We report on the structure and performance of 4H-SiC p + -n APDs fabricated in a fully planar technology. A dark current density lower than 10 nA/cm 2 at 30-V reverse bias and a breakdown voltage of ...88 V were observed. A gain as high as 10 5 was measured at 94-V reverse bias, confirming the avalanche multiplication working condition. The maximum responsivity value was measured at 270 nm, increasing from 0.06 A/W (QE = 29%) at 0-V bias to 0.10 A/W (QE of about 45%) at 30-V reverse bias.
The direct detection of high-energy cosmic rays up to the PeV region is one of the major challenges for the next generation of space-borne cosmic-ray detectors. The physics performance will be ...primarily determined by their geometrical acceptance and energy resolution. CaloCube is a homogeneous calorimeter whose geometry allows an almost isotropic response, so as to detect particles arriving from every direction in space, thus maximizing the acceptance. A comparative study of different scintillating materials and mechanical structures has been performed by means of Monte Carlo simulation. The scintillation-Cherenkov dual read-out technique has been also considered and its benefit evaluated.
Mutations in the PTEN-induced putative kinase1 (PINK1) represent the second most frequent cause of autosomal recessive Parkinson's disease. The PINK1 protein mainly localizes to mitochondria and ...interacts with a variety of proteins, including the pro-autophagy protein beclin1 and the ubiquitin-ligase parkin. Upon stress conditions, PINK1 is known to recruit parkin at the surface of dysfunctional mitochondria and to activate the mitophagy cascade. Aim of this study was to use a simple and highly reproducible catecholamine cell model and transmission electron microscopy to characterize whether PINK1 could affect mitochondrial homeostasis, the recruitment of specific proteins at mitochondria, mitophagy and apoptosis. Samples were analyzed both in baseline conditions and following treatment with methamphetamine (METH), a neurotoxic compound which strongly activates autophagy and produces mitochondrial damage. Our data provide robust sub-cellular evidence that the modulation of PINK1 levels dramatically affects the morphology and number of mitochondria and the amount of cell death. In particular, especially upon METH exposure, PINK1 is able to increase the total number of mitochondria, concurrently recruit beclin1, parkin and ubiquitin and enhance the clearance of damaged mitochondria. In the absence of functional PINK1 and upon autophagy stress, we observe a failure of the autophagy system at large, with marked accumulation of dysfunctional mitochondria and dramatic increase of apoptotic cell death. These findings highlight the strong neuroprotective role of PINK1 as a key protein in the surveillance and regulation of mitochondrial homeostasis.
Given the good performances in terms of geometrical acceptance and energy resolution, calorimeters are the best suited detectors to measure high energy cosmic rays directly in space. However, in ...order to exploit this potential, the design of calorimeters must be carefully optimized to take into account all limitations related to space missions, due mainly to the mass of the experimental apparatus. CaloCube is a three years R&D project, approved and financed by INFN in 2014, aiming to optimize the design of a space-borne calorimeter by the use of a cubic, homogeneous and isotropic geometry. In order to maximize detector performances with respect to the total mass of the apparatus, comparative studies on different scintillating materials, different sizes of crystals and different spacings among them have been performed making use of Monte Carlo simulations. In parallel to this activity, several prototypes instrumented with CsI:Tl cubic crystals have been constructed and tested with particle beams (muons, electrons, protons and ions). Both simulations and prototypes showed that the CaloCube design leads to a good particle energy resolution (< 2% for electromagnetic showers, < 40% for hadronic showers) and a good effective geometric factor (> 3:5 m2 sr for electromagnetic showers, > 2:5 m2 sr for hadronic showers). Thanks to these performances, in 5 years of operation it would be possible to measure the ux of electrons+positrons up to some tens of TeV and the uxes of protons and nuclei up to some units of PeV/nucleon, hence extending these measurements by at least one order of magnitude in energy compared to the experiments currently operating in space.
Formation, aggregation and transmission of abnormal proteins are common features in neurodegenerative disorders including Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, and ...Huntington's disease. The mechanisms underlying protein alterations in neurodegenerative diseases remain controversial. Novel findings highlighted altered protein clearing systems as common biochemical pathways which generate protein misfolding, which in turn causes protein aggregation and protein spreading. In fact, proteinaceous aggregates are prone to cell-to-cell propagation. This is reminiscent of what happens in prion disorders, where the prion protein misfolds thus forming aggregates which spread to neighbouring cells. For this reason, the term prionoids is currently used to emphasize how several misfolded proteins are transmitted in neurodegenerative diseases following this prion-like pattern. Histochemical techniques including the use of specific antibodies covering both light and electron microscopy offer a powerful tool to describe these phenomena and investigate specific molecular steps. These include: prion like protein alterations; glycation of prion-like altered proteins to form advanced glycation end-products (AGEs); mechanisms of extracellular secretion; interaction of AGEs with specific receptors placed on neighbouring cells (RAGEs). The present manuscript comments on these phenomena aimed to provide a consistent scenario of the available histochemical approaches to dissect each specific step.
The direct measurement of the cosmic-ray spectrum, up to the knee region, is one of the instrumental challenges for next generation space experiments. The main issue for these measurements is a ...steeply falling spectrum with increasing energy, so the physics performance of the space calorimeters are primarily determined by their geometrical acceptance and energy resolution. CaloCube is a three-year R&D project, approved and financed by INFN in 2014, aiming to optimize the design of a space-born calorimeter. The peculiarity of the design of CaloCube is its capability of detecting particles coming from any direction, and not only those on its upper surface. To ensure that the quality of the measurement does not depend on the arrival direction of the particles, the calorimeter will be designed as homogeneous and isotropic as possible. In addition, to achieve a high discrimination power for hadrons and nuclei with respect to electrons, the sensitive elements of the calorimeter need to have a fine 3-D sampling capability. In order to optimize the detector performances with respect to the total mass of the apparatus, which is the most important constraint for a space launch, a comparative study of different scintillating materials has been performed using detailed Monte Carlo simulation based on the FLUKA package. In parallel to simulation studies, a prototype consisting in 14 layers of 3 x 3 CsI(Tl) crystals per layer has been assembled and tested with particle beams. An overview of the obtained results during the first two years of the project will be presented and the future of the detector will be discussed too.
Trimethyltin (TMT) is a triorganotin compound which determines neurodegeneration of specific brain areas particularly damaging the limbic system. Earlier ultrastructural studies indicated the ...formation of autophagic vacuoles in neurons after TMT intoxication. However, no evaluation has been attempted to determine the role of the autophagic pathway in TMT neurotoxicity. To assess the contribution of autophagy to TMT-induced neuronal cell death, we checked the vulnerability of neuronal cultures to TMT after activation or inhibition of autophagy. Our results show that autophagy inhibitors (3-methyladenine and
l
-asparagine) greatly enhanced TMT neurotoxicity. Conversely, known activators of autophagy, such as lithium and rapamycin, displayed neuroprotection against this toxic compound. Due to its diverse targets, the action of lithium was complex. When lithium was administered according to a chronic treatment protocol (6 days pretreatment) it was able to rescue both hippocampal and cortical neurons from TMT (or from glutamate toxicity used as reference). This effect was accompanied by an increased phosphorylation of glycogen synthase kinase 3 which is a known target for lithium neuroprotection. If the pre-incubation time was reduced to 2 h (acute treatment protocol), lithium was still able to counteract TMT toxicity in hippocampal but not in cortical neurons. The neuroprotective effect of lithium acutely administered against TMT in hippocampal neurons can be completely reverted by an excess of inositol and is possibly related to the inactivation of inositol monophosphatase, a key regulator of autophagy. These data indicate that TMT neurotoxicity can be dramatically modified, at least in vitro, by lithium addition which seems to act through different mechanisms if acutely or chronically administered.
Homogeneous and isotropic calorimetry for space experiments Mori, N.; Adriani, O.; Basti, A. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
12/2013, Letnik:
732
Journal Article
Recenzirano
Calorimetry plays an essential role in experiments observing high energy gamma and cosmic rays in space. The observational capabilities are mainly limited by the geometrical dimensions and the mass ...of the calorimeter. Since deployable mass depends on the design of the detector and the total mass of the payload, it is important to optimize the geometrical acceptance of the calorimeter for rare events, its granularity for particle identification, and its absorption depth for the measurement of the particle energy. A design of a calorimeter that could simultaneously optimize these characteristics assuming a mass limit of about 1.6t has been studied. As a result, a homogeneous calorimeter instrumented with cesium iodide (CsI) crystals was chosen as the best compromise given the total mass constraint. The most suitable geometry found is cubic and isotropic, so as to detect particles arriving from every direction in space, thus maximizing the acceptance; granularity is obtained by filling the cubic volume with small cubic CsI crystals. The total radiation length in any direction is very large, and allows for optimal electromagnetic particle identification and energy measurement, while the interaction length is at least sufficient to allow a precise reconstruction of hadronic showers. Optimal values for the size of the crystals and spacing among them have been studied. Two prototypes have been constructed and preliminary tests with high energy ion and muon beams are reported.
The effects of training are dependent on complex, adaptive changes which are induced by acute physical exercise at different levels. In particular, evidence shows that the ...hypothalamus-pituitary-adrenocortical axis, as well as the sympatho-adrenomedullary system, is mainly involved in mediating the physiological effects of physical exercise. The aim of the present study was to investigate, through a morphological and biochemical approach, the effects of training on the adrenal gland of mice, following two different protocols consisting of either low- or high-intensity training. Mice were run daily on a motorised treadmill for 8 weeks, at a velocity corresponding to 60% (low-intensity exercise) or 90% (high-intensity exercise) of the maximal running velocity previously determined by an incremental exercise test. We found that physical exercise produced an increase in the adrenal gland size compared with the control (sedentary) mice. The increase was 31.04% for mice that underwent high-intensity exercise and 10.08% for mice that underwent low intensity exercise, and this appeared to be the result of an increase in the area of both the adrenal cortex and adrenal medulla. Morphological analysis of the adrenal cortex showed that both types of exercise produced an increase in cytoplasmic vacuoles in steroidogenic cells, appearing more abundant after high-intensity exercise. No change was found in the reticulate zone. In the adrenal medulla, despite the absence of morphological changes, immunohistochemistry for tyrosine hydroxylase, dopamine β-hydroxylase and phenyl-ethanolamine-N-methyltransferase demonstrated an increased immunopositivity for these cathecolamine-synthesizing enzymes after intense exercise. These results were confirmed by immunoblot accompanied by densitometric analysis.
: The monoamine neurotoxin methamphetamine (METH) is commonly used as an experimental model for Parkinson's disease (PD). In fact, METH‐induced striatal dopamine (DA) loss is accompanied by damage to ...striatal nerve endings arising from the substantia nigra. On the other hand, PD is characterized by neuronal inclusions within nigral DA neurons. These inclusions contain a‐synuclein, ubiquitin, and various components of a metabolic pathway named the ubiquitin‐proteasome (UP) system, while mutation of genes coding for various components of the UP system is responsible for inherited forms of PD. In this presentation we demonstrate for the first time the occurrence of neuronal inclusions in vivo in the nigrostriatal system of the mouse following administration of METH. We analyzed, in vivo and in vitro, the shape and the fine structure of these neuronal bodies by using transmission electron microscopy. Immunocytochemical investigation showed that these METH‐induced cytosolic inclusions stain for ubiquitin, a‐synuclein, and UP‐related molecules, thus sharing similar components with Lewy bodies occurring in PD, with an emphasis on enzymes belonging to the UP system. In line with this, blockade of this multicatalytic pathway by the selective inhibitor epoxomycin produced cell inclusions with similar features. Moreover, using a multifaceted pharmacological approach, we could demonstrate the need for endogenous DA in order to form neuronal inclusions.