bluuebunny/crossref_metadata_2025_split huggingface dataset:
Kinetic‐energy‐density dependent semilocal exchange‐correlation functionals
Authors: Della Sala Fabio , Fabiano Eduardo , Constantin Lucian A. 
Published: September 2016

AbstractWe 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.
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

ABSTRACTAroclor 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.1281This 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

ABSTRACTDetermination 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.
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

AbstractNeutrophils 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

AbstractGouty 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

AbstractThe 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

AbstractThe 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

AbstractThe 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

AbstractAs 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

AbstractDravet 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

AbstractWe 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.
The Comet Assay: Automated Imaging Methods for Improved Analysis and Reproducibility
Authors: Braafladt Signe , Reipa Vytas , Atha Donald H. 
Published: September 2016

AbstractSources of variability in the comet assay include variations in the protocol used to process the cells, the microscope imaging system and the software used in the computerized analysis of the images. Here we focus on the effect of variations in the microscope imaging system and software analysis using fixed preparations of cells and a single cell processing protocol. To determine the effect of the microscope imaging and analysis on the measured percentage of damaged DNA (% DNA in tail), we used preparations of mammalian cells treated with etoposide or electrochemically induced DNA damage conditions and varied the settings of the automated microscope, camera and commercial image analysis software. Manual image analysis revealed measurement variations in percent DNA in tail as high as 40% due to microscope focus, camera exposure time and the software image intensity threshold level. Automated image analysis reduced these variations as much as three-fold, but only within a narrow range of focus and exposure settings. The magnitude of variation, observed using both analysis methods, was highly dependent on the overall extent of DNA damage in the particular sample. Mitigating these sources of variability with optimal instrument settings facilitates an accurate evaluation of cell biological variability.
Unveiling the molecular mechanism of self-healing in a telechelic, supramolecular polymer network
Authors: Yan Tingzi , Schröter Klaus , Herbst Florian , Binder Wolfgang H. , Thurn-Albrecht Thomas 
Published: September 2016

AbstractReversible polymeric networks can show self-healing properties due to their ability to reassemble after application of stress and fracture, but typically the relation between equilibrium molecular dynamics and self-healing kinetics has been difficult to disentangle. Here we present a well-characterized, self-assembled bulk network based on supramolecular assemblies, that allows a clear distinction between chain dynamics and network relaxation. Small angle x-ray scattering and rheological measurements provide evidence for a structurally well-defined, dense network of interconnected aggregates giving mechanical strength to the material. Different from a covalent network, the dynamic character of the supramolecular bonds enables macroscopic flow on a longer time scale and the establishment of an equilibrium structure. A combination of linear and nonlinear rheological measurements clearly identifies the terminal relaxation process as being responsible for the process of self-healing.
Non-Volatile Ferroelectric Switching of Ferromagnetic Resonance in NiFe/PLZT Multiferroic Thin Film Heterostructures
Authors: Hu Zhongqiang , Wang Xinjun , Nan Tianxiang , Zhou Ziyao , Ma Beihai , Chen Xiaoqin , Jones John G. , Howe Brandon M. , Brown Gail J. , Gao Yuan , Lin Hwaider , Wang Zhiguang , Guo Rongdi , Chen Shuiyuan , Shi Xiaoling , Shi Wei , Sun Hongzhi , Budil David , Liu Ming , Sun Nian X. 
Published: September 2016

AbstractMagnetoelectric effect, arising from the interfacial coupling between magnetic and electrical order parameters, has recently emerged as a robust means to electrically manipulate the magnetic properties in multiferroic heterostructures. Challenge remains as finding an energy efficient way to modify the distinct magnetic states in a reliable, reversible and non-volatile manner. Here we report ferroelectric switching of ferromagnetic resonance in multiferroic bilayers consisting of ultrathin ferromagnetic NiFe and ferroelectric Pb0.92La0.08Zr0.52Ti0.48O3 (PLZT) films, where the magnetic anisotropy of NiFe can be electrically modified by low voltages. Ferromagnetic resonance measurements confirm that the interfacial charge-mediated magnetoelectric effect is dominant in NiFe/PLZT heterostructures. Non-volatile modification of ferromagnetic resonance field is demonstrated by applying voltage pulses. The ferroelectric switching of magnetic anisotropy exhibits extensive applications in energy-efficient electronic devices such as magnetoelectric random access memories, magnetic field sensors and tunable radio frequency (RF)/microwave devices.