The CUORE experiment is a ton-scale array of
TeO
2
cryogenic bolometers located at the underground Laboratori Nazionali del Gran Sasso of Istituto Nazionale di Fisica Nucleare (INFN), in Italy. The ...CUORE detector consists of 988 crystals operated as source and detector at a base temperature of
∼
10
mK. Such cryogenic temperature is reached and maintained by means of a custom built cryogen-free dilution cryostat, designed with the aim of minimizing the vibrational noise and the environmental radioactivity. The primary goal of CUORE is the search for neutrinoless double beta decay of
130
Te
, but thanks to its large target mass and ultra-low background it is suitable for the study of other rare processes as well, such as the neutrinoless double beta decay of
128
Te
. This tellurium isotope is an attractive candidate for the search of this process, due to its high natural isotopic abundance of 31.75%. The transition energy at (866.7 ± 0.7) keV lies in a highly populated region of the energy spectrum, dominated by the contribution of the two-neutrino double beta decay of
130
Te
. As the first ton-scale infrastructure operating cryogenic
TeO
2
bolometers in stable conditions, CUORE is able to achieve a factor
>
10
higher sensitivity to the neutrinoless double beta decay of this isotope with respect to past direct experiments.
Status and prospects for CUORE Canonica, L; Alduino, C; Alfonso, K ...
Journal of Physics. Conference Series (Online),
09/2017, Letnik:
888, Številka:
1
Journal Article, Conference Proceeding
Recenzirano
Odprti dostop
CUORE is a cryogenic detector consisting of 988 TeO2 crystals, 750 g each, and will be operated at a temperature of ∼10 mK, to search for neutrinoless double beta decay (0νββ) of 130Te. The detector, ...in the final stages of construction at the Laboratori Nazionali del Gran Sasso (Italy), will start its operations in 2016. CUORE-0, its pilot experiment, has proven the feasibility of CUORE, demonstrating that the target background of 0.01 counts/keV/kg/y and the energy resolution of 5 keV are within reach. CUORE-0 also made the most precise measurement of the 2νββ decay. The expected sensitivity of CUORE to the 0νββ 130Te half-life is 9 ·1025y, for 5 years of data taking. Here, we report the most recent results of CUORE-0, their implications for CUORE, and the current status of the CUORE experiment.
In this contribution we present the achievements of the CUORE experiment so far. It is the first tonne-scale bolometric detector and it is in stable data taking since 2018. We reached to collect ...about 1800 kg×yr of exposure of which more than 1 ton×year have been analysed. The CUORE detector is meant to search for the neutrinoless double β decay (0νββ) of the 130Te isotope. This is a beyond Standard Model process which could establish the nature of the neutrino to be Dirac or a Majorana particle. It is an alternative mode of the two-neutrinos double β decay, a rare decay which have been precisely measured by CUORE in the 130Te. We found no evidence of the 0νββ and we set a Bayesian lower limit of 2.2 ×1025yr on its half-life. The expertise achieved by CUORE set a milestone for any future bolometric detector, including CUPID, which is the planned next generation experiment searching for 0νββ with scintillating bolometers.
Results from the CUORE experiment Campani, A; Adams, DQ; Alduino, C ...
HAL (Le Centre pour la Communication Scientifique Directe),
2019, Letnik:
42, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Neutrinoless double beta decay (0νββ) is a rare, second-order nuclear transition that occurs only if neutrinos are massive Majorana particles or through new physics beyond Standard Model. This ...process explicitly violates the lepton number (L) by two units and, therefore, the observation of 0νββ would demonstrate that L is not a symmetry of nature. Combined with flavour mixing and cosmological measurements, it can provide unique contraints on neutrino mass scale and establish whether neutrinos are Dirac or Majorana particles. The Cryogenic Underground Observatory for Rare Events (CUORE) is an experiment located at the LNGS searching for 0νββ decay of 130Te. CUORE exploits the bolometric technique to reach high resolution around the Q-value (2527.5 keV). It consists of an array of 988 natural TeO2 cubic crystals grouped into 19 towers. With a total active mass of 742 kg (~206 kg of 130Te), CUORE is operated at very low temperature with a new 3He/4He refrigerator. Data taking started at the beginning of 2017. After a brief introduction on the detector and the way data analysis is performed, I describe CUORE first results for the search of the 0νββ decay that were published in March 2018.
Elevated pulse pressure (PP) is associated with increased cardiovascular risk and is thought to be secondary to elastin fragmentation with secondary collagen deposition and stiffening of the aortic ...wall, leading to a dilated, noncompliant vasculature.
By use of calibrated tonometry and pulsed Doppler, arterial stiffness and pulsatile hemodynamics were assessed in 128 subjects with uncomplicated systolic hypertension (supine systolic pressure > or =140 mm Hg off medication) and 30 normotensive control subjects of comparable age and gender. Pulse-wave velocity was assessed from tonometry and body surface measurements. Characteristic impedance (Zc) was calculated from the ratio of change in carotid pressure and aortic flow in early systole. Effective aortic diameter was assessed by use of the water hammer equation. Hypertensives were heavier (P<0.001) and had higher PP (P<0.001), which was attributable primarily to higher Zc (P<0.001), especially in women. Pulse-wave velocity was higher in hypertensives (P=0.001); however, this difference was not significant after adjustment for differences in mean arterial pressure (MAP) (P>0.153), whereas increased Zc remained highly significant (P<0.001). Increased Zc in women and in hypertensive men was attributable to decreased effective aortic diameter, with no difference in wall stiffness at comparable MAP and body weight.
Elevated PP in systolic hypertension was independent of MAP and was attributable primarily to elevated Zc and reduced effective diameter of the proximal aorta. These findings are not consistent with the hypothesis of secondary aortic degeneration, dilation, and wall stiffening but rather suggest that aortic function may play an active role in the pathophysiology of systolic hypertension.
Bone repair after trauma or surgical intervention involves a tightly regulated cascade of events that starts with hemostasis and an inflammatory response, which are critical for successful healing. ...Nonsteroidal anti‐inflammatory drugs (NSAID) are routinely prescribed for pain relief despite their potential inhibitory effect on bone repair. The goal of this study was to determine the impact of administration of the non‐selective NSAID diclofenac in the inflammatory phase of bone repair in mice with or without lipopolysaccharide‐induced systemic inflammation. Repair of femoral window defects was characterized using micro computed tomography imaging and histological analyses at 2 weeks postoperative. The data indicate (a) impaired bone regeneration associated with reduced osteoblast, osteoclast, and macrophage activity; (b) changes in the number, activity, and distribution of mast cells in regenerating bone; and (c) impaired angiogenesis due to a direct toxic effect of diclofenac on vascular endothelial cells. The results of this study provide strong evidence to support the conjecture that administration of NSAIDs in the first 2 weeks after orthopaedic surgery disrupts the healing cascade and exacerbates the negative effects of systemic inflammation on the repair process.
Bone repair in mice chronically treated with diclofenac, a nonselective nonsteroidal anti‐inflammatory drug (NSAID), with or without lipopolysaccharides‐induced systemic inflammation was found to be disrupted due to inhibitory effects on osteoblasts, osteoclasts, macrophages, and mast cells, as well as by a direct toxic effect on vascular endothelial cells. The results of this study provide strong evidence to support the conjecture that administration of NSAIDs in the first 2 weeks after orthopaedic surgery disrupts the healing cascade and also appears to exacerbate the negative effects of systemic inflammation on the repair process.
Increased pulse pressure, an indicator of conduit vessel stiffness, is a strong independent predictor of cardiovascular events in hypertensive cohorts, which suggests that reduction of conduit vessel ...stiffness may be desirable in hypertension.
We assessed changes in pulse pressure and conduit vessel stiffness in a 12-week double-blind, randomized clinical trial that compared monotherapy with the ACE inhibitor enalapril 40 mg daily (n=87) versus the vasopeptidase (dual ACE and neutral endopeptidase) inhibitor omapatrilat 80 mg daily (n=80) in patients with systolic hypertension. Patients were withdrawn from antihypertensive medications 1 to 2 weeks before enrollment, and systolic pressure was confirmed to be > or =160 mm Hg. With the use of calibrated tonometry and pulsed Doppler, pulsatile hemodynamics were assessed before randomization and at 12 weeks. Characteristic impedance (Z(c)), a direct measure of the stiffness of the central aorta, was calculated from the ratio of changes in carotid pressure and aortic flow in early systole. Omapatrilat compared with enalapril produced greater reductions in peripheral (-8.2+/-12.2 versus -4.0+/-12.2 mm Hg, P<0.05) and central (-10.2+/-16.2 versus -3.2+/-16.9 mm Hg, P<0.01) pulse pressures and Z(c) (237+/-83 to 208+/-70 versus 225+/-87 to 231+/-94 dyne x s/cm(5), P<0.001); the latter remained significant (P<0.05) after adjusting for change in mean pressure.
Greater reductions in pulse pressure and Z(c) in hypertensive subjects treated with omapatrilat compared with enalapril suggest that aortic stiffness is maintained by specific, partially reversible mechanisms and underscore a potential role for pharmacological modulation of natriuretic peptides in the treatment of hypertension.
The idea of model-based drug development championed by Lewis Sheiner, in which pharmacostatistical models of drug efficacy and safety are developed from preclinical and available clinical data, ...offers a quantitative approach to improving drug development and development decision-making. Examples are presented that support this paradigm. The first example describes a preclinical model of behavioral activity to predict potency and time-course of response in humans and assess the potential for differentiation between compounds. This example illustrates how modeling procedures expounded by Lewis Sheiner provided the means to differentiate potency and the lag time between drug exposure and response and allow for rapid decision making and dose selection. The second example involves planning a Phase 2a dose-ranging and proof of concept trial in Alzheimer's disease (AD). The issue was how to proceed with the study and what criteria to use for a go/no go decision. The combined knowledge of AD disease progression, and preclinical and clinical information about the drug were used to simulate various clinical trial scenarios to identify an efficient and effective Phase 2 study. A design was selected and carried out resulting in a number of important learning experiences as well as extensive financial savings. The motivation for this case in point was the "Learn-Confirm" paradigm described by Lewis Sheiner. The final example describes the use of Pharmacokinetic and Pharmacodynamic (PK/PD) modeling and simulation to confirm efficacy across doses. In the New Drug Application for gabapentin, data from two adequate and well-controlled clinical trials was submitted to the Food and Drug Administration (FDA) in support of the approval of the indication for the treatment of post-herpetic neuralgia. The clinical trial data was not replicated for each of the sought dose levels in the drug application presenting a regulatory dilemma. Exposure response analysis submitted in the New Drug Application was applied to confirm the evidence of efficacy across these dose levels. Modeling and simulation analyses showed that the two studies corroborate each other with respect to the pain relief profiles. The use of PK/PD information confirmed evidence of efficacy across the three studied doses, eliminating the need for additional clinical trials and thus supporting the approval of the product. It can be speculated that the work by Lewis Sheiner reflected in the FDA document titled "Innovation or Stagnation: Challenge and Opportunity on the Critical Path to New Medical Products" made this scientific approach to the drug approval process possible.
High prevalences of hindlimb deformities were recorded in wild-caught green frogs (Rana clamitans), northern leopard frogs (Rana pipiens), American toads (Bufo americanus), and bullfrogs (Rana ...catesbeiana) from agricultural sites exposed to pesticide runoff in the St. Lawrence River Valley of Québec, Canada, between July and September 1992 and 1993. Of 853 metamorphosing anurans examined in 14 farmland habitats, 106 (12%; range 0 to 69%) had severe degrees of ectromelia and ectrodactyly, compared to only two (0.7%; range 0 to 7.7%) of 271 in 12 control sites. However, the variation in the proportion of deformities among sites was too large to conclude that there was a significant difference between control and pesticide-exposed habitats. Clinical signs varied and were characterized by segmental hypoplasia or agenesis of affected limbs. Conspicuous abnormalities interfered with swimming and hopping, and likely constituted a survival handicap. Because of circumstances and the frequency of these malformations in nine distinct habitats, and in three different species from one of our study sites, we propose a teratogenic action of exogenous factors. Despite the fact that many biotic and abiotic agents are potentially harmful to limb development, agricultural contaminants were suspected as primary aggressors. Thus, clinical examination and frequency of deformities in anurans might be an economical screening tool to assess ecosystem health and the presence of environmental contaminants.
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