bluuebunny/crossref_metadata_2025 huggingface dataset:
Overlapping and distinct functions for cofilin, coronin and Aip1 in actin dynamics in vivo
Authors: Lin Meng-Chi , Galletta Brian J. , Sept David , Cooper John A.
Published: March 2010

Actin-filament disassembly is crucial for actin-based motility, to control filament network architecture and to regenerate subunits for assembly. Here, we examined the roles of three actin cytoskeletal proteins, coronin, cofilin and Aip1, which have been suggested to combine in various ways to control actin dynamics by promoting or regulating disassembly. We studied their functions during the endocytosis process in budding yeast, where actin-filament dynamics at the cortical actin ‘patch’ contribute to the formation and movement of endocytic vesicles. We found that all three proteins were recruited during the late phase of the life of the actin patch. They all arrived at the same time, when actin and other actin-associated proteins were leaving the patch. Cofilin point mutations influenced the localization of coronin and Aip1, but the complete loss of coronin had no effect on localization of cofilin or Aip1. Using quantitative patch motion analysis and comparing mutant alleles, the phenotypes for mutations of the three genes showed some commonalities, but also some striking differences. Cofilin was clearly the most important; it displayed the most severe mutant phenotypes affecting actin-patch assembly and movement. Together, the results suggest that all three proteins work together to promote actin disassembly, but not in a simple way, and not with equal importance.
Solving Talent Scheduling with Dynamic Programming
Authors: Garcia de la Banda Maria , Stuckey Peter J. , Chu Geoffrey
Published: March 2010

We give a dynamic programming solution to the problem of scheduling scenes to minimize the cost of the talent. Starting from a basic dynamic program, we show a number of ways to improve the dynamic programming solution by preprocessing and restricting the search. We show how by considering a bounded version of the problem, and determining lower and upper bounds, we can improve the search. We then show how ordering the scenes from both ends can drastically reduce the search space. The final dynamic programming solution is orders of magnitude faster than competing approaches and finds optimal solutions to larger problems than were considered previously.
The Robust Network Loading Problem Under Hose Demand Uncertainty: Formulation, Polyhedral Analysis, and Computations
Authors: Altın Ayşegül , Yaman Hande , Pınar Mustafa Ç.
Published: March 2010

We consider the network loading problem (NLP) under a polyhedral uncertainty description of traffic demands. After giving a compact multicommodity flow formulation of the problem, we state a decomposition property obtained from projecting out the flow variables. This property considerably simplifies the resulting polyhedral analysis and computations by doing away with metric inequalities. Then we focus on a specific choice of the uncertainty description, called the “hose model,” which specifies aggregate traffic upper bounds for selected endpoints of the network. We study the polyhedral aspects of the NLP under hose demand uncertainty and use the results as the basis of an efficient branch-and-cut algorithm. The results of extensive computational experiments on well-known network design instances are reported.
A Fully Distributed Lagrangean Solution for a Peer-to-Peer Overlay Network Design Problem
Authors: Boschetti Marco A. , Maniezzo Vittorio , Roffilli Matteo
Published: March 2010

Peer-to-peer (P2P) computing already accounts for a large part of the traffic on the Internet, and it is likely to become as ubiquitous as current client/server architectures in next generation information systems. This paper addresses a central problem of P2P systems: the design of an optimal overlay communication network for a set of processes on the Internet. Such a network defines membership to the P2P group and allows for members to disseminate information within the group. The problem, named the membership overlay problem (MOP), can be formulated as a dynamic optimization problem where classical combinatorial optimization techniques must face the further challenge of time-varying input data. This paper proposes an innovative, fully distributed, and asynchronous subgradient optimization algorithm for the Lagrangean relaxation of the MOP, which can run online in fully decentralized P2P systems, and integrates it with a distributed heuristic that can achieve sound hot-start states for fast response to varying network structures.
Are Foreign IT Workers Cheaper? U.S. Visa Policies and Compensation of Information Technology Professionals
Authors: Mithas Sunil , Lucas Henry C.
Published: March 2010

The use of H-1B and other work visas to hire foreign information technology (IT) professionals in the United States has attracted significant controversy and policy debates. On one hand, hiring high-skill foreign IT professionals on work visas can be advantageous for U.S. firms and the overall economy. On the other hand, high-skill immigration can adversely impact the wages of foreign and American IT professionals. This study uses data on skills and compensation of more than 50,000 IT professionals in the United States over the period 2000–2005 to study patterns in compensation of foreign and American IT professionals to inform these debates. Contrary to the popular belief that foreign workers are a cheap source of labor for U.S. firms, we find that after controlling for their human capital attributes, foreign IT professionals (those without U.S. citizenship and those with H-1B or other work visas) earn a salary premium when compared with IT professionals with U.S. citizenship. The salary premiums for non-U.S. citizens and for those on work visas fluctuate in response to supply shocks created by the annual caps on new H-1B visas. Setting lower and fully utilized annual caps results in higher salary premiums for non-U.S. citizens and those with work visas. We discuss implications of this study for crafting informed visa- and immigration-related policies by the U.S. government, for staffing practices of firms, and for human capital investments by IT professionals.
Working memory and cognitive styles in adolescents' attainment
Authors: Alloway Tracy Packiam , Banner Gloria E. , Smith Patrick
Published: March 2010

Background. Working memory, the ability to store and process information, is strongly related to learning outcomes.

Aims. The aim of the present study is to extend previous research on early learning and investigate the relationship between working memory, cognitive styles, and attainment in adolescents using both national curriculum tests and teacher‐based assessments.

Sample. A group of 164 13‐year‐olds from a school in England were recruited.

Methods. They took tests of working memory and cognitive styles. The school provided the attainment scores.

Results. Working memory was found to be the predictor of learning outcomes in English, Maths, and Science, as well as all teacher assessments. There was also a significant interplay between working memory, styles, and attainment. For students with high working memory, their style preference does not impact attainment. Students most at risk were analytics with low working memory as they performed worse in the most subjects.

Conclusions. The findings suggest that the interplay between working memory and cognitive styles can be useful in developing suitable interventions to support students.
A link between altruism and sexual selection: Genetic influence on altruistic behaviour and mate preference towards it
Authors: Phillips Tim. , Ferguson Eamonn. , Rijsdijk Fruhling.
Published: March 2010

Altruistic behaviour raises major questions for psychology and biology. One hypothesis proposes that human altruistic behaviour evolved as a result of sexual selection. Mechanisms that seek to explain how sexual selection works suggest genetic influence acting on both the mate preference for the trait and the preferred trait itself. We used a twin study to estimate whether genetic effects influenced responses to psychometric scales measuring mate preference towards altruistic traits (MPAT) and the preferred trait (i.e., ‘altruistic personality’). As predicted, we found significant genetic effects influencing variation in both. We also predicted that individuals expressing stronger MPAT and ‘altruistic personality’ would have mated at a greater frequency in ancestral populations. We found evidence for this in that 67% of the covariance in the phenotypic correlation between the two scales was associated with significant genetic effects. Both sets of findings are thus consistent with the hypothesized link between sexual selection and human altruism towards non‐kin. We discuss how this study contributes to our understanding of altruistic behaviour and how further work might extend this understanding.
Revisiones al tema numantino en Cervantes y Rojas Zorrilla: ritualización y desmitificación del mito patrio
Authors: García-Martín Elena
Published: March 2010

La versión cervantina del mito de Numancia ha recibido más atención que la de Rojas Zorrilla desde el Romanticismo, tanto en escenarios como en discusiones académicas. Este ensayo analiza las bases de esta preferencia y apunta a la contribución única de la Numancia cercada y Numancia destruida de Rojas Zorrilla, atendiendo a los contextos políticos de varias representaciones y a las bases dramáticas e historiográficas de ambas obras. El análisis de la historia de la representación de las obras indica que la clave del resurgimiento periódico de El cerco de Numancia de Cervantes es del todo independiente de convenciones dramáticas y más bien corresponde a la manera en que esta versión, a diferencia de la de Rojas Zorrilla, favorece la pervivencia de un mito profundamente arraigado en el imaginario colectivo.
El examen de maridos en El conde Partinuplés de Ana Caro: la agencia femenina en el Juicio de Paris
Authors: Gil-Oslé Juan Pablo
Published: March 2010

El deseo y la libertad femeninos? en El conde Partinuplés han sido dos temas fundamentales del análisis crítico de esta obra. Tras analizar los resultados de estos trabajos, se elabora aquí una nueva perspectiva basada en la mitografía del Juicio de Paris y sus aplicaciones a la política matrimonial y estatal de las sociedades europeas de la temprana modernidad. En todos estos acercamientos críticos existe una constante referencia a diferentes aspectos del matrimonio final—supuestamente feliz—para mostrar que existen numerosos matices en este himeneo: ¿cuáles son los subtextos con los que está en diálogo? ¿quién decide con quién se casa? ¿cómo es el procedimiento de elección? ¿cuál es el contexto histórico? Sin embargo, existe una cierta tensión respecto a cuál es el método más pertinente. En la filología histórica, se compara El conde Partinuplés con los libros de caballería; los especialistas en mitografía y écfrasis analizan el mito de Eros y Psique; desde la crítica feminista se enfatiza el contexto histórico social y la comparación con otras obras de la época. Aquí, en cambio, combinando todas estas técnicas críticas—la mitografía, el comparativismo, la teoría feminista y la historia literaria—examino el uso feminista del Juicio de Paris en la obra de Ana Caro, incluyendo su iconografía pictórica y propagandística en la temprana modernidad, en conjunción con las nociones teóricas de Saba Mahmood sobre la libertad, el sujeto y la agencia femenina.
Arte y privanza en La quinta de Florencia de Lope de Vega: De los Médicis al Duque de Lerma
Authors: Atienza Belén
Published: March 2010

En su tragicomedia La quinta de Florencia , Lope dramatiza un episodio de la historia de Alejandro de Médicis, en el que el Duque castiga a su privado César por cometer una violación. A partir de la inclusión en el texto de elementos que no estaban en sus fuentes (como referencias pictóricas y arquitectónicas), Lope construye un discurso moral en torno al contraste templanza/lujuria. Lope proyecta en la Florencia de los Médicis sus reservas y ansiedades sobre la España de Felipe III y Lerma, y conecta el tema de la violación con temas como la traición, la privanza y la decadencia de la clase aristocrática.
El juicio divino en El Nuevo Mundo de Lope de Vega, estrategia religiosa de apropiación
Authors: Terradas José Carlos
Published: March 2010

El Nuevo Mundo descubierto por Cristóbal Colón de Lope de Vega establece una relación de continuidad evidente entre la campaña de Granada y la conquista de América: Granada se fragua como palimpsesto donde se escribirá la historia de los territorios recién incorporados. El planteamiento de una audiencia divina al principio de la obra, donde la Providencia falla a favor de la cristiandad y le concede los derechos de posesión del Nuevo Mundo antes usurpados por el demonio, le sirve al propio Cristóbal Colón para entender la misión semántica y hasta etimológica (como portador de Cristo) de su proyecto y por lo tanto también la mejor forma de mercadear el producto y los magnates dispuestos a subsidiarlo. Lo que en un principio era concebido sólo en términos económicos y cuasi científicos se transforma en una empresa exclusivamente religiosa. El juicio divino se fragua como introspección y al mismo tiempo como colectivización que justifica el proyecto colombino ante Dios y ante Europa. La reedición de la conquista supera la incorporación de Granada, es una tarea sagrada que genera dividendos contables en almas, al tiempo que combate la idolatría. El resultado del juicio divino domina la obra como prolongación de la cosmología cristiana, tamiza a los nuevos acólitos e invita a la utopía en tanto permite la administración de justicia según los valores adquiridos: purga de la idolatría, el diablo y la pasión desbocada.
Entre el museo y el teatro: Oportunidades didácticas de la entrada real de Ana de Austria en Madrid
Authors: Laguna Ana María G.
Published: March 2010

El despliegue iconográfico y escénico de la entrada real de Ana de Austria en Madrid (1570) supone una sólida plataforma propagandística para Felipe II, a la vez que una significativa oportunidad didáctico-artística para su audiencia. A medio camino entre el festival político y el popular, el festejo celebra no sólo la presencia de los monarcas, sino también la de una variada colección de pinturas y esculturas que—gracias al arte efímero—inunda las calles de la ciudad durante las semanas anteriores y posteriores al evento. El presente estudio explora la disposición teatral y museológica de estas obras, y el impacto que hace en ellas y en su público la alta cultura visual renacentista.
From Homer to Hip Hop: Orature and Griots , Ancient and Present
Authors: Banks Daniel
Published: March 2010

Contemporary re-mixes of classic texts and narratives such as The Seven Against Thebes and Cain and Abel are prominent in the young canon of Hip Hop Theatre. In addition, Hip Hop Theatre's cultural and performative relationship to orality link it to the African diasporic performance aesthetic of Orature, while also connecting it to certain scholars' understanding of the role that oral composition plays in Homer and other Greek classics. The function of Hip Hop Theatre within a Hip Hop cultural context thus mirrors certain aspects of the sociological function of epic poetry and Athenian tragedy in classical Greek society.
Listening to Lyric: Accent and Ictus in the Latin Sapphic Stanza
Authors: Becker Andrew
Published: March 2010

Meter, as taught in ancient Rome, entailed not just the sounds of the words, but also the expectation of verse beat (ictus). Even Latin lyrics can include significant coincidence and counterpoint between the performed accent and a latent, learned ictus. This essay surveys evidence for ictus and accent in Sapphics, then considers counterpoint and coincidence in Horace's Odes , a poem of Ausonius, and Horace's Carmen Saeculare , where a regular caesura falling one syllable later than expected reflects a different relationship of accent to beat. This relationship explains Horace's directions to his youthful chorus ( Carm 4.6.35-36) and helps us notice an acoustic feature of Latin lyric.
From Hip Hop to Homer: Practicing Translation in Central Los Angeles
Authors: Dutsch Dorota
Published: March 2010

The "Page and Stage" program in Los Angeles Central Public Library allowed audiences to interact closely with several works of classical literature featuring heroic sagas (Homer's Iliad and Odyssey and Aeschylus' Seven against Thebes ). By introducing different translations of these ancient texts (Pope's and Fagles' Iliad ), their reinventions (Will Power's Seven ), and relevant works of contemporary literature (Joseph Heller's Catch 22 ) and film (Kurosawa's Seven Samurai ), the organizers opened a space for public debate on ancient and modern ideologies of heroism.
Cleopatra's Cocktail
Authors: Jones Prudence J.
Published: March 2010

Pliny the Elder's account of Cleopatra consuming a cocktail of vinegar and a pearl in order to win a bet with Antony was considered credible in the ancient world, but many modern scholars have relegated the anecdote to the realm of fantasy. This paper identifies possible reasons for this skepticism, including the visual tradition of the story and the belief that increasing concentration always increases reaction rate. Experiments reveal that, in the case of acetic acid and pearls, the concentration found in vinegar made from wine is ideal.
"Page and Stage": The Librarian's Perspective
Authors: Tessman Nancy
Published: March 2010

Sixteen public library members of the Urban Libraries Council participated with the Aquila Theatre in the NEH-funded "Page and Stage" project to bring a timely and fresh interpretation of classical literature to their communities through an in-depth exploration of Homer's first book of the Iliad. Libraries sponsored theater performances, book groups, lectures, workshop, films, and discussions that drew from this significant work to explore issues and themes that resound with contemporary audiences. This successful collaboration extended the reach and importance of the classics to new and diverse audiences who responded enthusiastically to the quality performances, pertinent topics, and lively discussions.
Translating the Iliad for a Wider Public
Authors: Lombardo Stanley
Published: March 2010

This paper considers key principles and strategies in producing a translation of Homer's Iliad that succeeds for a wide audience both as poetic text and in performance. The author's translation of the last c. 100 lines of Iliad 19 is analyzed in terms of tonal variation and authorial voice, foregrounding performance as the telos of Homeric translation.
Ten Reasons to Read Homer: Addressing Public Perceptions of Classical Literature
Authors: Connolly Joy
Published: March 2010

This essay, which is adapted from my opening lecture for the "Page and Stage" series in White Plains Public Library (delivered October 4, 2009), argues through a reading of the first ten words of Homer's Iliad that the poem prompts us to reflect on our core values without entangling ourselves in the passions and paradoxes of contemporary debates.
Warrior Ants: Elite Troops in the Iliad
Authors: Sears Matthew
Published: March 2010

In the Iliad , Achilles' Myrmidons and the troops under Telamonian Ajax represent elite infantry contingents distinct from the rest of the Achaean force, specifically in their use of phalanx formations. This is evinced by several passages within the Iliad itself, and also by the mythological origins of the Myrmidons. Importantly, the tactics used on both sides of the conflict at Troy were variegated rather than uniform. Apparent discrepancies in Homeric descriptions of battle, such as the portrayal of the phalanx at some points and loose formations at others, can thus be explained.
Konstruktionen im Spracherwerb
Authors: Behrens Heike
Published: March 2010

The concept of ‘constructions’ covers the range from fully unanalyzed or “frozen” units to abstract and productive schemas that can be used to form new utterances, even with verbs that usually have a different valency (coercion). The dynamic nature of the construction as well as its functional grounding makes the construction particularly suitable for describing and explaining the course of language acquisition. Distributional analyses of the linguistic structures used across development as well as experimental tests on the productivity of these structures are the methodological means to assess the degree of freedom of constructions used at each point in development. In the earliest stages of development children rely heavily on bottom up processes and generalize only slowly. But with growing productivity they are able to generate new utterances top down.
Noch einmal: Partikelverbkonstruktionen
Authors: Knobloch Clemens
Published: March 2010

Using the much debated German particle verb construction as an example, some basic questions of Construction Grammar are investigated: constructional meanings, compositionality of meaning, the role of lexical verb bases, morphological and/or syntactal analysis. It is argued that the traditional mode of presentation in historical-comparative grammar (as practiced by Neogrammarians like Hermann Paul) is “constructional” in spirit and mirrors empirical concern for constructional change and constructional meaning. Prototypical verb particles are analyzed within a pattern of grammaticalization and lexicalization of adverbial relators stemming from deictic “imperatives” comparable with English elements like Down!, Up!, Away!, Out!. These elements are the sources for the evolution of prepositions and copredicative adverbials used to build patterns of “phrasal verbs” and particle constructions.
Zur lexikografischen Inszenierung von Geschlecht. Ein Streifzug durch die Einträge von Frau und Mann in neueren Wörterbüchern
Authors: Nübling Damaris
Published: March 2010

This article analyzes, for the first time, the lexicographic construction of gender in more recent editions of German dictionaries (from 1980 onwards). The article starts by presenting a survey of studies on this topic in other languages (French, Swedish, English). Then the dictionary entries of Frau ‘woman’ and Mann ‘man’ are scrutinized with respect to their definition(s), their structure, and their use in sentences of exemplification. The study shows that a surprisingly high degree of stereotypes still exists, including grammatical differences such as men occurring more frequently in subject positions and women dominating in object positions. While some dictionaries represent clear progress with respect to the representation of gender over time, others are dominated by androcentric attitudes.
Protogenin Defines a Transition Stage during Embryonic Neurogenesis and Prevents Precocious Neuronal Differentiation
Authors: Wong Yu-Hui , Lu Ai-Chu , Wang Yu-Chiuan , Cheng Hsu-Chen , Chang Celia , Chen Po-Hao , Yu Jenn-Yah , Fann Ming-Ji
Published: March 2010

Many Ig superfamily members are expressed in the developing nervous system, but the functions of these molecules during neurogenesis are not all clear. Here, we explore the expression and function of one of members of this superfamily, protogenin (PRTG), in the developing nervous system. Expression of PRTG protein is strong in the neural tube of mouse embryos between embryonic days 7.75 and 9.5 but disappears after embryonic day 10.5 when the neural progenitor marker nestin expresses prominently. Perturbation of PRTG activity in P19 embryonal carcinoma cells and in chick embryos, by either RNA interference or a dominant-negative PRTG mutant, increases neuronal differentiation. Using yeast two-hybrid screening and anin situbinding assay, we were able to identify ERdj3 (a stress-inducible endoplasmic reticulum DnaJ homolog) as a putative PRTG ligand. Addition of purified ERdj3 protein into the P19 differentiation assay reduced neurogenesis. This effect was blocked by addition of either a neutralizing antibody against PRTG or purified PRTG ectodomain protein, indicating that the effect of ERdj3 on neurogenesis is mediated through PRTG. Forced expression of ERdj3 in the chick neural tube also impairs neuronal differentiation. Together, these results suggest that expression of PRTG defines a stage between pluripotent epiblasts and committed neural progenitors, and its signaling plays a critical role in suppressing premature neuronal differentiation during early neural development.
Transcranial Direct Current Stimulation Facilitates Decision Making in a Probabilistic Guessing Task
Authors: Hecht David , Walsh Vincent , Lavidor Michal
Published: March 2010

In a random sequence of binary events where one alternative occurs more often than the other, humans tend to guess which of the two alternatives will occur next by trying to match the frequencies of previous occurrences. Based on split-brain and unilaterally damaged patients' performances, it has been proposed that the left hemisphere (LH) tends to match the frequencies, while the right hemisphere (RH) tends toward maximizing and always choosing the most frequent alternative. The current study used transcranial direct current stimulation (tDCS) to test this hemispheric asymmetry hypothesis by stimulating the dorsolateral prefrontal cortex of each hemisphere and simultaneously inhibiting the corresponding region in the homotopic hemisphere, while participants were engaged in a probabilistic guessing task. Results showed no difference in strategy between the three groups (RH anodal/LH cathodal, LH anodal/RH cathodal, no stimulation) as participants predominantly matched the frequencies of the two alternatives. However, when anodal tDCS was applied to the LH and cathodal tDCS applied to the RH, participants became quicker to select the most frequent alternative. This finding is in line with previous evidence on the involvement of the LH in probabilistic learning and reasoning and adds to a number of demonstrations of anodal tDCS leading to some behavioral enhancement or change in bias.
Control of Postnatal Apoptosis in the Neocortex byRhoA-Subfamily GTPases Determines Neuronal Density
Authors: Sanno Hitomi , Shen Xiao , Kuru Nilgün , Bormuth Ingo , Bobsin Kristin , Gardner Humphrey A. R. , Komljenovic Dorde , Tarabykin Victor , Erzurumlu Reha S. , Tucker Kerry L.
Published: March 2010

Apoptosis of neurons in the maturing neocortex has been recorded in a wide variety of mammals, but very little is known about its effects on cortical differentiation. Recent research has implicated the RhoA GTPase subfamily in the control of apoptosis in the developing nervous system and in other tissue types. Rho GTPases are important components of the signaling pathways linking extracellular signals to the cytoskeleton. To investigate the role of the RhoA GTPase subfamily in neocortical apoptosis and differentiation, we have engineered a mouse line in which a dominant-negative RhoA mutant (N19–RhoA) is expressed from theMaptlocus, such that all neurons of the developing nervous system are expressing the N19–RhoA inhibitor. Postnatal expression of N19–RhoA led to no major changes in neocortical anatomy. Six layers of the neocortex developed and barrels (whisker-related neural modules) formed in layer IV. However, the density and absolute number of neurons in the somatosensory cortex increased by 12–26% compared with wild-type littermates. This was not explained by a change in the migration of neurons during the formation of cortical layers but rather by a large decrease in the amount of neuronal apoptosis at postnatal day 5, the developmental maximum of cortical apoptosis. In addition, overexpression of RhoA in cortical neurons was seen to cause high levels of apoptosis. These results demonstrate that RhoA-subfamily members play a major role in developmental apoptosis in postnatal neocortex of the mouse but that decreased apoptosis does not alter cortical cytoarchitecture and patterning.
The Functional Properties of Barrel Cortex Neurons Projecting to the Primary Motor Cortex
Authors: Sato Takashi R. , Svoboda Karel
Published: March 2010

Nearby neurons, sharing the same locations within the mouse whisker map, can have dramatically distinct response properties. To understand the significance of this diversity, we studied the relationship between the responses of individual neurons and their projection targets in the mouse barrel cortex. Neurons projecting to primary motor cortex (MI) or secondary somatosensory area (SII) were labeled with red fluorescent protein (RFP) using retrograde viral infection. We usedin vivotwo-photon Ca2+imaging to map the responses of RFP-positive and neighboring L2/3 neurons to whisker deflections. Neurons projecting to MI displayed larger receptive fields compared with other neurons, including those projecting to SII. Our findings support the view that intermingled neurons in primary sensory areas send specific stimulus features to different parts of the brain.
Essential Role of Dopamine D2Receptor in the Maintenance of Wakefulness, But Not in Homeostatic Regulation of Sleep, in Mice
Authors: Qu Wei-Min , Xu Xin-Hong , Yan Ming-Ming , Wang Yi-Qun , Urade Yoshihiro , Huang Zhi-Li
Published: March 2010

Dopamine (DA) and its D2receptor (R) are involved in cognition, reward processing, and drug addiction. However, their roles in sleep–wake regulation remain unclear. Herein we investigated the role of D2R in sleep–wake regulation by using D2R knock-out (KO) mice and pharmacological manipulation. Compared with WT mice, D2R KO mice exhibited a significant decrease in wakefulness, with a concomitant increase in non-rapid eye movement (non-REM, NREM) and REM sleep and a drastic decrease in the low-frequency (0.75–2 Hz) electroencephalogram delta power of NREM sleep, especially during the first 4 h after lights off. The KO mice had decreased mean episode duration and increased episode numbers of wake and NREM sleep, many stage transitions between wakefulness and NREM sleep during the dark period, suggesting the instability of the wake stage in these D2R KO mice. When the KO mice were subjected to a cage change or an intraperitoneal saline injection, the latency to sleep in the KO mice decreased to half of the level for WT mice. The D2R antagonist raclopride mimicked these effects in WT mice. When GBR12909, a dopamine transport inhibitor, was administered intraperitoneally, it induced wakefulness in WT mice in a dose-dependent manner, but its arousal effect was attenuated to one-third in the D2R KO mice. However, these 2 genotypes showed an identical response in terms of sleep rebound after 2, 4, and 6 h of sleep deprivation. These results indicate that D2R plays an essential role in the maintenance of wakefulness, but not in homeostatic regulation of NREM sleep.
“Slow Activity Transients” in Infant Rat Visual Cortex:A Spreading Synchronous Oscillation Patterned by Retinal Waves
Authors: Colonnese Matthew T. , Khazipov Rustem
Published: March 2010

A primary feature of the preterm infant electroencephalogram is the presence of large infra-slow potentials containing rapid oscillations called slow activity transients (SATs). Such activity has not been described in animal models, and their generative mechanisms are unknown. Here we use direct-current and multisite extracellular, as well as whole-cell, recordingin vivoto demonstrate the existence of regularly repeating SATs in the visual cortex of infant rats before eye opening. Present only in absence of anesthesia, SATs at postnatal day 10–11 were identifiable as a separate group of long-duration (∼10 s) events that consisted of large (>1 mV) negative local-field potentials produced by the summation of multiple bursts of rapid oscillatory activity (15–30 Hz). SATs synchronized the vast majority of neuronal activity (87%) in the visual cortex before eye opening. Enucleation eliminated SATs, and their duration, interevent interval, and sub-burst structure matched those of phase III retinal waves recordedin vitro. Retinal waves, however, lacked rapid oscillations, suggesting that they arise centrally. Multielectrode recordings showed that SATs spread horizontally in cortex and synchronize activity at coactive locales via the rapid oscillations. SATs were clearly different from ongoing cortical activity, which was observable as a separate class of short bursts from postnatal day 9. Together, our data suggest that,in vivo, early cortical activity is primarily determined by peripheral inputs—retinal waves in visual cortex—that provide excitatory input, and by thalamocortical circuitry, which transforms this input to beta oscillations. We propose that the synchronous oscillations of SATs participate in the formation of visual circuitry.
Somatostatin Signaling in Neuronal Cilia Is Criticalfor Object Recognition Memory
Authors: Einstein Emily B. , Patterson Carlyn A. , Hon Beverly J. , Regan Kathleen A. , Reddi Jyoti , Melnikoff David E. , Mateer Marcus J. , Schulz Stefan , Johnson Brian N. , Tallent Melanie K.
Published: March 2010

Most neurons possess a single, nonmotile cilium that projects out from the cell surface. These microtubule-based organelles are important in brain development and neurogenesis; however, their function in mature neurons is unknown. Cilia express a complement of proteins distinct from other neuronal compartments, one of which is the somatostatin receptor subtype SST3. We show here that SST3is critical for object recognition memory in mice.sst3knock-out mice are severely impaired in discriminating novel objects, whereas they retain normal memory for object location. Further, systemic injection of an SST3antagonist (ACQ090) disrupts recall of familiar objects in wild-type mice. To examine mechanisms of SST3, we tested synaptic plasticity in CA1 hippocampus. Electrically evoked long-term potentiation (LTP) was normal insst3knock-out mice, while adenylyl cyclase/cAMP-mediated LTP was impaired. The SST3antagonist also disrupted cAMP-mediated LTP. Basal cAMP levels in hippocampal lysate were reduced insst3knock-out mice compared with wild-type mice, while the forskolin-induced increase in cAMP levels was normal. The SST3antagonist inhibited forskolin-stimulated cAMP increases, whereas the SST3agonist L-796,778 increased basal cAMP levels in hippocampal slices but not hippocampal lysate. Our results show that somatostatin signaling in neuronal cilia is critical for recognition memory and suggest that the cAMP pathway is a conserved signaling motif in cilia. Neuronal cilia therefore represent a novel nonsynaptic compartment crucial for signaling involved in a specific form of synaptic plasticity and in novelty detection.
Gating Modes in AMPA Receptors
Authors: Prieto Martin Loynaz , Wollmuth Lonnie P.
Published: March 2010

AMPA receptors are ligand-gated ion channels that show multiple conductance levels, indicating that gating of individual AMPA subunits is to some extent independent of the other subunits. To study AMPAR subunit interactions during activation gating, we recorded from single channels in the absence of channel block and desensitization and at negative and positive membrane potentials. In saturating glutamate, the relative occupancies of the various conductance levels are consistent with complete subunit independence. In contrast, the relative occupancies in subsaturating glutamate indicate that the channel switches between a low open probability mode and a high open probability mode in which the behavior of the channel is identical to that in saturating glutamate. These gating modes occur at both negative and positive potentials, with the high open probability mode becoming more prominent at positive potentials. The switch between gating modes and its modulation by voltage and other factors may constitute a novel mechanism regulating AMPAR-mediated synaptic activity.
Negative Blood Oxygen Level Dependence in the Rat:A Model for Investigating the Role of Suppression in Neurovascular Coupling
Authors: Boorman Luke , Kennerley Aneurin J. , Johnston David , Jones Myles , Zheng Ying , Redgrave Peter , Berwick Jason
Published: March 2010

Modern neuroimaging techniques rely on neurovascular coupling to show regions of increased brain activation. However, little is known of the neurovascular coupling relationships that exist for inhibitory signals. To address this issue directly we developed a preparation to investigate the signal sources of one of these proposed inhibitory neurovascular signals, the negative blood oxygen level-dependent (BOLD) response (NBR), in rat somatosensory cortex. We found a reliable NBR measured in rat somatosensory cortex in response to unilateral electrical whisker stimulation, which was located in deeper cortical layers relative to the positive BOLD response. Separate optical measurements (two-dimensional optical imaging spectroscopy and laser Doppler flowmetry) revealed that the NBR was a result of decreased blood volume and flow and increased levels of deoxyhemoglobin. Neural activity in the NBR region, measured by multichannel electrodes, varied considerably as a function of cortical depth. There was a decrease in neuronal activity in deep cortical laminae. After cessation of whisker stimulation there was a large increase in neural activity above baseline. Both the decrease in neuronal activity and increase above baseline after stimulation cessation correlated well with the simultaneous measurement of blood flow suggesting that the NBR is related to decreases in neural activity in deep cortical layers. Interestingly, the magnitude of the neural decrease was largest in regions showing stimulus-evoked positive BOLD responses. Since a similar type of neural suppression in surround regions was associated with a negative BOLD signal, the increased levels of suppression in positive BOLD regions could importantly moderate the size of the observed BOLD response.
Deletion of M1Muscarinic Acetylcholine Receptors Increases Amyloid PathologyIn VitroandIn Vivo
Authors: Davis Albert A. , Fritz Jason J. , Wess Jürgen , Lah James J. , Levey Allan I.
Published: March 2010

Alzheimer's disease (AD) is a progressive neurological disorder that causes dementia and poses a major public health crisis as the population ages. Aberrant processing of the amyloid precursor protein (APP) is strongly implicated as a proximal event in AD pathophysiology, but the neurochemical signals that regulate APP processing in the brain are not completely understood. Activation of muscarinic acetylcholine receptors (mAChRs) has been shown to affect APP processing and AD pathology, but less is known about the roles of specific mAChR subtypes. In this study, we used M1mAChR knock-out mice (M1KO) to isolate the effects of the M1mAChR on APP processing in primary neurons and on the development of amyloid pathology in a transgenic mouse model of AD. We demonstrate that the loss of M1mAChRs increases amyloidogenic APP processing in neurons, as evidenced by decreased agonist-regulated shedding of the neuroprotective APP ectodomain APPsα and increased production of toxic Aβ peptides. Expression of M1mAChRs on the M1KO background rescued this phenotype, indicating that M1mAChRs are sufficient to modulate nonamyloidogenic APP processing. In APPSwe/Indtransgenic mice, the loss of M1mAChRs resulted in increased levels of brain Aβ and greater accumulation of amyloid plaque pathology. Analysis of APP metabolites in APPSwe/Indbrain tissue indicates that the loss of M1mAChRs increases amyloidogenic APP processing. These results indicate that the M1mAChR is an important regulator of amyloidogenesis in the brain and provide strong support for targeting the M1mAChR as a therapeutic candidate in AD.
Robust Rendezvous of Heterogeneous Euler-Lagrange Systems on Packet-Switched NetworksRobustes Rendezvous von heterogenen Euler-Lagrange Systemen mithilfe paketvermittelnder Netzwerke
Authors: Münz Ulrich , Papachristodoulou Antonis , Allgöwer Frank
Published: March 2010

A robust rendezvous controller design for multi-agent systems (MAS) is presented. The agents are modeled as Euler-Lagrange systems which exchange their position information on a packet-switched communication network, where the resulting communication delay is modeled in a distributed delay framework. A synthesis method for static position feedback controllers for these agents is proposed. It achieves rendezvous for uncertain communication delays with bounded average delay and for heterogeneous uncertain agent dynamics. The controllers only have to satisfy certain design conditions that relate sector bounds of the agent dynamics, Lipschitz bounds of the controllers, and the average communication delays of the network. A major advantage of the presented design condition is that the controller parameters depend only on the dynamics of the corresponding agent and the average communication delay to its neighbors, but not on the dynamics of the other agents or the delays in other parts of the network. This decentralized feature of the controller design is particularly useful for large and heterogeneous MAS. The performance of the controllers is illustrated by simulation.
Bioequivalence between novel ready-to-use liquid formulations of the recombinant human GH Omnitrope and the original lyophilized formulations for reconstitution of Omnitrope and Genotropin
Authors: Fuhr Uwe , Tuculanu Daniel , Berghout Alexander , Balser Sigrid , Schwebig Arnd , Saenger Paul
Published: March 2010

Objective

Two strengths of a novel ready-to-use liquid preparation of the recombinant human GH (rhGH) Omnitrope were developed to increase the convenience for the patients.

Design

Omnitrope 3.3 mg/ml solution or Omnitrope 6.7 mg/ml solution was compared to Omnitrope 5 mg/ml powder and Genotropin 5 mg/ml powder in terms of pharmacokinetics, pharmacodynamics, safety, and local tolerance after a single s.c. dose of 5 mg.

Methods

Two randomized, double-blind, single-dose, three-way crossover studies were carried out in 36 young healthy volunteers each. Endogenous GH secretion was suppressed with a 25-h continuous i.v. infusion of octreotide (40 μg/h) starting 1 h before rhGH administration.

Results

Pharmacokinetic parameters were similar for the three treatments in both studies respectively. Bioequivalence criteria were met for area under the concentration–time curve (AUC) andCmax. Likewise, the pharmacodynamic parameters for IGF1, IGF-binding protein 3, and non-esterified fatty acid were similar for all preparations. No differences in adverse events were observed between groups.

Conclusions

Omnitrope 3.3 mg/ml solution, 6.7 mg/ml solution, and 5 mg/ml powder, and Genotropin 5 mg/ml powder are bioequivalent, have similar pharmacokinetic and pharmacodynamic profiles, and are equally safe. Overall, the products can be considered to be therapeutically interchangeable.
Inflammatory and endothelial dysfunction markers and proteinuria in persons with type 1 diabetes mellitus
Authors: Sahakyan Karine , Klein Barbara E K , Lee Kristine E , Tsai Michael Y , Klein Ronald
Published: March 2010

Objective

We examined the relationship of inflammatory and endothelial dysfunction markers with the prevalence and incidence of gross proteinuria (GP) in persons with type 1 diabetes mellitus.

Design

A longitudinal population-based cohort of persons with type 1 diabetes mellitus was followed from 1990–1992 through 2005–2007.

Methods

Prevalence and 15-year cumulative incidence of GP were defined as outcome variables. Serum high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), soluble vascular cell adhesion molecule-1 (VCAM-1), soluble intercellular adhesion molecule-1, and serum total homocysteine were measured. Multivariate logistic and discrete linear logistic regression modeling was used for data analysis.

Results

After controlling for duration of diabetes and other confounding factors, TNF-α (odds ratio (OR) 3.64; 95% confidence interval (CI) 2.33, 5.70), IL-6 (OR 1.41; 95% CI 1.06, 1.88), VCAM-1 (OR 13.35; 95% CI 5.39, 33.07), and homocysteine (OR 2.98; 95% CI 1.73, 5.16) were associated with prevalent proteinuria. Only hsCRP (OR 1.47; 95% CI 1.02, 2.11) was associated with incident proteinuria.

Conclusions

These findings suggest a role of inflammation and endothelial dysfunction as markers and contributors of the development of diabetic nephropathy in persons with type 1 diabetes mellitus.
Electrophysiological and auditory behavioral evaluation of individuals with left temporal lobe epilepsy
Authors: Rocha Caroline Nunes , Miziara Carmen Silvia Molleis Galego , Manreza Maria Luiza Giraldes de , Schochat Eliane
Published: March 2010

The purpose of this study was to determine the repercussions of left temporal lobe epilepsy (TLE) for subjects with left mesial temporal sclerosis (LMTS) in relation to the behavioral test-Dichotic Digits Test (DDT), event-related potential (P300), and to compare the two temporal lobes in terms of P300 latency and amplitude. We studied 12 subjects with LMTS and 12 control subjects without LMTS. Relationships between P300 latency and P300 amplitude at sites C3A1,C3A2,C4A1, and C4A2, together with DDT results, were studied in inter-and intra-group analyses. On the DDT, subjects with LMTS performed poorly in comparison to controls. This difference was statistically significant for both ears. The P300 was absent in 6 individuals with LMTS. Regarding P300 latency and amplitude, as a group, LMTS subjects presented trend toward greater P300 latency and lower P300 amplitude at all positions in relation to controls, difference being statistically significant for C3A1 and C4A2. However, it was not possible to determine laterality effect of P300 between affected and unaffected hemispheres.
Characterization of language and phonological working memory in patients with myoclonic astatic epileptic syndrome
Authors: Fukuda Marisa Tomoe Hebihara , Kutscher Kellen , Frizzo Ana Cláudia Figueiredo , Isaac Myrian de Lima , Fernandes Regina Maria França , Funayama Carolina Araújo Rodrigues
Published: March 2010

The course of myoclonic astatic epileptic syndrome (MAES) is variable and little information is available about cortical functions in the presence of the disease. The objective of the present study was to assess the phonological working memory (PWM) and the verbal language of six patients between 8 and 18 years old, on treatment for at least 5 years, and good control of seizures, diagnosed in the Service of Epilepsy of Hospital of Clinics of Ribeirão Preto, São Paulo University in Brazil. The Test of Repetition of Meaningless Words was used to assess PWM. Video-recorded of language samples were collected during spontaneous and directed activities for the study of verbal language and pragmatics. A qualitative analysis showed that all patients presented deficits in the execution of the PWM test and only one patient showed poor mastery of all aspects studied. These finds contribute to strategies of treatment for language problems of patients with MAES, focusing on PWA.
Portal Doppler ultrasound evaluation in myelitis by Schistosoma mansoni
Authors: Vidal Claudio Henrique Fernandes , Gurgel Fernando Viana , Ferreira Maria Lucia Brito , Coutinho Ana Lúcia , Azevedo Filho Hildo Rocha Cirne de
Published: March 2010

The mechanism for development of schistosomal myelitis has not yet been completely understood. Few publications have tried to establish a link between the general clinical presentation of the illness and its neurological manifestations. Objective: To evaluated the portal blood flow in patients with schistosomal myelitis and controls. Method: Forty-three individuals were evaluated using portal Doppler ultrasound. Group I consisted of 13 patients with the spinal form of schistosomiasis. Group II included 10 patients with intestinal and hepatointestinal forms of schistosomiasis, but no neurological symptoms; while group III involved 20 healthy controls. Results: Portal venous speed and portal venous flow were significantly elevated in group I (p<0.001) compared with the others. Conclusion: Doppler ultrasound demonstrated a situation of high flow within the portal venous system of patients with schistosomal myelitis.