bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rotigotine polyoxazoline conjugate SER‐214 provides robust and sustained antiparkinsonian benefit
Authors: Eskow Jaunarajs Karen L. , Standaert David G. , Viegas Tacey X. , Bentley Michael D. , Fang Zhihao , Dizman Bekir , Yoon Kunsang , Weimer Rebecca , Ravenscroft Paula , Johnston Tom H. , Hill Michael P. , Brotchie Jonathan M. , Moreadith Randall W. 
Published: September 2013

ABSTRACTCurrently available dopaminergic drugs such as levodopa and dopamine (DA) receptor agonists impart considerable improvement in Parkinson's disease (PD) motor symptoms but often lead to significant motor complications including “wearing‐off” and dyskinesia. Such complications are believed to stem from the pulsatile nature of dopaminergic stimulation with these agents. Continuous dopaminergic drug delivery using polyoxazoline (POZ) polymer conjugation may improve motor symptoms, while avoiding development of side effects. The purposes of the current study are to characterize the in vitro and in vivo pharmacokinetics of POZ conjugation of a U.S. Food and Drug Administration (FDA)‐approved DA agonist, rotigotine, and to evaluate their effects in an established rat model of PD. After determination of release profiles of several POZ‐conjugated constructs (“fast”: SER‐212; “moderate”: SER‐213; and “slow”: SER‐214) using in vitro hydrolysis, normal male Sprague‐Dawley rats were used for determination of the pharmacokinetic profile of both acute and chronic exposure. Finally, a separate group of rats was rendered hemiparkinsonian using intracranial 6‐hydroxydopamine (6‐OHDA) infusions, treated acutely with POZ‐rotigotine, and assessed for rotational behavior and antiparkinsonian benefit using the cylinder test. POZ‐rotigotine formulations SER‐213 and SER‐214 led to substantial pharmacokinetic improvement compared to unconjugated rotigotine. In addition, SER‐214 led to antiparkinsonian effects in DA‐lesioned rats that persisted up to 5 days posttreatment. Repeated weekly dose administration of SER‐214 to normal rats for up to 12 weeks demonstrated highly reproducible pharmacokinetic profiles. The continuous dopaminergic stimulation profile afforded by SER‐214 could represent a significant advance in the treatment of PD, with potential to be a viable, once‐per‐week therapy for PD patients.
Volumetric correlates of cognitive functioning in nondemented patients with Parkinson's disease
Authors: Filoteo J. Vincent , Reed Jason D. , Litvan Irene , Harrington Deborah L. 
Published: September 2013

ABSTRACTA challenge in Parkinson's disease (PD) is to identify biomarkers of early cognitive change because functioning in some domains may be more prognostic of dementia. Few studies have investigated whether structural magnetic resonance imaging (MRI) correlates in a regionally specific manner with functioning in different cognitive domains. The aim of this study was to identify neuroanatomical correlates of executive functioning, memory, and visual cognition in PD without dementia. 3T MRI was conducted in 51 PD patients and 39 control participants. Brain volumes were measured in structures comprising the frontostriatal cognitive‐control system, the medial temporal memory system, the ventral object‐based system, and the dorsal spatial‐based system. Measures of executive functioning (Stroop Test; Letter Fluency), memory (California Verbal Learning Test), visuospatial cognition (Judgment of Line Orientation), and visuoconstruction (Pentagon Copy) were correlated with volumes comprising each system. Poorer executive functioning largely correlated with decreased frontostriatal volumes. Poorer memory correlated with decreased volumes in all medial temporal regions, but also with frontostriatal volumes. Poorer visuospatial cognition correlated with decreased volumes in the object‐based system, whereas poorer visuoconstruction correlated with decreased frontal and object‐based system volumes. These relationships were nonsignificant in the control group. This is the first study to demonstrate that subtle changes in multiple cognitive domains in PD without dementia correlate with regional volumes in specific systems implicated in the development of cognitive impairment. The findings suggest that structural MRI holds promise as a marker of early changes in different brain systems, some of which may predict future cognitive deterioration. © 2013 Movement Disorder Society
Task force report: Scales for screening and evaluating tremor: Critique and recommendations
Authors: Elble Rodger , Bain Peter , João Forjaz Maria , Haubenberger Dietrich , Testa Claudia , Goetz Christopher G. , Leentjens Albert F. G. , Martinez‐Martin Pablo , Pavy‐Le Traon Anne , Post Bart , Sampaio Cristina , Stebbins Glenn T. , Weintraub Daniel , Schrag Anette 
Published: September 2013

ABSTRACTThe Movement Disorder Society established a task force to review rating scales for the assessment of tremor. Screening instruments used in identifying patients with tremor were also reviewed. Seven tremor severity scales, six activities of daily living (ADL)/disability scales, four quality‐of‐life scales, and five screening instruments were identified by searching PubMed.gov. The availability, use, acceptability, reliability, validity, and sensitivity to change were reviewed for each scale; and each scale was classified as recommended, suggested or listed based on whether 3, 2, or 1 of the following criteria were met: (1) used in the assessment of tremor (yes/no), (2) used in published studies by people other than the developers (yes/no), and (3) successful clinimetric testing (yes/no). Five tremor severity scales (the Fahn‐Tolosa‐Marin Tremor Rating Scale, the Bain and Findley Clinical Tremor Rating Scale, the Bain and Findley Spirography Scale, the Washington Heights‐Inwood Genetic Study of Essential Tremor Rating Scale, and the Tremor Research Group Essential Tremor Rating Assessment Scale), one ADL/disability scale (the Bain and Findley Tremor ADL Scale), one quality‐of‐life scale (the Quality of Life in Essential Tremor Questionnaire), and one screening instrument (the Washington Heights‐Inwood Genetic Study of Essential Tremor Rating Scale, version 1) are recommended using these criteria. However, all scales need a more comprehensive analysis of sensitivity to change in order to judge their utility in clinical trials and individual patient assessments. The task force recommends that further work with existing recommended scales be performed as opposed to the development of new tremor scales. © 2013 International Parkinson and Movement Disorder Society
Identification of novel β‐lactoglobulin‐derived peptides, wheylin‐1 and ‐2, having anxiolytic‐like activity in mice
Authors: Yamada Ayako , Mizushige Takafumi , Kanamoto Ryuhei , Ohinata Kousaku 
Published: September 2013

ScopeWe found that thermolysin digest of β‐lactoglobulin, a major protein of bovine milk whey, exhibited anxiolytic‐like activity in a behavioral experiment in mice, and then identified active components from the digest.Methods and resultsIn the elevated plus‐maze test, thermolysin digest of β‐lactoglobulin had anxiolytic‐like activity after intraperitoneal administration in mice. We identified several low‐molecular‐weight peptides in a fraction separated by reverse‐phase HPLC having the most potent anxiolytic‐like activities. Among them, Met‐His and Met‐Lys‐Gly, corresponding to β‐lactoglobulin (145–146) and (7–9), had anxiolytic‐like activity at a dose of 0.3–1 and 3 mg/kg, respectively, after intraperitoneal administration. We named Met‐His and Met‐Lys‐Gly wheylin‐1 and ‐2, respectively. Next, we focused on wheylin‐1, a more potent peptide with anxiolytic‐like activity than wheylin‐2. Wheylin‐1 (1 mg/kg) had anxiolytic‐like activity after oral administration. In the open‐field test, wheylin‐1 was also active. The anxiolytic‐like activity of wheylin‐1 was blocked by bicuculline, an antagonist of γ‐amino butyric acid type A (GABAA) receptor, suggesting that wheylin‐1 exhibited anxiolytic‐like activity via the GABAA system.ConclusionNovel β‐lactoglobulin‐derived peptides, wheylin‐1 and ‐2, may exhibit anxiolytic‐like activities.
Antihyperglycemic effect of equol, a daidzein derivative, in cultured L6 myocytes and ob/ob mice
Authors: Cheong Sun Hee , Furuhashi Keisuke , Ito Katsuki , Nagaoka Masato , Yonezawa Takayuki , Miura Yutaka , Yagasaki Kazumi 
Published: September 2013

ScopeMolecular mechanisms for the potential antihyperglycemic effect of equol remain to be elucidated. In this study, we investigated the in vitro effect of equol on glucose uptake, AMP‐activated protein kinase (AMPK) phosphorylation, and glucose transporter 4 (GLUT4) translocation to plasma membrane in L6 myocytes, and its in vivo antihyperglycemic effect in obese‐diabetic model ob/ob mice.Methods and resultsEquol was found to promote glucose uptake, AMPK phosphorylation, and GLUT4 translocation detected by Western blotting analyses in L6 myotubes under a condition of insulin absence. Equol (0.05% in diet) suppressed the rise in serum glucose, cholesterol, triglyceride, and lipid peroxide concentrations and the hepatic triglyceride level as compared with those in the control group. Moreover, equol treatment suppressed the rises in fasting blood glucose level and improved the impaired glucose tolerance in ob/ob mice. Furthermore, equol treatment was demonstrated to improve expression of hepatic gluconeogenesis‐ and lipogenesis‐related genes in terms of glucose and lipid metabolism.ConclusionThe hypoglycemic effect of equol is related to increased GLUT4 translocation to the plasma membrane via AMPK activation. In addition, equol suppresses the fasting blood glucose level and gene expression of hepatic enzymes related to glucose metabolism. These results strongly suggest that equol has antidiabetic potential.
A constrained‐optimization methodology for the detection phase in contact mechanics simulations
Authors: Aragón Alejandro M. , Yastrebov Vladislav A. , Molinari Jean‐François 
Published: September 2013

SUMMARYThe detection phase in computational contact mechanics can be subdivided into a global search and a local detection. When potential contact is detected by the former, a rigorous local detection determines which surface elements come or may come in contact in the current increment. We first introduce a rigorous definition of the closest point for non‐differentiable lower‐dimensional manifolds. We then simplify the detection by formulating an optimization problem subject to inequality constraints. The formulation is then solved using different techniques from the field of mathematical optimization, for both linear and quadratic finite element meshes. The resulting general and robust detection scheme is tested on a set of problems and compared with other techniques commonly used in computational geometry. Copyright © 2013 John Wiley & Sons, Ltd.
Highly accurate surface and volume integration on implicit domains by means of moment‐fitting
Authors: Müller B. , Kummer F. , Oberlack M. 
Published: September 2013

SUMMARYWe introduce a new method for the numerical integration over curved surfaces and volumes defined by a level set function. The method is based on the solution of a small linear system based on a simplified variant of the moment‐fitting equations. Numerical experiments suggest that the accuracy of the resulting quadrature rules exceeds the accuracy of traditional methods by orders of magnitude. Using moments up to an order of p, the measured experimental orders of convergence exceed hp. Consequently, their construction is very efficient because only coarse computational grids are required. The conceptual simplicity allows for the application on very general grid types, which is demonstrated by numerical experiments on quadrilateral, triangular and hexahedral grids. Copyright © 2013 John Wiley & Sons, Ltd.
Lumped mass finite element implementation of continuum theories with micro‐inertia
Authors: Lombardo Mariateresa , Askes Harm 
Published: September 2013

SUMMARYContinuum theories can be equipped with additional inertia terms to make them capable of capturing wave dispersion effects observed in micro‐structured materials. Such terms, often called micro‐inertia, are convenient and straightforward extensions of classical continuum theories. Furthermore, the critical time step is usually increased via the inclusion of micro‐inertia. However, the drawback exists that standard finite element discretisation leads to mass matrices that cannot be lumped without losing the micro‐inertia terms. In this paper, we will develop a solution algorithm based on Neumann expansions by which this disadvantage is avoided altogether. The micro‐inertia terms are translated into modifications of the residual force vector, so that the system matrix is the usual lumped mass matrix and all advantages of explicit time integration are maintained. The numerical stability of the algorithm and its effect on the dispersive properties of the model are studied in detail. Numerical examples are used to illustrate the various aspects of the algorithm. Copyright © 2013 John Wiley & Sons, Ltd.
Syntheses of α‐bis(4‐aminophenyl)‐ and α,ω‐tetrakis(4‐aminophenyl)‐ functionalized polymers using 1,1‐bis(4‐aminophenyl)ethylene in atom transfer radical polymerization reactions
Authors: Summers Gabriel J , Ndawuni Mzikayise P , Summers Carol A 
Published: September 2013

AbstractThe preparation of a symmetrically disubstituted 1,1‐diphenylethylene derivative, 1,1‐bis(4‐aminophenyl)ethylene, by the Wittig reaction as well as the preparation of primary amine chain‐end‐functionalized polymers using that derivative in atom transfer radical polymerization (ATRP) reactions are reported. A new primary diamine initiator system was generated in situ by the atom transfer radical addition reaction of (1‐bromoethyl)benzene with 1,1‐bis(4‐aminophenyl)ethylene in the presence of copper(I) bromide/2,2′‐bipyridyl as the catalyst system and employed as the primary diamine‐functionalized initiator for the polymerization of styrene by ATRP methods to produce well‐defined α‐bis(4‐aminophenyl)‐functionalized polystyrene. The polymerization kinetic data for the synthesis of α‐bis(4‐aminophenyl)‐functionalized polystyrene shows that the polymerization process followed first‐order rate kinetics with respect to monomer consumption. The number‐average molecular weights (Mn = 1.1 × 103 to 13.14 × 103 g mol−1) of the α‐bis(4‐aminophenyl)‐functionalized polymers increased linearly with percentage monomer conversion and polymers with narrow molecular weight distributions (Mw/Mn = 1.1–1.25) were obtained. The polymerization processes were monitored using gas chromatographic analyses to determine the extent of monomer consumption as a function of time. In addition, α,ω‐tetrakis(4‐aminophenyl)‐functionalized polystyrene was prepared by a new, controlled/living, in situ post‐ATRP chain‐end functionalization reaction which involved the direct addition of 1,1‐bis(4‐aminophenyl)ethylene to the ω‐terminus of α‐bis(4‐aminophenyl)‐functionalized polystyrene, without the need for the isolation and purification of the polymeric precursor. The organic precursor compounds, the primary diamine‐functionalized 1,1‐diphenylethylene derivative and the functionalized polymers were characterized using 1H NMR, 13C NMR and Fourier transform infrared spectroscopy, size exclusion chromatography, thin‐layer chromatography and non‐aqueous titration measurements. © 2013 Society of Chemical Industry
Thermodynamic dissection of large‐scale domain motions coupled with ligand binding of enzyme I
Authors: Yun Young‐Joo , Choi Ban‐Seok , Kim Eun‐Hee , Suh Jeong‐Yong 
Published: September 2013

AbstractDomain motions are central to the biological functions of many proteins. The energetics of the motions, however, is often difficult to characterize when motions are coupled with the ligand binding. Here, we determined the thermodynamic parameters of individual domain motions and ligand binding of enzyme I (EI) using strategic domain‐deletion mutants that selectively removed particular motions. Upon ligand binding, EI employs two large‐scale domain motions, the hinge motion and the swivel motion, to switch between conformational states of distinct domain−domain orientations. Calorimetric analysis of the EI mutants separated the free energy changes of the binding and motions, demonstrating that the unfavorable hinge motion (ΔG = 1.5 kcal mol−1) was driven by the favorable swivel motion (ΔG = −5.2 kcal mol−1). The large free energy differences could be explained by the physicochemical nature of the domain interfaces associated with the motions; the hinge motion employed much narrower interface than the swivel motion without any hydrogen bonds or salt bridges. The small heat capacity further suggested that the packing of the domain interfaces associated with the hinge motion was less compact than that commonly observed in proteins. Lastly, thermodynamic analysis of phosphorylated EI suggests that the domain motions are regulated by the ligand binding and the phosphorylation states. Taken together, the thermodynamic dissection approach illustrates how multiple motions and ligand binding are energetically connected during the functional cycle of EI.
Glucuronidation of drugs in humanized UDP‐glucuronosyltransferase 1 mice: Similarity with glucuronidation in human liver microsomes
Authors: Kutsuno Yuki , Sumida Kyohei , Itoh Tomoo , Tukey Robert H. , Fujiwara Ryoichi 
Published: September 2013

AbstractUridine 5′‐diphosphate‐glucuronosyltransferases (UGTs) are phase II drug‐metabolizing enzymes that catalyze glucuronidation of various endogenous and exogenous substrates. Among 19 functional human UGTs, UGT1A family enzymes largely contribute to the metabolism of clinically used drugs. While the UGT1A locus is conserved in mammals such as humans, mice, and rats, species differences in drug glucuronidation have been reported. Recently, humanized UGT1 mice in which the original Ugt1 locus was disrupted and replaced with the human UGT1 locus (hUGT1 mice) have been developed. To evaluate the usefulness of hUGT1 mice to predict human glucuronidation of drugs, UGT activities, and inhibitory effects on UGTs were examined in liver microsomes of hUGT1 mice as well as in those of wild‐type mice and humans. Furosemide acyl‐glucuronidation was sigmoidal and best fitted to the Hill equation in hUGT1 mice and human liver microsomes, while it was fitted to the substrate inhibition equation in mouse liver microsomes. Kinetic parameters of furosemide glucuronidation were very similar between hUGT1 mice and human liver microsomes. The kinetics of S‐naproxen acyl‐glucuronidation and inhibitory effects of compounds on furosemide glucuronidation in hUGT1 liver microsomes were also slightly, but similar to those in human liver microsomes, rather than in wild‐type mice. While wild‐type mice lack imipramine and trifluoperazine N‐glucuronidation potential, hUGT1 mice showed comparable N‐glucuronidation activity to that of humans. Our data indicate that hUGT1 mice are promising tools to predict not only in vivo human drug glucuronidation but also potential drug‐drug interactions.
Atomistic modeling of dynamical quantum transport
Authors: Oppenländer Christian , Korff Björn , Frauenheim Thomas , Niehaus Thomas A. 
Published: September 2013

We present dynamical transport calculations based on a tight‐binding approximation to adiabatic time‐dependent density functional theory (TD‐DFTB). The reduced device density matrix is propagated through the Liouville–von Neumann equation. For the model system, 1,4‐benzenediol coupled to aluminum leads, we are able to confirm the equality of the steady state current resulting from a time‐dependent calculation to a static calculation in the conventional Landauer framework. We also investigate the response of the junction subjected to alternating bias voltages with frequencies up to the optical regime. Here we can clearly identify capacitive behaviour of the molecular device and a significant resonant enhancement of the conductance. The results are interpreted using an analytical single level model comparing the device transmission and admittance. In order to aid future calculations under alternating bias, we shortly review the use of Fourier transform techniques to obtain the full frequency response of the device from a single current trace.
Analysis of absorption enhancement in tailor‐made periodic polycrystalline silicon microarrays
Authors: Preidel Veit , Lockau Daniel , Sontheimer Tobias , Back Franziska , Rudigier‐Voigt Eveline , Rech Bernd , Becker Christiane 
Published: September 2013

AbstractWe present a design study of 3D photonic poly‐Si microarchitectures on 2 µm periodically textured glass substrates for application as absorber layers in crystalline Si thin‐film solar cells. Different arrays of microholes and microcones were fabricated in a low‐cost process, by combining high rate electron beam evaporation, nanoimprint technology and self‐organized solid phase crystallization. Two promising designs exhibiting strong absorption enhancement were identified by optical analysis. High angular acceptance and calculated maximum achievable short‐circuit current density of 27.6 mA/cm2 for an effective Si thickness of 1.1 µm highlight the optical potential of these microarchitectures as broadband absorbers in polycrystalline Si thin‐film solar cells.magnified imageTailor‐made 2 µm periodic polycrystalline silicon micro‐arrays on nanoimprint patterned glass substrates for an application as light harvesting architectures in polycrystalline Si thin‐film solar cells.(© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
GUIDING OUT‐MIGRATING JUVENILE SEA LAMPREY (PETROMYZON MARINUS) WITH PULSED DIRECT CURRENT
Authors: Johnson N. S. , Miehls S. 
Published: September 2013

ABSTRACTNon‐physical stimuli can deter or guide fish without affecting water flow or navigation and therefore have been investigated to improve fish passage at anthropogenic barriers and to control movement of invasive fish. Upstream fish migration can be blocked or guided without physical structure by electrifying the water, but directional downstream fish guidance with electricity has received little attention. We tested two non‐uniform pulsed direct current electric systems, each having different electrode orientations (vertical versus horizontal), to determine their ability to guide out‐migrating juvenile sea lamprey (Petromyzon marinus) and rainbow trout (Oncorhynchus mykiss). Both systems guided significantly more juvenile sea lamprey to a specific location in our experimental raceway when activated than when deactivated, but guidance efficiency decreased at the highest water velocities tested. At the electric field setting that effectively guided sea lamprey, rainbow trout were guided by the vertical electrode system, but most were blocked by the horizontal electrode system. Additional research should characterize the response of other species to non‐uniform fields of pulsed DC and develop electrode configurations that guide fish over a range of water velocity. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.