bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dopamine transporter comparative molecular modeling and binding site prediction using the LeuTAaleucine transporter as a template
Authors: Indarte Martín , Madura Jeffry D. , Surratt Christopher K. 
Published: September 2007

AbstractPharmacological and behavioral studies indicate that binding of cocaine and the amphetamines by the dopamine transporter (DAT) protein is principally responsible for initiating the euphoria and addiction associated with these drugs. The lack of an X‐ray crystal structure for the DAT or any other member of the neurotransmitter:sodium symporter (NSS) family has hindered understanding of psychostimulant recognition at the atomic level; structural information has been obtained largely from mutagenesis and biophysical studies. The recent publication of a crystal structure for the bacterial leucine transporter LeuTAa, a distantly related NSS family homolog, provides for the first time a template for three‐dimensional comparative modeling of NSS proteins. A novel computational modeling approach using the capabilities of the Molecular Operating Environment program MOE 2005.06 in conjunction with other comparative modeling servers generated the LeuTAa‐directed DAT model. Probable dopamine and amphetamine binding sites were identified within the DAT model using multiple docking approaches. Binding sites for the substrate ligands (dopamine and amphetamine) overlapped substantially with the analogous region of the LeuTAacrystal structure for the substrate leucine. The docking predictions implicated DAT side chains known to be critical for high affinity ligand binding and suggest novel mutagenesis targets in elucidating discrete substrate and inhibitor binding sites. The DAT model may guide DAT ligand QSAR studies, and rational design of novel DAT‐binding therapeutics. Proteins 2008. © 2007 Wiley‐Liss, Inc.
HingeProt: Automated prediction of hinges in protein structures
Authors: Emekli Ugur , Schneidman‐Duhovny Dina , Wolfson Haim J. , Nussinov Ruth , Haliloglu Turkan 
Published: September 2007

AbstractProteins are highly flexible molecules. Prediction of molecular flexibility aids in the comprehension and prediction of protein function and in providing details of functional mechanisms. The ability to predict the locations, directions, and extent of molecular movements can assist in fitting atomic resolution structures to low‐resolution EM density maps and in predicting the complex structures of interacting molecules (docking). There are several types of molecular movements. In this work, we focus on the prediction of hinge movements. Given a single protein structure, the method automatically divides it into the rigid parts and the hinge regions connecting them. The method employs the Elastic Network Model, which is very efficient and was validated against a large data set of proteins. The output can be used in applications such as flexible protein–protein and protein–ligand docking, flexible docking of protein structures into cryo‐EM maps, and refinement of low‐resolution EM structures. The web server of HingeProt provides convenient visualization of the results and is available with two mirror sites at http://www.prc.boun.edu.tr/appserv/prc/HingeProt3 and http://bioinfo3d.cs.tau.ac.il/HingeProt/. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Structural analysis of substance P using molecular dynamics and NMR spectroscopy
Authors: Corcho Francesc J. , Salvatella Xavier , Canto Josep , Giralt Ernest , Perez Juan J. 
Published: September 2007

AbstractThe present work is a combined structural study, using Nuclear Magnetic Resonance (NMR) and Molecular Dynamics(MD), of the amidated and the free acid forms of substance P in water and methanol. The results obtained using both approaches were compared in order to characterize the structural features of both peptides in solution. From the NMR experiments it was derived that the free acid form adopts an extended conformation at the N‐terminus and a helical conformation at the C‐terminal segment of the peptide in both water and methanol; these structural features are in qualitative agreement with the results of the MD simulations. No significant differences in behavior were observed between the amidated and the free acid forms of the peptide in the simulations and in the experiments carried out in water, suggesting that the different activities of these analogs are due to their different mode of interaction with the receptor rather than to their structural preferences. Finally, we propose that the structure of substance P can be partially inferred from its sequence due to the presence of a Pro‐X‐Pro motif on the N‐terminus and a Gly–Leu sequence on the C‐terminus. Copyright © 2007 European Peptide Society and John Wiley & Sons, Ltd.
A relatively stable antifungal peptide from buckwheat seeds with antiproliferative activity toward cancer cells
Authors: Leung Edwin H. W. , Ng T. B. 
Published: September 2007

AbstractAn antifungal peptide with a molecular mass of approximately 4 kDa was isolated from buckwheat seeds by using ion‐exchange chromatography on SP‐Sepharose and Q‐Sepharose, and gel filtration on Superdex peptide. The peptide was adsorbed on SP‐Sepharose in 10 mM NH4OAc buffer (pH 4.5) and on Q‐Sepharose in 10 mM NH4HCO3 buffer (pH 9.4), and appeared to be highly purified after these two steps. It inhibited mycelial growth in Fusarium oxysporum and Mycosphaerella arachidicola with an IC50 of 35 and 40 µM, respectively. Its antifungal activity was stable between 0 and 70 °C, and between pH 1.0/2.0 and 13. It inhibited proliferation of Hep G2 (hepatoma) cells, L1210 (leukemia) cells, breast cancer (MCF‐7) cells, and liver embryonic WRL 68 cells with an IC50 of 33, 4, 25, and 37 µM, respectively. On the other hand, the peptide was unable to evoke a mitogenic response from splenocytes or induce nitric oxide production by macrophages. It inhibited HIV‐1 reverse transcriptase with an IC50 of 5.5 µM. Copyright © 2007 European Peptide Society and John Wiley & Sons, Ltd.
QSAR modeling and computer‐aided design of antimicrobial peptides
Authors: Jenssen HÅvard , Fjell Christopher D. , Cherkasov Artem , Hancock Robert E. W. 
Published: September 2007

AbstractThe drastic increase in multi‐drug‐resistant bacteria has created an urgent need for new therapeutic interventions, including antimicrobial peptides, an interesting template for novel drug development. However, the process of optimizing peptide antimicrobial activity and specificity using large peptide libraries is both tedious and expensive. Here we confirm the use of a mathematical model for prediction, prior to synthesis, of peptide antibacterial activity toward the antibiotic resistant pathogen Pseudomonas aeruginosa. By the use of novel descriptors quantifying the contact energy between neighboring amino acids, as well as a set of inductive and conventional QSAR descriptors, we were able to model the antibacterial activity of peptides. Cross‐correlation and optimization of the implemented descriptor values enabled us to build two models, using very limited sets of peptides, which were able to correctly predict the activity of 85 or 71% of the tested peptides, within a twofold deviation window of the corresponding previously assessed IC50 values, measured earlier. Though these two models were significantly different in size, they demonstrated no significant difference in their predictive power, implying that it is possible to build powerful predictive models using even small sets of structurally different peptides, when using contact‐energy descriptors and inductive and conventional QSAR descriptors in the model design. Copyright © 2007 European Peptide Society and John Wiley & Sons, Ltd.
Thermoelectric properties of p‐type Mg2Si0.6Ge0.4 fabricated by bulk mechanical alloying and hot pressing
Authors: Song R. B. , Liu Y. Z. , Aizawa T. 
Published: September 2007

AbstractBulk mechanical alloying (BMA) followed by hot pressing (HP) was used to prepare Mg2Si0.6Ge0.4 thermoelectric material with high densification. Starting from the elemental power mixture, the Mg2Si0.6Ge0.4 solid solution was solid‐state synthesized via BMA. In fact, the peaks for the cubic‐structured Mg2Si0.6Ge0.4 solid solution phase were detected after 300 cycles in BMA. The single phase of Mg2Si0.6Ge0.4 was synthesized at 600 cycles in BMA. Mg2Si0.6Ge0.4 showed p‐type semiconduction without doping. Effects of hot pressing conditions on thermoelectric properties were investigated. With increasing hot pressing temperature from 673 to 773 K and pressure from 500 MPa to 1 GPa, the electrical conductivity increased and the Seebeck coefficient decreased. The maximum figure of merit was obtained with the processing parameter of 600 cycles BMA and hot pressing at 773 K, 1 GPa for 1 h. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Conditional approval: discussion points from the PSI conditional approval expert group
Authors: Carroll Kevin , Ross Hilary Chaudri , Evans Dan , France Lesley , Hemmings Rob , Hughes Sara , Lynn Frances , Mahoney Paul , Phillips Alan 
Published: September 2007

AbstractThe European Agency for the Evaluation of Medicinal Products has recently completed the consultation of a draft guidance on how to implement conditional approval. This route of application is available for orphan drugs, emergency situations and serious debilitating or life‐threatening diseases. Although there has been limited experience in implementing conditional approval to date, PSI (Statisticians in the Pharmaceutical Industry) sponsored a meeting of pharmaceutical statisticians with an interest in the area to discuss potential issues. This article outlines the issues raised and resulting discussions, based on the group's interpretation of the legislation. Conditional approval seems to fit well with the accepted regulatory strategy in HIV. In oncology, conditional approval may be most likely when (a) compelling phase II data are available using accepted clinical outcomes (e.g. progression/recurrence‐free survival or overall survival) and Phase III has been planned or started, or (b) when data are available using a surrogate endpoint for clinical outcome (e.g. response rate or biochemical measures) from a single‐arm study in rare tumours with high response, compared with historical data. The use of interim analyses in Phase III for supporting conditional approval raises some challenging issues regarding dissemination of information, maintenance of blinding, potential introduction of bias, ethics, switching, etc. Copyright © 2007 John Wiley & Sons, Ltd.
Precolumn derivatization of cysteine residues for quantitative analysis of five major cytochrome P450 isoenzymes by liquid chromatography/tandem mass spectrometry
Authors: Duan Xiaotao , Chen Xiaoyan , Yang Yiming , Zhong Dafang 
Published: September 2007

AbstractThe development of a novel method for absolute quantification of the five most clinically relevant CYP450 isoenzymes is described based on chemical derivatization of cysteine residues. The sulfhydryl‐reactive reagents, 2‐bromo‐4′‐chloroacetophenone (p‐CPB) and 2‐bromo‐4′‐bromoacetophenone (p‐BPB), are proposed for use in quantitative proteomics. After reducing and denaturing, the P450s are derivatized with p‐CPB for sulfhydryl alkylation then subjected to trypsin digestion. The resulting p‐CPB‐attached peptides are enriched using a phenyl resin solid‐phase cartridge, then separated on a Zorbax 300SB reversed‐phase column, and detected under positive electrospray ionization in the multiple reaction monitoring mode. Quantification is achieved using p‐BPB‐modified peptides as internal standards. Validation results demonstrated that this method showed good linearity between the concentration range of 10 fmol/µg to 5 pmol/µg for the six selected peptides in a complex matrix (rat liver microsomal protein). Intra‐day and inter‐day precision, expressed by relative standard deviation, were all less than 18%. Assay accuracy was within ± 20% in terms of relative error. The quantitative derivatization approach proved to be reproducible, cost‐effective and readily suitable for high‐throughput assays. The reliability of this method for quantification of intact P450s was demonstrated through comparing with the well‐applied isotope‐coded affinity tag (ICAT) method. Copyright © 2007 John Wiley & Sons, Ltd.
Simultaneous determination of aflatoxins, ochratoxin A andFusariumtoxins in maize by liquid chromatography/tandem mass spectrometry after multitoxin immunoaffinity cleanup
Authors: Lattanzio Veronica Maria Teresa , Solfrizzo Michele , Powers Steve , Visconti Angelo 
Published: September 2007

AbstractA liquid chromatography/tandem mass spectrometry method was developed for the simultaneous determination of aflatoxins (B1, B2, G1, G2), ochratoxin A, fumonisins (B1, B2), deoxynivalenol, zearalenone, T‐2 and HT‐2 toxins in maize. A double extraction approach, using a phosphate‐buffered solution followed by methanol, was applied to achieve effective co‐extraction of the 11 mycotoxins under investigation having quite different polarities and chemical structures. A new multitoxin immunoaffinity column containing antibodies for all these mycotoxins was used to clean up the extract. Detection and quantification of the 11 mycotoxins were performed by reversed‐phase liquid chromatography coupled with electrospray ionization triple quadrupole mass spectrometry (LC/ESI‐MS/MS) using, as chromatographic mobile phase, a linear gradient of methanol/water containing 0.5% acetic acid and 1 mM ammonium acetate. Method performances were quite satisfactory for all tested mycotoxins at contamination levels close to or below the relevant EU maximum permitted or recommended levels. Limits of detection in maize ranged from 0.3 to 4.2 µg/kg. Recoveries higher than 79% were obtained for all tested mycotoxins with relative standard deviations less than 13%. Copyright © 2007 John Wiley & Sons, Ltd.
Tests for the homogeneity of two binomial proportions in extremely unbalanced 2 × 2 contingency tables
Authors: Kang Seung‐Ho , Ahn Chul W. 
Published: September 2007

AbstractAsymptotic tests such as the Pearson chi‐square test are unreliable for testing the homogeneity of two binomial probabilities in extremely unbalanced cases. Two exact tests (conditional and unconditional) are available as alternatives and can be implemented easily in StatXact 6.0. In equal sample cases it is well known that the unconditional exact test is more powerful than the conditional exact test. However, in this paper, we show that the opposite result holds in extremely unbalanced cases. The reason is that the peaks of the type I error occur at the extremes of the nuisance parameter when the imbalance among the sample sizes becomes severe. After we show that the conditional exact test is more powerful than the unconditional exact test in extremely unbalanced cases whose sample ratio is greater than 20, we compare the conditional exact test with the Berger and Boos approach (J. Amer. Stat. Assoc. 1994; 89:1012–1016) in which the supremum is taken over a confidence interval for the nuisance parameter. The Berger and Boos approach turns out to be slightly more powerful than the conditional exact test in extremely unbalanced data. A real example is provided. Copyright © 2007 John Wiley & Sons, Ltd.
Influence of Soluble Polymer Residues in Crosslinked Carboxymethyl Starch on some Physical Properties of its Hydrogels
Authors: Heß Christoph , Hartmann Brigitte , Lechner M. Dieter , Nierling Wolfgang , Seidel Christian , Kulicke Werner‐Michael 
Published: September 2007

AbstractCrosslinked carboxymethyl starch (CMS) was synthesized from potato starch in a single‐step procedure with mono‐ (MCA) and dichloroacetic acid (DCA), using the well‐known Williamson reaction. The products varied in their degree of substitution DS (average number of carboxymethyl groups per monomer unit) and crosslinker ratio Fz (number of crosslinker molecules offered per monomer unit). After neutralizing and removal of the formed salt, one part of the synthesized CMS networks was pre‐swollen in water in an additional purification step in order to wash out unlinked, soluble polymer chains. The rest of the product remained unwashed. Different swelling experiments were performed with the two samples, before being dried and ground. Both, the Free Swelling Capacity (FSC) and the Absorption Capacity Under Mechanical Load (AUL) of the hydrogels were strongly influenced by chemically unlinked CMS chains that were only physically entangled in the network structure. These mobile polymer segments were responsible for a significant weight loss of the swollen, unwashed hydrogels over the course of time. Rheological oscillatory experiments showed that, in order to achieve comparable values for the storage and loss moduli (G′ and G′′), the polymer content of an unwashed hydrogel had to be more than twice as high as that of the corresponding purified product. By using a special rheological test procedure with a cyclic temperature program, the long‐term stability of CMS gels could be measured and verified.
Analysis of the Material and Tablet Formation Properties of four Dioscorea Starches
Authors: Odeku Oluwatoyin A. , Picker‐Freyer Katharina M. 
Published: September 2007

AbstractThe material and tablet formation properties of starches from four different Dioscorea species, namely White (D. rotundata), Bitter (D. dumetorum), Chinese (D. oppositifolia) and Water yam (D. alata), was characterized to determine their applicability as direct compression excipient. The physicochemical, thermal, morphological and material properties of the starches were investigated. The tablet formation properties were assessed using the 3‐D modeling parameters, the Heckel equation and the force‐displacement profiles. The tablet properties were evaluated using the elastic recovery and compactibility plots. The results indicate that the chemical composition, thermal and material properties of the starches varied considerably among the four species. The sorption isotherms show that the relative humidity (RH) during tablet production and storage should be carefully controlled. The tableting results show that all four starches exhibit similar time dependent deformation (d). The ranking for pressure plasticity (e) was Water > Chinese > White > Bitter, which indicates that Water deforms more easily and Bitter less easily. The ranking for fast elastic decompression was White > Water ≥ Chinese > Bitter. The amylose content, size and shape of the starch granules and specific surface area appears to play a significant role in the compressibility. Thus, White and Water with larger granules and high amylose content exhibited poor compressibility and did not form compacts except at high ρrel,max, while Bitter and Chinese with polygonal shape, small particle size and high specific surface area were more compressible and formed tablets of acceptable crushing force. Thus, Chinese and Bitter could be useful as excipient in direct compression.
Characteristics of Novel Starch‐based Hydrogels Prepared by UV Photopolymerization of Acryloylated Starch and A Zwitterionic Monomer
Authors: Li Jie‐Mei , Zhang Li‐Ming 
Published: September 2007

AbstractNew starch‐based hydrogels were prepared by the UV‐induced polymerization of acryloylated starch with the zwitterionic monomer 3‐dimethyl(methacryloyloxyethyl) ammonium propane sulfonate (DMAPS). The swelling kinetics of the resultant hydrogels in distilled water and their equilibrium swelling ratios in aqueous NaCl and CaCl2 solutions were investigated. With increasing amount of incorporated DMAPS, the formed hydrogel had an enhanced swelling ability in distilled water and in aqueous salt solutions. In particular, antipolyelectrolyte swelling behavior of the hydrogel was observed in aqueous salt solutions.
Combined heat and mass transfer in magneto‐micropolar fluid flow from radiate surface with variable permeability in slip‐flow regime
Authors: Chaudhary R.C. , Jain P. 
Published: September 2007

AbstractAn analysis is presented to study the effects of radiation on the hydromagnetic free convection flow (set up due to temperature as well as species concentration) of an electrically conducting micropolar fluid past a vertical porous plate through porous medium in slip‐flow regime. A uniform magnetic field acts perpendiculary to the porous surface which absorbs the micropolar fluid with variable suction velocity. The Rosseland approximation is used to describe the radiative heat flux in energy equation. The numerical results of velocity distribution of micropolar fluids are compared with the corresponding flow problems for a Newtonian fluid. Assuming variable permeability of the medium, numerical results are presented graphically in the form of velocity, micro rotation, and temperature profiles for different material parameters entering into the analysis. Also, the results of the skin‐friction coefficient, the couple stress coefficient, the rate of heat and mass transfers at the wall are discussed with the help of figures.
An interior point method for a parabolic optimal control problem with regularized pointwise state constraints
Authors: Prüfert U. , Tröltzsch F. 
Published: September 2007

AbstractA primal‐dual interior point method for state‐constrained parabolic optimal control problems is considered. By a Lavrentiev type regularization, the state constraints are transformed to mixed control‐state constraints which, after a simple transformation, can be handled as control constraints. Existence and convergence of the central path are shown. Moreover, the convergence of a short step interior point algorithm is proven in a function space setting. The theoretical properties of the algorithm are confirmed by numerical examples.
Existence results for a contact problem with varying friction coefficient and nonlinear forces
Authors: Schmid F. , Mielke A. 
Published: September 2007

AbstractWe consider the rate‐independent problem of a particle moving in a three‐dimensional half space subject to a time‐dependent nonlinear restoring force having a convex potential and to Coulomb friction along the flat boundary of the half space, where the friction coefficient may vary along the boundary. Our existence result allows for solutions that may switch arbitrarily often between unconstrained motion in the interior and contact where the solutions may switch between sticking and frictional sliding. However, our existence result is local and guarantees continuous solutions only as long as the convexity of the potential is strong enough to compensate the variation of the friction coefficient times the contact force. By simple examples we show that our sufficient conditions are also necessary.Our method is based on the energetic formulation of rate‐independent systems as developed in [MTL02, MiT04]. We generalize the time‐incremental minimization procedure of [MiR06] for the present situation of a non‐associative flow rule.
A method of shell theory in determination of the surface from components of its two fundamental forms
Authors: Pietraszkiewicz W. , Vallée C. 
Published: September 2007

AbstractWe introduce the tensor which maps the Cartesian plane into the tangent plane of the surface. Then by analogy to the polar decomposition theorem widely used in the non‐linear theory of thin shells the tensor is represented as composition of the surface stretch and 3D rotation fields. Left and right polar decompositions are analysed. For each of them the position vector of the surface in space is established uniquely from the surface metric and curvature components in three subsequent steps: 1) the stretch field is found by pure algebra, 2) the rotation field is obtained by solving the system of linear first‐order PDEs, and 3) the position vector of the surface follows by quadrature. Integrability conditions for the rotation field are shown to be alternative forms of the Gauss‐Mainardi‐Codazzi equations. The results are illustrated by a simple analytically solved example. The proposed method is expected to be more appealing and in some cases also more efficient than those used in classical differential geometry. We also briefly discuss the relation of our method to the one associated with integrable surfaces and soliton equations.