Huntington disease (HD) is a neurodegenerative disorder produced by an expansion of CAG repeats in the HTT gene. Patients of HD show involuntary movements, cognitive decline and psychiatric ...impairment. People carrying abnormally long expansions of CAGs (more than 35 CAG repeats) produce mutant huntingtin (mHtt), which encodes tracks of polyglutamines (polyQs). These polyQs make the protein prone to aggregate and cause it to acquire a toxic gain of function. Principally affecting the frontal cortex and the striatum, mHtt disrupts many cellular functions. In addition, this protein is expressed ubiquitously, and some reports show that many other cell types are affected by the toxicity of mHtt. Several studies reported that metformin, a widely-used anti-diabetic drug, is neuroprotective in models of HD. Here, we provide a review of the benefits of this substance to treat HD. Metformin is a pleiotropic drug, modulating different targets such as AMPK, insulin signalling and many others. These molecules regulate autophagy, chaperone expression, and more, which in turn reduce mHtt toxicity. Moreover, metformin alters gut microbiome and its metabolic processes. The study of potential targets, interactions between the drug, host and microbiome, or genomic and pharmacogenomic approaches may allow us to design personalised medicine to treat HD.
•Huntington disease is a multi-system disorder and huntingtin is expressed ubiquitously.•Metformin is a pleiotropic drug which may reach most tissues, and activates a range of targets beneficial to treat HD.•Gut microbiota interplay with metformin substantially increases complexity of using this drug to treat HD.•Studying targets of metformin, gut microbiota and using pharmacogenetics, may help design personalised medicine to treat HD.
Abstract
The search for neutrinoless double beta decay (0
νββ
) remains one of the most compelling experimental avenues for the discovery in the neutrino sector. Electroluminescent gas-phase time ...projection chambers are well suited to 0
νββ
searches due to their intrinsically precise energy resolution and topological event identification capabilities. Scalability to ton- and multi-ton masses requires readout of large-area electroluminescent regions with fine spatial resolution, low radiogenic backgrounds, and a scalable data acquisition system. This paper presents a detector prototype that records event topology in an electroluminescent xenon gas TPC via VUV image-intensified cameras. This enables an extendable readout of large tracking planes with commercial devices that reside almost entirely outside of the active medium. Following further development in intermediate scale demonstrators, this technique may represent a novel and enlargeable method for topological event imaging in 0
νββ
.
Abstract
NEXT-100 is currently being constructed at the Laboratorio
Subterráneo de Canfranc in the Spanish Pyrenees and will search
for neutrinoless double beta decay using a high-pressure gaseous
...time projection chamber (TPC) with 100 kg of xenon. Charge
amplification is carried out via electroluminescence (EL) which is
the process of accelerating electrons in a high electric field
region causing secondary scintillation of the medium proportional to
the initial charge. The NEXT-100 EL and cathode regions are made
from tensioned hexagonal meshes of 1 m diameter. This paper
describes the design, characterization, and installation of these
parts for NEXT-100. Simulations of the electric field are performed
to model the drift and amplification of ionization electrons
produced in the detector under various EL region alignments and
rotations. Measurements of the electrostatic breakdown voltage in
air characterize performance under high voltage conditions and
identify breakdown points. The electrostatic deflection of the mesh
is quantified and fit to a first-principles mechanical model.
Measurements were performed with both a standalone test EL region
and with the NEXT-100 EL region before its installation in the
detector. Finally, we describe the parts as installed in NEXT-100,
following their deployment in Summer 2023.
Abstract
Polytetrafluoroethylene (PTFE) is an excellent diffuse reflector widely used in light collection systems for particle physics experiments. In noble element systems, it is often coated with ...tetraphenyl butadiene (TPB) to allow detection of vacuum ultraviolet scintillation light. In this work this dependence is investigated for PTFE coated with TPB in air for light of wavelengths of 200 nm, 260 nm, and 450 nm. The results show that TPB-coated PTFE has a reflectance of approximately 92% for thicknesses ranging from 5 mm to 10 mm at 450 nm, with negligible variation as a function of thickness within this range. A cross-check of these results using an argon chamber supports the conclusion that the change in thickness from 5 mm to 10 mm does not affect significantly the light response at 128 nm. Our results indicate that pieces of TPB-coated PTFE thinner than the typical 10 mm can be used in particle physics detectors without compromising the light signal.
We present a tunable metal ion beam that deliverscontrollable ion currents in the picoamp range for testing ofdry-phase ion sensors. Ion beams are formed by sequential atomicevaporation and single or ...multiple electron impact ionization,followed by acceleration into a sensing region. Controllability ofthe ionic charge state is achieved through tuning of electrodepotentials that influence the retention time in the ionizationregion. Barium, lead, and cadmium samples have been used to test thesystem, with ion currents identified and quantified using aquadrupole mass analyzer. Realization of a clean Ba2+ ion beam within a bench-top system represents an important technicaladvance toward the development and characterization of bariumtagging systems for neutrinoless double beta decay searches in xenongas. This system also provides a testbed for investigation of novelion sensing methodologies for environmental assay applications, withdication beams of Pb2+ and Cd2+ also demonstrated for thispurpose.
Abstract
We present a tunable metal ion beam that delivers
controllable ion currents in the picoamp range for testing of
dry-phase ion sensors. Ion beams are formed by sequential atomic
evaporation ...and single or multiple electron impact ionization,
followed by acceleration into a sensing region. Controllability of
the ionic charge state is achieved through tuning of electrode
potentials that influence the retention time in the ionization
region. Barium, lead, and cadmium samples have been used to test the
system, with ion currents identified and quantified using a
quadrupole mass analyzer. Realization of a clean Ba
2+
ion beam within a bench-top system represents an important technical
advance toward the development and characterization of barium
tagging systems for neutrinoless double beta decay searches in xenon
gas. This system also provides a testbed for investigation of novel
ion sensing methodologies for environmental assay applications, with
dication beams of Pb
2+
and Cd
2+
also demonstrated for this
purpose.
The molecular complexes formed by nitric acid with one, two, and three water molecules have been investigated by high level ab initio calculations. The B3LYP/aug-cc-pVTZ method and basis set have ...been used to derive equilibrium geometries and binding energies and to predict the infrared spectra of these complexes. It has been found that the complexes become stable through the formation of several hydrogen bonds. The main one is established between the acid, which acts as a donor, and the first water molecule, but further bonds are created between successive water molecules, with a weaker bond making a closed structure between the last water unit and the acid. Films of nitric acid mono-, di-, and trihydrates (NAM, NAD, and NAT) have been prepared by deposition on a cold surface and annealing to induce crystallization. RAIR spectra have been taken of these films. The spectra are compared to previous investigations, and the assignments of the spectra and the structure of the crystals are discussed. A global good agreement is obtained with previous transmission and RAIR spectra of thin films and extinction spectra of aerosols.
Long-lived radon daughters are a critical background source in experiments searching for low-energy rare events. Originating from radon in ambient air, radioactive polonium, bismuth and lead isotopes ...plate-out on materials that are later employed in the experiment. In this paper, we examine cleaning procedures for their capability to remove radon daughters from PTFE surfaces, a material often used in liquid xenon TPCs. We found a large difference between the removal efficiency obtained for the decay chains of \(^{222}\)Rn and \(^{220}\)Rn, respectively. This indicates that the plate-out mechanism has an effect on the cleaning success. While the long-lived \(^{222}\)Rn daughters could be reduced by a factor of ~2, the removal of \(^{220}\)Rn daughters was up to 10 times more efficient depending on the treatment. Furthermore, the impact of a nitric acid based PTFE cleaning on the liquid xenon purity is investigated in a small-scale liquid xenon TPC.
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