bluuebunny/crossref_metadata_2025 huggingface dataset:
Identifizierung der Zielproteine bioaktiver Verbindungen: Die Suche nach der Nadel im Heuhaufen
Authors: Ziegler Slava , Pries Verena , Hedberg Christian , Waldmann Herbert
Published: February 2013

Die Identifizierung und Validierung von Zielmolekülen biologisch aktiver niedermolekularer Verbindungen ist ein äußerst wichtiger, oft maßgebender Schritt in der akademischen und pharmazeutischen Forschung. Dank der Entwicklung und der Verfügbarkeit diverser neuer experimenteller Verfahren ist die Identifizierung von Zielmolekülen prinzipiell realisierbar, und die Anzahl der erfolgreichen Beispiele wächst stetig. Allerdings ist bislang keine generische, breit anwendbare Methodik etabliert worden. Dieser Aufsatz fasst die gängigen Methoden zur Identifizierung der Zielmoleküle niedermolekularer Substanzen in erster Linie für Chemiker, aber auch für Biologen zusammen, die z. B. den molekularen Angriffspunkt (Target) einer bestimmten biologisch aktiven Substanz finden wollen. Wir beschreiben die am häufigsten eingesetzten experimentellen Ansätze zur Zielprotein‐Identifizierung und geben repräsentative Beispiele, die den neuesten Stand der Forschung demonstrieren. Von den derzeit verfügbaren Methoden werden die Affinitätsisolierung von Proteinen mittels geeigneter Affinitätssonden (pull down) und die anschließende massenspektrometrische Analyse der angereicherten Proteine am häufigsten eingesetzt. Um eine Anleitung für einen schnellen Einstieg in dieses Feld zu geben, beschreiben wir basierend auf unseren eigenen Erfahrungen einen typischen Ablauf der Zielprotein‐Identifizierung, der auf dem Einsatz der chemischen Proteomik als Schlüsselschritt für die Formulierung einer Hypothese für potentielle Zielproteine beruht.
125 Years of Chemistry in the Mirror of “Angewandte”
Authors: Diederich François
Published: February 2013

This Review investigates the development of Angewandte Chemie since the founding of the journal in 1887 and analyzes how its content reflects the changes in chemical research over these 125 years. Although Angewandte Chemie was originally founded as a journal for applied (“angewandte”)—technical and analytical—chemistry, numerous review articles and abstracts published even in its first 50 years enable the milestones in chemical research in a much broader sense to be traced nicely. With the introduction of the International Edition in 1962, the author base, which had until then been primarily limited to German‐speaking countries, became increasingly international, and the journal experienced impressive growth. Today, with its attractive layout, successful mix of articles, and high impact factor, Angewandte Chemie covers chemical research around the world in its full breadth, with its many achievements and future challenges.
A novel mechanism of exfoliation and physical properties of PU/organoclay nanocomposites
Authors: Bae Soo Bin , Kim Chang Kee , Kim Youn Cheol , Chung In Jae
Published: February 2013

The novel mechanism of exfoliation of silicate was investigated. Exfoliation and intercalation was achieved even at 15 wt % in the polyurethane (PU) matrix via in situ polymerization. Through using IR consumption graph of curing agent, crosslinking equation could be derived. The diffusion rate of curing agent, Isophorone diisocyanate, brought the different morphologies as well as crosslinking densities of nanocomposites. Dodecylamine, the organifier having similar hydrogen‐bonding component with Isophorone diisocyanate than octadecylamine, affected the faster diffusion of isophorone diisocyanate in hydroxyl terminated polybutadiene/organoclay composite. This phenomenon was confirmed by DSC graph, XRD, SAXS, and TEM images. The nanocomposites showed high physical properties until at 10 wt % clay. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013
The tribological properties of benzoxazine‐bismaleimides composites with functionalized nano‐SiO2
Authors: Yan Hong‐Xia , Jia Yuan , Li Mei‐Li , Li Ting‐Ting
Published: February 2013

To improve the tribological properties of benzoxazine (BOZ) resin, bismaleimides (BMI) resin is chosen as organic phase, hyperbranched polysilane functionalized SiO2 nanoparticles (HBPSi‐SiO2) are chosen as inorganic modifiers to prepare HBPSi‐SiO2/BOZ‐BMI composites using high shear and ultrasonic processes. The effect of content of HBPSi‐SiO2 on the mechanical properties and tribological properties of the composites are investigated. The results show that suitable addition of HBPSi‐SiO2 can largely enhance the impact strength, reduce the friction coefficient, and wear rate of BOZ‐BMI resin. Scanning electron microscopy is employed to research the wearing mechanism of materials. The severe wear of the BOZ pure resin is owing to fatigue wear, and the moderate wear of BOZ‐BMI resin is attributed to adhesive wear. While, the mild wear of the composites with HBPSi‐SiO2 is due to abrasive wear. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013
Multilayered mouse preosteoblast MC3T3‐E1 sheets harvested from temperature‐responsive poly(N‐isopropylacrylamide‐co‐acrylamide) grafted culture surface for cell sheet engineering
Authors: Wong‐In Sopita , KhanhThuyen Nguyen Thi , Siriwatwechakul Wanwipa , Viravaidya‐Pasuwat Kwanchanok
Published: February 2013

A novel temperature‐responsive tissue culture surface was prepared using ultraviolet irradiation to graft poly(N‐isopropylacrylamide‐co‐acrylamide) (PNIAM‐co‐AM) onto commercial tissue culture surfaces. The physical properties of the grafted surfaces were confirmed by Fourier Transform Infrared Spectroscopy, contact angle measurement, and Atomic Force Microscopy. The grafted surface was also tested and shown to be nontoxic using mouse preosteoblast MC3T3‐E1 cells. The cells grew as successfully on the grafted surface as those on ungrafted surface. When the temperature was reduced from 37 to 10°C for 30 min, followed by 20°C for 60 min, the confluent cells could be detached as a continuous sheet. A histological examination showed that the harvested cell sheet preserved tight junctions and extracellular matrix proteins, allowing the sheet to adhere to other cell sheets as multilayers. The resulting multilayered sheets were in good condition, as indicated by the LIVE/DEAD stain. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013
Conformational diversity and ligand tunnels of mammalian cytochrome P450s
Authors: Yu Xiaofeng , Cojocaru Vlad , Wade Rebecca C.
Published: February 2013

The mammalian cytochrome P450 (CYP) enzymes play important roles in drug metabolism, steroid biosynthesis, and xenobiotic degradation. The active site of CYPs is buried in the protein and thus the ligands have to enter and exit the active site via ligand tunnels. Conformational changes of flexible parts of the protein usually accompany the entrance and exit of ligands. Comparison of the crystal structures of mammalian CYPs in closed, open, and partially open states reveals that the greatest conformational diversity associated with ligand tunnel opening is in the regions of the B–C and F–G loops. Some CYPs have been observed to adopt different open and closed conformations when bound to different ligands, suggesting that the ligand entrance and exit routes might differ according to the ligand properties. Mammalian CYPs are mostly membrane‐bound enzymes, making them difficult to characterize structurally and dynamically. A range of molecular dynamics simulation techniques has been applied to investigate the dynamics and the ligand tunnels of these proteins both in the aqueous environment, and more recently, in lipid bilayers. These simulations not only reveal multiple tunnels through which ligands can pass but also show that different tunnels are preferred by different ligands and that the lipid bilayer can influence the protein dynamics and tunnel opening. The results indicate that not only the active site but also the ligand tunnels can contribute to the different substrate specificity profiles of the mammalian CYPs.
Electrophysiological analysis of the role of novelty in the von Restorff effect
Authors: Rangel‐Gomez Mauricio , Meeter Martijn
Published: February 2013

Items that are distinctive with respect to their context tend to be recalled better than nondistinctive items, a finding known as the von Restorff effect. The goal of this study was to elucidate the role of novelty in this effect. In two experiments, participants performed a dual task in which they had to study words presented visually while to‐be ignored sounds were played over earphones. Sounds could be either standard or novel, and words could be presented in standard or novel font. Sounds were presented either simultaneously with the words (Experiment 1) or preceding them (Experiment 2). Electrophysiological correlates of novelty processing, the N2b and P3a ERP components, were recorded while the words were studied. It was seen that cued recall was better for words presented in novel fonts than for words in a standard font (the von Restorff effect). Words presented while novel sounds were played were remembered worse (Experiment 1) or equally well (Experiment 2) than those combined with standard sounds. Words presented in novel fonts elicited enhanced N2b, P3a, P3b, and N400 components; however, none of these components were specifically larger for subsequently recalled novel‐font words. A larger N2b was found for recalled than for nonrecalled words, but this effect was not specific for words presented in novel font. We hypothesized that if novelty was beneficial for memory processing, the N2–P3 complex would be more enhanced for novel words that were later recalled than for those not recalled. The data showed otherwise. This suggests that novelty processing, as indexed by the N2–P3 novelty components, is not the main cause of the von Restorff effect.
Complexity in cancer biology: is systems biology the answer?
Authors: Koutsogiannouli Evangelia , Papavassiliou Athanasios G. , Papanikolaou Nikolaos A.
Published: February 2013

Complex phenotypes emerge from the interactions of thousands of macromolecules that are organized in multimolecular complexes and interacting functional modules. In turn, modules form functional networks in health and disease. Omics approaches collect data on changes for all genes and proteins and statistical analysis attempts to uncover the functional modules that perform the functions that characterize higher levels of biological organization. Systems biology attempts to transcend the study of individual genes/proteins and to integrate them into higher order information. Cancer cells exhibit defective genetic and epigenetic networks formed by altered complexes and network modules arising in different parts of tumor tissues that sustain autonomous cell behavior which ultimately lead tumor growth. We suggest that an understanding of tumor behavior must address not only molecular but also, and more importantly, tumor cell heterogeneity, by considering cancer tissue genetic and epigenetic networks, by characterizing changes in the types, composition, and interactions of complexes and networks in the different parts of tumor tissues, and by identifying critical hubs that connect them in time and space.
Regioselective Sequential Additions of Nucleophiles and Electrophiles to Perfluoroalkylfullerenes: Which Cage C Atoms Are the Most Reactive and Why?
Authors: Clikeman Tyler T. , Kuvychko Igor V. , Shustova Natalia B. , Chen Yu‐Sheng , Popov Alexey A. , Boltalina Olga V. , Strauss Steven H.
Published: February 2013

The sequential addition of CN− or CH3− and electrophiles to three perfluoroalkylfullerenes (PFAFs), Cs‐C70(CF3)8, C1‐C70(CF3)10, and Cs‐p‐C60(CF3)2, was carried out to determine the most reactive individual fullerene C atoms (as opposed to the most reactive CC bonds, which has previously been studied). Each PFAF reacted with CH3− or CN− to generate metastable PFAF(CN)− or PFAF(CH3)22− species with high regioselectivity (i.e., one or two predominant isomers). They were treated with electrophiles E+ to generate PFAF(CN)(E) or PFAF(CH3)2(E)2 derivatives, also with high regioselectivity (E+=CN+, CH3+, or H+). All of the predominant products, characterized by mass spectrometry and 19F NMR spectroscopy, are new compounds. Some could be purified by HPLC to give single isomers. Two of them, C70(CF3)8(CN)2 and C70(CF3)10(CH3)2(CN)2, were characterized by single‐crystal X‐ray diffraction. DFT calculations were used to propose whether a particular reaction is under kinetic or thermodynamic control.
pH‐Controlled Reversible Formation of a Supramolecular Hyperbranched Polymer Showing Fluorescence Switching
Authors: Yu Bingran , Wang Baoyan , Guo Shuwen , Zhang Qian , Zheng Xiaorui , Lei Haitao , Liu Weisheng , Bu Weifeng , Zhang Yun , Chen Xin
Published: February 2013

A π‐conjugated AB2 monomer 1 with a dibenzo[24]crown‐8 (DB24C8) ring and two secondary amine centres has been synthesised. Treatment of a solution of 1 in dichloromethane with trifluoroacetic acid (TFA) leads to protonation of the amine groups, and then the DB24C8 rings are threaded by the dialkylammonium ion centres of other monomer molecules, leading to the formation of a supramolecular hyperbranched polymer, TFA‐1. Rather strong π–π stacking interactions between the conjugated cores are evident in this polymer. The supramolecular hyperbranched polymer (SHP) can be completely depolymerised by adding a slight excess of N‐tert‐butyl‐N′,N′,N′′,N′′,N′′′,N′′′‐hexamethylphosphorimidic triamide, tetrabutylammonium fluoride, or tetrabutylammonium acetate. The acid–base‐controlled process induces a reversible change in the fluorescence intensities of the solutions due to the controllable presence of the π–π stacking interactions between the conjugated cores. This dynamic behaviour is significant with respect to “smart” supramolecular polymer materials.
Studies on the Effect of Physico‐Chemical Soot Properties and Feed Gas Composition on the Kinetics of Soot Oxidation on Fe2O3 Catalyst
Authors: Waglöhner Steffen , Reichert Dirk , Bockhorn Henning , Kureti Sven
Published: February 2013

Three commercial carbon black samples as well as self‐made C3H6 soot were investigated for their reactivity in the oxidation on an α‐Fe2O3 catalyst. These studies were performed by temperature programmed oxidation (TPO) using a packed bed. For reference purposes, TPO studies in the absence of the catalyst were made as well. The carbon black samples were characterized towards the content of C, H, N and O as well as higher heating value, specific surface area, moisture and volatile matter and were deemed to be suitable model substances for diesel soot of different maturity. The correlation of these physico‐chemical properties with the kinetics in catalytic TPO indicated that the soot oxidation on Fe2O3 is significantly affected by the initial number of surface oxygen compounds of the soot. The decomposition of these surface species causes the formation of active carbon sites, which are supposed to accelerate the soot oxidation.
Monochloramination of Oxytetracycline: Kinetics, Mechanisms, Pathways, and Disinfection By‐Products Formation
Authors: Bi Xiangyu , Xu Bin , Lin Yi‐Li , Hu Chen‐Yan , Ye Tao , Qin Cao
Published: February 2013

This study investigated the degradation kinetics, formation of disinfection by‐products (DBPs), and degradation pathways during monochloramination of oxytetracycline (OTC). The degradation kinetics can be well described by a second‐order kinetic model, first‐order in monochloramine (NH2Cl), and first‐order in OTC. Reaction of OTC with NH2Cl shows a high reactivity, with the apparent rate constant of 17.64/M/s at pH 7. The apparent rate constant declined as pH increased from 5 to 10. Six DBPs were detected during monochloramination of OTC, including chloroform (CF), 1,1‐dichloro‐2‐propanone (1,1‐DCP), 1,1,1‐trichloro‐2‐propanone (1,1,1‐TCP), dichloroacetonitrile (DCAN), trichloronitromethane (TCNM), and N‐nitrosodimethlyamine (NDMA). CF, DCAN and NDMA had the maximum yields at neutral pH, while 1,1‐DCP and 1,1,1‐TCP had the maximum yields at pH 4. However, TCNM concentration increased as pH increased. Degradation pathways of OTC monochloramination were then proposed. Hydroxylation and Cl‐substitution are found to be the dominant mechanisms in monochloramination of OTC.
Marine Bioactive Steryl Esters from the Red Sea Black Coral Antipathes dichotoma
Authors: Alarif Walied M. , Abdel‐lateff Ahmed , AL‐lihaibi Sultan S. , Ayyad Seif‐Eldin N. , Badria Farid A. , Alsofyani Abdulmohsin A. , Abou‐Elnaga Zeinab S.
Published: February 2013

Two new marine steryl hexadecanoates, 3β‐hexadecanoylcholest‐5‐en‐7‐one (1) and 3β‐hexadecanoylcholest‐5‐en‐7β‐ol (2), along with seven known compounds, cholest‐5‐en‐3β‐yl‐formate (3), thymidine (4), indole‐3‐carboxaldehyde (5), 3β‐hydroxycholest‐5‐en‐7‐one (6), cholesterol (7), 22‐dehydrocholestrol (8), and 24‐methylenecholesterol (9), were isolated from the anthozoan black coral, Antipathes dichotoma. The structures of all isolated compounds were determined by interpretation of their spectral data 1D (1H, 13C and DEPT) and 2D (COSY, HSQC and HMBC) NMR, UV, IR, and MS. Compounds 1–5 were evaluated for their anticancer activities, employing four cancer panels; HepG2, WI 38, VERO, and MCF‐7. All tested compounds, except 4, showed moderate activities. Compound 4 exhibited significant anticancer activity against VERO and MCF‐7, with IC50 20.5 and 20.2 µg/mL, respectively.
Photocatalytic Degradation of Dye C.I. Direct Blue 78 Using TiO2 Nanoparticles Immobilized on Recycled Wool‐Based Nonwoven Material
Authors: Marković Darka , Jokić Bojan , Šaponjić Zoran , Potkonjak Branislav , Jovančić Petar , Radetić Maja
Published: February 2013

This paper discusses the possibility of immobilization of TiO2 nanoparticles onto recycled wool‐based nonwoven material, which can be utilized for removal of dyes from wastewater. The photocatalytic activity of TiO2 nanoparticles deposited on the nonwoven material was evaluated in the aqueous solution of direct dye C.I. Direct Blue 78 under the UV illumination. Nonwoven material modified with TiO2 nanoparticles provides complete removal of dye from the solution already after 4–6 h of UV illumination. However, photodegradation of the dye adsorbed on the nonwoven material was obtained within 24 h of UV illumination. The rate of dye adsorption and photodegradation depends on the amount of deposited TiO2 nanoparticles. The increase of initial dye concentration induced decrease in photocatalytic efficiency of immobilized TiO2 nanoparticles. The highest photodegradation rate was achieved in acidic conditions. Elevated temperatures positively affected the removal of dye from solution. Photocatalytic activity of TiO2 nanoparticles deposited on nonwoven material was preserved after three photodegradation cycles.
Estimating the Sampling Uncertainty for the Analysis of Solid Refused Fuel
Authors: Prikler Simon , Garvens Hans‐Jürgen , Winterstein Michael , Einax Jürgen W.
Published: February 2013

Uncertainty assessment of the parameters used for the reporting in the emissions trading system (ETS) to characterize fuels includes not only the processes in a laboratory but has to be expanded for inclusion of sampling and sample preparation. Analysis of variance was used to allocate the contributing uncertainties to the steps described. Apart from some specific results for sampling methods, it was observed that the uncertainty of sampling was in the same order of magnitude than the analytical and the sample preparation error. Several measures to enhance quality assurance in sampling and sample preparation could be derived from specific results. The results were used in the European Monitoring and Reporting Regulation, which set out the requirements for ETS. Sampling and sample preparation have to be included in uncertainty assessment as well as sampling procedures and sampling plans (including quality assurance) have to be agreed upon by the laboratories, carrying out the analytics of those samples.
Revealing the Nano‐Level Molecular Packing in Chitosan–NiO Nanocomposite by Using Positron Annihilation Spectroscopy and Small‐Angle X‐ray Scattering
Authors: Sharma Sandeep K. , Bahadur Jitendra , Patil Pushkar N. , Maheshwari Priya , Mukherjee Saurabh , Sudarshan Kathi , Mazumder Subhasish , Pujari Pradeep K.
Published: February 2013

Chitosan–NiO nanocomposite (CNC) is shown to be a potential dielectric material with promising properties. CNCs containing NiO nanoparticles (0.2, 0.6, 1, 2, 5 wt %) are prepared through chemical methods. The inclusion of NiO nanoparticles in the chitosan matrix is confirmed by scanning electron microscopy (SEM) and X‐ray diffraction. The morphology of the NiO nanoparticles and the nanocomposites is investigated by transmission electron microscopy and SEM, respectively. Positron annihilation lifetime spectroscopy (PALS) and the coincidence Doppler broadening (CDB) technique are used to quantify the free volume and molecular packing in the nanocomposites. The triplet‐state positronium lifetime and the corresponding intensity show the changes in nanohole size, density, and size distribution as a function of NiO loading. Small‐angle X‐ray scattering indicates that the NiO aggregates are identical in all the CNCs. The momentum density distribution obtained from CDB measurements excludes the possibility of a contribution of vacant spaces (pores) available in NiO aggregates to the free volume of nanocomposites upon determination by using PALS. The results show systematic variation in free‐volume properties and nano‐level molecular packing as a function of NiO loading, which is presumed to play a vital role in determining the various properties of the nanocomposites.
Concurrent multipath traffic impersonating for enhancing communication privacy
Authors: Liu Huisheng , Wang Zhenxing , Miao Fu
Published: February 2013

Network communication traditionally only uses encryption techniques for privacy and a single path for routing, which makes the communication vulnerable to attackers. Attackers easily obtain much important information by eavesdropping on the path and analyzing the communication traffic. To overcome the problem, we propose concurrent multipath traffic impersonating (CMTI), which obscures traffic features by camouflaging the traffic flow and dividing it into multiple parts. We propose a traffic impersonating technique based on statistical simulation, which make the secret traffic look like another normal and inconspicuous class to deceive attackers. And we present the packet scheduling algorithm to transfer the impersonating flows on multipath, for enhancing the communication efficiency and further increasing significantly the cost inflicted on attackers who wish to eavesdrop communication sessions. The empirical analysis demonstrates that concurrent multipath traffic imitating can effectively thwart traffic analysis and enhance communication efficiency. Copyright © 2013 John Wiley & Sons, Ltd.
Performance analysis of S‐MAC protocol
Authors: Chang Li‐Wei , Huang Yueh‐Min , Lin Chun‐Cheng
Published: February 2013

Wireless sensor networks have been developed in the way of higher speed, more stability, and more energy efficiency in recent years. Because most wireless sensors are powered by energy‐constrained batteries, efficient energy consumption plays the most important role in the design of wireless sensor networks. For energy efficiency, aside from economizing the use of power in the sensor hardware, extensive research efforts have been dedicated towards designing energy‐efficient protocols in the MAC layer. Among them, the S‐MAC (sensor medium access control) protocol proposed a combined scheduling and contention scheme to decide when to put sensors into the sleep state for saving energy. In this paper, we further conduct the performance analysis of S‐MAC protocol, in which the mathematical equations for the saturation throughput analysis of S‐MAC protocol are derived, and then simulation data are substituted into those equations and the S‐MAC protocol, respectively. The simulated throughput results have shown that our derived equations can capture the characteristics of the S‐MAC protocol. In addition, as compared with the conventional carrier sense multiple access/collision avoidance protocol, the simulation results show that the S‐MAC protocol performs better in terms of power consumption, delay, and collision rate. Copyright © 2013 John Wiley & Sons, Ltd.
Tuning the Bioactivity of Tensioactive Deoxy Glycosides to Structure: Antibacterial Activity Versus Selective Cholinesterase Inhibition Rationalized by Molecular Docking
Authors: Martins Alice , Santos Maria S. , Dias Catarina , Serra Patrícia , Cachatra Vasco , Pais João , Caio João , Teixeira Vítor H. , Machuqueiro Miguel , Silva Marta S. , Pelerito Ana , Justino Jorge , Goulart Margarida , Silva Filipa V. , Rauter Amélia P.
Published: February 2013

New octyl/dodecyl 2,6‐dideoxy‐D‐arabino‐hexopyranosides have been synthesized by a simple but efficient methodology based on the reaction of glycals with alcohols catalysed by triphenylphosphane hydrobromide, deprotection, regioselective tosylation and reduction. Their surface‐active properties were evaluated in terms of adsorption and aggregation parameters and compared with those of 2‐deoxy‐D‐glycosides and 2,6‐dideoxy‐L‐glycosides. Deoxygenation at the 6‐position led to a decrease in the critical micelle concentration, and an increase in the adsorption efficiency (pC20) promoting aggregation more efficiently than adsorption. With regard to the antibacterial activity, dodecyl 2,6‐dideoxy‐α‐L‐arabino‐hexopyranoside was the most active compound towards Bacillus anthracis (MIC 25 μM), whereas its enantiomer exhibited a MIC value of 50 μM. Both 2,6‐dideoxy glycosides were active towards Bacillus cereus, Bacillus subtilis, Enterococcus faecalis and Listeria monocytogenes. In contrast, none of the 2‐deoxy glycosides was significantly active. These results and the data on surface activity suggest that aggregation is a key issue for antimicrobial activity. Beyond infection, Alzheimer's disease also threatens elderly populations. In the search for butyrylcholinesterase (BChE) selective inhibition, 2‐deoxy glycosides were screened in vitro by using Ellman's assay. Octyl 2‐deoxy‐α‐D‐glycoside was found to be a BChE selective inhibitor promoting competitive inhibition. Docking studies supported these results as they pinpoint the importance of the primary OH group in stabilizing the BChE inhibitor complex. A size‐exclusion mechanism for inhibition has been proposed based on the fact that acetylcholinesterase (AChE) exhibits several bulky residues that hinder access to the active‐site cavity. This work shows how the deoxygenation pattern, configuration and functionality of the anomeric centre can tune physical and surface properties as well as the bioactivity of these multifunctional and stereochemically rich molecules.
Heat‐assisted extraction for the determination of methylarginines in serum by CE
Authors: Linz Thomas H. , Lunte Susan M.
Published: February 2013

Methylarginines (MAs) are potent vasoconstrictors that have been reported to be present at elevated concentrations in the blood of patients suffering from cardiovascular disease. To determine the diagnostic potential of MAs for cardiovascular disease, a method capable of rapidly quantifying their endogenous concentrations from serum samples is required. To that end, a heat‐assisted extraction method was developed. Serum was first rapidly heated, causing it to congeal into a gel, and then subjected to solid–liquid extraction. The extraction solution was then derivatized with a fluorogenic dye and analyzed by CE‐LIF to permit quantitation of the MAs. This heat‐assisted extraction procedure allowed a no‐net‐dilution extraction of the analytes to be performed into a solvent compatible with the subsequent CE analysis. This enabled direct detection of low‐abundance analytes, such as MAs, without the need for a preconcentration step. This sample preparation method was compared with a commonly used solid‐phase extraction method for MA analysis. Endogenous MA concentrations determined by both the heating and solid‐phase extraction methods were found to be in good agreement with each other and with values previously reported in the literature.
Factors controlling the morphology and volume (V)–length (L) relations of permanent gullies in the northern Ethiopian Highlands
Authors: Frankl Amaury , Poesen Jean , Scholiers Nelles , Jacob Miró , Haile Mitiku , Deckers Jozef , Nyssen Jan
Published: February 2013

Small‐scale aerial photographs and high‐resolution satellite images, available for Ethiopia since the second half of the twentieth century as for most countries, allow only the length of gullies to be determined. Understanding the development of gully volumes therefore requires that empirical relations between gully volume (V) and length (L) are established in the field. So far, such V–L relations have been proposed for a limited number of gullies/environments and were especially developed for ephemeral gullies. In this study, V–L relations were established for permanent gullies in northern Ethiopia, having a total length of 152 km. In order to take the regional variability in environmental characteristics into account, factors that control gully cross‐sectional morphology were studied from 811 cross‐sections. This indicated that the lithology and the presence of check dams or low‐active channels were the most important controls of gully cross‐sectional shape and size. Cross‐sectional size could be fairly well predicted by their drainage area. The V–L relation for the complete dataset was V = 0 · 562 L 1·381 (n = 33, r2 = 0 · 94, with 34 · 9% of the network having check dams and/or being low‐active). Producing such relations for the different lithologies and percentages of the gully network having check dams and/or being low‐active allows historical gully development from historical remote sensing data to be assessed. In addition, gully volume was also related to its catchments area (A) and catchment slope gradient (Sc). This study demonstrates that V–L and V–A × Sc relations can be very suitable for planners to assess gully volume, but that the establishment of such relations is necessarily region‐specific. Copyright © 2013 John Wiley & Sons, Ltd.
Evidence of transient topographic disequilibrium in a landward passive margin river system: knickpoints and paleo‐landscapes of the New River basin, southern Appalachians
Authors: Prince Philip S. , Spotila James A.
Published: February 2013

The upper New River basin of the southern Appalachian Mountains, a major tributary of the modern Ohio River, represents the unglaciated headwaters of the Tertiary Teays River system of eastern North America. Dating of relict fluvial gravels have suggested that New River incision may be outpacing lowering of the surrounding uplands, but physical evidence of transient topographic disequilibrium has yet to be identified. We use focused topographic analysis of the upper New River basin to delineate a perched, low‐relief paleo‐landscape that is experiencing transgressive dissection due to incision by the New River and its tributaries. Accelerated incision has decoupled hillslopes from the drainage network, generating knickpoints which represent the boundary between remnants of the paleo‐landscape and actively adjusting topography downstream. Steepening of hillslopes downstream of knickpoints suggests dynamic headward migration which, along with knickpoint occurrence throughout the drainage network, is inconsistent with the development of fixed stream profile convexities atop strike‐extensive geologic contacts. In the absence of tectonic forcing, we favor a climatically‐forced drop in external base level as driver of the incision pattern we observe. Plio‐Pleistocene glacial damming and diversion of the Teays River to form the modern Ohio River lowered regional base level for the study area, potentially forcing the paleo‐landscape developed during the Teays era to adjust to the modern drainage pattern. The upper New River may therefore represent the potential for glacially‐driven drainage rearrangement to drive transient topographic evolution hundreds of kilometers away from the ice margin, long after the disappearance of ice sheets. Copyright © 2013 John Wiley & Sons, Ltd.
Improved error and work estimates for high‐order elements
Authors: Löhner Rainald
Published: February 2013

Work estimates for high‐order elements are derived. The comparison of error and work estimates shows that even for relative accuracy in the 0.1% range, which is one order below the typical accuracy of engineering interest (1% range), linear elements may outperform all higher‐order elements. As expected, the estimates also show that the optimal order of element in terms of work and storage demands depends on the desired relative accuracy. The comparison of work estimates for high‐order elements and their finite difference counterparts reveals a work‐ratio of several orders of magnitude. It thus becomes questionable if general geometric flexibility via micro‐unstructured grids is worth such a high cost. Copyright © 2013 John Wiley & Sons, Ltd.
Altered relationship between electrophysiological response to errors and gray matter volumes in an extended network for error‐processing in pediatric obsessive‐compulsive disorder
Authors: Liu Yanni , Hanna Gregory L. , Carrasco Melisa , Gehring William J. , Fitzgerald Kate D.
Published: February 2013

Pediatric patients with obsessive‐compulsive disorder (OCD) show an increased electrophysiological response to errors that is thought to be localized to the posterior medial prefrontal cortex (pMFC). However, the relation of this response, the error‐related negativity (ERN), to underlying brain structures remains unknown. In an examination of 20 pediatric OCD patients and 20 healthy youth, we found that more negative ERN amplitude was correlated with lower gray matter (GM) density in pMFC and orbital frontal cortex. The association of the ERN with pMFC gray matter volume was driven by the patient group. In addition, a group difference in the association of ERN with gray matter in right insula was observed, showing an association of these measures in healthy youth (more negative ERN amplitude was associated with lower GM density in insula), but not in patients. These findings provide preliminary evidence linking gray matter volumes in an extended network for error processing to the ERN, and suggest that structural alterations in this network may underlie exaggeration of the ERN in pediatric OCD. Hum Brain Mapp 35:1143–1153, 2014. © 2013 Wiley Periodicals, Inc.
Hierarchical fusion of features and classifier decisions for Alzheimer's disease diagnosis
Authors: Liu Manhua , Zhang Daoqiang , Shen Dinggang ,   the Alzheimer's Disease Neuroimaging Initiative
Published: February 2013

Pattern classification methods have been widely investigated for analysis of brain images to assist the diagnosis of Alzheimer's disease (AD) and its early stage such as mild cognitive impairment (MCI). By considering the nature of pathological changes, a large number of features related to both local brain regions and interbrain regions can be extracted for classification. However, it is challenging to design a single global classifier to integrate all these features for effective classification, due to the issue of small sample size. To this end, we propose a hierarchical ensemble classification method to combine multilevel classifiers by gradually integrating a large number of features from both local brain regions and interbrain regions. Thus, the large‐scale classification problem can be divided into a set of small‐scale and easier‐to‐solve problems in a bottom‐up and local‐to‐global fashion, for more accurate classification. To demonstrate its performance, we use the spatially normalized grey matter (GM) of each MR brain image as imaging features. Specifically, we first partition the whole brain image into a number of local brain regions and, for each brain region, we build two low‐level classifiers to transform local imaging features and the inter‐region correlations into high‐level features. Then, we generate multiple high‐level classifiers, with each evaluating the high‐level features from the respective brain regions. Finally, we combine the outputs of all high‐level classifiers for making a final classification. Our method has been evaluated using the baseline MR images of 652 subjects (including 198 AD patients, 225 MCI patients, and 229 normal controls (NC)) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. The experimental results show that our classification method can achieve the accuracies of 92.0% and 85.3% for classifications of AD versus NC and MCI versus NC, respectively, demonstrating very promising classification performance compared to the state‐of‐the‐art classification methods. Hum Brain Mapp 35:1305–1319, 2014. © 2013 Wiley Periodicals, Inc.
Cerebral correlates of visuospatial neglect: A direct cerebral stimulation study
Authors: Vallar Giuseppe , Bello Lorenzo , Bricolo Emanuela , Castellano Antonella , Casarotti Alessandra , Falini Andrea , Riva Marco , Fava Enrica , Papagno Costanza
Published: February 2013

Objective

To assess the role of the superior longitudinal fascicle, the inferior fronto‐occipital fascicle, and the posterior parietal lobe in visuospatial attention in humans during awake brain surgery.

Experimental design

Seven patients with hemispheric gliomas (six in the right hemisphere) entered the study. During surgery in asleep/awake anesthesia, guided by Diffusion Tensor Imaging Fiber Tractography, visuospatial neglect was assessed during direct electrical stimulation by computerized line bisection.

Principal observations

A rightward deviation, indicating left visuospatial neglect, was induced in six of seven patients by stimulation of the parietofrontal connections, in a location consistent with the trajectory of the second branch of the superior longitudinal fascicle. Stimulation of the medial and dorsal white matter of the superior parietal lobule (corresponding to the first branch of the superior longitudinal fascicle), of the ventral and lateral white matter of the supramarginal gyrus (corresponding to the third branch of the superior longitudinal fascicle), and of the inferior occipitofrontal fasciculus, was largely ineffective. Stimulation of the superior parietal lobule (Brodmann's area 7) caused a marked rightward deviation in all of the six assessed patients, while stimulation of Brodmann's areas 5 and 19 was ineffective.

Conclusions

The parietofrontal connections of the dorso‐lateral fibers of the superior longitudinal fascicle (i.e., the second branch of the fascicle), and the posterior superior parietal lobe (Brodmann's area 7) are involved in the orientation of spatial attention. Spatial neglect should be assessed systematically during awake brain surgery, particularly when the right parietal lobe may be involved by the neurosurgical procedure.Hum Brain Mapp 35:1334–1350, 2014. © 2013 Wiley Periodicals, Inc.
Synthesis of Functionalized Lipids, and Their Use for a Tunable Hydrophobization of Nucleosides and Nucleic Acids
Authors: Korneev Sergei , Rosemeyer Helmut
Published: February 2013

Two series of functionalized single and double side‐chained lipid molecules (Schemes 1 and 2) were prepared. The compounds carry either terminal COOH, OH, or halogen substituents. Moreover, the double side‐chained lipid 18 carries an internal alkyne functionality. The latter compound was used to hydrophobize thymidine at N(3) by base‐catalyzed alkylation. Additionally, fully protected thymidine, 32, was N(3)‐alkylated with the double side‐chained alcohol 9 applying Mitsunobu reaction conditions.
Base‐Induced Decarboxylation of Polyunsaturated α‐Cyano Acids Derived from Malonic Acid: Synthesis of Sesquiterpene Nitriles and Aldehydes with β‐, φ‐, and ψ‐End Groups
Authors: Dufossé Laurent , Cartier Dominique , Valla Benoist , Fouillaud Mireille , Labia Roger , Valla Alain
Published: February 2013

Catalytic base‐induced decarboxylation of polyunsaturated α‐cyano‐β‐methyl acids derived from malonic acid led to the corresponding nitriles 3 (Schemes 2 and 3), 6 (Scheme 5), and 9 (Scheme 6). This decarboxylation occurred with previous deconjugation of the α,β‐alkene moiety of the α‐cyano‐β‐methyl acid, leading to an α‐cyano‐β‐methylene propanoic acid which was easily decarboxylated (see Scheme 2). β‐Methylene intermediates, in some cases, could be isolated; mechanistic pathways are proposed. The nitriles 3, 6, and 9 were reduced to the sesquiterpene aldehydes 4 (β‐end group), 7 (φ‐end group), and 10 (ψ‐end group), respectively.
Stereoselective Total Synthesis of Multiplolide A and of a Diastereoisomer
Authors: Reddy Bandi Chennakesava , Bangade Vikas Madhukar , Ramesh Palakuri , Meshram Harshadas Mitaram
Published: February 2013

A stereoselective total synthesis of multiplolide A (1) and of its diastereoisomer 2 was described from easily accessible starting materials (Schemes 2–4). The synthetic strategy involves a Jacobsen resolution, Sharpless epoxidation, Swern oxidation, Yamaguchi reaction, and ring‐closing metathesis (RCM).
Two New Abietane Diterpenoids from the Roots of Tripterygium wilfordiiHook. f.
Authors: Li Jian‐You , Peng Ying , Li Ling‐Zhi , Gao Pin‐Yi , Gao Chang , Xia Su‐Xia , Song Shao‐Jiang
Published: February 2013

Two new abietane‐type diterpenoids, named triptobenzene R (1) and triptobenzene S (2), together with three known abietane‐type diterpenoids, triptophenolide (3), triptonodiol (4), and triptonoterpene methyl ether (5), were isolated from the roots of Tripterygium wilfordii Hook. f. Their structures and relative configurations were established by detailed spectral studies, including 1D‐ and 2D‐NMR (HSQC, HMBC, and NOESY), and HR‐ESI‐TOF‐MS, and by comparison with published data. Their absolute configurations were assigned by the CD technique, applied for the first time to abietane diterpenes from Tripterygium wilfordii. Compound 2 is the first abietane‐type norditerpenoid isolated from the genus Tripterygium.
Conformational Preferences of a β‐Octapeptide as Function of Solvent and Force‐Field Parameters
Authors: Choutko Alexandra , van Gunsteren Wilfred F.
Published: February 2013

The ability to design properly folded β‐peptides with specific biological activities requires detailed insight into the relationship between the amino acid sequence and the secondary and/or tertiary structure of the peptide. One of the most frequently used spectroscopic techniques for resolving the structure of a biomolecule is NMR spectroscopy. Because only signal intensities and frequencies are recorded in the experiment, a conformational interpretation of the recorded data is not straightforward, especially for flexible molecules. The occurrence of conformational and/or time averaging, and the limited amount and accuracy of experimental data hamper the precise conformational determination of a biomolecule. In addition, the relation between experimental observables with the underlying conformational ensemble is often only approximately known, thereby aggravating the difficulty of structure determination of biomolecules. The problematic aspects of structure refinement based on NMR nuclear Overhauser effect (NOE) intensities and 3J‐coupling data are illustrated by simulating a β‐octapeptide in explicit MeOH and H2O as solvents using three different force fields. NMR Data indicated that this peptide would fold into a 314‐helix in MeOH and into a hairpin in H2O. Our analysis focused on the conformational space visited by the peptide, on structural properties of the peptide, and on agreement of the MD trajectories with available NMR data. We conclude that 1) although the 314‐helical structure is present when the peptide is solvated in MeOH, it is not the only relevant conformation, and that 2) the NMR data set available for the peptide, when solvated in H2O, does not provide sufficient information to derive a single secondary structure, but rather a multitude of folds that fulfill the NOE data set.
Four New Alkaloids from the Fermentation Broth of Armillaria mellea
Authors: Wang Yun‐Chao , Zhang Yu‐Wei , Zheng Li‐Hua , Bao Yong‐Li , Wu Yin , Yu Chun‐Lei , Huang Yan‐Xin , Sun Lu‐Guo , Zhang Yu , Jia Xiu‐Juan , Li Yu‐Xin
Published: February 2013

Four compounds with similar structures and UV spectra were isolated from the fermentation broth of Armillaria mellea by means of preparative HPLC. Their structures were established as methyl (2S)‐1‐[2‐(furan‐2‐yl)‐2‐oxoethyl]‐5‐oxopyrrolidine‐2‐carboxylate (1), (2S)‐1‐[2‐(furan‐2‐yl)‐2‐oxoethyl]‐5‐oxopyrrolidine‐2‐carboxylic acid (2), 1‐[2‐(furan‐2‐yl)‐2‐oxoethyl]pyrrolidin‐2‐one (3) and 1‐[2‐(furan‐2‐yl)‐2‐oxoethyl]piperidin‐2‐one (4) on the basis of their 1D‐ and 2D‐NMR, and HR‐MS data. The absolute configurations of compounds 1 and 2 were determined by comparison of the experimental and calculated electronic circular dichroism (ECD) data. Additionally, four known compounds, 5–8, were also isolated.
Silica‐Bound 3‐{2‐[Poly(ethylene Glycol)]ethyl}‐Substituted 1‐Methyl‐1H‐imidazol‐3‐ium Bromide: A Recoverable Phase‐Transfer Catalyst for Smooth and Regioselective Conversion of Oxiranes to β‐Hydroxynitriles in Water
Authors: Reza Kiasat Ali , Ayashi Neda , Fallah‐Mehrjardi Mehdi
Published: February 2013

A series of β‐hydroxynitriles were efficiently synthesized from the regioselective ring opening of oxiranes by cyanide anion in the presence of silica‐bound 3‐{2‐[poly(ethylene glycol)]ethyl}‐substituted 1‐methyl‐1H‐imidazol‐3‐ium bromide (SiO2PEGImBr) as a novel recoverable phase‐transfer catalyst in H2O (Scheme 1 and Table 2). The workup procedure was straightforward, and the catalyst could be reused over four times with almost no loss of catalytic activity and selectivity.
1‐Thiacyclooct‐4‐yne (=5,6‐Didehydro‐3,4,7,8‐tetrahydro‐2H‐thiocin), and Its Sulfoxide and Its Sulfone
Authors: Schuhmacher Hans , Beile Bernhard , Meier Herbert
Published: February 2013

1‐Thiacyclooct‐4‐yne (=5,6‐didehydro‐3,4,7,8‐tetrahydro‐2H‐thiocin; 9) can be prepared from thiocan‐5‐one (6) in three steps by applying the so‐called selenadiazole method. The heterocyclic alkyne can be oxidized to the corresponding sulfoxide 16 and sulfone 17. Due to their geometrical strain, all three cyclic alkynes show high reactivities in DielsAlder and 1,3‐dipolar cycloadditions. Moreover, tetrathiafulvalenes can be prepared from 9 and 16 by the reaction with CS2.
Synthesis of 3‐Aryl‐2‐methoxyinden‐1‐one (Z)‐Phenylhydrazones via Hydrobromic Acid‐Mediated Cyclization of 2‐(1‐Aryl‐2‐methoxyethenyl)benzaldehyde Phenylhydrazones
Authors: Kobayashi Kazuhiro , Miyatani Wataru , Matsumoto Naoki
Published: February 2013

2‐(1‐Aryl‐2‐methoxyethenyl)benzaldehydes 2, obtained by successive treatment of 1‐(1‐aryl‐2‐methoxyethenyl)‐2‐bromobenzenes 1 with BuLi and 1‐formylpiperidine, were transformed to the corresponding phenylhydrazones 3 on treatment with PhNHNH2. When these hydrazones were allowed to react with conc. HBr, cyclization, followed by dehydrogenation with air occurred, furnished 3‐aryl‐2‐methoxyinden‐1‐one (Z)‐phenylhydrazones 4.
Two New Chemical Constituents of Veratrum dahuricum (Turcz.) Loes. f.
Authors: Cong Yue , Guo Jing‐Gong , Liu Jing
Published: February 2013

Two new chemical constituents, one new steroid, neoveratrenone (1), and one new glycerol ester, 1‐[11‐(ferulyloxy)undecanoyl)]glycerol (2), were isolated and characterized from the roots and rhizomes of Veratrum dahuricum (Turcz.) Loes. f., together with five known compounds, i.e., hexacosanoic acid 2,3‐dihydroxypropyl ester (3), syringaresinol (4), prosapogenin A of dioscin (5), verapatulin (6), and oxyresveratrol (7). Their structures were established by extensive analysis of spectroscopic data as well as by comparison with literature reports. The compounds were evaluated for cytotoxic activity against three tumor cell lines of HepG‐2, HeLa, and K562/S.
Reply to Commentaries
Authors: Brinck Ingar , Liljenfors Rikard
Published: February 2013

In our response, we address four themes arising from the commentaries. First, we discuss the distinction between cognition and metacognition and show how to draw it within our framework. Next, we explain how metacognition differs from social cognition. The underlying mechanisms of metacognitive development are then elucidated in terms of interaction patterns. Finally, we consider measures of metacognition and suitable methods for investigating it. Copyright © 2013 John Wiley & Sons, Ltd.