bluuebunny/crossref_metadata_2025 huggingface dataset:
Finite Element Analysis on Aerodynamic Noise of the High-Speed Train Head Based on Computational Fluid Dynamics and Acoustic Analogy Methods
Authors: Wang Yan-song , Tang Chao , Bai Chang-an
Published: May 2014

As train speed increases, the aerodynamic noise gradually exceeds the wheel-rail noise and becomes the main noise source of high-speed trains. The aerodynamic noise affects the interior environment of a train in two ways: turbulent wall pressure fluctuation (TWPF) and acoustic wall pressure fluctuation (AWPF). In this paper, a hybrid aerodynamic model for noise analysis of high-speed trains based on the computational fluid dynamics (CFD) method and the Lighthill's acoustic analogy (LAA) algorithm, so-called CFD-LAA method, is established and solved by using the finite-element acoustic simulator of Actran software. The noise contributions of both the TWPF and the AWPF are examined and discussed. The method presented in this paper may be a valuable reference for revealing the generation mechanism of aerodynamic noises and evaluating their effects on a train interior noise.
Effects of External and Internal Attention Focus Training on Foot-Strike Patterns in Running
Authors: Chow Jia Yi , Woo Mei Teng , Koh Michael
Published: May 2014

The provision of instructions is an important task constraint when altering movement behaviours. Using instructions as a form of task constraint could be an effective approach to help learners improve their performances. Specifically, changing running gait from a heel to forefoot strike pattern can reduce incidences of injuries. By providing different attentional instructions, external and internal focus instructions, which emphasise movement effect and movement form respectively, can be used to alter foot strike patterns in running gait. The purpose of this study was to investigate the effectiveness of external or internal focus instructions in facilitating a change from a heel strike to a forefoot strike pattern. Sixteen participants (9 males, 7 females), were randomly assigned to either an external focus condition (n=8) or an internal focus condition (n=8). Participants underwent six training sessions with their respective instructional conditions over three weeks with 10 one-minute running trials per session during the intervention phase. A 3D motion analysis system was used to determine kinematic changes between pre and post-test sessions. Both external (0.025m ± 0.006) and internal (0.027m ± 0.008) participants showed a significant change in calcaneus displacement at initial contact (IC) by post-test, which indicates the change from heel strike to forefoot strike pattern. However, cycle time and stride length were not significantly different at post-test for participants in internal and external conditions. The effectiveness of both focus instructions could be task and individual dependent.
Put Your Money Where Your Mouth is: Verbal Self-Reported Tactical Skills versus on-Line Tactical Performance in Soccer
Authors: Nortje Liesel , Dicks Matt , Coopoo Yoga , Savelsbergh Geert J.P.
Published: May 2014

The main goal of the study was to examine whether a relationship existed between self-reported and in situ tactical decision-making in the form of actions for small-sided soccer games, namely 4-vs.-4 and 8-vs.-8 games. Sixteen skilled male soccer players participated and completed the Tactical Skills Inventory for Sport Questionnaire (TACSIS). In addition, their decision-making performance was assessed for two 4-vs.-4 and one 8-vs.-8 small-sided soccer games. Video-analysis of the small-sided games was conducted to determine the successful and unsuccessful actions of each player. A performance ratio was calculated for each player based on the small-sided game analyses, which reflected the number of successful decisions made by players; that is, the number of successful ball actions divided by total ball actions. Correlation analysis revealed no significant relationship between the procedural knowledge TACSIS questionnaire scores and performance in the small-sided games. The findings are discussed within the theoretical framework of the two-visual system model and the repercussion for the use of questionnaires for talent identification.
Autonomy-Supportive Pedagogical Approach to Sports Coaching: Research, Challenges and Opportunities
Authors: Occhino Joseph L. , Mallett Clifford J. , Rynne Steven B. , Carlisle Kristy N.
Published: May 2014

There has been an increasing body of research on autonomy- or need-support specific to a coaching context that warrants some review of what we know and don't know, and what might be generative for future research. The previous studies reviewed within this article have shown consistent support for Self-determination theory with autonomy-supportive environments linked with adaptive outcomes, such as superior performance, enhanced self-worth, increased effort, and self-determined motivation; while controlling environments have been linked with increased attrition and extrinsic motivation or amotivation. In this way, much of the research in autonomy-supportive coaching has focused on the impact of coaching behaviours on athlete outcomes. While this is an important focus of inquiry, there has been a dearth of research examining those causal factors that impact coaches' pedagogical behaviours in the first case. This review underscores the need for future research to examine the antecedents to coaching behaviours, which is central to understanding the complexity and challenges in promoting an autonomy-supportive approach to sport coaching.
A Decomposition-Based Heuristic for Collaborative Scheduling in a Network of Open-Pit Mines
Authors: Blom Michelle L. , Burt Christina N. , Pearce Adrian R. , Stuckey Peter J.
Published: May 2014

We consider the short-term production scheduling problem for a network of multiple open-pit mines and ports. Ore produced at each mine is transported by rail to a set of ports and blended into signature products for shipping. Consistency in the grade and quality of production over time is critical for customer satisfaction, whereas the maximal production of blended products is required to maximise profit. In practice, short-term schedules are formed independently at each mine, tasked with achieving the grade and quality targets outlined in a medium-term plan. However, because of uncertainty in the data available to a medium-term planner and the dynamics of the mining environment, such targets may not be feasible in the short term. We present a decomposition-based heuristic for this short-term scheduling problem in which the grade and quality goals assigned to each mine are collaboratively adapted—ensuring the satisfaction of blending constraints at each port and exploiting opportunities to maximise production in the network that would otherwise be missed.
Symmetry analysis of talus bone
Authors: Islam K. , Dobbe A. , Komeili A. , Duke K. , El-Rich M. , Dhillon S. , Adeeb S. , Jomha N. M.
Published: May 2014

Objective

The main object of this study was to use a geometric morphometric approach to quantify the left-right symmetry of talus bones.

Methods

Analysis was carried out using CT scan images of 11 pairs of intact tali. Two important geometric parameters, volume and surface area, were quantified for left and right talus bones. The geometric shape variations between the right and left talus bones were also measured using deviation analysis. Furthermore, location of asymmetry in the geometric shapes were identified.

Results

Numerical results showed that talus bones are bilaterally symmetrical in nature, and the difference between the surface area of the left and right talus bones was less than 7.5%. Similarly, the difference in the volume of both bones was less than 7.5%. Results of the three-dimensional (3D) deviation analyses demonstrated the mean deviation between left and right talus bones were in the range of -0.74 mm to 0.62 mm. It was observed that in eight of 11 subjects, the deviation in symmetry occurred in regions that are clinically less important during talus surgery.

Conclusions

We conclude that left and right talus bones of intact human ankle joints show a strong degree of symmetry. The results of this study may have significance with respect to talus surgery, and in investigating traumatic talus injury where the geometric shape of the contralateral talus can be used as control. Cite this article: Bone Joint Res 2014;3:139–45.
Dos versiones del constitucionalismo
Authors: Atienza Rodríguez Manuel
Published: May 2014

El trabajo se divide en tres partes. En la primera se muestra por qué es equivocada la caracterización que Ferrajoli hace del constitucionalismo al que llama «principialista» o «argumentativo». En la segunda se aclara qué es lo que esa concepción del Derecho (a la que el autor prefiere denominar «postpositivismo») realmente sostiene. Y en la tercera se señalan cuáles son las tesis que Ferrajoli (el constitucionalismo «normativista») debería abandonar para poder cumplir con los objetivos que él mismo plantea para la teoría del Derecho.
Un baluarte de la modernidad: notas defensivas sobre el constitucionalismo garantista
Authors: Chiassoni Pierluigi
Published: May 2014

El constitucionalismo garantista de Ferrajoli representa uno de los últimos baluartes de la modernidad en la filosofía jurídica contemporánea. Los argumentos que Ferrajoli opone al constitucionalismo principialista en lo que atañe al objetivismo y cognoscitivismo moral y a la tesis de la conexión necesaria entre Derecho y moral pueden ser complementados, brindando el ataque al corazón mismo del enfoque objetivista y conexionista.
Neoconstitucionalismo: dos (o tres) perros para un solo collar. Notas a propósito del constitucionalismo juspositivista de Luigi Ferrajoli
Authors: García Figueroa Alfonso
Published: May 2014

El objeto de este trabajo consiste en criticar la compatibilidad asumida como posible por Luigi Ferrajoli entre el positivismo jurídico y el llamado «neoconstitucionalismo», lo cual vale para cualquier significado coherente posible de esta ambigua corriente jurídica. Los argumentos principales son los siguientes: 1) El neoconstitucionalismo no es compatible con el esencialismo que no sólo positivistas, sino también jusnaturalistas asumen implícitamente al definir Derecho. 2) El neoconstitucionalismo tampoco es compatible con el formalismo de Ferrajoli. 3) El neoconstitucionalismo no es compatible con la tesis de la separación. 4) El neoconstitucionalismo no es compatible con la metaética que subyace a la filosofía jurídica de Ferrajoli.
Antígona como defeater: sobre el constitucionalismo garantista de Ferrajoli
Authors: Moreso Mateos Josep Joan
Published: May 2014

En este trabajo se critica la defensa que Ferrajoli hace del constitucionalismo garantista o normativo, que contrapone al constitucionalismo principialista o argumentativo. Se intenta mostrar que los rasgos definitorios del constitucionalismo principialista no tienen las consecuencias perniciosas que el autor les atribuye. En particular, se rechazan los argumentos que consideran que el objetivismo moral hace imposible el liberalismo político y la democracia. Se rechaza también que la distinción entre principios y reglas menoscabe la dimensión normativa del Derecho y se muestra que el activismo judicial que la ponderación en la aplicación del Derecho comporta es plenamente asumible en la concepción del constitucionalismo. Se vindica el denominado constitucionalismo incorporacionista: se mantiene la tesis de la no conexión necesaria entre el Derecho y la moral, se asume el objetivismo moral y se adopta que, al incorporar consideraciones morales, los sistemas jurídicos incorporan criterios morales en la identificación y la aplicación del Derecho.
Ferrajoli y el neoconstitucionalismo principialista: ensayo de interpretación de algunas divergencias
Authors: Prieto Sanchís Luis
Published: May 2014

La teoría jurídica de Ferrajoli asume el nuevo paradigma del Estado constitucional de Derecho. Sin embargo se distancia de las construcciones más habituales del neoconstitucionalismo en dos aspectos capitales, que aquí son objeto de análisis. En el aspecto metodológico o conceptual se mantiene firmemente la perspectiva ilustrada y positivista de la separación conceptual entre Derecho y moral. En el aspecto teórico, se mantiene una posición más escéptica o menos confiada en las posibilidades de la argumentación jurídica, lo que tiene dos consecuencias principales: una visión más restrictiva de la aplicación directa de la Constitución y una visión no conflictivista de los derechos fundamentales.
Las cuentas que no cuadran en el constitucionalismo de Ferrajoli
Authors: Ruiz Miguel Alfonso
Published: May 2014

El artículo analiza tres puntos del escrito de Ferrajoli «Constitucionalismo principialista y constitucionalismo garantista» en los que existen tensiones no resueltas: el primero, relativo al objetivismo moral, el segundo al positivismo jurídico, sea como enfoque metodológico sea como ideología sobre el Derecho, y, en fin, el último al problema de la interpretación jurídica.
Customer Complaints and Recovery Effectiveness: A Customer Base Approach
Authors: Knox George , van Oest Rutger
Published: May 2014

Although customer complaints are a well-studied aspect of business, no study has measured the impact of actual complaints and recoveries on subsequent customer purchasing. The authors develop a customer base model to investigate the effectiveness of recovery in preventing customer churn. They calibrate it on panel data that track actual purchases, complaints, and recoveries for 20,000 new customers of an Internet and catalog retailer over 2.5 years. Complaints are associated with a substantial increase in the probability that the customer stops buying, but the size of the increase depends on prior customer experiences: prior purchases mitigate the effect, and their impact is long-lasting, whereas prior complaints exacerbate the effect, but their impact is short-lived. Thus, unless the customer leaves the company after a complaint, or a second failure occurs shortly after the first, the relationship quickly returns to normal. Recovery counters the effect of the complaint but, in almost all cases, does not entirely offset it. The authors use simulation to translate the results to financial impact and discuss implications for researchers and managers.
GABABAgonism Promotes Sleep and Reduces Cataplexy in Murine Narcolepsy
Authors: Black Sarah Wurts , Morairty Stephen R. , Chen Tsui-Ming , Leung Andrew K. , Wisor Jonathan P. , Yamanaka Akihiro , Kilduff Thomas S.
Published: May 2014

γ-Hydroxybutyrate (GHB) is an approved therapeutic for the excessive sleepiness and sudden loss of muscle tone (cataplexy) characteristic of narcolepsy. The mechanism of action for these therapeutic effects is hypothesized to be GABABreceptor dependent. We evaluated the effects of chronic administration of GHB and the GABABagonistR-baclofen (R-BAC) on arousal state and cataplexy in two models of narcolepsy:orexin/ataxin-3(Atax) andorexin/tTA; TetO diphtheria toxinmice (DTA). Mice were implanted for EEG/EMG monitoring and dosed with GHB (150 mg/kg),R-BAC (2.8 mg/kg), or vehicle (VEH) bid for 15 d–a treatment paradigm designed to model the twice nightly GHB dosing regimen used by human narcoleptics. In both models,R-BAC increased NREM sleep time, intensity, and consolidation during the light period; wake bout duration increased and cataplexy decreased during the subsequent dark period. GHB did not increase NREM sleep consolidation or duration, although NREM delta power increased in the first hour after dosing. Cataplexy decreased from baseline in 57 and 86% of mice after GHB andR-BAC, respectively, whereas cataplexy increased in 79% of the mice after VEH. At the doses tested,R-BAC suppressed cataplexy to a greater extent than GHB. These results suggest utility ofR-BAC-based therapeutics for narcolepsy.
Global Selection of Saccadic Target Features by Neurons in Area V4
Authors: Burrows Brittany E. , Zirnsak Marc , Akhlaghpour Hessameddin , Wang Megan , Moore Tirin
Published: May 2014

Psychophysical and neurophysiological studies indicate that during the preparation of saccades, visual processing at the target location is facilitated automatically by the deployment of attention. It has been assumed that the neural mechanisms involved in presaccadic shifts of attention are purely spatial in nature. Saccade preparation modulates the visual responses of neurons within extrastriate area V4, where the responses to targets are enhanced and responses to nontargets are suppressed. We tested whether this effect also engages a nonspatial form of modulation. We measured the responses of area V4 neurons to oriented gratings in two monkeys (Macaca mulatta) making delayed saccades to targets distant from the neuronal receptive field (RF). We varied the orientation of both the RF stimulus and the saccadic target. We found that, in addition to the spatial modulation, saccade preparation involves a feature-dependent modulation of V4 neuronal responses. Specifically, we found that the suppression of area V4 responses to nontarget stimuli during the preparation of saccades depends on the features of the saccadic target. Presaccadic suppression was absent when the features of the saccadic target matched the features preferred by individual V4 neurons. This feature-dependent modulation occurred in the absence of any feature-attention task. We show that our observations are consistent with a computational framework in which feature-based effects automatically emerge from saccade-related feedback signals that are spatial in nature.
An Intact Action-Perception Coupling Depends on the Integrity of the Cerebellum
Authors: Christensen Andrea , Giese Martin A. , Sultan Fahad , Mueller Oliver M. , Goericke Sophia L. , Ilg Winfried , Timmann Dagmar
Published: May 2014

It is widely accepted that action and perception in humans functionally interact on multiple levels. Moreover, areas originally suggested to be predominantly motor-related, as the cerebellum, are also involved in action observation. However, as yet, few studies provided unequivocal evidence that the cerebellum is involved in the action perception coupling (APC), specifically in the integration of motor and multisensory information for perception. We addressed this question studying patients with focal cerebellar lesions in a virtual-reality paradigm measuring the effect of action execution on action perception presenting self-generated movements as point lights. We measured the visual sensitivity to the point light stimuli based on signal detection theory. Compared with healthy controls cerebellar patients showed no beneficial influence of action execution on perception indicating deficits in APC. Applying lesion symptom mapping, we identified distinct areas in the dentate nucleus and the lateral cerebellum of both hemispheres that are causally involved in APC. Lesions of the right ventral dentate, the ipsilateral motor representations (lobules V/VI), and most interestingly the contralateral posterior cerebellum (lobule VII) impede the benefits of motor execution on perception. We conclude that the cerebellum establishes time-dependent multisensory representations on different levels, relevant for motor control as well as supporting action perception. Ipsilateral cerebellar motor representations are thought to support the somatosensory state estimate of ongoing movements, whereas the ventral dentate and the contralateral posterior cerebellum likely support sensorimotor integration in the cerebellar-parietal loops. Both the correct somatosensory as well as the multisensory state representations are vital for an intact APC.
Fear from the Heart: Sensitivity to Fear Stimuli Depends on Individual Heartbeats
Authors: Garfinkel Sarah N. , Minati Ludovico , Gray Marcus A. , Seth Anil K. , Dolan Raymond J. , Critchley Hugo D.
Published: May 2014

Cognitions and emotions can be influenced by bodily physiology. Here, we investigated whether the processing of brief fear stimuli is selectively gated by their timing in relation to individual heartbeats. Emotional and neutral faces were presented to human volunteers at cardiac systole, when ejection of blood from the heart causes arterial baroreceptors to signal centrally the strength and timing of each heartbeat, and at diastole, the period between heartbeats when baroreceptors are quiescent. Participants performed behavioral and neuroimaging tasks to determine whether these interoceptive signals influence the detection of emotional stimuli at the threshold of conscious awareness and alter judgments of emotionality of fearful and neutral faces. Our results show that fearful faces were detected more easily and were rated as more intense at systole than at diastole. Correspondingly, amygdala responses were greater to fearful faces presented at systole relative to diastole. These novel findings highlight a major channel by which short-term interoceptive fluctuations enhance perceptual and evaluative processes specifically related to the processing of fear and threat and counter the view that baroreceptor afferent signaling is always inhibitory to sensory perception.
Genetic Analysis Reveals that Amyloid Precursor Protein and Death Receptor 6 Function in the Same Pathway to Control Axonal Pruning Independent of β-Secretase
Authors: Olsen Olav , Kallop Dara Y. , McLaughlin Todd , Huntwork-Rodriguez Sarah , Wu Zhuhao , Duggan Cynthia D. , Simon David J. , Lu Yanmei , Easley-Neal Courtney , Takeda Kentaro , Hass Philip E. , Jaworski Alexander , O'Leary Dennis D.M. , Weimer Robby M , Tessier-Lavigne Marc
Published: May 2014

In the developing brain, initial neuronal projections are formed through extensive growth and branching of developing axons, but many branches are later pruned to sculpt the mature pattern of connections. Despite its widespread occurrence, the mechanisms controlling pruning remain incompletely characterized. Based on pharmacological and biochemical analysisin vitroand initial genetic analysisin vivo, prior studies implicated a pathway involving binding of the Amyloid Precursor Protein (APP) to Death Receptor 6 (DR6) and activation of a downstream caspase cascade in axonal pruning. Here, we further test their involvement in pruningin vivoand their mechanism of action through extensive genetic and biochemical analysis. Genetic deletion ofDR6was previously shown to impair pruning of retinal axonsin vivo. We show that genetic deletion ofAPPsimilarly impairs pruning of retinal axonsin vivoand provide evidence that APP and DR6 act cell autonomously and in the same pathway to control pruning. Prior analysis had suggested that β-secretase cleavage of APP and binding of an N-terminal fragment of APP to DR6 is required for their actions, but further genetic and biochemical analysis reveals that β-secretase activity is not required and that high-affinity binding to DR6 requires a more C-terminal portion of the APP ectodomain. These results provide direct support for the model that APP and DR6 function cell autonomously and in the same pathway to control pruningin vivoand raise the possibility of alternate mechanisms for how APP and DR6 control pruning.
Cyclic AMP and Afferent Activity Govern Bidirectional Synaptic Plasticity in Striatopallidal Neurons
Authors: Augustin Shana M. , Beeler Jeff A. , McGehee Daniel S. , Zhuang Xiaoxi
Published: May 2014

Recent experimental evidence suggests that the low dopamine conditions in Parkinson's disease (PD) cause motor impairment through aberrant motor learning. Those data, along with computational models, suggest that this aberrant learning results from maladaptive corticostriatal plasticity and learned motor inhibition. Dopaminergic modulation of both corticostriatal long-term depression (LTD) and long-term potentiation (LTP) is proposed to be critical for these processes; however, the regulatory mechanisms underlying bidirectional corticostriatal plasticity are not fully understood. Previously, we demonstrated a key role for cAMP signaling in corticostriatal LTD. In this study, mouse brain slices were used to perform a parametric experiment that tested the impact of varying both intracellular cAMP levels and the strength of excitatory inputs on corticostriatal plasticity. Using slice electrophysiology in the dorsolateral striatum, we demonstrate that both LTP and LTD can be sequentially induced in the same D2-expressing neuron and that LTP was strongest with high intracellular cAMP and LFS, whereas LTD required low intracellular cAMP and high-frequency stimulation. Our results provide a molecular and cellular basis for regulating bidirectional corticostriatal synaptic plasticity and may help to identify novel therapeutic targets for blocking or reversing the aberrant synaptic plasticity that likely contributes to motor deficits in PD.
Scale-Free Bursting in Human Cortex following Hypoxia at Birth
Authors: Roberts James A. , Iyer Kartik K. , Finnigan Simon , Vanhatalo Sampsa , Breakspear Michael
Published: May 2014

The human brain is fragile in the face of oxygen deprivation. Even a brief interruption of metabolic supply at birth challenges an otherwise healthy neonatal cortex, leading to a cascade of homeostatic responses. During recovery from hypoxia, cortical activity exhibits a period of highly irregular electrical fluctuations known as burst suppression. Here we show that these bursts have fractal properties, with power-law scaling of burst sizes across a remarkable 5 orders of magnitude and a scale-free relationship between burst sizes and durations. Although burst waveforms vary greatly, their average shape converges to a simple form that is asymmetric at long time scales. Using a simple computational model, we argue that this asymmetry reflects activity-dependent changes in the excitatory–inhibitory balance of cortical neurons. Bursts become more symmetric following the resumption of normal activity, with a corresponding reorganization of burst scaling relationships. These findings place burst suppression in the broad class of scale-free physical processes termed crackling noise and suggest that the resumption of healthy activity reflects a fundamental reorganization in the relationship between neuronal activity and its underlying metabolic constraints.
Selective Modulation of Auditory Cortical Alpha Activity in an Audiovisual Spatial Attention Task
Authors: Frey Julia N. , Mainy Nelly , Lachaux Jean-Philippe , Müller Nadia , Bertrand Olivier , Weisz Nathan
Published: May 2014

Despite substantial research on attentional modulations of visual alpha activity, doubts remain as to the existence and functional relevance of auditory cortical alpha-band oscillations. It has been argued that auditory cortical alpha does not exist, cannot be measured noninvasively, or that it is dependent on visual alpha generators. This study aimed to address these remaining doubts concerning auditory cortical alpha. A magnetoencephalography study was conducted using a combined audiovisual spatial cueing paradigm. In each trial, a cue indicated the side (left or right) and the modality (auditory or visual) to attend, followed by a short lateralized auditory or visual stimulus. Participants were instructed to respond to the stimuli by a button press. Results show that auditory cortical alpha power is selectively modulated by the audiospatial, but not the visuospatial, attention task. These findings provide further evidence for a distinct auditory cortical alpha generator, which can be measured noninvasively.
Mitochondria Modify Exercise-Induced Development of Stem Cell-Derived Neurons in the Adult Brain
Authors: Steib Kathrin , Schäffner Iris , Jagasia Ravi , Ebert Birgit , Lie D. Chichung
Published: May 2014

Neural stem cells in the adult mammalian hippocampus continuously generate new functional neurons, which modify the hippocampal network and significantly contribute to cognitive processes and mood regulation. Here, we show that the development of new neurons from stem cells in adult mice is paralleled by extensive changes to mitochondrial mass, distribution, and shape. Moreover, exercise—a strong modifier of adult hippocampal neurogenesis—accelerates neuronal maturation and induces a profound increase in mitochondrial content and the presence of mitochondria in dendritic segments. Genetic inhibition of the activity of the mitochondrial fission factor dynamin-related protein 1 (Drp1) inhibits neurogenesis under basal and exercise conditions. Conversely, enhanced Drp1 activity furthers exercise-induced acceleration of neuronal maturation. Collectively, these results indicate that adult hippocampal neurogenesis requires adaptation of the mitochondrial compartment and suggest that mitochondria are targets for enhancing neurogenesis-dependent hippocampal plasticity.
Differential Effects of Presynaptic versus Postsynaptic Adenosine A2AReceptor Blockade on Δ9-Tetrahydrocannabinol (THC) Self-Administration in Squirrel Monkeys
Authors: Justinová Zuzana , Redhi Godfrey H. , Goldberg Steven R. , Ferré Sergi
Published: May 2014

Different doses of an adenosine A2Areceptor antagonist MSX-3 [3,7-dihydro-8-[(1E)-2-(3-ethoxyphenyl)ethenyl]-7 methyl-3-[3-(phosphooxy)propyl-1-(2 propynil)-1H-purine-2,6-dione] were found previously to either decrease or increase self-administration of cannabinoids delta-9-tetrahydrocannabinol (THC) or anandamide in squirrel monkeys. It was hypothesized that the decrease observed with a relatively low dose of MSX-3 was related to blockade of striatal presynaptic A2Areceptors that modulate glutamatergic neurotransmission, whereas the increase observed with a higher dose was related to blockade of postsynaptic A2Areceptors localized in striatopallidal neurons. This hypothesis was confirmed in the present study by testing the effects of the preferential presynaptic and postsynaptic A2Areceptor antagonists SCH-442416 [2-(2-furanyl)-7-[3-(4-methoxyphenyl)propyl]-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine] and KW-6002 [(E)-1, 3-diethyl-8-(3,4-dimethoxystyryl)-7-methyl-3,7-dihydro-1H-purine-2,6-dione], respectively, in squirrel monkeys trained to intravenously self-administer THC. SCH-442416 produced a significant shift to the right of the THC self-administration dose–response curves, consistent with antagonism of the reinforcing effects of THC. Conversely, KW-6002 produced a significant shift to the left, consistent with potentiation of the reinforcing effects of THC. These results show that selectively blocking presynaptic A2Areceptors could provide a new pharmacological approach to the treatment of marijuana dependence and underscore corticostriatal glutamatergic neurotransmission as a possible main mechanism involved in the rewarding effects of THC.
Combined Effects of Alzheimer Risk Variants in theCLUandApoEGenes on Ventricular Expansion Patterns in the Elderly
Authors: Roussotte Florence F. , Gutman Boris A. , Madsen Sarah K. , Colby John B. , Thompson Paul M. ,   for the Alzheimer's Disease Neuroimaging Initiative
Published: May 2014

The C allele at the rs11136000 locus in the clusterin (CLU) gene is the third strongest known genetic risk factor for late-onset Alzheimer's disease (LOAD). A recent genome-wide association study of LOAD found the strongest evidence of association withCLUat rs1532278, in high linkage disequilibrium with rs11136000. Brain structure and function are related to theCLUrisk alleles, not just in LOAD patients but also in healthy young adults. We tracked the volume of the lateral ventricles across baseline, 1-year, and 2-year follow-up scans in a large sample of elderly human participants (N= 736 at baseline), from the Alzheimer's Disease Neuroimaging Initiative, to determine whether theseCLUrisk variants predicted longitudinal ventricular expansion. The rs11136000 major C allele—previously linked with reducedCLUexpression and with increased risk for dementia—predicted faster expansion, independently of dementia status orApoEgenotype. Further analyses revealed that theCLUandApoErisk variants had combined effects on both volumetric expansion and lateral ventricle surface morphology. The rs1532278 locus strongly resembles a regulatory element. Its association with ventricular expansion was slightly stronger than that of rs11136000 in our analyses, suggesting that it may be closer to a functional variant. Clusterin affects inflammation, immune responses, and amyloid clearance, which in turn may result in neurodegeneration. Pharmaceutical agents such as valproate, which counteract the effects of genetically determined reduced clusterin expression, may help to achieve neuroprotection and contribute to the prevention of dementia, especially in carriers of theseCLUrisk variants.
Surgical remission of Cushing's syndrome reduces cardiovascular risk
Authors: Terzolo M , Allasino B , Pia A , Peraga G , Daffara F , Laino F , Ardito A , Termine A , Paccotti P , Berchialla P , Migliaretti G , Reimondo G
Published: May 2014

Objective

Recent studies have questioned the reversibility of complications of Cushing's syndrome (CS) after successful surgical treatment. The aim of this study was to assess the outcome of patients with CS who achieved disease remission compared with those patients with persistent hypercortisolism and matched controls.

Design

A retrospective study of 75 patients with CS followed at an academic center.

Methods

Cardiovascular risk profile was evaluated in 51 patients with CS in remission (group 1) and 24 patients with persistent disease (group 2) and compared with 60 controls. Mortality of patients with CS was compared with the background population.

Results

In group 1, the frequency of cardiovascular risk factors dropped after disease remission even if it remained higher at the last follow-up than in the control group. In group 2, the frequency of cardiovascular risk factors remained unchanged during follow-up. The rate of cardiovascular and thromboembolic events was higher in group 2 than in group 1, as was the mortality rate (two deaths in group 1 and nine in group 2; ratio of two SMRs, 0.11; 95% CI, 0.011–0.512). Survival was significantly longer in group 1 than in group 2 (87 months, 80–98 vs 48 months, 38–62;P<0.0001).

Conclusions

Successful surgical treatment of hypercortisolism significantly improves cardiovascular risk and may reduce the mortality rate. Patients with persistent disease have increased morbidity and mortality when compared with patients in remission.
Associations between thyroid function and mortality: the influence of age
Authors: van de Ven Annenienke C , Netea-Maier Romana T , de Vegt Femmie , Ross H Alec , Sweep Fred C G J , Kiemeney Lambertus A , Smit Johannes W , Hermus Ad R , den Heijer Martin
Published: May 2014

Objective

The aim of this study was to investigate the influence of age on the association between thyroid function and mortality.

Design

The Nijmegen Biomedical Study is a population-based study, comprising 5816 randomly selected adults of all age groups without previously known thyroid disease.

Methods

TSH, free thyroxine (FT4) and peroxidase antibodies were measured in 2002–2003. The number of deaths were established in 2012 (median follow-up time 9.4 years).

Results

Subclinical thyrotoxicosis was associated with mortality in subjects aged <65 years (hazard ratio (HR) 2.5, 95% CI 1.1–5.7), but not in subjects aged >65 years. As for thyroid function within the normal range: in the 493 participants aged 80 years or older, an FT4 level in the high-normal range (18.5–22 pmol/l) was associated with a higher mortality in comparison with FT4 levels in the middle range (11.5–15.0 pmol/l): HR 1.7 (95% CI 1.0–2.9). In these elderly, TSH levels within the high-normal range (3.0–4.0 mIU/l) were also associated with a higher mortality in comparison with TSH levels within the middle range (1.0–2.0 mIU/l): HR 1.8 (95% CI 1.0–3.1).

Conclusions

The relationship between thyroid function and mortality differs according to age. This finding might (partially) explain the discrepant results of previous studies examining the relationship between thyroid function and mortality in different age groups.
Psychological morbidity and impaired quality of life in patients with stable treatment for primary adrenal insufficiency: cross-sectional study and review of the literature
Authors: Tiemensma Jitske , Andela Cornelie D , Kaptein Ad A , Romijn Johannes A , van der Mast Roos C , Biermasz Nienke R , Pereira Alberto M
Published: May 2014

Context

A high prevalence of psychological morbidity and maladaptive personality as well as impaired quality of life (QoL) is observed in patients with and without hydrocortisone dependency following (cured) Cushing's syndrome. However, it is currently unclear whether a similar pattern is present in patients with chronic glucocorticoid replacement for primary adrenal insufficiency (PAI).

Objective

To evaluate psychological functioning, personality traits, and QoL in patients with PAI.

Design and subjects

A cross-sectional study including 54 patients with stable treatment for PAI and 54 healthy matched controls. Both patients and controls completed questionnaires on psychological functioning (Apathy Scale, Irritability Scale, Mood and Anxiety Symptoms Questionnaire short form, and Hospital Anxiety and Depression Scale), personality traits (Dimensional Assessment of Personality Pathology short form), and QoL (Multidimensional Fatigue Inventory, Short Form 36, EuroQoL-5D, Nottingham Health Profile, and Physical Symptom Checklist).

Results

Patients with PAI suffered from more psychological morbidity (i.e. irritability and somatic arousal) and QoL impairments compared with controls (allP<0.01). There were no differences regarding maladaptive personality traits between patients and controls. However, there was a strong and consistent positive association between the daily hydrocortisone dose and prevalence of maladaptive personality traits (i.e. identity problems, cognitive distortion, compulsivity, restricted expression, callousness, oppositionality, rejection, conduct problems, social avoidance, narcissism, and insecure attachment, allP<0.05). There was also a strong relation between the mean daily hydrocortisone dose and both psychological morbidity (i.e. depression,P<0.05) and QoL impairments (i.e. general health perception, several measures of physical functioning, and vitality, allP<0.05).

Conclusion

Patients on stable glucocorticoid replacement therapy for PAI report psychological morbidity and impaired QoL. Psychological morbidity, impaired QoL, and maladaptive personality traits were all associated with higher dosages of hydrocortisone.
Effect of long-term GH replacement therapy on cardiovascular outcomes in isolated GH deficiency compared with multiple pituitary hormone deficiencies: a sub-analysis from the Dutch National Registry of Growth Hormone Treatment in Adults
Authors: van Bunderen Christa C , van den Dries Carline J , Heymans Martijn W , Franken Anton A M , Koppeschaar Hans P F , van der Lely Aart J , Drent Madeleine L
Published: May 2014

Objective

Isolated GH deficiency (IGHD) could provide a model to investigate the influence of GH deficiency per se and the effect of GH replacement therapy without the influence from other pituitary hormone deficiencies or their treatment. The aim of this study is to address the questions about differences between IGHD and multiple pituitary hormone deficiencies (MPHDs) in clinical presentation and in responsiveness to GH treatment.

Design

A nationwide surveillance study was carried out to describe the difference in the clinical presentation and responsiveness to GH treatment of patients with IGHD and MPHDs.

Methods

The Dutch National Registry of GH Treatment in Adults was founded in 1998 to gain more insight into long-term efficacy and safety of GH therapy. Out of 2891 enrolled patients, 266 patients with IGHD at the start of GH treatment were identified and compared with 310 patients with MPHDs. Cardiovascular indices will be investigated at baseline and during long-term follow-up, including body composition, lipid profile, glucose metabolism, blood pressure, and morbidity.

Results

Patients with IGHD and MPHDs were demonstrated to be different entities at clinical presentation. Metabolically, patients with MPHDs had a larger waist circumference, lower HDL cholesterol level, and higher triglyceride level. The effect of GH treatment was comparable between patient groups. GH seems to protect against rising lipid levels and blood pressure, even after excluding patients using corresponding concomitant medication. The risk for cardiovascular disease or diabetes mellitus during follow-up was not different between patients with IGHD and MPHDs.

Conclusions

Patients with IGHD had a less impaired metabolic profile than patients with MPHDs at baseline. Influence of other pituitary hormone replacement therapies on the effect of GH treatment is not demonstrated.
The activating TERT promoter mutation C228T is recurrent in subsets of adrenal tumors
Authors: Liu Tiantian , Brown Taylor C , Juhlin C Christofer , Andreasson Adam , Wang Na , Bäckdahl Martin , Healy James M , Prasad Manju L , Korah Reju , Carling Tobias , Xu Dawei , Larsson Catharina
Published: May 2014

The telomerase reverse transcriptase gene (TERT) encodes the reverse transcriptase component of the telomerase complex, which is essential for telomere stabilization and cell immortalization. Recent studies have demonstrated a transcriptional activation role for theTERTpromoter mutations C228T and C250T in many human cancers, as well as a role in aggressive disease with potential clinical applications. Although telomerase activation is known in adrenal tumors, the underlying mechanisms are not established. We assessed C228T and C250TTERTmutations by direct Sanger sequencing in tumors of the adrenal gland, and further evaluated potential associations with clinical parameters and telomerase activation. A total of 199 tumors were evaluated, including 34 adrenocortical carcinomas (ACC), 47 adrenocortical adenomas (ACA), 105 pheochromocytomas (PCC; ten malignant and 95 benign), and 13 abdominal paragangliomas (PGL; nine malignant and four benign).TERTexpression levels were determined by quantitative RT-PCR. The C228T mutation was detected in 4/34 ACCs (12%), but not in any ACA (P=0.028). C228T was also observed in one benign PCC and in one metastatic PGL. The C250T mutation was not observed in any case. In the ACC and PGL groups,TERTmutation-positive cases exhibitedTERTexpression, indicating telomerase activation; however, since expression was also revealed inTERTWT cases, this could denote additional mechanisms ofTERTactivation. To conclude, theTERTpromoter mutation C228T is a recurrent event associated withTERTexpression in ACCs, but rarely occurs in PGL and PCC. The involvement of theTERTgene in ACC represents a novel mutated gene in this entity.
Involvement of VCAM1 in the bovine conceptus adhesion to the uterine endometrium
Authors: Bai Rulan , Bai Hanako , Kuse Mariko , Ideta Atsushi , Aoyagi Yoshito , Fujiwara Hiroshi , Okuda Kiyoshi , Imakawa Kazuhiko , Sakurai Toshihiro
Published: May 2014

Following bidirectional communication, the conceptus and the uterine epithelium must establish a proper cell–cell interaction, resulting in the progression of implantation processes. To clarify the mechanism of conceptus attachment to the uterine endometrium, we studied whether vascular cell adhesion molecule (VCAM1) was expressed in bovine conceptuses or endometrium during the peri-attachment period. UterineVCAM1expression was minimal in day 17 (day 0=day of estrus) cyclic and pregnant animals, but increased between days 20 and 22 of pregnancy. In the intercaruncular regions, VCAM1 protein was localized to the luminal and glandular epithelia, whereas in the caruncular regions, VCAM1 protein was detected in the stroma and endothelia of the uterine endometrium. In cultured endometrial epithelial cells (EECs),VCAM1expression was up-regulated when treated with uterine flushings or growth factor and further increased when EECs were cocultured with bovine trophoblast CT1 cells.VCAM1expression in CT1 cells was also up-regulated with the use of uterine flushings, and further increased when these cells were cocultured with EECs. Expression of VCAM1 receptor, integrin α 4 (ITGA4) mRNA, increased significantly in day 22 conceptuses. In day 22 pregnant uteri, VCAM1 protein was found in both EECs and conceptuses, but ITGA4 was localized only to trophoblasts. These observations indicate that cell–cell interactions between conceptuses and uterine epithelial cells are required for sufficient VCAM1 and ITGA4 expression in the bovine species and suggest that uterine VCAM1 and conceptus ITGA4 play a role in the establishment of conceptus adhesion to the uterine endometrium.
Effects of pH in the incorporation of Mn2+ in Ce1-xMnxO2-x (0.05 ≤ x ≤ 0.25) solid solutions using oxalate co-precipitation technique and its characterizations
Authors: Ong P. S. , Tan Y. P. , Taufiq-Yap Y. H. , Zainal Z.
Published: May 2014

Mn-doped CeO2 electrolytes formulated as Ce1-xMnxO2-x (0.05 ≤ x ≤ 0.25) were prepared via soft chemical technique which involved co-precipitation of Mn2+ and Ce4+ using oxalic acid as the precipitant. The optimized pH for a stable incorporation of Mn dopant into ceria was found to be pH = 10. The solubility limit of MnO in the CeO2 fluorite lattice structure was suggested to be x = 0.20. The phase composition, morphology properties and elemental analysis of the oxalate and derived-powder was characterized using X-ray diffraction, SEM and X-ray fluorescence (XRF) respectively. The electrical conductivity of sintered samples of Mn-doped CeO2 ceramics were investigated in air using AC impedance spectroscopy. The bulk conductivities of the Mn-doped CeO2 ceramics sintered at 1200 °C at a test temperature of 800 °C were determined to be 4.223 x 10-4 ohm-1 cm-1 for Mn content x = 0.10 with activation energy, Ea = 0.88 eV.
dLow Temperature of formation of Nickel Germanide by reaction of Nickel and Crystalline Germanium
Authors: Algahtani Fahid , Leech Patrick W , Reeves Geoffrey K , Holland Anthony S , Blackford Mark , Thorogood Gordon , McCallum Jeffrey C , Johnson Brett C
Published: May 2014

The formation of nickel germanide has been examined over a range of low temperatures (200-400 °C) in an attempt to minimize the thermal budget for the process. Cross-sectional Transmission Electron Microscopy (TEM) was used to determine the texture of the germanide layer and the morphology and constituent composition of the Ge/NiGe interface. The onset and completion of reaction between Ni and Ge were identified by means of a heated stage in combination with in-situ x-ray diffraction (XRD) measurements. The stages of reaction were also monitored using measurements of sheet resistance of the germanides by the Van der Pauw technique. The results have shown that the minimum temperature for the initiation of reaction of Ni and Ge to form NiGe was 225 °C. However, an annealing temperature > 275 °C was necessary for the extensive (and practical) formation of NiGe. Between 200 and 300 °C, the duration of annealing required for the formation of NiGe was significantly longer than at higher temperatures. The stoichiometry of the germanide was very close to NiGe (1:1) as determined using energy dispersive spectroscopy (EDS).
Multishell EXAFS Fitting Analysis of a Compositionally Precise Thiolate-Gold Nanocluster
Authors: Chevrier Daniel M. , Chatt Amares , Zhang Peng , Zeng Chenjie , Jin Rongchao
Published: May 2014

Thiolate-gold nanoclusters exhibit unique optical, magnetic and chiral properties, which are attractive for novel applications in nanotechnology. A fundamental challenge facing these nanomaterials is being able to study and understand their physical properties in various experimental conditions. To overcome this, extended X-ray absorption fine structure (EXAFS) spectroscopy can be employed to probe the Au local structure of thiolate-gold nanoclusters in a variety of conditions, providing valuable structural information from multiple bonding environments (i.e. metal-metal and metal-ligand interactions). This study discusses a methodology for conducting a multishell EXAFS fitting analysis that can be implemented for thiolate-gold nanocluster systems. Specifically, experimental and simulated EXAFS data for Au36(SR)24 nanoclusters are examined with a total of 5 scattering paths fitted to the experimental data.