bluuebunny/crossref_metadata_2025 huggingface dataset:
Sorption Properties of Ordered Mesoporous Silica for Toluene and Ethyl Acetate
Authors: Jin Weiyang , Wang Yuejuan , Wang Xueli , Jin Lingyun , Lu Jiqing , Luo Mengfei
Published: November 2011

The sorption properties of SBA-15 and MCM-41 for toluene and ethyl acetate were investigated by temperature programmed desorption (TPD) techniques and an analysis of breakthrough curves. The amount of toluene adsorbed onto SBA-15 was distinctly larger than that onto MCM-41, while the desorption temperature of toluene from the former was also higher than that from MCM-41. However, in the case of ethyl acetate, similar adsorption and desorption behaviours were observed on these two samples. The interaction between organic molecules and adsorbents was evaluated in terms of the affinity index. It was found that both SBA-15 and MCM-41 exhibited positive adsorption properties towards ethyl acetate but negative behaviours towards toluene. Compared to the MCM-41, the larger quantity of toluene retained by SBA-15 and the higher desorption temperature for toluene relative to MCM-41 were ascribed to the higher adsorption potential existing in the secondary pores of SBA-15.
Adsorption of Sulphur Dioxide Using Natural and Modified Gördes Clinoptilolites
Authors: Alver Burcu Erdoğan , Sakizci Meryem , Yörükoğullari Ertuğrul
Published: November 2011

The adsorption of SO2 onto clinoptilolite-rich zeolite tuff from Gördes (Turkey) (natural-G) and its cation-exchanged (Na+, K+, Ca2+ and Mg2+) forms was investigated up to 100 kPa pressure at two different temperatures (273 K and 293 K). The structural properties of the clinoptilolites were studied by X-ray diffraction (XRD) and Fourier-transform infrared (FT-IR) spectroscopy. Quantitative XRD analysis showed that the major component of the natural-G sample was clinoptilolite, together with minor amounts of feldspar, opal-CT, smectite, mica-illite and amorphous material (opal-A). It was established that the uptake of SO2 onto the adsorbents increased in the order Ca-G < natural-G < Mg-G < K-G < Na-G at both temperatures.
On the Resilience of Ad Hoc Distributed Simulation of Surface Transportation Systems with Unreliable Communications
Authors: Seshasayee Balasubramanian , Hunter Michael , Fujimoto Richard M. , Guensler Randall , Schwan Karsten , Kim Hoe Kyoung , Sirichoke Jason , Suh Wonho
Published: November 2011

The Dynamic Data Driven Application Systems (DDDAS) concept is examined in the context of monitoring and managing surface transportation systems in day-to-day and emergency scenarios. An approach to predicting future system states termed ad hoc distributed simulations is described. This approach uses on-line distributed simulation models that can incorporate real-time data and utilizes rollback operations to update state predictions as new information becomes available. This paper focuses on examining the reliability of ad hoc distributed simulations in mobile computing environments, and specifically, assessing the accuracy of future state predictions in the face of unreliable communications.
Data Driven Simulation to Support Model Building in the Social Sciences
Authors: Kennedy Catriona , Theodoropoulos Georgios , Sorge Volker , Ferrari Edward , Lee Peter , Skelcher Chris
Published: November 2011

Artificial intelligence (AI) can contribute to the management of a data driven simulation system, in particular with regard to adaptive selection of data and refinement of the model on which the simulation is based. We consider two different classes of intelligent agent that can control a data driven simulation: (a) an autonomous agent using internal simulation to test and refine a model of its environment and (b) an assistant agent managing a data-driven simulation to help humans understand a complex system (assisted model-building). We present a prototype implementation of an assistant agent to apply DDDAS to social simulations. The automation of the data-driven model development requires content interpretation of both the simulation and the corresponding real-world data. The paper discusses the use of Association Rule Mining to produce general logical statements about simulation and data content as well as the use of logical consistency checking to detect observations that refute the simulation predictions. Finally we consider ways in which this kind of assistant agent can cooperate with autonomous data collection and analysis agents to build a more complete and reliable picture of the observed system.
AMBROSia: An Overview and Recent Results
Authors: Golubchik Leana , Caron David , Das Abhimanyu , Dhariwal Amit , Govindan Ramesh , Kempe David , Oberg Carl , Sharma Abhishek , Stauffer Beth , Sukhatme Gaurav , Zhang Bin
Published: November 2011

Observing systems facilitate scientific studies by instrumenting the real world and collecting corresponding measurements, with the aim of detecting and tracking phenomena of interest. A wide range of critical environmental monitoring objectives in resource management, environmental protection, and public health all require distributed observing systems. The goal of such systems is to help scientists verify or falsify hypotheses with useful samples taken by the stationary and mobile units, as well as to analyze data autonomously to discover interesting trends or alarming conditions. In our AMBROSia project, we focus on a class of observing systems which are embedded into the environment, consist of stationary and mobile sensors, and react to collected observations by reconfiguring the system and adapting which observations are collected next. In this paper, we give an overview of AMBROSia.
Government's Role In Facilitating An Innovative Economy
Authors: Jacknis Norman
Published: November 2011

Governments have historically played a role in facilitating innovation in the private economy. This paper identifies the techniques that have been used in the modern industrial era, which are by now quite refined and widespread across the globe and at all levels of government. However because the innovation process itself needs some innovation, this paper also discusses the changing nature of the economy and innovation in this century and the implications for future effective government policies.
Signs of Potentially Disruptive Innovation in the Space Sector
Authors: Summerer Leopold
Published: November 2011

This paper reviews and analyses some specific conditions for innovation in the European space sector. Innovation has enabled the first steps of humans into space and remained a key central parameter ever since. On the other hand, the space sector lacks key parameters encouraging innovation. While governments have put in place instruments to overcome these deficiencies, the current mechanisms seem to address mainly incremental/sustaining innovation. It is argued that this situation might be leaving the space sector prone to changes coming from radical and disruptive innovation. Applying mechanisms developed for understanding disruptive innovation processes in the private sector, two specific current developments in the space sector are analyzed.
Leading Innovation Change - The Kotter Way
Authors: Gupta Praveen
Published: November 2011

Innovation has been considered necessary for solving every problem today. In any business meeting, conference or media innovation is discussed and desired. However, key challenges in realizing innovation are a well understood framework and an infrastructure for its successful deployment. Current frameworks including Open Innovation, Crowd Sourcing and many others do not address corporate needs in terms of credibility and for its body of knowledge for developing competency. Having established a credible and teachable framework for innovation, the author realized that organization leadership is unable to drive innovation due to misunderstanding of innovation principles and change management at the leadership level. Recognizing success of Prof. Kotter's Leading Change model, the author adapts the model to managing the innovation change [1]. This paper presents application of the Leading Change to innovation management and providing guidance to organization leadership for innovation deployment. Innovation deployment has become a necessity for organizations in knowledge age for achieving competitive edge and sustaining profitable growth.
Interaction of Wind-Waves and Currents in the Ems-Dollard Estuary
Authors: Hein H. , Mai S. , Barjenbruch U.
Published: November 2011

Physical processes in coastal waters and estuaries extend their influences on many economic and ecological processes in the coastal regions and affect the safety of the coastal defences. In a context with the global climate change, these physical processes underlie also inherent modifications. In order to win an impression of such future changes and of the probability of their occurrence, physically consistent simulations of these processes are used to describe how wind-waves and currents interact.

This paper presents an offline-coupled simulation using the models HAMSOM (HAMburg Shelf Ocean Model) and SWAN (Simulating Waves Nearshore). These state-of-the-art models excel by high computing speed, so that they offer an opportunity to simulate hydrological conditions and physical processes over longer time periods, e.g. decades. For the influence of currents on the waves, we estimate less influence on tidal flats, but stronger influence in the tidal channels.

Improvements in parameter estimation that were achieved by the interaction of currents and waves are described and discussed; we estimate new drag-coefficients for the hydrodynamic simulation. Because long-term simulations need to be simplified, a method is examined and presented that by-passes the direct online-coupling of models. For the aim of long term simulation improvements of the surface drag coefficient are useful, because online-coupled wind-wave models overcome the available machine time for climate runs. Our method yields an optimization regarding computing economy and physical consistency of simulations.
Acute Liver Injury Caused by Intravenous Amiodarone;Myoclonus Associated with Long-term Use of Diltiazem;Involuntary Movements Associated with Cetirizine;Cocaine-Induced Ischemic Bowel;Asenapine and Severe Allergic Reactions;Dapsone-Induced Methemoglobinemia;Neurotoxic Effects Associated with Antibiotic Use
Authors: Joel Sinister
Published: November 2011

The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration's (FDA's) MEDWATCH program (800-FDA-1088). If you have reported an interesting, preventable ADR to MEDWATCH, please consider sharing the account with our readers.
Rosuvastatin: Extended-Interval Dosing
Authors: Joyce A. Generali , Dennis J. Cada
Published: November 2011

This Hospital Pharmacy feature is extracted from Off-Label Drug Pacts, a quarterly publication available from Wolters Kluwer Health. Off-Label Drug Pacts is a practitioner-oriented resource for information about specific drug uses that are unapproved by the US Food and Drug Administration. This new guide to the literature enables the health care professional or clinician to quickly identify published studies on off-label uses and determine if a specific use is rational in a patient care scenario. References direct the reader to the full literature for more comprehensive information before patient care decisions are made. Direct questions or comments regarding Off-Label Drug Uses to jgeneral@kumc.edu .
Pharmacist Documentation of Fentanyl Patch Orders in an Academic Medical Center
Authors: Farivar Jahansouz , Judy Hsiao , Krisbma Dhillon , Pieter Helmons , Lamott Jo Anna , Shobha Kolan , Rabia Atayee
Published: November 2011

Purpose

The fentanyl transdermal patch label carries a boxed warning indicating that it should only be used in opioid-tolerant patients. Both prescribers and pharmacists must adhere to these recommendations to ensure safe use of the patches. Our goal was to determine the fentanyl patch documentation rate at our institution and evaluate the quality of documentation, and to make recommendations for improvement if appropriate to ensure patient safety.

Methods

We conducted a retrospective data analysis to determine pharmacist adherence rate to medical center documentation practices for fentanyl patch orders at UC San Diego Medical Center between July 2009 and July 2010.

Results

A total of 296 adult fentanyl patch orders were prescribed during the study period. Sixty-four of these orders were new initiations and 232 orders were continued from outpatient regimens. Overall, pharmacist documentation rate, without regard to completeness of notation, was 97.0%, with no difference between new and continuing orders. Evaluation of the quality of documentation showed that the most important factor lacking in the majority of documentations was duration of previous opioid therapy.

Conclusion

Examination of fentanyl patch documentation data suggests that the existing pharmacy notation system can be improved. We believe that a revised documentation template that includes source of information, chronic pain indication, opioid regimen, duration, daily oral morphine equivalent, pain assessment, and final patch plan will help to ensure the safety of prescribed patches and completeness of documentation. These findings can be used to develop policies and procedures to achieve complete adherence to transdermal fentanyl's boxed warning at any institution.
Pharmacy Residents' Experiences and Attitudes toward Participation in Cardiopulmonary Resuscitation (CPR) Events at Academic Medical Centers
Authors: Marcy T. DelMonte , John S. Clark
Published: November 2011

Purpose

To investigate practices related to pharmacy residents' involvement in cardiopulmonary resuscitation (CPR) events and attitudes of pharmacy residents toward their participation.

Methods

An online survey was sent to pharmacy residents using the University HealthSystem Consortium (UHC) e-mail listserv. Data were obtained from residents currently participating in CPR events as well as those not participating. The objectives of this study were to (a) determine the number of residents currently participating in CPR events, (b) describe their responsibilities and the training opportunities made available to them, and (c) describe residents' attitudes toward their training and overall participation.

Results

A total of 253 pharmacy residents completed the survey (44% response rate), with the majority being in their PGY1 year. Eighty-nine percent reported involvement in CPR events, with 82% reporting required participation. Although 52% of CPR participants reported feeling only “somewhat prepared” to attend CPR events, most felt useful to the CPR team. CPR participants were significantly more likely to “strongly agree” or “agree” that all pharmacy residents should be required to participate in CPR events (86% vs 46%; P < .001) and that CPR team members see pharmacy residents as important participants (69% vs 43%; P = .013). When asked if they would support initiating pharmacy resident CPR participation at their institution, the majority of non-participants “strongly agreed” or “agreed.”

Conclusion

Most residents participating in CPR events recognize the value of their services and view participation in CPR events as an important part of their residency experience.
The Role of Health System Pharmacy in Improving Influenza Vaccination Rates among Health Care Workers
Authors: Crystal Y. Girardot , Robert J. Weber
Published: November 2011

The Director's Forum series is written and edited by Robert J. Weber and Scott M. Mark and is designed to guide pharmacy leaders in establishing patient-centered services in hospitals and health systems. During the autumn months, health care professions and the media will advocate for immunizing all patients to prevent the occurrence and spread of influenza. A potential source of influenza in hospitalized patients is health care workers (HCWs) who have not been vaccinated. Pharmacists have long served as vaccine immunizers, advocates, and educators and may play an active role in improving vaccination rates among HCWs. Pharmacy directors should consider their department's role in influenza vaccination by becoming active partners in influenza prevention. By actively participating in making vaccines available in a variety of ways to HCWs, pharmacy directors can maximize the benefits of a hospital's employee vaccination program.
Chlorine-free catalysts for green synthesis of cyclic carbonates from carbon dioxide
Authors: Li Rui , Tong Xin , Li Xiaofang , Hu Changwen
Published: November 2011

This article provides an overview on recent progress in the green synthesis of cyclic carbonates (CCs) from carbon dioxide (CO2) catalyzed by chlorine-free catalysts. Special emphasis is placed on the synthetic routes and catalyst structures that govern the reactivity and selectivity.
Searching in Choice Mode: Consumer Decision Processes in Product Search with Recommendations
Authors: Dellaert Benedict G.C. , HÄubl Gerald
Published: November 2011

This article examines how a common form of decision assistance— recommendations that present products in order of their predicted attractiveness to a consumer—transforms decision processes during product search. Such recommendations induce a shift in consumers' decision orientation in search from being directed at whether additional alternatives should be inspected to identifying the best alternative among those already encountered, which is common when choosing from predetermined sets of alternatives. That is, recommendations cause consumers to search in “choice mode.” Evidence from three studies provides support for such a transformation of search decisions, which manifests itself in two respects. First, compared with unassisted search, recommendations lead consumers to assess a product they encounter in their search by comparing it less with the best one discovered up to that point and more with other previously inspected alternatives. Second, recommendations transform how variability in product attractiveness affects stopping decisions such that greater variability causes consumers to search less, which is contrary to what is commonly observed in search without recommendations.
Empfehlungen zur Diagnostik der Paroxysmalen nächtlichen Hämoglobinurie: deutsch – österreichischer Konsensus/Recommendations for the diagnosis of paroxysmal nocturnal hemoglobinuria: a German-Austrian consensus
Authors: Schrezenmeier Hubert , Bettelheim Peter , Panse Jens , Schubert Jörg , Höchsmann Britta , Röth Alexander , Nebe Thomas
Published: November 2011

Die paroxysmale nächtliche Hämoglobinurie (PNH) ist eine seltene, lebensbedrohliche hämatologische Erkrankung. Durch eine erworbene Mutation im PIG-A Gen von hämatopoetischen Progenitorzellen kommt es zu einem Fehlen des Glycosylphosphatidylinositols (GPI), einem gemeinsamen Ankermolekül für bestimmte Oberflächenproteine. Die Folge ist unter anderem ein Mangel des „decay-accelerating factor„ (DAF, charakterisiert durch CD55-Antkörper) und des „membrane inhibitor of reactive lysis„ (MIRL, markiert durch CD59-Antikörper) an der Oberfläche von Blutzellen mit daraus resultierender fehlender Komplementregulation, so dass es zu der charakteristischen intravasalen Hämolyse und thromboembolischen Komplikationen kommt. Die Analyse der Expression GPI-verankerter Proteine auf Blutzellen ist in der PNH-Diagnostik und Verlaufskontrolle der anerkannte Goldstandard. In den kürzlich veröffentlichten internationalen Leitlinien stehen manche Aspekte weiterhin zur Diskussion. Wir haben auf der Grundlage dieser Leitlinien praktische Empfehlungen diskutiert und sind zu dem vorliegenden deutsch-österreichischen Konsensuspapier gelangt, welches konkrete Vorschläge, beginnend von der Indikationsstellung über präanalytische Aspekte bis hin zur Durchführung der Immunphänotypisierung und Befundinterpretation, präsentiert. Vorgeschlagen wird eine Zweistufendiagnostik: Die Stufe 1 ist als Screening zu sehen. Die Diagnostikstufe 2 dient der Befundbestätigung. Diese Stufe sollten Speziallabore übernehmen, welche umfassende Erfahrung mit PNH haben. Anhand eines Algorithmus zur Stufendiagnostik werden konkrete Empfehlungen gegeben, welches Antikörperpanel in welcher Diagnostikstufe sinnvoll zum Einsatz kommen sollte. In Tabellenform werden die gängigen Fehlerquellen und deren Behebung aufgegriffen. Dieser Konsens soll Labore unterstützen, möglichst zeitig eine korrekte Diagnose zu stellen, was für den Patienten therapeutisch und prognostisch von entscheidender Bedeutung ist. Dabei sollen jedoch Praktikabilität und Wirtschaftlichkeit der Maßnahmen nicht unberücksichtigt gelassen werden.
Cosine Directional Tuning of Theta Cell Burst Frequencies: Evidence for Spatial Coding by Oscillatory Interference
Authors: Welday Adam C. , Shlifer I. Gary , Bloom Matthew L. , Zhang Kechen , Blair Hugh T.
Published: November 2011

The rodent septohippocampal system contains “theta cells,” which burst rhythmically at 4–12 Hz, but the functional significance of this rhythm remains poorly understood (Buzsáki, 2006). Theta rhythm commonly modulates the spike trains of spatially tuned neurons such as place (O'Keefe and Dostrovsky, 1971), head direction (Tsanov et al., 2011a), grid (Hafting et al., 2005), and border cells (Savelli et al., 2008; Solstad et al., 2008). An “oscillatory interference” theory has hypothesized that some of these spatially tuned neurons may derive their positional firing from phase interference among theta oscillations with frequencies that are modulated by the speed and direction of translational movements (Burgess et al., 2005, 2007). This theory is supported by studies reporting modulation of theta frequency by movement speed (Rivas et al., 1996; Geisler et al., 2007; Jeewajee et al., 2008a), but modulation of theta frequency by movement direction has never been observed. Here we recorded theta cells from hippocampus, medial septum, and anterior thalamus of freely behaving rats. Theta cell burst frequencies varied as the cosine of the rat's movement direction, and this directional tuning was influenced by landmark cues, in agreement with predictions of the oscillatory interference theory. Computer simulations and mathematical analysis demonstrated how a postsynaptic neuron can detect location-dependent synchrony among inputs from such theta cells, and thereby mimic the spatial tuning properties of place, grid, or border cells. These results suggest that theta cells may serve a high-level computational function by encoding a basis set of oscillatory signals that interfere with one another to synthesize spatial memory representations.
Increase in Cortical Pyramidal Cell Excitability Accompanies Depression-Like Behavior in Mice: A Transcranial Magnetic Stimulation Study
Authors: Sun Peng , Wang Furong , Wang Li , Zhang Yu , Yamamoto Ryo , Sugai Tokio , Zhang Qing , Wang Zhengda , Kato Nobuo
Published: November 2011

Clinical evidence suggests that cortical excitability is increased in depressives. We investigated its cellular basis in a mouse model of depression. In a modified version of forced swimming (FS), mice were initially forced to swim for 5 consecutive days and then were treated daily with repetitive transcranial magnetic stimulation (rTMS) or sham treatment for the following 4 weeks without swimming. On day 2 through day 5, the mice manifested depression-like behaviors. The next and last FS was performed 4 weeks later, which revealed a 4 week maintenance of depression-like behavior in the sham mice. In slices from the sham controls, excitability in cingulate cortex pyramidal cells was elevated in terms of membrane potential and frequencies of spikes evoked by current injection. Depolarized resting potential was shown to depend on suppression of large conductance calcium-activated potassium (BK) channels. This BK channel suppression was confirmed by measuring spike width, which depends on BK channels. Chronic rTMS treatment during the 4 week period significantly reduced the depression-like behavior. In slices obtained from the rTMS mice, normal excitability and BK channel activity were recovered. Expression of a scaffold protein Homer1a was reduced by the FS and reversed by rTMS in the cingulate cortex. Similar recovery in the same behavioral, electrophysiological, and biochemical features was observed after chronic imipramine treatment. The present study demonstrated that manifestation and disappearance of depression-like behavior are in parallel with increase and decrease in cortical neuronal excitability in mice and suggested that regulation of BK channels by Homer1a is involved in this parallelism.
On the Distribution of Firing Rates in Networks of Cortical Neurons
Authors: Roxin Alex , Brunel Nicolas , Hansel David , Mongillo Gianluigi , van Vreeswijk Carl
Published: November 2011

The distribution ofin vivoaverage firing rates within local cortical networks has been reported to be highly skewed and long tailed. The distribution of average single-cell inputs, conversely, is expected to be Gaussian by the central limit theorem. This raises the issue of how a skewed distribution of firing rates might result from a symmetric distribution of inputs. We argue that skewed rate distributions are a signature of the nonlinearity of thein vivo f–Icurve. Duringin vivoconditions, ongoing synaptic activity produces significant fluctuations in the membrane potential of neurons, resulting in an expansive nonlinearity of thef–Icurve for low and moderate inputs. Here, we investigate the effects of single-cell and network parameters on the shape of thef–Icurve and, by extension, on the distribution of firing rates in randomly connected networks.
The Anticonvulsant Response to Valproate in Kindled Rats Is Correlated with Its Effect on Neuronal Firing in the Substantia Nigra Pars Reticulata: A New Mechanism of Pharmacoresistance
Authors: Töllner Kathrin , Wolf Saskia , Löscher Wolfgang , Gernert Manuela
Published: November 2011

Resistance to antiepileptic drugs (AEDs) is a major problem in epilepsy treatment. However, mechanisms of resistance are only incompletely understood. We have recently shown that repeated administration of the AED phenytoin allows selecting resistant and responsive rats from the amygdala kindling model of epilepsy, providing a tool to study mechanisms of AED resistance. We now tested whether individual amygdala-kindled rats also differ in their anticonvulsant response to the major AED valproate (VPA) and which mechanism may underlie the different response to VPA. VPA has been proposed to act, at least in part, by reducing spontaneous activity in the substantia nigra pars reticulata (SNr), a main basal ganglia output structure involved in seizure propagation, seizure control, and epilepsy-induced neuroplasticity. Thus, we evaluated whether poor anticonvulsant response to VPA is correlated with low efficacy of VPA on SNr firing rate and pattern in kindled rats. We found (1) that good and poor VPA responders can be selected in kindled rats by repeatedly determining the effect of VPA on the electrographic seizure threshold, and (2) a significant correlation between the anticonvulsant response to VPA in kindled rats and its effect on SNr firing rate and pattern. The less VPA was able to raise seizure threshold, the lower was the VPA-induced reduction of SNr firing rate and the VPA-induced regularity of SNr firing. The data demonstrate for the first time an involvement of the SNr in pharmacoresistant experimental epilepsy and emphasize the relevance of the basal ganglia as target structures for new treatment options.
Dendritic Spine Dynamics Regulate the Long-Term Stability of Synaptic Plasticity
Authors: O'Donnell Cian , Nolan Matthew F. , van Rossum Mark C. W.
Published: November 2011

Long-term synaptic plasticity requires postsynaptic influx of Ca2+and is accompanied by changes in dendritic spine size. Unless Ca2+influx mechanisms and spine volume scale proportionally, changes in spine size will modify spine Ca2+concentrations during subsequent synaptic activation. We show that the relationship between Ca2+influx and spine volume is a fundamental determinant of synaptic stability. If Ca2+influx is undercompensated for increases in spine size, then strong synapses are stabilized and synaptic strength distributions have a single peak. In contrast, overcompensation of Ca2+influx leads to binary, persistent synaptic strengths with double-peaked distributions. Biophysical simulations predict that CA1 pyramidal neuron spines are undercompensating. This unifies experimental findings that weak synapses are more plastic than strong synapses, that synaptic strengths are unimodally distributed, and that potentiation saturates for a given stimulus strength. We conclude that structural plasticity provides a simple, local, and general mechanism that allows dendritic spines to foster both rapid memory formation and persistent memory storage.
Glutamate Spillover Promotes the Generation of NMDA Spikes
Authors: Chalifoux Jason R. , Carter Adam G.
Published: November 2011

NMDA spikes are prominent in the basal dendrites of cortical pyramidal neurons and greatly expand their ability to integrate synaptic inputs. Calcium (Ca) signals during these spikes are important for synaptic plasticity and fundamentally depend on activation of NMDA receptors. However, the factors that shape the activation of these receptors and the initiation of NMDA spikes remain unclear. Here we examine the properties of NMDA spikes in the basal dendrites of layer 5 pyramidal neurons in the mouse prefrontal cortex. Using two-photon imaging, we demonstrate that NMDA spikes evoke large Ca signals in both postsynaptic spines and nearby dendrites. We find that the dendrite Ca signals depend on NMDA and AMPA receptors but not sodium (Na) or Ca channels. Using voltage-clamp recordings, we show that activation of dendrite NMDA receptors is enhanced by concerted synaptic activity. Blocking glutamate reuptake further increases activation of these receptors and promotes the initiation of NMDA spikes. We conclude that glutamate spillover and recruitment of extrasynaptic receptors contribute to the initiation of NMDA spikes. These results have important implications for how synaptic activity generates both electrical and biochemical signals in dendrites and spines.
Overexpression of CREB in the Nucleus Accumbens Shell Increases Cocaine Reinforcement in Self-Administering Rats
Authors: Larson Erin B. , Graham Danielle L. , Arzaga Rose R. , Buzin Nicole , Webb Joseph , Green Thomas A. , Bass Caroline E. , Neve Rachael L. , Terwilliger Ernest F. , Nestler Eric J. , Self David W.
Published: November 2011

Chronic exposure to addictive drugs enhances cAMP response element binding protein (CREB)-regulated gene expression in nucleus accumbens (NAc), and these effects are thought to reduce the positive hedonic effects of passive cocaine administration. Here, we used viral-mediated gene transfer to produce short- and long-term regulation of CREB activity in NAc shell of rats engaging in volitional cocaine self-administration. Increasing CREB expression in NAc shell markedly enhanced cocaine reinforcement of self-administration behavior, as indicated by leftward (long-term) and upward (short-term) shifts in fixed ratio dose–response curves. CREB also increased the effort exerted by rats to obtain cocaine on more demanding progressive ratio schedules, an effect highly correlated with viral-induced modulation of BDNF protein in the NAc shell. CREB enhanced cocaine reinforcement when expressed either throughout acquisition of self-administration or when expression was limited to postacquisition tests, indicating a direct effect of CREB independent of reinforcement-related learning. Downregulating endogenous CREB in NAc shell by expressing a short hairpin RNA reduced cocaine reinforcement in similar tests, while overexpression of a dominant-negative CREBS133Amutant had no significant effect on cocaine self-administration. Finally, increasing CREB expression after withdrawal from self-administration enhanced cocaine-primed relapse, while reducing CREB levels facilitated extinction of cocaine seeking, but neither altered relapse induced by cocaine cues or footshock stress. Together, these findings indicate that CREB activity in NAc shell increases the motivation for cocaine during active self-administration or after withdrawal from cocaine. Our results also highlight that volitional and passive drug administration can lead to substantially different behavioral outcomes.
Phox2b-Expressing Neurons of the Parafacial Region Regulate Breathing Rate, Inspiration, and Expiration in Conscious Rats
Authors: Abbott Stephen B. G. , Stornetta Ruth L. , Coates Melissa B. , Guyenet Patrice G.
Published: November 2011

The retrotrapezoid nucleus contains Phox2b-expressing glutamatergic neurons (RTN-Phox2b neurons) that regulate breathing in a CO2-dependent manner. Here we use channelrhodopsin-based optogenetics to explore how these neurons control breathing in conscious and anesthetized adult rats. Respiratory entrainment (pacing) of breathing frequency (fR) was produced over 57% (anesthetized) and 28% (conscious) of the natural frequency range by burst activation of RTN-Phox2b neurons (3–8 × 0.5–20 ms pulses at 20 Hz). In conscious rats, pacing under normocapnic conditions increased tidal volume (VT) and each inspiration was preceded by active expiration, denoting abdominal muscle contraction. During long-term pacing VTreturned to prestimulation levels, suggesting that central chemoreceptors such as RTN-Phox2b neurons regulate VTpartly independently of their effect on fR. Randomly applied light trains reset the respiratory rhythm and shortened the expiratory phase when the stimulus coincided with late-inspiration or early-expiration. Importantly, continuous (20 Hz) photostimulation of the RTN-Phox2b neurons and a saturating CO2concentration produced similar effects on breathing that were much larger than those elicited by phasic RTN stimulation.

In sum, consistent with their anatomical projections, RTN-Phox2b neurons regulate lung ventilation by controlling breathing frequency, inspiration, and active expiration. Adult RTN-Phox2b neurons can entrain the respiratory rhythm if their discharge is artificially synchronized, but continuous activation of these neurons is much more effective at increasing lung ventilation. These results suggest that RTN-Phox2b neurons are no longer rhythmogenic in adulthood and that their average discharge rate may be far more important than their discharge pattern in driving lung ventilation.
Segregation and Pathfinding of Callosal Axons through EphA3 Signaling
Authors: Nishikimi Mitsuaki , Oishi Koji , Tabata Hidenori , Torii Kenichi , Nakajima Kazunori
Published: November 2011

The corpus callosum, composed of callosal axons, is the largest structure among commissural connections in eutherian animals. Axon pathfinding of callosal neurons has been shown to be guided by intermediate targets, such as midline glial structures. However, it has not yet been understood completely how axon-axon interactions, another major mechanism for axon pathfinding, are involved in the pathfinding of callosal neurons. Here, we show that callosal axons from the medial and lateral regions of the mouse cerebral cortex pass through the dorsal and ventral parts, respectively, of the corpus callosum. Using an explant culture system, we observed that the axons from the medial and lateral cortices were segregated from each otherin vitro, and that this segregation was attenuated by inhibition of EphA3 signaling. We also found that knockdown of EphA3, which is preferentially expressed in the lateral cortex, resulted in disorganized segregation of the callosal axons and disrupted axon pathfindingin vivo. These results together suggest the role of axonal segregation in the corpus callosum, mediated at least in part by EphA3, in correct pathfinding of callosal neurons.
CX3CL1 Is Neuroprotective in Permanent Focal Cerebral Ischemia in Rodents
Authors: Cipriani Raffaela , Villa Pia , Chece Giuseppina , Lauro Clotilde , Paladini Alessandra , Micotti Edoardo , Perego Carlo , De Simoni Maria-Grazia , Fredholm Bertil B. , Eusebi Fabrizio , Limatola Cristina
Published: November 2011

The chemokine CX3CL1 and its receptor CX3CR1 are constitutively expressed in the nervous system. In this study, we usedin vivomurine models of permanent middle cerebral artery occlusion (pMCAO) to investigate the protective potential of CX3CL1. We report that exogenous CX3CL1 reduced ischemia-induced cerebral infarct size, neurological deficits, and caspase-3 activation. CX3CL1-induced neuroprotective effects were long lasting, being observed up to 50 d after pMCAO in rats. The neuroprotective action of CX3CL1 in different models of brain injuries is mediated by its inhibitory activity on microglia and,in vitro, requires the activation of adenosine receptor 1 (A1R). We show that, in the presence of the A1R antagonist 1,3-dipropyl-8-cyclopentylxanthine and inA1R−/−mice, the neuroprotective effect of CX3CL1 on pMCAO was abolished, indicating the critical importance of the adenosine system in CX3CL1 protection alsoin vivo. In apparent contrast with the above reported data but in agreement with previous findings,cx3cl1−/−andcx3cr1GFP/GFPmice, respectively, deficient in CX3CL1 or CX3CR1, had less severe brain injury on pMCAO, and the administration of exogenous CX3CL1 increased brain damage incx3cl1−/−ischemic mice. We also report that CX3CL1 induced a different phagocytic activity in wild type andcx3cl1−/−microgliain vitroduring cotreatment with the medium conditioned by neurons damaged by oxygen-glucose deprivation. Together, these data suggest that acute administration of CX3CL1 reduces ischemic damage via an adenosine-dependent mechanism and that the absence of constitutive CX3CL1–CX3CR1 signaling changes the outcome of microglia-mediated effects during CX3CL1 administration to ischemic brain.
Focal Manipulations of Formant Trajectories Reveal a Role of Auditory Feedback in the Online Control of Both Within-Syllable and Between-Syllable Speech Timing
Authors: Cai Shanqing , Ghosh Satrajit S. , Guenther Frank H. , Perkell Joseph S.
Published: November 2011

Within the human motor repertoire, speech production has a uniquely high level of spatiotemporal complexity. The production of running speech comprises the traversing of spatial positions with precisely coordinated articulator movements to produce 10–15 sounds/s. How does the brain use auditory feedback, namely the self-perception of produced speech sounds, in the online control of spatial and temporal parameters of multisyllabic articulation? This question has important bearings on the organizational principles of sequential actions, yet its answer remains controversial due to the long latency of the auditory feedback pathway and technical challenges involved in manipulating auditory feedback in precisely controlled ways during running speech. In this study, we developed a novel technique for introducing time-varying, focal perturbations in the auditory feedback during multisyllabic, connected speech. Manipulations of spatial and temporal parameters of the formant trajectory were tested separately on two groups of subjects as they uttered “I owe you a yo-yo.” Under these perturbations, significant and specific changes were observed in both the spatial and temporal parameters of the produced formant trajectories. Compensations to spatial perturbations were bidirectional and opposed the perturbations. Furthermore, under perturbations that manipulated the timing of auditory feedback trajectory (slow-down or speed-up), significant adjustments in syllable timing were observed in the subjects' productions. These results highlight the systematic roles of auditory feedback in the online control of a highly over-learned action as connected speech articulation and provide a first look at the properties of this type of sensorimotor interaction in sequential movements.
Optimal Control of Natural Eye-Head Movements Minimizes the Impact of Noise
Authors: Sağlam Murat , Lehnen Nadine , Glasauer Stefan
Published: November 2011

When shifting gaze to foveate a new target, humans mostly choose a unique set of eye and head movements from an infinite number of possible combinations. This stereotypy suggests that a general principle governs the movement choice. Here, we show that minimizing the impact of uncertainty, i.e., noise affecting motor performance, can account for the choice of combined eye–head movements. This optimization criterion predicts all major features of natural eye–head movements—including the part where gaze is already on target and the eye counter-rotates—such as movement durations, relative eye–head contributions, velocity profiles, and the dependency of gaze shifts on initial eye position. As a critical test of this principle, we show that it also correctly predicts changes in eye and head movement imposed by an experimental increase in the head moment of inertia. This suggests that minimizing the impact of noise is a simple and powerful principle that explains the choice of a unique set of movement profiles and segment coordination in goal-directed action.
Tonic Nanomolar Dopamine Enables an Activity-Dependent Phase Recovery Mechanism That Persistently Alters the Maximal Conductance of the Hyperpolarization-Activated Current in a Rhythmically Active Neuron
Authors: Rodgers Edmund W. , Fu Jing Jing , Krenz Wulf-Dieter C. , Baro Deborah J.
Published: November 2011

The phases at which network neurons fire in rhythmic motor outputs are critically important for the proper generation of motor behaviors. The pyloric network in the crustacean stomatogastric ganglion generates a rhythmic motor output wherein neuronal phase relationships are remarkably invariant across individuals and throughout lifetimes. The mechanisms for maintaining these robust phase relationships over the long-term are not well described. Here we show that tonic nanomolar dopamine (DA) acts at type 1 DA receptors (D1Rs) to enable an activity-dependent mechanism that can contribute to phase maintenance in the lateral pyloric (LP) neuron. The LP displays continuous rhythmic bursting. The activity-dependent mechanism was triggered by a prolonged decrease in LP burst duration, and it generated a persistent increase in the maximal conductance (Gmax) of the LP hyperpolarization-activated current (Ih), but only in the presence of steady-state DA. Interestingly, micromolar DA produces an LP phase advance accompanied by a decrease in LP burst duration that abolishes normal LP network function. During a 1 h application of micromolar DA, LP phase recovered over tens of minutes because, the activity-dependent mechanism enabled by steady-state DA was triggered by the micromolar DA-induced decrease in LP burst duration. Presumably, this mechanism restored normal LP network function. These data suggest steady-state DA may enable homeostatic mechanisms that maintain motor network output during protracted neuromodulation. This DA-enabled, activity-dependent mechanism to preserve phase may be broadly relevant, as diminished dopaminergic tone has recently been shown to reduceIhin rhythmically active neurons in the mammalian brain.
Spinocerebellar Ataxia Type 7 Cerebellar Disease Requires the Coordinated Action of Mutant Ataxin-7 in Neurons and Glia, and Displays Non-Cell-Autonomous Bergmann Glia Degeneration
Authors: Furrer Stephanie A. , Mohanachandran Mathini S. , Waldherr Sarah M. , Chang Christopher , Damian Vincent A. , Sopher Bryce L. , Garden Gwenn A. , La Spada Albert R.
Published: November 2011

Spinocerebellar ataxia type 7 (SCA7) is a dominantly inherited disorder characterized by cerebellum and brainstem neurodegeneration. SCA7 is caused by a CAG/polyglutamine (polyQ) repeat expansion in the ataxin-7 gene. We previously reported that directed expression of polyQ-ataxin-7 in Bergmann glia (BG) in transgenic mice leads to ataxia and non-cell-autonomous Purkinje cell (PC) degeneration. To further define the cellular basis of SCA7, we derived a conditional inactivation mouse model by inserting a loxP-flanked ataxin-7 cDNA with 92 repeats into the translational start site of the murine prion protein (PrP) gene in a bacterial artificial chromosome (BAC). ThePrP-floxed-SCA7-92Q BACmice developed neurological disease, and exhibited cerebellar degeneration and BG process loss. To inactivate polyQ-ataxin-7 expression in specific cerebellar cell types, we crossedPrP-floxed-SCA7-92Q BACmice withGfa2-Cretransgenic mice (to direct Cre to BG) orPcp2-Cretransgenic mice (which yields Cre in PCs and inferior olive). Excision of ataxin-7 from BG partially rescued the behavioral phenotype, but did not prevent BG process loss or molecular layer thinning, while excision of ataxin-7 from PCs and inferior olive provided significantly greater rescue and prevented both pathological changes, revealing a non-cell-autonomous basis for BG pathology. When we prevented expression of mutant ataxin-7 in BG, PCs, and inferior olive by derivingGfa2-Cre;Pcp2-Cre;PrP-floxed-SCA7-92Q BACtriple transgenic mice, we noted a dramatic improvement in SCA7 disease phenotypes. These findings indicate that SCA7 disease pathogenesis involves a convergence of alterations in a variety of different cell types to fully recapitulate the cerebellar degeneration.
From Synapse to Nucleus and Back Again—Communication over Distance within Neurons: Figure 1.
Authors: Fainzilber Mike , Budnik Vivian , Segal Rosalind A. , Kreutz Michael R.
Published: November 2011

How do neurons integrate intracellular communication from synapse to nucleus and back? Here we briefly summarize aspects of this topic covered by a symposium at Neuroscience 2011. A rich repertoire of signaling mechanisms link both dendritic terminals and axon tips with neuronal soma and nucleus, using motor-dependent transport machineries to traverse the long intracellular distances along neuronal processes. Activation mechanisms at terminals include localized translation of dendritic or axonal RNA, proteolytic cleavage of receptors or second messengers, and differential phosphorylation of signaling moieties. Signaling complexes may be transported in endosomes, or as non-endosomal complexes associated with importins and dynein. Anterograde transport of RNA granules from the soma to neuronal processes, coupled with retrograde transport of proteins translated locally at terminals or within processes, may fuel ongoing bidirectional communication between soma and synapse to modulate synaptic plasticity as well as neuronal growth and survival decisions.