bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety, tolerability, and pharmacokinetics of multiple ascending doses of naloxegol
Authors: Eldon Michael A. , Kugler Alan R. , Medve Robert A. , Bui Khanh , Butler Kathleen , Sostek Mark
Published: June 2015

Opioid‐induced constipation (OIC) is the most common and often a treatment‐limiting adverse event (AE) of opioid therapy for chronic pain. Naloxegol (previously NKTR‐118), a PEGylated derivative of naloxone that has minimal penetration of the central nervous system, has received regulatory approval as an oral therapy for OIC. This randomized, double‐blind, placebo‐controlled, multiple‐dose, dose‐escalation study was performed to assess safety, tolerability, and pharmacokinetics of multiple doses of naloxegol in healthy volunteers. Four cohorts, each with 4 male and 4 female volunteers, were randomized 3:1 to a twice‐daily naloxegol solution (25, 60, 125, and 250 mg) or matching placebo solution. Doses were given every 12 hours for 7 days, with a single final dose on the morning of day 8. All 32 subjects completed the study. The incidence of most AEs was similar in the naloxegol and placebo groups; no AE led to study discontinuation. Naloxegol was rapidly absorbed. Plasma naloxegol pharmacokinetics showed dose proportionality, negligible accumulation at steady state, and no sex differences. Naloxegol in doses up to 250 mg every 12 hours was generally safe and well tolerated in this healthy volunteer population.
Pharmacokinetics and pharmacodynamics of mepolizumab, an anti–interleukin 5 monoclonal antibody, in healthy Japanese male subjects
Authors: Tsukamoto Naohiro , Takahashi Naoki , Itoh Hiroshi , Pouliquen Isabelle
Published: June 2015

Interleukin 5 (IL‐5) and eosinophils are thought to play an important role in the pathology of asthma. This study evaluated the pharmacokinetics, pharmacodynamics, safety, and tolerability of mepolizumab, a humanized anti‐IL5 IgG1 monoclonal antibody, in development for the treatment of severe eosinophilic asthma. This single‐blind study randomized 35 healthy Japanese male subjects (3:1) to receive either a single mepolizumab intravenous dose (10, 75, 250, or 750 mg) or placebo. Subjects were observed for up to 151 days postdose, depending on the dose administered. Blood samples were collected to measure mepolizumab concentrations, blood eosinophils, IL‐5, and antibodies to mepolizumab. Mepolizumab exhibited dose‐proportional pharmacokinetics. The terminal phase half‐life was 19.7–34.6 days, independent of dose. Higher mepolizumab plasma concentrations were associated with lower blood eosinophil counts. Mepolizumab 75–750 mg reduced blood eosinophils for ≥3 months postdose. Mepolizumab demonstrated a favorable safety profile: of 41 reported adverse events, most were mild in severity and none were serious. No neutralizing antibodies to mepolizumab were detected. Sustained reduction in blood eosinophils after single intravenous mepolizumab doses ≥ 75 mg, along with mepolizumab pharmacokinetics and a favorable tolerability profile in healthy Japanese subjects, provides a solid foundation for future studies with mepolizumab in Japanese patients with asthma.
Safer Electrolytes for Lithium‐Ion Batteries: State of the Art and Perspectives
Authors: Kalhoff Julian , Eshetu Gebrekidan Gebresilassie , Bresser Dominic , Passerini Stefano
Published: June 2015

Lithium‐ion batteries are becoming increasingly important for electrifying the modern transportation system and, thus, hold the promise to enable sustainable mobility in the future. However, their large‐scale application is hindered by severe safety concerns when the cells are exposed to mechanical, thermal, or electrical abuse conditions. These safety issues are intrinsically related to their superior energy density, combined with the (present) utilization of highly volatile and flammable organic‐solvent‐based electrolytes. Herein, state‐of‐the‐art electrolyte systems and potential alternatives are briefly surveyed, with a particular focus on their (inherent) safety characteristics. The challenges, which so far prevent the widespread replacement of organic carbonate‐based electrolytes with LiPF6 as the conducting salt, are also reviewed herein. Starting from rather “facile” electrolyte modifications by (partially) replacing the organic solvent or lithium salt and/or the addition of functional electrolyte additives, conceptually new electrolyte systems, including ionic liquids, solvent‐free, and/or gelled polymer‐based electrolytes, as well as solid‐state electrolytes, are also considered. Indeed, the opportunities for designing new electrolytes appear to be almost infinite, which certainly complicates strict classification of such systems and a fundamental understanding of their properties. Nevertheless, these innumerable opportunities also provide a great chance of developing highly functionalized, new electrolyte systems, which may overcome the afore‐mentioned safety concerns, while also offering enhanced mechanical, thermal, physicochemical, and electrochemical performance.
Study of Metal Etching Using Ozone Water
Authors: Hatsuki Ryuji , Yamamoto Takatoki
Published: June 2015

We have proposed and experimentally demonstrated an environmental friendly, simple, and inexpensive etching method for metal using ozone water. We experimentally measured the dependencies of ozone water etching on the temperature and ozone concentration for several metals (Cr, Ni, Al, Au, and Ti), and also evaluated the surface roughness of the etched surface. The etching mechanism using ozone water can be explained by the activation energy obtained using an Arrhenius plot and a pH‐potential diagram. As a result, it was found that the etching rate was proportional to the dissolved ozone concentration and temperature, and that an atomically flat surface was obtained after etching with ozone water, although it was also found that the etching rate was very low at a few tens of nanometers per hour. It is therefore difficult to use this method for performing conventional macro‐ and microscale etching, whereas the rate is sufficiently high to use it for nanoscale (i.e., a few tens of nanometers) metal etching in nanoscience and nanotechnology.
Variable Dynamic Threshold of Jerk Signal for Contact Detection in Industrial Robots without Force Sensor
Authors: Shimada Naoki , Yoshioka Takashi , Ohishi Kiyoshi , Miyazaki Toshimasa , Yokokura Yuki
Published: June 2015

This study proposes a variable dynamic threshold for a jerk signal for achieving contact detection in industrial robots. Sensorless force control is useful in applications in advanced industrial robots. The external torque of each joint is estimated accurately by using a disturbance observer and by inverse dynamics calculations. However, the phase lag of the disturbance observer and the dynamic parameter error create force estimation errors. These errors hamper quick and reliable contact detection in industrial robots. Therefore, this study proposes a useful approach to contact detection that uses a variable dynamic threshold for a jerk signal. The proposed variable dynamic threshold reduces contact detection failures caused by force estimation errors during the free motion of a robot. The proposed threshold is suitable for robot motion and improves the speed of contact detection. Numerical simulation results show that the proposed method is valid for the parameter variations in an actual industrial robot. In addition, experimental results show that the dynamic threshold is a useful technique for application to general robot systems as well. The dynamic threshold is useful in applications for any industrial sensorless force control system.
Synthesis and Reactivity of N‐tert‐Butanesulfinyl Glycosylamines
Authors: Cocaud Chloé , Nicolas Cyril , Bayle Alexandre , Poisson Thomas , Pannecoucke Xavier , Martin Olivier R.
Published: June 2015

A study of the preparation and of the reactivity of N‐tert‐butanesulfinyl glycosylamines is reported for the first time. As they react readily as latent imine equivalents with a variety of carbon nucleophiles, these new carbohydrate derivatives constitute very useful precursors for the diastereoselective synthesis of bioactive compounds such as iminosugar‐C‐glycosides.
Organically complexed iron enhances bioavailability of antimony to maize (Zea mays) seedlings in organic soils
Authors: Ptak Corey , McBride Murray
Published: June 2015

Antimony (Sb) is a metalloid belonging to group 15 of the periodic table. Chemical similarities between arsenic (As) and Sb produce concerns about potential health effects of Sb and enrichment in the environment. Antimony is found in oxic environments predominately as an oxyanionic species, antimonite (Sb[OH]6–). As a result of its net negative charge, Sb[OH]6– was not initially predicted to have strong interactions with natural organic matter. Oxyanionic species could bind the negatively charged organic matter via a ternary complexation mechanism, in which cationic metals mediate the strong association between organic matter functional groups and oxyanions. However, these interactions are poorly understood in how they influence the bioavailability of oxyanionic contaminants to plants. Iron (Fe) additions to organic soils have been found to increase the number of organically complexed Fe sites suitable for Sb exchange, resulting in a reduced bioavailable fraction of Sb. The bioavailability of Sb to maize seedlings as a function of organically complexed Fe was examined using a greenhouse study. A significant increase in plant tissue Sb was observed as organically complexed Fe increased, which was not predicted by methods commonly used to assess bioavailable Sb. Extraction of soils with organic acids common to the maize rhizosphere suggested that organic acid exudation can readily mobilize Sb bound by organic Fe complexes. Environ Toxicol Chem 2015;34:2732–2738. © 2015 SETAC
Evaluating the TOEFL Junior® Standard Test as a Measure of Progress for Young English Language Learners
Authors: Gu Lin , Lockwood John , Powers Donald E.
Published: June 2015

Standardized tests are often designed to provide only a snapshot of test takers' knowledge, skills, or abilities at a single point in time. Sometimes, however, they are expected to serve more demanding functions, one of them is assessing change in knowledge, skills, or ability over time because of learning effects. The latter is the case for the newly developed TOEFL Junior® Standard test, which measures improvement in young learners' proficiency in English as a foreign language. In this study, we used nonexperimental‐repeated measures data from approximately 4,600 students from multiple countries to examine the extent to which observed patterns in within‐individual changes in test scores were consistent with changes in underlying language proficiency because of learning. Because most students were actively participating in English language learning programs, the time interval between test administrations, which varied among students, served as a proxy for the extent of English language learning opportunities. We used hierarchical linear models to model growth in test performance as a function of the time interval between test administrations and found a positive, statistically significant relationship; that is, test takers with longer intervals between retesting exhibited greater gains than did test takers who retested at shorter intervals. The estimated relationship for the total score corresponded to between .16 and .24 test standard deviations of growth per year, depending on model specification. The findings are robust to sensitivity analyses that explore potential biasing factors. Overall, the findings are consistent with the hypothesis that the TOEFL Junior Standard test is capable of reflecting change in English language proficiency over time.
Germacra‐1(10),5‐dien‐4α‐ol in Fortunella sp. leaf oils
Authors: Sutour Sylvain , Bradesi Pascale , Luro François , Casanova Joseph , Tomi Félix
Published: June 2015

The composition of an oil sample isolated from leaves of Fortunella japonica (Thunb.) Swingle was investigated by combination of chromatographic and spectroscopic techniques. Among the compounds present at appreciable amounts, a special attention was brought to sesquiterpenes bearing a tertiary alcohol function and particularly to germacra‐1(10),5‐dien‐4α‐ol. Indeed, identification of diastereoisomers α and β of germacra‐1(10),5‐dien‐4‐ol has been the subject of controversy in the literature. We report here for the first time 13C NMR data of the α isomer. The criteria for differentiation of both diastereoisomers are discussed. In parallel, leaf oils from four other Fortunella species (F. crassifolia, F. hindsii, F. margarita and F. obovata) have been analyzed by GC(RI) and 13C NMR. The main components of the investigated Fortunella leaf oils were β‐elemol (8.7‐30.9%), germacrene D (2.1–16.3%), β‐eudesmol (4.6–13.1%) and Δ9‐10‐eremophilen‐11‐ol (1.4–11.2%). The occurrence of germacra‐1(10),5‐dien‐4α‐ol (1.1–7.7%) was observed in the five Fortunella leaf oils. Copyright © 2015 John Wiley & Sons, Ltd.
Lynch syndrome and cervical cancer
Authors: Antill Yoland C. , Dowty James G. , Win Aung Ko , Thompson Tina , Walsh Michael D. , Cummings Margaret C. , Gallinger Steven , Lindor Noralane M. , Le Marchand Loïc , Hopper John L. , Newcomb Polly A. , Haile Robert W. , Church James , Tucker Katherine M. , Buchanan Daniel D. , Young Joanne P. , Winship Ingrid M. , Jenkins Mark A.
Published: June 2015

Carriers of germline mutations in DNA mismatch repair (MMR) genes are at increased risk of several cancers including colorectal and gynecologic cancers (Lynch syndrome). There is no substantial evidence that these mutations are associated with an increased risk of cervical cancer. A total of 369 families with at least one carrier of a mutation in a MMR gene (133 MLH1, 174 MSH2, 35 MSH6 and 27 PMS2) were ascertained via population cancer registries or via family cancer clinics in Australia, New Zealand, Canada, and USA. Personal and family histories of cancer were obtained from participant interviews. Modified segregation analysis was used to estimate the hazard ratio (incidence rates for carriers relative to those for the general population), and age‐specific cumulative risks of cervical cancer for carriers. A total of 65 cases of cervical cancer were reported (including 10 verified by pathology reports). The estimated incidence was 5.6 fold (95% CI: 2.3–13.8; p = 0.001) higher for carriers than for the general population with a corresponding cumulative risk to 80 years of 4.5% (95% CI: 1.9–10.7%) compared with 0.8% for the general population. The mean age at diagnosis was 43.1 years (95% CI: 40.0–46.2), 3.9 years younger than the reported USA population mean of 47.0 years (p = 0.02). Women with MMR gene mutations were found to have an increased risk of cervical cancer. Due to limited pathology verification we cannot be certain that a proportion of these cases were not lower uterine segment endometrial cancers involving the endocervix, a recognized cancer of Lynch syndrome.
A potential with low point charges for pure siliceous zeolites
Authors: Sahoo Sudhir K. , Nair Nisanth N.
Published: June 2015

A modified CHARMM force‐field (ZHB potential) with low point charges for silica was previously proposed by Zimmerman et al. (J. Chem. Theory Comput. 2011, 7, 1695). The ZHB potential is advantageous for quantum mechanics/molecular mechanics simulations as it minimizes the electron spill‐out problems. In the same spirit, here we propose a modified ZHB potential (MZHB) by reformulating its bonding potential, while retaining the nonbonding potential as in the ZHB force‐field. We show that several structural and dynamic properties of silica, like the IR spectrum, distribution functions, mechanical properties, and negative thermal expansion computed using the MZHB potential agree well with experimental data. Further, transferability of MZHB is also tested for reproducing the crystallographic structures of several polymorphs of silica. © 2015 Wiley Periodicals, Inc.
Microgrid dynamic responses enhancement using artificial neural network‐genetic algorithm for photovoltaic system and fuzzy controller for high wind speeds
Authors: Rezvani Alireza , Izadbakhsh Maziar , Gandomkar Majid
Published: June 2015

The microgrid (MG) is described as an electrical network of small modular distributed generation, energy storage devices and controllable loads. In order to maximize the output of solar arrays, maximum power point tracking (MPPT) technique is used by artificial neural network (ANN), and also, control of turbine output power in high wind speeds is proposed using pitch angle control technic by fuzzy logic. To track the maximum power point (MPP) in the photovoltaic (PV), the proposed ANN is trained by the genetic algorithm (GA). In other word, the data are optimized by GA, and then these optimum values are used in ANN. The simulation results show that the ANN‐GA in comparison with the conventional algorithms with high accuracy can track the peak power point under different insolation conditions and meet the load demand with less fluctuation around the MPP; also it can increase convergence speed to achieve MPP. Moreover, pitch angle controller based on fuzzy logic with wind speed and active power as inputs that have faster responses which leads to have flatter power curves enhances the dynamic responses of wind turbine. The models are developed and applied in Matlab/Simulink. Copyright © 2015 John Wiley & Sons, Ltd.
To create without losing face: The effects of face cultural logic and social‐image affirmation on creativity
Authors: Miron‐Spektor Ella , Paletz Susannah B. F. , Lin Chun‐Chi
Published: June 2015

Creativity is universally valued and desired. Yet, people are often reluctant to engage in creativity out of fear of being dismissed by others and losing face—the positive social image that individuals want to maintain in the presence of others. This paper investigates the effect of face logic endorsement on creativity and proposes face as a possible new explanation for cross‐cultural differences in creativity. In three studies using different creativity tasks and with participants from Japan, Israel, and the United States, participants who endorsed the cultural logic of face were less creative than those less endorsing this logic. Face logic endorsement mediated the effect of culture on the novelty and fluency dimensions of creativity (Study 1). Furthermore, social‐image affirmation moderated the effects of culture and face logic endorsement on creativity. When individuals' social image was affirmed, cultural differences in creativity were weakened (Study 2), and the within‐culture association between face logic endorsement and creativity disappeared (Study 3). We discuss the theoretical and practical implications for fostering creativity in different cultures and in multicultural settings. Copyright © 2015 John Wiley & Sons, Ltd.
Contributing factors to Koshava wind characteristics
Authors: Romanić Djordje , Ćurić Mladjen , Lompar Miloš , Jovičić Ilija
Published: June 2015

Koshava is a local wind usually observed in the cold part of the year over the large part of Serbia, parts of Romania, parts of Hungary, and east Croatia. The main characteristics of the Koshava wind are its high wind speed, southeasterly direction, persistence, and gustiness. This paper analyses the synoptic [Mediterranean cyclones (MCs) and Eurasian anticyclones (EAs)] as well as the mesoscale contributors to the Koshava wind. Time and spatial features of the pressure systems have been analysed using an automatic cyclone tracking scheme. The results show that the MCs and EAs that generate Koshava are approximately 1000 km away from the Koshava region. It is demonstrated that the strong anticyclones are the main trigger for the Koshava wind. Less than 3% of the Koshava winds occurred without the occurrence of either an anticyclone or a cyclone. The Synoptic Koshava Index (SKI), developed in this study and defined as the difference between the area‐averaged mean sea level pressures in the anticyclone and cyclone regions, has been shown to be a good indicator of the Koshava occurrence. Koshava has also been investigated from the perspective of the gap flow windstorm. The across‐mountain pressure difference, ΔP, is the most important mesoscale contributor to the Koshava characteristics. The across‐mountain potential temperature difference, Δθ, together with ΔP, can be successfully used to predict Koshava's occurrence. A simple (linear) probabilistic model for forecasting the Koshava mean hourly wind speed has been constructed. The results demonstrate that the occurrence of the Koshava wind can be predicted with the significantly higher accuracy than the Koshava mean hourly speed. The correlation between Koshava and winds at higher levels is small.
Separation of cannabinoids on three different mixed‐mode columns containing carbon/nanodiamond/amine‐polymer superficially porous particles
Authors: Hung Chuan‐Hsi , Zukowski Janusz , Jensen David S. , Miles Andrew J. , Sulak Clayton , Dadson Andrew E. , Linford Matthew R.
Published: June 2015

Three mixed‐mode high‐performance liquid chromatography columns packed with superficially porous carbon/nanodiamond/amine‐polymer particles were used to separate mixtures of cannabinoids. Columns evaluated included: (i) reversed phase (C18), weak anion exchange, 4.6 × 33 mm, 3.6 μm, and 4.6 × 100 mm, 3.6 μm, (ii) reversed phase, strong anion exchange (quaternary amine), 4.6×33 mm, 3.6 μm, and (iii) hydrophilic interaction liquid chromatography, 4.6 × 150 mm, 3.6 μm. Different selectivities were achieved under various mobile phase and stationary phase conditions. Efficiencies and peak capacities were as high as 54 000 N/m and 56, respectively. The reversed phase mixed‐mode column (C18) retained tetrahydrocannabinolic acid strongly under acidic conditions and weakly under basic conditions. Tetrahydrocannabinolic acid was retained strongly on the reversed phase, strong anion exchange mixed‐mode column under basic polar organic mobile phase conditions. The hydrophilic interaction liquid chromatography column retained polar cannabinoids better than the (more) neutral ones under basic conditions. A longer reversed phase (C18) mixed‐mode column (4.6 × 100 mm) showed better resolution for analytes (and a contaminant) than a shorter column. Fast separations were achieved in less than 5 min and sometimes 2 min. A real world sample (bubble hash extract) was also analyzed by gradient elution.
LESSONS FROM INNOVATION, REINVENTION, AND ENTREPRENEURSHIP
Authors: Bias Lauren Maillian
Published: June 2015

Entrepreneurs fall into two classes, Bias contends. A successful entrepreneur herself, she believes that some are builders and some are initiators. She counts herself in the latter group, which gets “bored after they get their businesses up and running. They're continually looking to take on the next challenge and to create the next success.” In order to do this, you must learn new skills and learn new subject areas, as well as engage in personal reinvention. This means mastering such competencies as getting out of your comfort zone and beyond your job description, communicating clearly, and being reliable, straightforward, and self‐motivated.
LEADING THROUGH CORE VALUES
Authors: Carlson Lucas
Published: June 2015

According to successful entrepreneur Carlson, core values are foundational for success. He describes these as “the things you deem most important in every facet of your life.” These values will help guide you through such rough patches as when and how to fire an employee. He suggests building an acronym of your own personal values, and provides a handy chart. He writes that if your core values are “creativity, happiness, adventure, service, and ethics, your acronym might be CHASE.” Call on your core values when you are determining who will or won't work for your company, what deals you will or won't do, and who you will or won't take investments from.
Development of Supramolecular Pseudo‐Block Conjugates Based on Star‐Shaped Polycation for DNA Delivery
Authors: Kong Yunna , Li Wenyu , Mao Qianying , Wang Youxiang
Published: June 2015

Supramolecular assembly provides a new strategy for designing various gene carriers for deoxyribonucleic acid (DNA) delivery. In this work, supramolecular pseudo‐block conjugates based on star‐shaped polycation are developed as novel nonviral gene vector. First, cyclodextrin (CD) is selected as core and grafted with low molecular weight polyethylenimine (PEI1800) as arms to obtain high molecular weight star‐shaped polycation CD‐PEI8 (SCP). Then, azobenzene (Az) modified poly(ethylene glycol) is synthesized and named as azobenzene modified poly(ethylene glycol) (Az‐PEG). Subsequently, the supramolecular pseudo‐block conjugates are prepared via host–guest interaction between CD and Az. The result suggests that SCP/Az‐PEG condenses DNA into spherical nanoparticles with sizes of around 150 nm. The in vitro experiment shows that the cell viability of DNA/SCP/Az‐PEG polyplexes is significantly improved compared with that of PEI25k/DNA polyplexes. The PEGylation does not decrease the cellular uptake efficiency and transfection efficiency. Furthermore, the cellular trafficking shows that PEGylation does not significantly influence nuclear entry. The star‐shaped architecture of polycation plays an important role in gene delivery.

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Chicory, a typical vegetable in Mediterranean diet, exerts a therapeutic role in established atherosclerosis in apolipoprotein E‐deficient mice
Authors: Lin Weiqun , Liu Chaoqun , Yang Hai , Wang Wenting , Ling Wenhua , Wang Dongliang
Published: June 2015

Scope

Since protocatechuic acid exerts an atheroprotective role, we investigated how chicory (Cichorium intybus L. var. foliosum, Belgian endive) rich in protocatechuic acid, a typical vegetable in Mediterranean diet, affects preestablished atherosclerosis progression.

Methods and results

Apolipoprotein E‐deficient mice fed AIN diets containing 0.5% freeze‐dried chicory for 10 weeks displayed a reduction in lesion size with a concomitant improvement in lesion stability indicated by fewer macrophages and more collagen content. Chicory consumption suppressed aortic cholesterol accumulation and intercellular adhesion molecule‐1, vascular cell adhesion molecule‐1, and monocyte chemoattractant protein‐1 expression, whereas it increased aortic ATP‐binding cassette transporter A1 (ABCA1) and G1 (ABCG1) expression. Furthermore, chicory consumption improved peritoneal macrophage phenotype with less cellular cholesterol associated with an enhancement of cholesterol efflux capacity through upregulation of ABCA1 and ABCG1, less cellular oxidative stress associated with an inhibition of nicotinamide adenine dinucleotide phosphate oxidase activity, and weaker inflammatory responses associated with an inhibition of nuclear factor‐κB activation. Interestingly, ABCA1 and ABCG1 silencing tended to completely block beneficial effects of chicory in peritoneal macrophages.

Conclusion

Chicory exerts an atheroprotective role in mice possibly by regulating lesional macrophage content and phenotype, suggesting that chicory is one underrated contributor to Mediterranean Diet‐induced atheroprotection.
Enantiospecific pharmacokinetics of isoxanthohumol and its metabolite 8‐prenylnaringenin in the rat
Authors: Martinez Stephanie E. , Davies Neal M.
Published: June 2015

Scope

Isoxanthohumol (IX) is a bioactive dietary prenylflavanone found in hops (Humulus lupulus L.), beer and nutraceuticals. IX is formed in vivo by xanthohumol and is a prodrug of 8‐prenylnaringenin (8PN). IX and 8PN chirality has largely been ignored in the literature due to lack of enantiospecific bioanalytical methods. No single dose pharmacokinetic study of IX exists in the literature for any species. This study elucidates the enantiospecific pharmacokinetics of IX in rats and monitors the appearance of 8PN following intravenous and oral administration of ±IX.

Methods and results

After intravenous (10 mg/kg) or oral (100 mg/kg) administration of ±IX to rats, serum, and urine were collected for 120 h and analyzed for IX and 8PN. Both were found as aglycones and glucuronide conjugates and displayed multiple peaking in serum suggestive of enterohepatic recycling. IX is primarily excreted through nonrenal routes. S‐8PN was found excreted in the urine in greater amounts than R‐8PN. Bioavailability was determined to be ∼4–5% for IX.

Conclusion

Further enantiospecific pharmacokinetics of IX, subsequent 8PN and other metabolites are warranted along with continued enantiospecific bioactivity studies, especially in relation to gut microbial metabolism of IX and subsequent formation of 8PN.
Foot Health Education for People with Rheumatoid Arthritis: '…. A Game of Chance…' – A Survey of Patients' Experiences
Authors: Graham Andrea S. , Williams Anita E.
Published: June 2015

Objective

Up to 90% of people with rheumatoid arthritis (RA) experience foot problems leading to reduced function, mobility, quality of life and social participation, and impacts on body image, but these can be improved with general foot care, orthoses, footwear and patient education. Foot health patient education is lacking, so the aim of the present study was to identify the foot health educational needs of people with RA in relation to its content, timing, mode of delivery and the perceived barriers to its provision.

Methods

People with RA completed an online survey and provided free‐text comments for thematic analysis.

Results

A total of 249 people completed the free‐text section of the survey. Five main themes emerged: ‘Forgotten feet’; ‘Too little, too late’; ‘Lacks and gaps’; ‘I am my feet’ and ‘Game of chance’.

Conclusion

Foot pathology in people with RA has a bio‐psychosocial impact on their lives. Foot health and related information appears to be considered rarely within the medical consultation. Access to foot health information and services is limited owing to a lack of patient and/or health professional awareness, with a detrimental impact on the prognosis of their foot health. The importance of foot health in people with RA should be reinforced for patients and health professionals alike. Opportunities to discuss foot health within the medical consultation should be provided regularly. Copyright © 2015 John Wiley & Sons, Ltd.
Immiscible polydiene blocks in linear copolymer and terpolymer sequences
Authors: Zapsas George , Moschovas Dimitrios , Ntetsikas Konstantinos , Rangou Sofia , Lee Jae‐Hwang , Thomas Edwin L. , Zafeiropoulos Nikolaos E. , Avgeropoulos Apostolos
Published: June 2015

Synthesis, molecular, and morphological characterization of two linear diblock copolymers consisting of two polydienes with specific geometric isomerisms and two triblock terpolymers with a combination of the same polydienes with polystyrene are investigated for both lower and very high molecular weights. This work is inspired from a previous research study which demonstrated that linear ABC terpolymers consisting of polystyrene, poly(butadiene), and poly(isoprene), with specific geometric isomerisms for the polydienes, lead to 3‐phase microphase separated systems. We report also the coexistence of the core‐shell double gyroid and the 3‐phase 4‐layer alternating lamellae morphologies with the majority fraction being the lamellar structure. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2015, 53, 1238–1246
Atmospheric Non‐Equilibrium Plasma Promotes Cell Death and Cell‐Cycle Arrest in a Lymphoma Cell Line
Authors: Gherardi Matteo , Turrini Eleonora , Laurita Romolo , De Gianni Elena , Ferruzzi Lorenzo , Liguori Anna , Stancampiano Augusto , Colombo Vittorio , Fimognari Carmela
Published: June 2015

Atmospheric non‐equilibrium plasma is drawing interest as a promising tool for cancer treatment due to its blend of physical and chemical components that can exert anti‐tumor effects. In this work, we investigate the effects of plasma treatment, performed by means of a wand electrode DBD driven by nanosecond high voltage pulses, on the viability, proliferation, and cell‐cycle distribution of cells of mouse lymphoma. Results for direct treatment, with cell exposed to plasma while suspended in culture medium, and indirect treatment, where cells were added to culture medium previously activated by plasma treatment, are compared. A qualitative characterization by means of high‐speed and iCCD imaging of the plasma discharges produced for the different operating conditions adopted in biological experiments, as well as a semi‐quantitative study of the reactive species produced by plasma treatment in the culture medium, are also presented.
New t‐butyl based aspartate protecting groups preventing aspartimide formation in Fmoc SPPS
Authors: Behrendt Raymond , Huber Simon , Martí Roger , White Peter
Published: June 2015

Obtaining homogenous aspartyl‐containing peptides via Fmoc/tBu chemistry is often an insurmountable obstacle. A generic solution for this issue utilising an optimised side‐chain protection strategy that minimises aspartimide formation would therefore be most desirable. To this end, we developed the following new derivatives: Fmoc‐Asp(OEpe)‐OH (Epe = 3‐ethyl‐3‐pentyl), Fmoc‐Asp(OPhp)‐OH (Php = 4‐n‐propyl‐4‐heptyl) and Fmoc‐Asp(OBno)‐OH (Bno = 5‐n‐butyl‐5‐nonyl). We have compared their effectiveness against that of Fmoc‐Asp(OtBu)‐OH and Fmoc‐Asp(OMpe)‐OH in the well‐established scorpion toxin II model peptide variants H‐Val‐Lys‐Asp‐Asn/Arg‐Tyr‐Ile‐OH by treatments of the peptidyl resins with the Fmoc removal reagents containing piperidine and DBU at both room and elevated temperatures. The new derivatives proved to be extremely effective in minimising aspartimide by‐products in each application. Copyright © 2015 European Peptide Society and John Wiley & Sons, Ltd.
Die Netzschale der Jinji Lake Mall
Authors: Plieninger Sven , Gebreiter Daniel , Mühlberger Jörg , Justiz Stefan
Published: June 2015

Für eines der künftig größten Einkaufszentren Chinas in Suzhou hat schlaich bergermann und partner eine 35.000 Quadratmeter große freigeformte Netzschale geplant. Die Herausforderung bestand darin, für den 400 Meter langen Komplex aus vier statisch unabhängigen Gebäuden ein fugenloses Dach in Form von Phoenix‐Schwingen zu realisieren, das großen Relativverschiebungen aus Temperatur‐ und Erdbebeneinwirkungen standhält. Eine aufgrund ihrer Flexibilität vorteilhafte regelmäßige Viereckstruktur wurde mittels eigens entwickelter Modellierungsmethoden gefunden. Dieser digitale Entwurfsprozess ermöglichte die gekoppelte Optimierung von Netz und Tragwerk hin zu einer zugleich harmonischen und filigranen Struktur.

The grid‐shell of Jinji Lake Mall. Jinji Lake Mall, a 290,000 m² shopping and entertainment centre, will be centrepiece to a development of several super‐high‐rise buildings by the waterfront of Jinji Lake in Suzhou, China. Visible from the surrounding skyscrapers, the appearance of the “fifth façade” became of paramount importance. In response, the architectural design foresaw a continuous, 35,000 m² free‐form glass roof to cover the four individual buildings of the mall ensemble.

schlaich bergermann and partner structural consulting engineers were tasked with the structural design of the roof whose shape was inspired by the wings of a phoenix. To alleviate excessive in‐plane stresses in the roof, a rigid triangulated grid was discarded in favour of a more elastic quadrangular frame system, requiring the generation of a quad‐dominant topology on the free‐form surface. The complex interplay between base buildings and roof structure required that all analysis be done on a combined model including roof, tree columns and sub‐structure.

Multi‐resolution mesh modelling stood at the core of a generative work‐flow which mathematically optimized for geometric and structural criteria in the same process. Furthermore, geometrically similar facets were grouped and subsequently assigned the same panel, reducing the unique panel count.
Die Sonderfassaden des Doha Convention Centers, Qatar
Authors: Blandini Lucio , Winterstetter Thomas , Sobek Werner
Published: June 2015

Das Doha Convention Center in Qatar ist ein neues Kongresszentrum, das die wirtschaftliche Bedeutung des Golfstaats im Mittleren Osten stärken soll. Herausragendes Merkmal des Gebäudes ist eine äußerst transparente Seilfassade an der Südseite. Die Fassade nimmt Windlasten durch horizontal verlaufende, vorgespannte Edelstahlseile auf. Die Seile haben einen Durchmesser von 28 mm. Sie spannen bis zu 180 m zwischen zwei vertikalen, bogenartigen Trägern. Ein wichtiges Ziel der Planung war es, horizontale Verformungen (und daraus resultierende Verwindungen in den Glasscheiben) auf ein absolutes Minimum zu reduzieren; dies war angesichts der großen Spannweiten eine besondere Herausforderung.

The Special Facades of Doha Convention Center. The Doha Convention Center in Qatar is a building aiming at strengthen and outline the role of the Gulf state as a business hub in the Middle East. A special feature of the building is the transparent cable‐stayed facade at the south side. Wind loads are carried by horizontal prestressed stainless steel cables. These cables span up to 180 m between two vertical bow‐string columns. Given the long spans, keeping control of horizontal deflections and of the resulting warping in the insulated glass panes was a particular challenge.
Standards der Zukunft: EnEV 2014 und Effizienzhaus Plus
Authors: Hegner Hans‐Dieter
Published: June 2015

Das neu gebildete Bundesministerium für Umwelt, Naturschutz, Bau und Reaktorsicherheit hat aufbauend auf den Forderungen des Koalitionsvertrages der aktuellen Bundesregierung ein “Aktionsprogramm Klimaschutz“ vorlegt, um zusätzliche CO2‐Einsparungen zu generieren. Es wurde am 03.12.2014 im Bundeskabinett verabschiedet. Teil der Maßnahmen ist die Umsetzung der neuen Energieeinsparverordnung, die ab 2016 eine Verschärfung um 25 % vorsieht. Gleichzeitig soll mit dem “Bündnis für bezahlbares Wohnen und Bauen“ dafür gesorgt werden, dass Wohnen bezahlbar bleibt und mehr Sozialwohnungen insbesondere in Ballungsräumen errichtet werden. Beides gelingt nur, wenn innovative Ansätze beim Wohnungsbau und dem energieeffizienten und nachhaltigen Bauen umgesetzt werden. Die Forschungsinitiative Zukunft Bau und das Netzwerk der Effizienzhäuser Plus leisten dabei umfangreiche Unterstützung.

Future standards: the Energy Conservation Regulations 2014 and the plus energy house. The new Federal Ministry for the Environment, Nature Conservation, Building and Nuclear Safety has submitted a Climate Action Programme 2020 based on the Coalition Agreement of the current government to achieve additional CO2 savings. It was decided by the Federal Government on the 3th of December 2014. One of the instruments is the implementation of the new Energy Conservation Regulations (EnEV). The EnEV standards will be raised by 25 % starting in 2016. At the same time the Alliance for Affordable Housing and Building aims to keep housing affordable and to ensure that more social housing is built, in particular in conurbations. These two goals can only be attained if we consistently implement innovative approaches in housing development and energy‐efficient, sustainable building. The research initiative Future Building (Zukunft Bau) and the network “plus energy houses” make a vital contribution to this.
Die Gebäudehülle des Heydar Aliyev Cultural Centre in Baku, Aserbaidschan
Authors: Winterstetter Thomas , Sobek Werner , Berger Radu‐Florin , Toth Agatha
Published: June 2015

Das Design des neuen nationalen Kulturzentrums von Aserbaidschan ist geprägt von der Freiformflächen‐Architektur von Zaha Hadid. Wesentliche innovative Konstruktionsweisen wie die GFK/GFB‐Außenhülle, die 3D‐Innenausbauten und die extrem großformatigen Glas‐Elementfassaden wurden von Werner Sobek Stuttgart speziell für dieses Projekt entwickelt, ausgeschrieben und bei Produktion und Einbau überwacht. Der Beitrag zeigt die sehr hohen Anforderungen und die verschiedenen ingenieurtechnischen Lösungsansätze für Planung und Realisierung.

The building envelope of Heydar Aliyev Cultural Centre in Baku, Azerbaijan. The design of the new national cultural center of Azerbaijan is characterized by the freeform architecture of Zaha Hadid. Significant innovative construction methods as the GRP / GRC‐outer shell, the 3D interior fit‐out and the extremely large size glass‐curtain wall units were developed by Werner Sobek Stuttgart specifically for this project and were advertised and monitored during production and installation. The article shows the very high standards and the different engineering approaches to planning and implementation.
Glazed Link Library Walk − Manchester
Authors: Weimann Gert , Henriksen Thomas , Keri Samir
Published: June 2015

In der Mitte des Vereinigten Königreichs [UK] verbindet Waagner Biro mit dem sogenannten “Glazed Link Library Walk” das Rathaus von Manchester mit der benachbarten Zentralbibliothek (Bild 1‐1). Der Entwurf stammt von dem britischen Architekturbüro “Ian Simpson Associates”. Die Hauptabmessungen dieser Glaskonstruktion mit der nierenförmigen Grundfläche sind ca. 10,6 m x 20,5 m x 7,9 m. Auf 7,4 m hohen tragenden Glaswand‐Elementen ruht eine komplett verschweißte Freiformfläche aus poliertem Edelstahl, deren Gestalt einer Wolkenformation nachempfunden ist. Die 26 laminierten Glasscheiben (13 zylindrisch gebogen, 13 eben) fungieren hierbei als selbstaussteifendes Fassadentragwerk. Absolute Präzision in den Bereichen Engineering, Fertigung und Montage ermöglichten die Realisierung dieser neuartigen und spektakulären Glas‐Skulptur.

Glazed Link Library Walk – Manchester. The Glazed Link Building forms a link between the Manchester Town Hall and the neighbouring Central Library. The architectural office is “Ian Simpson Associates”. The Glazed Link rises approx. 7,9 m and measures approx. 10,6 m x 20,5 m. The roof is made of welded stainless steel and features a mirror polished soffit built in a highly curved cloud shape. It is supported by a circumferential glass wall which consists of 26 laminated glass elements (13 single curved, 13 flat). Absolute precision in engineering, manufacturing and installation are the guarantor for the realisation of this novel and spectacular glass sculpture.
Untersuchungen an thermo‐mechanisch beanspruchten Glasklebverbindungen mit integrierten faseroptischen Sensoren
Authors: Ganß Martin , Daum Maximilian , Breidenbach Marie L. , Beinersdorf Heiko , Kuhne Michael , Hildebrand Jörg
Published: June 2015

Auf Grund vieler Vorteile spielen Klebverbindungen im Bauwesen und speziell im konstruktiven Glasbau eine immer größere Rolle. Polymere Klebstoffe können aber ihre Eigenschaften in Folge mechanischer und klimatischer Umgebungseinflüsse verändern, so dass die Klebschicht oftmals eine kritische Stelle der Klebverbindung ist. Speziell bei lasttragenden und sicherheitsrelevanten Verbindungen ist eine zeitliche Überprüfung der Klebverbindung sinnvoll. Im Beitrag wird die Integration von dünnen faseroptischen Sensoren in die Klebschicht der Verbindung zur Erfassung von Dehnungen unter thermo‐mechanischer Belastung vorgestellt und diskutiert.

Investigations on thermo‐mechanically loaded glass joints using integrated fibre optic sensors. Due to their numerous advantages, adhesive joints play an increasing role in civil engineering and especially in glass constructions. The physical and mechanical properties of polymeric adhesives can be altered by mechanical and climatic influences. Thus, the adhesive layer is often a critical part of the joint. Therefore, especially for load bearing and safety‐related joints a monitoring of the adhesive layer in the joint is useful. In the contribution the integration and application of thin optical fibre sensors for strain monitoring in the adhesive layer of joints under thermo‐mechanical influences is discussed.
Wellenlängenabhängige Kenngrößen verschiedener Verglasungen beim Durchdringen von Sonnenstrahlung
Authors: Burda Clara , Hildebrand Jörg
Published: June 2015

Im modernen Fassadenbau finden große Glasflächen immer häufiger Anwendung. Ihre energetischen Kenngrößen sind für den Wärmeeintrag in das Gebäude maßgebend. Die Bestimmung kann experimentell oder numerisch erfolgen. In diesem Beitrag werden die spektralen Energieverluste bei der Leistungsdichteverteilung der Sonnenstrahlung beim Durchdringen von Kalk‐Natron‐Silicatglas analysiert. Dabei werden die Ergebnisse für Einfach‐, Doppel‐ und Dreifachverglasungen mit unterschiedlichen Beschichtungen dargestellt. Grundlage der Berechnungen ist die VDI 6007 Blatt 2 und die in ihr genannten Regelwerke.

Energy dissipation of solar radiation while piercing through various glazing. Large glass surfaces are more and more common in façade engineering. Their energetic indicators are decisive for the building’s temperature profile. Therefore they are defined by means of complex calculations. In this article, there is an analysis of spectral energy dissipation occurring with power density distribution of solar radiation while penetrating through soda lime silica glass. In this context, the results for single, double and triple glazing with various coatings are provided. The calculations are based on the VDI Guideline 6007 Part 2 and its set of rules.
Untersuchungen zum Resttragverhalten von Verbundglas
Authors: Kuntsche Johannes , Franz Johannes , Schneider Jens
Published: June 2015

Der Beitrag behandelt den Einfluss von Steifigkeit und Haftung der Zwischenfolie auf das Resttragverhalten von Verbundglas. Es wurden zwei Versuchsserien in Bauteilgröße mit sechs unterschiedlichen Folien untersucht, die auf Polyvinylbutyral (PVB) basieren. Die erste Versuchsserie untersucht die maximale kurzzeitige Belastbarkeit von gebrochenen vierseitig gelagerten Verbundgläsern. Im Anschluss wurden aufbauend auf den Ergebnisse der ersten Versuchsserie Resttragfähigkeitsversuche mit einer Standzeit von einer Stunde durchgeführt, um den Einfluss von Steifigkeit und Haftung auf die Resttragfähigkeit zu bewerten. Es zeigt sich, dass eine niedrige Haftung sowie eine hohe Steifigkeit zu einem günstigeren Resttragverhalten führen.

Investigations on the post‐breakage behaviour of laminated glass. The paper discusses the influence of stiffness and adhesion of the interlayer to the post‐breakage behaviour of laminated glass. Two test series were performed in component size with six different interlayer materials based on polyvinyl butyral (PVB). The first series examines the maximum short‐term bearing capacity of broken four side supported laminated glass. Based on the results of the first series, residual strength tests with a load period of one hour were conducted to evaluate the influence of stiffness and adhesion on the post‐breakage performance. It is shown that a low adhesion and high stiffness lead to a better residual structural behaviour.
Kriechverhalten von Klebverbindungen am Beispiel von Holz‐Glas‐Verbundelementen
Authors: Nicklisch Felix , Weller Bernhard
Published: June 2015

Tragende Holz‐Glas‐Verbundelemente gehören zu den neuen Entwicklungen im Glasbau. Die Klebverbindung in diesen Elementen wird teilweise durch ständige Einwirkungen beansprucht. Gleichzeitig weisen Klebstoffe ein zeitabhängiges Materialverhalten auf. In einer Langzeitstudie wurden drei verschiedenen Klebstoffen näher untersucht. Die Versuchsserie an Prüfkörpern mit realitätsnaher Klebfugengeometrie gliedert sich in drei Schritte: Tragfähigkeitsversuche unter Kurzzeitbelastung, Kriechversuche mit einer Dauer von jeweils 1000 Stunden und die Ermittlung der verbleibenden Tragfähigkeit nach Entlastung. Anhand der Ergebnisse lässt sich das Kriechverhalten der Klebfuge beurteilen und das langzeitige Tragvermögen der Elemente ableiten.

Creep behaviour of adhesives joints in timber‐glass composite elements. Load‐bearing timber‐glass composites belong to novel developments in the field of structural glass. The adhesive bond of such elements is exposed to long‐term static loading. At the same time, adhesives exhibit a time‐dependent material behaviour. The paper contributes to this topic by a long‐term study on three different adhesives. The test sequence divides into three major steps: the assessment of the load bearing capacity on mid‐size specimen by means of short‐term testing, several 1000 hour creep tests and the determination of their residual load‐bearing capacity after being preloaded in the creep tests. The results enable conclusions on the creep behaviour and prediction of long‐term structural performance of the bond.