Microwave spectro-polarimetry of matter and radiation across space and time

From Springer Nature via Jisc Publications RouterHistory: received 2020-07-29, accepted 2021-03-02, registration 2021-03-03, pub-print 2021-06, pub-electronic 2021-07-03, online 2021-07-03Publication status: PublishedAbstract: This paper discusses the science case for a sensitive spectro-polarimetric survey of the microwave sky. Such a survey would provide a tomographic and dynamic census of the three-dimensional distribution of hot gas, velocity flows, early metals, dust, and mass distribution in the entire Hubble volume, exploit CMB temperature and polarisation anisotropies down to fundamental limits, and track energy injection and absorption into the radiation background across cosmic times by measuring spectral distortions of the CMB blackbody emission. In addition to its exceptional capability for cosmology and fundamental physics, such a survey would provide an unprecedented view of microwave emissions at sub-arcminute to few-arcminute angular resolution in hundreds of frequency channels, a data set that would be of immense legacy value for many branches of astrophysics. We propose that this survey be carried out with a large space mission featuring a broad-band polarised imager and a moderate resolution spectro-imager at the focus of a 3.5 m aperture telescope actively cooled to about 8K, complemented with absolutely-calibrated Fourier Transform Spectrometer modules observing at degree-scale angular resolution in the 10–2000 GHz frequency range. We propose two observing modes: a survey mode to map the entire sky as well as a few selected wide fields, and an observatory mode for deeper observations of regions of specific interest

Imaging in cell-based therapy for neurodegenerative diseases.

Fetal cell transplantation for the treatment of Parkinsonrsquos and Huntingtonrsquos diseases has been developed over the past two decades and is now in early clinical testing phase. Direct assessment of the graftrsquos survival, integration into the host brain and impact on neuronal functions requires advanced in vivo neuroimaging techniques. Owing to its high sensitivity, positron emission tomography is today the most widely used tool to evaluate the viability and function of the transplanted tissue in the brain. Nuclear magnetic resonance techniques are opening new possibilities for imaging neurochemical events in the brain. The ultimate goal will be to use the combination of multiple imaging modalities for complete functional monitoring of the repair processes in the central nervous system

Utilisation combinée des essais pressiométriques et diagraphies instantanées pour mieux évaluer le risque géotechnique en reconnaissance des sols

Dans le contexte actuel, l'étude géotechnique menée dans le cadre d'un projet de construction de taille courante ne comporte que peu de sondages. L'hétérogénéité du sol ne peut être convenablement appréciée et la vision très partielle du site, obtenue à l'issue des investigations, conduit à des résultats variables selon le nombre et la localisation des points de sondages. Nous présentons le développement d'une méthodologie mettant en œuvre l'utilisation combinée des essais pressiométriques, donnant une image lissée des caractéristiques mécaniques des matériaux, et des diagraphies instantanées, peu coûteuses, mesures de la réponse du sol vis à vis du processus de forage et permettant le repérage des hétérogénéités locales. Le processus développé à partir des données issues d'un site expérimental de la région bordelaise et testé sur des données réelles est basé sur l'établissement de corrélations entre paramètres pressiométriques et paramètres de forage. Le processus propose de déterminer une lithologie sous forme de log. de probabilités à l'échelle du forage conforme aux informations diagraphiques et initialisée par une coupe lithologique a priori s'appuyant sur l'expérience du sondeur ou du géotechnicien. La détermination de la distribution statistique de la portance du sol pour un site et une fondation donnés permet d'estimer le risque associé à la valeur proposée par l'ingénieur via les règles de calcul usuelles et inversement de proposer, pour un niveau de fiabilité choisi, la contrainte à prendre en compte dans le dimensionnement des fondations. Dans la continuité des résultats obtenus, nous esquissons également un mode de détermination du nombre optimal de sondages à réaliser pour un niveau de risque donné.BORDEAUX1-BU Sciences-Talence (335222101) / SudocMARNE LA VALLEE-ENPC-RECHERCHE (774682302) / SudocSudocFranceF

The functional impact of the intrastriatal dopamine neuron grafts in parkinsonian rats is reduced with advancing disease

Clinical trials involving intrastriatal transplants of human embryonic mesencephalic tissue have provided proof-of-principle that nigral dopamine (DA) neurons can survive and functionally integrate into the host neural circuitry. However, the degree of graft-induced symptomatic relief differs significantly between the patients. This variability has led to investigations aimed at identifying factors that could affect the clinical outcome. The extent and pattern of dopaminergic denervation in the brain may be one of the major determinants of the functional outcome after intrastriatal DA cell grafts. Here, we report that in animals subjected to an intrastriatal 6-hydroxydopamine lesion of the striatal dopaminergic afferent, the integrity of the host dopaminergic innervation outside the areas innervated by the graft is critical for optimal function of DA neurons placed in the striatum. Established graft-induced functional recovery, as assessed in the stepping and cylinder tests, was compromised in animals in which the dopaminergic lesion was extended to include also the medial and ventral striatum as well as the cortical and limbic DA projections. Poor clinical outcome after transplantation may, thus, at least in part, be caused by dopaminergic denervation in areas outside the graft-innervated territories, and similarly beneficial effects initially observed in patients may regress if the degeneration of the host extrastriatal DA projection systems proceeds with advancing disease. This would have two implications: first, patients with advanced disease involving the ventral striatum and/ or nonstriatal DA projections would be unlikely to respond well to intrastriatal DA grafts and, second, to retain the full benefit of the grafts, progression of the disease should be avoided by, for example, combining cell therapy with a neuroprotective approach

Comparative study of five antiepileptic drugs on a translational cognitive measure in the rat: relationship to antiepileptic property.

International audienceRATIONALE: Antiepileptic drugs (AEDs) have been available for many years; yet, new members of this class continue to be identified and developed due to the limitations of existing drugs, which include a propensity for cognitive impairment. However, there is little preclinical information about the cognitive effects they produce, which clinically include deficits in attention and slowing of reaction time. OBJECTIVES: The purpose of this study was to profile two first-generation AEDs, phenytoin and valproate, and three second-generation AEDs, levetiracetam, pregabalin and lacosamide. Initially, each drug was examined across a range of well characterised preclinical seizure tests, and then each drug was evaluated in the five-choice serial reaction time test (5-CSRTT) based on efficacious doses from the seizure tests. MATERIALS AND METHODS: Each AED was tested for anti-seizure efficacy in either (1) the maximal electroshock seizure test, (2) s.c. PTZ seizure test, (3) amygdala-kindled seizures and (4) the genetic absence epilepsy rat of Strasbourg model of absence seizures. On completion of these studies, each drug was tested in rats trained to asymptotic performance in the 5-CSRTT (0.5 s SD, 5 s ITI, 100 trials). Male rats were used in all studies. RESULTS: Each AED was active in at least one of the seizure tests, although only valproate was active in each test. In the 5-CSRT test, all drugs with the exception of levetiracetam, significantly slowed reaction time and increased omissions. Variable effects were seen on accuracy. The effect on omissions was reversed by increasing stimulus duration from 0.5 to 5 s, supporting a drug-induced attention deficit. Levetiracetam had no negative effect on performance; indeed, reaction time was slightly increased (i.e. faster). CONCLUSIONS: These results highlight somewhat similar effects of phenytoin, valproate, pregabalin and lacosamide on attention and reaction time, and comparison to efficacious doses from the seizure tests support the view that there may be a better separation with the newer AEDs. Levetiracetam had no detrimental effect in the 5-CSRTT, which may be consistent with clinical experience where the drug is considered to be well tolerated amongst the AED class

P2X7 receptor mediated release of microglial prostanoids and miRNAs correlates with reversal of neuropathic hypersensitivity in rats

BACKGROUND: P2X7 receptor antagonists have potential for treating various CNS diseases, including neuropathic pain, although none have been approved for clinical use. Reasons may include insufficient understanding of P2X7 receptor signaling in pain and the lack of a corresponding preclinical mechanistic biomarker. METHODS: Lu AF27139 is a highly selective and potent small molecule antagonist at rat, mouse, and human forms of the P2X7 receptor, with excellent pharmacokinetic and CNS permeability properties. In the current experiments, we probed the utility of previously characterized and novel signaling cascades exposed to Lu AF27139 using cultured microglia combined with release assays. Subsequently, we assessed the biomarker potential of identified candidate molecules in the rat chronic constriction injury (CCI) model of neuropathic pain; study design limitations precluded their assessment in spared nerve injury (SNI) rats. RESULTS: Lu AF27139 blocked several pain-relevant pathways downstream of P2X7 receptors in-vitro. At brain and spinal cord receptor occupancy levels capable of functionally blocking P2X7 receptors, it diminished neuropathic hypersensitivity in SNI rats, and less potently in CCI rats. Although tissue levels of numerous molecules previously linked to neuropathic pain and P2X7 receptor function (e.g. IL-6, IL-1β, cathepsin-S, 2-AG) were unaffected by CCI, Lu AF27139-mediated regulation of spinal PGE2 and miRNA (e.g. rno-miR-93-5p) levels increased by CCI aligned with its ability to diminish neuropathic hypersensitivity. CONCLUSIONS: We have identified a pain-relevant P2X7 receptor-regulated mechanism in neuropathic rats that could hold promise as a translatable biomarker and by association enhance the clinical progression of P2X7 receptor antagonists in neuropathic pain