Non-equilibrium quasiparticles can deteriorate the performance of superconducting qubits by reducing their coherence. We are investigating a source of quasiparticles that has been too long neglected, ...namely radioactivity: cosmic rays, environmental radioactivity and contaminants in the materials can all generate phonons of energy sufficient to break Cooper pairs and thus increase the number of quasiparticles. In this contribution, we describe the status of the project and its perspectives.
Progestogens progesterone (P(4)) and its products play fundamental roles in the development and/or function of the central nervous system during pregnancy. We, and others, have investigated the role ...of pregnane neurosteroids for a plethora of functional effects beyond their pro-gestational processes. Emerging findings regarding the effects, mechanisms, and sources of neurosteroids have challenged traditional dogma about steroid action. How the P(4) metabolite and neurosteroid, 3α-hydroxy-5α-pregnan-20-one (3α,5α-THP), influences cellular functions and behavioral processes involved in emotion/affect, motivation, and reward, is the focus of the present review. To further understand these processes, we have utilized an animal model assessing the effects, mechanisms, and sources of 3α,5α-THP. In the ventral tegmental area (VTA), 3α,5α-THP has actions to facilitate affective, and motivated, social behaviors through non-traditional targets, such as GABA, glutamate, and dopamine receptors. 3α,5α-THP levels in the midbrain VTA both facilitate, and/or are enhanced by, affective and social behavior. The pregnane xenobiotic receptor (PXR) mediates the production of, and/or metabolism to, various neurobiological factors. PXR is localized to the midbrain VTA of rats. The role of PXR to influence 3α,5α-THP production from central biosynthesis, and/or metabolism of peripheral P(4), in the VTA, as well as its role to facilitate, or be increased by, affective/social behaviors is under investigation. Investigating novel behavioral functions of 3α,5α-THP extends our knowledge of the neurobiology of progestogens, relevant for affective/social behaviors, and their connections to systems that regulate affect and motivated processes, such as those important for stress regulation and neuropsychiatric disorders (anxiety, depression, schizophrenia, drug dependence). Thus, further understanding of 3α,5α-THP's role and mechanisms to enhance affective and motivated processes is essential.
The REG2 anticoagulation system consists of pegnivacogin, a subcutaneously administered aptamer factor IXa inhibitor, and its intravenous control agent, anivamersen.
To assess the safety, ...tolerability and pharmacokinetic and pharmacodynamic responses of REG2.
In this phase 1a study, 36 healthy volunteers were enrolled into five cohorts and given one dose of pegnivacogin. Cohorts 1 (n = 6) and 1A (n = 4) received 0.5 mg kg(-1); cohort 2 (n = 6) received 1.0 mg kg(-1); cohort 3 (n = 6) received 3.0 mg kg(-1); and cohort 4 (n = 8) received 2.0 mg kg(-1) . In cohorts 1-3, two subjects were randomized to placebo. Cohort 4 subjects were subsequently randomized to single-dose (n = 4) or multidose (n = 4) anivamersen.
The mean maximum observed concentrations of pegnivacogin in cohorts 1, 1A, 2 and 3 at median time were 5.16 μg mL(-1) at 84 h, 5.19 μg mL(-1) at 72 h, 9.32 μg mL(-1) at 90 h, and 32.5 μg mL(-1) at 84 h, respectively. The maximum relative activated partial thromboplastin time and time needed to achieve this were 1.18 at 2 days, 1.16 at 2 days, 1.27 at 3 days, and 1.85 at 2 days, respectively. The calculated mean half-life and mean residence times of pegnivacogin were 6.12 days and 9.6 days, respectively. There was rapid reversal with intravenous anivamersen, although subsequent reaccumulation of pegnivacogin was observed.
In our first-in-human study, REG2 was well tolerated and provided dose-proportional anticoagulation for several days after a single subcutaneous dose, with complete, although transient, reversal by its control agent. This study demonstrates the first application of a subcutaneously administered aptamer, and represents a potential advance in aptamer therapeutics.
Heparin and protamine are the standard anticoagulant-antidote regimen used in almost every cardiopulmonary bypass (CPB) procedure even though both are associated with an array of complications and ...toxicities. Here we demonstrate that an anticoagulant aptamer-antidote pair targeting factor IXa can replace heparin and protamine in a porcine CPB model and also limit the adverse effects on thrombin generation, inflammation, and cardiac physiology associated with heparin and protamine use. These results demonstrate that targeting clotting factors upstream of thrombin in the coagulation cascade can potentially reduce the perioperative pathologies associated with CPB and suggest that the aptamer-antidote pair to FIXa may improve the outcome of patients undergoing CPB. In particular, this novel anticoagulant-antidote pair may prove to be useful in patients diagnosed with heparin-induced thrombocytopenia or those who have been sensitized to protamine, particularly patients who have insulin-dependent diabetes.
.
For the first time a Vanadium-based crystal was operated as cryogenic particle detector. The scintillating low temperature calorimetric technique was used for the characterization of a 22g YVO
4
...crystal aiming at the investigation of the 4-fold forbidden non-unique
β
-
decay of
50
V. The excellent bolometric performance of the compound together with high light output of the crystal make it an outstanding technique for the study of such elusive rate process. The internal radioactive contaminations of the crystal are also investigated showing that an improvement on the current status of material selection and purification are needed,
235/238
U and
232
Th are measured at the level of 28mBq/kg, 1.3 Bq/kg and 28m Bq/kg, respectively. In this work, we also discuss a future upgrade of the experimental set-up which may pave the road for the detection of the rare
50
V
β
-
decay.
The CUORE Cryostat D’Addabbo, A.; Alduino, C.; Bersani, A. ...
Journal of low temperature physics,
12/2018, Letnik:
193, Številka:
5-6
Journal Article
Recenzirano
Odprti dostop
The Cryogenic Underground Observatory for Rare Events (CUORE) is a bolometric experiment for neutrinoless double-beta decay in
130
Te
search, currently taking data at the underground facility of ...Laboratori Nazionali del Gran Sasso (LNGS). The CUORE cryostat successfully cooled down a mass of about 1 ton at
∼
7
mK
, delivering a uniform and constant base temperature. This result marks a fundamental milestone in low-temperature detector techniques, opening the path for future ton-scale bolometric experiments searching for rare events. In this paper, we present the CUORE cryogenic infrastructure, briefly describing its critical subsystems.
A convincing observation of neutrino-less double beta decay (0vDBD) relies on the possibility of operating high-energy resolution detectors in background-free conditions. Scintillating cryogenic ...calorimeters are one of the most promising tools to fulfill the requirements for a next-generation experiment. Several steps have been taken to demonstrate the maturity of this technique, starting form the successful experience of CUPID-0. The CUPID-0 experiment collected almost 10 kg y of exposure, running 26 Zn82Se crystals during two years of continuous detector operation. The complete rejection of the dominant α background was demonstrated, measuring the lowest counting rate in the region of interest for this technique. Furthermore, the most stringent limit on the 82Se 0vDBD was established. In this contribution we present the final results of CUPID-0 phase-I, including a detailed model of the background and the measurement of the 2vDBD half-life.
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