bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of a thermostable glycoside hydrolase (CMbg0408) from the hyperthermophilic archaeon Caldivirga maquilingensisIC‐167
Authors: Letsididi Rebaone , Hassanin Hinawi AM , Koko Marwa YF , Ndayishimiye Jean B , Zhang Tao , Jiang Bo , Stressler Timo , Fischer Lutz , Mu Wanmeng
Published: September 2016

BACKGROUND

Hyperthermophilic archaea capable of functioning optimally at very high temperatures are a good source of unique and industrially important thermostable enzymes.

RESULTS

A glycoside hydrolase family 1 β‐galactosidase gene (BglB) from a hyperthermophilic archaeon Caldivirga maquilingensis IC‐167 was cloned and expressed in Escherichia coli. The recombinant enzyme (CMbg0408) displayed optimum activity at 110 °C and pH 5.0. It also retained 92% and 70% of its maximal activity at 115 and 120 °C, respectively. The enzyme was completely thermostable and active after 120 min of incubation at 80 and 90 °C. It also showed broad substrate specificity with activities of 8876 ± 185 U mg−1 for p‐nitrophenyl‐β‐d‐galactopyranoside, 4464 ± 172 U mg−1 for p‐nitrophenyl‐β‐d‐glucopyranoside, 1486 ± 68 U mg−1 for o‐nitrophenyl‐β‐d‐galactopyranoside, 2250 ± 86 U mg−1 for o‐nitrophenyl‐β‐d‐xylopyranoside and 175 ± 4 U mg−1 for lactose. A catalytic efficiency (kcat/Km) of 3059 ± 122 mmol L−1 s−1 and Km value of 8.1 ± 0.08 mmol L−1 were displayed towards p‐nitrophenyl‐β‐d‐galactopyranoside.

CONCLUSION

As a result of its remarkable thermostability and high activity at high temperatures, this novel β‐galactosidase may be useful for food and pharmaceutical applications. © 2016 Society of Chemical Industry
Room Enough in the Narrowest of Pipes
Authors: Kalawrytinos Stephan
Published: September 2016

Whether they are transmission components or conveyor systems, the problem is always the same: in industrial manufacturing processes, heavy‐duty components are always the Achilles' heel of overall plant efficiency. Customized surface treatment per laser cladding can render such components fit for the extreme stresses of their tasks. But this style of optimization technology is challenged when it comes to difficult‐to‐access surfaces or bores. Tight aperture diameters, large working depths or internal steps soon confront conventional laser cladding heads with their limits. But not the special processing head iClad.
Metal Optics — New Chances for Laser Focusing Mirrors
Authors: Lehndorff Michael
Published: September 2016

All reflective laser focusing heads have been in use for industrial high‐power laser machining systems for more than thirty years now. Originally inevitable for multi‐kilowatt “macro” lasers, now better metal mirror machining technologies open the field for metal optics to mid‐power and even to low‐power applications. Especially the advantage of cost effective flexible manufacturing of aspherical and free form surfaces even in lowest quantities gives the optical engineers the versatility to manufacture laser focusing systems for interesting new applications: Bessel beams will go beyond the diffraction limit, polygon scanners with smallest focus spots will deliver high power densities, e.g. for dicing, extremely compact focusing for 3D metal printing or remote welding is realized with a few mirrors only. Complete “focusing‐boxes” or just single mirrors as well as matched mirror sets are available and help laser machine builders and system integrators to realize never‐seen‐before products.
Improving the Efficiency of the DMLD Process
Authors: Wolf Markus
Published: September 2016

Direct metal laser deposition (DMLD) is commonly used for improving the surface quality of parts and for additive manufacturing of components. It can achieve faster throughput, better‐quality cladding, very low dilution levels, reduced heat input, minimal distortion, extremely low porosity, and improved surface uniformity. Taken together, these properties substantially reduce the need for time‐consuming and costly post‐processing. DMLD also offers a wide range of design options. Software‐assisted approaches make it possible to create a wide range of geometries. Multi‐layer additive manufacturing of parts is feasible, and it is even possible to build new parts that connect to existing components.
Moving science forward in a competitive marketplace
Authors: Fitzpatrick Kelley C.
Published: September 2016

Scientific information is the foundation of the food and health market, the availability of which can influence the success of a product and provide a competitive advantage. Flaxseed (Linum usitatissimum) has a significant advantage in this regard as it has strong clinical efficacy data that can be used to build consumer and food product company interest. Flax is an oilseed that is grown in cool, northern climates such as found in the western Canadian prairies and northern U.S. It can be consumed in whole seed, meal or oil form.
CACNA2D3 is downregulated in gliomas and functions as a tumor suppressor
Authors: Jin Yi , Cui Daming , Ren Jie , Wang Ke , Zeng Tao , Gao Liang
Published: September 2016

CACNA2D3, an auxiliary member of the alpha‐2/delta subunit three family of the voltage‐dependent calcium channel complex, plays a critical role in tumor suppression. However, its role in glioma carcinogenesis remains largely unknown. Here, we investigated the putative tumor suppressive role of CACNA2D3 in gliomas. Downregulation of CACNA2D3 was frequently detected in glioma tissues and cells compared with their non‐tumorigenic counterparts, and correlated with poor survival. To investigate the underlying mechanism of CACNA2D3 in the development and progression of glioma, we performed CACNA2D3 ectopic expression in glioma cells (U87 and U251) and knockdown of CACNA2D3 in LN229 cells and conducted in vitro and in vivo functional assays. Our findings showed that increased intracellular calcium (Ca2+) mediated by overexpression of CACNA2D3 induced mitochondrial‐mediated apoptosis, upregulation of NLK (through the Wnt/Ca2+pathway) and inhibition of the epithelial‐to‐mesenchymal transition. Ectopic expression of CACNA2D3 inhibited cell proliferation, migration, invasion, and tumor growth in vitro and in vivo, whereas CACNA2D3 depletion inhibited cell viability and invasion. Furthermore, we confirmed that CACNA2D3 increased NLK expression in vitro by immunostaining and found that downregulation of CACNA2D3 in glioma cells and high‐grade glioma tissue was accompanied by increased methylation. A reporter assay showed increased luciferase activity in NLK knockdown glioma cells and transcriptional activity of β‐cantenin/TCF was remarkably enhanced, which further confirmed that NLK antagonizes Wnt signaling‐mediated anchorage‐dependent and independent cell proliferation and invasion. This mechanism may contribute to a better understanding of glioma cancer pathogenesis and facilitate the development of new therapeutic strategies for the treatment of this disease. © 2016 Wiley Periodicals, Inc.
On generalized Poisson–Nernst–Planck equations with inhomogeneous boundary conditions: a‐priori estimates and stability
Authors: Kovtunenko Victor A. , Zubkova Anna V.
Published: September 2016

In this paper, we consider the strongly nonlinear Nernst–Planck equations coupled with the quasi‐linear Poisson equation under inhomogeneous, moreover, nonlinear boundary conditions. This system describes joint multi‐component electrokinetics in a pore phase. The system is supplemented by the force balance and by the volume and positivity constraints. We establish well‐posedness of the problem in the variational setting. Namely, we prove the existence theorem supported by the energy and the entropy a‐priori estimates, and we provide the Lyapunov stability of the solution as well as its uniqueness in special cases. Copyright © 2016 John Wiley & Sons, Ltd.
P‐moment stability under small Gauss type random excitation of stochastic system
Authors: Lu Zhanhui , Hao Zhiqi , Zhao Weixiang , Xie Di
Published: September 2016

In this paper, the stochastic stability under small Gauss type random excitation is investigated theoretically and numerically. When p is larger than 0, the p‐moment stability theorem of stochastic models is proved by Lyapunov method, Ito isometry formula, matrix theory and so on. Then the application of p‐moment such as k‐order moment of the origin and k‐order moment of the center is introduced and analyzed. Finally, p‐moment stability of the power system is verified through the simulation example of a one machine and infinite bus system. Copyright © 2016 John Wiley & Sons, Ltd.
Narrated video of a re‐do colposuspension
Authors: Cardozo Linda , Robinson Dudley , Shakir Fevzi
Published: September 2016

Aims

To present a narrated video designed to demonstrate the steps involved in an open re‐do colposuspension.

Methods

This was in a 70‐year‐old woman who presented with recurrent severe stress urinary incontinence. Urodynamics confirmed severe urodynamic stress incontinence, with no detrusor over activity. Her maximum urethral closure pressure (MUCP) was 8 cm/water. She previously had a total abdominal hysterectomy (TAH), bilateral salpingo‐oophorectomy (BSO) and colposuspension in 1998. Subsequently, she had a TVT in 2002 and then partial excision of the tape in 2003 due to erosion. This was followed by a Zuidex bulking agent in 2005 and subsequent TOT in 2006. After counselling she opted for a re‐do colposuspension.

Results

If primary urinary incontinence surgery has failed the decision as to what treatment should then be undertaken is controversial. The options that are available include a repeat mid urethral sling (either retropubic or transobturator), urethral bulking agents, autologous fascial slings and re‐do colposuspension.

Conclusion

A re‐do colposuspension is a sensible choice that is likely to achieve a better success rate than a second tape procedure. Although, colposuspension is an operation that most gynaecologists have now become deskilled in and rarely perform, mainly due to the popularity of tapes. This video demonstrates a re‐do colposuspension, with particular attention to the specific nuances that can results in a successful operation.
Stochastic regret minimization for revenue management problems with nonstationary demands
Authors: Zhang Huanan , Shi Cong , Qin Chao , Hua Cheng
Published: September 2016

We study an admission control model in revenue management with nonstationary and correlated demands over a finite discrete time horizon. The arrival probabilities are updated by current available information, that is, past customer arrivals and some other exogenous information. We develop a regret‐based framework, which measures the difference in revenue between a clairvoyant optimal policy that has access to all realizations of randomness a priori and a given feasible policy which does not have access to this future information. This regret minimization framework better spells out the trade‐offs of each accept/reject decision. We proceed using the lens of approximation algorithms to devise a conceptually simple regret‐parity policy. We show the proposed policy achieves 2‐approximation of the optimal policy in terms of total regret for a two‐class problem, and then extend our results to a multiclass problem with a fairness constraint. Our goal in this article is to make progress toward understanding the marriage between stochastic regret minimization and approximation algorithms in the realm of revenue management and dynamic resource allocation. © 2016 Wiley Periodicals, Inc. Naval Research Logistics 63: 433–448, 2016
Perceived weight discrimination, changes in health, and daily stressors
Authors: Sutin Angelina R. , Stephan Yannick , Grzywacz Joseph G. , Robinson Eric , Daly Michael , Terracciano Antonio
Published: September 2016

Objective

To examine whether perceived weight discrimination is associated with change in health markers over time and whether it is associated with daily stressors, physical symptoms, and affect.

Methods

Participants were selected from the Midlife in the United States (MIDUS) study if they had data on perceived weight discrimination and health markers at MIDUS II (2004–2006), health markers at MIDUS III (2013–2014), and a body mass index ≥25 kg/m2 (N = 1,841). A subset of these participants (N = 1,153) reported on their experiences daily for 8 days as part of the second National Study of Daily Experiences.

Results

Perceived weight discrimination was associated with declines in mental and physical health over time (median β = 0.06). Participants who reported weight discrimination experienced more daily stressors (β = 0.13), physical symptoms (β = 0.13), and negative affect (β = 0.13) and less positive affect (β = −0.12) over the 8 days of the second National Study of Daily Experiences. Weight discrimination was most strongly associated with interpersonal stressors (median β = 0.14), feelings of anger (β = 0.16) and frustration (β = 0.14), lower attention (β = −0.14) and activity (β = −0.16), and more nonspecific physical symptoms (e.g., fatigue; β = 0.10).

Conclusions

This research replicates the association between perceived weight discrimination and worse health over time and extends this literature to show that people who experience weight discrimination have more daily stressors, physical symptoms, and negative emotions.
Lautlos fährt das Thermoboot
Authors: Suhr Wilfried
Published: September 2016

Mit seiner bestechend einfachen Konstruktion macht sich das Thermoboot thermokapillare Kräfte für seinen Vortrieb zu Nutze. Dass es dabei ohne beweglichen Antriebsmechanismus vorankommt, verdankt es einem Kollektor, der darauf fallendes Licht in thermische Energie wandelt. Diese wird dazu verwendet, um im Fahrwasser des Bootes einen Unterschied in der Oberflächenspannung herzustellen, woraus die Antriebskraft resultiert.
Marktführer mit Zukunft
Authors: Joos Sebastian , Hahn Giso
Published: September 2016

Seit 2000 stieg die jährliche Produktion von Solarzellen und ‐modulen um das Hundertfache. Der prinzipielle Aufbau der Solarzellen hat sich aber kaum verändert. Mono‐ und multikristallines Silizium dominieren nach wie vor den Markt. Mit Bor dotierte Wafer sind immer noch das Ausgangsmaterial der meisten industriellen Solarzellen. Der Siebdruck von Metallpasten zur Kontaktierung wird bereits seit den 1970er Jahren eingesetzt. Der etablierte Standardprozess wird aktuell durch neue Schritte erweitert. Selektive Emitterstrukturen erlauben höhere Wirkungsgrade. Dies gilt besonders für PERC‐Solarzellen. Sie kommen derzeit in die Massenfertigung und übertreffen die Grenze von 20 Prozent Wirkungsgrad.
Erfolgreicher Grenzgang
Authors: Nesterov‐Müller Alexander
Published: September 2016

1859 bauten Robert Bunsen und Gustav Kirchhoff den ersten Spektrographen. Die Spektralanalyse revolutionierte viele Gebiete der Naturwissenschaften. Sie machte die Bestimmung von chemischen Elementen nicht nur auf der Erde, sondern im Licht von der Sonne und den Sternen möglich. Erst so wurde die chemische Zusammensetzung weit entfernter kosmischer Objekte der Analyse zugänglich. Die Entdeckung der Spektralanalyse ist ein zudem frühes Beispiel für eine erfolgreiche interdisziplinäre Forschung zwischen dem Chemiker Bunsen und dem Physiker Kirchhoff.
LXCat: an Open‐Access, Web‐Based Platform for Data Needed for Modeling Low Temperature Plasmas
Authors: Pitchford Leanne C. , Alves Luis L. , Bartschat Klaus , Biagi Stephen F. , Bordage Marie‐Claude , Bray Igor , Brion Chris E. , Brunger Michael J. , Campbell Laurence , Chachereau Alise , Chaudhury Bhaskar , Christophorou Loucas G. , Carbone Emile , Dyatko Nikolay A. , Franck Christian M. , Fursa Dmitry V. , Gangwar Reetesh K. , Guerra Vasco , Haefliger Pascal , Hagelaar Gerjan J. M. , Hoesl Andreas , Itikawa Yukikazu , Kochetov Igor V. , McEachran Robert P. , Morgan W. Lowell , Napartovich Anatoly P. , Puech Vincent , Rabie Mohamed , Sharma Lalita , Srivastava Rajesh , Stauffer Allan D. , Tennyson Jonathan , de Urquijo Jaime , van Dijk Jan , Viehland Larry A. , Zammit Mark C. , Zatsarinny Oleg , Pancheshnyi Sergey
Published: September 2016

LXCat is an open‐access platform (www.lxcat.net) for curating data needed for modeling the electron and ion components of technological plasmas. The data types presently supported on LXCat are scattering cross sections and swarm/transport parameters, ion‐neutral interaction potentials, and optical oscillator strengths. Twenty‐four databases contributed by different groups around the world can be accessed on LXCat. New contributors are welcome; the database contributors retain ownership and are responsible for the contents and maintenance of the individual databases. This article summarizes the present status of the project.
Structural aspects of HDAC8 mechanism and dysfunction in Cornelia de Lange syndrome spectrum disorders
Authors: Deardorff Matthew A. , Porter Nicholas J. , Christianson David W.
Published: September 2016

Cornelia de Lange Syndrome (CdLS) encompasses a broad spectrum of phenotypes characterized by distinctive craniofacial abnormalities, limb malformations, growth retardation, and intellectual disability. CdLS spectrum disorders are referred to as cohesinopathies, with ∼70% of patients having a mutation in a gene encoding a core cohesin protein (SMC1A, SMC3, or RAD21) or a cohesin regulatory protein (NIPBL or HDAC8). Notably, the regulatory function of HDAC8 in cohesin biology has only recently been discovered. This Zn2+‐dependent hydrolase catalyzes the deacetylation of SMC3, a necessary step for cohesin recycling during the cell cycle. To date, 23 different missense mutants in the gene encoding HDAC8 have been identified in children with developmental features that overlap those of CdLS. Enzymological, biophysical, and structural studies of CdLS HDAC8 protein mutants have yielded critical insight on compromised catalysis in vitro. Most CdLS HDAC8 mutations trigger structural changes that directly or indirectly impact substrate binding and catalysis. Additionally, several mutations significantly compromise protein thermostability. Intriguingly, catalytic activity in many HDAC8 mutants can be partially or fully restored by an N‐acylthiourea activator, suggesting a plausible strategy for the chemical rescue of compromised HDAC8 catalysis in vivo.
Phage display and structural studies reveal plasticity in substrate specificity of caspase‐3a from zebrafish
Authors: Tucker Matthew B. , MacKenzie Sarah H. , Maciag Joseph J. , Dirscherl Ackerman Hayley , Swartz Paul , Yoder Jeffrey A. , Hamilton Paul T. , Clay Clark A.
Published: September 2016

The regulation of caspase‐3 enzyme activity is a vital process in cell fate decisions leading to cell differentiation and tissue development or to apoptosis. The zebrafish, Danio rerio, has become an increasingly popular animal model to study several human diseases because of their transparent embryos, short reproductive cycles, and ease of drug administration. While apoptosis is an evolutionarily conserved process in metazoans, little is known about caspases from zebrafish, particularly regarding substrate specificity and allosteric regulation compared to the human caspases. We cloned zebrafish caspase‐3a (casp3a) and examined substrate specificity of the recombinant protein, Casp3a, compared to human caspase‐3 (CASP3) by utilizing M13 bacteriophage substrate libraries that incorporated either random amino acids at P5‐P1′ or aspartate fixed at P1. The results show a preference for the tetrapeptide sequence DNLD for both enzymes, but the P4 position of zebrafish Casp3a also accommodates valine equally well. We determined the structure of zebrafish Casp3a to 2.28Å resolution by X‐ray crystallography, and when combined with molecular dynamics simulations, the results suggest that a limited number of amino acid substitutions near the active site result in plasticity of the S4 sub‐site by increasing flexibility of one active site loop and by affecting hydrogen‐bonding with substrate. The data show that zebrafish Casp3a exhibits a broader substrate portfolio, suggesting overlap with the functions of caspase‐6 in zebrafish development.
Growth, magnetic and transport properties of Li‐doped SrFe2As2 single crystals
Authors: Shlyk Larysa , Bischoff Markus , Rose Eva , Niewa Rainer
Published: September 2016

Single crystals of Li‐doped SrFe2As2 up to 2 × 2 mm2 in size were grown from LiCl flux. The obtained material contains only a minor amount of Li, but shows distinct differences in physical properties as compared to the pure material synthesized via other techniques. It orders antiferromagnetically below 6.2 K and does not show any indication of superconductivity above 1.2 K. The large negative Curie–Weiss temperature θW⊥ = −206.5 (μW|| = −200.5 K) points to the dominance of antiferromagnetic Fe–Fe interactions. The reduced effective magnetic moments of Fe2+ μeff⊥ = 2.31 μB (μeff|| = 2.27 μB) indicate itinerant character of magnetism in this system. According to electrical resistivity measurements this material is a semimetal. In the temperature range of 12–70 K ρ(T) follows a Fermi‐liquid T2‐dependence. In the vicinity of antiferromagnetic ordering ρ(T) deviates from Fermi‐liquid behavior. Below about 12 K, a transport law of the obtained single crystals requires a substantial linear non‐Fermi contribution to successfully describe the data.
Electrical and transport properties of nearly stoichiometric transparent n‐type silver indium oxide thin films
Authors: Keerthi K. , Tarachand P. , Okram G. S. , Shripathi T. , Ganesan V. , Nair B. G. , Abraham A. , Philip R. R.
Published: September 2016

The possibility of combining both optical transparency and high electrical conductivity in the same material makes transparent conducting oxides one of the most sought after materials in transparent electronics. This paper presents the investigations done on the conductivity mechanisms of n‐type transparent conducting silver indium oxide thin films in different temperature ranges varying from 6 to 333 K. X‐ray diffraction indicates the films to be amorphous, and the morphology of the films from scanning electron microscopy and atomic force microscopy shows agglomerations with average particle size ∼30 nm. X‐ray photoelectron spectroscopy and energy‐dispersive analysis of X‐rays establish the films to be nearly stoichiometric with In/Ag at.% ratio in the range 1.1–1.2. The transmittance percentage obtained from optical transmittance and absorbance spectra is moderately high and the bandgap energy of the thin films is ∼3.5 eV. Transport parameters, such as carrier mobility ∼103 cm2/V s and carrier concentration ∼1018/cm3, are elucidated from Hall and thermopower data.
Kinetic‐energy‐density dependent semilocal exchange‐correlation functionals
Authors: Della Sala Fabio , Fabiano Eduardo , Constantin Lucian A.
Published: September 2016

We present the theory of semilocal exchange‐correlation (XC) energy functionals which depend on the Kohn–Sham kinetic energy density (KED), including the relevant class of meta‐generalized gradient approximation (meta‐GGA) functionals. Thanks to the KED ingredient, meta‐GGA functionals can satisfy different exact constraints for XC energy and can be made one‐electron self‐correlation free. This leads to a better accuracy over a wider range of properties with respect to GGAs, often reaching the accuracy of hybrid functionals, but at much reduced computational cost. An extensive survey of the relevant literature on existing KED dependent XC functionals is provided, considering nonempirical, semi‐empirical, and fully empirical ones. A deeper analysis and a wide benchmark are presented for functionals derived considering only exact constraints and parameters obtained from model and/or atomic systems.
Objective Bayesian model selection for Cox regression
Authors: Held Leonhard , Gravestock Isaac , Sabanés Bové Daniel
Published: September 2016

There is now a large literature on objective Bayesian model selection in the linear model based on theg‐prior. The methodology has been recently extended to generalized linear models using test‐based Bayes factors. In this paper, we show that test‐based Bayes factors can also be applied to the Cox proportional hazards model. If the goal is to select a single model, then both the maximuma posterioriand the median probability model can be calculated. For clinical prediction of survival, we shrink the model‐specific log hazard ratio estimates with subsequent calculation of the Breslow estimate of the cumulative baseline hazard function. A Bayesian model average can also be employed. We illustrate the proposed methodology with the analysis of survival data on primary biliary cirrhosis patients and the development of a clinical prediction model for future cardiovascular events based on data from the Second Manifestations of ARTerial disease (SMART) cohort study. Cross‐validation is applied to compare the predictive performance with alternative model selection approaches based on Harrell's c‐Index, the calibration slope and the integrated Brier score. Finally, a novel application of Bayesian variable selection to optimal conditional prediction via landmarking is described. Copyright © 2016 John Wiley & Sons, Ltd.
A practical Bayesian design to identify the maximum tolerated dose contour for drug combination trials
Authors: Zhang Liangcai , Yuan Ying
Published: September 2016

Drug combination therapy has become the mainstream approach to cancer treatment. One fundamental feature that makes combination trials different from single‐agent trials is the existence of the maximum tolerated dose (MTD) contour, that is, multiple MTDs. As a result, unlike single‐agent phase I trials, which aim to find a single MTD, it is often of interest to find the MTD contour for combination trials. We propose a new dose‐finding design, the waterfall design, to find the MTD contour for drug combination trials. Taking the divide‐and‐conquer strategy, the waterfall design divides the task of finding the MTD contour into a sequence of one‐dimensional dose‐finding processes, known as subtrials. The subtrials are conducted sequentially in a certain order, such that the results of each subtrial will be used to inform the design of subsequent subtrials. Such information borrowing allows the waterfall design to explore the two‐dimensional dose space efficiently using a limited sample size and decreases the chance of overdosing and underdosing patients. To accommodate the consideration that doses on the MTD contour may have very different efficacy or synergistic effects because of drug–drug interaction, we further extend our approach to a phase I/II design with the goal of finding the MTD with the highest efficacy. Simulation studies show that the waterfall design is safer and has higher probability of identifying the true MTD contour than some existing designs. The R package “BOIN” to implement the waterfall design is freely available from CRAN. Copyright © 2016 John Wiley & Sons, Ltd.
Lipoic acid and Calligonum comosumon attenuate aroclor 1260‐induced testicular toxicity in adult rats
Authors: Aly Hamdy A. A. , Alahdal Abdulrahman M. , Nagy Ayman A. , Abdallah Hossam M. , Abdel‐Sattar Essam A. , Azhar Ahmad S.
Published: September 2016

Aroclor 1260 is one of the more representative polychlorinated biphenyls found in biota. This study was designed to delineate the testicular toxicity of Aroclor 1260 and to elucidate the potential protective role of Calligonum comosum (C. comosum) and lipoic acid in adult rats. Aroclor 1260 was dissolved in corn oil and given to rats by gavage at doses 0, 20, 40, or 60 mg/kg/day for 15 consecutive days (Groups I, II, III, and IV, respectively). Groups V and VI were pretreated with C. comosum (200 mg/kg/day) and lipoic acid (35 mg/kg/day) respectively 24 h before Aroclor 1260 (40 mg/kg/day) treatment for 15 consecutive days. Aroclor 1260 (20, 40 or 60 mg/kg/day) treatment significantly decreased testes weight, sperm count and motility and daily sperm production. Serum testosterone was significantly decreased in response to treatment with 40 and 60 mg/kg/day of Aroclor 1260. LDH‐X activity was significantly decreased at the three dose levels. Hydrogen peroxide (H2O2) production (in a dose‐related manner) and lipid peroxidation were significantly increased in response to Aroclor 1260 (20, 40, or 60 mg/kg/day) treatment. Aroclor 1260 at the three dose levels decreased the activities of the antioxidant enzymes SOD, CAT, GPx, and GR and the non‐enzymatic antioxidant GSH level. CAT, GPx and GSH showed a dose‐response effect. These abnormalities were effectively attenuated by pretreatment with C. comosum (200 mg/kg/day) or lipoic acid (35 mg/kg/day). Histopathological examination showed a dose‐related increase in morphological abnormalities of the testis in response to Aroclor 1260 treatment. In conclusion, Aroclor 1260 induced testicular toxicity at least, in part, by induction of oxidative stress. By reversal of biochemical and morphological changes towards normalcy, the cytoprotective role of C. comosum and lipoic acid is illuminated. In comparison, lipoic acid was more protective than C. comosum extract against testicular toxicity induced by Aroclor 1260. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1147–1157, 2017.
Application of quantum mechanics/molecular mechanics methods in the study of enzymatic reaction mechanisms
Authors: Sousa Sérgio Filipe , Ribeiro António J. M. , Neves Rui P. P. , Brás Natércia F. , Cerqueira Nuno M. F. S. A. , Fernandes Pedro A. , Ramos Maria João
Published: September 2016

Quantum mechanics/molecular mechanics (QM/MM) methods offer a very appealing option for the computational study of enzymatic reaction mechanisms, by separating the problem into two parts that can be treated with different computational methods. Hence, in a QM/MM formalism, the part of the system in which catalysis actually occurs and that involves the active site, substrates and directly participating amino acid residues is treated at an adequate quantum mechanical level to describe the chemistry taking place. For the remaining of the enzyme, which does not participate directly in the reaction, but that typically involves a much larger number of atoms, molecular mechanics is employed, traditionally through the application of a biomolecular force field. When applied with care, QM/MM methods can be used with great advantage in comparing, at a structural and energetic level, different mechanistic proposals, discarding mechanistic alternatives and proposing new mechanistic pathways that are consistent with the available experimental data. With time, diverse flavors within the QM/MM methods have emerged, differing in a variety of technical and conceptual aspects. Hence present alternatives differ between additive and subtractive QM/MM schemes, the type of boundary schemes, and the way in which the electrostatic interactions between the two regions are accounted for. Also, single‐conformation QM/MM, multi‐PES approaches, and QM/MM Molecular Dynamics coexist today, each type with its own advantages and limitations. This review focuses on the application of QM/MM methods in the study of enzymatic reaction mechanisms, briefly presenting also the most important technical aspects involved in these calculations. Particular attention is dedicated to the application of the single‐conformation QM/MM, multi‐PES QM/MM studies, and QM/MM‐FEP methods and to the advantages and disadvantages of the different types of QM/MM. Recent breakthroughs are also introduced. A selection of hand‐picked examples is used to illustrate such features. WIREs Comput Mol Sci 2017, 7:e1281. doi: 10.1002/wcms.1281

This article is categorized under:

Structure and Mechanism > Computational Biochemistry and Biophysics

Structure and Mechanism > Reaction Mechanisms and Catalysis

Electronic Structure Theory > Combined QM/MM Methods
Optimisation of runway orientations for three-runway configurations
Authors: Oktal H. , Yıldırım N.
Published: September 2016

Determination of runway orientation is a prime factor affecting the layout of airport facilities. This paper presents a new computer model called TORO (Tool for Optimum Runway Orientation) which is developed with an approach different from that of the Federal Aviation Administration's (FAA) wind rose method. All models previously developed are based on this traditional method. In the new model, each wind observation is evaluated individually in the computations without grouping them. Thus, the errors arising from the partial coverage problem and the FAA's assumption related to distribution of winds in each cell of wind rose are eliminated. The new model is written in CSharp (C#) programming language and the wind data tables are prepared in Access format. The accuracy, reliability and flexibility of the model are tested with three numerical examples. The results demonstrate that the TORO model may be a valuable tool for airport planners and designers.
Responding to health inequities: Indigenous health system innovations
Authors: Lavoie J. G. , Kornelsen D. , Wylie L. , Mignone J. , Dwyer J. , Boyer Y. , Boulton A. , O'Donnell K.
Published: September 2016

Over the past decades, Indigenous communities around the world have become more vocal and mobilized to address the health inequities they experience. Many Indigenous communities we work with in Canada, Australia, Latin America, the USA, New Zealand and to a lesser extent Scandinavia have developed their own culturally-informed services, focusing on the needs of their own community members. This paper discusses Indigenous healthcare innovations from an international perspective, and showcases Indigenous health system innovations that emerged in Canada (the First Nation Health Authority) and Colombia (Anas Wayúu). These case studies serve as examples of Indigenous-led innovations that might serve as models to other communities. The analysis we present suggests that when opportunities arise, Indigenous communities can and will mobilize to develop Indigenous-led primary healthcare services that are well managed and effective at addressing health inequities. Sustainable funding and supportive policy frameworks that are harmonized across international, national and local levels are required for these organizations to achieve their full potential. In conclusion, this paper demonstrates the value of supporting Indigenous health system innovations.
The Old Bailey Proceedings, 1674–1913: Text Mining for Evidence of Court Behavior
Authors: Hitchcock Tim , Turkel William J.
Published: September 2016

The shortest trial report in the Old Bailey Proceedings is precisely eight words in length. In February, 1685:

Elizabeth Draper, Indicted for Felony, was found Guilty.
Nitric oxide-mediated apoptosis of neutrophils through caspase-8 and caspase-3-dependent mechanism
Authors: Dubey Megha , Nagarkoti Sheela , Awasthi Deepika , Singh Abhishek K , Chandra Tulika , Kumaravelu J , Barthwal Manoj K , Dikshit Madhu
Published: September 2016

Neutrophils play an indispensable role in killing of invading pathogens by enhancing reactive oxygen species (ROS) and NO generation, and subsequently undergoing apoptosis. Unlike ROS/NOX2, role of NO/NOS still remains undefined in the apoptosis of neutrophils (PMNs) and the present study attempts to decipher the importance of NO/NOS in the neutrophil apoptosis. Prolonged treatment of human PMNs or mice bone marrow derived neutrophils (BMDN) with NO led to enhanced ROS generation, caspase-8/caspase-3 cleavage, reduced mitochondrial membrane potential and finally cellular apoptosis. NO-induced ROS generation led to caspase-8 deglutathionylation and activation, which subsequently activated mitochondrial death pathway via BID (Bcl-2 family protein) cleavage. NO-mediated augmentation of caspase-8 and BID cleavage was significantly prevented in BMDN from neutrophil cytosolic factor-1 (NCF-1) knockout (KO) mice, implying the involvement of NOX2 in NO-induced apoptosis of PMNs. Furthermore, ROS, NO generation and inducible nitric oxide synthase (iNOS) expression were enhanced in a time-dependent manner in human PMNs and mice BMDN undergoing spontaneous apoptosis. Pharmacological and genetic ablation of iNOS in human PMNs and mice BMDN significantly reduced the levels of apoptosis. Impaired apoptosis of BMDN from iNOS KO mice was due to reduced caspase-8 activity which subsequently prevented caspase-3 and -9 activation. Altogether, our results suggest a crucial role of NO/iNOS in neutrophil apoptosis via enhanced ROS generation and caspase-8 mediated activation of mitochondrial death pathway.
Kinsenoside screening with a microfluidic chip attenuates gouty arthritis through inactivating NF-κB signaling in macrophages and protecting endothelial cells
Authors: Han Qiao , Bing Wang , Di Yin , Hua Li , Shi-he Li , Yu-hua Zheng , Xiu-guo Han , Yu-gang Wang , Qi-ming Fan , Shih-mo Yang , Ting-ting Tang
Published: September 2016

Gouty arthritis is a rheumatic disease that is characterized by the deposition of monosodium urate (MSU) in synovial joints cause by the increased serum hyperuricemia. This study used a three-dimensional (3D) flowing microfluidic chip to screen the effective candidate against MSU-stimulated human umbilical vein endothelial cell (HUVEC) damage, and found kinsenoside (Kin) to be the leading active component ofAnoectochilus roxburghi, one of the Chinese medicinal plant widely used in the treatment of gouty arthritis clinically. Cell viability and apoptosis of HUVECs were evaluated, indicating that direct Kin stimulation and conditioned medium (CM) from Kin-treated macrophages both negatively modulated with MSU crystals. Additionally, Kin was capable of attenuating MSU-induced activation of nuclear factor-κB/mitogen-activated protein kinase (NF-κB/MAPK) signaling, targeting IκB kinase-α(IKKα) and IKKβkinases of macrophages and influencing the expressions of NF-κB downstream cytokines and subsequent HUVEC bioactivity. Inflammasome NLR pyrin domain-containing 3 (NALP3) and toll-like receptor 2 (TLR2) were also inhibited after Kin treatment. Also, Kin downregulated CD14-mediated MSU crystals uptake in macrophages.In vivostudy with MSU-injected ankle joints further revealed the significant suppression of inflammatory infiltration and endothelia impairment coupled with alleviation of ankle swelling and nociceptive response via Kin treatments. Taken together, these data implicated that Kin was the most effective candidate fromAnoectochilus roxburghito treat gouty arthritis clinically.
Experimental characterization of extreme events of inertial dissipation in a turbulent swirling flow
Authors: Saw E. -W. , Kuzzay D. , Faranda D. , Guittonneau A. , Daviaud F. , Wiertel-Gasquet C. , Padilla V. , Dubrulle B.
Published: September 2016

The three-dimensional incompressible Navier–Stokes equations, which describe the motion of many fluids, are the cornerstones of many physical and engineering sciences. However, it is still unclear whether they are mathematically well posed, that is, whether their solutions remain regular over time or develop singularities. Even though it was shown that singularities, if exist, could only be rare events, they may induce additional energy dissipation by inertial means. Here, using measurements at the dissipative scale of an axisymmetric turbulent flow, we report estimates of such inertial energy dissipation and identify local events of extreme values. We characterize the topology of these extreme events and identify several main types. Most of them appear as fronts separating regions of distinct velocities, whereas events corresponding to focusing spirals, jets and cusps are also found. Our results highlight the non-triviality of turbulent flows at sub-Kolmogorov scales as possible footprints of singularities of the Navier–Stokes equation.
Sequences flanking the core-binding site modulate glucocorticoid receptor structure and activity
Authors: Schöne Stefanie , Jurk Marcel , Helabad Mahdi Bagherpoor , Dror Iris , Lebars Isabelle , Kieffer Bruno , Imhof Petra , Rohs Remo , Vingron Martin , Thomas-Chollier Morgane , Meijsing Sebastiaan H.
Published: September 2016

The glucocorticoid receptor (GR) binds as a homodimer to genomic response elements, which have particular sequence and shape characteristics. Here we show that the nucleotides directly flanking the core-binding site, differ depending on the strength of GR-dependent activation of nearby genes. Our study indicates that these flanking nucleotides change the three-dimensional structure of the DNA-binding site, the DNA-binding domain of GR and the quaternary structure of the dimeric complex. Functional studies in a defined genomic context show that sequence-induced changes in GR activity cannot be explained by differences in GR occupancy. Rather, mutating the dimerization interface mitigates DNA-induced changes in both activity and structure, arguing for a role of DNA-induced structural changes in modulating GR activity. Together, our study shows that DNA sequence identity of genomic binding sites modulates GR activity downstream of binding, which may play a role in achieving regulatory specificity towards individual target genes.
Proteome-wide association studies identify biochemical modules associated with a wing-size phenotype in Drosophila melanogaster
Authors: Okada Hirokazu , Ebhardt H. Alexander , Vonesch Sibylle Chantal , Aebersold Ruedi , Hafen Ernst
Published: September 2016

The manner by which genetic diversity within a population generates individual phenotypes is a fundamental question of biology. To advance the understanding of the genotype–phenotype relationships towards the level of biochemical processes, we perform a proteome-wide association study (PWAS) of a complex quantitative phenotype. We quantify the variation of wing imaginal disc proteomes in Drosophila genetic reference panel (DGRP) lines using SWATH mass spectrometry. In spite of the very large genetic variation (1/36 bp) between the lines, proteome variability is surprisingly small, indicating strong molecular resilience of protein expression patterns. Proteins associated with adult wing size form tight co-variation clusters that are enriched in fundamental biochemical processes. Wing size correlates with some basic metabolic functions, positively with glucose metabolism but negatively with mitochondrial respiration and not with ribosome biogenesis. Our study highlights the power of PWAS to filter functional variants from the large genetic variability in natural populations.
Spin–orbit torque-assisted switching in magnetic insulator thin films with perpendicular magnetic anisotropy
Authors: Li Peng , Liu Tao , Chang Houchen , Kalitsov Alan , Zhang Wei , Csaba Gyorgy , Li Wei , Richardson Daniel , DeMann August , Rimal Gaurab , Dey Himadri , Jiang J. S. , Porod Wolfgang , Field Stuart B. , Tang Jinke , Marconi Mario C. , Hoffmann Axel , Mryasov Oleg , Wu Mingzhong
Published: September 2016

As an in-plane charge current flows in a heavy metal film with spin–orbit coupling, it produces a torque on and thereby switches the magnetization in a neighbouring ferromagnetic metal film. Such spin–orbit torque (SOT)-induced switching has been studied extensively in recent years and has shown higher efficiency than switching using conventional spin-transfer torque. Here we report the SOT-assisted switching in heavy metal/magnetic insulator systems. The experiments used a Pt/BaFe12O19 bilayer where the BaFe12O19 layer exhibits perpendicular magnetic anisotropy. As a charge current is passed through the Pt film, it produces a SOT that can control the up and down states of the remnant magnetization in the BaFe12O19 film when the film is magnetized by an in-plane magnetic field. It can reduce or increase the switching field of the BaFe12O19 film by as much as about 500 Oe when the film is switched with an out-of-plane field.
Temperature-dependent changes in neuronal dynamics in a patient with an SCN1A mutation and hyperthermia induced seizures
Authors: Peters C. , Rosch R. E. , Hughes E. , Ruben P. C.
Published: September 2016

Dravet syndrome is the prototype of SCN1A-mutation associated epilepsies. It is characterised by prolonged seizures, typically provoked by fever. We describe the evaluation of an SCN1A mutation in a child with early-onset temperature-sensitive seizures. The patient carries a heterozygous missense variant (c3818C > T; pAla1273Val) in the NaV1.1 brain sodium channel. We compared the functional effects of the variant vs. wild type NaV1.1 using patch clamp recordings from channels expressed in Chinese Hamster Ovary Cells at different temperatures (32, 37 and 40 °C). The variant channels produced a temperature-dependent destabilization of activation and fast inactivation. Implementing these empirical abnormalities in a computational model predicts a higher threshold for depolarization block in the variant, particularly at 40 °C, suggesting a failure to autoregulate at high-input states. These results reveal direct effects of abnormalities in NaV1.1 biophysical properties on neuronal dynamics. They illustrate the value of combining cellular measurements with computational models to integrate different observational scales (gene/channel to patient).
Projecting the COPD population and costs in England and Scotland: 2011 to 2030
Authors: McLean Susannah , Hoogendoorn Martine , Hoogenveen Rudolf T. , Feenstra Talitha L. , Wild Sarah , Simpson Colin R. , Mölken Maureen Rutten-van , Sheikh Aziz
Published: September 2016

We aimed to estimate the prevalence, healthcare costs and number of deaths among people with chronic obstructive pulmonary disease (COPD) in England and Scotland 2011–2030. We adapted the Dutch COPD Model by using English and Scottish demographic, COPD incidence, COPD prevalence, smoking prevalence and mortality data to make projections. In England, the prevalence of COPD was estimated to be 1.79% (95% uncertainty interval 1.77–1.81) in 2011, increasing to 2.19% (1.85–2.33) by 2030. In Scotland, prevalence was 2.03% (1.96–2.10) in 2011 increasing to 2.20% (1.98–2.40) in 2030. These increases were driven by more women developing COPD. Annual direct healthcare costs of COPD in England were estimated to increase from £1.50 billon (1.18–2.50) in 2011 to £2.32 (1.85–3.08) billion in 2030. In Scotland, costs increased from £159 million (128–268) in 2011 to £207 (165–274) million in 2030. The deaths in England were estimated to increase from 99,200 (92,500–128,500) in 2011, to 129,400 (126,400–133,400) by 2030. In Scotland, in 2011 there were 9,700 (9,000–12,300) deaths and 13,900 (13,400–14,500) deaths in 2030. The number of people with COPD will increase substantially over the coming years in England and Scotland, particularly in females. Services need to adapt to this increasing demand.
Correction: Corrigendum: Interoccurrence time statistics in fully-developed turbulence
Authors: Manshour Pouya , Anvari Mehrnaz , Reinke Nico , Sahimi Muhammad , Tabar M. Reza Rahimi
Published: September 2016

Scientific Reports 6: Article number: 27452; published online: 10 June 2016; updated: 01 September 2016. The original version of this Article contained a typographical error in the spelling of the author Muhammad Sahimi, which was incorrectly given as Muhammad Sahim. This has now been corrected in the PDF and HTML versions of the Article.