NEDA—NEutron Detector Array

The NEutron Detector Array, NEDA, will form the next generation neutron detection system that has been designed to be operated in conjunction with γ-ray arrays, such as the tracking-array AGATA, to aid nuclear spectroscopy studies. NEDA has been designed to be a versatile device, with high-detection efficiency, excellent neutron-γ discrimination, and high rate capabilities. It will be employed in physics campaigns in order to maximise the scientific output, making use of the different stable and radioactive ion beams available in Europe. The first implementation of the neutron detector array NEDA with AGATA 1π was realised at GANIL. This manuscript reviews the various aspects of NEDA

Pathogenesis of peroxisomal deficiency disorders (Zellweger syndrome) may be mediated by misregulation of the GABAergic system via the diazepam binding inhibitor

BACKGROUND: Zellweger syndrome (ZS) is a fatal inherited disease caused by peroxisome biogenesis deficiency. Patients are characterized by multiple disturbances of lipid metabolism, profound hypotonia and neonatal seizures, and distinct craniofacial malformations. Median live expectancy of ZS patients is less than one year. While the molecular basis of peroxisome biogenesis and metabolism is known in considerable detail, it is unclear how peroxisome deficiency leads to the most severe neurological symptoms. Recent analysis of ZS mouse models has all but invalidated previous hypotheses. HYPOTHESIS: We suggest that a regulatory rather than a metabolic defect is responsible for the drastic impairment of brain function in ZS patients. TESTING THE HYPOTHESIS: Using microarray analysis we identify diazepam binding inhibitor/acyl-CoA binding protein (DBI) as a candidate protein that might be involved in the pathogenic mechanism of ZS. DBI has a dual role as a neuropeptide antagonist of GABA(A) receptor signaling in the brain and as a regulator of lipid metabolism. Repression of DBI in ZS patients could result in an overactivation of GABAergic signaling, thus eventually leading to the characteristic hypotonia and seizures. The most important argument for a misregulation of GABA(A) in ZS is, however, provided by the striking similarity between ZS and "benzodiazepine embryofetopathy", a malformation syndrome observed after the abuse of GABA(A) agonists during pregnancy. IMPLICATIONS OF THE HYPOTHESIS: We present a tentative mechanistic model of the effect of DBI misregulation on neuronal function that could explain some of the aspects of the pathology of Zellweger syndrome

TSPO ligand residence time influences human glioblastoma multiforme cell death/life balance

Abstract Ligands addressed to the mitochondrial Translocator Protein (TSPO) have been suggested as cell death/life and steroidogenesis modulators. Thus, TSPO ligands have been proposed as drug candidates in several diseases; nevertheless, a correlation between their binding affinity and in vitro efficacy has not been demonstrated yet, questioning the specificity of the observed effects. Since drug-target residence time is an emerging parameter able to influence drug pharmacological features, herein, the interaction between TSPO and irDE-MPIGA, a covalent TSPO ligand, was investigated in order to explore TSPO control on death/life processes in a standardized glioblastoma cell setting. After 90 min irDE-MPIGA cell treatment, 25 nM ligand concentration saturated irreversibly all TSPO binding sites; after 24 h, TSPO de-novo synthesis occurred and about 40 % TSPO binding sites resulted covalently bound to irDE-MPIGA. During cell culture treatments, several dynamic events were observed: (a) early apoptotic markers appeared, such as mitochondrial membrane potential collapse (at 3 h) and externalization of phosphatidylserine (at 6 h); (b) cell viability was reduced (at 6 h), without cell cycle arrest. After digitonin-permeabilized cell suspension treatment, a modulation of mitochondrial permeability transition pore was evidenced. Similar effects were elicited by the reversible TSPO ligand PIGA only when applied at micromolar dose. Interestingly, after 6 h, irDE-MPIGA cell exposure restored cell survival parameters. These results highlighted the ligand-target residence time and the cellular setting are crucial parameters that should be taken into account to understand the drug binding affinity and efficacy correlation and, above all, to translate efficiently cellular drug responses from bench to bedside

Mitochondrial dysfunction and biogenesis: do ICU patients die from mitochondrial failure?

Mitochondrial functions include production of energy, activation of programmed cell death, and a number of cell specific tasks, e.g., cell signaling, control of Ca2+ metabolism, and synthesis of a number of important biomolecules. As proper mitochondrial function is critical for normal performance and survival of cells, mitochondrial dysfunction often leads to pathological conditions resulting in various human diseases. Recently mitochondrial dysfunction has been linked to multiple organ failure (MOF) often leading to the death of critical care patients. However, there are two main reasons why this insight did not generate an adequate resonance in clinical settings. First, most data regarding mitochondrial dysfunction in organs susceptible to failure in critical care diseases (liver, kidney, heart, lung, intestine, brain) were collected using animal models. Second, there is no clear therapeutic strategy how acquired mitochondrial dysfunction can be improved. Only the benefit of such therapies will confirm the critical role of mitochondrial dysfunction in clinical settings. Here we summarized data on mitochondrial dysfunction obtained in diverse experimental systems, which are related to conditions seen in intensive care unit (ICU) patients. Particular attention is given to mechanisms that cause cell death and organ dysfunction and to prospective therapeutic strategies, directed to recover mitochondrial function. Collectively the data discussed in this review suggest that appropriate diagnosis and specific treatment of mitochondrial dysfunction in ICU patients may significantly improve the clinical outcome

The new neutron multiplicity filter NEDA and its first physics campaign with AGATA

A new neutron multiplicity filter NEDA, after a decade of design, R&D and construction, was employed in its first physics campaign with the AGATA spectrometer. Properties and performance of the array are discussed

Étude et réalisation d'un TDC numérique dans le cadre du trigger du GANIL

In nuclear physics, the interaction between the ion beam and the target produces a a large amount of events. Some of these events have no interest for the studied physical phenomenon ; the useful events are sorted using a trigger. We have studied and realized a new trigger suitable for the GANIL (Grands Accélérateur National d'Ions Lourds) experiments. After an overview of the triggers used up to now at GANIL, we give the main features of the new trigger (GANIL Master Trigger, GMT) such as modularity, universality and versality. After a description of the trigger operating modes, we depict the trigger realization steps. The trigger informs about fired detectors in a beam to target collision but gives no information about timing, nevertheless the timing is a very important piece of information if the trigger analysis duration in several times greater than the beam period. We suggest a timing measurement structure (Time to Digital Converter, TDC) able to eliminate this imprecision. The Dead time, the low level intégration and the consumption contraisnts lead us to prefer a digital architecture based on a digital counter associated with delay lines. Simple equations are given in order to define the operating area of the TDC. This area depends on the clock duty cycle and the delay line taps. Measures of Differential Non Linearity (DNL) for different time résolutions (1 ,2, 5 and 10 ns) allow to establish the limits of this system and to underline some solutions to improve these features.En physique nucléaire, l'interaction faisceau-cible engendre une multitude d'événements qui ne sont pas tous d'intérêt pour le phénomène physique étudié. Il est donc important de disposer d'un système de sélection nommé trigger. Nous avons étudié et réalisé un nouveau trigger adapté aux expériences menées au GANIL. Nous avons présenté un historique des différents triggers utilisés aux GANIL (Grand Accélérateur National d'Ions Lourds) et avons montré la nécessité d'un nouveau trigger modulaire, universel et ouvert. Après une description des différents modes de fonctionnement du nouveau trigger (GANIL Master Trigger, GMT) nous avons décrit les phases de sa conception et de sa réalisation. Le trigger renseigne sur la configuration des détecteurs temporels, or cette information peut être fondamentale dans le cas où la fenêtre d'analyse du trigger couvre plusieurs périodes du faisceau. Nous avons donc proposé une structure de mesure de temps (Time to Digital Converter, TDC) qui permet de lever cette indétermination. Les contraintes de temps mort, d'intégration et de consommation nous ont conduit à proposer une architecture numérique basée sur un compteur associé à une ligne A Retard (LAR). Des calculs simples ont permis de définir la zone de fonctionnement du TDC. Cette zone dépend du rapport cyclique de l'horloge et des retards de la LAR. Des mesures de Non Linéarité Différentielle (NLD) pour des résolutions différentes (1,2,5 et 10 ns) ont permis d'établir les limites de ce système et de mettre en évidence des solutions d'amélioration de ces caractéristiques

The new GANIL data acquisition system

International audienceWe report on the new GANIL DAQ system based on VXI-C crates and electronic modules (trigger, converters, scalers...) with a complete software running under LynxOS real-time kernel. The system elements can be used in various configurations depending on the type of experiments undertaken by the physicists. Moreover the older electronic subsystems (VXI-D, CAMAC...) can be easily coupled with the newest ones. The easiness of use and the modularity characterize the hardware equipment and the software application. The real-time software is implemented on one or several VME CPUs based on a PowerPC processor. The number of processes can be distributed on these CPUs and are dedicated to a specific job. The data flow is sent by such a task onto the Ethernet 10/100 network using TCP/IP protocol towards the “tapeserver” alpha workstation. This whole “new generation” DAQ system is operational from several months and many experiments have already used it in different configuration

Etude et réalisation d'un TDC numérique dans le cadre du trigger du GANIL

CAEN-BU Sciences et STAPS (141182103) / SudocSTRASBOURG-Bib.Central Recherche (674822133) / SudocSudocFranceF