bluuebunny/crossref_metadata_2025 huggingface dataset:
Gas-Phase Spectroscopy of a Vinylheptafulvene Chromophore
Authors: Elm Jonas , Stockett Mark H. , Houmøller Jørgen , Petersen Michael Åxman , Mikkelsen Kurt V. , Nielsen Mogens Brøndsted , Nielsen Steen Brøndsted
Published: May 2015

The intrinsic spectral properties of the dihydroazulene (DHA)/vinylheptafulvene (VHF) photo/thermoswitch, free of solvent interactions, were investigated both experimentally and theoretically. A quaternary ammonium group was incorporated via an ethylene bridge to allow for the transfer of charged molecules to the gas phase by electrospray ionization, leaving the chromophore part itself neutral. Absorption by the two isomers was identified from ion dissociation (i.e., action spectroscopy) using a home-built sector instrument. Several fragment ions were observed, and dissociation occurred both at the charge tag side chain and at the chromophore unit itself. We measured an absorption band of VHF with a maximum at 430 ± 20 nm (2.9 eV ± 0.1 eV) but no band was discernible for the DHA in the visible region. This shows that little interconversion between the two isomers occurs during the electrospray and the subsequent trapping in an octopole for 25 ms; the latter is needed to produce ion bunches for spectroscopy where a pulsed laser system is used. For comparison, density functional theoretical calculations predicted lowest-energy vertical excitations of 3.33 eV to 3.48 eV for the DHA and 3.02 eV to 3.08 eV for the VHF (the ranges are based on the use of different functionals), which correspond to a maximal deviation between theory and experiment of 0.1 eV in the case of the VHF. The absorption by the bare ions is significantly blue-shifted compared to that by VHF in acetonitrile solution (2.64 eV), but similar within the experimental uncertainty to that by VHF in cyclohexane (2.78 eV); the transition, therefore has a significant charge-transfer character. Finally, we find that the absorption of two photons is needed to cause fragmentation of the VHF on the microsecond time scale, which indicates that prompt fragmentation from the electronically excited state or prior to the intramolecular vibrational redistribution of the excess energy plays no role. This is of particular importance for the use of the photosystem in advanced materials or molecular electronics where high photostability is required to allow for numerous isomerization cycles.
Newsvendor Selling to Loss-Averse Consumers with Stochastic Reference Points
Authors: Baron Opher , Hu Ming , Najafi-Asadolahi Sami , Qian Qu
Published: May 2015

We study a newsvendor who sells a perishable asset over repeated periods to consumers with a given consumption valuation for the product. The market size in each period is random, following a stationary distribution. Consumers are loss averse with stochastic reference points that represent their beliefs about possible price and product availability. Given the distribution of reference points, they choose purchase plans to maximize their expected total utility, including gain-loss utility, before visiting the store, and follow the plans in the store. In anticipation of consumers' purchase plans, in each period, before demand uncertainty resolves, the firm chooses an initial order quantity. After the uncertainty resolves, the firm chooses a contingent price depending on the demand realization, with the option of clearing inventory by charging a sale price, and otherwise, posting a full price. Over repeated periods, the interaction of the firm’s operational decisions about ordering and contingent pricing and the consumers' purchase actions results in a distribution of reference points, and, in equilibrium, this distribution is consistent with consumers' beliefs. Under this framework of endogenized reference points, we fully characterize the firm’s optimal inventory and contingent pricing policies. We identify conditions under which the firm’s expected price and profit are increasing in the consumer loss aversion level. We also show that the firm can prefer demand variability over no-demand uncertainty. We obtain a set of insights into how consumers' loss aversion affects the firm’s optimal operational policies that are in stark contrast to those obtained in classic newsvendor models. As examples, the optimal full price increases in the initial order quantity; and the optimal full price decreases, while the optimal sales frequency increases, in the procurement cost.
Joint Selling of Complementary Components Under Brand and Retail Competition
Authors: He Yuhong , Yin Shuya
Published: May 2015

Suppliers of complementary goods often package their items together when selling to downstream retailers. One motivation behind this behavior is to reduce double marginalization through coordinated pricing so that system efficiency is improved and individual members can also benefit. The objective of this paper is to understand how competition in supply chains would impact such joint selling partnerships among complementary suppliers. We first model competition at the supply level, which is generated from the existence of multiple partially substitutable brands (or suppliers) for a particular component. We then extend the analysis to a model that also involves retail competition caused by decentralization among retailers who assemble suppliers' components into final products and sell to customers. The analysis of a model with two complementary components, one of which has multiple brands, indicates that the supply-level competition discourages joint selling of complementary goods. That is, when competing brands become more alike (or substitutable), complementary suppliers act more independently in pricing and selling their items. However, retail competition leads to an opposite effect: Competition among retailers would actually encourage complementary suppliers to package their goods together and act jointly.
Inventory Models with Shelf-Age and Delay-Dependent Inventory Costs
Authors: Federgruen Awi , Wang Min
Published: May 2015

In this paper, we show how any model with a general shelf-age-dependent holding cost and delay-dependent backlogging cost structure may be transformed into an equivalent model in which all expected inventory costs are level dependent. We develop our equivalency results, first, for periodic review models with full backlogging of stockouts. These equivalency results permit us to characterize the optimal procurement strategy in various settings and to adopt known algorithms to compute such strategies. For models in which all or part of stockouts are lost, we show that the addition of any shelf-age and delay-dependent cost structure does not complicate the structure of the model beyond what is required under the simplest, i.e., linear, holding and backlogging costs. We proceed to show that our results carry over to continuous review models, with demands generated by compound renewal processes; the continuous review models with shelf-age and delay-dependent carrying and backlogging costs are shown to be equivalent to periodic review models with convex level-dependent inventory cost functions.
A Constructive Approach to Estimating Pure Characteristics Demand Models with Pricing
Authors: Pang Jong-Shi , Su Che-Lin , Lee Yu-Ching
Published: May 2015

Discrete-choice demand models are important and fundamental tools for understanding consumers’ choice behavior and for analyzing firms’ operations and pricing strategies. In these models, products are often described as a vector of observed characteristics. A consumer chooses the product that maximizes her utility, assumed to be a function of the observed product characteristics and the consumer’s preference over these product characteristics. One central task in the demand estimation literature is to infer, based on observed data, consumers’ preferences on product characteristics. We consider such an estimation problem for pure characteristics models, a class of random coefficients demand models without the idiosyncratic logit error term in a consumer’s utility function. The absence of the logit error term and the use of numerical integration to approximate the integral in aggregate market shares lead to a nonsmooth formulation of approximated market share equations. As a result, solving the approximated market share equations and estimating the model by using existing methods proposed in the econometrics literature remain computationally intractable. To overcome this difficulty, we first characterize consumers’ purchase decisions by a system of complementarity constraints. This new characterization leads to smooth approximated market share equations and allows us to cast the corresponding generalized method of moments (GMM) estimation problem essentially as a quadratic program with linear complementarity constraints, parameterized by an exponential, thus nonlinear, function of the structural parameter on price. We also extend this estimation framework to incorporate an endogenous pricing mechanism that captures the competitive profit maximization behavior of the producing firms. We provide existence results of a solution for the GMM estimator and present numerical results to demonstrate the computational effectiveness of our approach.
Multi-Product Price and Assortment Competition
Authors: Federgruen Awi , Hu Ming
Published: May 2015

We address a generic price competition model in an industry with an arbitrary number of competitors, each offering all or a subset of a given line of N products. The products are substitutes in the sense that the demand volume of each product weakly increases whenever the price of another product increases. The cost structure is linear, with arbitrary cost rates. Our demand model is the unique regular extension of a set of demand functions that are affine in a limited polyhedral subset of the price space. A set of demand functions is regular if it satisfies the following conditions: Under any given price vector, when some product is priced out of the market, i.e., has zero demand, any increase of its price has no impact on the demand volumes. Depending on the set of prices selected by the competing firms, a different product assortment is offered in the market. We characterize the equilibrium prices, product assortment, and sales volumes in the price competition model, under this demand model. Under minimal conditions, we show that a pure Nash equilibrium always exists; while multiple price equilibria may arise, they are equivalent in the sense of generating an identical product assortment and sales volumes.
Clinical use of cold atmospheric pressure argon plasma in chronic leg ulcers: A pilot study
Authors: Ulrich C. , Kluschke F. , Patzelt A. , Vandersee S. , Czaika V.A. , Richter H. , Bob A. , Hutten J. von , Painsi C. , Hüge R. , Kramer A. , Assadian O. , Lademann J. , Lange-Asschenfeldt B.
Published: May 2015

Objective:

In the age of multiresistant microbes and the increasing lack of efficient antibiotics, conventional antiseptics play a critical role in the prevention and therapy of wound infections. Recent studies have demonstrated the antiseptic effects of cold atmospheric pressure plasma (APP). In this pilot, study we investigate the overall suitability of one of the first APP sources for wound treatment focusing on its potential antimicrobial effects.

Method:

The wound closure rate and the bacterial colonisation of the wounds were investigated. Patients suffering from chronic leg ulcers were treated in a clinical controlled monocentric trial with either APP or octenidine (OCT). In patients who presented with more than one ulceration in different locations, one was treated with APP and the other one with OCT. Each group was treated three times a week over a period of two weeks. The antimicrobial efficacy was evaluated immediately after and following two weeks of treatment.

Results:

Wounds treated with OCT showed a significantly higher microbial reduction (64%) compared to wounds treated with APP (47%) immediately after the treatment. Over two weeks of antiseptic treatment the bacterial density was reduced within the OCT group (-35%) compared to a slight increase in bacterial density in the APP-treated group (+12%). Clinically, there were no signs of delayed wound healing observed in either group and both treatments were well tolerated.

Conclusion:

The immediate antimicrobial effects of the APP prototype source were almost comparable to OCT without any signs of cytotoxicity. This pilot study is limited by current configurations of the plasma source, where the narrow plasma beam made it difficult to cover larger wound surface areas and in order to avoid untreated areas of the wound bed, smaller wounds were assigned to the APP-treatment group. This limits the significance of AAP-related effects on the wound healing dynamics, as smaller wounds tend to heal faster than larger wounds. However, clinical wound healing studies on a larger scale now seem justifiable. A more advanced plasma source prototype allowing the treatment of larger wounds will address APP's influence on healing dynamics, synergetic treatment with current antiseptics and effects on multiresistant bacteria.
Multilayer Aluminum Thin Films as Effective Encapsulation for Flexible Organic Devices
Authors: Dollinger Felix , Nehm Frederik , Müller-Meskamp Lars , Leo Karl
Published: May 2015

Thin film organic devices like organic solar cells require encapsulation against water vapor. Depending on the device, water vapor transmission rates (WVTR) in the range of $10^{-5}\cdot g/(m^2\cdot day)$ are needed for lifetimes of at least five years. In this work we aim at improving the encapsulation properties of opaque vacuum-evaporated aluminum back-electrodes to fulfill these barrier requirements. Water diffusion through aluminum layers is defect-driven. To reduce defect densities, the growt h behavior of the aluminum layer is modified by underlying metallic seed-layers which have shown improved performance in transparent metal thin-film electrodes. Significant improvement of WVTR can be achieved with multilayer structures. Thin interlayers that decouple the defect positions in consecutive aluminum layers provide long and tortuous diffusion-paths for water-molecules. In our study, we use the electrical calcium-test to investigate stacks of aluminum layers with various interlayers with respect to steady-state WVTR and lag-time. The interlayers consist of different planarizing, diffusion-limiting, or getter materials that absorb water-molecules as they diffuse through the barrier. These optimized aluminum multilayers are promising candidates for organic thin-film encapsulation.
A multi agent based system to enable dynamic vehicle routing
Authors: Aragão Dmontier Pinheiro , Novaes Antônio Galvão , Mendes Luna Mônica Maria
Published: May 2015

A realização das atividades de transporte comumente envolve diferentes atores e veículos dispersos numa rede, de forma que responder aos eventos dinâmicos presentes nas operações é uma tarefa complexa. Neste contexto, o uso de sistemas baseados em agentes (MAS) na tomada de decisões autônoma tem se mostrado potencialmente interessante e sido discutido na literatura recente. Neste artigo, é apresentado um sistema baseado em agentes para lidar com o problema de roteirização dinâmica de veículos, mais precisamente em um problema de coleta de peças e componentes, onde parte das tarefas previamente alocadas ao veículo pode ser eventualmente transferida para outros veículos, sempre que o MAS constatar que o tempo de ciclo pode exceder o limite diário da jornada de trabalho. A transferência das tarefas entre agentes é realizada através do método de negociação de Vickrey. O sistema proposto permite tomada de decisão de forma colaborativa entre os agentes envolvidos, permitindo a realização de ajustes durante a realização da rota inicial.
O transporte e a consolidação de um campus regional no interior do nordeste
Authors: Meira Leonardo Herszon , Andrade Maurício Oliveira de , Maia Maria Leonor Alves , Brasileiro Anísio
Published: May 2015

A política de interiorização das Instituições Federais de Ensino Superior ocorrida nos últimos 10 anos no Brasil possibilitou a abertura de 2 novos campi da Universidade Federal de Pernambuco em municípios do interior do Estado.
Observa-se, no entanto, que essas estruturas foram instaladas em municípios que ofertam, de forma precária, serviços de transporte urbano e regional, impactando no acesso dos usuários a essas estruturas e afetando o desempenho acadêmico dos estudantes. Este trabalho investiga as condições de mobilidade ao Centro Acadêmico do Agreste – CAA, cujas atividades iniciaram em 2006. Foram realizadas seis pesquisas de campo: de contagem de veículos; de pessoas; de origem/destino; de opinião no transporte público; de opinião no transporte fretado; e de sobe-e-desce. Como principal resultado, aponta-se a atratividade do transporte fretado e sua importância para a consolidação do campus regional, com tempos de deslocamento semelhantes aos outros modos, para viagens até 40 km, sendo também vantajoso para viagens maiores. O transporte fretado
ainda possibilita a utilização do CAA por residentes em cidades até 100 km, sem forçar a mudança de moradia para locais mais próximos.
Efeitos em preço do compartilhamento de voos de companhias aéreas como reação à presença de um competidor de baixo custo
Authors: Costa Wellington Carlos , Oliveira Alessandro Vinícius Marques
Published: May 2015

Este trabalho analisa os efeitos concorrenciais de um tipo de aliança estratégica que vem recebendo maior atenção por parte das companhias aéreas: o acordo de compartilhamento de voos (Codesharing). Busca avaliar os efeitos em preços gerados com a implementação do codesharing quando efetuado entre duas grandes companhias aéreas incumbentes frente à entrada de um competidor de operação de custo baixo (Low Cost Carrier), tema ainda não explorado na literatura. Para isso, foi desenvolvida uma modelagem econométrica com emprego de estimador de efeitos fixos para aplicação em um estudo de caso evidenciado no início dos anos 2000, o “Codeshare Varig-TAM”. O modelo investiga os efeitos no preço das passagens das empresas incumbentes após entrada do competidor Low Cost. Os resultados indicam reduções do preço médio em todos os casos. Para condições em que não existia o codeshare implementado, a redução de preços era 12,4%. Por outro lado, quando o codeshare já estava em vigor, a redução foi apenas 8,3%. Estes resultados permitem inferir que o codeshare, pode ser uma ferramenta estratégica das grandes empresas para suavizar a ação de redução de preços (e perdas de lucratividade) quando competindo diretamente com Low Cost Carriers.
Variáveis que influenciam no uso da bicicleta e as crenças da teoria do comportamento planejado
Authors: Da Silveira Mariana Oliveira , Maia Maria Leonor Alves
Published: May 2015

Pesquisas sobre bicicleta que trabalham o componente ‘comportamento’ vêm ganhando destaque no intuito de entender as barreiras e os motivadores ao uso deste modo de transporte e ajudam a planejar melhores formas de estimular seu uso. O objetivo deste artigo é apresentar um panorama das variáveis que influenciam no uso da bicicleta e classificá-las junto às crenças e constructos da Teoria do Comportamento Planejado (TCP). Este panorama foi baseado em pesquisa da base SCOPUS e em artigos de anais e periódicos, teses e dissertações nacionais, o qual, além de enumerar fatores que influenciam no uso da bicicleta, servirá de apoio às pesquisas que pretendem aplicar a Teoria do Comportamento Planejado na avaliação de comportamentos de uso deste modo de transporte. As variáveis ‘tempo de deslocamento com o uso da bicicleta’, ‘condições meteorológicas’, ‘segurança do trânsito’, ‘infraestrutura cicloviária’ e ‘comportamento no trânsito entre motoristas e ciclistas’ foram as que mais se destacaram, de acordo com o levantamento bibliográfico, na interferência de intenção e de comportamento de uso da bicicleta.

  
A Process for Keeping Pace with Evolving Web Mapping Technologies
Authors: Roth Robert E. , Donohue Richard G. , Sack Carl M. , Wallace Timothy R. , Buckingham Tanya M. A.
Published: May 2015

The current pace of technological innovation in web mapping offers new opportunities and creates new challenges for web cartographers. The continual development of new technological solutions produces a fundamental tension: the more flexible and expansive web mapping options become, the more difficult it is to maintain fluency in the teaching and application of these technologies. We addressed this tension by completing a three-stage, empirical process for understanding how best to learn and implement contemporary web mapping technologies. To narrow our investigation, we focused upon education at the university level, rather than a professional production environment, and upon open-source client-side web mapping technologies, rather than complementary server-side or cloud-based technologies. The process comprised three studies: (1) a competitive analysis study of contemporary web mapping technologies, (2) a needs-assessment survey of web map designers/developers regarding past experiences with these technologies, and (3) a diary study charting the implementation of a subset of potentially viable technologies, as identified through the first two studies. The process successfully achieved the practical goal of identifying a candidate set of web mapping technologies for teaching web mapping, and also revealed broader insights into web map design and education generally as well as ways to cope with evolving web mapping technologies.
Pushing Wittgenstein and Quine Closer Together
Authors: Kemp Gary
Published: May 2015

As against the view represented here by Peter Hacker and John Canfield, I urge that the philosophies of Quine and Wittgenstein can be reconciled. Both replace the orthodox view of language as resting on reference: Quine with the notion of linguistic disposition, Wittgenstein with the notions of grammar and forms of life. I argue that Wittgenstein's insistence, in the rule-following discussion, that at bottom these are matters of practice, of ‘what we do’, is not only compatible in a rough sort of way with Quine's outlook, but is very close to Quine's naturalistic view of language. And I argue that the likely objections to this can on the one hand be explained away as Quine's having been interested in a very narrow slice of language in comparison with Wittgenstein, and on the other by a failure to take into account later developments in Quine’s views.
Frege’s Performative Argument Against Truth Relativism
Authors: Greimann Dirk
Published: May 2015

The purpose of this paper is to reconstruct Frege’s argument against the relativity of truth contained in his posthumous writing Logic from 1897. Two points are made. The first is that the argument is a performative version of the common objection that truth relativism is incoherent: it is designed to show that the assertion of the relativity of truth involves a performative incoherence, because the absoluteness of truth is a success condition for making assertions. From a modern point of view, the central premise of the argument, that the successful making of assertions depends on the absoluteness of truth, is highly doubtful. The second point is that this premise can be made plausible within the framework of Frege’s conception of truth and assertion: it can be derived from his thesis that, in order to put something forward as true, we do not need the word ‘true’, but only the assertoric force.
Michael Beaney (ed.), The Oxford Handbook of the History of Analytic Philosophy
Authors: Korhonen Anssi
Published: May 2015

Michael Beaney (ed.) The Oxford Handbook of the History of Analytic Philosophy. Oxford: Oxford University Press, 2013. 1161 pp.ISBN: 978–0–19–923884–2.
Physical Demands of Multimodal Training Competitions and Their Relationship to Measures of Performance
Authors: Jagim Andrew R. , Rader Owen , Jones Margaret T. , Oliver Jonathan M.
Published: May 2015

Jagim, AR, Rader, O, Jones, MT, and Oliver, JM. Physical demands of multimodal training competitions and their relationship to measures of performance. J Strength Cond Res 31(5): 1212–1220, 2017—The purpose of this study was to identify the physical demands of multimodal training (MMT) competitions and to determine the extent of their relationship to select measures of performance. Eighteen (>1.5 years of strength training experience) men (n = 10) and women (n = 8) (mean ± SD; age: 37.8 ± 10.6 years, height: 172.8 ± 8 cm, weight: 77.4 ± 13.2 kg, 16.6 ± 6% body fat) with experience performing MMT participated in a simulated MMT competition. All participants were assessed for body composition, countermovement vertical jump, and aerobic capacity during baseline testing. All participants then participated in a simulated MMT-style competition on a separate day within 10 days of baseline testing. The simulated MMT-style competition consisted of 3 events with 90 minutes of recovery allowed in between events. During the events, changes in blood lactate (La), heart rate (HR), and estimated V̇o
2 were recorded. Bivariate (Pearson) correlations were computed to determine if a relationship existed between traditional measures of performance and those of the MMT-style competition. Significance was set at p ≤ 0.05. Mean change in La ranged between 9 and 12 mmol·L−1 during the events. Mean HR and estimated V̇o
2 values ranged from 145 to 172 b·min−1 and 24 to 35 ml·kg−1·min−1, respectively, during the events. A strong correlation was observed (r = −0.722; p < 0.001) between aerobic capacity and time to completion for event 1. There was a strong correlation between lean body mass and lower-body strength performance (r = 0.882; p < 0.001) and time to completion for event 3 (r = −0.792; p < 0.001). A strong correlation was observed between lower-body power and time to completion for event 1 (r = −0.755; p < 0.001) and event 3 (r = −0.818; p < 0.001). Based on the results of this study, MMT-style competitions appear to be physically demanding activities performed at a high intensity with a great involvement of the anaerobic energy system and that some measures of aerobic capacity and power correlate with performance. When training for MMT-style competitions, it may be beneficial to focus on improving lower-body power and/or aerobic capacity.
Neurons in the Primate Medial Basal Forebrain Signal Combined Information about Reward Uncertainty, Value, and Punishment Anticipation
Authors: Monosov Ilya E. , Leopold David A. , Hikosaka Okihide
Published: May 2015

It has been suggested that the basal forebrain (BF) exerts strong influences on the formation of memory and behavior. However, what information is used for the memory-behavior formation is unclear. We found that a population of neurons in the medial BF (medial septum and diagonal band of Broca) of macaque monkeys encodes a unique combination of information: reward uncertainty, expected reward value, anticipation of punishment, and unexpected reward and punishment. The results were obtained while the monkeys were expecting (often with uncertainty) a rewarding or punishing outcome during a Pavlovian procedure, or unexpectedly received an outcome outside the procedure.In vivoanterograde tracing using manganese-enhanced MRI suggested that the major recipient of these signals is the intermediate hippocampal formation. Based on these findings, we hypothesize that the medial BF identifies various contexts and outcomes that are critical for memory processing in the hippocampal formation.
The Specification of Cortical Subcerebral Projection Neurons Depends on the Direct Repression of TBR1 by CTIP1/BCL11a
Authors: Cánovas José , Berndt F. Andrés , Sepúlveda Hugo , Aguilar Rodrigo , Veloso Felipe A. , Montecino Martín , Oliva Carlos , Maass Juan C. , Sierralta Jimena , Kukuljan Manuel
Published: May 2015

The acquisition of distinct neuronal fates is fundamental for the function of the cerebral cortex. We find that the development of subcerebral projections from layer 5 neurons in the mouse neocortex depends on the high levels of expression of the transcription factor CTIP1; CTIP1 is coexpressed with CTIP2 in neurons that project to subcerebral targets and with SATB2 in those that project to the contralateral cortex. CTIP1 directly repressesTbr1in layer 5, which appears as a critical step for the acquisition of the subcerebral fate. In contrast, lower levels of CTIP1 in layer 6 are required for TBR1 expression, which directs the corticothalamic fate. CTIP1 does not appear to play a critical role in the acquisition of the callosal projection fate in layer 5. These findings unravel a key step in the acquisition of cell fate for closely related corticofugal neurons and indicate that differential dosages of transcriptions factors are critical to specify different neuronal identities.
Increased Prefrontal Cortex Neurogranin Enhances Plasticity and Extinction Learning
Authors: Zhong Ling , Brown Joshua , Kramer Audra , Kaleka Kanwardeep , Petersen Amber , Krueger Jamie N. , Florence Matthew , Muelbl Matthew J. , Battle Michelle , Murphy Geoffrey G. , Olsen Christopher M. , Gerges Nashaat Z.
Published: May 2015

Increasing plasticity in neurons of the prefrontal cortex (PFC) has been proposed as a possible therapeutic tool to enhance extinction, a process that is impaired in post-traumatic stress disorder, schizophrenia, and addiction. To test this hypothesis, we generated transgenic mice that overexpress neurogranin (a calmodulin-binding protein that facilitates long-term potentiation) in the PFC. Neurogranin overexpression in the PFC enhanced long-term potentiation and increased the rates of extinction learning of both fear conditioning and sucrose self-administration. Our results indicate that elevated neurogranin function within the PFC can enhance local plasticity and increase the rate of extinction learning across different behavioral tasks. Thus, neurogranin can provide a molecular link between enhanced plasticity and enhanced extinction.
Inhibitory Interneurons That Express GFP in thePrP-GFPMouse Spinal Cord Are Morphologically Heterogeneous, Innervated by Several Classes of Primary Afferent and Include Lamina I Projection Neurons among Their Postsynaptic Targets
Authors: Ganley Robert P. , Iwagaki Noboru , del Rio Patricia , Baseer Najma , Dickie Allen C. , Boyle Kieran A. , Polgár Erika , Watanabe Masahiko , Abraira Victoria E , Zimmerman Amanda , Riddell John S. , Todd Andrew J.
Published: May 2015

The superficial dorsal horn of the spinal cord contains numerous inhibitory interneurons, which regulate the transmission of information perceived as touch, pain, or itch. Despite the importance of these cells, our understanding of their roles in the neuronal circuitry is limited by the difficulty in identifying functional populations. One group that has been identified and characterized consists of cells in the mouse that express green fluorescent protein (GFP) under control of the prion protein (PrP) promoter. Previous reports suggested that PrP-GFP cells belonged to a single morphological class (central cells), received inputs exclusively from unmyelinated primary afferents, and had axons that remained in lamina II. However, we recently reported that the PrP-GFP cells expressed neuronal nitric oxide synthase (nNOS) and/or galanin, and it has been shown that nNOS-expressing cells are more diverse in their morphology and synaptic connections. We therefore used a combined electrophysiological, pharmacological, and anatomical approach to reexamine the PrP-GFP cells. We provide evidence that they are morphologically diverse (corresponding to “unclassified” cells) and receive synaptic input from a variety of primary afferents, with convergence onto individual cells. We also show that their axons project into adjacent laminae and that they target putative projection neurons in lamina I. This indicates that the neuronal circuitry involving PrP-GFP cells is more complex than previously recognized, and suggests that they are likely to have several distinct roles in regulating the flow of somatosensory information through the dorsal horn.
Neurons Forming Optic Glomeruli Compute Figure–Ground Discriminations inDrosophila
Authors: Aptekar Jacob W. , Keleş Mehmet F. , Lu Patrick M. , Zolotova Nadezhda M. , Frye Mark A.
Published: May 2015

Many animals rely on visual figure–ground discrimination to aid in navigation, and to draw attention to salient features like conspecifics or predators. Even figures that are similar in pattern and luminance to the visual surroundings can be distinguished by the optical disparity generated by their relative motion against the ground, and yet the neural mechanisms underlying these visual discriminations are not well understood. We show in flies that a diverse array of figure–ground stimuli containing a motion-defined edge elicit statistically similar behavioral responses to one another, and statistically distinct behavioral responses from ground motion alone. From studies in larger flies and other insect species, we hypothesized that the circuitry of the lobula—one of the four, primary neuropiles of the fly optic lobe—performs this visual discrimination. Using calcium imaging of input dendrites, we then show that information encoded in cells projecting from the lobula to discrete optic glomeruli in the central brain group these sets of figure–ground stimuli in a homologous manner to the behavior; “figure-like” stimuli are coded similar to one another and “ground-like” stimuli are encoded differently. One cell class responds to the leading edge of a figure and is suppressed by ground motion. Two other classes cluster any figure-like stimuli, including a figure moving opposite the ground, distinctly from ground alone. This evidence demonstrates that lobula outputs provide a diverse basis set encoding visual features necessary for figure detection.
Sp3/REST/HDAC1/HDAC2 Complex Represses and Sp1/HIF-1/p300 Complex Activates ncx1 Gene Transcription, in Brain Ischemia and in Ischemic Brain Preconditioning, by Epigenetic Mechanism
Authors: Formisano Luigi , Guida Natascia , Valsecchi Valeria , Cantile Maria , Cuomo Ornella , Vinciguerra Antonio , Laudati Giusy , Pignataro Giuseppe , Sirabella Rossana , Di Renzo Gianfranco , Annunziato Lucio
Published: May 2015

The Na+-Ca2+exchanger 1 (NCX1) is reduced in stroke by the RE1-silencing transcription factor (REST), whereas it is increased in ischemic brain preconditioning (PC) by hypoxia-inducible factor 1 (HIF-1). Because ncx1 brain promoter (ncx1-Br) has five putative consensus sequences, named Sp1A–E, for the specificity protein (Sp) family of transcription factors (Sp1–4), we investigated the role of this family in regulating ncx1 transcription in rat cortical neurons. Here we found that Sp1 is a transcriptional activator, whereas Sp3 is a transcriptional repressor of ncx1, and that both bind ncx1-Br in a sequence-specific manner, modulating ncx1 transcription through the Sp1 sites C–E. Furthermore, by transient middle cerebral artery occlusion (tMCAO) in rats, the transcriptional repressors Sp3 and REST colocalized with the two histone-deacetylases (HDACs) HDAC1 and HDAC2 on the ncx1-Br, with a consequent hypoacetylation. Contrarily, in PC+tMCAO the transcriptional activators Sp1 and HIF-1 colocalized with histone acetyltransferase p300 on ncx1-Br with a consequent hyperacetylation. In addition, in neurons silenced with siRNA of NCX1 and subjected to oxygen and glucose deprivation (OGD) (3 h) plus reoxygenation (RX) (24 h), the neuroprotection of Class I HDAC inhibitor MS-275 was counteracted, whereas in neurons overexpressing NCX1 and subjected to ischemic preconditioning (PC+OGD/RX), the neurotoxic effect of p300 inhibitor C646 was prevented. Collectively, these results demonstrate that NCX1 expression is regulated by the Sp3/REST/HDAC1/HDAC2 complex in tMCAO and by the Sp1/HIF-1/p300 complex in PC+tMCAO and that epigenetic intervention, by modulating the acetylation of ncx1-Br, may be a strategy for the development of innovative therapeutic intervention in stroke.
Activation of Group I and Group II Metabotropic Glutamate Receptors Causes LTD and LTP of Electrical Synapses in the Rat Thalamic Reticular Nucleus
Authors: Wang Zemin , Neely Ryan , Landisman Carole E.
Published: May 2015

Compared with the extensive characterization of chemical synaptic plasticity, electrical synaptic plasticity remains poorly understood. Electrical synapses are strong and prevalent among the GABAergic neurons of the rodent thalamic reticular nucleus. Using paired whole-cell recordings, we show that activation of Group I metabotropic glutamate receptors (mGluRs) induces long-term depression of electrical synapses. Conversely, activation of the Group II mGluR, mGluR3, induces long-term potentiation of electrical synapses. By testing downstream targets, we show that modifications induced by both mGluR groups converge on the same signaling cascade—adenylyl cyclase to cAMP to protein kinase A—but with opposing effects. Furthermore, the magnitude of modification is inversely correlated to baseline coupling strength. Thus, electrical synapses, like their chemical counterparts, undergo both strengthening and weakening forms of plasticity, which should play a significant role in thalamocortical function.
Memory of Occasional Events in Rats: Individual Episodic Memory Profiles, Flexibility, and Neural Substrate
Authors: Veyrac Alexandra , Allerborn Marina , Gros Alexandra , Michon Frederic , Raguet Louise , Kenney Jana , Godinot Florette , Thevenet Marc , Garcia Samuel , Messaoudi Belkacem , Laroche Serge , Ravel Nadine
Published: May 2015

In search for the mechanisms underlying complex forms of human memory, such as episodic recollection, a primary challenge is to develop adequate animal models amenable to neurobiological investigation. Here, we proposed a novel framework and paradigm that provides means to quantitatively evaluate the ability of rats to form and recollect a combined knowledge of what happened, where it happened, and when or in which context it happened (referred to as episodic-like memory) after a few specific episodes in situations as close as possible to a paradigm we recently developed to study episodic memory in humans. In this task, rats have to remember two odor–drink associations (what happened) encountered in distinct locations (where it happened) within two different multisensory enriched environments (in which context/occasion it happened), each characterized by a particular combination of odors and places. By analyzing licking behavior on each drinking port, we characterized quantitatively individual recollection profiles and showed that rats are able to incidentally form and recollect an accurate, long-term integrated episodic-like memory that can last ≥24 d after limited exposure to the episodes. Placing rats in a contextually challenging recollection situation at recall reveals the ability for flexible use of episodic memory as described in humans. We further report that reversible inactivation of the dorsal hippocampus during recall disrupts the animal's capacity to recollect the complete episodic memory. Cellular imaging of c-Fos and Zif268 brain activation reveals that episodic memory recollection recruits a specific, distributed network of hippocampal-prefrontal cortex structures that correlates with the accuracy of the integrated recollection performance.
Mapping the Macaque Superior Temporal Sulcus: Functional Delineation of Vergence and Version Eye-Movement-Related Activity
Authors: Ward Matthew K. , Bolding Mark S. , Schultz Kevin P. , Gamlin Paul D.
Published: May 2015

It is currently thought that the primate oculomotor system has evolved distinct but interrelated subsystems to generate different types of visually guided eye movements (e.g., saccades/smooth pursuit/vergence). Although progress has been made in elucidating the neural basis of these movement types, no study to date has investigated all three movement types on a large scale and within the same animals. Here, we used fMRI in rhesus macaque monkeys to map the superior temporal sulcus (STS) for BOLD modulation associated with visually guided eye movements. Further, we ascertained whether modulation in a given area was movement type specific and, if not, the modulation each movement type elicited relative to the others (i.e., dominance). Our results show that multiple areas within STS modulate during all movement types studied, including the middle temporal, medial superior temporal, fundus of the superior temporal, lower superior temporal, and dorsal posterior inferotemporal areas. Our results also reveal an area in dorsomedial STS that is modulated almost exclusively by vergence movements. In contrast, we found that ventrolateral STS is driven preferentially during versional movements. These results illuminate an STS network involved in processes associated with multiple eye movement types, illustrate unique patterns of modulation within said network as a function of movement type, and provide evidence for a vergence-specific area within dorsomedial STS. We conclude that producing categorically different eye movement types requires access to a common STS network and that individual network nodes are recruited differentially based upon the type of movement generated.
Activation of Metabotropic Glutamate Receptor 7 Is Required for Induction of Long-Term Potentiation at SC-CA1 Synapses in the Hippocampus
Authors: Klar Rebecca , Walker Adam G. , Ghose Dipanwita , Grueter Brad A. , Engers Darren W. , Hopkins Corey R. , Lindsley Craig W. , Xiang Zixiu , Conn P. Jeffrey , Niswender Colleen M.
Published: May 2015

Of the eight metabotropic glutamate (mGlu) receptor subtypes, only mGlu7is expressed presynaptically at the Schaffer collateral (SC)-CA1 synapse in the hippocampus in adult animals. Coupled with the inhibitory effects of Group III mGlu receptor agonists on transmission at this synapse, mGlu7is thought to be the predominant autoreceptor responsible for regulating glutamate release at SC terminals. However, the lack of mGlu7-selective pharmacological tools has hampered direct testing of this hypothesis. We used a novel, selective mGlu7-negative allosteric modulator (NAM), ADX71743, and a newly described Group III mGlu receptor agonist, LSP4-2022, to elucidate the role of mGlu7in modulating transmission in hippocampal area CA1 in adult C57BL/6J male mice. Interestingly, although mGlu7agonists inhibit SC-CA1 EPSPs, we found no evidence for activation of mGlu7by stimulation of SC-CA1 afferents. However, LSP4-2022 also reduced evoked monosynaptic IPSCs in CA1 pyramidal cells and, in contrast to its effect on SC-CA1 EPSPs, ADX71743 reversed the ability of high-frequency stimulation of SC afferents to reduce IPSC amplitudes. Furthermore, blockade of mGlu7prevented induction of LTP at the SC-CA1 synapse and activation of mGlu7potentiated submaximal LTP. Together, these data suggest that mGlu7serves as a heteroreceptor at inhibitory synapses in area CA1 and that the predominant effect of activation of mGlu7by stimulation of glutamatergic afferents is disinhibition, rather than reduced excitatory transmission. Furthermore, this mGlu7-mediated disinhibition is required for induction of LTP at the SC-CA1 synapse, suggesting that mGlu7could serve as a novel therapeutic target for treatment of cognitive disorders.
TheN-Ethylmaleimide-Sensitive Factor and Dysbindin Interact To Modulate Synaptic Plasticity
Authors: Gokhale Avanti , Mullin Ariana P. , Zlatic Stephanie A. , Easley Charles A. , Merritt Megan E. , Raj Nisha , Larimore Jennifer , Gordon David E. , Peden Andrew A. , Sanyal Subhabrata , Faundez Victor
Published: May 2015

Dysbindin is a schizophrenia susceptibility factor and subunit of the biogenesis of lysosome-related organelles complex 1 (BLOC-1) required for lysosome-related organelle biogenesis, and in neurons, synaptic vesicle assembly, neurotransmission, and plasticity. Protein networks, or interactomes, downstream of dysbindin/BLOC-1 remain partially explored despite their potential to illuminate neurodevelopmental disorder mechanisms. Here, we conducted a proteome-wide search for polypeptides whose cellular content is sensitive to dysbindin/BLOC-1 loss of function. We identified components of the vesicle fusion machinery as factors downregulated in dysbindin/BLOC-1 deficiency in neuroectodermal cells and iPSC-derived human neurons, among them theN-ethylmaleimide-sensitive factor (NSF). Human dysbindin/BLOC-1 coprecipitates with NSF and vice versa, and both proteins colocalized in aDrosophilamodel synapse. To test the hypothesis that NSF and dysbindin/BLOC-1 participate in a pathway-regulating synaptic function, we examined the role for NSF in dysbindin/BLOC-1-dependent synaptic homeostatic plasticity inDrosophila. As previously described, we found that mutations indysbindinprecluded homeostatic synaptic plasticity elicited by acute blockage of postsynaptic receptors. Thisdysbindinmutant phenotype is fully rescued by presynaptic expression of either dysbindin orDrosophilaNSF. However, neither reduction of NSF alone or in combination withdysbindinhaploinsufficiency impaired homeostatic synaptic plasticity. Our results demonstrate that dysbindin/BLOC-1 expression defects result in altered cellular content of proteins of the vesicle fusion apparatus and therefore influence synaptic plasticity.
Predictions of Visual Content across Eye Movements and Their Modulation by Inferred Information
Authors: Ehinger Benedikt V. , König Peter , Ossandón José P.
Published: May 2015

The brain is proposed to operate through probabilistic inference, testing and refining predictions about the world. Here, we search for neural activity compatible with the violation of active predictions, learned from the contingencies between actions and the consequent changes in sensory input. We focused on vision, where eye movements produce stimuli shifts that could, in principle, be predicted. We compared, in humans, error signals to saccade-contingent changes of veridical and inferred inputs by contrasting the electroencephalographic activity after saccades to a stimulus presented inside or outside the blind spot. We observed early (<250 ms) and late (>250 ms) error signals after stimulus change, indicating the violation of sensory and associative predictions, respectively. Remarkably, the late response was diminished for blind-spot trials. These results indicate that predictive signals occur across multiple levels of the visual hierarchy, based on generative models that differentiate between signals that originate from the outside world and those that are inferred.
MSH3 Promotes Dynamic Behavior of Trinucleotide Repeat Tracts In Vivo
Authors: Williams Gregory M , Surtees Jennifer A
Published: May 2015

Trinucleotide repeat (TNR) expansions are the underlying cause of more than 40 neurodegenerative and neuromuscular diseases, including myotonic dystrophy and Huntington’s disease, yet the pathway to expansion remains poorly understood. An important step in expansion is the shift from a stable TNR sequence to an unstable, expanding tract, which is thought to occur once a TNR attains a threshold length. Modeling of human data has indicated that TNR tracts are increasingly likely to expand as they increase in size and to do so in increments that are smaller than the repeat itself, but this has not been tested experimentally. Genetic work has implicated the mismatch repair factor MSH3 in promoting expansions. Using Saccharomyces cerevisiae as a model for CAG and CTG tract dynamics, we examined individual threshold-length TNR tracts in vivo over time in MSH3 and msh3Δ backgrounds. We demonstrate, for the first time, that these TNR tracts are highly dynamic. Furthermore, we establish that once such a tract has expanded by even a few repeat units, it is significantly more likely to expand again. Finally, we show that threshold- length TNR sequences readily accumulate net incremental expansions over time through a series of small expansion and contraction events. Importantly, the tracts were substantially stabilized in the msh3Δ background, with a bias toward contractions, indicating that Msh2-Msh3 plays an important role in shifting the expansion-contraction equilibrium toward expansion in the early stages of TNR tract expansion.