bluuebunny/crossref_metadata_2025 huggingface dataset:
Methoden zur Reduktion des Teilsicherheitsbeiwerts für Eigenlasten bei Bestandsbrücken
Authors: Löschmann Jens , Ahrens Alexander , Dankmeyer Uwe , Ziem Eberhard , Mark Peter
Published: August 2017

Die Nachrechnungsrichtlinie für Straßenbrücken im Bestand erlaubt eine Reduktion des Teilsicherheitsbeiwerts für Eigenlasten von γG = 1,35 auf den Wert des Modellunsicherheitsfaktors, der konservativ abgeschätzt 1,20 beträgt. Dazu müssen Geometrie, Materialwichten und Bewehrungsgrad durch ausreichende und repräsentative Messungen bekannt sein. Die durch diese drei Größen bestimmte Streuung des Eigengewichts wird im Zuge der Nachrechnung direkt durch die Lastverteilung auf das Bauwerk berücksichtigt. Angaben zu Anforderungen und erforderlichen Genauigkeiten der Messungen werden nicht formuliert.

Der Beitrag zeigt, wie durch Kombinationen von Messungen und empirischen Literaturdaten angepasste Teilsicherheitsbeiwerte abgeleitet werden können. Dabei bietet es sich bei Bestandsbrücken an, die Geometrie aufzumessen, die Streuung der Wichte abzuschätzen und den Bewehrungsgrad aus Bestandsplänen zu entnehmen. Das Vorgehen wird an einer Großbrücke in Düsseldorf angewendet, die in Kooperation mit dem Vermessungs‐ und Katasteramt der Landeshauptstadt Düsseldorf mittels 3‐D‐Laserscanning und Multikopterüberflügen vermessen und zu einem digitalen Brückenmodell aufgearbeitet wurde. Das Verfahren ist relevant für die Nachrechnung, Umnutzung, aber auch den planmäßigen Rückbau von Bestandsbrücken.
Addressing small sample size bias in multiple‐biomarker trials: Inclusion of biomarker‐negative patients and Firth correction
Authors: Habermehl Christina , Benner Axel , Kopp‐Schneider Annette
Published: August 2017

In recent years, numerous approaches for biomarker‐based clinical trials have been developed. One of these developments are multiple‐biomarker trials, which aim to investigate multiple biomarkers simultaneously in independent subtrials. For low‐prevalence biomarkers, small sample sizes within the subtrials have to be expected, as well as many biomarker‐negative patients at the screening stage. The small sample sizes may make it unfeasible to analyze the subtrials individually. This imposes the need to develop new approaches for the analysis of such trials. With an expected large group of biomarker‐negative patients, it seems reasonable to explore options to benefit from including them in such trials. We consider advantages and disadvantages of the inclusion of biomarker‐negative patients in a multiple‐biomarker trial with a survival endpoint. We discuss design options that include biomarker‐negative patients in the study and address the issue of small sample size bias in such trials. We carry out a simulation study for a design where biomarker‐negative patients are kept in the study and are treated with standard of care. We compare three different analysis approaches based on the Cox model to examine if the inclusion of biomarker‐negative patients can provide a benefit with respect to bias and variance of the treatment effect estimates. We apply the Firth correction to reduce the small sample size bias. The results of the simulation study suggest that for small sample situations, the Firth correction should be applied to adjust for the small sample size bias. Additional to the Firth penalty, the inclusion of biomarker‐negative patients in the analysis can lead to further but small improvements in bias and standard deviation of the estimates.
Constitutive Expression of Chimeric Transcription Factors Enables Cellulase Synthesis under Non‐Inducing Conditions in Penicillium oxalicum
Authors: Gao Liwei , Xia Chengqiang , Xu Jiadi , Li Zhonghai , Yu Lele , Liu Guodong , Song Xin , Qu Yinbo
Published: July 2017

Industrial production of cellulase by filamentous fungi is largely dependent on cellulose, which serves as a natural inducer of cellulase expression. However, insoluble cellulose is unfavorable to submerged fermentation and thus limits the production level of cellulase. The possibility of cellulase production under non‐inducing conditions is explored in Penicillium oxalicum by overexpressing two chimeric transcription factors. The chimeric transcription factors contain the DNA binding domain of cellulase transcriptional activator ClrB linked to the C‐terminal sequences of XlnRA871V, a constitutively active mutant of hemicellulase transcriptional activator. The obtained recombinant mutants exhibited dramatically improved basal production of cellulase, which was not observed with the overexpression of intact ClrB. When cultivated in a complex cellulosic medium, one of these mutants, OE‐CXC‐S‐1, displayed a 7.3‐fold increase in cellulase production (2.8 U mL−1) relative to the parent strain. The results demonstrate that the dependence of cellulase synthesis on cellulose could be reduced by the overexpression of artificially designed chimeric transcription factors, and offers a potential strategy to engineer fungal strains for improving cellulase production.
Three dimensional ultrasound and hdlive technology as possible tools in teaching embryology
Authors: Popovici Razvan , Pristavu Anda , Sava Anca
Published: August 2017

Embryology is an important subject in order to gain an understanding of medicine and surgery; however, sometimes students find the subject difficult to grasp and apply to clinical practice. Modern imaging techniques can be useful aids in teaching and understanding embryology. Imaging techniques have very rapidly evolved over the last few years, advancing from two‐ to three‐dimensional (3D) ultrasound. HDlive is an innovative ultrasound technique that generates near‐realistic images of the human fetus. In order to evince the capabilities of 3D ultrasound and HDlive technology in teaching embryology, we evaluated using this technique the normal evolution of the embryo and fetus from the fifth to eleventh week of amenorrhea. Our conclusion is that by yielding clear and impressive images, 3D ultrasound and HDlive could be useful tools in teaching embryology to medical students. Clin. Anat. 30:953–957, 2017. © 2017 Wiley Periodicals, Inc.
A new space of the face: The bucco‐mandibular space
Authors: Iwanaga Joe , Kamura Yasuhiko , Tanaka Tsuyoshi , Watanabe Koichi , Kusukawa Jingo , Oskouian Rod J. , Tubbs R. Shane
Published: August 2017

Our previous studies based on intraoral dissection of fresh cadavers demonstrated the fissure and loose connective tissues behind the mucosa between the incisivus labii inferioris (ILI) and buccinator (BM) muscles. However, this raised new questions about the relationship among these muscles, the fissure and the buccal space. To our knowledge, no pathway to the oral cavity from the buccal space has been previously demonstrated, although such a pathway would better explain some routes of infection. Therefore, the aim of this study was to clarify the relationship among the mimetic muscles attached to the mandible, the fissure, and the buccal space. Twenty sides from 10 fresh frozen adult cadaveric Caucasian heads were used. The relationships among the ILI, BM, mandible, and buccal space were investigated with dissection and fluoroscopy. In all specimens, the fissure between the lateral border of the ILI and the anterior border of the BM formed the entrance of a space (here termed the bucco‐mandibular space), which corresponded to the buccal mucosa in the premolar region. The superior border of this space was formed by the platysma and associated fascia, which was continuous with the masseteric fascia. This fascia clearly separated this space from the buccal space, which was located lateral to the BM and superior to this space. Clin. Anat. 30:958–962, 2017. © 2017 Wiley Periodicals, Inc.
Symmetry‐Directed Self‐Assembly of a Tetrahedral Protein Cage Mediated by de Novo‐Designed Coiled Coils
Authors: Badieyan Somayesadat , Sciore Aaron , Eschweiler Joseph D. , Koldewey Philipp , Cristie‐David Ajitha S. , Ruotolo Brandon T. , Bardwell James C. A. , Su Min , Marsh E. Neil G.
Published: August 2017

The organization of proteins into new hierarchical forms is an important challenge in synthetic biology. However, engineering new interactions between protein subunits is technically challenging and typically requires extensive redesign of protein–protein interfaces. We have developed a conceptually simple approach, based on symmetry principles, that uses short coiled‐coil domains to assemble proteins into higher‐order structures. Here, we demonstrate the assembly of a trimeric enzyme into a well‐defined tetrahedral cage. This was achieved by genetically fusing a trimeric coiled‐coil domain to its C terminus through a flexible polyglycine linker sequence. The linker length and coiled‐coil strength were the only parameters that needed to be optimized to obtain a high yield of correctly assembled protein cages.
Carbonylative Suzuki Coupling Reaction Catalyzed by a Hydrospirophosphorane Palladium Complex
Authors: Wójcik Przemysław , Sygellou Labrini , Gniewek Andrzej , Skarżyńska Anna , Trzeciak Anna
Published: July 2017

A Pd complex with the H‐spirophosphorane ligand, PdCl2{P(OCMe2CMe2O)OC6H4NH2} (Cat. 1), was used as the catalyst in the carbonylative Suzuki coupling of substituted iodobenzenes with arylboronic acids and with sodium tetraphenylborate. Substituted diarylketones were obtained in good to excellent yields and a selectivity over 95 % under 1 atm of CO with 1.5 mol % of the catalyst. The promoting role of the H‐spirophosphorane ligand in the catalytic process was evidenced. We used X‐ray photoelectron spectroscopy, TEM, and 31P NMR spectroscopy to reveal that during the reaction Cat. 1 undergoes transformation into Pd complexes that bear the spirophosphorane ligand or other P ligands formed by its dealkylation and to Pd nanoparticles. All these Pd species contribute to the high productivity of the system.
Velocity Uniformity of Microchannels in a Laminated‐Sheet Structure Under Parallel and Series Methods
Authors: Pan Minqiang , Zhang Yi , Vafai Kambiz
Published: August 2017

An integral microchannel device is generally formed by lamination of multiple microchannel sheets. Uniform velocity distribution among the microchannels in each sheet shows a large influence on the device's performance. The effects of microchannel and manifold structure on the velocity uniformity in each sheet with different structural parameters under parallel and series laminated structures are investigated. For the laminated‐sheet structure where each sheet has the same structural parameters, a more uniform velocity distribution exists as compared to where the structural parameters are different. There exists a direct correlation between the velocity values in each sheet and structural parameters, whereas an inverse correlation is found under series laminated structure.
Experimental and Theoretical Investigation of the Light‐Driven Hydrogen Evolution by Polyoxometalate–Photosensitizer Dyads
Authors: Schönweiz Stefanie , Heiland Magdalena , Anjass Montaha , Jacob Timo , Rau Sven , Streb Carsten
Published: August 2017

The visible‐light‐driven hydrogen evolution reaction (HER) by covalent photosensitizer–catalyst dyads is one of the most elegant concepts in supramolecular homogeneous solar energy conversion. The intricacies of catalyst reactivity and photosensitizer–catalyst interactions require a detailed fundamental understanding of the system to rationalize the observed reactivities. Here, we report three dyads based on the covalent imine‐bond linkage of an iridium photosensitizer and an organo‐functionalized Anderson polyoxometalate anion [MMo6O18{(OCH2)3CNH2}2]3− (M=Mn3+, Fe3+, Co3+). Modification of the central metal ion M is used to modulate the HER activity. Detailed theoretical and experimental studies examine the role of the central metal ion M and provide critical understanding of the redox activity and light‐driven HER activity of the novel dyads. Thus, the study enables a knowledge‐based optimization of HER dyads by chemical modification of the reactive metal oxide components.
Structure–Property Relationship Study of Donor and Acceptor 2,6‐Disubstituted BODIPY Derivatives for High Performance Dye‐Sensitized Solar Cells
Authors: Yeh Shih‐Chieh , Wang Li‐Jing , Yang Hong‐Ming , Dai Yu‐Huei , Lin Chao‐Wen , Chen Chin‐Ti , Jeng Ru‐Jong
Published: August 2017

Seven donor and acceptor 2,6‐disubstituted 4,4‐difluoro‐4‐bora‐3a,4a‐diaza‐s‐indacene (BODIPY) dyes have been synthesized and characterized. Including MPBTCA, which is a known compound, the seven BODIPY dyes have been characterized by varied physical methods, such as UV/Visible absorption spectroscopy, low energy photo‐electron spectroscopy (AC‐2), and HOMO‐LUMO DFT/TDDFT calculation. All seven BODIPY dyes have absorption λmax around 535–545 nm, which is significantly longer than 499 nm of 4,4‐difluoro‐1,3,5,7,8‐pentamethyl‐4‐bora‐3a,4a‐diaza‐s‐indacene (PM 546). Having structural variation on donor group, acceptor group, donor π‐spacer, acceptor π‐spacer, and the substituent on boron, some BODIPY dyes exhibit small extinction coefficients or spectral integrals in solution (MPCtBTCA, MPBT‐pyO, MPBTT‐pyO, MTBTCA), broadening absorption spectral profile (MTBTCA), weak intramolecular charge transfer characteristics (MPBT‐pyO, MPBTT‐pyO, MTBTCA), too low LUMO energy level (PPBTCA), or insufficient dye‐uptake by TiO2 FTO (MPBT‐pyO, MPBTT‐pyO, MTBTCA). Two of the seven BODIPY dyes, MPBTCA and MPBTTCA, do not show the adverse properties like other BODIPY dyes. With our improved TiO2 FTO (fluorine doped tin oxide) dyeing method, namely a solution dropping method, high performance dye‐sensitized solar cells (DSCs) have been realized by MPBTCA and MPBTTCA photosensitizers. Power conversion efficiencies of 6.3 and 6.4 % have been achieved by MPBTCA and MPBTTCA DSCs, respectively. To the best of our knowledge, MPBTCA and MPBTTCA are the most efficient dyes for the donor and acceptor 2,6‐disubstituted BODIPY DSCs so far.
Laying Waste to Mercury: Inexpensive Sorbents Made from Sulfur and Recycled Cooking Oils
Authors: Worthington Max J. H. , Kucera Renata L. , Albuquerque Inês S. , Gibson Christopher T. , Sibley Alexander , Slattery Ashley D. , Campbell Jonathan A. , Alboaiji Salah F. K. , Muller Katherine A. , Young Jason , Adamson Nick , Gascooke Jason R. , Jampaiah Deshetti , Sabri Ylias M. , Bhargava Suresh K. , Ippolito Samuel J. , Lewis David A. , Quinton Jamie S. , Ellis Amanda V. , Johs Alexander , Bernardes Gonçalo J. L. , Chalker Justin M.
Published: August 2017

Mercury pollution threatens the environment and human health across the globe. This neurotoxic substance is encountered in artisanal gold mining, coal combustion, oil and gas refining, waste incineration, chloralkali plant operation, metallurgy, and areas of agriculture in which mercury‐rich fungicides are used. Thousands of tonnes of mercury are emitted annually through these activities. With the Minamata Convention on Mercury entering force this year, increasing regulation of mercury pollution is imminent. It is therefore critical to provide inexpensive and scalable mercury sorbents. The research herein addresses this need by introducing low‐cost mercury sorbents made solely from sulfur and unsaturated cooking oils. A porous version of the polymer was prepared by simply synthesising the polymer in the presence of a sodium chloride porogen. The resulting material is a rubber that captures liquid mercury metal, mercury vapour, inorganic mercury bound to organic matter, and highly toxic alkylmercury compounds. Mercury removal from air, water and soil was demonstrated. Because sulfur is a by‐product of petroleum refining and spent cooking oils from the food industry are suitable starting materials, these mercury‐capturing polymers can be synthesised entirely from waste and supplied on multi‐kilogram scales. This study is therefore an advance in waste valorisation and environmental chemistry.
Soluble Platinum Nanoparticles Ligated by Long‐Chain N‐Heterocyclic Carbenes as Catalysts
Authors: Martínez‐Prieto Luis M. , Rakers Lena , López‐Vinasco Angela M. , Cano Israel , Coppel Yannick , Philippot Karine , Glorius Frank , Chaudret Bruno , van Leeuwen Piet W. N. M.
Published: August 2017

Invited for the cover of this issue are the groups of Frank Glorius, Bruno Chaudret, and Piet W. N. M. van Leeuwen at the University of Münster (Germany) and at the Laboratoire de Physique et Chimie des Nano‐objets (LPCNO) of Toulouse (France). The image depicts a soluble Pt nanoparticle ligated by a long‐chain N‐heterocyclic carbene (represented as a force field) as an efficient catalyst in hydroboration of acetylenes. Read the full text of the article at 10.1002/chem.201702288.
HBr–DMPU: The First Aprotic Organic Solution of Hydrogen Bromide
Authors: Li Zhou , Ebule Rene , Kostyo Jessica , Hammond Gerald B. , Xu Bo
Published: August 2017

HBr and DMPU (1,3‐dimethyl‐3,4,5,6‐tetrahydro‐2‐pyrimidinone) form a room‐temperature‐stable complex that provides a mild, effective, and selective hydrobrominating reagent toward alkynes, alkenes, and allenes. HBr–DMPU could also replace other halogenating reagents in the halo‐Prins reaction, ether cleavage, and deoxy‐bromination reactions.
Chemical Tagging with tert‐Butyl and Trimethylsilyl Groups for Measuring Intermolecular Nuclear Overhauser Effects in a Large Protein–Ligand Complex
Authors: Jabar Shereen , Adams Luke A. , Wang Yao , Aurelio Luigi , Graham Bim , Otting Gottfried
Published: August 2017

Intermolecular 1H‐1H nuclear Overhauser effects (NOE) present a powerful tool to assess contacts between proteins and binding partners, but are difficult to identify for complexes of high molecular weight. This report shows that intermolecular NOEs can readily be observed following chemical labeling with tert‐butyl or trimethylsilyl (TMS) groups. Proteins can be furnished with tert‐butyl or TMS groups site‐specifically using genetically encoded unnatural amino acids or by chemical modification of single cysteine residues. No isotope labeling is required. The approach is demonstrated with the 95 kDa complex between tetrameric E. coli single‐stranded DNA binding protein (SSB) and single‐stranded DNA.
Facile Synthesis of Novel Perfluorocarbon‐Modulated 4‐Anilinoquinazoline Analogues
Authors: Shi Huiping , Lai Bonan , Chen Shizhen , Zhou Xin , Nie Jing , Ma Jun‐An
Published: August 2017

4‐Anilinoquinazoline analogues stand out among many kinds of small molecules that inhibit the tyrosine kinase activities of epidermal growth factor receptor (EGFR), thus serving as significant molecular targets for anticancer drug design. Herein, a series of novel perfluorocarbon (PFC) modulated 4‐anilinoquinazolines were designed and prepared straightforwardly by nucleophilic substitution reaction of various anilinoquinazolines and PFC‐derived methanesulfonate. In the presence of base, the reaction proceeded smoothly to afford a wide range of 4‐anilinoquinazolines with different substituents on aniline moiety in good to high yields. Furthermore, the PFC‐modified analogues of gefitinib and erlotinib were also obtained in 93% and 90% respectively, which may have potential for developing new inhibitors of the epidermal growth factor receptor (EGFR) tyrosine kinase and fluorinated contrast agents (CA) for 19F MRI.
Two New C19‐Diterpenoid Alkaloids with Anti‐inflammatory Activity from Aconitum iochanicum
Authors: Guo Ruihua , Guo Chengxin , He Dan , Zhao Dake , Shen Yong
Published: August 2017

Two new C19‐diterpenoid alkaloids, 7,8‐epoxy‐franchetine (1) and N(19)‐en‐austroconitine A (2), were isolated from Aconitum iochanicum. Compound 1 was a new C19‐diterpenoid alkaloid with a 7,8‐epoxy unit. Their structures were elucidated by comprehensive spectroscopic analyses including UV, IR, MS, 1D and 2D NMR. Biological activity tests indicated that two new compounds exhibited inhibitory activity against nitric oxide (NO) production in LPS‐activated RAW264.7 macrophages. Compared with positive control, the two new compounds showed weak anti‐inflammatory effects with the inhibition rate of 27.3% and 29.2%, respectively.
CloudMe forensics: A case of big data forensic investigation
Authors: Teing Yee‐Yang , Dehghantanha Ali , Choo Kim‐Kwang Raymond
Published: August 2017

The significant increase in the volume, variety, and velocity of data complicates cloud forensic efforts, and such (big) evidential data will, at some point, become too (computationally) expensive to be fully identified, collected, and analysed in a timely manner. Thus, it is important for digital forensic practitioners to have an up‐to‐date knowledge of relevant data artefacts that could be forensically recovered from the cloud product under investigation. In this paper, CloudMe, a popular cloud storage service, is studied. The types and locations of the artefacts relating to the installation and uninstallation of CloudMe client application, logging in and out, and file synchronization events from the computer desktop and mobile clients are described. Findings from this research will also help inform future development of tools and techniques (e.g., data mining techniques) for cloud‐enabled big data endpoint forensics investigation.
Electrostatics Explains the Position‐Dependent Effect of G⋅U Wobble Base Pairs on the Affinity of RNA Kissing Complexes
Authors: Abi‐Ghanem Josephine , Rabin Clémence , Porrini Massimiliano , Dausse Eric , Toulmé Jean‐Jacques , Gabelica Valérie
Published: August 2017

In the RNA realm, non‐Watson–Crick base pairs are abundant and can affect both the RNA 3D structure and its function. Here, we investigated the formation of RNA kissing complexes in which the loop–loop interaction is modulated by non‐Watson–Crick pairs. Mass spectrometry, surface plasmon resonance, and UV‐melting experiments show that the G⋅U wobble base pair favors kissing complex formation only when placed at specific positions. We tried to rationalize this effect by molecular modeling, including molecular mechanics Poisson–Boltzmann surface area (MMPBSA) thermodynamics calculations and PBSA calculations of the electrostatic potential surfaces. Modeling reveals that the G⋅U stabilization is due to a specific electrostatic environment defined by the base pairs of the entire loop–loop region. The loop is not symmetric, and therefore the identity and position of each base pair matters. Predicting and visualizing the electrostatic environment created by a given sequence can help to design specific kissing complexes with high affinity, for potential therapeutic, nanotechnology or analytical applications.
Supramolecular Architecture of Substituted Tetraphenyl‐carbo‐benzenes from the Energetic Viewpoint
Authors: Shishkina Svitlana V. , Dyakonenko Viktoriya V. , Shishkin Oleg V. , Maraval Valérie , Chauvin Remi
Published: August 2017

The use of DFT‐calculated energy‐vector diagrams (EVDs) featuring the topology of pairwise intermolecular interaction energies is applied to crystals of carbo‐benzenes. A homogeneous set of six ideally centrosymmetric tetraphenyl‐carbo‐benzenes is selected, with various substituents R in para positions: R=4‐anisyl, 1‐ethyl‐2‐phenyl‐1H‐indol‐3‐yl, 2‐chloro‐2‐(1‐ethyl‐2‐phenyl‐1H‐indol‐3‐yl)ethenyl, tetradecyl, and 9,9‐dihexyl‐9H‐fluoren‐2‐yl, 2‐(9,9‐dihexyl‐9H‐fluoren‐2‐yl)ethynyl. The basic structural motifs (BSMs) of the crystals vary from layers to columns, depending on the size and shape of the substituents R. The BSM cohesion is shown to rely on π‐stacking, CH‐π and dispersive interactions. Solvate molecules are shown to have a negligible role in the formation of the BSM, whereas they loosen the interaction between neighbouring BSMs.
A Real‐Time Cytotoxicity Assay as an Alternative to the Standard Chromium‐51 Release Assay for Measurement of Human NK and T Cell Cytotoxic Activity
Authors: Fassy Julien , Tsalkitzi Kyriaki , Goncalves‐Maia Maria , Braud Véronique M.
Published: August 2017

This unit describes the monitoring and quantification of cellular cytotoxicity using a non‐radioactive and real‐time cytotoxic assay. The extent of target‐cell lysis is monitored over time by imaging and quantifying live fluorescent target cells using a cell‐imaging multimode reader. This assay is performed in a 96 well plate in optimized culture conditions at 37°C in the presence of 5% CO2. The basic protocol describes natural killer cell‐mediated cytotoxic assay that can be adapted to include antibodies blocking inhibitory NK receptors or triggering antibody‐dependent cell‐mediated cytotoxicity (ADCC). The assay is also suitable for antigen specific T‐cell cytotoxic assays. Until now, the standard chromium 51 (51Cr)‐release assay has remained the sole sensitive assay but its major drawbacks include cost and hazard of handling radioactivity. The real‐time cytotoxic assay is therefore an effective alternative providing a robust and sensitive assay that accurately monitors lysis of target cells over time. © 2017 by John Wiley & Sons, Inc.
Universal Precautions: Necessary Safety Procedures When Handling Human Blood, Body Fluids, and Specimens
Authors: Bierer Barbara E.
Published: August 2017

Universal precautions are observed whenever handling human blood, body fluids, or specimens as a means of preventing exposure to blood‐borne pathogens. This appendix outlines safety procedures to follow whenever undertaking research activities that involve human blood, body fluids, and specimens. © 2017 by John Wiley & Sons, Inc.
Mass‐Tag Labeling Using Acyl‐PEG Exchange for the Determination of Endogenous Protein S‐Fatty Acylation
Authors: Percher Avital , Thinon Emmanuelle , Hang Howard
Published: August 2017

The covalent coupling of fatty acids to proteins provides an important mechanism of regulation in cells. In eukaryotes, cysteine fatty acylation (S‐fatty acylation) has been shown to be critical for protein function in a variety of cellular pathways as well as microbial pathogenesis. While methods developed over the past decade have improved the detection and profiling of S‐fatty acylation, these are hampered in their ability to characterize endogenous protein S‐fatty acylation levels under physiological conditions. Furthermore, understanding the contribution of specific sites and levels of S‐fatty acylation remains a major challenge. To evaluate S‐fatty acylation of endogenous proteins as well as to determine the number of S‐fatty acylation events, we developed the acyl‐PEG exchange (APE) that utilizes cysteine‐specific chemistry to exchange S‐fatty acylation sites with mass‐tags of defined size, which can be readily observed by western blotting. APE provides a readily accessible approach to investigate endogenous S‐fatty acylation from any sample source, with high sensitivity and broad applicability that complements the current toolbox of methods for thioester‐based post‐translational modifications. © 2017 by John Wiley & Sons, Inc.
The Universally Unrecognized Assumption in Predicting Drug Clearance and Organ Extraction Ratio
Authors: Benet LZ , Liu S , Wolfe AR
Published: August 2017

For almost a half‐century clearance concepts have been utilized in pharmacokinetics to understand the relationship between the dose administered and the time course of systemic concentrations to predict efficacy and safety, as well as how dosing should be modified in disease states. Various models of organ clearance/elimination have been proposed and tested. Surprisingly, however, the theoretical basis for the appropriate data collection to test these models has never been evaluated. Here we show that in vivo data collection limitations and the extraction ratio concept itself are only consistent with the well‐stirred model of hepatic elimination. Evaluating measures of drug concentrations entering and leaving an organ will appear to best fit the well‐stirred model, since driving force concentrations within the organ of elimination cannot be measured.
Use of Early Clinical Trial Data to Support Thorough QT Study Waiver for Upadacitinib and Utility of Food Effect to Demonstrate ECG Assay Sensitivity
Authors: Mohamed Mohamed‐Eslam F. , Zeng Jiewei , Jiang Ping , Hosmane Balakrishna , Othman Ahmed A.
Published: August 2017

Exposure–response analyses of QT data from early‐stage clinical studies represent a valuable tool to assess the QT prolongation potential for drugs in development in lieu of standalone thorough QT (TQT) studies. However, demonstrating adequate electrocardiogram assay sensitivity can be challenging in the absence of a positive pharmacological control. Upadacitinib is a Janus kinase 1 inhibitor currently being evaluated in phase III rheumatoid arthritis trials. Exposure–response analyses to evaluate the QT prolongation potential for upadacitinib from phase I trials and the utility of the effect of food on QTcF to demonstrate ECG assay sensitivity are presented. The analyses demonstrated no effect of upadacitinib on QT interval and confirmed the sensitivity of the ECG assay to detect the small QT shortening effect caused by food. Lack of bias from manual ECG adjudication was also demonstrated. These analyses supported requesting a waiver for the regulatory requirement for a dedicated thorough QT study for upadacitinib.
Voronoi‐Tessellated Graphite Produced by Low‐Temperature Catalytic Graphitization from Renewable Resources
Authors: Zhao Leyi , Zhao Xiuyun , Burke Luke T. , Bennett J. Craig , Dunlap Richard A. , Obrovac Mark N.
Published: August 2017

A highly crystalline graphite powder was prepared from the low temperature (800–1000 °C) graphitization of renewable hard carbon precursors using a magnesium catalyst. The resulting graphite particles are composed of Voronoi‐tessellated regions comprising irregular sheets; each Voronoi‐tessellated region having a small “seed” particle located near their centroid on the surface. This suggests nucleated outward growth of graphitic carbon, which has not been previously observed. Each seed particle consists of a spheroidal graphite shell on the inside of which hexagonal graphite platelets are perpendicularly affixed. This results in a unique high surface area graphite with a high degree of graphitization that is made with renewable feedstocks at temperatures far below that conventionally used for artificial graphites.
Distributed‐element modelling for spiral resonators used in wireless power transfer
Authors: Najjarzadegan M. , Ghotbi I. , Bassirian P. , Jafarabadi Ashtiani S. , Shoaei O. , Shahabadi M.
Published: August 2017

In this paper, a circuit model for the printed circular spiral resonators based on the piece electrical equivalent circuit is presented. Lumped circuit elements such as inductors, resistors, and mutual inductances are calculated using the conventional formulae for circular loops, whereas the mutual capacitances are calculated by a numerical algorithm. These capacitances are renormalized by scaling factors derived from a simulation‐based library of the self‐resonant frequency of the spiral resonators. It is shown that involving minuscule effects such as mutual capacitances of nonadjacent turns causes a more accurate estimation of the current distribution and high‐frequency characteristics of the resonator. Finally, a closed‐form formula for estimating the capacitor values is extracted by curve fitting leading to a decrease in analysis time. The proposed model predicts the input impedance, quality factor, and current distribution along the resonator in agreement with the results generated by full‐wave simulation and experimental results.
Peptide Technologies in the Development of Chemical Tools for Chromatin‐Associated Machinery
Authors: Barnash Kimberly D. , Lamb Kelsey N. , James Lindsey I. , Frye Stephen V.
Published: August 2017

Preclinical Research

Discerning a mechanistic understanding of the cause‐and‐effect relationships between chromatin post‐translational modifications (PTMs) and DNA accessibility for replication, transcription, and repair is an elusive goal being pursued using molecular and cellular biology, biochemistry, and more recently chemical inhibition. Chemical intervention of the chromatin‐associated complexes that regulate PTM maintenance and chromatin structure faces numerous challenges due to the broad surface‐groove interactions between many of these proteins and histones; yet, the increasing interest in understanding chromatin‐modifying complexes suggests tractable lead compounds will be critical for elucidating the mechanisms of chromatin dysregulation in disease states and validating the druggability of these domains. Peptides and peptidomimetics afford several advantages to efficient inhibitor development including a rational starting point, modular assembly, and retention of secondary structure. Numerous peptide technologies have been employed in the chromatin field to characterize substrate interactions, evaluate ligand selectivity, and optimize potent peptidomimetic inhibitors. We describe the progress and advantages of these efforts, and provide a perspective on their implications for future chemical probe and drug discovery efforts. Drug Dev Res 78 : 300–312, 2017. © 2017 Wiley Periodicals, Inc.
Cross‐species comparison of behavioral neurodevelopmental milestones in the common marmoset monkey and human child
Authors: Ausderau Karla K. , Dammann Caitlin , McManus Kathy , Schneider Mary , Emborg Marina E. , Schultz‐Darken Nancy
Published: August 2017

The common marmoset (Callithrix jacchus) is an increasingly popular non‐human primate species for developing transgenic and genomic edited models of neurological disorders. These models present an opportunity to assess from birth the impact of genetic mutations and to identify candidate predictive biomarkers of early disease onset. In order to apply findings from marmosets to humans, a cross‐species comparison of typical development is essential. Aiming to identify similarities, differences, and gaps in knowledge of neurodevelopment, we evaluated peer‐reviewed literature focused on the first 6 months of life of marmosets and compared to humans. Five major developmental constructs, including reflexes and reactions, motor, feeding, self‐help, and social, were compared. Numerous similarities were identified in the developmental sequences with differences often influenced by the purpose of the behavior, specifically for marmoset survival. The lack of detailed knowledge of marmoset development was exposed as related to the vast resources for humans.
Intriguing Electrophilic Reactivity of Donor–Acceptor Cyclopropanes: Experimental and Theoretical Studies
Authors: Dousset Maxime , Parrain Jean‐Luc , Chouraqui Gaëlle
Published: August 2017

A new reactivity of donor–acceptor cyclopropanes (DACs) has been highlighted and, for the first time, we report that they could formally behave as nucleophiles and be functionalized at their C3 position. The donor–acceptor cyclopropane acts as a formal nucleophilic synthetic equivalent of a 1,2‐zwitterion and could be described as an umpolung synthon. A highly substituted lactone is reached, and even more impressive is the formation of four stereogenic centers with complete control of their relative configuration. Both experimental and computational studies were performed to provide an overall picture of the mechanism.
Nanomaterials as stationary phases and supports in liquid chromatography
Authors: Beeram Sandya R. , Rodriguez Elliott , Doddavenkatanna Suresh , Li Zhao , Pekarek Allegra , Peev Darin , Goerl Kathryn , Trovato Gianfranco , Hofmann Tino , Hage David S.
Published: August 2017

The development of various nanomaterials over the last few decades has led to many applications for these materials in liquid chromatography (LC). This review will look at the types of nanomaterials that have been incorporated into LC systems and the applications that have been explored for such systems. A number of carbon‐based nanomaterials and inorganic nanomaterials have been considered for use in LC, ranging from carbon nanotubes, fullerenes and nanodiamonds to metal nanoparticles and nanostructures based on silica, alumina, zirconia and titanium dioxide. Many ways have been described for incorporating these nanomaterials into LC systems. These methods have included covalent immobilization, adsorption, entrapment, and the synthesis or direct development of nanomaterials as part of a chromatographic support. Nanomaterials have been used in many types of LC. These applications have included the reversed‐phase, normal‐phase, ion‐exchange, and affinity modes of LC, as well as related methods such as chiral separations, ion‐pair chromatography and hydrophilic interaction liquid chromatography. Both small and large analytes (e.g., dyes, drugs, amino acids, peptides and proteins) have been used to evaluate possible applications for these nanomaterial‐based methods. The use of nanomaterials in columns, capillaries and planar chromatography has been considered as part of these efforts. Potential advantages of nanomaterials in these applications have included their good chemical and physical stabilities, the variety of interactions many nanomaterials can have with analytes, and their unique retention properties in some separation formats.
Preparation and characterization of a Cu (II)‐IDA poly HEMA monolith syringe for proteomic applications
Authors: Khaparde Ashish , M. A. Vijayalakshmi , Tetala Kishore K. R.
Published: August 2017

Herein, we report the preparation of a metal‐chelate immobilized hydrophilic poly hydroxyethylmethacrylate‐based monolith of 100 μL volume in a plastic syringe. The monolith is elastic in nature, contains well interconnected pores with a permeability (k) of 1.3 × 10−12 m2. Immobilization of iminodiacetic acid (IDA) is performed via schiff base reaction. Adsortion of IgG on this copper‐IDA monolith is of langmuir isotherm with a maximum adsorption capacity of ∼25 mg IgG per g monolith. IgG adsorption capacity of this affinity monolith remained unaffected with increase of flow rate. This proposed metal‐chelate monolith in syringe format has the potential for application in proteomics.
Embodiment Mediates the Relationship between Avoidant Attachment and Eating Disorder Psychopathology
Authors: Monteleone Alessio Maria , Castellini Giovanni , Ricca Valdo , Volpe Umberto , De Riso Francesco , Nigro Massimiliano , Zamponi Francesco , Mancini Milena , Stanghellini Giovanni , Monteleone Palmiero , Treasure Janet , Maj Mario
Published: August 2017

Objective

The overvaluation of body shape and weight of persons with eating disorders (EDs) is putatively explained by a disturbance in the way they experience their own body (embodiment). Moreover, attachment disorders seem to promote the use of body as source for self‐definition. Therefore, we assessed the role of embodiment in the connection between attachment styles and ED psychopathology.

Method

One‐hundred and thirteen ED patients and 117 healthy subjects completed the Identity and Eating Disorders (IDEA) Questionnaire, the Eating Disorder Inventory‐2 (EDI‐2) and the Experiences in Close Relationships Scale.

Results

Eating disorder patients displayed IDEA, EDI‐2 and Experiences in Close Relationships scores significantly higher than controls. IDEA total and subtotal scores mediated entirely the influence of avoidant attachment on EDI‐2 interoceptive awareness and impulsivity.

Discussion

These findings demonstrate a relationship between insecure attachment and disorders of identity and embodiment and point to embodiment as a possible mediator between avoidant attachment and specific ED psychopathological traits. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.
The influence of climate and microclimate (aspect) on soil creep efficiency: Cinder cone morphology and evolution along the eastern Mediterranean Golan Heights
Authors: Ben‐Asher Matan , Haviv Itai , Roering Joshua J. , Crouvi Onn
Published: August 2017

Although hillslope evolution has been subject to much investigation for more than a century, the effect of climate on the morphology of soil‐mantled hillslopes remains poorly constrained. In this study, we perform numerical simulations of volcanic cinder cones in the Golan Heights (eastern Mediterranean) to estimate soil transport efficiency across a significant north–south gradient in mean annual precipitation (1100 to 500 mm). We use the initial cinder cone morphology (constrained by stratigraphy), the modern hillslope form (surveyed with sub‐meter accuracy) and the eruption age (based on 40Ar–39Ar chronology) to predict the best‐fit value of the soil transport coefficient (‘diffusivity’) based on a nonlinear transport model. Our results indicate that the best‐fit diffusivity (K) varies from 1 to 6 m2 ka−1 among the five cinder cones in our field area. Diffusivity (K) values vary systematically with precipitation and hillslope aspect; specifically, K is higher on south‐facing (drier) hillslopes and decreases with mean annual precipitation. We interpret this climate dependency to reflect vegetation‐driven variations in apparent soil cohesion, which increases with root network density, and attenuation of rain splash and overland flow erosion, which increases with vegetative ground cover. To assess how vegetative root mass and ground cover vary with precipitation and aspect, we quantified the spatial distribution of NDVI (normalized difference vegetation index) from ASTER satellite images and observed spatial variations that correlate with our calibrated values of K. Analysis of previously studied cinder cones in the USA can be used to extend our framework to arid domains. This endeavor suggests a humped relationship between K and precipitation with maximum diffusivity at mean annual precipitation of 400–600 mm. Copyright © 2017 John Wiley & Sons, Ltd.
Examining Students' Ability to Critique Arguments and Exploring the Implications for Assessment and Instruction
Authors: Song Yi , Deane Paul , Fowles Mary
Published: August 2017

This study assessed 1,706 eighth‐grade students' reasoning abilities through a critique task in an integrated argumentative reading and writing test. Results indicate that the majority of students did not detect fallacious arguments or clearly explain problems in the arguments. They encountered various challenges in critiquing an argument: (a) being off‐task, (b) failing to identify fallacious arguments, (c) having difficulty explaining specific problems in reasoning, and (d) not connecting their criticisms with particular parts of the text being critiqued. Task design and instructional implications are discussed.
Variational multiscale approximation of the one‐dimensional forced Burgers equation: The role of orthogonal subgrid scales in turbulence modeling
Authors: Bayona Camilo , Baiges Joan , Codina Ramon
Published: August 2017

A numerical approximation for the one‐dimensional Burgers equation is proposed by means of the orthogonal subgrid scales–variational multiscale (OSGS‐VMS) method. We evaluate the role of the variational subscales in describing the Burgers “turbulence” phenomena. Particularly, we seek to clarify the interaction between the subscales and the resolved scales when the former are defined to be orthogonal to the finite‐dimensional space. Direct numerical simulation is used to evaluate the resulting OSGS‐VMS energy spectra. The comparison against a large eddy simulation model is presented for numerical discretizations in which the grid is not capable of solving the small scales. An accurate approximation to the phenomena of turbulence is obtained with the addition of the purely dissipative numerical terms given by the OSGS‐VMS method without any modification of the continuous problem.
Procedure to select test organisms for environmental risk assessment of genetically modified crops in aquatic systems
Authors: Hilbeck Angelika , Bundschuh Rebecca , Bundschuh Mirco , Hofmann Frieder , Oehen Bernadette , Otto Mathias , Schulz Ralf , Trtikova Miluse
Published: July 2017

For a long time, the environmental risk assessment (ERA) of genetically modified (GM) crops focused mainly on terrestrial ecosystems. This changed when it was scientifically established that aquatic ecosystems are exposed to GM crop residues that may negatively affect aquatic species. To assist the risk assessment process, we present a tool to identify ecologically relevant species usable in tiered testing prior to authorization or for biological monitoring in the field. The tool is derived from a selection procedure for terrestrial ecosystems with substantial but necessary changes to adequately consider the differences in the type of ecosystems. By using available information from the Water Framework Directive (2000/60/EC), the procedure can draw upon existing biological data on aquatic systems. The proposed procedure for aquatic ecosystems was tested for the first time during an expert workshop in 2013, using the cultivation of Bacillus thuringiensis (Bt) maize as the GM crop and 1 stream type as the receiving environment in the model system. During this workshop, species executing important ecological functions in aquatic environments were identified in a stepwise procedure according to predefined ecological criteria. By doing so, we demonstrated that the procedure is practicable with regard to its goal: From the initial long list of 141 potentially exposed aquatic species, 7 species and 1 genus were identified as the most suitable candidates for nontarget testing programs. Integr Environ Assess Manag 2017;13:974–979. © 2017 SETAC

Key Points

A species selection procedure is described to identify potential test species that are likely exposed in the field and may be at risk to suffer from the cultivation of genetically modified (GM) crops. Thereby this procedure could support the environmental risk assessment of GM crops. Potential improvements for the selection procedure are discussed.
Risk of appendiceal endometriosis among women with deep‐infiltrating endometriosis
Authors: Moulder Janelle K. , Siedhoff Matthew T. , Melvin Kathryn L. , Jarvis Elizabeth G. , Hobbs Kumari A. , Garrett Joanne
Published: July 2017

Objective

To determine whether deep‐infiltrating endometriosis (DE) carries an increased risk of appendiceal endometriosis (AppE) as compared with superficial endometriosis or no endometriosis.

Methods

In a retrospective study, data were obtained by chart review of an internal database for women who underwent coincidental appendectomy during benign gynecologic surgery between July 2009 and February 2014 at a tertiary referral center in the USA. Univariate, bivariate, and regression analyses were performed. The primary exposure was surgically documented endometriosis (DE, superficial, or no endometriosis). The primary outcome was AppE.

Results

Endometriosis was diagnosed for 151 (38.2%) of 395 women; 82 (54.3%) had DE. The prevalence of AppE was 13.2% (52/395) overall; 8 (11.6%) of 69 women with superficial endometriosis and 32 (39.0%) of 82 with DE were affected. Frequency of AppE was increased among women with DE, abnormal appendix appearance, and surgical indication (all P<0.001). Women with DE had a 5.9‐fold (95% confidence interval [CI] 2.9–11.9) higher risk of AppE compared with women without endometriosis, controlling for appendiceal appearance and surgical indication, and a 2.7‐fold (95% CI 1.2–6.2) higher risk of AppE compared with those with superficial endometriosis.

Conclusion

Women with DE have increased risk of AppE. Coincidental appendectomy should form part of complete endometriosis excision for these patients.