the investigation of two different classes of adducts of the nerve agent VX with human serum albumin (HSA). Phosphonylated tyrosine residues and novel disulfide adducts at cysteine residues of HSA were produced by enzymatic cleavage with pronase and detected simultaneously. Notably, the thiol containing leaving group of VX (2‐(diisopropylamino)ethanethiol, DPAET) formed disulfide adducts that were released as cysteine and proline containing dipeptides originating from at least two different sites of HSA. Aim of this study was to identify assumed and novel adducts of DPAET with HSA using synthetic peptide reference compounds. Two novel tripeptides were identified representing disulfide adducts with DPAET (Met‐Pro‐Cys‐DPAET, MPC‐DPAET and Asp‐Ile‐Cys‐DPAET, DIC‐DPAET). MPC‐DPAET was shown to undergo partial in‐source decay during electrospray ionization for MS detection thereby losing the N‐terminal Met residue. This results in the more stable Pro‐Cys‐DPAET (PC‐DPAET) dipeptide detectable as protonated ion. The limit of detection for MPC‐DPAET was evaluated, revealing toxicologically relevant VX plasma concentrations. The results provide novel insights into the reactivity of VX and its endogenous targets. Copyright © 2016 John Wiley & Sons, Ltd.
In vitro studies on flubromazolam metabolism and detection of its metabolites in authentic forensic samples
Authors: Noble Carolina , Mardal Marie , Bjerre Holm Niels , Stybe Johansen Sys , Linnet Kristian
Published: December 2016

Flubromazolam is a triazole benzodiazepine with high potency and long‐lasting central nervous system depressant effects; however, limited data about its pharmacokinetics are available. Here, we report in vitro studies of the human flubromazolam metabolism analyzed by liquid chromatography high‐resolution mass spectrometry (LC‐HRMS). In vitro investigations were carried out in pooled human liver microsomes (pHLM) and recombinant cytochrome P450 (CYP)‐enzymes. To confirm those metabolites detected in vitro, authentic samples obtained from two forensic cases were also analyzed by LC‐HRMS. Additionally, determination of the unbound fraction of flubromazolam in pHLM and in plasma was performed by equilibrium dialysis with subsequent prediction of its hepatic clearance (CLH) using well‐stirred and parallel‐tube models. Additional findings obtained by routine screening methods of these forensic cases are also reported. Studies using incubations with nicotinamide adenine dinucleotide phosphate‐fortified pHLM with or without uridine 5'‐diphosphoglucuronic acid and incubations with CYP‐enzymes identified the main metabolic pathway of flubromazolam as hydroxylation on the α‐ and/or 4‐position mediated by CYP3A4 and CYP3A5, with subsequent glucuronidation of the hydroxylated metabolites as well as of the parent drug. Further, α‐hydroxy‐flubromazolam and its corresponding glucuronide were detected in vivo together with the N‐glucuronide of flubromazolam. The predicted CLH of flubromazolam using the well‐stirred and parallel‐tube models were 0.42 and 0.43 mL/min/kg, respectively. Based on the data presented here, flubromazolam is primarily metabolized by CYP3A4/5 with a high protein‐binding and a predicted low clearance. Analysis of authentic samples suggested that analytical targets for flubromazolam should be the compound itself and α‐hydroxy‐flubromazolam. Copyright © 2016 John Wiley & Sons, Ltd.