bluuebunny/crossref_metadata_2025 huggingface dataset:
Competence Implies Credibility
Authors: Moscarini Giuseppe
Published: March 2007

The (reputation for) competence of a central bank at doing its job makes monetary policy under discretion credible and transparent. Based on its reading of the state of the economy, the central bank announces its policy intentions to the public in a cheap-talk game. The precision of its private signal measures its competence. The fineness of the equilibrium message space measures its credibility and transparency. This is increasing in the competence/inflation bias ratio: the public expects a competent central bank to use its discretion more to pursue its “objective” targets than to surprise expectations and stimulate output. (JEL E52, E58)
What Are Stock Investors' Actual Historical Returns? Evidence from Dollar-Weighted Returns
Authors: Dichev Ilia D
Published: March 2007

The existing literature typically does not differentiate between security returns and the returns of investors in these securities. This study clarifies that investor and security returns differ because of the timing and magnitude of investor capital flows into and out of these securities. The empirical results indicate that actual investor returns are systematically lower than buy-and-hold returns for nearly all major international stock markets. These results imply that the historical equity premium and the cost of equity capital are likely lower than previously thought. (JEL G11, G12, G15)
Consumer Bankruptcy: A Fresh Start
Authors: Livshits Igor , MacGee James , Tertilt Michèle
Published: March 2007

Consumer bankruptcy provides partial insurance against bad luck, but, by driving up interest rates, makes life-cycle smoothing more difficult. We argue that to assess this trade-off one needs a quantitative model of consumer bankruptcy with three key features: life-cycle component, idiosyncratic earnings uncertainty, and expense uncertainty (exogenous negative shocks to household balance sheets). We find that transitory and persistent earnings shocks have very different implications for evaluating bankruptcy rules. More persistent shocks make the bankruptcy option more desirable. Larger transitory shocks have the opposite effect. Our findings suggest the current US bankruptcy system may be desirable for reasonable parameter values. (JEL D14, D91, K35)
Structural Change in a Multisector Model of Growth
Authors: Ngai L. Rachel , Pissarides Christopher A
Published: March 2007

We study a multisector model of growth with differences in TFP growth rates across sectors and derive sufficient conditions for the coexistence of structural change, characterized by sectoral labor reallocation and balanced aggregate growth. The conditions are weak restrictions on the utility and production functions. Along the balanced growth path, labor employed in the production of consumption goods gradually moves to the sector with the lowest TFP growth rate, until in the limit it is the only sector with nontrivial employment of this kind. The employment shares of intermediate and capital goods remain constant during the reallocation process. (JEL O41)
Individual Perceptions of the Criminal Justice System
Authors: Lochner Lance
Published: March 2007

This paper empirically examines belief updating of the perceived probability of arrest and its criminal deterrence effects using two longitudinal data sources. While beliefs about the probability of arrest are positively correlated with local official arrest rates, they are unresponsive to information acquired from random individuals and local neighborhood conditions. Importantly, perceptions respond to changes in an individual's criminal and arrest history. Young males who engage in crime without getting arrested revise their perceived probability of arrest downward, while those who are arrested revise their probability upward. Estimates suggest that beliefs about the probability of arrest significantly deter crime. (JEL K42)
Vignettes and Self-Reports of Work Disability in the United States and the Netherlands
Authors: Kapteyn Arie , Smith James P , Soest Arthur van
Published: March 2007

In contrast to the believed similarity in their health outcomes, workers in different Western countries report very different rates of work disability. Using new data from the United States and the Netherlands, we offer a partial resolution to this paradox. We find that observed differences in reported work disability largely stem from the fact that Dutch respondents have a lower threshold in reporting whether they have a work disability than American respondents. For those who do not suffer from pain, work disability is similar in both countries once thresholds are the same. For respondents with pain, however, a significant difference remains. (JEL J14, J28)
Credible Commitment to Optimal Escape from a Liquidity Trap: The Role of the Balance Sheet of an Independent Central Bank
Authors: Jeanne Olivier , Svensson Lars E. O
Published: March 2007

Central banks target CPI inflation; independent central banks are concerned about their balance sheet and the level of their capital. The first fact makes it difficult for a central bank to implement the optimal escape from a liquidity trap, because it undermines a commitment to overshoot the inflation target. We show that the second fact provides a solution. Capital concerns provide a mechanism for an independent central bank to commit to inflate ex post. The optimal policy can take the form of a currency depreciation combined with a crawling peg, a policy advocated by Svensson as the “Foolproof Way” to escape from a liquidity trap. (JEL E31, E52, E58, E62)
Panitumumab: A Fully Human Monoclonal Antibody with Activity in Metastatic Colorectal Cancer
Authors: Saadeh Claire E , Lee H Stephen
Published: March 2007

Objective:

To review the pharmacology, pharmacokinetics, clinical trials, adverse effects, and drug interactions of panitumumab.

Data Sources:

A MEDLINE search was conducted (1966–February 2007) using the search terms panitumumab, ABX-EGF, E7.6.3, monoclonal antibody, colorectal neoplasm, epidermal growth factor receptor, EGFr, and epidermal growth factor receptor signal transduction. Articles and abstracts were further identified from the American Society of Clinical Oncology and the National Comprehensive Cancer Network.

Study Selection and Data Extraction:

Clinical trials evaluating panitumumab for solid tumors were selected from the data sources. All published relevant abstracts were included.

Data Synthesis:

The most recent developments in the treatment of metastatic colorectal cancer include the monoclonal antibodies targeted against vascular endothelial growth factor and the epidermal growth factor receptor (EGFr). Panitumumab is the first fully human monoclonal antibody that binds to EGFr. Clinical activity has been demonstrated, most notably in patients with EGFr-positive metastatic colorectal cancer who have failed prior therapy. Phase III study results indicate a 46% reduction in the rate of tumor progression in treated patients compared with those who received best supportive care alone. Panitumumab is well tolerated, with acneiform rash the most common dose-dependent adverse effect. Studies thus far indicate a low rate of infusion-related reactions (1%, grade 3–4).

Conclusions:

Panitumumab is a fully human monoclonal antibody with promising activity in treatment of patients with metastatic colorectal cancer who have failed previous therapy, offering a favorable safety profile.
Silencing of Neuroligin Function by Postsynaptic Neurexins
Authors: Taniguchi Hiroki , Gollan Leora , Scholl Francisco G. , Mahadomrongkul Veeravan , Dobler Elizabeth , Limthong Nicolas , Peck Morgen , Aoki Chiye , Scheiffele Peter
Published: March 2007

The formation of neuronal circuits during development involves a combination of synapse stabilization and elimination events. Synaptic adhesion molecules are thought to play an important role in synaptogenesis, and several trans-synaptic adhesion systems that promote the formation and maturation of synapses have been identified. The neuroligin–neurexin complex is a heterophilic adhesion system that promotes assembly and maturation of synapses through bidirectional signaling. In this protein complex, postsynaptic neuroligins are thought to interact trans-synaptically with presynaptic neurexins. However, the subcellular localization of neurexins has not been determined. Using immunoelectron microscopy, we found that endogenous neurexins and epitope-tagged neurexin-1β are localized to axons and presynaptic terminalsin vivo. Unexpectedly, neurexins are also abundant in the postsynaptic density.cis-expression of neurexin-1β with neuroligin-1 inhibits trans-binding to recombinant neurexins, blocks the synaptogenic activity of neuroligin-1, and reduces the density of presynaptic terminals in cultured hippocampal neurons. Our results demonstrate that the function of neurexin proteins is more diverse than previously anticipated and suggest that postsynapticcis-interactions might provide a novel mechanism for silencing the activity of a synaptic adhesion complex.
The Glutamate-Activated Anion Conductance in Excitatory Amino Acid Transporters Is Gated Independently by the Individual Subunits
Authors: Koch Hans Peter , Lane Brown Ronald , Larsson Hans Peter
Published: March 2007

Excitatory amino acid transporters (EAATs) use sodium and potassium gradients to remove glutamate from the synapse and surrounding extracellular space, thereby sustaining efficient synaptic transmission and maintaining extracellular glutamate concentrations at subneurotoxic levels. In addition to sodium-driven glutamate uptake, EAATs also mediate a glutamate-activated chloride conductance via a channel-like mechanism. EAATs are trimeric proteins and are thought to comprise three identical subunits. Previous studies have shown that the sodium-driven uptake of glutamate occurs independently in each of the three subunits. In contrast, a recent study reports high Hill coefficients for the activation of EAAT anion currents by glutamate and suggests that the subunits function cooperatively in gating the chloride conductance. In the present work, we find that the Hill coefficient for the activation of the anion current by glutamate is ∼1 in both EAAT3 and EAAT4. Furthermore, we also used fluorescent labeling and inactivation correlation on EAAT3 and EAAT4 to determine whether the glutamate-activated chloride conductance is gated independently or cooperatively by the transporters. We found that both glutamate uptake currents and glutamate-activated chloride currents are mediated independently by each subunit of an EAAT multimer. It has been suggested that EAAT subtypes with particularly large anion conductances can directly influence the excitability of presynaptic terminals in certain neurons. Thus, the finding that the anion conductance is gated independently, rather than cooperatively, is important because it significantly alters predictions of the influence that EAAT-mediated anion currents will have on synaptic transmission at low glutamate concentrations.
Robo1 and Robo2 Control the Development of the Lateral Olfactory Tract
Authors: Fouquet Coralie , Di Meglio Thomas , Ma Le , Kawasaki Takahiko , Long Hua , Hirata Tatsumi , Tessier-Lavigne Marc , Chédotal Alain , Nguyen-Ba-Charvet Kim T.
Published: March 2007

The development of olfactory bulb projections that form the lateral olfactory tract (LOT) is still poorly understood. It is known that the septum secretes Slit1 and Slit2 which repel olfactory axonsin vitroand that inSlit1−/−;Slit2−/−mutant mice, the LOT is profoundly disrupted. However, the involvement of Slit receptors, the roundabout (Robo) proteins, in guiding LOT axons has not been demonstrated. We show here that both Robo1 and Robo2 receptors are expressed on early developing LOT axons, but that only Robo2 is present at later developmental stages. Olfactory bulb axons fromRobo1−/−;Robo2−/−double-mutant mice are not repelled by Slitin vitro. The LOT develops normally inRobo1−/−mice, but is completely disorganized inRobo2−/−andRobo1−/−;Robo2−/−double-mutant embryos, with many LOT axons spreading along the ventral surface of the telencephalon. Finally, the position of lot1-expressing cells, which have been proposed to be the LOT guidepost cells, appears unaffected inSlit1−/−;Slit2−/−mice and inRobo1−/−;Robo2−/−mice. Together, our results indicate that Robo1 and Robo2 directly mediate the repulsive activity of Slit receptors on LOT axons, and are required for normal guidance of these axonsin vivo.
Neural Correlates of Perceptual Choice and Decision Making during Fear–Disgust Discrimination
Authors: Thielscher Axel , Pessoa Luiz
Published: March 2007

In the present study, we tested the hypothesis that brain activation would reflect perceptual choices. To probe this question, we used functional magnetic resonance imaging (fMRI) during a challenging fear–disgust, two-choice discrimination task. We investigated how moment-to-moment fluctuations in fMRI signals were correlated with perceptual choice by computing a choice probability index that quantified how well behavioral choice could be predicted by single-trial fMRI amplitude. Our analyses revealed that reporting a neutral face as “fearful” was associated with activation in a broad network of brain regions that process emotionally arousing stimuli, whereas reporting a neutral face as “disgusted” was associated with activation in a focused set of sites that included the putamen and anterior insula. Responses predictive of perceptual reports were not only observed at the group level but also at the single-subject level. Thus, voxel-by-voxel fluctuations in fMRI amplitude for an individual participant could be used to reliably predict the perceptual choice of individual trials for that subject. In addition to the investigation of choice, we also isolated the neural correlates of decision making per se by using reaction time as an index of decision processes. Overall, our findings revealed that brain responses dynamically shifted according to perceptual choices. In addition, the neural correlates of decision making involved at least the anterior cingulate cortex, middle frontal gyrus, and inferior frontal gyrus/insula, consistent with recent proposals that decisions may emerge from distributed processes.
Acute Psychosocial Stress Reduces Cell Survival in Adult Hippocampal Neurogenesis without Altering Proliferation
Authors: Thomas Rosanne M. , Hotsenpiller Gregory , Peterson Daniel A.
Published: March 2007

Factors modulating neurogenesis may contribute to the pathophysiology of affective disorders such as major depression. Environmental stressors in animal models have been proposed to alter neurogenesis, suggesting a mechanism for this contribution. The effect of an acute psychosocial stressor on either proliferation or survival (immediate, short term, and long term) was examined along with subsequent neuronal differentiation in the hippocampus of adult male Sprague Dawley rats. Subjects were exposed to a widely used social dominance paradigm that elicits behavioral and physiological responses to an acute psychosocial stressor. This social dominance paradigm may mimic human relational stress more realistically than laboratory stressors and provides a socially relevant model. We found that exposure to an acute psychosocial stressor at the time of cell generation resulted in a decreased number of newly generated cells in the hippocampus. By using sequential thymidine analog administration to provide temporal discrimination of DNA replication, we showed that short-term survival but not initial proliferation or immediate survival was altered in response to stress. Furthermore, we determined that stress experienced subsequent to proliferation also diminished long-term survival of cells. Thus, an acute episode of a social stress produces long-lasting effects on the incorporation of new hippocampal neurons by reducing their survival.
Ghrelin Effects on the Circadian System of Mice
Authors: Yannielli Paola C. , Molyneux Penny C. , Harrington Mary E. , Golombek Diego A.
Published: March 2007

The orexigenic peptide ghrelin stimulates both food intake and growth hormone release and is synthesized in the stomach and in hypothalamic areas involved in feeding control. The suprachiasmatic nuclei of the hypothalamus (SCN) control most circadian rhythms, although there is evidence that some oscillators, such as food-entrainable oscillators, can drive activity rhythms even after SCN ablation. Ghrelin levels exhibit a circadian rhythm and closely follow feeding schedules, making this peptide a putative candidate for food-related entraining signals. We examined the response of the SCN to ghrelin treatmentsin vitro, by means of electrophysiological and bioluminescence recordings, andin vivo, by assessing effects on the phase of locomotor activity rhythms. Ghrelin applied at circadian time 6in vitroto cultured SCN slices induced an ∼3 h phase advance. In addition, ghrelin phase advanced the rhythm of PER2::LUC (Period2::Luciferase) expression in cultured SCN explants frommPer2Luctransgenic mice.In vivo, intraperitoneal administration of ghrelin or a synthetic analog, growth hormone-releasing protein-6 (GHRP-6), toad libitumfed animals failed to alter circadian phase. When injected after 30 h of food deprivation, GHRP-6 induced a phase advance compared with saline-injected animals. These results indicate that ghrelin may play a role in the circadian system by exerting a direct action on the SCN and that the system as a whole may become sensitive to ghrelin and other feeding-related neuropeptides under conditions of food restriction.
Seizure Suppression bytop1Mutations inDrosophila
Authors: Song Juan , Hu Joyce , Tanouye Mark
Published: March 2007

DNA topoisomerase I is an essential nuclear enzyme involved in resolving the torsional stress associated with DNA replication, transcription, and chromatin condensation. Here we report the discovery of a seizure-suppressor mutant,top1JS, which suppresses seizures in aDrosophilamodel of human epilepsy. A P-element mutagenesis screen usingeasily shockedseizure-sensitive mutant as a genetic background identifiedtop1JS, which plays a novel role in regulating nervous system excitability. Plasmid rescue, excision, complementation, and sequencing analyses verified thattop1JSresults from a P-element insertion in the 5′ untranslated region. Quantitative reverse transcription analysis on wild-type and mutant fly heads showed that thetop1JSmutation causes reduced transcription level in the CNS, suggesting a partial loss-of-function mutation. Electrophysiological experiments revealed normal seizure thresholds intop1JSmutants, which are different from other seizure suppressors identified previously, suggesting a novel mechanism underlying seizure suppression bytop1JS. The pharmacological camptothecin feeding experiment and cell death analysis suggested that the seizure suppression bytop1JSmay occur via increased neuronal apoptosis. Furthermore, overexpression of theDIAP1(Drosophilainhibitor of apoptosis 1) gene rescuestop1JSsuppression, providing additional support for a neural apoptosis suppression mechanism. Thetop1JSmutation is the first viable partial loss-of-function mutation identified in higher eukaryotes, and the results presented here point to a novel function for topo I in construction and/or maintenance of circuits required for seizure propagationin vivo.
Repeated Cocaine Administration Impairs Group II Metabotropic Glutamate Receptor-Mediated Long-Term Depression in Rat Medial Prefrontal Cortex
Authors: Huang Chiung-Chun , Yang Ping-Chun , Lin Hsiao-Ju , Hsu Kuei-Sen
Published: March 2007

Drug-induced neuroadaptations within the medial prefrontal cortex (mPFC) are thought to underlie the development of cocaine sensitization. Here, we report that repeated cocaine administrationin vivoimpaired the long-term depression (LTD) induced by bath application of group II metabotropic glutamate receptor (mGluR) agonists DCG-IV [2S, 2′R, 3′R)-2-(2′, 3′-dicarboxycyclopropyl)glycine] or LY379268 [(1R,4R,5S,6R)-4-amino-2-oxabicyclo[3.1.0]hexane-4,6-dicarboxylic acid] at excitatory synapses onto layer V pyramidal neurons of rat mPFC. In contrast, this impairment was not found in slices from rats treated with saline or a single dose of cocaine. Such effect of cocaine was selectively prevented when cocaine was coadministered with the selective D1-like receptor antagonist SCH23390 [(R)-(+)-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine]. In slices from control rats, a brief application of either protein kinase C (PKC) activator phorbol-12,13-dibutyrute or adenosine A3receptor agonist 2-chloro-N6-(3-iodobenzyl)-adenosine-5-N-methyluronamide mimicked the effect of repeated cocaine treatment to impair the induction of LTD. Bilateral intra-mPFC infusion of PKC inhibitor bisindolylmaleimide I or adenosine A3receptor antagonist MRS1220 (N-[9-chloro-2-(2-furanyl)[1,2,4]-triazolo[1,5-c]quinazolin-5-benzeneacetamide) before cocaine injection prevented cocaine-induced impairment of LTD induction. Furthermore, endogenous adenosine tone is greater in slices from cocaine-treated rats than from the saline-treated controls. When the metabolism of cAMP to adenosine was blocked, the extent of LTD in slices from saline and cocaine-treated rats was similar. These results suggest that cocaine-induced impairment of group II mGluR-mediated LTD is caused, at least in part, by an increase in adenosine subsequent to the rise in cAMP after D1-like receptor activation, which leads to an adenosine A3receptor-mediated upregulation of PKC activity and thereby triggers an inhibition of group II metabotropic glutamate receptor function.
The Origin of Quantal Size Variation: Vesicular Glutamate Concentration Plays a Significant Role
Authors: Wu Xin-Sheng , Xue Lei , Mohan Raja , Paradiso Kenneth , Gillis Kevin D. , Wu Ling-Gang
Published: March 2007

Fusion of a single vesicle induces a quantal response, which is critical in determining synaptic strength. Quantal size varies at most synapses. Its underlying mechanisms are not well understood. Here, we examined five sources of variation: vesicular glutamate concentration ([Glu]v), vesicle volume, ultrafast fusion pore closure, the postsynaptic receptor, and the location between release and the postsynaptic receptor cluster at glutamatergic, calyx of Held synapses. By averaging 2.66 million fusion events from 459 synapses, we resolved the capacitance jump evoked by single vesicle fusion. This capacitance jump, an indicator of vesicle volume, was independent of the amplitude of the miniature EPSC (mEPSC) recorded simultaneously at the same synapses. Thus, vesicle volume is not the main source of mEPSC variation. The capacitance jump was not followed by submillisecond endocytosis, excluding ultrafast endocytosis as a source of variation. Larger mEPSCs were increased to a lesser extent by presynaptic glutamate dialysis, and reduced to a lesser extent by γ-DGG (γ-d-glutamylglycine), a competitive AMPA receptor blocker, suggesting that a higher glutamate concentration in the synaptic cleft contributes to the large size of mEPSCs. Larger mEPSCs were not accompanied by briefer rise times, inconsistent with the prediction by, and thus arguing against, the scenario that larger mEPSCs are caused by a shorter distance between the release site and the postsynaptic receptor cluster. In summary, the different amplitudes of mEPSCs were mainly attributable to release of vesicles having similar volumes, but different glutamate amounts, suggesting that [Glu]vis a main source of quantal size variation.
Synchronization of Neural Activity across Cortical Areas Correlates with Conscious Perception
Authors: Melloni Lucia , Molina Carlos , Pena Marcela , Torres David , Singer Wolf , Rodriguez Eugenio
Published: March 2007

Subliminal stimuli can be deeply processed and activate similar brain areas as consciously perceived stimuli. This raises the question which signatures of neural activity critically differentiate conscious from unconscious processing. Transient synchronization of neural activity has been proposed as a neural correlate of conscious perception. Here we test this proposal by comparing the electrophysiological responses related to the processing of visible and invisible words in a delayed matching to sample task. Both perceived and nonperceived words caused a similar increase of local (gamma) oscillations in the EEG, but only perceived words induced a transient long-distance synchronization of gamma oscillations across widely separated regions of the brain. After this transient period of temporal coordination, the electrographic signatures of conscious and unconscious processes continue to diverge. Only words reported as perceived induced (1) enhanced theta oscillations over frontal regions during the maintenance interval, (2) an increase of the P300 component of the event-related potential, and (3) an increase in power and phase synchrony of gamma oscillations before the anticipated presentation of the test word. We propose that the critical process mediating the access to conscious perception is the early transient global increase of phase synchrony of oscillatory activity in the gamma frequency range.
Identification of a Novel Endocannabinoid-Hydrolyzing Enzyme Expressed by Microglial Cells
Authors: Muccioli Giulio G. , Xu Cong , Odah Emma , Cudaback Eiron , Cisneros Jose Antonio , Lambert Didier M. , López Rodríguez María Luz , Bajjalieh Sandra , Stella Nephi
Published: March 2007

The endocannabinoids (eCBs) anandamide and 2-arachidonoyl glycerol (2-AG) are inactivated by a two-step mechanism. First, they are carried into cells, and then anandamide is hydrolyzed by fatty acid amide hydrolase (FAAH) and 2-AG by monoacylglycerol lipase (MGL). Here we provide evidence for a previously undescribed MGL activity expressed by microglial cells. We found that the mouse microglial cell line BV-2 does not express MGL mRNA and yet efficiently hydrolyzes 2-AG. URB597 (3′-carbamoyl-biphenyl-3-yl-cyclohexylcarbamate) reduces this hydrolysis by 50%, suggesting the involvement of FAAH. The remaining activity is blocked by classic MGL inhibitors [[1,1-biphenyl]-3-yl-carbamic acid, cyclohexyl ester (URB602) and MAFP (methylarachidonyl fluorophosphate)] and is unaffected by inhibitors of COXs (cyclooxygenases), LOXs (lipooxygenases), and DGLs (diacylglycerol lipases), indicating the involvement of a novel MGL activity. Accordingly, URB602 leads to selective accumulation of 2-AG in intact BV-2 cells. Although MGL expressed in neurons is equally distributed between the cytosolic, mitochondrial, and nuclear fractions, the novel MGL activity expressed by BV-2 cells is enriched in mitochondrial and nuclear fractions. A screen for novel inhibitors of eCB hydrolysis identified several compounds that differentially block MGL, FAAH, and the novel MGL activity. Finally, we provide evidence for expression of the novel MGL by mouse primary microglia in culture. Our results suggest the presence of a novel, pharmacologically distinct, MGL activity that controls 2-AG levels in microglia.
Erythropoietin Enhances Hippocampal Response during Memory Retrieval in Humans
Authors: Miskowiak Kamilla , O'Sullivan Ursula , Harmer Catherine J.
Published: March 2007

Although erythropoietin (Epo) is best known for its effects on erythropoiesis, recent evidence suggests that it also has neurotrophic and neuroprotective properties in animal models of hippocampal function. Such an action in humans would make it an intriguing novel compound for the treatment of neurological and psychiatric disorders. The current study therefore aimed to explore the effects of Epo on neural and behavioral measures of hippocampal function in humans using a functional magnetic resonance imaging paradigm. Volunteers were randomized to receive intravenous injection of Epo (40,000 IU) or saline in a between-subjects, double-blind, randomized design. Neural response during picture encoding and retrieval was tested 1 week later. Epo increased hippocampus response during picture retrieval (n= 11) compared with placebo (n= 12;p= 0.04) independent of changes in hematocrit. This is consistent with upregulation of hippocampal BDNF and neurotrophic actions found in animals and highlights Epo as a promising candidate for treatment of psychiatric disorders.
Time Course of Precision in Smooth-Pursuit Eye Movements of Monkeys
Authors: Osborne Leslie C. , Hohl Sonja S. , Bialek William , Lisberger Stephen G.
Published: March 2007

To evaluate the nature and possible sources of variation in sensory–motor behavior, we measured the signal-to-noise ratio for the initiation of smooth-pursuit eye movements as a function of time and computed thresholds that indicate how well the pursuit system discriminates small differences in the direction, speed, or time of onset of target motion. Thresholds improved rapidly as a function of time and came close to their minima during the interval when smooth eye movement is driven only by visual motion inputs. Many features of the data argued that motor output and sensory discrimination are limited by the same noise source. Pursuit thresholds reached magnitudes similar to those for perception: <2–3° of direction, ∼11–15% of target speed, and 8 ms of change in the time of onset of target motion. Pursuit and perceptual thresholds had similar dependencies on the duration of the motion stimulus and showed similar effects of target speed. The evolution of information about direction of target motion followed the same time course in pursuit behavior and in a previously reported sample of neuronal responses from extrastriate area MT. Changing the form of the sensory input while keeping the motor response fixed had significant effects on the signal-to-noise ratio in pursuit for direction discrimination, whereas holding the sensory input constant while changing the combination of muscles used for the motor output did not. We conclude that noise in sensory processing of visual motion provides the major source of variation in the initiation of pursuit.
Recognition Memory for Objects, Place, and Temporal Order: A Disconnection Analysis of the Role of the Medial Prefrontal Cortex and Perirhinal Cortex
Authors: Barker Gareth R. I. , Bird Flora , Alexander Victoria , Warburton E. Clea
Published: March 2007

Recognition memory requires judgments of the previous occurrence of stimuli made on the basis of the relative familiarity of individual objects, or by integrating information concerning objects and location, or by using recency information. The present study examined the role of the medial prefrontal cortex (mPFC) and perirhinal cortex (PRH) in these distinct recognition memory processes using a series of behavioral tests: a novel object preference task, an object-in-place task, and a temporal order memory task. Also, a disconnection procedure was used to test whether these regions form components of an integrated system for recognition memory. Male DA rats received bilateral lesions in the PRH or mPFC or unilateral lesions placed in both cortices in either the same (PRH–mPFC IPSI) or contralateral (PRH–mPFC CONTRA) hemispheres. A fifth group underwent sham surgery (SHAM). In the object-in-place and temporal order memory tasks, the PRH, mPFC, and PRH–mPFC CONTRA groups were significantly impaired. However, performance in the novel object preference task was only impaired in the PRH group. No group was impaired in the object location task. These results demonstrate that the mPFC and PRH are crucial for object-in-place associational and recency discriminations, whereas the PRH but not the mPFC is important for the discrimination of novel and familiar individual objects. Importantly, these results provide direct support for the hypothesis that to make discriminations based on associational or recency information, both cortical regions operate within an integrated neural network for recognition memory.
Dynamics of Protein Kinase A Signaling at the Membrane, in the Cytosol, and in the Nucleus of Neurons in Mouse Brain Slices
Authors: Gervasi Nicolas , Hepp Régine , Tricoire Ludovic , Zhang Jin , Lambolez Bertrand , Paupardin-Tritsch Danièle , Vincent Pierre
Published: March 2007

The cAMP-dependent protein kinase A (PKA) plays a ubiquitous role in the regulation of neuronal activity, but the dynamics of its activation have been difficult to investigate. We used the genetically encoded fluorescent probe AKAR2 to record PKA activation in the cytosol and the nucleus of neurons in mouse brain slice preparations, whereas the potassium current underlying the slow afterhyperpolarization potential (sAHP) in thalamic intralaminar neurons was used to monitor PKA activation at the membrane. Adenylyl cyclase was stimulated either directly using forskolin or via activation of 5-HT7receptors. Both stimulations produced a maximal effect on sAHP, whereas in the cytosol, the amplitude of the 5-HT7receptor-mediated response was half of that after direct adenylyl cyclase stimulation with forskolin. 5-HT7-mediated PKA responses were obtained in 30 s at the membrane, in 2.5 min in the cytosol, and in 13 min in the nucleus. Our results show in morphologically intact mammalian neurons the potential physiological relevance of PKA signal integration at the subcellular level: neuromodulators produce fast and powerful effects on membrane excitability, consistent with a highly efficient functional coupling between adenylyl cyclases, PKA, and target channels. Phosphorylation in the cytosol is slower and of graded amplitude, showing a differential integration of the PKA signal between the membrane and the cytosol. The nucleus integrates these cytosolic signals over periods of tens of minutes, consistent with passive diffusion of the free catalytic subunit of PKA into the nucleus, eventually resulting in a graded modulation of gene expression.
“Breakthrough” Dopamine Supersensitivity during Ongoing Antipsychotic Treatment Leads to Treatment Failure over Time
Authors: Samaha Anne-Noël , Seeman Philip , Stewart Jane , Rajabi Heshmat , Kapur Shitij
Published: March 2007

Antipsychotics often lose efficacy in patients despite chronic continuous treatment. Why this occurs is not known. It is known, however, that withdrawal from chronic antipsychotic treatment induces behavioral dopaminergic supersensitivity in animals. How this emerging supersensitivity might interact with ongoing treatment has never been assessed. Therefore, we asked whether dopamine supersensitivity could overcome the behavioral and neurochemical effects of antipsychotics while they are still in use. Using two models of antipsychotic-like effects in rats, we show that during ongoing treatment with clinically relevant doses, haloperidol and olanzapine progressively lose their efficacy in suppressing amphetamine-induced locomotion and conditioned avoidance responding. Treatment failure occurred despite high levels of dopamine D2receptor occupancy by the antipsychotic and was at least temporarily reversible by an additional increase in antipsychotic dose. To explore potential mechanisms, we studied presynaptic and postsynaptic elements of the dopamine system and observed that antipsychotic failure was accompanied by opposing changes across the synapse: tolerance to the ability of haloperidol to increase basal dopamine and dopamine turnover on one side, and 20–40% increases in D2receptor number and 100–160% increases in the proportion of D2receptors in the high-affinity state for dopamine (D2High) on the other. Thus, the loss of antipsychotic efficacy is linked to an increase in D2receptor number and sensitivity. These results are the first to demonstrate that “breakthrough” supersensitivity during ongoing antipsychotic treatment undermines treatment efficacy. These findings provide a model and a mechanism for antipsychotic treatment failure and suggest new directions for the development of more effective antipsychotics.
Cocaine- and Amphetamine-Regulated Transcript: Stimulation of Expression in Rat Vagal Afferent Neurons by Cholecystokinin and Suppression by Ghrelin
Authors: de Lartigue Guillaume , Dimaline Rod , Varro Andrea , Dockray Graham J.
Published: March 2007

The neuropeptide transmitter cocaine- and amphetamine-regulated transcript (CART) inhibits food intake and is expressed by both vagal afferent and hypothalamic neurons. Here we report that cholecystokinin (CCK) regulates CART expression in rat vagal afferent neurons. Thus, CART was virtually undetectable after energy restriction for 24 h, but administration of CCK to fasted rats increased CART immunoreactivity, and refeeding of fasted animals promptly increased CART by a mechanism sensitive to a CCK-1 receptor antagonist. In vagal afferent neurons incubated in serum-free medium, CART was virtually undetectable, whereas the orexigenic peptide melanin-concentrating hormone (MCH) was readily detected. The addition of CCK rapidly induced CART expression and downregulated MCH. Using a CART promoter–luciferase reporter vector transfected into cultured vagal afferent neurons, we showed that CCK stimulation of CART transcription was mediated by activation of protein kinase C and cAMP response element-binding protein (CREB). The action of CCK on CART expression was inhibited by the orexigenic peptide ghrelin, through a mechanism that involved exclusion of phosphorylated CREB from the nucleus. Thus, CCK reciprocally regulates expression of CART and MCH within the same vagal afferent neuron; ghrelin inhibits the effect of CCK at least in part through control of the nuclear localization of phosphoCREB, revealing previously unsuspected modulation of gut–brain signals implicated in control of food intake.
Stabilitätsnachweis für weiche strukturvariable Regelungen mit Zustandsbeobachter (Stability of Soft Variable-Structure Controls with Observer)
Authors: Adamy Jürgen , Lens Hendrik
Published: March 2007

Weiche strukturvariable Regler sind nichtlineare Zustandsregler für lineare Regelstrecken mit Stellgrößenbeschränkung. Ihr lineares Regelgesetz wird über einen zustandsabhängigen Parameter kontinuierlich verändert. Dabei erfolgt die Regleränderung so, dass die vorhandene Stellgrößenbeschränkung möglichst gut ausgenutzt wird, wodurch sich ein nahezu zeitoptimales Verhalten einstellt. Unter praktischen Gesichtspunkten erfordert eine Zustandsregelung — so auch diese — den Einsatz eines Beobachters, da oft nicht alle Zustände messbar sind. In diesem Artikel werden Beobachter für weiche strukturvariable Regler und der Nachweis der Stabilität des Regelkreises mit Beobachter behandelt.
Beobachtung der Verdrillung in einem Kfz-Antriebsstrang mit Lose (Observing the Torque of a Powertrain with Backlash)
Authors: Haschka Markus S. , Krebs Volker
Published: March 2007

Der Fahrkomfort von Kraftfahrzeugen kann gesteigert werden, wenn die Momentenübertragung im Antriebsstrang geregelt wird. Praktisch stehen zur Lösung dieser regelungstechnischen Aufgabe nicht alle Zustandsgrößen messtechnisch zur Verfügung. Daher soll in diesem Beitrag der Entwurf eines neuartigen nichtlinearen Beobachters, basierend auf einem vereinfachten nichtlinearen Antriebsstrangmodell dritter Ordnung vorgestellt werden. Dieser Beobachter schätzt aus den gemessenen Drehzahlen des Motors und der Antriebsräder die Verdrillung des Antriebsstrangs. Die Stabilität des in diesem Beitrag vorgestellten Beobachters wird mit dem Popov-Kriterium beziehungsweise mit der Aiserman-Vermutung nachgewiesen. Die Leistungsfähigkeit dieses Beobachters wird abschließend anhand von Simulationen mit einem komplexen Antriebsstrangmodell demonstriert.
The Elastic View Graph Framework for Autonomous, Surface-based 3D-SLAM Part I: Concept and Local Layer (Schritthaltendes flächenbasiertes 3D-SLAM mit elastisch gekoppelten Teilkarten)
Authors: Kohlhepp Peter , Strand Marcus , Bretthauer Georg , Dillmann Rüdiger
Published: March 2007

This paper introduces a new framework for incremental localization and mapping (3D-SLAM) that integrates submaps of surface features extracted from dense range images. Its local layer estimates unknown motion and feature associations between adjacent views. The global layer tries to ensure map consistency and to close loops, using multiple hypotheses offered by the local layer. The local algorithm crucially affects the map quality. An interpretation tree (IPT) is compared to Orthogonal Surface Assignment (OSA), a new algorithm tracing a building coordinate system inside man-made work spaces. During indoor experiments, performed with the rotating laser scanner RoSi, OSA proved much more reliable than IPT. Another experiment, running a simple on-line surface classification, indicates that the maps are useful for mission planning.
Use of Site Occupancy Models to Estimate Prevalence of Myxobolus cerebralis Infection in Trout
Authors: Thompson Kevin G.
Published: March 2007

Empirical estimates of pathogen prevalence in samples of fish may underestimate true prevalence because available detection techniques are incapable of perfect detection. Trout of several species were collected from enzootic (Myxobolus cerebralis, causative agent in whirling disease) habitats, and individual fish were examined for presence of the parasite two or six times by one of four methods: pepsin–trypsin digest (brown trout Salmo trutta), plankton centrifuge (brown trout), polymerase chain reaction (rainbow trout Oncorhynchus mykiss), or histopathology (brook trout Salvelinus fontinalis). The presence–absence data were modeled for prevalence of infection (ψ) and probability of detection (p) of the parasite via occupancy models that accounted for imperfect detection of the organism. Based on estimates from the most-supported model for comparison, two myxospore concentration methods underestimated prevalence by about 12% for whole-head results and 34% for the expected value of half-head analysis. Polymerase chain reaction and histopathology gave virtually the same prevalence estimates for whole-head results as the best models but underestimated prevalence by about 6% and 12%, respectively, for the expected value of half-head analysis. The probability of detecting the parasite in a single survey of a fish head, conditional on the parasite's presence, was 0.66 for myxospore concentration methods, 0.81 for histopathology, and 1.0 (left halves) or 0.89 (right halves) for polymerase chain reaction. The occupancy models used in this study may be extended to large-scale monitoring of M. cerebralis to estimate expansion or contraction of the parasite's range over time.
An Improved Technique for Small‐Scale Radio‐Tracking of Crayfish and Benthic Fishes in Upland Streams
Authors: Broadhurst Ben , Ebner Brendan
Published: March 2007

This study measured the accuracy of two radio‐tracking techniques: (1) triangulation using a Yagi antenna and (2) a form of direct location, the extended‐reach technique, which uses a small loop antenna attached to a lightweight 9‐m telescopic pole. The study was conducted in the Cotter River, an upland stream in the Australian Capital Territory. Radio tags were positioned instream to determine whether depth, substrate, or local bank profile affected radio‐tracking accuracy. The extended‐reach technique was more accurate (mean error ± SE = 1.00 ± 0.21 m) than triangulation (2.57 ± 0.21 m). Decreased accuracy resulted from the triangulation of radio tags positioned close to boulders or in water more than 1 m deep. These variables had no effect on the accuracy of the extended‐reach technique. The presence or absence of a steep rocky bank did not affect the accuracy of either radio‐tracking method. The increased accuracy of the extended‐reach technique provides an improvement over traditional methods for studying the small‐scale movement and microhabitat use of crayfishes (e.g., Eustacus spp.) and benthic fishes in upland streams.
Uso da gordura e fáscia muscular autólogas no tratamento da insuficiência glótica
Authors: Carneiro Christiano de Giacomo , Tsuji Domingos Hiroshi , Sennes Luiz Ubirajara , Ximenes Filho João Aragão , Imamura Rui
Published: March 2007

Uma das alterações mais complexas que acometem as pregas vocais é a incompetência ou insuficiência glótica. Pode ser causada por alterações de mobilidade, fibroses, atrofias ou arqueamento das pregas vocais, e pode levar, entre outras situações como aspiração e tosse pouco efetiva, a graus variados de disfonia. A partir do início do século 20, surgiram vários procedimentos cirúrgicos para a reabilitação da competência aerodinâmica e valvular da glote, por meio da injeção de substâncias heterólogas no espaço paraglótico. Os enxertos autólogos, como a gordura e a fáscia muscular, inseridos ou injetados nas pregas vocais inicialmente mostraram resultados promissores além de segurança e riscos mínimos de reações indesejadas. Neste artigo de revisão, os autores discutem o uso da gordura e da fáscia muscular na incompetência glótica, abordando aspectos históricos, o processo inflamatório gerado após a enxertia, as técnicas cirúrgicas mais utilizadas e o rendimento dos enxertos.
Correção do nariz desviado utilizando spreader graft no lado convexo do desvio
Authors: Oliveira Pedro Wey Barbosa de , Pezato Rogério , Gregório Luiz Carlos
Published: March 2007

O nariz desviado é resultado de um conjunto de alterações anatômicas e por isso existe um grande número de técnicas para sua correção, sendo que um único método não deve ser utilizado em todos os casos. OBJETIVO: Avaliar um novo método para a correção destas deformidades, o uso do spreader graft no lado convexo do nariz desviado. FORMA DE ESTUDO: Prospectivo. MATERIAL E MÉTODO: Seis pacientes com nariz desviado foram submetidos à rinoplastia com colocação de spreader graft no lado convexo do desvio nasal e acompanhados por um período de 2 anos. RESULTADOS: Todos os pacientes apresentaram melhora da estética facial. Conclusão: Este estudo mostrou ser possível utilizar o spreader graft no lado convexo do desvio nasal em casos específicos.
Gestão ambiental portuária: desafios e possibilidades
Authors: Kitzmann Dione , Asmus Milton
Published: March 2007

Este artigo trata dos desafios trazidos pela implementação de reformas portuárias a partir da Lei de Modernização dos Portos (Lei nº 8.630/93). Entre eles, está o da gestão ambiental, ainda não adequadamente incorporada ao sistema portuário brasileiro. As iniciativas de gestão ambiental não fazem parte do setor de planejamento portuário, levando a ações desarticuladas e reativas, fruto da visão que considera a regulamentação ambiental um fator que ameaça a competitividade das empresas. Para os autores, a adequação às normas ambientais traz oportunidades de melhoria para o negócio portuário. O artigo apresenta panoramas da gestão ambiental portuária nacional e internacional, assim como exemplos de ecoinovações e de práticas de gestão ambiental em portos europeus e norte-americanos, ressaltando que a gestão ambiental deve ir além da microescala (a gestão dos problemas rotineiros), incorporando-se à macroescala (a gestão da zona costeira), para que o novo modelo portuário seja economicamente competitivo com benefícios socioambientais.