bluuebunny/crossref_metadata_2025_split huggingface dataset:
Challenges in drug development for muscle disease: A stakeholders' meeting
Authors: Mendell Jerry R. , Csimma Cristina , McDonald Craig M. , Escolar Diana M. , Janis Scott , Porter John D. , Hesterlee Sharon E. , Howell R. Rodney 
Published: October 2006

AbstractCurrent treatment benefits for patients with muscle disease are limited, but progress in legislative and scientific initiatives have set the stage for the development of new therapies. The MD‐CARE Act (Public Law 107‐84), which allocates federal resources to muscular dystrophy, was approved by Congress and signed into law by the President of the United States in 2001. This has shifted the emphasis toward translational research. To facilitate a push toward therapy for muscle disorders, the Muscular Dystrophy Association (MDA) sponsored a meeting with representatives from industry, the Food and Drug Administration (FDA), the National Institutes of Health (NIH), and other government agencies and academia. Each contributed in different ways. The FDA helped define the necessary data to support investigational new drug (IND) applications including the design of proof‐of‐principle studies, outcome measures for clinical trials, and the pathway for developing surrogate measures for fast‐tracking promising new drugs. The NIH, other government agencies, and the MDA described potential funding sources for translational research. Industry delineated a complementary role with academia, and academic investigators elucidated the current strengths and weaknesses of available clinical endpoints. The meeting provided a format for communication for diverse disciplines that usually have no common meeting ground, helping to lay the foundation for bringing products to market in a timely fashion. Muscle Nerve, 2006
On the mechanics of contact between a flexible transducer diaphragm located at a rigid boundary and an elastic material
Authors: Selvadurai A. P. S. , Labanieh S. , Boulon M. J. 
Published: October 2006

AbstractIn this paper we examine the mechanics of contact between a flexible elastic diaphragm and an isotropic elastic halfspace region where contact is established through the application of a normal stress. It is shown that a convenient solution for the maximum displacement and maximum flexural moment in the flexible diaphragm can be obtained by employing a variational technique. Copyright © 2006 John Wiley & Sons, Ltd.
A second‐order immersed interface technique for an elliptic Neumann problem
Authors: Bouchon François , Peichl Gunther H. 
Published: October 2006

AbstractA second‐order finite difference scheme for mixed boundary value problems is presented. This scheme does not require the tangential derivative of the Neumann datum. It is designed for applications in which the Neumann condition is available only in discretized form. The second‐order convergence of the scheme is proven and the theory is validated by numerical examples. © 2006 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq 23: 400–420, 2007
Superconvergence of discontinuous Galerkin finite element method for the stationary Navier‐Stokes equations
Authors: Li Jian , He Yinnian 
Published: October 2006

AbstractThis article focuses on discontinuous Galerkin method for the two‐ or three‐dimensional stationary incompressible Navier‐Stokes equations. The velocity field is approximated by discontinuous locally solenoidal finite element, and the pressure is approximated by the standard conforming finite element. Then, superconvergence of nonconforming finite element approximations is applied by using least‐squares surface fitting for the stationary Navier‐Stokes equations. The method ameliorates the two noticeable disadvantages about the given finite element pair. Finally, the superconvergence result is provided under some regular assumptions. © 2006 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq 23: 421–436, 2007
An analysis for a high‐order difference scheme for numerical solution to utt = A(x, t)uxx + F(x, t, u, ut, ux)
Authors: Li Wei‐Dong , Sun Zhi‐Zhong , Zhao Lei 
Published: October 2006

AbstractThis article is concerned with a high‐order implicit difference scheme presented by Mohanty, Jain, and George for the nonlinear hyperbolic equation utt = A(x, t)uxx + F(x, t, u, ut, ux) with Dirichlet boundary conditions. Some prior estimates of the difference solution are obtained by the energy methods. The solvability of the difference scheme is proved by the energy method and Brower's fixed point theorem. Similarly, the uniqueness, the convergence in L∞‐norm and the stability of the difference solution are obtained. A numerical example is provided to demonstrate the validity of the theoretical results. © 2006 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq 23: 484–498, 2007
Photolabile and thermally labile polymers as templates and for surface patterning
Authors: Voit B. , Braun F. , Gernert M. , Sieczkowska B. , Millaruelo M. , Messerschmidt M. , Mertig M. , Opitz J. 
Published: October 2006

AbstractThe successful selective metal deposition using a photolabile polymer consisting of a diazosulfonate side chain group has been reported. In addition to 20 mol% diazosulfonate monomer the terpolymer contains 5 mol% of a silane compound, which is necessary for the covalent anchoring of the film onto the substrate. Furthermore, films were prepared using photolabile polymers containing protected amines onto glass and silicon substrates. These films are suitable for imagewise structuring by UV‐light and laser irradiation, and nanoelements like DNA strands could be attached individually in further steps. These polymeric amines with similar structure like the diazosulfonate terpolymers were synthesized by free radical polymerization of three monomer units which are methyl methacrylate (MMA) (spacer), 3‐(trimethoxysilyl)propylmethacrylate (anchoring group) and N‐(N‐nitroveratryloxycarbonyl‐aminopropyl)‐methacrylamide (photolabile compound). The anchoring groups were varied to enable covalent attachment of the polymers, for example, onto gold substrates. Azosulfonates, sulfonate esters, and both protected amines and carboxylic acid groups were used as thermally labile or photolabile functionalities. Selective deprotection using heat or light could be varied. Finally block copolymers based on orthogonally protected hydroxystyrenes could be prepared by controlled radical polymerization. A highly ordered nanostructure could be realized in thin films of these polymers exhibiting strong changes using heat or light treatment. Copyright © 2006 John Wiley & Sons, Ltd.
Cathepsin protease activity modulates amyloid load in extracerebral amyloidosis
Authors: Röcken C , Fändrich M , Stix B , Tannert A , Hortschansky P , Reinheckel T , Saftig P , Kähne T , Menard R , Ancsin JB , Bühling F 
Published: October 2006

AbstractIn cerebral amyloidoses, such as Alzheimer's disease, proteolytic processing of the precursor protein is a fundamental mechanism of the disease, since it generates the amyloid protein. However, the putative significance of proteases in extracerebral amyloidoses is less well defined. In this study, we investigated the biological significance of cathepsin (Cath) B, CathK, and CathL in the pathology and pathogenesis of extracerebral amyloidoses by using the murine model of reactive or secondary AA amyloidosis with three different cathepsin‐deficient mouse strains. Extracerebral AA amyloid was induced by injecting amyloid‐enhancing factor and silver nitrate into CathB−/−, CathK−/−, and CathL−/− mice. Wild‐type mice served as a control. CathK−/− mice deposited over 90% more amyloid and CathL−/− mice 60% less amyloid than the control (p < 0.0001). The amyloid load in CathB−/− mice did not differ from that in wild‐type mice. In vitro degradation experiments with recombinant human and murine serum amyloid A (SAA) 1.1 and CathK and CathL showed that CathL generates a large number of differently sized SAA cleavage products. One of these fragments spans the heparin/heparan sulphate binding site and the neutral cholesterol ester hydrolase activating region of SAA. CathK showed only endoproteolytic activity and did not generate any AA amyloid‐like peptides. This study provides unequivocal evidence that proteases modulate amyloid load in extracerebral amyloidosis. CathL was identified as an amyloid‐promoting and CathK as an amyloid‐retarding cysteine protease. CathB may only modulate the primary structure of the amyloid peptide without affecting amyloid load. Copyright © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Isolation and antimicrobial evaluation of isomeric hydroxy ketones in leaf cuticular waxes of Annona squamosa
Authors: Shanker K. Shiva , Kanjilal S. , Rao B. V. S. K. , Kishore K. Hara , Misra S. , Prasad R. B. N. 
Published: October 2006

AbstractA novel natural compound, 11‐hydroxy‐16‐hentriacontanone, has been isolated from the leaf cuticular wax of Annona squamosa along with its known isomer 10‐hydroxy‐16‐hentriacontanone in a ratio of 67:33. This isomeric mixture of hydroxy ketones constituted together 16.5% of the total cuticular waxes. The new compound was characterised using spectral and chromatographic techniques. The major component was found to be 16‐hentriacontanone (palmitone), which constituted up to 48% of the total cuticular wax, together with a homologous series of hydrocarbons, fatty aldehydes, fatty alcohols, fatty acids and sterols as minor components. The antimicrobial activity of the isomeric hydroxy ketones was tested against selected Gram‐positive and Gram‐negative bacterial strains, and also some selected fungal strains, and compared with palmitone. The antibacterial activity of palmitone was significantly higher than that of the isomeric hydroxy ketones, but their antifungal activities were comparable. Copyright © 2006 John Wiley & Sons, Ltd.
Analysis of phenolic acids in honeys of different floral origin by solid‐pase extraction and high‐performance liquid chromatography
Authors: Dimitrova Burya , Gevrenova Reneta , Anklam Elke 
Published: October 2006

AbstractThe determination of 18 aromatic and arylaliphatic carboxylic acids in honey from different floral origin using solid‐phase extraction (SPE) and reversed‐phase high performance liquid chromatography (RP‐HPLC) is reported. The behaviour of the solutes on SPE cartridges was predicted from preliminary calculations involving the pKa constants of the carboxylic groups, the n‐octanol:water partition coefficients and the distribution coefficients at different pH values of the conditioning and washing solvents. The proposed SPE isolation and pre‐concentration of the acids was achieved on reversed‐phase Bond Elut C18 cartridges using an acetonitrile:tetrahydrofuran (1:1, v/v) elution system. RP‐HPLC separations were performed on a Spherisorb ODS‐2 column using linear gradient elution with a mobile phase composed of 20 mm phosphate buffer (pH 2.92) and methanol, and with UV detection. The reported SPE and RP‐HPLC methods were applied to the analysis of 49 authentic honey samples from various floral sources and the results indicate that they may serve with respect to the quantitative control of a number of phenolic acids in plant‐derived foods and medicinal plants. Copyright © 2006 John Wiley & Sons, Ltd.
Homology models of dipeptidyl peptidases 8 and 9 with a focus on loop predictions near the active site
Authors: Rummey Christian , Metz Günther 
Published: October 2006

AbstractDipeptidyl peptidase 4 (DP4) inhibitors are currently under intensive investigation in late‐stage clinical trials as a treatment for type II diabetes. Lack of selectivity toward the related enzymes DP8 and DP9 has recently emerged as a possible source of drug‐induced toxicity. Unlike DP4, X‐ray structures of DP8 and DP9 are not yet available. As an aid to understanding the structural basis for selectivity, the authors have constructed homology models of DP8 and DP9 based on the X‐ray coordinates of DP4. Accurate sequence alignment reveals common structural features indicative for a well‐preserved overall fold comprising two domains, namely, a hydrolase domain and a so‐called β‐propeller, which together form the active site deeply buried within the protein. The conformation of two loops inside this deep cavity is particularly relevant for the active sites. The authors used a published protocol for loop prediction based on conformational sampling and energy analysis to generate plausible solutions for these two loops. The predictive power of the approach was successfully evaluated for the template protein DP4 and two additional known structures from the same protein family, namely, FAP and DPX. The authors also show that inclusion of the covalent ligand NVP‐728 greatly enhances the refinement. Based on the established evaluation protocol, the corresponding loops of DP8 and DP9 were predicted and the resulting active sites were compared with DP4. In particular, the authors conclude that differences in the P2‐pocket are relevant for the design of selective DP4 inhibitors. The loss of key interactions in DP8 and DP9 as predicted from their models is consistent with the selectivity profile of the DP4 clinical candidate MK‐431. Proteins 2007. © 2006 Wiley‐Liss, Inc.
Critical evaluation of methods to incorporate entropy loss upon binding in high‐throughput docking
Authors: Salaniwal Sumeet , Manas Eric S. , Alvarez Juan C. , Unwalla Rayomand J. 
Published: October 2006

AbstractProper accounting of the positional/orientational/conformational entropy loss associated with protein–ligand binding is important to obtain reliable predictions of binding affinity. Herein, we critically examine two simplified statistical mechanics‐based approaches, namely a constant penalty per rotor method, and a more rigorous method, referred to here as the partition function‐based scoring (PFS) method, to account for such entropy losses in high‐throughput docking calculations. Our results on the estrogen receptor β and dihydrofolate reductase proteins demonstrate that, while the constant penalty method over‐penalizes molecules for their conformational flexibility, the PFS method behaves in a more “ΔG‐like” manner by penalizing different rotors differently depending on their residual entropy in the bound state. Furthermore, in contrast to no entropic penalty or the constant penalty approximation, the PFS method does not exhibit any bias towards either rigid or flexible molecules in the hit list. Preliminary enrichment studies using a lead‐like random molecular database suggest that an accurate representation of the “true” energy landscape of the protein–ligand complex is critical for reliable predictions of relative binding affinities by the PFS method. Proteins 2007. © 2006 Wiley‐Liss, Inc.
Theoretical studies on farnesyltransferase: The distances paradox explained
Authors: Sousa Sérgio Filipe , Fernandes Pedro Alexandrino , Ramos Maria João 
Published: October 2006

AbstractIn spite of the enormous interest that has been devoted to its study, the mechanism of the enzyme farnesyltransferase (FTase) remains the subject of several crucial doubts. In this article, we shed a new light in one of the most fundamental dilemmas that characterize the mechanism of this puzzling enzyme commonly referred to as the “distances paradox”, which arises from the existence of a large 8‐Å distance between the two reactive atoms in the reaction catalyzed by this enzyme: a Zn‐bound cysteine sulphur atom from a peptidic substrate and the farnesyldiphosphate (FPP) carbon 1. This distance must be overcome for the reaction to occur. In this study, the two possible alternatives were evaluated by combining molecular mechanics (AMBER) and quantum chemical calculations (B3LYP). Basically, our results have shown that an activation of the Zn‐bound cysteine thiolate with subsequent displacement from the zinc coordination sphere towards the FPP carbon 1 is not a realistic hypothesis of overcoming the large distance reported in the crystallographic structures of the ternary complexes between the two reactive atoms, but that a rotation involving the FPP molecule can bring the two atoms closer with moderate energetic cost, coherent with previous experimental data. This conclusion opens the door to an understanding of the chemical step in the farnesylation reaction. Proteins 2007. © 2006 Wiley‐Liss, Inc.
Molecular Surface Features in Modeling the HIV‐1 RT Inhibitory Activity of 2‐(2,6‐Disubstituted phenyl)‐3‐(substituted pyrimidin‐2‐yl)‐thiazolidin‐4‐ones
Authors: Rawal Ravindra K. , Prabhakar Yenamandra S. , Katti Setu B. 
Published: October 2006

AbstractInhibitory activity of 2‐(2,6‐disubstituted phenyl)‐3‐(substituted pyrimidin‐2‐yl)‐thiazolidin‐4‐ones the Human Immunodeficiency Virus‐1 Reverse Transcriptase (HIV‐1 RT) have been analyzed using Combinatorial Protocol in Multiple Linear Regression (CP‐MLR) with several electronic and molecular surface area features of the compounds obtained from Molecular Operating Environment (MOE) software. The study has indicated the role of different charged molecular surface areas in modeling the inhibitory activity of the compounds. The derived models collectively suggested that the compounds should be compact without bulky substitutions on its peripheries for better HIV‐1 RT inhibitory activity. It also emphasized the necessity of hydrophobicity and compact structural features for their activity. The scope of the descriptors identified for these analogues have been verified by extending the dataset with different 2‐(disubstituted phenyl)‐3‐(substituted pyridin‐2‐yl)‐thiazolidin‐4‐ones. The joint analysis of extended dataset highlighted the information content of identified descriptors in modeling the HIV‐1 RT inhibitory activity of the compounds.
How Many Free Radicals can be Trapped by (Hydroxylphenylimino)methylphenol in the Free‐Radical‐Induced Peroxidation of Triolein in Micelles?
Authors: Liu Zai‐Qun 
Published: October 2006

AbstractThis work focused on assessing the antioxidant capacity of two hydroxyl‐substituent Schiff bases, 2‐(o‐hydroxylphenylimino)methylphenol (OsH) and 2‐(p‐hydroxylphenylimino)methylphenol (PsH) used alone or in combination with α‐tocopherol (TocH) and 6‐hydroxyl‐2,5,7,8‐tetramethylchroman‐2‐carboxylic acid (Trolox) in 2,2′‐azobis(2‐amidinopropane hydrochloride) (AAPH)‐induced peroxidation of triolein (GtH) dispersed in cetyl trimethyl ammonium Bromide (CTAB, a cationic micelle), sodium dodecyl sulfate (SDS, an anionic micelle), and Triton X‐100 (a neutral micelle), respectively. The present findings indicate that OsH and PsH are not only concentration‐dependent antioxidants, but also protect GtH with Trolox and TocH synergistically. Especially, the reason for the higher antioxidant capacity of OsH than PsH can be ascribed to the fact that OsH contains a hydroxyl group adjacent to the nitrogen atom. Furthermore, the number of trapped peroxyl radicals by Schiff base, n, can be calculated on the basis of chemical kinetic deduction. As a result, n of OsH and PsH increase in SDS micelle but decrease in CTAB, implicating that their antioxidant capacities are not only related to their structures but also to the charge property of micelles, dispersed GtH also affect their antioxidant behavior prominently. In addition, the synergistic antioxidant capacities of OsH and PsH used in conjuction with Trolox and TocH were investigated in the above micelles, and, it was found that PsH+Trolox in Triton X‐100 and CTAB exhibited a mutual promoting effect, whereas OsH+Trolox in SDS plays a mutual demoting effect. Nevertheless, the n of Schiff bases or other antioxidants in the mixed usage are rather different from that used alone, implying that an interaction among these compounds exists in protecting GtH against AAPH‐induced peroxidation.
QSAR Modeling of PeripheralVersusCentral Benzodiazepine Receptor Binding Affinity of 2‐Phenylimidazo[1,2‐a]pyridineacetamides using Optimal Descriptors Calculated with SMILES
Authors: Roy Kunal , Toropov Andrey , Raska Ivan 
Published: October 2006

AbstractThe optimization of correlation weights scheme has been applied to model Peripheral Benzodiazepine Receptor (PBR) binding affinity (ovary and cortex) and PBR binding selectivity (peripheralversuscentral benzodiazepine receptor) of 2‐phenylimidazo[1,2‐a]pyridineacetamides. In the present study, optimal descriptors based on Simplified Molecular Input Line Entry System (SMILES) notation have been used for the modeling purpose. The optimized descriptor formulated based on the data of training set generated statistically acceptable relations (for PBR cortex,q2=0.717,r2=0.756; for PBR ovary,q2=0.836,r2=0.852; for PBR cortex selectivity,q2=0.732,r2=0.784; for PBR ovary selectivity,q2=0.828,r2=0.845). When the relations of PBR binding affinity or selectivity with the optimized molecular descriptor formulated based on the data of the training set was used for the calculation of the corresponding response parameters of the test set,$\rm{ r_{{\rm{Pred}}}^{\rm{2}} }$values were found to be satisfactory (for PBR cortex, 0.692; for PBR ovary, 0.682; for PBR ovary selectivity, 0.772) except in the case of PBR cortex selectivity ($\rm{ r_{{\rm{Pred}}}^{\rm{2}} }$being 0.321). The results indicate promising potential of the optimization of correlation weights based on SMILES notation in modeling studies.
Non‐sequential MIMO QFT control of the X‐29 aircraft using a generalized formulation
Authors: Kerr Murray L. , Lan Chen‐yang , Jayasuriya Suhada 
Published: October 2006

AbstractThis paper presents a generalized formulation for multi‐input multi‐output (MIMO) quantitative feedback theory (QFT) based controller design and analysis, and its application to the control of the X‐29 aircraft. The formulation is based on a more general control structure, where input and output transfer function matrices are included to provide additional degrees of freedom in the decentralized MIMO QFT feedback structure, that facilitates the exploitation of directions in MIMO QFT designs. The formulation captures existing design approaches for fully populated MIMO QFT controller design and provides for a directional design logic involving the plant and controller alignment and the directional properties of their multivariable poles and zeros. Horowitz's Singular‐G design methodology is placed in the context of the generalized formulation and the Singular‐G design for the X‐29 is analysed and redesigned using non‐sequential MIMO QFT and the formulation, demonstrating its utility. The results highlight a fundamental trade‐off between multivariable controller directions for stability and performance in classically formulated design methodologies, elucidate the properties of Singular‐G designed controllers for the X‐29 and validate recent contributions to the theory for non‐sequential MIMO QFT. Copyright © 2006 John Wiley & Sons, Ltd.