bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evoked myotonia can be “dialed‐up” by increasing stimulus train length in myotonic dystrophy type 1
Authors: Logigian Eric L. , Twydell Paul , Dilek Nuran , Martens William B. , Quinn Chris , Wiegner Allen W. , Heatwole Chad R. , Thornton Charles A. , Moxley Richard T. 
Published: September 2009

AbstractIt is unknown how evoked myotonia varies with stimulus frequency or train length, or how it compares to voluntary myotonia in myotonic dystrophy type 1 (DM1). First dorsal interosseous (FDI) tetanic contractions evoked by trains of 10–20 ulnar nerve stimuli at 10–50 HZ were recorded in 10 DM1 patients and 10 normals. For comparison, maximum voluntary handgrip contractions were also recorded. An automated computer program placed cursors along the declining (relaxation) phase of the force recordings at 90% and 5% of peak force (PF) and calculated relaxation times (RTs) between these points. For all stimulus frequencies and train lengths, evoked RTs were much shorter, and evoked PFs were much greater in normals than in DM1. In normals, evoked RT was independent of stimulus frequency and train length, while in DM1 RT was longer for train lengths of 20 stimuli (mean: 9 s in DM1; 0.20 in normals) than for 10 stimuli (mean: 3 s in DM1, 0.19 in normals), but it did not change with stimulus frequency. In both groups PF increased greatly as stimulus frequency rose from 10–50 HZ but only slightly as train length rose from 10–20 stimuli. Voluntary handgrip RT (mean: 1.9 s) was less than evoked FDI RT (mean: 9 s). In DM1, evoked RT can be “dialed up” by increasing stimulus train length. Evoked myotonia testing utilizing a stimulus paradigm of at least 20 stimuli at 30–50 HZ may be useful in antimyotonic drug trials, particularly when grip RT is normal or equivocal. Muscle Nerve, 2010
Rheological characteristics of solid–fluid transition in dry granular dense flows: A thermodynamically consistent constitutive model with a pressure‐ratio order parameter
Authors: Fang Chung 
Published: September 2009

AbstractDry granular flows are characterized as quasi‐static, dense and collisional states by the interactions among the grains, which is indexed macroscopically by an internal variable, called the order parameter defined as the square root of the static pressure to the total pressure. The solid–fluid state transition is regarded as a second‐order phase transition process, and is described by a kinematic evolution of the order parameter. The thermodynamic analysis, based on the Müller–Liu entropy principle, is employed to deduce the equilibrium responses of the constitutive equations, while the dynamic responses are postulated on the basis of a quasi‐linear and the second‐order Ginzburg–Landau phase transition theories. The obtained model is applied to study the rheological characteristics of a dry granular dense flow between two infinite parallel plates, of which the results are compared with those from DEM simulations to estimate the model validity. The present study provides a general framework for the theoretical justifications on the thermodynamic consistencies of order‐parameter‐based constitutive models, and can be extended to flows in quasi‐static or collisional states. Copyright © 2009 John Wiley & Sons, Ltd.
Steady‐state solution for cylindrical penetrometers
Authors: Klar Assaf , Pinkert Shmulik 
Published: September 2009

AbstractThis paper suggests a new method for obtaining steady‐state solutions for ‘full‐flow’ penetrometers. The method is based on the numerical solution of the small strain plastic‐flow problem (i.e. rigid plastic material) with an inhomogeneous strength field, which is determined by converting changes of material properties over time in a stationary frame of reference into spatial distribution of strength in a moving frame of reference. Rather than building streamlines from back integration of soil element distortion, as previous methods have suggested, the method treats the domain as continuous with the associated field equations. The method employs an upstream weighting technique for the determination of information flow within the domain. The execution order for the calculation is based on topological ordering. This results in the calculation having a complexity of O(N), as compared with O(N1.5) for the strain path or streamline methods (N is the number of discretized points), which significantly reduces the calculation time. The formulation is presented for the cylindrical (T‐bar) penetrometer, and includes aspects of soil strength degradation, strain rate effects, strength anisotropy, and interface strength law. Comparison to previously published values, based on large displacement finite element simulations with remeshing, showed good agreement, indicating on the correctness of the suggested approach. Investigation into the soil rigid‐body rotation and the remolding effect on anisotropy characteristics showed an interesting behavior, where the decrease of strength anisotropy due to remolding has a greater influence when the soil strength is higher in the vertical direction. Copyright © 2009 John Wiley & Sons, Ltd.
An adaptive stabilization strategy for enhanced strain methods in non‐linear elasticity
Authors: Ten Eyck Alex , Lew Adrian 
Published: September 2009

AbstractThis paper proposes and analyzes an adaptive stabilization strategy for enhanced strain (ES) methods applied to quasistatic non‐linear elasticity problems. The approach is formulated for any type of enhancements or material models, and it is distinguished by the fact that the stabilization term is solution dependent. The stabilization strategy is first constructed for general linearized elasticity problems, and then extended to the non‐linear elastic regime via an incremental variational principle. A heuristic choice of the stabilization parameters is proposed, which in the numerical examples proved to provide stable approximations for a large range of deformations, different problems and material models. We also provide explicit lower bounds for the stabilization parameters that guarantee that the method will be stable. These are not advocated, since they are generally larger than the ones based on heuristics, and hence prone to deteriorate the locking‐free behavior of ES methods. Numerical examples with two different non‐linear elastic models in thin geometries and incompressible situations show that the method remains stable and locking free over a large range of deformations. Finally, the method is strongly based on earlier developments for discontinuous Galerkin methods, and hence throughout the paper we offer a perspective about the similarities between the two. Copyright © 2009 John Wiley & Sons, Ltd.
Error estimation in a stochastic finite element method in electrokinetics
Authors: Clénet S. , Ida N. 
Published: September 2009

AbstractInput data to a numerical model are not necessarily well known. Uncertainties may exist both in material properties and in the geometry of the device. They can be due, for instance, to ageing or imperfections in the manufacturing process. Input data can be modelled as random variables leading to a stochastic model. In electromagnetism, this leads to solution of a stochastic partial differential equation system. The solution can be approximated by a linear combination of basis functions rising from the tensorial product of the basis functions used to discretize the space (nodal shape function for example) and basis functions used to discretize the random dimension (a polynomial chaos expansion for example). Some methods (SSFEM, collocation) have been proposed in the literature to calculate such approximation. The issue is then how to compare the different approaches in an objective way. One solution is to use an appropriate a posteriori numerical error estimator. In this paper, we present an error estimator based on the constitutive relation error in electrokinetics, which allows the calculation of the distance between an average solution and the unknown exact solution. The method of calculation of the error is detailed in this paper from two solutions that satisfy the two equilibrium equations. In an example, we compare two different approximations (Legendre and Hermite polynomial chaos expansions) for the random dimension using the proposed error estimator. In addition, we show how to choose the appropriate order for the polynomial chaos expansion for the proposed error estimator. Copyright © 2009 John Wiley & Sons, Ltd.
MALDI‐TOF MS‐based drug susceptibility testing of pathogens: The example of Candida albicans and fluconazole
Authors: Marinach Carine , Alanio Alexandre , Palous Martine , Kwasek Stéphanie , Fekkar Arnaud , Brossas Jean‐Yves , Brun Sophie , Snounou Georges , Hennequin Christophe , Sanglard Dominique , Datry Annick , Golmard Jean‐Louis , Mazier Dominique 
Published: September 2009

AbstractMALDI‐TOF MS can be used for the identification of microorganism species. We have extended its application to a novel assay of Candida albicans susceptibility to fluconazole, based on monitoring modifications of the proteome of yeast cells grown in the presence of varying drug concentrations. The method was accurate, and reliable, and showed full agreement with the Clinical Laboratory Standards Institute's reference method. This proof‐of‐concept demonstration highlights the potential for this approach to test other pathogens.
Mechanism of formation of the C‐terminal β‐hairpin of the B3 domain of the immunoglobulin binding protein G from Streptococcus. III. Dynamics of long‐range hydrophobic interactions
Authors: Lewandowska Agnieszka , Ołdziej Stanisław , Liwo Adam , Scheraga Harold A. 
Published: September 2009

AbstractA 20‐residue peptide, IG(42–61), derived from the C‐terminal β‐hairpin of the B3 domain of the immunoglobulin binding protein G from Streptoccocus was studied using circular dichroism, nuclear magnetic resonance (NMR) spectroscopy at various temperatures and by differential scanning calorimetry (DSC). Unlike other related peptides studied so far, this peptide displays two heat capacity peaks in DSC measurements (at a scanning rate of 1.5 deg/min at a peptide concentration of 0.07 mM), which suggests a three‐state folding/unfolding process. The results from DSC and NMR measurements suggest the formation of a dynamic network of hydrophobic interactions stabilizing the structure, which resembles a β‐hairpin shape over a wide range of temperatures (283–313 K). Our results show that IG (42–61) possesses a well‐organized three‐dimensional structure stabilized by long‐range hydrophobic interactions (Tyr50 ··· Phe57 and Trp48 ··· Val59) at T = 283 K and (Trp48 ··· Val59) at 305 and 313 K. The mechanism of β‐hairpin folding and unfolding, as well as the influence of peptide length on its conformational properties, are also discussed. Proteins 2010. © 2009 Wiley‐Liss, Inc.
Backbone dynamics of TFE‐induced native‐like fold of region 4 of Escherichia coli RNA polymerase σ70 subunit
Authors: Kaczka Piotr , Polkowska‐Nowakowska Agnieszka , Bolewska Krystyna , Zhukov Igor , Poznański Jarosław , Wierzchowski Kazimierz L. 
Published: September 2009

AbstractFolding of a recombinant protein rECσ comprising domain 4 of E. coli RNA polymerase σ70 subunit, upon addition of 2,2,2‐trifluoroethanol (TFE) to its aqueous solution, was monitored by heteronuclear NMR spectroscopy. The TFE‐induced migration of resonance signals in a series of 15N‐HSQC spectra displayed sequence‐dependent heterogeneity. A common trend of uniform upfield shift in both 1H and 15N dimensions, indicative of generation of helical structures, breaks down for some residues almost cooperatively at 10–15% TFE (v/v), pointing to the buildup of non‐helical regions separating the initially induced helices. The preferences of residues to assume either helical or non‐helical conformation are correlated with the location in the sequence rather than with their type. CSI descriptors and 15N relaxation data obtained for the protein at 10% TFE allowed characterization of the stability of the pre‐folded state of rECσ. By all the criteria applied, three highly populated α‐helical regions separated by much more flexible residues forming a loop and a turn in the DNA‐binding HLHTH motif were identified. The location of the secondary structure elements along the protein sequence coincides with those found in homologous proteins, and with the helix nucleation regions determined in unfolded rECσ at low pH. The bimodal distribution of the 15N relaxation parameters enabled identification of residues forming a framework of the folded protein strictly corresponding to the HLHTH motif, bracketed by unfolded terminal regions. Thus, in respect to rECσ in aqueous solution TFE acts not only as a strong helix inducer, but also as a folding agent. Proteins 2010. © 2009 Wiley‐Liss, Inc.
Slow formation of aggregation‐resistant β‐sheet folding intermediates
Authors: Junker Mirco , Clark Patricia L. 
Published: September 2009

AbstractProtein folding has been studied extensively for decades, yet our ability to predict how proteins reach their native state from a mechanistic perspective is still rudimentary at best, limiting our understanding of folding‐related processes in vivo and our ability to manipulate proteins in vitro. Here, we investigate the in vitro refolding mechanism of a large β‐helix protein, pertactin, which has an extended, elongated shape. At 55 kDa, this single domain, all‐β‐sheet protein allows detailed analysis of the formation of β‐sheet structure in larger proteins. Using a combination of fluorescence and far‐UV circular dichroism spectroscopy, we show that the pertactin β‐helix refolds remarkably slowly, with multiexponential kinetics. Surprisingly, despite the slow refolding rates, large size, and β‐sheet‐rich topology, pertactin refolding is reversible and not complicated by off‐pathway aggregation. The slow pertactin refolding rate is not limited by proline isomerization, and 30% of secondary structure formation occurs within the rate‐limiting step. Furthermore, site‐specific labeling experiments indicate that the β‐helix refolds in a multistep but concerted process involving the entire protein, rather than via initial formation of the stable core substructure observed in equilibrium titrations. Hence pertactin provides a valuable system for studying the refolding properties of larger, β‐sheet‐rich proteins, and raises intriguing questions regarding the prevention of aggregation during the prolonged population of partially folded, β‐sheet‐rich refolding intermediates. Proteins 2010. © 2009 Wiley‐Liss, Inc.
Fipronil resistance in the whitebacked planthopper (Sogatella furcifera): possible resistance mechanisms and cross‐resistance
Authors: Tang Jian , Li Jian , Shao Ying , Yang Baojun , Liu Zewen 
Published: September 2009

AbstractBACKGROUND: The whitebacked planthopper (WBPH), Sogatella furcifera (Horváth), is a major rice pest in many parts of Asia. Fipronil has been widely used to control rice pests, and resistance to fipronil has been reported in some important species.RESULTS: A field population (F) of WBPH was collected, with 50.5‐fold resistance to fipronil, which increased to 137.5‐fold (F‐se) after continuous selection for 11 generations. The F‐se population did not show significant cross‐resistance to the insecticides examined by comparison with the F population. TPP (synergism ratio 1.9), DEM (1.5) and PBO (1.1) showed only slight synergism on fipronil in the F‐se population. A large increase was found in esterase and P450 monooxygenase activity in the F‐se population. In vitro, PBO inhibited both esterase and P450 monooxygenase activity, and TPP inhibited esterase activity in the F‐se population.CONCLUSION: Synergistic study in vivo and biochemical study in vitro indicated that esterase and P450 monooxygenases might be important factors for fipronil resistance in the selected population F‐se. However, these biochemical factors could not lead to such high resistance (137.5‐fold) in the F‐se population, and target‐site insensitivity would be another or more important factor. Copyright © 2009 Society of Chemical Industry
Quality specifications for peptide drugs: a regulatory‐pharmaceutical approach
Authors: Vergote Valentijn , Burvenich Christian , Van de Wiele Christophe , De Spiegeleer Bart 
Published: September 2009

AbstractPeptide drugs, as all types of pharmaceuticals, require adequate specifications (i.e. quality attributes, procedures and acceptance criteria) as part of their quality assurance to ensure the safety and efficacy of drug substances (i.e. active pharmaceutical ingredients) and drug products (i.e. finished pharmaceutical dosage forms). Compendial monographs are updated regularly to keep up with the most recent advances in peptide synthesis (e.g. reduced by‐products) and analytical technology. Nevertheless, currently applied pharmacopoeial peptide specifications are barely harmonized yet (e.g. large differences between the European Pharmacopoeia and the United States Pharmacopeia), increasing the manufacturers' burden of performing analytical procedures in different ways, using different acceptance criteria. Additionally, the peptide monographs are not always consistent within a single pharmacopoeia. In this review, we highlight the main differences and similarities in compendial peptide specifications (including identification, purity and assay). Based on comparison, and together with additional information from peptide drug substance manufacturers and public evaluation reports on registration files of non‐pharmacopoeial peptide drugs, a consistent monograph structure is proposed. Copyright © 2009 European Peptide Society and John Wiley & Sons, Ltd.
Reinforcement learning design for cancer clinical trials
Authors: Zhao Yufan , Kosorok Michael R. , Zeng Donglin 
Published: September 2009

AbstractWe develop reinforcement learning trials for discovering individualized treatment regimens for life‐threatening diseases such as cancer. A temporal‐difference learning method called Q‐learning is utilized that involves learning an optimal policy from a single training set of finite longitudinal patient trajectories. Approximating the Q‐function with time‐indexed parameters can be achieved by using support vector regression or extremely randomized trees. Within this framework, we demonstrate that the procedure can extract optimal strategies directly from clinical data without relying on the identification of any accurate mathematical models, unlike approaches based on adaptive design. We show that reinforcement learning has tremendous potential in clinical research because it can select actions that improve outcomes by taking into account delayed effects even when the relationship between actions and outcomes is not fully known. To support our claims, the methodology's practical utility is illustrated in a simulation analysis. In the immediate future, we will apply this general strategy to studying and identifying new treatments for advanced metastatic stage IIIB/IV non‐small cell lung cancer, which usually includes multiple lines of chemotherapy treatment. Moreover, there is significant potential of the proposed methodology for developing personalized treatment strategies in other cancers, in cystic fibrosis, and in other life‐threatening diseases. Copyright © 2009 John Wiley & Sons, Ltd.
Nonviral in Situ Green Fluorescent Protein Labeling and Culture of Primary, Adult Human Hair Follicle Epithelial Progenitor Cells
Authors: Tiede Stephan , Koop Norbert , Kloepper Jennifer E. , Fässler Reinhard , Paus Ralf 
Published: September 2009

Abstract
In this article we show that cloning of the human K15 promoter before a green fluorescence protein (GFP)/geneticin-resistance cassette and transfection of microdissected, organ-cultured adult human scalp hair follicles generates specific K15 promoter–driven GFP expression in their stem cell–rich bulge region. K15-GFP+ cells can be visualized in situ by GFP fluorescence and 2-photon laser scanning microscopy. Vital K15-GFP+ progenitor cells can then be selected by using the criteria of their green fluorescence, adhesion to collagen type IV and fibronectin, and geneticin resistance. Propagated K15-GFP+ cells express epithelial progenitor markers, show the expected differential gene expression profile of human bulge epithelium, and form holoclones. This application of nonretroviral, K15 promoter–driven, GFP labeling to adult human hair follicles facilitates the characterization and manipulation of human epithelial stem cells, both in situ and in vitro, and should be transferable to other complex human tissues.
Disclosure of potential conflicts of interest is found at the end of this article.
Multipathway Kinase Signatures of Multipotent Stromal Cells Are Predictive for Osteogenic Differentiation
Authors: Platt Manu O. , Wilder Catera L. , Wells Alan , Griffith Linda G. , Lauffenburger Douglas A. 
Published: September 2009

Abstract
Bone marrow-derived multipotent stromal cells (MSCs) offer great promise for regenerating tissue. Although certain transcription factors have been identified in association with tendency toward particular MSC differentiation phenotypes, the regulatory network of key receptor-mediated signaling pathways activated by extracellular ligands that induce various differentiation responses remains poorly understood. Attempts to predict differentiation fate tendencies from individual pathways in isolation are problematic due to the complex pathway interactions inherent in signaling networks. Accordingly, we have undertaken a multivariate systems approach integrating experimental measurement of multiple kinase pathway activities and osteogenic differentiation in MSCs, together with computational analysis to elucidate quantitative combinations of kinase signals predictive of cell behavior across diverse contexts. In particular, for culture on polymeric biomaterial surfaces presenting tethered epidermal growth factor, type I collagen, neither, or both, we have found that a partial least-squares regression model yields successful prediction of phenotypic behavior on the basis of two principal components comprising the weighted sums of eight intracellular phosphoproteins: phospho-epidermal growth factor receptor, phospho-Akt, phospho-extracellular signal-related kinase 1/2, phospho-heat shock protein 27, phospho-c-Jun, phospho-glycogen synthase kinase 3α/β, phospho-p38, and phospho-signal transducer and activator of transcription 3. This combination provides the strongest predictive capability for 21-day differentiated phenotype status when calculated from day-7 signal measurements; day-4 and day-14 signal measurements are also significantly predictive, indicating a broad time frame during MSC osteogenesis wherein multiple pathways and states of the kinase signaling network are quantitatively integrated to regulate gene expression, cell processes, and ultimately, cell fate.
Disclosure of potential conflicts of interest is found at the end of this article.