bluuebunny/crossref_metadata_2025 huggingface dataset:
Aromatase Activity and Bone Loss in Men
Authors: Merlotti Daniela , Gennari Luigi , Stolakis Konstantinos , Nuti Ranuccio
Published: June 2011

Aromatase is a specific component of the cytochrome P450 enzyme system responsible for the transformation of androgen precursors into estrogens. This enzyme is encoded by theCYP19A1gene located at chromosome 15q21.2, that is, expressed in ovary and testis, but also in many extraglandular sites such as the placenta, brain, adipose tissue, and bone. The activity of aromatase regulates the concentrations of estrogens with endocrine, paracrine, and autocrine effects on target issues including bone. Importantly, extraglandular aromatization of circulating androgen precursors is the major source of estrogen in men. Clinical and experimental evidences clearly indicate that aromatase activity and estrogen production are necessary for longitudinal bone growth, the attainment of peak bone mass, pubertal growth spurt, epiphyseal closure, and normal bone remodeling in young individuals. Moreover, with aging, individual differences in aromatase activity may significantly affect bone loss and fracture risk in men.
Stress Degradation Behavior of Paliperidone, an Antipsychotic Drug, and Development of Suitable Stability-Indicating RP-LC Method
Authors: Jadhav Sanjay A. , Landge Shashikant B. , Choudhari Pramod M. , Solanki Pavankumar V. , Bembalkar Saroj R. , Mathad Vijayavitthal T.
Published: June 2011

A new, simple, rapid, and stability-indicating reversed phase liquid chromatographic (RP-LC) method for the determination of both assay and related substances in paliperidone has been developed and validated. During the forced degradation at hydrolysis, oxidative, photolytic, and thermal stressed conditions, the degradation was observed in the oxidative and acid stress conditions. Five process-related impurities (Imp-A to Imp-E) in test sample of paliperidone have been detected using newly developed RP-LC method. Among the five, Imp-C and Imp-D were found to be degrdants. Good resolution between the peaks corresponding to degradation and process-related impurities from the analyte was achieved on a Hypersil BDS C18 (250×4.6 mm, 5 μm) column. The stress samples were assayed against a qualified reference standard, and the mass balance was found to be close to 99.0%. The method was validated as per ICH guideline and was found to be robust. The proposed RP-LC method was successfully applied to the analysis of commercial formulation and was found to be specific and selective.
The Evidence for Efficacy of Osteoporosis Treatment in Men with Primary Osteoporosis: A Systematic Review and Meta-Analysis of Antiresorptive and Anabolic Treatment in Men
Authors: Schwarz Peter , Jorgensen Niklas Rye , Mosekilde Leif , Vestergaard Peter
Published: June 2011

Purpose. Fragility fractures in men constitute a major worldwide public health problem with a life-time risk of 13%. It cannot be directly inferred that antiosteoporotic drugs effective in women have the same effect in men. Our aim was to appraise the existing evidence for efficacy of osteoporosis treatment in men.Methods. This study was a systematic review of the published literature on the clinical efficacy of medical osteoporosis therapy in the reduction of fracture risk in men (age>50 years). Studies included were randomised, placebo-controlled trials of men.Results. Five BMD studies of antiresorptive treatment were included. All studies showed an increase in BMD, but there was only a nonsignificant trend in the reduction of clinical fractures. Three BMD studies of anabolic treatment with teriparatide were also included. These showed a significant mean increase in spine BMD and for vertebral fractures a non-significant trend towards a reduction was seen.Conclusion. The evidence of medical osteoporosis treatment in men is scant and inconclusive due to the lack of prospective RCT studies with fracture prevention as primary end point. So far, all evidence is based on BMD increases in small RCT studies showing BMD increases comparable to those reported in postmenopausal women.
Stripping Voltammetric Determination of Analgesics in Their Pharmaceuticals Using Nano-Riboflavin-Modified Glassy Carbon Electrode
Authors: Gopu Gopalakrishnan , Manisankar Paramasivam , Muralidharan Baladhandapani , Vedhi Chinnapiyan
Published: June 2011

Cyclic voltammetric behaviors of three analgesics, acetaminophen (AAP), acetylsalicylic acid (ASA), and dipyrone (DP), were studied using nano-riboflavin-modified glassy carbon electrode. One well-defined oxidation peak each for AAP and ASA and three oxidation peaks for DP were observed. The influence of pH, scan rate, and concentration reveals irreversible diffusion controlled reaction. The SEM analysis confirmed good accumulation of the drugs on the electrode surface. Calibration was made under the maximum peak current conditions. The concentration range studied for the determination of drugs was 0.02 to 0.4 μg mL−1for AAP and ASA and 0.025 to 0.4 μg mL−1for DP. The lower limit of detection observed for AAP, ASA, and DP was 0.016, 0.007 μg mL−1, and 0.013 μg mL−1, respectively. The suitability of the method for the determination of these analgesics in pharmaceutical preparations and urine samples was also ascertained.
Fabry Disease and Early Stroke
Authors: Feldt-Rasmussen U.
Published: June 2011

Fabry disease, an X-linked lysosomal storage disorder, results from deficient activity of the enzyme α-galactosidase A. Affected males with the classic phoenotype have acroparaesthesias, hypohidrosis, and corneal opacities in childhood and develop renal failure, cardiac hypertrophy or strokes in the third to fifth decade of life. Some female heterozygotes are asymptomatic, some as severely affected as males. The natural history of Fabry patients includes transitory cerebral ischaemia and strokes, even in very young persons of both genders. The mechanism is partly due to vascular endothelial accumulation of GL-3. White matter lesions on MRI occur. Both males and females can be safely treated with enzyme replacement; and thus screening for Fabry disease of young stroke populations should be considered. There are, however, no hard data of treatment effect on mortality and morbidity. The analyses of results from ongoing studirs will add to the decision on whether or not to screen young stroke patients for Fabry disease. Finally, stroke prophylactic therapy should be used liberally in patients of both genders with verified Fabry disease. This includes primary prevention such as lifestyle counseling, targeting blood pressure, managing atrial fibrillation, diabetes mellitus, hyperlipidaemia, and ASA.
How to Treat a Signal? Current Basis for RET-Genotype-Oriented Choice of Kinase Inhibitors for the Treatment of Medullary Thyroid Cancer
Authors: Prazeres Hugo , Torres Joana , Rodrigues Fernando , Couto Joana P. , Vinagre João , Sobrinho-Simões Manuel , Soares Paula
Published: June 2011

The significance ofRETin thyroid cancer comes from solid evidence that, when inherited, anRETactivating mutation primes C-cells to transform into medullary carcinomas. Moreover, environmental exposure to radiation also induces rearranged transforming RET “isoforms” that are found in papillary thyroid cancer. TheRETgene codes for a tyrosine kinase receptor that targets a diverse set of intracellular signaling pathways. The nature ofRETpoint mutations predicts differences in the mechanisms by which the receptor becomes activated and correlates with different forms of clinical presentation, age of onset, and biological aggressiveness. A number of RET-targeting Tyrosine Kinase Inhibitors (TKIs) are currently undergoing clinical trials to evaluate their effectiveness in the treatment of thyroid cancer, and it is conceivable that the RET genotype may also influence response to these compounds. The question that now emerges is whether, in the future, the rational for treatment of refractory thyroid cancer will be based on the management of an abnormal RET signal. In this paper we address the RET-targeting TKIs and review studies about the signaling properties of distinct RET mutants as a means to predict response and design combinatorial therapies for the soon to be available TKIs.
Character Sums with Division Polynomials
Authors: Shparlinski Igor E. , Stange Katherine E.
Published: June 2011

We obtain nontrivial estimates of quadratic character sums of division polynomials Ψn(P), n = 1, 2, … , evaluated at a given point P on an elliptic curve over a finite field of q elements. Our bounds are nontrivial if the order of P is at least q1/2+∈ for some fixed ∈ > 0. This work is motivated by an open question about statistical indistinguishability of some cryptographically relevant sequences that was recently brought up by K. Lauter and the second author.
Single Step Synthesis of Amino-Functionalized Magnetic Nanoparticles with Polyol Technique at Low Temperature
Authors: Songvorawit Nut , Tuitemwong Kooranee , Tuitemwong Pravate
Published: June 2011

The synthesis and characterization of amino-functionalized magnetic nanoparticles (amino-MNPs) were carried out. Amino-MNPs were prepared using polyol technique in an autoclave (121°C) without inert gas. The characterization of particles employed conventional SEM-EDS, TEM, XRD, FTIR, and VSM techniques. Results showed that amount of NaOH affected to the speed of MNP formation. The desirable uniform cubic shape of amino-MNPs was obtained from the addition of 2.50% w/v NaOH for 3 reaction cycles (2 hours/cycle). The amino-MNPs obtained from this condition have cubic shapes with the average size of 43 ± 9 nm. Results from elemental and structure analyses confirmed that the product was pure magnetite. The magnetic properties were ferromagnetism and were very close to a complete superparamagnetism. Fourier transform infrared (FT-IR) spectrum showed that the amino group existed on particle surface. The amino-MNPs of cubic shape were synthesized with facile single step at low temperature, and they have potential to be used for rapid microbial detection and many biological applications.
Iterative Smooth Variable Structure Filter for Parameter Estimation
Authors: Al-Shabi Mohammad , Habibi Saeid
Published: June 2011

The smooth variable structure filter (SVSF) is a recently proposed predictor-corrector filter for state and parameter estimation. The SVSF is based on the sliding mode control concept. It defines a hyperplane in terms of the state trajectory and then applies a discontinuous corrective action that forces the estimate to go back and forth across that hyperplane. The SVSF is robust and stable to modeling uncertainties making it suitable for fault detection application.
The discontinuous action of the SVSF results in a chattering effect that can be used to correct modeling errors and uncertainties in conjunction with adaptive strategies. In this paper, the SVSF is complemented with a novel parameter estimation technique referred to as the iterative bi-section/shooting method (IBSS). This combined strategy is used for estimating model parameters and states for systems in which only the model structure is known. This combination improves the performance of the SVSF in terms of rate of convergence, robustness, and stability. The benefits of the proposed estimation method are demonstrated by its application to an electrohydrostatic actuator.
Optimization of Operation Sequencing in CAPP Using Superhybrid Genetic Algorithms-Simulated Annealing Technique
Authors: Nallakumarasamy G. , Srinivasan PSS. , Raja K. Venkatesh , Malayalamurthi R.
Published: June 2011

Computer-aided process planning (CAPP) is an important interface between computer-aided design (CAD) and computer-aided manufacturing (CAM) in computer-integrated manufacturing environment. A problem in traditional CAPP system is that the multiple planning tasks are treated in a linear approach. This leads to an overconstrained overall solution space, and the final solution is normally far from optimal or even nonfeasible. A single sequence of operations may not be the best for all the situations in a changing production environment with multiple objectives such as minimizing number of setups, maximizing machine utilization, and minimizing number of tool changes. In general, the problem has combinatorial characteristics and complex precedence relations, which makes the problem more difficult to solve. The main contribution of this work is to develop an intelligent CAPP system for shop-floor use that can be used by an average operator and to produce globally optimized results. In this paper, the feasible sequences of operations are generated based on the precedence cost matrix (PCM) and reward-penalty matrix (REPMAX) using superhybrid genetic algorithms-simulated annealing technique (S-GENSAT), a hybrid metaheuristic. Also, solution space reduction methodology based on PCM and REPMAX upgrades the procedure to superhybridization. In this work, a number of benchmark case studies are considered to demonstrate the feasibility and robustness of the proposed super-hybrid algorithm. This algorithm performs well on all the test problems, exceeding or matching the solution quality of the results reported in the literature. The main contribution of this work focuses on reducing the optimal cost with a lesser computational time along with generation of more alternate optimal feasible sequences. Also, the proposed S-GENSAT integrates solution space reduction, hybridization, trapping out of local minima, robustness, and convergence; it consistently outperformed both a conventional genetic algorithm and a conventional simulated annealing algorithm.
General Approach to the Synthesis of Prochiral Atropisomeric Biaryls
Authors: Kielar Katarzyna , Demchuk Oleg M. , Pietrusiewicz K. Michał
Published: June 2011

General approach to the synthesis of prochiral precursors of chiral atropisomeric biaryls based on several complementary methods has been developed. Biaryls were obtained in good to excellent yields depending on their structure and selected method of synthesis. Furthermore, we demonstrate a possibility of utilisation of the obtained compounds possessing 2 or 3 ortho substituents around the aryl-aryl bond in direct and directed arylation reaction leading through transition metal-mediated C–H bond activation to atropisomeric compounds.
Drying Models, Myths, and Misconceptions
Authors: Kemp I. C.
Published: June 2011

Several fallacies commonly appear in articles or papers on drying. They fall into two main categories: inadequate or discredited theory which continues to be repeated, and theoretical models which are too complex for practical use, generate results in the wrong form, or do not take account of measurement limitations. Cases are highlighted where published theory is inadequate (e.g., Page's equation) and where simplified models can have better fitness for purpose than complex ones (e.g., in fluidized bed drying). The universal drying curve (UDC) is a useful concept for rapid evaluation of drying in deep well‐mixed beds.
Structural characterization and identification of biflavones in Selaginella tamariscina by liquid chromatography‐diode‐array detection/electrospray ionization tandem mass spectrometry
Authors: Zhang Yi‐Xuan , Li Qiu‐Yue , Yan Li‐Li , Shi Yue
Published: June 2011

Biflavonoids, a special class of flavonoids, are widely distributed in gymnosperm plants and have various biological activities. They are also major bioactive ingredients in Selaginella tamariscina. In this work, we report the use of high‐performance liquid chromatography with a diode‐array detector (HPLC‐DAD) and electrospray ionization multi‐stage tandem mass spectrometry (ESI‐MSn) to study the fragmentation behavior of three main types of biflavonoids using seven biflavonoid reference compounds and analyze the biflavonoids in Selaginella tamariscina. The most useful fragmentations in terms of structural identification are those involving the C‐ring cleavage of biflavonoids. For amentoflavone‐type biflavonoids (containing flavonoid parts I and II), fragmentation on the flavonoid part II at positions 1/3 and 0/4 are the primary pathways, whereas the chances are greater for C‐ring cleavage fragmentation occurring on flavonoid part I at positions 1/3 and 1/4 for robustaflavone‐type biflavonoids. However, the predominant diagnostic ions of the specific C‐O‐C‐connected hinokiflavone‐type biflavonoids are a series of ions resulting from the rupture of the connective C–O bond. Based on the fragmentation patterns of these reference compounds, 17 biflavonoids were identified in an extract of Selaginella tamariscina, three of which have not been previously reported as constituents of this plant. This study provides a powerful approach for the online structural elucidation and identification of different types of biflavonoids and positional isomers from Selaginella tamariscina and other biflavonoids distributed in related plants and prescriptions. Copyright © 2011 John Wiley & Sons, Ltd.
Nonlinear behavior during semi‐quantitative analysis of thin organic layers by laser desorption mass spectrometry
Authors: Mavrinskaya Natalia , Räder Hans Joachim , Müllen Klaus
Published: June 2011

Characterization of the surface coverage and thickness of an organic thin film is particularly important in organic electronics and optoelectronics. For surface coverage down to the submonolayer level there is still a need for characterization methods which are easily applicable. In the present work we report on the evaluation of laser desorption mass spectrometry (LD‐MS) for its use in thickness determination of organic thin films. Whereas LD‐MS is well established as a soft ionization method for small molecules, its capability for use in quantitative analysis is nearly unexplored.

We carried out experiments with two different molecules, 7,7,8,8‐tetracyanoquinodimethane and hexabenzocoronene, in a series of experiments with increasing surface coverage. The obtained data were analyzed by plotting the LD signal intensities versus the relative layer thickness and they reveal a nonlinear behavior, which can be classified into regions of different desorption/ionization efficiencies. Visualization by atomic force microscopy reveals that the first efficiency change corresponds to the transition between incomplete and complete coverage of the metal surface by analyte molecules. A second transition is observed at high layer thickness where the signal intensity stays constant, independent of further thickness increments, and this is attributed to the limited penetration depth of the laser beam. The intermediate region between the two transitions shows a linear behavior and can thus be used for semi‐quantitative thickness measurements. The efficiency change observed at the point of complete surface coverage is particularly useful for thin layer preparation of organic field effect transistors, where complete surface coverage is a minimum requirement. Copyright © 2011 John Wiley & Sons, Ltd.
Columbus—a program system for advanced multireference theory calculations
Authors: Lischka Hans , Müller Thomas , Szalay Péter G. , Shavitt Isaiah , Pitzer Russell M. , Shepard Ron
Published: June 2011

The COLUMBUS Program System allows high‐level quantum chemical calculations based on the multiconfiguration self‐consistent field, multireference configuration interaction with singles and doubles, and the multireference averaged quadratic coupled cluster methods. The latter method includes size‐consistency corrections at the multireference level. Nonrelativistic (NR) and spin–orbit calculations are available within multireference configuration interaction (MRCI). A prominent feature of COLUMBUS is the availability of analytic energy gradients and nonadiabatic coupling vectors for NR MRCI. This feature allows efficient optimization of stationary points and surface crossings (minima on the crossing seam). Typical applications are systematic surveys of energy surfaces in ground and excited states including bond breaking. Wave functions of practically any sophistication can be constructed limited primarily by the size of the CI expansion rather than by its complexity. A massively parallel CI step allows state‐of‐the art calculations with up to several billion configurations. Electrostatic embedding of point charges into the molecular Hamiltonian gives access to quantum mechanical/molecular mechanics calculations for all wave functions available in COLUMBUS. The analytic gradient modules allow on‐the‐fly nonadiabatic photodynamical simulations of interesting chemical and biological problems. Thus, COLUMBUS provides a wide range of highly sophisticated tools with which a large variety of interesting quantum chemical problems can be studied. © 2011 John Wiley & Sons, Ltd. WIREs Comput Mol Sci 2011 1 191‐199 DOI: 10.1002/wcms.25

This article is categorized under:

Software > Quantum Chemistry
Metadynamics
Authors: Barducci Alessandro , Bonomi Massimiliano , Parrinello Michele
Published: June 2011

Metadynamics is a powerful technique for enhancing sampling in molecular dynamics simulations and reconstructing the free‐energy surface as a function of few selected degrees of freedom, often referred to as collective variables (CVs). In metadynamics, sampling is accelerated by a history‐dependent bias potential, which is adaptively constructed in the space of the CVs. Since its first appearance, significant improvements have been made to the original algorithm, leading to an efficient, flexible, and accurate method that has found many successful applications in several domains of science. Here, we discuss first the theory underlying metadynamics and its recent developments. In particular, we focus on the crucial issue of choosing an appropriate set of CVs and on the possible strategies to alleviate this difficulty. Later in the second part, we present a few recent representative applications, which we have classified into three main classes: solid‐state physics, chemical reactions, and biomolecules. © 2011 John Wiley & Sons, Ltd. WIREs Comput Mol Sci 2011 1 826‐843 DOI: 10.1002/wcms.31

This article is categorized under:

Molecular and Statistical Mechanics > Free Energy Methods
Polarization effects in molecular interactions
Authors: Luque F. Javier , Dehez François , Chipot Christophe , Orozco Modesto
Published: June 2011

Standard, additive force fields used in the vast majority of molecular simulations have proven valuable for describing the essential structural and energetic features of complex chemical systems. There is, however, a growing body of evidence that such nonpolarizable force fields cannot provide a fine description in systems where induction effects are significant. Polarizable force fields are designed to account for the variations of the charge distribution in response to the local electric fields created by the environment. Over the past decade, the molecular modeling arena has witnessed the development of new nonadditive force fields at an accelerated pace, which include distinct strategies for the accurate treatment of induction effects. Unavoidably, these developments proved more challenging than anticipated, necessitating various approximations. This contribution aims to provide a concise overview of the recent advances and current status in this field. © 2011 John Wiley & Sons, Ltd.WIREs Comput Mol Sci2011 1 844‐854 DOI: 10.1002/wcms.32

This article is categorized under:

Structure and Mechanism > Molecular Structures

Structure and Mechanism > Computational Biochemistry and Biophysics

Molecular and Statistical Mechanics > Molecular Dynamics and Monte-Carlo Methods
Geometry optimization
Authors: Schlegel H. Bernhard
Published: June 2011

Geometry optimization is an important part of most quantum chemical calculations. This article surveys methods for optimizing equilibrium geometries, locating transition structures, and following reaction paths. The emphasis is on optimizations using quasi‐Newton methods that rely on energy gradients, and the discussion includes Hessian updating, line searches, trust radius, and rational function optimization techniques. Single‐ended and double‐ended methods are discussed for transition state searches. Single‐ended techniques include quasi‐Newton, reduced gradient following and eigenvector following methods. Double‐ended methods include nudged elastic band, string, and growing string methods. The discussions conclude with methods for validating transition states and following steepest descent reaction paths. © 2011 John Wiley & Sons, Ltd. WIREs Comput Mol Sci 2011 1 790–809 DOI: 10.1002/wcms.34

This article is categorized under:

Electronic Structure Theory > Ab Initio Electronic Structure Methods
Representation of chemical structures
Authors: Warr Wendy A.
Published: June 2011

At the root of applications for substructure and similarity searching, reaction retrieval, synthesis planning, drug discovery, and physicochemical property prediction is the need for a machine‐readable representation of a structure. Systematic nomenclature is unsuitable, and notations and fragment codes have been superseded, except in certain specific applications. Connection tables are widely used, but there is no formal standard. Recently the International Union of Pure and Applied Chemistry (IUPAC) International Chemical Identifier (InChI) has started to attract interest. This review also summarizes the representation of chemical reactions and three‐dimensional structures. © 2011 John Wiley & Sons, Ltd. WIREs Comput Mol Sci 2011 1 557–579 DOI: 10.1002/wcms.36

This article is categorized under:

Computer and Information Science > Chemoinformatics
Green's function methods for calculating ionization potentials, electron affinities, and excitation energies
Authors: Danovich David
Published: June 2011

Green's function (GF; electron propagator) methods represent a very useful set of tools for direct calculation of electron detachment (ionization potentials), electron attachment (electron affinities), excitation energies, electron transition probabilities, and other properties. The main idea of GF methods is that for description of various properties of a many‐body system, one does not need to describe all the particles of the system but rather needs information about one or two particles belonging to the system. The corresponding required quantities are the one‐ and two‐particle GFs. Within one‐ or two‐particle GF methods, the energy difference between an initial state and a state with one additional or one less electron is calculated directly, thus eliminating errors due to inconsistent treatment of the initial and final states. © 2011 John Wiley & Sons, Ltd. WIREs Comput Mol Sci 2011 1 377–387 DOI: 10.1002/wcms.38

This article is categorized under:

Electronic Structure Theory > Ab Initio Electronic Structure Methods
Vibrational circular dichroism
Authors: Magyarfalvi Gábor , Tarczay György , Vass Elemér
Published: June 2011

This review focuses on the theoretical background of vibrational circular dichroism (VCD) spectroscopy. Besides discussing the first‐principle approaches of the theoretical evaluation of VCD spectra, practical computational considerations, such as the available electronic structure computational levels and program packages, are summarized. Illustrative examples are shown for the absolute configuration and conformation determination of mid‐sized molecules based on the comparison of calculated end experimental VCD spectra, including the comparison of the performance of different computational levels. The conformational analysis of larger biomolecules, such as carbohydrates, nucleotides, and peptides by VCD spectroscopy, and the theoretical simulation of solvent effects are also discussed. The review is concluded by a short summary of the present stage of the computation of VCD spectra and the expected future direction of theoretical developments. © 2011 John Wiley & Sons, Ltd. WIREs Comput Mol Sci 2011 1 403–425 DOI: 10.1002/wcms.39

This article is categorized under:

Electronic Structure Theory > Ab Initio Electronic Structure Methods
The atomistic simulation of DNA
Authors: Laughton Charles A. , Harris Sarah A.
Published: June 2011

We review the current state of the art relating to the atomistic simulation of the structure and dynamics of DNA. We begin with a brief historical overview to set the scene and introduce some of the key issues that had to be addressed to progress the field and then we divide our discussion of the current situation into two sections. First, we overview the role that simulation has played, closely intertwined with experimental studies, in increasing our understanding of the biomechanical properties of DNA, for example, the way in which its structure responds to perturbations such as stretching and over‐ and under‐twisting. Second, we discuss how atomistic simulations are contributing to our deeper understanding of nucleic acid recognition—both by proteins and by small‐molecule ligands. In both areas, we emphasize not only where simulation has been particularly successful but also where thorny problems remain to tax the ingenuity of computational scientists in close collaboration with their experimental colleagues. © 2011 John Wiley & Sons, Ltd.WIREs Comput Mol Sci2011 1 590–600 DOI: 10.1002/wcms.46

This article is categorized under:

Structure and Mechanism > Computational Biochemistry and Biophysics
NWChem: scalable parallel computational chemistry
Authors: van Dam H.J.J. , de Jong W.A. , Bylaska E. , Govind N. , Kowalski K. , Straatsma T.P. , Valiev M.
Published: June 2011

NWChem is a general‐purpose computational chemistry code specifically designed to run on distributed memory parallel computers. The core functionality of the code focuses on molecular dynamics, Hartree–Fock theory, and density functional theory methods for both plane‐wave basis sets as well as Gaussian basis sets, tensor contraction engine‐based coupled cluster capabilities, and combined quantum mechanics/molecular mechanics descriptions. It was realized from the beginning that scalable implementations of these methods required a programming paradigm inherently different from what message‐passing approaches could offer. In response, a global address space library, the Global Array toolkit, was developed. The programming model it offers is based on using predominantly one‐sided communication. This model underpins most of the functionality in NWChem, and the power of it is exemplified by the fact that the code scales to tens of thousands of processors. In this paper, the core capabilities of NWChem are described as well as their implementation to achieve an efficient computational chemistry code with high parallel scalability. © 2011 John Wiley & Sons, Ltd. WIREs Comput Mol Sci 2011 1 888–894 DOI: 10.1002/wcms.62

This article is categorized under:

Software > Quantum Chemistry
NMR spectroscopy: quantum‐chemical calculations
Authors: Bühl Michael , van Mourik Tanja
Published: June 2011

The first‐principles computation of nuclear magnetic resonance parameters, in particular chemical shift and spin–spin coupling tensors, is reviewed. After a brief nontechnical introduction into the methodology behind such calculations, selected applications from chemistry and biochemistry in solution and the solid state are highlighted. Special attention is called to cases wherein theory can help in structure determination and refinement, as well as in the interpretation of the observables. © 2011 John Wiley & Sons, Ltd. WIREs Comput Mol Sci 2011 1 634–647 DOI: 10.1002/wcms.63

This article is categorized under:

Theoretical and Physical Chemistry > Spectroscopy
Nonadiabatic dynamics with trajectory surface hopping method
Authors: Barbatti Mario
Published: June 2011

The trajectory surface hopping (TSH) method is a general methodology for dynamics propagation of nonadiabatic systems. It is based on the hypothesis that the time evolution of a wave packet through a potential‐energy branching region can be approximated by an ensemble of independent semiclassical trajectories stochastically distributed among the branched surfaces. As it was proposed about 40 years ago, the TSH methodology has become one of the main tools for nonadiabatic dynamics propagation in molecular physics and chemistry. One reason for this success lies on its intuitive conceptual background allied to its high computational efficiency when compared to full quantum mechanical propagation. In this work, the TSH method is reviewed and applications from different fields are surveyed. © 2011 John Wiley & Sons, Ltd. WIREs Comput Mol Sci 2011 1 620–633 DOI: 10.1002/wcms.64

This article is categorized under:

Theoretical and Physical Chemistry > Reaction Dynamics and Kinetics
Mifepristone Treatment Results in Differential Regulation of Glycerolipid Biosynthesis in Baby Hamster Kidney Cells Expressing a Mifepristone‐Inducible ABCA1
Authors: Hauff Kristin D. , Mitchell Ryan W. , Xu Fred Y. , Dembinski Thomas , Mymin David , Zha Xiaohui , Choy Patrick C. , Hatch Grant M.
Published: June 2011

ATP binding cassette A1 (ABCA1) transports cholesterol, phospholipids and lipophilic molecules to and across cellular membranes. We examined if ABCA1 expression altered cellular de novo glycerolipid biosynthesis in growing Baby hamster kidney (BHK) cells. Mock BHK cells or cells expressing a mifepristone‐inducible ABCA1 (ABCA1) were incubated plus or minus mifepristone and then with [3H]serine or [3H]inositol or [3H]ethanolamine or [methyl‐3H]choline or [3H]glycerol or [14C]oleate and radioactivity incorporated into glycerolipids determined. Mifepristone did not affect [1,3‐3H]glycerol or [14C]oleate or [3H]ethanolamine or [methyl‐3H]choline uptake in BHK cells. In contrast, [3H]glycerol and [14C]oleate incorporated into phosphatidylserine (PtdSer) were elevated 2.4‐fold (p < 0.05) and 54% (p < 0.05), respectively, upon ABCA1 induction confirming increased PtdSer biosynthesis from these precursors. However, mifepristone inhibited [3H]serine uptake and incorporation into PtdSer indicating that PtdSer synthesis from serine in BHK cells is dependent on serine uptake. Mifepristone stimulated [3H]inositol uptake in mock and ABCA1 cells but not its incorporation into phosphatidylinositol indicating that its synthesis from inositol is independent of inositol uptake in BHK cells. [3H]glycerol and [14C]oleate incorporated into triacylglycerol were reduced and into diacylglycerol elevated only in mifepristone‐induced ABCA1 expressing cells due to a decrease in diacylglycerol acyltransferase‐1 (DGAT‐1) activity. The presence of trichostatin A, a class I and II histone deacetylase inhibitor, reversed the ABCA1‐mediated reduction in DGAT‐1 activity but did not affect DGAT‐1 mRNA expression. Thus, mifepristone has diverse effects on de novo glycerolipid synthesis. We suggest that caution should be exercised when using mifepristone‐inducible systems for studies of glycerolipid metabolism in cells expressing glucocorticoid responsive receptors.
Can widespread hypersensitivity in carpal tunnel syndrome be substantiated if neck and arm pain are absent?
Authors: Schmid A.B. , Soon B.TC. , Wasner G. , Coppieters M.W.
Published: June 2011

Recent studies demonstrated that patients with carpal tunnel syndrome (CTS) have signs of thermal and mechanical hyperalgesia in extra‐median territories suggesting an involvement of central pain mechanisms. As previous studies included patients with shoulder/arm symptoms or neck pain, a potential influence of these coexisting disorders cannot be excluded. This study therefore evaluated whether widespread sensory changes (hypoesthesia or hyperalgesia) are present in patients with unilateral CTS in the absence of coexisting disorders. Twenty‐six patients with unilateral CTS with symptoms localised to their hand and 26 healthy controls participated in the study. A comprehensive quantitative sensory testing (QST) protocol including thermal and mechanical detection and pain thresholds was performed over the hands (median, ulnar and radial innervation area), lateral elbows, neck and tibialis anterior muscle. Patients with CTS demonstrated thermal and mechanical hypoesthesia in the hand but not at distant sites. Thermal or mechanical hyperalgesia was not identified at any location with traditional QST threshold testing. However, patients with CTS rated the pain during thermal pain testing significantly higher than healthy participants. This was especially apparent for heat pain ratings which were elevated not only in the affected hand but also in the neck and tibialis anterior muscle. In conclusion, CTS alone in the absence of coexisting neck and arm pain does not account for sensory changes outside the affected hand as determined by traditional QST threshold testing. Elevated pain ratings may however be an early indication of central pain mechanisms.
Is adherence to pain self‐management strategies associated with improved pain, depression and disability in those with disabling chronic pain?
Authors: Nicholas M.K. , Asghari A. , Corbett M. , Smeets R.J.E.M. , Wood B.M. , Overton S. , Perry C. , Tonkin L.E. , Beeston L.
Published: June 2011

There is generally good evidence that pain management interventions that include self‐management strategies can substantially reduce disability and improve psychological well‐being in patients with chronic pain. Reductions in unhelpful responses, especially catastrophising and fear‐avoidance beliefs, have been established as key contributors to these gains. In contrast, there is surprisingly little evidence that adherence to self‐management strategies contributes to achieving these outcomes. Difficulties in defining and measuring the use of pain self‐management strategies have been obstacles for this research. Using a pragmatic way of assessing the practice of specific strategies this study investigated their ability to account for changes in pain, disability and depressive symptoms after a 3‐week cognitive‐behavioural pain management program. The post‐treatment outcomes on these dimensions were found to be statistically and, for many, clinically significant. Consistent with previous research, reductions in catastrophising and fear‐avoidance beliefs, and increased pain self‐efficacy beliefs, were also associated with these gains. But the key new finding was that there was a clear gradient between adherence to specific self‐management strategies and reductions in pain, disability and depressive symptoms. Furthermore, adherence to the self‐management strategies was predictive of better outcomes even after controlling for the moderating effects of initial catastrophising, fear‐avoidance and pain self‐efficacy beliefs.
Evidence for direct binding of glycerol to photosystem I
Authors: Hussels Martin , Brecht Marc
Published: June 2011

The interaction between glycerol and photosystem I (PSI) was investigated using low temperature single‐molecule spectroscopy. PSI complexes were dissolved in three different solutions: in buffer solution, in 66% glycerol/buffer solution, and in 66% glycerol/buffer solution that was afterwards diluted by buffer; the final glycerol concentration was <1‰. Mean fluorescence spectra and intercomplex heterogeneity of PSI complexes in 66% glycerol/buffer solution and in the re‐diluted solution show high similarity, but differ from complexes in buffer solution indicating that the glycerol concentration is not the determining factor modifying the spectral properties. However, the exposure of PSI to a high glycerol concentration during sample preparation affects PSI and the effect is maintained if glycerol is removed from the solution.
Impaired hypoxic response in senescent mouse brain
Authors: Rabie Tamer , Kunze Reiner , Marti Hugo H.
Published: June 2011

Tissue hypoxia leads to activation of endogenous adaptive responses that involve a family of prolyl hydroxylase domain proteins (PHD1‐3) with oxygen sensing properties, hypoxia inducible transcription factors (HIFs), and cytoprotective HIF target genes such as erythropoietin (EPO) and vascular endothelial growth factor (VEGF). The hypoxic induction of these genes is regulated by oxygen‐dependent hydroxylation of HIFα subunits by PHDs, which signals their proteasomal degradation. In this study, mice of different age were exposed to hypoxia or subjected to cerebral ischemia after hypoxic pre‐conditioning. We found an impaired hypoxic response in the brain, characterized by elevated levels and impaired downregulation of PHD1. Furthermore, an attenuated hypoxic activation of VEGF and EPO, as well as of other HIF‐target genes such glucose transporter‐1 and carbonic anhydrase 9 was found in senescent brain. Finally, we observed a loss of the protective effect of hypoxic pre‐conditioning on subsequent cerebral ischemia with increasing age. Thus, the impaired hypoxic adaptation, resulting in compromised hypoxic activation of neuroprotective factors, could contribute to neurodegenerative processes with increasing age, and might have implications for treating age‐related disorders.
Development of an animal model for chronic mild hyperhomocysteinemia and its response to oxidative damage
Authors: Scherer Emilene B.S. , da Cunha Aline Andrea , Kolling Janaína , da Cunha Maira J. , Schmitz Felipe , Sitta Angela , Lima Daniela D. , Delwing Débora , Vargas Carmem R. , Wyse Angela T.S.
Published: June 2011

The purpose of this study was to develop a chronic chemically induced model of mild hyperhomocysteinemia in adult rats. We produced levels of Hcy in the blood (30 μM), comparable to those considered a risk factor for the development of neurological and cardiovascular diseases, by injecting homocysteine subcutaneously (0.03 μmol/g of body weight) twice a day, from the 30th to the 60th postpartum day. Controls received saline in the same volumes. Using this model, we evaluated the effect of chronic administration of homocysteine on redox status in the blood and cerebral cortex of adult rats. Reactive oxygen species and thiobarbituric acid reactive substances were significantly increased in the plasma and cerebral cortex, while nitrite levels were reduced in the cerebral cortex, but not in the plasma, of rats subjected to chronic mild hyperhomocysteinemia. Homocysteine was also seen to disrupt enzymatic and non‐enzymatic antioxidant defenses in the blood and cerebral cortex of rats. Since experimental animal models are useful for understanding the pathophysiology of human diseases, the present model of mild hyperhomocysteinemia may be useful for the investigation of additional mechanisms involved in tissue alterations caused by homocysteine.
Umbilical cord blood biomarkers of neurologic injury and the risk of cerebral palsy or infant death
Authors: Costantine Maged M. , Weiner Steven J. , Rouse Dwight J. , Hirtz Deborah G. , Varner Michael W. , Spong Catherine Y. , Mercer Brian M. , Iams Jay D. , Wapner Ronald J. , Sorokin Yoram , Thorp John M. , Ramin Susan M. , O'Sullivan Mary J. , Peaceman Alan M. , Simhan Hyagriv N. ,   For the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal‐Fetal Medicine Units Network
Published: June 2011

To evaluate the association between cerebral palsy (CP) or infant death and putative cord blood biomarkers of neurologic injury, we performed a nested case–control secondary analysis of a multicenter randomized trial of magnesium sulfate (MgSO4) versus placebo to prevent CP or death among offspring of women with anticipated delivery from 24 to 31 weeks’ gestation. Cases were infants who died by 1 year (n = 25) or developed CP (n = 16), and were matched 1:2 to a control group (n = 82) that survived without developing CP. Umbilical cord sera concentrations of S100B, neuron‐specific enolase (NSE) and the total soluble form of the receptor for advanced glycation end‐products (sRAGE) were measured by ELISA in duplicates. Maternal characteristics were similar between the 2 groups. Cases were born at a lower gestational age (GA) and had lower birth weight compared with controls. There were no differences in concentrations of the three biomarkers and the composite outcome of CP or infant death. However, S100B was higher (median 847.3 vs. 495.7 pg/ml; P = 0.03) in infants who had CP and total sRAGE was lower (median 1259.3 vs. 1813.1 pg/ml; P = 0.02) in those who died compared with the control group. When corrected for delivery GA and treatment group, both differences lost statistical significance. In conclusion, cord blood S100B level may be associated with CP, but this association was not significant after controlling for GA and MgSO4 treatment.
Using Uniject to increase the use of prophylactic oxytocin for management of the third stage of labor in Latin America
Authors: Althabe Fernando , Mazzoni Agustina , Cafferata María L. , Gibbons Luz , Karolinski Ariel , Armbruster Deborah , Buekens Pierre , Belizán José M. ,   Oxytocin in Uniject Study Group
Published: June 2011

Objective

To evaluate a multifaceted intervention for effectiveness in increasing the use of prophylactic oxytocin by birth attendants (obstetricians, midwives, and nurses) working in small maternity hospitals in Argentina.

Methods

A before‐and‐after quasi‐experimental study was conducted in 5 small maternity hospitals. The study intervention consisted of training birth attendants in the active management of the third stage of labor, distributing oxytocin in Uniject (Hipofisina BIOL Uniject; Laboratorios BIOL, Buenos Aires, Argentina), and using posters as reminders. The primary outcome was the rate of prophylactic oxytocin use in the 6 months before and the 6 months of the intervention period. Secondary outcomes included use of controlled cord traction and uterine massage, and birth attendants' acceptance of the use of oxytocin in Uniject.

Results

The use of prophylactic oxytocin showed a median rate of 14.6% at baseline and 85.6% during the intervention period. 96% of birth attendants reported that the Uniject device facilitated oxytocin 1administration.

Discussion

Prophylactic oxytocin in the third stage of labor is a beneficial intervention with current low use, particularly in low‐ and middle‐income countries. If the results shown in the present study were further replicated, this strategy could be an effective method for improving prophylactic oxytocin use in other similar Latin American hospitals.
Mango modulates body fat and plasma glucose and lipids in mice fed a high-fat diet
Authors: Lucas Edralin A. , Li Wenjia , Peterson Sandra K. , Brown Angela , Kuvibidila Solo , Perkins-Veazie Penny , Clarke Stephen L. , Smith Brenda J.
Published: June 2011

Consumption of fruits and vegetables has been investigated for their role in the prevention of many chronic conditions. Among the fruits, mango provides numerous bioactive compounds such as carotenoids, vitamin C and phenolic compounds, which have been shown to have antioxidant and anti-inflammatory properties. The present study examined the effects of dietary supplementation of freeze-dried mango pulp, in comparison with the hypolipidaemic drug, fenofibrate, and the hypoglycaemic drug, rosiglitazone, in reducing adiposity and alterations in glucose metabolism and lipid profile in mice fed a high-fat (HF) diet. Male C57BL/6J mice were randomly divided into six treatment groups (eight to nine/group): control (10 % energy from fat); HF (60 % energy from fat); HF+1 or 10 % freeze-dried mango (w/w); HF+fenofibrate (500 mg/kg diet); HF+rosiglitazone (50 mg/kg diet). After 8 weeks of treatment, mice receiving the HF diet had a higher percentage body fat (P = 0·0205) and epididymal fat mass (P = 0·0037) compared with the other treatment groups. Both doses of freeze-dried mango, similar to fenofibrate and rosiglitazone, prevented the increase in epididymal fat mass and the percentage of body fat. Freeze-dried mango supplementation at the 1 % dose improved glucose tolerance as shown by approximately 35 % lower blood glucose area under the curve compared with the HF group. Moreover, freeze-dried mango lowered insulin resistance, as indicated by the homeostasis model assessment of insulin resistance, to a similar extent as rosiglitazone and modulated NEFA. The present findings demonstrate that incorporation of freeze-dried mango in the diet of mice improved glucose tolerance and lipid profile and reduced adiposity associated with a HF diet.