bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gas‐phase basicities of polyfunctional molecules. Part 1: Theory and methods
Authors: Bouchoux Guy 
Published: September 2007

AbstractThe experimental and theoretical methods of determination of gas‐phase basicities, proton affinities and protonation entropies are presented in a tutorial form. Particularities and limitations of these methods when applied to polyfunctional molecules are emphasized. Structural effects during the protonation process in the gas‐phase and their consequences on the corresponding thermochemistry are reviewed and classified. The role of the nature of the basic site (protonation on non‐bonded electron pairs or on π‐electron systems) and of substituent effects (electrostatic and resonance) are first examined. Then, linear correlations observed between gas‐phase basicities and ionization energies or substituent constants are recalled. Hydrogen bonding plays a special part in proton transfer reactions and in the protonation characteristics of polyfunctional molecules. A survey of the main properties of intermolecular and intramolecular hydrogen bonding in both neutral and protonated species is proposed. Consequences on the protonation thermochemistry, particularly of polyfunctional molecules are discussed. Finally, chemical reactions which may potentially occur inside protonated clusters during the measurement of gas‐phase basicities or inside a protonated polyfunctional molecule is examined. Examples of bond dissociations with hydride or alkyl migrations, proton transport catalysis, tautomerization, cyclization, ring opening and nucleophilic substitution are presented to illustrate the potentially complex chemistry that may accompany the protonation of polyfunctional molecules. © 2007 Wiley Periodicals, Inc., Mass Spec Rev 26:775–835, 2007
Impact of psychogenic movement disorders versus Parkinson's on disability, quality of life, and psychopathology
Authors: Anderson Karen E. , Gruber‐Baldini Ann L. , Vaughan Christopher G. , Reich Stephen G. , Fishman Paul S. , Weiner William J. , Shulman Lisa M. 
Published: September 2007

AbstractPatients with psychogenic movement disorders (PMD) often report severe impairment, yet the impact of PMD on disability and quality of life has not been examined. We compared 66 patients with PMD and 704 patients with Parkinson's disease (PD) on measures of disability (Older Americans Resources and Services Scale, OARS); quality of life (QOL; SF‐12v2 Health Survey) and psychiatric symptomatology (Brief Symptom Inventory 18, BSI‐18). On the total OARS, PMD and PD patients reported similar levels of disability (17.6 ± 6.6, 19.8 ± 10.9, P = 0.490 at “best” function and 24.1 ± 11.2, 26.2 ± 14.3, P = 0.497 at their “worst” function). PMD patients reported similar Physical Health QOL to PD patients (38.9 ± 14.5, 39.8 ± 11.6, P = 0.652) but worse mental health QOL (41.6 ± 13.4 vs. 48.9 ± 11.0, P < 0.001). On the BSI‐18, PMD patients reported higher levels of distress on the Global Symptom Index (62.03 ± 9.6 vs. 53.7 ± 9.9, P < 0.001) and on Anxiety, Depression and Somatization subscales (PMD vs. PD scores: Anxiety 58.9 ± 12.0 vs. 52.3 ± 10.1, P < 0.001; Depression 58.8 ± 11.9 vs. 51.3 ± 10.3, P < 0.001; Somatization 60.5 ± 11.0 vs. 54.7 ± 8.7, P < 0.001). Thus, severity of disability reported by the PMD group was equal to that seen in a progressive neurodegenerative condition. Quality of life and mental health implications of PMD were also evident. PMD impacts several aspects of patient function and daily life. © 2007 Movement Disorder Society
Dietary advanced lipid oxidation endproducts are risk factors to human health
Authors: Kanner Joseph 
Published: September 2007

AbstractLipid oxidation in foods is one of the major degradative processes responsible for losses in food quality. The oxidation of unsaturated fatty acids results in significant generation of dietary advanced lipid oxidation endproducts (ALEs) which are in part cytotoxic and genotoxic compounds. The gastrointestinal tract is constantly exposed to dietary oxidized food compounds, after digestion a part of them are absorbed into the lymph or directly into the blood stream. After ingestion of oxidized fats animals and human have been shown to excrete in urine increase amounts of malondialdehyde but also lipophilic carbonyl compounds. Oxidized cholesterol in the diet was found to be a source of oxidized lipoproteins in human serum. Some of the dietary ALEs, which are absorbed from the gut to the circulatory system, seems to act as injurious chemicals that activate an inflammatory response which affects not only circulatory system but also organs such as liver, kidney, lung, and the gut itself. We believe that repeated consumption of oxidized fat in the diet poses a chronic threat to human health. High concentration of dietary antioxidants could prevent lipid oxidation and ALEs generation not only in foods but also in stomach condition and thereby potentially decrease absorption of ALEs from the gut. This could explains the health benefit of diets containing large amounts of dietary antioxidants such those present in fruits and vegetables, or products such as red‐wine or tea consuming during the meal.Introduction: http://dx.doi.org/10.1002/mnfr.200700030Contra arguments: http://dx.doi.org/10.1002/mnfr.200600287
A method for calculating meshless finite difference weights
Authors: Roberts J. L. 
Published: September 2007

AbstractAn exact method for calculating the finite difference weights for arbitrary distributed points in multiple dimensions is presented. The method avoids the numerical ill conditioning associated with a small‐scale factor (ε) by delaying the limiting of ε → 0. The Gaussian Radial Basis function is approximated by a Taylor's series expansion in the variable ε, and the resultant matrix equation is solved using the Fraction Free LU decomposition method. Copyright © 2007 John Wiley & Sons, Ltd.
Down‐regulation of ATM protein in HRS cells of nodular sclerosis Hodgkin's lymphoma in children occurs in the absence of ATM gene inactivation
Authors: Bose S , Starczynski J , Chukwuma M , Baumforth K , Wei W , Morgan S , Byrd P , Ying J , Grundy R , Mann JR , Tao Q , Taylor AMR , Murray PG , Stankovic T 
Published: September 2007

AbstractThe tumour component of classical Hodgkin's lymphoma (cHL), Hodgkin Reed–Sternberg (HRS) cells, are believed to be derived from germinal centre (GC) B cells but intriguingly display a characteristic loss of B cell receptor (BCR) expression. The precise mechanisms by which BCR‐negative HRS cell progenitors survive negative selection during the GC reaction remain obscure. Individuals with ataxia telangiectasia, caused by biallelic inactivation of the DNA damage response gene, ataxia telangiectasia mutated (ATM), have a higher risk of cHL development. Here we show that, in contrast to normal GC B cells that expressed low but detectable ATM protein, ATM protein was not detected in HRS cells of 17/18 cases of paediatric cHL, all but one with nodular sclerosis (NS) subtype. A comprehensive analysis of the ATM gene in microdissected HRS cells of nine representative tumours showed no evidence of either loss of heterozygosity or consistent pathogenic mutations. Furthermore, bisulphite sequencing of the ATM promoter from HRS cells of five tumours also revealed the absence of hypermethylation. Since our microarray data suggested significantly reduced ATM transcription in HRS cells compared to GC B cells, we conclude that loss of ATM expression could be the result of alterations in upstream regulators of ATM transcription. Importantly, ATM loss in paediatric cHLs has clinical implications and could be potentially exploited to guide future, less toxic, tumour‐specific treatments. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Differential protein expression in male and female human lumbar cerebrospinal fluid using iTRAQ reagents after abundant protein depletion
Authors: Ogata Yuko , Charlesworth M. Cristine , Higgins LeeAnn , Keegan B. Mark , Vernino Steven , Muddiman David C. 
Published: September 2007

AbstractCerebrospinal fluid (CSF) has become one of the most frequently used biological medium for physiological studies for neurological disorders due to its proximity to the brain and clinical availability; however, before undertaking a rational approach to biomarker discovery or diagnostics, it is crucial to understand the underlying characteristics of CSF proteome in subpopulations. In this study, we examined the differential expression of proteins in pooled male and female CSF utilizing isobaric tags for relative and absolute quantification (iTRAQ™) reagents after the depletion of six high abundant proteins using a multiple affinity removal system (MARS). A total of 219 proteins were identified (95% confidence level), and 12 proteins showed difference in expression levels. Eleven out of 12 differentially expressed proteins showed ratios of male/female between 1.15 and 1.29 (duplicate average), indicating a remarkable similarity between male and female CSF. One notable exception was the slightly lower expression level of ceruloplasmin (ferroxidase) in male CSF (0.81), a copper containing protein that catalyzes the conversion of ferrous iron to ferric iron with antioxidant properties. We also examined the levels of ceruloplasmin in each individual patient sample which constituted the pooled CSF using Western blot analysis which confirmed the lower expression levels of ceruloplasmin in male CSF.
On‐plate digestion of proteins using novel trypsin‐immobilized magnetic nanospheres for MALDI‐TOF‐MS analysis
Authors: Li Yan , Yan Bo , Deng Chunhui , Tang Jia , Liu Junyan , Zhang Xiangmin 
Published: September 2007

AbstractIn this study, a novel method of on‐plate digestion using trypsin‐immobilized magnetic nanospheres was developed followed by MALDI‐TOF‐MS for rapid and effective analysis and identification of proteins. We utilized a facile one‐pot method for the direct preparation of amine‐functionalized magnetic nanospheres with highly magnetic properties and the amino groups on the outer surface. Through the reaction of the aldehyde groups with amine groups, trypsin was simply and stably immobilized onto the magnetic nanospheres. The obtained trypsin‐linked magnetic nanospheres were then applied for on‐plate digestion of sample proteins (myoglobin and Cytochrome c). Moreover, after digestion, the trypsin‐linked nanospheres could be easily removed from the plate due to their magnetic property, which would avoid causing contamination on the ion source chamber in MS. The effects of the temperature and incubation time on the digestion efficiency were characterized. Within only 5 min, proteins could be efficiently digested with the peptide sequence coverage higher than or equal to that of the traditional in‐solution digestion for 12 h. Furthermore, RPLC fractions of rat liver extract were also successfully processed using this novel method. These results suggested that our improved on‐plate digestion protocol for MALDI‐MS may find further application in automated analysis of large sets of proteins.
Multiphoton‐gated photochromic reaction of diarylethene derivatives in PMMA solid film
Authors: Ryo Senichi , Ishibashi Yukihide , Murakami Masataka , Miyasaka Hiroshi , Kobatake Seiya , Irie Masahiro 
Published: September 2007

AbstractCycloreversion (ring‐opening) process of a photochromic diarylethene derivative in PMMA polymer solid film was investigated by means of picosecond laser photolysis. As was observed in our previous work in solution phase, the drastic enhancement of the cycloreversion reaction yield was observed under picosecond laser exposure. The excitation intensity effect of the reaction profiles revealed that the successive multiphoton absorption process leading to higher excited states opened the efficient cycloreversion process with reaction yield of (50 ± 10)%. These results indicate that the multiphoton‐gated reaction takes place also in the polymer solid and its efficiency was almost comparable with that in solution phase. Copyright © 2007 John Wiley & Sons, Ltd.
A stroma targeted therapy enhances castration effects in a transplantable rat prostate cancer model
Authors: Johansson Anna , Jones Jonathan , Pietras Kristian , Kilter Sigrid , Skytt Åsa , Rudolfsson Stina Häggström , Bergh Anders 
Published: September 2007

AbstractBACKGROUNDCastration results in a major involution of the normal prostate gland. This process is initiated by effects in the prostate stroma and vasculature. Castration‐induced regression of androgen sensitive prostate tumors is however less prominent and hypothetically this could be related to a limited stromal/vascular response. We therefore used animal tumor models to explore the importance of stroma and vascular effects, and if castration effects could be enhanced by a simultaneous therapy targeting the tumor stroma.METHODSUsing rats with Dunning PAP and H tumors, stereological methods, immunohistochemistry, and Western blotting, we studied the tumor response 7 and 28 days after castration and after the addition of stroma targeted therapies.RESULTSIn the normal ventral prostate (VP) nuclear androgen receptors (AR) were rapidly downregulated after castration. In contrast, the Dunning tumors downregulated the AR in the cancerous epithelium, but not in the surrounding stroma. Vascular regulators such as the angiopoietins, tie 2, and PDGF‐Rβ were not decreased in the stroma after castration, as observed in the VP, creating an environment that prevents vascular involution. When a tumor stroma targeted therapy inhibiting the tie 2 receptor and the PDGF‐Rβ simultaneously was added to castration it resulted in a decreased vascular density, increased tumor cell apoptosis and decreased tumor growth compared to castration alone.CONCLUSIONSThe stroma in highly differentiated androgen sensitive Dunning tumors is apparently androgen insensitive. If this unresponsive stroma is targeted the effects of castration can be enhanced. Prostate 67: 1664–1676, 2007. © 2007 Wiley‐Liss, Inc.
Receptor‐specific scoring functions derived from quantum chemical models improve affinity estimates for in‐silico drug discovery
Authors: Fischer Bernhard , Fukuzawa Kaori , Wenzel Wolfgang 
Published: September 2007

AbstractThe adaptation of forcefield‐based scoring function to specific receptors remains an important challenge for in‐silico drug discovery. Here we compare binding energies of forcefield‐based scoring functions with models that are reparameterized on the basis of large‐scale quantum calculations of the receptor. We compute binding energies of eleven ligands to the human estrogen receptor subtype α (ERα) and four ligands to the human retinoic acid receptor of isotype γ (RARγ). Using the FlexScreen all‐atom receptor‐ligand docking approach, we compare docking simulations parameterized by quantum‐mechanical calculation of a large protein fragment with purely forcefield‐based models. The use of receptor flexibility in the FlexScreen permits the treatment of all ligands in the same receptor model. We find a high correlation between the classical binding energy obtained in the docking simulation and quantum mechanical binding energies and a good correlation with experimental affinities R=0.81 for ERα and R=0.95 for RARγ using the quantum derived scoring functions. A significant part of this improvement is retained, when only the receptor is treated with quantum‐based parameters, while the ligands are parameterized with a purely classical model. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Full correlation analysis of conformational protein dynamics
Authors: Lange Oliver F. , Grubmüller Helmut 
Published: September 2007

AbstractCorrelated motions in biomolecules are often essential for their function, for example, allosteric signal transduction or mechanical/thermodynamic energy transport. Principal component analysis (PCA) is a widely used method to extract functionally relevant collective motions from a molecular dynamics (MD) trajectory. Being based on the covariance matrix, however, PCA detects only linear correlations. Here we present a new method, full correlation analysis (FCA), which is based on mutual information and thus quantifies all correlations, including nonlinear and higher order correlations. For comparison, we applied both, PCA and FCA, to ∼100 ns MD trajectories of T4 lysozyme and the hexapeptide neurotensin. For both systems, FCA yielded better resolved conformational substates and aligned its modes more often with actual transition pathways. This improved resolution is shown to be due to a strongly increased anharmonicity of FCA modes as compared to the respective PCA modes. The high anharmonicity further suggests that the motions extracted by FCA are functionally more relevant than those captured by PCA. In summary, FCA should provide improved collective degrees of freedom for dimension‐reduced descriptions of macromolecular dynamics. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Position‐resolved free energy of solvation for amino acids in lipid membranes from molecular dynamics simulations
Authors: Johansson Anna C.V. , Lindahl Erik 
Published: September 2007

AbstractStudies of insertion and interactions of amino acids in lipid membranes are pivotal to our understanding of membrane protein structure and function. Calculating the insertion cost as a function of transmembrane helix sequence is thus an important step towards improved membrane protein prediction and eventually drug design. Here, we present position‐dependent free energies of solvation for all amino acid analogs along the membrane normal. The profiles cover the entire region from bulk water to hydrophobic core, and were produced from all‐atom molecular dynamics simulations. Experimental differences corresponding to mutations and costs for entire segments match experimental data well, and in addition the profiles provide the spatial resolution currently not available from experiments. Polar side‐chains largely maintain their hydration and assume quite ordered conformations, which indicates the solvation cost is mainly entropic. The cost of solvating charged side‐chains is not only significantly lower than for implicit solvation models, but also close to experiments, meaning these could well maintain their protonation states inside the membrane. The single notable exception to the experimental agreement is proline, which is quite expensive to introduce in vivo despite its hydrophobicity—a difference possibly explained by kinks making it harder to insert helices in the translocon. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Exploring the extremes of sequence/structure space with ensemble fold recognition in the program Phyre
Authors: Bennett‐Lovsey Riccardo M. , Herbert Alex D. , Sternberg Michael J. E. , Kelley Lawrence A. 
Published: September 2007

AbstractStructural and functional annotation of the large and growing database of genomic sequences is a major problem in modern biology. Protein structure prediction by detecting remote homology to known structures is a well‐established and successful annotation technique. However, the broad spectrum of evolutionary change that accompanies the divergence of close homologues to become remote homologues cannot easily be captured with a single algorithm. Recent advances to tackle this problem have involved the use of multiple predictive algorithms available on the Internet. Here we demonstrate how such ensembles of predictors can be designed in‐house under controlled conditions and permit significant improvements in recognition by using a concept taken from protein loop energetics and applying it to the general problem of 3D clustering. We have developed a stringent test that simulates the situation where a protein sequence of interest is submitted to multiple different algorithms and not one of these algorithms can make a confident (95%) correct assignment. A method of meta‐server prediction (Phyre) that exploits the benefits of a controlled environment for the component methods was implemented. At 95% precision or higher, Phyre identified 64.0% of all correct homologous query–template relationships, and 84.0% of the individual test query proteins could be accurately annotated. In comparison to the improvement that the single best fold recognition algorithm (according to training) has over PSI‐Blast, this represents a 29.6% increase in the number of correct homologous query–template relationships, and a 46.2% increase in the number of accurately annotated queries. It has been well recognised in fold prediction, other bioinformatics applications, and in many other areas, that ensemble predictions generally are superior in accuracy to any of the component individual methods. However there is a paucity of information as to why the ensemble methods are superior and indeed this has never been systematically addressed in fold recognition. Here we show that the source of ensemble power stems from noise reduction in filtering out false positive matches. The results indicate greater coverage of sequence space and improved model quality, which can consequently lead to a reduction in the experimental workload of structural genomics initiatives. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Electronic structure of the Co4Sn6Te6ternary skutterudite phase
Authors: Bertini Luca , Cenedese Simone 
Published: September 2007

AbstractThe electronic structure of Co4Sn6–xTe6+x(x= 0, 1) ternary skutterudite systems has been investigated usingab‐initioband structure computation. Thex= 0 system is a semiconductor like the binary Co4Sb12, but with a lower band gap. The best dopant concentration for Co4Sn6Te6is estimated to be lower than that of Co4Sb12, with the highest electronic fig‐ ure‐of‐meritZeTfor the n‐doped system. Finally, the increased charge transfer between the 8cCo and 24gSn and Te atoms in Co4Sn6Te6compared to that of Co4Sb12could be one reason for the observed decrease of thermal conductivity in ternary skutterudite systems. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Unified Physicochemical QSPR Model of the Partitioning and Solubility of Chemicals in the Triple System “Water–Octanol–Air”
Authors: Raevsky Oleg A. , Schaper Klaus‐J. 
Published: September 2007

AbstractFor the three‐phase system “water–octanol–air” a unified physicochemical Quantitative Structure–Property Relationship (QSPR) model of the pertinent three partition coefficients [log P(octanol–water), log P(air–octanol), and log P(air–water)] of monofunctional chemicals and of their solubilities in the three phases was generated on the basis of three Hydrogen Bond Thermodynamics (HYBOT) descriptors: molecular polarizability, H‐bond acceptor, and H‐bond donor factors. Within the framework of the water–octanol–air system, it is possible to construct separate QSPR models for any single property on the basis of different combinations of QSPR models for other properties. This mutual derivation of relationships provides a better recognition of their physical meaning and also enables a test of their stability.