bluuebunny/crossref_metadata_2025 huggingface dataset:
ARWU ranking uncertainty and sensitivity: What if the award factor was Excluded?
Authors: Dobrota Milan , Dobrota Marina
Published: June 2015

The Academic Ranking of World Universities (ARWU) uses six university performance indicators, including “Alumni” and “Awards”—the number of alumni and staff winning Nobel Prizes and Fields Medals. These two indicators raised doubts about the reliability of this ranking method because they are difficult to cope with. Recently, a newsletter was published featuring a reduced ARWU ranking list, leaving out Nobel Prize and Fields Medal indicators: the Alternative Ranking (Excluding Award Factor). We used uncertainty and sensitivity analyses to examine and compare the stability and confidence of the official ARWU ranking and the Alternative Ranking. The results indicate that if the ARWU ranking is reduced to the 4‐indicator Alternative Ranking, it shows greater certainty and stability in ranking universities.
An automatic method for assessing the teaching impact of books from online academic syllabi
Authors: Kousha Kayvan , Thelwall Mike
Published: June 2015

Scholars writing books that are widely used to support teaching in higher education may be undervalued because of a lack of evidence of teaching value. Although sales data may give credible evidence for textbooks, these data may poorly reflect educational uses of other types of books. As an alternative, this article proposes a method to search automatically for mentions of books in online academic course syllabi based on Bing searches for syllabi mentioning a given book, filtering out false matches through an extensive set of rules. The method had an accuracy of over 90% based on manual checks of a sample of 2,600 results from the initial Bing searches. Over one third of about 14,000 monographs checked had one or more academic syllabus mention, with more in the arts and humanities (56%) and social sciences (52%). Low but significant correlations between syllabus mentions and citations across most fields, except the social sciences, suggest that books tend to have different levels of impact for teaching and research. In conclusion, the automatic syllabus search method gives a new way to estimate the educational utility of books in a way that sales data and citation counts cannot.
How much does the expected number of citations for a publication change if it contains the address of a specific scientific institute? A new approach for the analysis of citation data on the institutional level based on regression models
Authors: Bornmann Lutz
Published: June 2015

Citation data for institutes are generally provided as numbers of citations or as relative citation rates (as, for example, in theLeiden Ranking). These numbers can then be compared between the institutes. This study aims to present a new approach for the evaluation of citation data at the institutional level, based on regression models. As example data, the study includes all articles and reviews from the Web of Science for the publication year 2003 (n = 886,416 papers). The study is based on an in‐house database of theMaxPlanck Society. The study investigates how much the expected number of citations for a publication changes if it contains the address of an institute. The calculation of the expected values allows, on the one hand, investigating how the citation impact of the papers of an institute appears in comparison with the total of all papers. On the other hand, the expected values for several institutes can be compared with one another or with a set of randomly selected publications. Besides the institutes, the regression models include factors which can be assumed to have a general influence on citation counts (e.g., the number of authors).
The effects of research level and article type on the differences between citation metrics and F1000 recommendations
Authors: Du Jian , Tang Xiaoli , Wu Yishan
Published: June 2015

F1000 recommendations were assessed as a potential data source for research evaluation, but the reasons for differences between F1000 Article Factor (FFa scores) and citations remain unexplored. By linking recommendations for 28,254 publications in F1000 with citations in Scopus, we investigated the effect of research level (basic, clinical, mixed) and article type on the internal consistency of assessments based on citations and FFa scores. The research level has little impact on the differences between the 2 evaluation tools, while article type has a big effect. These 2 measures differ significantly for 2 groups: (a) nonprimary research or evidence‐based research are more highly cited but not highly recommended, while (b) translational research or transformative research are more highly recommended but have fewer citations. This can be expected, since citation activity is usually practiced by academic authors while the potential for scientific revolutions and the suitability for clinical practice of an article should be investigated from a practitioners' perspective. We conclude with a recommendation that the application of bibliometric approaches in research evaluation should consider the proportion of 3 types of publications: evidence‐based research, transformative research, and translational research. The latter 2 types are more suitable for assessment through peer review.
URL decay at year 20: A research note
Authors: Oguz Fatih , Koehler Wallace
Published: June 2015

All text is ephemeral. Some texts are more ephemeral than others. The web has proved to be among the most ephemeral and changing of information vehicles. The research note revisits Koehler's original data set after about 20 years since it was first collected. By late 2013, the number of URLs responding to a query had fallen to 1.6% of the original sample. A query of the 6 remaining URLs in February 2015 showed only 2 still responding.
A G/G(n)/C/C state‐dependent simulation model for metro station corridor width design
Authors: Jiang Yangsheng , Zhu Juanxiu , Hu Lu , Lin Xi , Khattak Afaq
Published: June 2015

Metro station corridor and passengers are described as a G/G(n)/C/C state‐dependent queuing system with a general random arrival interval G and a general random and state‐dependent service time G(n) to offset the shortcomings in existing design methods. The corresponding G/G(n)/C/C state‐dependent discrete event simulation model is developed, and its high‐fidelity is tested. Then the optimization algorithm based on the simulation model is designed to determine corridor width. The proposed simulation optimization method and the existing analytical optimization methods, based on M/G(n)/C/C and D/D/1/C queuing models, are applied to design corridor width in a numerical example of 48 combinations of passenger flow rates and level of service (LOS). The designed corridor widths are tested in a micro‐simulation model, and the performance measure is compared. The result shows that the corridor widths obtained by the new method are 0.357 m (7.4%) larger than that of the other two methods on average; the area per passenger of the new method increases 10.53% and 11.63%, respectively, compared with that of the other two methods; the widths designed by the new method satisfy the requirement of LOS under various passenger flows, whereas 93% of the corridor widths obtained by the other two methods fail to meet the requirement of LOS, and the corridor widths designed by the new method have high elasticity coefficients of LOS‐width. Copyright © 2015 John Wiley & Sons, Ltd.
Spannbett‐Vorspannung dünner Carbonbeton‐Platten
Authors: Forstlechner Franz Xaver , Freytag Bernhard , Peters Stefan
Published: June 2015

Der vorliegende Bericht beschreibt Untersuchungen über die Eignung besandeter CFK‐Lamellen als Spannglieder für dünne Carbonbeton‐Platten. Da die Einleitung der Vorspannkraft ausschließlich über Verbund zwischen Spannglied und Beton erfolgt, werden im Rahmen der Arbeit Auszieh‐ und Spannkraft‐Einleitungsversuche durchgeführt. Durch die Versuche wird die Verbund‐Arbeitslinie ermittelt und die Einleitungslänge der Vorspannkraft abgeschätzt. Darüber hinaus wird durch 4‐Punkt‐Biegeversuche das Tragverhalten vorgespannter Carbonbeton‐Platten untersucht und die Einflüsse der Verbundfestigkeit erörtert. Auf Grundlage der gewonnen Erkenntnisse wird ein Modell zur Beschreibung des Biegetragverhaltens erstellt und ein Bemessungskonzept abgeleitet.

Pre‐tensioning of thin‐walled carbon‐concrete slabs

The present article describes investigations on the suitability of sanded CFRP‐slats as tendons for thin‐walled carbon‐concrete slabs. Since the pre‐stressing force is introduced into the member only by bond between tendon and concrete, pull‐out and pre‐stress introduction tests are performed in the context of this work. Based on the results of these tests the bond‐slip diagram is determined and the pre‐stress introduction length is estimated. Furthermore, the structural behaviour of pre‐stressed carbon‐concrete slabs is investigated by means of bending tests, and the influences of reinforcement's bond characteristics are discussed. From the obtained test results a model is derived describing the bending behaviour. Finally, dimensioning recommendations for pre‐stressed carbon‐concrete slabs are proposed.
Zeitliche Entwicklung der Betondruckfestigkeit und ihr Einfluss auf das Tragverhalten von Befestigungen
Authors: Zeman Oliver , Schwenn Michael , Bergmeister Konrad
Published: June 2015

Die Zunahme der Betondruckfestigkeit im Laufe der Zeit ist ein durch eine Vielzahl an Versuchen und Untersuchungen bekanntes Phänomen. Die zur Abschätzung der zeitlichen Entwicklung bekannten semi‐empirischen Formelapparate lassen nur die Bestimmung eines Schätzwerts zu. Im Rahmen dieses Beitrags soll gezeigt werden, dass auf Grundlage vorhandener Prüfergebnisse die Gültigkeit dieser Abschätzung für eine statistisch relevante Vielzahl an Ergebnissen auch bei von den Standardbedingungen abweichenden Lagerungsbedingungen angenommen werden kann. Darüber hinaus wird auf Grundlage der sich zeitlich verändernden Betondruckfestigkeit von Probekörpern die Entwicklung der Ausbruchslasten in Beton mit einer erhöhten Betondruckfestigkeit im Vergleich zum Standardbeton C20/25 betrachtet. Anhand von Versuchsreihen, welche an verschiedenen Befestigungssystemen durchgeführt wurden, kann gezeigt werden, dass auch bei höherer Betondruckfestigkeit bei vergleichbaren Versagensmechanismen davon ausgegangen werden kann, dass die Einzelresultate derselben statistischen Grundgesamtheit entstammen.

Time dependent development of concrete compressive strength and the influence on the bearing capacity of post‐installed anchorages

The increase of the concrete compressive strength is a well‐known phenomenon and has been proved by lots of investigations. Nevertheless the semi‐empiric formulas only allow the determination of an estimated value. Within this contribution based on test results it is discussed if these formulas can also be applied in deviating environmental conditions of the test members. In addition based on the time dependent behaviour of the concrete compressive strength test series of post‐installed anchorages in standard concrete C20/25 are compared to tests which have been performed in concrete with a higher strength which does no longer fulfil the requirements of the relevant regulations. In case of invariant failure modes it is shown that on a few test series of anchorages the test results in the higher strength concrete can be seen statistically based from the same population.
Inhibition of cell adhesion and immune responses in the mouse model of collagen‐induced arthritis with a peptidomimetic that blocks CD2‐CD58 interface interactions
Authors: Gokhale Ameya S. , Sable Rushikesh , Walker Jason D. , McLaughlin Leslie , Kousoulas Konstantin G. , Jois Seetharama D.
Published: June 2015

CD2 and CD58 are two important costimulatory molecules involved in generating the signal II required for normal immune signaling. However, this interaction can be targeted to be of benefit in cases of abnormal immune signaling seen in autoimmune diseases. Our objective in this study was to design a peptidomimetic (compound 7) based on a β‐strand structure of the adhesion domain of CD2 protein to inhibit CD2‐CD58 protein‐protein interaction and its effect on immunomodulation in the collagen‐induced arthritis (CIA) model. The ability of compound 7 to bind to CD58 protein was assessed using flow cytometry. The effect of compound 7 on modulating the immune response was evaluated in an autoimmune disease using CIA in mice. The stability of compound 7 was evaluated in mouse serum using mass spectrometry. Antibody (Ab) binding inhibition studies suggested that compound 7 binds to CD58 protein. Compound 7 was successful in modulating immune responses when administered in the CIA mouse model along with reducing anti‐collagen Ab levels and decreasing the level of interferon gamma (IFN‐γ) relative to control treatments. Compound 7 was found to be nonimmunogenic and stable in mouse serum up to 48 h. Results suggest that compound 7 can serve as a lead compound for immunomodulation, and could be a therapeutic agent for the autoimmune disease rheumatoid arthritis (RA). © 2015 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 104: 733–742, 2015.
Automated pipeline for rapid production and screening of HIV‐specific monoclonal antibodies using pichia pastoris
Authors: Shah Kartik A. , Clark John J. , Goods Brittany A. , Politano Timothy J. , Mozdzierz Nicholas J. , Zimnisky Ross M. , Leeson Rachel L. , Love J.Christopher , Love Kerry R.
Published: June 2015

Monoclonal antibodies (mAbs) that bind and neutralize human pathogens have great therapeutic potential. Advances in automated screening and liquid handling have resulted in the ability to discover antigen‐specific antibodies either directly from human blood or from various combinatorial libraries (phage, bacteria, or yeast). There remain, however, bottlenecks in the cloning, expression and evaluation of such lead antibodies identified in primary screens that hinder high‐throughput screening. As such, “hit‐to‐lead identification” remains both expensive and time‐consuming. By combining the advantages of overlap extension PCR (OE–PCR) and a genetically stable yet easily manipulatable microbial expression host Pichia pastoris, we have developed an automated pipeline for the rapid production and screening of full‐length antigen‐specific mAbs. Here, we demonstrate the speed, feasibility and cost‐effectiveness of our approach by generating several broadly neutralizing antibodies against human immunodeficiency virus (HIV). Biotechnol. Bioeng. 2015;112: 2624–2629. © 2015 Wiley Periodicals, Inc.
Von der Krebsschale in die Creme
Authors: Brück Wolfram , Bracharz Felix , Brück Dieter W. , Brück Thomas B.
Published: June 2015

Chitin ist eines der am häufigsten vorkommenden Biopolymere der Erde. Große Mengen dieses Rohstoffes können aus Schalenresten der Fischerei‐Industrie gewonnen werden. Allerdings sind die etablierten chemischen Technologien mit hohen Umweltbelastungen verbunden. Die mikrobiologische Fermentation und der Einsatz von Enzymen zur Gewinnung des Polymers haben sich als wertvolle Alternative erwiesen, bei der gleichzeitig auch andere Wertstoffe gewonnen werden können. Allerdings ist durch die Vielfalt der benutzten Organismen und Bedingungen und die daraus folgenden unterschiedlichen Ausbeuten schwer zu beurteilen, welche Methode sich am besten zur industriellen Produktion eignet. Chitin und seine Derivate zeigen jedoch großes Potenzial als Antioxidantien, Antimikrobiotika und Bindemittel und finden bereits in der Lebensmitteltechnik, der Medizin, in der Landwirtschaft und in Konsumgütern Verwendung. Um die Innovation auf diesem Gebiet voranzutreiben, ist ein interdisziplinärer Ansatz aus Biologie und Chemie erforderlich.
Krieg der Korallen
Authors: Knop Daniel
Published: June 2015

Korallen haben als festsitzende Nesseltiere zahlreiche Strategien entwickelt, um im Kampf um die begrenzte Ressource Siedlungsraum zu bestehen. Dazu gehören neben Konfliktvermeidung durch schnelles Wachstum und ausgeprägten Höhenwuchs auch aggressives Verhalten, bei dem das gegnerische Körpergewebe nicht nur zerstört, sondern sogar verdaut und resorbiert wird, um aus dessen Untergang Vorteile zu ziehen.
“Flora Graeca” – das teuerste Botanik‐Buch der Welt in der Universitätsbibliothek Darmstadt
Authors: Schneckenburger Stefan
Published: June 2015

Zwischen 1806 und 1840 erschien in England die zehnbändige “Flora Graeca”, die als das schönste und teuerste je gedruckte botanische Buch gilt. Darüber hinaus ist es eines der seltensten Werke: Es wurden nur 25 Exemplare produziert. Seit einigen Monaten erst ist bekannt, dass die Hessische Universitäts‐ und Landesbibliothek in Darmstadt eines davon besitzt.
Vom Labor in die Küche: Alginat
Authors: Hauk Andrea
Published: June 2015

Wussten Sie, dass sich Spitzenköche aus dem Fundus der Labormethoden inspirieren lassen? So finden verschiedene Techniken in der so genannten “molekularen Küche” Verwendung. Neben der Eisherstellung mittels flüssigem Stickstoff, der Fleischzubereitung im Vakuumgarer oder dem Aufschäumen verschiedener Flüssigkeiten kommt die Alginat‐Methode, die wir unter anderem aus Laborexperimenten kennen, zur Anwendung.
Wollbienen und Weinschwärmer: Insekten‐Highlights im Hochsommer
Authors: Petrischak Hannes
Published: June 2015

Die Vielfalt der Insekten wird auch im Garten durch verblüffende Verhaltensweisen, einen manchmal skurril anmutenden Körperbau und interessante Lebenszyklen repräsentiert. So regen Wollbienen‐Männchen, die einen ganzen Sommer lang auf der Terrasse ihre Lavendelblüten unermüdlich gegen alle anderen Blütenbesucher verteidigen, nicht selten zu stundenlangen Beobachtungen an.
Charge Transfer and Photocatalytic Activity in CuO/TiO2 Nanoparticle Heterojunctions Synthesised through a Rapid, One‐Pot, Microwave Solvothermal Route
Authors: Moniz Savio J. A. , Tang Junwang
Published: June 2015

The front cover artwork for Issue 11/2015 is provided by the group of Dr. Junwang Tang, University College London. The image shows how solar energy can be utilised to efficiently decontaminate wastewater supplies by using nanostructured heterojunction photocatalysts. See the Full Paper itself at http://dx.doi.org/10.1002/cctc.201500315.
Energy Optimization for a Multistage Crude Oil Distillation Process
Authors: Gu Wugen , Wang Kan , Huang Yuqing , Zhang Bingjian , Chen Qinglin , Hui Chi‐Wai
Published: June 2015

Energy optimization is a hot research topic for design and operation of crude oil distillation plants. Optimum energy utilization in a multistage crude oil distillation process is achieved by optimizing the distillation load of each distillation column as well as the yield of the sidestreams of distillation columns. A generalized multistage distillation energy consumption model is proposed, and the optimal distillation load distribution is accomplished by minimizing the total energy consumption. Based on the optimal distillation loads, a nonlinear programming model is then formulated to determine the yields of sidestreams by maximizing the thermal exergy recovery for the crude oil plant. Finally, a four‐stage crude oil distillation plant is investigated to demonstrate the performance of the proposed approach. The results show a decrease in energy consumption and an increase in heat recovery.
In Situ Formation of Dual‐Phase Thermosensitive Ultrasmall Gold Nanoparticles
Authors: He Zidong , Zhong Aiqing , Zhang Hui , Xiong Linfeng , Xu Yang , Wang Tianqi , Zhou Minghong , Huang Kun
Published: June 2015

A novel method for the in situ synthesis of dual‐phase thermosensitive ultrasmall gold nanoparticles (USGNPs) with diameters in the range of 1–3 nm was developed by using poly(N‐isopropylacrylamide)‐block‐poly(N‐phenylethylenediamine methacrylamide) (PNIPAM‐b‐PNPEDMA) amphiphilic diblock copolymers as ligands. The PNPEDMA block promotes the in situ reduction of gold precursors to zero‐valent gold and subsequently binds to the surface of gold nanoparticles, while PNIPAM acts as a stabilizing and thermosensitive block. The as‐synthesized USGNPs stabilized by a thermosensitive PNIPAM layer exhibit a sharp, reversible, clear–opaque transition in aqueous solution between 30 and 38 °C. An unprecedented finding is that these USGNPs also show a reversible soluble–precipitate transition in nonpolar organic solvents such as chloroform at around 0 °C under acidic conditions.
Mask‐Like Symmetrical Microclusters through a Diffusion‐Limited Assembly Approach
Authors: Wu Hong , Tian Chunyong , Zhang Yufei , Shi Jiafu , Yang Chen , Zhang Songping , Jiang Zhongyi
Published: June 2015

A diffusion‐limited assembly approach was explored to fabricate symmetrical [Cu(Succinate)]n microclusters with a different shape and size for the first time. The molecular structure of succinate and its coordination reaction capability towards copper(II) ions governed the one‐dimensional growth of the nanofibers and the concomitant formation of the microclusters. In detail, a symmetrical concentration gradient was formed around the endpoints of the nanofibers caused by the diffusion‐limited process at high reactant concentrations. The concentration gradient forced the nanofibers to grow divergently and further aggregate into open microcluster structure. The shape and size of the microclusters could be tuned by altering the concentration of the reactants. Particularly, mask‐like double‐hole symmetrical microclusters (MDHSMs) were obtained when the concentration of both reactants was as high as 140 mM. The resultant MDHSMs showed high selectivity in adsorption of dyes and proteins, and may find potential applications in water treatment, bioseparation, and immobilization of biomacromolecules.
Dual Role of the 1,2,3‐Triazolium Ring as a Hydrogen‐Bond Donor and Anion–π Receptor in Anion‐Recognition Processes
Authors: Zapata Fabiola , Gonzalez Lidia , Caballero Antonio , Alkorta Ibón , Elguero Jose , Molina Pedro
Published: June 2015

Several bis(triazolium)‐based receptors have been synthesized as chemosensors for anion recognition. The central naphthalene core features two aryltriazolium side‐arms. NMR experiments revealed differences between the binding modes of the two triazolium rings: one triazolium ring acts as a hydrogen‐bond donor, the other as an anion–π receptor. Receptors 92+⋅2BF4− (C6H5), 112+⋅2BF4− (4‐NO2C6H4), and 132+⋅2BF4− (ferrocenyl) bind HP2O73− anions in a mixed‐binding mode that features a combination of hydrogen‐bonding and anion–π interactions and results in strong binding. On the other hand, receptor 102+⋅2 BF4− (4‐CH3OC6H4) only displays combined Csp2H/anion–π interactions between the two arms of the receptors and the bound anion rather than triazolium (CH)+⋅⋅⋅anion hydrogen bonding. All receptors undergo a downfield shift of the triazolium protons, as well as the inner naphthalene protons, in the presence of H2PO4− anions. That suggests that only hydrogen‐bonding interactions exist between the binding site and the bound anion, and involve a combination of cationic (triazolium) and neutral (naphthalene) CH donor interactions. Theoretical calculations relate the electronic structure of the substituent on the aromatic group with the interaction energies and provide a minimum‐energy conformation for all the complexes that explains their measured properties.
Spontaneous Generation of Chirality in Simple Diaryl Ethers
Authors: Lennartson Anders , Hedström Anna , Håkansson Mikael
Published: June 2015

We studied the spontaneous formation of chiral crystals of four diaryl ethers, 3‐phenoxybenzaldehyde, 1; 1,3‐dimethyl‐2‐phenoxybenzene, 2; di(4‐aminophenyl) ether, 3; and di(p‐tolyl) ether, 4. Compounds 1, 3, and 4 form conformationally chiral molecules in the solid state, while the chirality of 2 arises from the formation of supramolecular helices. Compound 1 is a liquid at ambient temperature, but 2, 3, 4 are crystalline, and solid‐state CD‐spectroscopy showed that they could be obtained as optically active bulk samples. It should be noted that the optical activity arise upon crystallization, and no optically active precursors were used. Indeed, even commercial samples of 3 and 4 were found to be optically active, giving evidence for the ease at which total spontaneous resolution may occur in certain systems. Chirality 27:425‐429, 2015. © 2015 Wiley Periodicals, Inc.
Synthesis, Chiral Separation, Absolute Configuration Assignment, and Biological Activity of Enantiomers of Retro‐1 as Potent Inhibitors of Shiga Toxin
Authors: Abdelkafi Hajer , Michau Aurélien , Clerget Alexandra , Buisson David‐Alexandre , Johannes Ludger , Gillet Daniel , Barbier Julien , Cintrat Jean‐Christophe
Published: June 2015

The Shiga toxin (Stx) family is composed of related protein toxins produced by the bacteria Shigella dysenteriae and certain pathogenic strains of E. coli. No effective therapies for Stx intoxication have been developed yet. However, inhibitors that act on the intracellular trafficking of these toxins may provide new options for the development of therapeutic strategies. This study reports the synthesis, chromatographic separation, and pharmacological evaluation of the two enantiomers of Retro‐1, a compound active against Stx and other such protein toxins. Retro‐1 works by inhibiting retrograde transport of these toxins inside cells. In vitro experiments proved that the configuration of the stereocenter at position 5 is not crucial for the activity of this compound. X‐ray diffraction data revealed (S)‐Retro‐1 to be slightly more active than (R)‐Retro‐1.
MA‐NOTMP: A Triazacyclononane Trimethylphosphinate Based Bifunctional Chelator for Gallium Radiolabelling of Biomolecules
Authors: Poty Sophie , Désogère Pauline , Šimeček Jakub , Bernhard Claire , Goncalves Victor , Goze Christine , Boschetti Frédéric , Notni Johannes , Wester Hans J. , Denat Franck
Published: June 2015

In the past few years, gallium‐68 has demonstrated significant potential as a radioisotope for positron emission tomography (PET), and the optimization of chelators for gallium coordination is a major goal in the development of radiopharmaceuticals. Methylaminotriazacyclononane trimethylphosphinate (MA‐NOTMP), a new C‐functionalized triazacyclononane derivative with phosphinate pendant arms, presents excellent coordination properties for 68Ga (low ligand concentration, labelling at low pH even at room temperature). A “ready‐to‐be‐grafted” bifunctional chelating agent (p‐NCS‐Bz‐MA‐NOTMP) was prepared to allow 68Ga labelling of sensitive biological vectors. Conjugation to a bombesin(7–14) derivative was performed, and preliminary in vitro experiments demonstrated the potential of MA‐NOTMP in the development of radiopharmaceuticals. This new chelator is therefore of major interest for labelling sensitive biomolecules, and further in vivo experiments will soon be performed.
Computational Study of Proton Transfer in Tautomers of 3‐ and 5‐Hydroxypyrazole Assisted by Water
Authors: Trujillo Cristina , Sánchez‐Sanz Goar , Alkorta Ibon , Elguero José
Published: June 2015

The tautomerism of 3‐ and 5‐hydroxypyrazole is studied at the B3LYP, CCSD and G3B3 computational levels, including the gas phase, PCM–water effects, and proton transfer assisted by water molecules. To understand the propensity of tautomerization, hydrogen‐bond acidity and basicity of neutral species is approached by means of correlations between donor/acceptor ability and H‐bond interaction energies. Tautomerism processes are highly dependent on the solvent environment, and a significant reduction of the transition barriers upon solvation is seen. In addition, the inclusion of a single water molecule to assist proton transfer decreases the barriers between tautomers. Although the second water molecule further reduces those barriers, its effect is less appreciable than the first one. Neutral species present more stable minima than anionic and cationic species, but relatively similar transition barriers to anionic tautomers.
Self‐Alignment of Beads and Cell Trapping in Precipitate Tubes
Authors: Batista Bruno C. , Cruz Patrick , Steinbock Oliver
Published: June 2015

Propagating reaction fronts allow the formation of materials in self‐sustained, steep concentration gradients, which would otherwise rapidly decay. These conditions can result in macroscopic, noncrystallographic structures, such as tubes with large aspect ratios. For hollow silica/Zn(OH)2 tubes, we report the inclusion of diverse mesoscopic building blocks ranging from polymer beads to biological cells. For agarose beads, we observe spontaneous alignment along vertical tracks; the nearly periodic spacing of the beads along these tracks follows a log‐normal distribution. We interpret this patterning in terms of hydrodynamic recruitment and discuss similarities to the adhesion dynamics of leukocytes in blood vessels. For diatoms and other cells, we observe novel surface textures, and yeast tagged with a green fluorescent protein shows strong fluorescence activity after trapping. The inclusion of these guest units should improve the possibilities for the application of these tubes in microfluidics and biotechnology.
Physiologically based and population PK modeling in optimizing drug development: A predict–learn–confirm analysis
Authors: Suri A , Chapel S , Lu C , Venkatakrishnan K
Published: June 2015

Physiologically based pharmacokinetic (PBPK) modeling and classical population pharmacokinetic (PK) model‐based simulations are increasingly used to answer various drug development questions. In this study, we propose a methodology to optimize the development of drugs, primarily cleared by the kidney, using model‐based approaches to determine the need for a dedicated renal impairment (RI) study. First, the impact of RI on drug exposure is simulated via PBPK modeling and then confirmed using classical population PK modeling of phase 2/3 data. This methodology was successfully evaluated and applied to an investigational agent, orteronel (nonsteroidal, reversible, selective 17,20‐lyase inhibitor). A phase 1 RI study confirmed the accuracy of model‐based predictions. Hence, for drugs eliminated primarily via renal clearance, this modeling approach can enable inclusion of patients with RI in phase 3 trials at appropriate doses, which may be an alternative to a dedicated RI study, or suggest that only a reduced‐size study in severe RI may be sufficient.
Recycled Poly(vinyl alcohol) Sponge for Carbon Encapsulation of Size‐Tunable Tin Dioxide Nanocrystalline Composites
Authors: Ma Yue , Tai Cheuk‐Wai , Gustafsson Torbjörn , Edström Kristina
Published: June 2015

The recycling of industrial materials could reduce their environmental impact and waste haulage fees and result in sustainable manufacturing. In this work, commercial poly(vinyl alcohol) (PVA) sponges are recycled into a macroporous carbon matrix to encapsulate size‐tunable SnO2 nanocrystals as anode materials for lithium‐ion batteries (LIBs) through a scalable, flash‐combustion method. The hydroxyl groups present copiously in the recycled PVA sponges guarantee a uniform chemical coupling with a tin(IV) citrate complex through intermolecular hydrogen bonds. Then, a scalable, ultrafast combustion process (30 s) carbonizes the PVA sponge into a 3D carbon matrix. This PVA‐sponge‐derived carbon could not only buffer the volume fluctuations upon the Li–Sn alloying and dealloying processes but also afford a mixed conductive network, that is, a continuous carbon framework for electrical transport and macropores for facile electrolyte percolation. The best‐performing electrode based on this composite delivers a rate performance up to 9.72 C (4 A g−1) and long‐term cyclability (500 cycles) for Li+ ion storage. Moreover, cyclic voltammograms demonstrate the coexistence of alloying and dealloying processes and non‐diffusion‐controlled pseudocapacitive behavior, which collectively contribute to the high‐rate Li+ ion storage.
Contrasting developmental axon regrowth and neurite sprouting of Drosophila mushroom body neurons reveals shared and unique molecular mechanisms
Authors: Marmor‐Kollet Neta , Schuldiner Oren
Published: June 2015

The molecular mechanisms regulating intrinsic axon growth potential during development or following injury remain largely unknown despite their vast importance. Here, we have established a neurite sprouting assay of primary cultured mushroom body (MB) neurons. We used the MARCM technique to both mark and manipulate MB neurons, enabling us to quantify the sprouting abilities of single WT and mutant neurons originating from flies at different developmental stages. Sprouting of dissociated MB neurons was dependent on wnd, the DLK ortholog, a conserved gene that is required for axon regeneration. Next, and as expected, we found that the sprouting ability of adult MB neurons was significantly decreased. In contrast, and to our surprise, we found that pupal‐derived neurons exhibit increased sprouting compared with neurons derived from larvae, suggesting the existence of an elevated growth potential state. We then contrasted the molecular requirements of neurite sprouting to developmental axon regrowth of MB ɣ neurons, a process that we have previously shown requires the nuclear receptor UNF acting via the target of rapamycin (TOR) pathway. Strikingly, we found that while TOR was required for neurite sprouting, UNF was not. In contrast, we found that PTEN inhibits sprouting in adult neurons, suggesting that TOR is regulated by the PI3K/PTEN pathway during sprouting and by UNF during developmental regrowth. Interestingly, the PI3K pathway as well as Wnd were not required for developmental regrowth nor for initial axon outgrowth suggesting that axon growth during circuit formation, remodeling, and regeneration share some molecular components but differ in others. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 262–276, 2016
Environmental factors prevail over dispersal constraints in determining the distribution and assembly of Trichoptera species in mountain lakes
Authors: de Mendoza Guillermo , Ventura Marc , Catalan Jordi
Published: June 2015

Aiming to elucidate whether large‐scale dispersal factors or environmental species sorting prevail in determining patterns of Trichoptera species composition in mountain lakes, we analyzed the distribution and assembly of the most common Trichoptera (Plectrocnemia laetabilis, Polycentropus flavomaculatus, Drusus rectus, Annitella pyrenaea, and Mystacides azurea) in the mountain lakes of the Pyrenees (Spain, France, Andorra) based on a survey of 82 lakes covering the geographical and environmental extremes of the lake district. Spatial autocorrelation in species composition was determined using Moran's eigenvector maps (MEM). Redundancy analysis (RDA) was applied to explore the influence of MEM variables and in‐lake, and catchment environmental variables on Trichoptera assemblages. Variance partitioning analysis (partial RDA) revealed the fraction of species composition variation that could be attributed uniquely to either environmental variability or MEM variables. Finally, the distribution of individual species was analyzed in relation to specific environmental factors using binomial generalized linear models (GLM). Trichoptera assemblages showed spatial structure. However, the most relevant environmental variables in the RDA (i.e., temperature and woody vegetation in‐lake catchments) were also related with spatial variables (i.e., altitude and longitude). Partial RDA revealed that the fraction of variation in species composition that was uniquely explained by environmental variability was larger than that uniquely explained by MEM variables. GLM results showed that the distribution of species with longitudinal bias is related to specific environmental factors with geographical trend. The environmental dependence found agrees with the particular traits of each species. We conclude that Trichoptera species distribution and composition in the lakes of the Pyrenees are governed predominantly by local environmental factors, rather than by dispersal constraints. For boreal lakes, with similar environmental conditions, a strong role of dispersal capacity has been suggested. Further investigation should address the role of spatial scaling, namely absolute geographical distances constraining dispersal and steepness of environmental gradients at short distances.
LC‐MS untargeted metabolomic analysis of drug‐induced hepatotoxicity in HepG2 cells
Authors: García‐Cañaveras Juan Carlos , Jiménez Nuria , Gómez‐Lechón M. José , Castell José V. , Donato M. Teresa , Lahoz Agustín
Published: June 2015

Hepatotoxicity is the number one cause for agencies not approving and withdrawing drugs for the market. Drug‐induced human hepatotoxicity frequently goes undetected in preclinical safety evaluations using animal models. Human‐derived in vitro models represent a common alternative to in vivo tests to detect toxic effects during preclinical testing. Most current in vitro toxicity assays rely on the measurement of nonspecific or low sensitive endpoints, which result in poor concordance with human liver toxicity. Therefore, making more accurate predictions of the potential hepatotoxicity of new drugs remains a challenge. Metabolomics, whose aim is to globally assess all the metabolites present in a biological sample, may represent an alternative in the search for sensitive sublethal markers of drug‐induced hepatotoxicity. To this end, a comprehensive LC‐MS‐based untargeted metabolite profiling analysis of HepG2 cells, exposed to a set of well‐described model hepatotoxins and innocuous compounds, was performed. It allowed to determine meaningful metabolic changes triggered by a toxic insult and gave a first estimation of the main toxicity‐related pathways. Based on these metabolic patterns, a partial least squares‐discriminant analysis model, able to discriminate between nontoxic and hepatotoxic compounds, was constructed. The approach described herein may provide an alternative for animal testing in preclinical stages of drug development and a controlled experimental approach to gain a better understanding of the underlying causes of hepatotoxicity.
Assessing the risk to green sturgeon from application of imidacloprid to control burrowing shrimp in Willapa Bay, Washington—Part I: Exposure characterization
Authors: Frew John A. , Sadilek Martin , Grue Christian E.
Published: June 2015

Willapa Bay and Grays Harbor (WA, USA) comprise the largest region of commercial oyster cultivation on the Pacific Coast. The activities of 2 species of burrowing shrimp impair growth and survival of oysters reared on the intertidal mudflats. To maintain viable harvests, the oyster growers have proposed controlling the shrimp by applying the insecticide imidacloprid onto harvested beds. Green sturgeon (listed in the Endangered Species Act) forage on burrowing shrimp and could be exposed to imidacloprid in the sediment porewater and through consumed prey. Studies were conducted to evaluate the likelihood that green sturgeon would be exposed to imidacloprid and to characterize the subsequent environmental exposure. Comparisons between treated and untreated control beds following test application of the insecticide suggested that green sturgeon fed opportunistically on imidacloprid-impaired shrimp. The highest interpolated imidacloprid residue concentrations in field samples following chemical application were 27.8 µg kg–1 and 31.4 µg kg–1 in porewater and shrimp, respectively. Results from modeled branchial and dietary uptake, based on conservative assumptions, indicated that the porewater exposure route had the greatest contribution to systemic absorption of imidacloprid. The highest average daily uptake from porewater (177.9 µg kg–1 body wt) was 9.5-fold greater than total dietary uptake (18.8 µg kg–1 body wt). Concentrations and durations of exposure would be lower than the levels expected to elicit direct acute or chronic toxic effects. Environ Toxicol Chem 2015;34:2533–2541. © 2015 SETAC
Response of bacteria and meiofauna to iron oxide colloids in sediments of freshwater microcosms
Authors: Höss Sebastian , Frank-Fahle Béatrice , Lueders Tillmann , Traunspurger Walter
Published: June 2015

The use of colloidal iron oxide (FeOx) in the bioremediation of groundwater contamination implies its increasing release into the environment and requires an assessment of its ecotoxicological risk. Therefore, microcosm experiments were carried out to investigate the impact of ferrihydrite colloids on the bacterial and meiofaunal communities of pristine freshwater sediments. The effects of ferrihydrite colloids were compared with those of ferrihydrite macroaggregates to discriminate between colloid-specific and general FeOx impacts. The influence of ferrihydrite colloids on the toxicity of sediment-bound fluoranthene was also considered. At high concentrations (496 mg Fe kg−1 sediment dry wt), ferrihydrite colloids had a significant, but transient impact on bacterial and meiofaunal communities. Although bacterial community composition specifically responded to ferrihydrite colloids, a more general FeOx effect was observed for meiofauna. Bacterial activity responded most sensitively (already at 55 mg Fe kg−1 dry wt) without the potential of recovery. Ferrihydrite colloids did not influence the toxicity of sediment-bound fluoranthene. Significant correlations between bacterial activity and meiofaunal abundances were indicative of trophic interactions between bacteria and meiofauna and therefore of the contribution of indirect food web effects to the observed impacts. The results suggest that the application of ferrihydrite colloids for remediation purposes in the field poses no risk for benthic communities, given that, with the exception of generic bacterial activity, any negative effects on communities were reversible. Environ Toxicol Chem 2015;34:2660–2669. © 2015 SETAC
A third‐order implicit discontinuous Galerkin method based on a Hermite WENO reconstruction for time‐accurate solution of the compressible Navier–Stokes equations
Authors: Xia Yidong , Liu Xiaodong , Luo Hong , Nourgaliev Robert
Published: June 2015

A space and time third‐order discontinuous Galerkin method based on a Hermite weighted essentially non‐oscillatory reconstruction is presented for the unsteady compressible Euler and Navier–Stokes equations. At each time step, a lower‐upper symmetric Gauss–Seidel preconditioned generalized minimal residual solver is used to solve the systems of linear equations arising from an explicit first stage, single diagonal coefficient, diagonally implicit Runge–Kutta time integration scheme. The performance of the developed method is assessed through a variety of unsteady flow problems. Numerical results indicate that this method is able to deliver the designed third‐order accuracy of convergence in both space and time, while requiring remarkably less storage than the standard third‐order discontinous Galerkin methods, and less computing time than the lower‐order discontinous Galerkin methods to achieve the same level of temporal accuracy for computing unsteady flow problems. Copyright © 2015 John Wiley & Sons, Ltd.
Augmenting the immersed boundary method with Radial Basis Functions (RBFs) for the modeling of platelets in hemodynamic flows
Authors: Shankar Varun , Wright Grady B. , Kirby Robert M. , Fogelson Aaron L.
Published: June 2015

We present a new computational method by extending the immersed boundary (IB) method with a geometric model based on parametric radial basis function (RBF) interpolation of the Lagrangian structures. Our specific motivation is the modeling of platelets in hemodynamic flows, although we anticipate that our method will be useful in other applications involving surface elasticity. The efficacy of our new RBF‐IB method is shown through a series of numerical experiments. Specifically, we test the convergence of our method and compare our method with the traditional IB method in terms of computational cost, maximum stable time‐step size, and volume loss. We conclude that the RBF‐IB method has advantages over the traditional IB method and is well‐suited for modeling of platelets in hemodynamic flows. Copyright © 2015 John Wiley & Sons, Ltd.
TBM performance and disc cutter wear prediction based on ten years experience of TBM tunnelling in Iran
Authors: Hassanpour Jafar , Rostami Jamal , Zhao Jian , Azali Sadegh Tarigh
Published: June 2015

Accurate estimation of rate of penetration (ROP), daily rate of advance (AR), and cutter cost/life is necessary for the justification and successful use of a TBM on any tunneling project. Various models have been introduced over the years to provide such estimates. In many cases, these models have been successful with pin point accuracy, and in other instances off by a wide margin. Improving the accuracy of performance prediction models for hard rock TBMs has been the subject of many studies, some yielding project‐based models and some more universal models that can be used elsewhere. This paper will discuss the latest version of a new empirical model for estimating penetration rate and disc cutter life for hard rock TBM tunneling based on recent tunneling projects, constructed during the period 2002–2009. The new model was then applied to predict TBM performance and disc cutter wear in different mechanized tunneling projects under construction since 2009. Accuracy and validity of the model for prediction of ROP were checked by comparing predicted and measured values of TBM performance in 24 km of newly bored tunnel. The results indicate that despite some minor deviations in estimates in some tunnel sections, reasonable agreement can be observed between predicted and actual ROP of TBMs.
Darstellung von Wasserdrücken im Boden mit strömendem Grundwasser
Authors: Goldscheider Michael
Published: June 2015

Ausgehend vom Netz der Strom‐ und Äquipotentiallinien einer Grundwasserströmung wird für verschiedene Fälle der Zusammenhang zwischen den auf ein Volumenelement des Bodens wirkenden Wasserdruckkräften und den von diesen Kräften abgeleiteten Größen Auftriebskraft und Strömungskraft nach Terzaghi dargestellt. Die Strömungskraft erweist sich dabei als diejenige Kraft, die zu der im Falle von ruhendem Grundwasser wirkenden Auftriebskraft in Strömungsrichtung vektoriell hinzugefügt werden muss, um die bei Durchströmung wirkende resultierende Wasserdruckkraft zu erhalten. Es wird gezeigt, wie sich die effektive resultierende Volumenkraft eines Bodenkörpers, die für die effektiven Spannungen bestimmend ist, nach diesen beiden statisch äquivalenten Konzepten ergibt. Als Beispiel werden die Bedingungen für einen hydraulischen Grundbruch betrachtet.

Representation of water pressures in the soil with flowing ground water. Based on a groundwater flow net consisting of flow lines and equipotential lines, the relations between the pore water pressure forces acting on a volume element of the soil and the deduced uplift and seepage forces after Terzaghi are depicted for different cases. The seepage force turns out to be the force that has to be added as a vector in the flow direction to the uplift force acting in case of stagnant groundwater to obtain the resultant water pressure force in case of flowing groundwater. It is depicted how the effective resultant volume force of a soil body, which is determinant for the effective stresses, arises by the two statically equivalent concepts. As an example, the conditions of seepage failure are considered.