bluuebunny/crossref_metadata_2025_split huggingface dataset:
Commissural Gain Control Enhances the Midbrain Representation of Sound Location
Authors: Orton Llwyd David , Papasavvas Christoforos A. , Rees Adrian 
Published: April 2016

Accurate localization of sound sources is essential for survival behavior in many species. The inferior colliculi (ICs) are the first point in the auditory pathway where cues used to locate sounds, ie, interaural time differences (ITDs), interaural level differences (ILDs), and pinna spectral cues, are all represented in the same location. These cues are first extracted separately on each side of the midline in brainstem nuclei that project to the ICs. Because of this segregation, each IC predominantly represents stimuli in the contralateral hemifield. We tested the hypothesis that commissural connections between the ICs mediate gain control that enhances sound localization acuity. We recorded IC neurons sensitive to either ITDs or ILDs in anesthetized guinea pig, before, during, and following recovery from deactivation of the contralateral IC by cryoloop cooling or microdialysis of procaine. During deactivation, responses were rescaled by divisive gain change and additive shifts, which reduced the dynamic range of ITD and ILD response functions and the ability of neurons to signal changes in sound location. These data suggest that each IC exerts multiplicative gain control and subtractive shifts over the other IC that enhances the neural representation of sound location. Furthermore, this gain control operates in a similar manner on both ITD- and ILD-sensitive neurons, suggesting a shared mechanism operates across localization cues. Our findings reveal a novel dependence of sound localization on commissural processing.SIGNIFICANCE STATEMENTSound localization, a fundamental process in hearing, is dependent on bilateral computations in the brainstem. How this information is transmitted from the brainstem to the auditory cortex, through several stages of processing, without loss of signal fidelity, is not clear. We show that the ability of neurons in the auditory midbrain to encode azimuthal sound location is dependent on gain control mediated by the commissure of the inferior colliculi. This finding demonstrates that commissural processing between homologous auditory nuclei, on either side of the midline, enhances the precision of sound localization.
Ligand Specificity and Evolution of Mammalian Musk Odor Receptors: Effect of Single Receptor Deletion on Odor Detection
Authors: Sato-Akuhara Narumi , Horio Nao , Kato-Namba Aya , Yoshikawa Keiichi , Niimura Yoshihito , Ihara Sayoko , Shirasu Mika , Touhara Kazushige 
Published: April 2016

Musk odors have been used widely for fragrance and medicine for >2000 years because of their fascinating scent and physiological effects. Therefore, fragrance manufacturers have been eager to develop high-quality musk compounds that are safe and easily synthesized. We recently identified muscone-responsive olfactory receptors (ORs) MOR215-1 and OR5AN1 in mice and humans, respectively (Shirasu et al., 2014). In this study, we identified musk ORs that are evolutionarily closely related to MOR215-1 or OR5AN1 in various primates and investigated structure–activity relationships for various musk odorants and related compounds. We found that each species has one or two functional musk ORs that exhibit specific ligand spectra to musk compounds. Some of them, including the human OR5AN1, responded to nitro musks with chemical properties distinct from muscone. The ligand specificity of OR5AN1 reflects the perception of musk odors in humans. Genetic deletion of MOR215-1 in mice resulted in drastic reduction of sensitivity to muscone, suggesting that MOR215-1 plays a critical role in muscone perception. Therefore, the current study reveals a clear link between the identified OR and muscone perception. Moreover, the strategy established for screening ligands for the muscone OR may facilitate the development of novel and commercially useful musk odors.SIGNIFICANCE STATEMENTThe long-sought musk odor receptor family in mammals was discovered and found to be well conserved and narrowly tuned to musk odors. In mice, deletion of the most sensitive musk receptor resulted in drastic reduction in sensitivity to muscone, demonstrating a strong link between receptor and odor perception. In humans, we found one musk receptor that recognized both macrocyclic and nitro musks that had distinct chemical structures. The structure–activity relationships were in a good agreement with human sensory perception and therefore may be used to develop novel musk aroma in fragrance fields. Finally, identification of a natural ligand(s) for musk receptors in mammals other than musk deer would reveal an evolutionarily pivotal role in each species in the future.
The Unique Dopamine/Ecdysteroid Receptor Modulates Ethanol-Induced Sedation inDrosophila
Authors: Petruccelli Emily , Li Qi , Rao Yi , Kitamoto Toshihiro 
Published: April 2016

Steroids profoundly influence behavioral responses to alcohol by activating canonical nuclear hormone receptors and exerting allosteric effects on ion channels. Accumulating evidence has demonstrated that steroids can also trigger biological effects by directly binding G-protein-coupled receptors (GPCRs), yet physiological roles of such unconventional steroid signaling in controlling alcohol-induced behaviors remain unclear. The dopamine/ecdysteroid receptor (DopEcR) is a GPCR that mediates nongenomic actions of ecdysteroids, the major steroid hormones in insects. Here, we report thatDrosophilaDopEcR plays a critical role in ethanol-induced sedation.DopEcRmutants took longer than control flies to become sedated during exposure to ethanol, despite having normal ethanol absorption or metabolism. RNAi-mediated knockdown ofDopEcRexpression revealed that this receptor is necessary after eclosion, and is required in particular neuronal subsets, including cholinergic and peptidergic neurons, to mediate this behavior. Additionally, flies ubiquitously overexpressingDopEcRcDNA had a tendency to become sedated quickly upon ethanol exposure. These results indicate that neuronal subset-specific expression of DopEcR in adults is required for normal sedation upon exposure to ethanol. We also obtained evidence indicating that DopEcR may promote ethanol sedation by suppressing epidermal growth factor receptor/extracellular signal-regulated kinase signaling. Last, genetic and pharmacological analyses suggested that in adult flies ecdysone may serve as an inverse agonist of DopEcR and suppress the sedation-promoting activity of DopEcR in the context of ethanol exposure. Our findings provide the first evidence for the involvement of nongenomic G-protein-coupled steroid receptors in the response to alcohol, and shed new light on the potential roles of steroids in alcohol-use disorders.SIGNIFICANCE STATEMENTAlcohol abuse is an alarming personal and societal burden. The improvement of prevention and treatment strategies for alcohol-use disorders requires a better understanding of their biological basis. Steroid hormones profoundly affect alcohol-induced behaviors, but the contribution of their unconventional, nongenomic actions during these responses has not yet been elucidated. We found thatDrosophilaDopEcR, a unique G-protein-coupled receptor (GPCR) with dual specificity for dopamine and steroids, mediates noncanonical steroid actions to promote ethanol-induced sedation. Because steroid signaling and the behavioral response to alcohol are evolutionarily well conserved, our findings suggest that analogous mammalian receptors likely play important roles in alcohol-use disorders. Our work provides a foundation for further characterizing the function and mechanisms of action of nonclassical steroid GPCR signaling.
Bok Is Not Pro-Apoptotic But Suppresses Poly ADP-Ribose Polymerase-Dependent Cell Death Pathways and Protects against Excitotoxic and Seizure-Induced Neuronal Injury
Authors: D'Orsi Beatrice , Engel Tobias , Pfeiffer Shona , Nandi Saheli , Kaufmann Thomas , Henshall David C. , Prehn Jochen H. M. 
Published: April 2016

Bok (Bcl-2-related ovarian killer) is a Bcl-2 family member that, because of its predicted structural homology to Bax and Bak, has been proposed to be a pro-apoptotic protein. In this study, we demonstrate that Bok is highly expressed in neurons of the mouse brain but thatbokwas not required for staurosporine-, proteasome inhibition-, or excitotoxicity-induced apoptosis of cultured cortical neurons. On the contrary, we found thatbok-deficient neurons were more sensitive to oxygen/glucose deprivation-induced injuryin vitroand seizure-induced neuronal injuryin vivo. Deletion ofbokalso increased staurosporine-, excitotoxicity-, and oxygen/glucose deprivation-induced cell death inbax-deficient neurons. Single-cell imaging demonstrated thatbok-deficient neurons failed to maintain their neuronal Ca2+homeostasis in response to an excitotoxic stimulus; this was accompanied by a prolonged deregulation of mitochondrial bioenergetics.bokdeficiency led to a specific reduction in neuronal Mcl-1 protein levels, and deregulation of both mitochondrial bioenergetics and Ca2+homeostasis was rescued by Mcl-1 overexpression. Detailed analysis of cell death pathways demonstrated the activation of poly ADP-ribose polymerase-dependent cell death inbok-deficient neurons. Collectively, our data demonstrate that Bok acts as a neuroprotective factor rather than a pro-death effector during Ca2+- and seizure-induced neuronal injuryin vitroandin vivo.SIGNIFICANCE STATEMENTBcl-2 proteins are essential regulators of the mitochondrial apoptosis pathway. The Bcl-2 protein Bok is highly expressed in the CNS. Because of its sequence similarity to Bax and Bak, Bok has long been considered part of the pro-apoptotic Bax-like subfamily, but no studies have yet been performed in neurons to test this hypothesis. Our study provides important new insights into the functional role of Bok during neuronal apoptosis and specifically in the setting of Ca2+- and seizure-mediated neuronal injury. We show that Bok controls neuronal Ca2+homeostasis and bioenergetics and, contrary to previous assumptions, exerts neuroprotective activitiesin vitroandin vivo. Our results demonstrate that Bok cannot be placed unambiguously into the Bax-like Bcl-2 subfamily of pro-apoptotic proteins.
Theta Rhythmic Clock-Like Activity of Single Units in the Mouse Hippocampus
Authors: Zhang Lu , Ma Xiaoyu , Chen Guifen , Barkai Edi , Lin Longnian 
Published: April 2016

Theta rhythmic clock-like activity was observed in a small group of hippocampal CA1 neurons in freely behaving mice. These neurons were only persistently activated during theta states of waking exploration and rapid eye movement sleep, but were almost silent during the non-theta state of slow-wave sleep. Interestingly, these cells displayed a theta clock-like simple-spike firing pattern, and were capable of firing one spike per theta cycle during theta states. This is the first report of a unique class of hippocampal neurons with a clock-like firing pattern at the theta rhythm. We speculate that these cells may act as a temporal reference to participate in the theta-related temporal coding in the hippocampus.SIGNIFICANCE STATEMENTTheta oscillations, as the predominant rhythms in the hippocampus during waking exploration and rapid eye movement sleep, may be critical for temporal coding/decoding of neuronal information, and theta-phase precession in hippocampal place cells is one of the best demonstrations of such temporal coding. Here, we show that a unique small class of hippocampal CA1 neurons fired with a theta rhythmic clock-like firing pattern during theta states. These firing characteristics support the notion that these neurons may play a critical role in theta-related temporal coding in the hippocampus.
The Medial Orbitofrontal Cortex Regulates Sensitivity to Outcome Value
Authors: Gourley Shannon L. , Zimmermann Kelsey S. , Allen Amanda G. , Taylor Jane R. 
Published: April 2016

An essential component of goal-directed decision-making is the ability to maintain flexible responding based on the value of a given reward, or “reinforcer.” The medial orbitofrontal cortex (mOFC), a subregion of the ventromedial prefrontal cortex, is uniquely positioned to regulate this process. We trained mice to nose poke for food reinforcers and then stimulated this region using CaMKII-driven Gs-coupled designer receptors exclusively activated by designer drugs (DREADDs). In other mice, we silenced the neuroplasticity-associated neurotrophin brain-derived neurotrophic factor (BDNF). Activation of Gs-DREADDs increased behavioral sensitivity to reinforcer devaluation, whereasBdnfknockdown blocked sensitivity. These changes were accompanied by modifications in breakpoint ratios in a progressive ratio task, and they were recapitulated inBdnf+/−mice. Replacement of BDNF selectively in the mOFC inBdnf+/−mice rescued behavioral deficiencies, as well as phosphorylation of extracellular-signal regulated kinase 1/2 (ERK1/2). Thus, BDNF expression in the mOFC is both necessary and sufficient for the expression of typical effort allocation relative to an anticipated reinforcer. Additional experiments indicated that expression of the immediate-early gene c-foswas aberrantly elevated in theBdnf+/−dorsal striatum, and BDNF replacement in the mOFC normalized expression. Also, systemic administration of an MAP kinase kinase inhibitor increased breakpoint ratios, whereas the addition of discrete cues bridging the response–outcome contingency rescued breakpoints inBdnf+/−mice. We argue that BDNF–ERK1/2 in the mOFC is a key regulator of “online” goal-directed action selection.SIGNIFICANCE STATEMENTGoal-directed response selection often involves predicting the consequences of one's actions and the value of potential payoffs. Lesions or chemogenetic inactivation of the medial orbitofrontal cortex (mOFC) in rats induces failures in retrieving outcome identity memories (Bradfield et al., 2015), suggesting that the healthy mOFC serves to access outcome value information when it is not immediately observable and thereby guide goal-directed decision-making. Our findings suggest that the mOFC also bidirectionally regulates effort allocation for a given reward and that expression of the neurotrophin BDNF in the mOFC is both necessary and sufficient for mice to sustain stable representations of reinforcer value.
El modelo lineal de probabilidad y el modelo logit, un ejemplo aplicado
Authors: Moscote Orlando , Rincón William 
Published: April 2016

<p class="p1">Los modelos de regresi´on con respuesta cualitativa son modelos en los cuales la variable dependiente puede ser de naturaleza cualitativa, mientras que las variables independientes pueden ser cualitativas o cuantitativas o una mezcla de las dos, por ejemplo si se est´a estudiando la relación entre ingresos y el poseer o no una vivienda, la respuesta solo puede tomar dos valores (si posee una vivienda o no la posee), la variable independiente puede ser los ingresos familiares, el estrato social de esa familia y la cantidad de personas en el hogar, entre otras. Los modelos de respuesta cualitativa no tienen que restringirse simplemente a respuestas de sí o no; la variable respuesta puede tomar más de dos valores, ser tricotómica o politomica, también se establecen modelos en los que la variable dependiente es de carácter ordinal o de carácter nominal en donde no hay preestablecido ningún tipo de orden.</p><p class="p1">En el presente arículo se analiza el modelo lineal de probabilidad (MLP) y el modelo logit como alternativa al MLP con la idea de subsanar algunos de los problemas que presenta dicho modelo. Los modelos mencionados son ilustrados utilizando una muestra de datos seleccionados del archivo de datos ”seguimiento a usuarios de una línea base”, la cual es parte de las bases de datos del estudio que se desarrolló en el marco del convenio interadministrativo 012 en el año 2009, entre la UAES (Unidad Administrativa especial de servicios públicos) y la Universidad Distrital Francisco José de Caldas, convenio en el cual participó uno de los autores de este artículo.</p>
Cuantificación de variantes genéticas utilizando modelos jerárquicos bayesianos
Authors: Velez Jorge Ivan , Angel Jairo Arturo , Correa Juan Carlos 
Published: April 2016

En biología molecular, los estudios funcionales son útiles para la caracterización de variantes o mutaciones en el genoma humano vía experimentación con modelos animales (embriones de peces, por ejemplo). Estos experimentos consisten en modificar genéticamente dichos embriones inyect\'andolos con mol\'eculas de ácido ribonucleico mensajero (mRNA, en inglés) y se caracterizan por ser destructivos, tomar mucho tiempo y generar poca información. En este trabajo se propone e ilustra, con datos reales, una metodología para el análisis estadístico de este tipo de experimentos utilizando un enfoque Bayesiano.
Relación entre los procesos de reservas que se generan con dos reclamaciones relacionadas en el tiempo
Authors: Másmela Caita Luis Alejandro , Castillo Carreño Edwin Javier 
Published: April 2016

El proceso de reservas es para las compañías aseguradoras base fundamental para el control de las carteras que se tienen contratadas, para facilitar la manipulación del modelo matemático y probabilístico en ocasiones se discretiza el modelo de manera que los resultados aproximen a la solución real en el continuo, en este caso se utiliza el modelo binomial compuesto para dicho propósito. <br />En la mayoría de contextos se parte del supuesto de independencia, el caso que aquí se considera se supone dependencia entre dos tipos de reclamaciones denominadas la reclamación principal y la sobre-reclamación o reclamación subsecuente, esta última estará asociada siempre que exista una reclamación principal. El tipo de modelo con reclamaciones relacionadas en el tiempo genera dos procesos de reservas, uno para cuando la reclamación subsecuente no es retrasada a un siguiente periodo de tiempo y otro donde se cubre el total reclamado tanto por la reclamación principal como por la subsecuente. Ya que manipular dichos procesos por separado es innecesario y poco práctico, se genera a partir de las probabilidades de supervivencia de ambos procesos y la manipulación de funciones generadoras de probabilidad, una ecuación que recopila la información de los dos procesos de reservas.
Estudio de simulación para comparar varios estimadores de varianza en el marco de la regresión no paramétrica
Authors: Flórez Alvaro José , Olaya Javier 
Published: April 2016

<p>En este trabajo se prueban varios estimadores de varianza basados en diferencias en el marco de la regresión no paramétrica. Estos estimadores tiene la principal ventaja de no depender de los parámetros de suavización, además de que son poco exigente en términos computacionales. Se usan principalmente estimadores basados en diferencias ordinarias y basados en las diferencias óptimas de Hall. Se crean escenarios utilizando diferentes funciones de regresión, tamaños de muestra y distribuciones de los errores y se introduce el uso de la distribución semi-normal para probar los estimadores de varianza en casos de distribuciones asimétricas de los errores. Los resultados parecen apoyar la idea de que los estimadores basados en diferencias óptimas de Hall no son mejores en todos los escenarios planteados.</p>
Preguntas abiertas en encuestas ¿cómo realizar su análisis?
Authors: Gómez William Arley Rincón 
Published: April 2016

<div class="page" title="Page 1"><div class="layoutArea"><div class="column"><p><span>El presente artículo, muestra algunas de las ventajas que tiene en una encuesta la utilización de preguntas abiertas, preguntas que debido a la complejidad de su análisis, son utilizadas con poca frecuencia, o cuando se utilizan, simplemente se dejan como parte en el cuestionario pero no se analizan las respuestas a este tipo de preguntas. Técnicas estadísticas como el análisis de datos textuales, desarrolladas inicialmente por Ludovic Lebart, son presentadas en este artículo como una alternativa a los métodos tradicionales de análisis de grandes masas de datos de tipo textual como la poscodificación y como una motivación al estudio de técnicas y software que permitan analizar datos de tipo textual. </span></p></div></div></div>
New digital demodulator with matched filters and curve segmentation techniques for BFSK demodulation: FPGA implementation and results
Authors: Torres Gómez Jorge , Hernández Fidel , Habermann Joachim 
Published: April 2016

<p>The current article addresses digital implementation of new demodulation schemes for Binary Frequency Shift Keying (BFSK), and has two main objectives: of the description of the performance of the new processing method and its implementation on FPGA technology. Performance is analyzed by means of the total number of demodulated bits free of errors without noise, and by means of the BER parameter. The proposed method exhibits to have better performance than the solutions reported. Additionally, the solution obtained shows lower complexity than reported methods in regard to the total number of adders and multipliers. The implementation is described for FPGA systems, and the System Generator software is used for testing and simulating the results.</p>
Optimization of the linear quadratic regulator (LQR) control quarter car suspension system using genetic algorithm
Authors: Nagarkar Mahesh , Vikhe Patil G. J. 
Published: April 2016

<p>In this paper, a genetic algorithm (GA) based in an optimization approach is presented in order to search the optimum weighting matrix parameters of a linear quadratic regulator (LQR). A Macpherson strut quarter car suspension system is implemented for ride control application. Initially, the GA is implemented with the objective of minimizing root mean square (RMS) controller force. For single objective optimization, RMS controller force is reduced by 20.42% with slight increase in RMS sprung mass acceleration. Trade-off is observed between controller force and sprung mass acceleration. Further, an analysis is extended to multi-objective optimization with objectives such as minimization of RMS controller force and RMS sprung mass acceleration and minimization of RMS controller force, RMS sprung mass acceleration and suspension space deflection. For multi-objective optimization, Pareto-front gives flexibility in order to choose the optimum solution as per designer’s need.</p>