bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacological and pharmacokinetic properties of JNJ‐40411813, a positive allosteric modulator of the mGlu2 receptor
Authors: Lavreysen Hilde , Ahnaou Abdellah , Drinkenburg Wilhelmus , Langlois Xavier , Mackie Claire , Pype Stefan , Lütjens Robert , Le Poul Emmanuel , Trabanco Andrés A. , Nuñez José María Cid 
Published: December 2014

AbstractCompounds modulating metabotropic glutamate type 2 (mGlu2) receptor activity may have therapeutic benefits in treating psychiatric disorders like schizophrenia and anxiety. The pharmacological and pharmacokinetic properties of a novel mGlu2 receptor‐positive allosteric modulator (PAM), 1‐butyl‐3‐chloro‐4‐(4‐phenyl‐1‐piperidinyl)‐2(1H)‐pyridinone (JNJ‐40411813/ADX71149) are described here. JNJ‐40411813 acts as a PAM at the cloned mGlu2 receptor: EC50 = 147 ± 42 nmol/L in a [35S]GTPγS binding assay with human metabotropic glutamate type 2 (hmGlu2) CHO cells and EC50 = 64 ± 29 nmol/L in a Ca2+ mobilization assay with hmGlu2 Gα16 cotransfected HEK293 cells. [35S]GTPγS autoradiography on rat brain slices confirmed PAM activity of JNJ‐40411813 on native mGlu2 receptor. JNJ‐40411813 displaced [3H]JNJ‐40068782 and [3H]JNJ‐46281222 (mGlu2 receptor PAMs), while it failed to displace [3H]LY341495 (a competitive mGlu2/3 receptor antagonist). In rats, JNJ‐40411813 showed ex vivo mGlu2 receptor occupancy using [3H]JNJ‐46281222 with ED50 of 16 mg/kg (p.o.). PK‐PD modeling using the same radioligand resulted in an EC50 of 1032 ng/mL. While JNJ‐40411813 demonstrated moderate affinity for human 5HT2A receptor in vitro (Kb = 1.1 μmol/L), higher than expected 5HT2A occupancy was observed in vivo (in rats, ED50 = 17 mg/kg p.o.) due to a metabolite. JNJ‐40411813 dose dependently suppressed REM sleep (LAD, 3 mg/kg p.o.), and promoted and consolidated deep sleep. In fed rats, JNJ‐40411813 (10 mg/kg p.o.) was rapidly absorbed (Cmax 938 ng/mL at 0.5 h) with an absolute oral bioavailability of 31%. Collectively, our data show that JNJ‐40411813 is an interesting candidate to explore the therapeutic potential of mGlu2 PAMs, in in vivo rodents experiments as well as in clinical studies.
Genetic variation in aryl N‐acetyltransferase results in significant differences in the pharmacokinetic and safety profiles of amifampridine (3,4‐diaminopyridine) phosphate
Authors: Haroldsen Peter E. , Garovoy Marvin R. , Musson Donald G. , Zhou Huiyu , Tsuruda Laurie , Hanson Boyd , O'Neill Charles A. 
Published: December 2014

AbstractThe clinical use of amifampridine phosphate for neuromuscular junction disorders is increasing. The metabolism of amifampridine occurs via polymorphic aryl N‐acetyltransferase (NAT), yet its pharmacokinetic (PK) and safety profiles, as influenced by this enzyme system, have not been investigated. The objective of this study was to assess the effect of NAT phenotype and genotype on the PK and safety profiles of amifampridine in healthy volunteers (N = 26). A caffeine challenge test and NAT2 genotyping were used to delineate subjects into slow and fast acetylators for PK and tolerability assessment of single, escalating doses of amifampridine (up to 30 mg) and in multiple daily doses (20 mg QID) of amifampridine. The results showed that fast acetylator phenotypes displayed significantly lower Cmax, AUC, and shorter t1/2 for amifampridine than slow acetylators. Plasma concentrations of the N‐acetyl metabolite were approximately twofold higher in fast acetylators. Gender differences were not observed. Single doses of amifampridine demonstrated dose linear PKs. Amifampridine achieved steady state plasma levels within 1 day of dosing four times daily. No accumulation or time‐dependent changes in amifampridine PK parameters occurred. Overall, slow acetylators reported 73 drug‐related treatment‐emergent adverse events versus 6 in fast acetylators. Variations in polymorphic NAT corresponding with fast and slow acetylator phenotypes significantly affects the PK and safety profiles of amifampridine.
Chemical control of the Asian citrus psyllid and of huanglongbing disease in citrus
Authors: Boina Dhana Raj , Bloomquist Jeffrey R 
Published: December 2014

AbstractBy 2014, huanglongbing (HLB), the most destructive disease of citrus, and its insect vector, the Asian citrus psyllid (ACP), Diaphorina citri (Kuwayama), became established in all major citrus‐growing regions of the world, including the United States, with the exception of California. At present, application of insecticides is the most widely followed option for reducing ACP populations, while application of antibiotics for suppressing HLB disease/symptoms is being practiced in some citrus‐growing regions. Application of insecticides during the dormant winter season, along with cultivation of HLB‐free seedlings and early detection and removal of symptomatic and asymptomatic trees, has been very effective in managing ACP. Area‐wide management of ACP by application of insecticides at low volume in large areas of citrus cultivation has been shown to be effective in managing HLB and reducing management costs. As insecticide resistance is a major problem in sustainable management of ACP, rotation/alternation of insecticides with different chemistries and modes of action needs to be followed. Besides control of the insect vector, use of antibiotics has temporarily suppressed the symptoms of HLB in diseased trees. Recent efforts to discover and screen existing as well as new compounds for their antibiotic and antimicrobial activities have identified some promising molecules for HLB control. There is an urgent need to find a sustainable solution to the HLB menace through chemical control of ACP populations and within HLB‐infected trees through the judicious use of labeled insecticides (existing and novel chemistries) and antibiotics in area‐wide management programs with due consideration to the insecticide resistance problem. © 2014 Society of Chemical Industry
Analysis on the enhanced hole concentration in p‐type GaN grown by indium‐surfactant‐assisted Mg delta doping
Authors: Chen Yingda , Wu Hualong , Yue Guanglong , Chen Zimin , Zheng Zhiyuan , Wu Zhisheng , Wang Gang , Jiang Hao 
Published: December 2014

AbstractWe have investigated the influence of indium surfactant on the hole‐concentration enhancement in Mg‐delta‐doped p‐type GaN grown at 920 °C. The hole concentration can be effectively enhanced from 7.8 × 1017 cm−3 to 1.5 × 1018 cm−3 when introducing the indium surfactant into the delta‐doping process. Analysis by secondary ion mass spectroscopy and low‐temperature photoluminescence results indicates that the increase of hole concentration is primarily contributed from the improved Mg incorporation and the suppressed N vacancy induced by the indium surfactant, while the contribution from unintentional C, Si, and O impurities and Ga‐vacancy‐related defects can be ruled out. On the other hand, it is shown that the acceptor activation energy, deduced from the temperature‐dependent photoluminescence, is decreased by indium surfactant, which is another factor accounting for the enhanced hole concentration.
Free‐electron concentration and polarity inversion domains in plasmonic (Zn,Ga)O
Authors: Sadofev Sergey , Kalusniak Sascha , Schäfer Peter , Kirmse Holm , Henneberger Fritz 
Published: December 2014

AbstractHeavily Ga‐doped ZnO layers are grown on bulk ZnO wafers by molecular beam epitaxy. The layers grow in a two‐dimensional pseudomorphic mode with high structural quality under increase of the c‐lattice constant up to free‐electron concentrations of cm. Formation of Zn‐polar inversion domains in the O‐polar ZnO matrix is identified as the limiting factor for the incorporation of electrically active Ga. The domain formation can be inhibited by growing with larger excess of Zn. This results in a shift of surface plasmon frequency of meV and allows for covering the telecommunication wavelength range.
Classes of structures in the stable atmospheric boundary layer
Authors: Kang Yanfei , Belušić Danijel , Smith‐Miles Kate 
Published: December 2014

This article analyses ubiquitous flow structures which affect the dynamics of stable atmospheric boundary layers. These structures introduce non‐stationarity and intermittency to turbulent mixing, thus invalidating the usual scaling laws and numerical model parametrizations, but their characteristics and generating mechanisms are still generally unknown. Detecting these unknown events from time series requires techniques that do not assume particular geometries or amplitudes of the flow structures. We use a recently developed such method with some modifications to study the night‐time structures over a three‐month period during the FLOSSII experiment.The structures cover about 26% of the dataset, and can be categorized using clustering into only three classes with similar characteristics. The largest class, including about 50% of the events, contains smooth structures, often with wave‐like shapes, which occur in stronger winds and weak stability. The second class, including sharper structures with large kurtosis, is characterized by weaker winds and stronger stability. The smallest class, including about 20% of the events, contains predominantly sharp step‐like structures, or microfronts. They occur in the weakest winds with strong stability.Sharper, and particularly shallower, structures are related to transient low‐level wind maxima which create inflection points and may affect generation of turbulence. Furthermore, large wind directional shear, which is another source of transient inflection points, is generated even by deep coherent structures when the background wind is weaker than the structure intensity.These results show that the complexity of structures can be reduced for the purpose of further analysis using a proper classification. Mapping common characteristics of such events leads to their better understanding, which, if combined with similar analyses of other boundary‐layer data, could lead to improving their effects in numerical models.
Output feedback control of discrete‐time systems with self‐triggered controllers
Authors: Zhang Jinhui , Zhao Danyang , Zheng Wei Xing 
Published: December 2014

SummaryThis paper is concerned with the self‐triggered output feedback control for discrete‐time systems, where an updating instants scheduler is implemented to determine when the controller is updated. For both the full‐order and reduced‐order observer cases, the updating instants are determined, respectively, where only the information of the estimated state at the current updating instant is required to obtain the next updating instant. It is shown that, with the proposed self‐triggered control schemes, not only the updating frequency is significantly reduced, but also the uniform ultimate boundedness of the closed‐loop system is guaranteed. Finally, a numerical example is used to verify the effectiveness and the merits of the proposed approaches. Copyright © 2014 John Wiley & Sons, Ltd.
Structure‐function relationships of starch components
Authors: Vamadevan Varatharajan , Bertoft Eric 
Published: December 2014

AbstractStarch continues to be an important renewable biopolymer in both the food and non‐food industries. Its properties, which vary depending on the plant source, stem directly from its structure. The recent substantial increase in knowledge of the molecular structure of starch components and the architecture of starch granules has contributed significantly to an enhanced understanding of the structural base of starch functionality. This résumé provides an overview of the present views of the starch structure‐function relationships with an emphasis on industrially important starch sources.
Activation of 5‐HT receptors inhibits GABAergic transmission by pre‐and post‐synaptic mechanisms in layer II/III of the juvenile rat auditory cortex
Authors: García‐Oscos Francisco , Torres‐Ramírez Oswaldo , Dinh Lu , Galindo‐Charles Luis , Pérez Padilla Elsy Arlene , Pineda Juan Carlos , Atzori Marco , Salgado Humberto 
Published: December 2014

ABSTRACTThe specific mechanisms by which serotonin (5‐HT) modulates synaptic transmission in the auditory cortex are still unknown. In this work, we used whole‐cell recordings from layer II/III of pyramidal neurons in rat brain slices to characterize the influence of 5‐HT on inhibitory synaptic activity in the auditory cortex after pharmacological blockade of excitatory glutamatergic transmission. We found that bath application of 5‐HT (5 µM) reduced the frequency and amplitude of both spontaneous and miniature inhibitory postsynaptic currents (IPSCs), reduced the amplitude of evoked IPSCs, and enhanced facilitation of paired pulse ratio (PPR), suggesting presynaptic inhibition. To determine which the serotonin receptors were involved in this effect, we studied the influence of specific 5‐HT receptor agonists and antagonists on ɣ‐aminobutyric acid (GABA)ergic synaptic transmission. The inhibiting influence of 5‐HT in the GABAergic synaptic activity was mimicked by using the selective agonists of the 5‐HT1A and 5‐HT2A receptors, 8(OH)‐DPAT (10 µM) and DOI (10 µM), respectively; and it was prevented by their respective antagonists NAN‐190 (1 µM) and ritanserin (1 μM). Furthermore, the application of the selective agonist of 5‐HT1A receptors, 8‐(OH)‐DPAT (10 µM), produced PPR facilitation, while DOI application (5‐HT2A agonist) did not change the PPR. Moreover, the 5‐HT2A agonist reduced the amplitude of the IPSCs evoked by application of the selective GABA agonist, muscimol. These results suggest a presynaptic and postsynaptic reduction of GABAergic transmission mediated by 5‐HT1A and 5‐HT2A serotonergic receptors, respectively. Synapse 69:115–127, 2015.  © 2014 Wiley Periodicals, Inc.
Climate change and Chinese history: a review of trends, topics, and methods
Authors: Fan Ka‐wai 
Published: December 2014

The history of China is richly documented, and it is therefore possible to reconstruct the climatic characteristics of different historical periods using written records rather than other techniques. Historians, scientists, climatologists, and geographers have all considered climate change to explain macro‐historical issues. This paper provides a comprehensive review of the current research findings relating to the historical climatology of China, including the relationship between climate change and the dynastic conquest by northern nomads, wars, riots, dynastic decline, and changes in population, economy, and agriculture. This will provide a solid foundation for further developments in Chinese historical climatology.WIREs Clim Change2015, 6:225–238. doi: 10.1002/wcc.331This article is categorized under:Climate, History, Society, Culture > World Historical Perspectives
Advanced quality of services with security integration in wireless sensor networks
Authors: Rachedi Abderrezak , Hasnaoui Amina 
Published: December 2014

AbstractIn this paper, we focus on the coexistence between security and quality of services (QoS) guarantee in wireless sensor networks. The idea is to integrate the security services: authentication, integrity, confidentiality, and non‐repudiation with QoS guarantee. In literature, the major proposed solutions consider QoS and security separately. In addition, it has been shown that it is difficult to offer the end‐users multiple levels of security while offering a high level of QoS, because security and QoS are opposite parameters. To tackle this main issue, we propose a new model based on proportional integral derivative controller in order to dynamically select the security level adapted to QoS requirements while considering the energy consumption. The stability parameters in terms of security level and QoS are taken into account by using the principle of proportional integral derivative which is based on the past parameters (history), the current system state (present), and the predictable system change (future). In order to evaluate the proposed model, we consider the case of routing protocol, and we introduce this model into the well‐known ad‐hoc on‐demand distance vector (AODV) protocol called QwS‐AODV protocol. Unlike the classical secure AODV, the QwS‐AODV protocol aims at adding or removing security services dynamically according to the network performance. Moreover, the validation and the evaluation of the proposed solution are carried out by simulation. The performance evaluation is presented with different network parameters such as throughput, delay, energy consumption, and security services. In addition, the comparison with a classical secure AODV is carried out, and the results obtained with the simulation illustrate that the security is always ensured with lower costs in terms of QoS and energy consumption. Copyright © 2014 John Wiley & Sons, Ltd.
Item Response Models for Forced-Choice Questionnaires: A Common Framework
Authors: Brown Anna 
Published: December 2014

In forced-choice questionnaires, respondents have to make choices between two or more items presented at the same time. Several IRT models have been developed to link respondent choices to underlying psychological attributes, including the recent MUPP (Stark et al. in Appl Psychol Meas 29:184–203, 2005) and Thurstonian IRT (Brown and Maydeu-Olivares in Educ Psychol Meas 71:460–502, 2011) models. In the present article, a common framework is proposed that describes forced-choice models along three axes: (1) the forced-choice format used; (2) the measurement model for the relationships between items and psychological attributes they measure; and (3) the decision model for choice behavior. Using the framework, fundamental properties of forced-choice measurement of individual differences are considered. It is shown that the scale origin for the attributes is generally identified in questionnaires using either unidimensional or multidimensional comparisons. Both dominance and ideal point models can be used to provide accurate forced-choice measurement; and the rules governing accurate person score estimation with these models are remarkably similar.
Fabric Softener Technology: A Review
Authors: Murphy Dennis S. 
Published: December 2014

AbstractThis paper reviews current and emerging fabric softener technologies including various benefits that can be achieved by manipulating quat active structure, polymer/quat active combination systems, single rinse products, consumer product forms, softening‐through‐the‐wash, and fragrances used in fabric softeners. The technologies reviewed are aimed at the consumer market. Insights are provided into the drivers behind the technologies as well as their influence on market trends.
A randomized noninferiority trial of condensed protocols for genetic risk disclosure of Alzheimer's disease
Authors: Green Robert C. , Christensen Kurt D. , Cupples L. Adrienne , Relkin Norman R. , Whitehouse Peter J. , Royal Charmaine D.M. , Obisesan Thomas O. , Cook‐Deegan Robert , Linnenbringer Erin , Butson Melissa Barber , Fasaye Grace‐Ann , Levinson Elana , Roberts J. Scott ,   REVEAL Study Group
Published: December 2014

AbstractIntroductionConventional multisession genetic counseling is currently recommended when disclosing apolipoprotein E (APOE) genotype for the risk of Alzheimer's disease (AD) in cognitively normal individuals. The objective of this study was to evaluate the safety of brief disclosure protocols for disclosing APOE genotype for the risk of AD.MethodsA randomized, multicenter noninferiority trial was conducted at four sites. Participants were asymptomatic adults having a first‐degree relative with AD. A standard disclosure protocol by genetic counselors (SP‐GC) was compared with condensed protocols, with disclosures by genetic counselors (CP‐GC) and by physicians (CP‐MD). Preplanned co‐primary outcomes were anxiety and depression scales 12 months after disclosure.ResultsThree hundred and forty‐three adults (mean age 58.3, range 33–86 years, 71% female, 23% African American) were randomly assigned to the SP‐GC protocol (n = 115), CP‐GC protocol (n = 116), or CP‐MD protocol (n = 112). Mean postdisclosure scores on all outcomes were well below cut‐offs for clinical concern across protocols. Comparing CP‐GC with SP‐GC, the 97.5% upper confidence limits at 12 months after disclosure on co‐primary outcomes of anxiety and depression ranged from a difference of 1.2 to 2.0 in means (all P < .001 on noninferiority tests), establishing noninferiority for condensed protocols. Results were similar between European Americans and African Americans.ConclusionsThese data support the safety of condensed protocols for APOE disclosure for those free of severe anxiety or depression who are actively seeking such information.
The transitional association between β‐amyloid pathology and regional brain atrophy
Authors: Insel Philip S. , Mattsson Niklas , Donohue Michael C. , Mackin R. Scott , Aisen Paul S. , Jack Clifford R. , Shaw Leslie M. , Trojanowski John Q. , Weiner Michael W. ,   Alzheimer's Disease Neuroimaging Initiative
Published: December 2014

AbstractIntroductionAlzheimer's disease (AD) is characterized by the accumulation of β‐amyloid (Aβ) associated with brain atrophy and cognitive decline. The functional form to model the association between Aβ and regional brain atrophy has not been well defined. To determine the relationship between Aβ and atrophy, we compared the performance of the usual dichotomization of cerebrospinal fluid (CSF) Aβ to identify subjects as Aβ+ and Aβ− with a trilinear spline model of CSF Aβ.MethodsOne hundred and eighty‐three subjects with mild cognitive impairment and 108 cognitively normal controls with baseline CSF Aβ and up to 4 years of longitudinal magnetic resonance imaging data from the Alzheimer's Disease Neuroimaging Initiative were analyzed using mixed‐effects regression. Piecewise‐linear splines were used to evaluate the nonlinear nature of the association between CSF Aβ and regional atrophy and to identify points of acceleration of atrophy with respect to Aβ. Several parameterizations of CSF Aβ were compared using likelihood ratio tests and the Akaike information criterion. Periods of acceleration of atrophy in which subjects transition from CSF Aβ negativity to CSF Aβ positivity were estimated from the spline models and tested for significance.ResultsSpline models resulted in better fits for many temporal and parietal regions compared with the dichotomous models. The trilinear model showed that periods of acceleration of atrophy varied greatly by region with early changes seen in the insula, amygdala, precuneus, hippocampus, and other temporal regions, occurring before the clinical threshold for CSF Aβ positivity.DiscussionThe use of piecewise‐linear splines provides an improved model of the nonlinear association between CSF Aβ and regional atrophy in regions implicated in the progression of AD. The important biological finding of this work is that some brain regions show periods of accelerated volume loss well before the CSF Aβ42 threshold. This implies that signs of brain atrophy develop before the current conventional definition of “preclinical AD”.
CHOOSING EXPERT STATISTICAL ADVICE: PRACTICAL COSTS AND EPISTEMIC JUSTIFICATION
Authors: González De Prado Salas Javier , Teira David 
Published: December 2014

AbstractWe discuss the role of practical costs in the epistemic justification of a novice choosing expert advice, taking as a case study the choice of an expert statistician by a lay politician. First, we refine Goldman's criteria for the assessment of this choice, showing how the costs of not being impartial impinge on the epistemic justification of the different actors involved in the choice. Then, drawing on two case studies, we discuss in which institutional setting the costs of partiality can play an epistemic role. This way we intend to show how the sociological explanation of the choice of experts can incorporate its epistemic justification.