State-of-the-art physics experiments require high-resolution, low-noise, and low-threshold detectors to achieve competitive scientific results. However, experimental environments invariably introduce ...sources of noise, such as electrical interference or microphonics. The sources of this environmental noise can often be monitored by adding specially designed “auxiliary devices” (e.g. microphones, accelerometers, seismometers, magnetometers, and antennae). A model can then be constructed to predict the detector noise based on the auxiliary device information, which can then be subtracted from the true detector signal. Here, we present a multivariate noise cancellation algorithm which can be used in a variety of settings to improve the performance of detectors using multiple auxiliary devices. To validate this approach, we apply it to simulated data to remove noise due to electromagnetic interference and microphonic vibrations. We then employ the algorithm to a cryogenic light detector in the laboratory and show an improvement in the detector performance. Finally, we motivate the use of nonlinear terms to better model vibrational contributions to the noise in thermal detectors. We show a further improvement in the performance of a particular channel of the CUORE detector when using the nonlinear algorithm in combination with optimal filtering techniques.
Over the past 10 years, it has emerged that pervasive transcription in mammalian genomes has a tremendous impact on several biological functions. Most of transcribed RNAs are lncRNAs and repetitive ...elements. In this review, we will detail the discovery of a new functional class of natural and synthetic antisense lncRNAs that stimulate translation of sense mRNAs. These molecules have been named SINEUPs since their function requires the activity of an embedded inverted SINEB2 sequence to UP-regulate translation. Natural SINEUPs suggest that embedded Transposable Elements may represent functional domains in long non-coding RNAs. Synthetic SINEUPs may be designed by targeting the antisense sequence to the mRNA of choice representing the first scalable tool to increase protein synthesis of potentially any gene of interest. We will discuss potential applications of SINEUP technology in the field of molecular biology experiments, in protein manufacturing as well as in therapy of haploinsufficiencies.
TRAF and TNF receptor-associated protein (TTRAP) is a multifunctional protein that can act in the nucleus as a 5'-tyrosyl DNA phosphodiesterase and in the cytoplasm as a regulator of cell signaling. ...In this paper we show that in response to proteasome inhibition TTRAP accumulates in nucleolar cavities in a promyelocytic leukemia protein-dependent manner. In the nucleolus, TTRAP contributes to control levels of ribosomal RNA precursor and processing intermediates, and this phenotype is independent from its 5'-tyrosyl DNA phosphodiesterase activity. Our findings suggest a previously unidentified function for TTRAP and nucleolar cavities in ribosome biogenesis under stress.
Mutations in PARK7 DJ-1 have been associated with autosomal-recessive early-onset Parkinson's disease (PD). This gene encodes for an atypical peroxiredoxin-like peroxidase that may act as a regulator ...of transcription and a redox-dependent chaperone. Although large gene deletions have been associated with a loss-of-function phenotype, the pathogenic mechanism of several missense mutations is less clear. By performing a yeast two-hybrid screening from a human fetal brain library, we identified TRAF and TNF receptor-associated protein (TTRAP), an ubiquitin-binding domain-containing protein, as a novel DJ-1 interactor, which was able to bind the PD-associated mutations M26I and L166P more strongly than wild type. TTRAP protected neuroblastoma cells from apoptosis induced by proteasome impairment. In these conditions, endogenous TTRAP relocalized to a detergent-insoluble fraction and formed cytoplasmic aggresome-like structures. Interestingly, both DJ-1 mutants blocked the TTRAP protective activity unmasking a c-jun N-terminal kinase (JNK)- and p38-MAPK (mitogen-activated protein kinase)-mediated apoptosis. These results suggest an active role of DJ-1 missense mutants in the control of cell death and position TTRAP as a new player in the arena of neurodegeneration.
A measurement is reported of the ratio of branching fractions R(J/ψ)=B(B_{c}^{+}→J/ψτ^{+}ν_{τ})/B(B_{c}^{+}→J/ψμ^{+}ν_{μ}), where the τ^{+} lepton is identified in the decay mode ...τ^{+}→μ^{+}ν_{μ}νover ¯_{τ}. This analysis uses a sample of proton-proton collision data corresponding to 3.0 fb^{-1} of integrated luminosity recorded with the LHCb experiment at center-of-mass energies of 7 and 8 TeV. A signal is found for the decay B_{c}^{+}→J/ψτ^{+}ν_{τ} at a significance of 3 standard deviations corrected for systematic uncertainty, and the ratio of the branching fractions is measured to be R(J/ψ)=0.71±0.17(stat)±0.18(syst). This result lies within 2 standard deviations above the range of central values currently predicted by the standard model.
Glial cell-derived neurotrophic factor (GDNF) has a potent action in promoting the survival of dopamine (DA) neurons. Several studies indicate that increasing GDNF levels may be beneficial for the ...treatment of Parkinson’s disease (PD) by reducing neurodegeneration of DA neurons. Despite a plethora of preclinical studies showing GDNF efficacy in PD animal models, its application in humans remains questionable for its poor efficacy and side effects due to its uncontrolled, ectopic expression. Here we took advantage of SINEUPs, a new class of antisense long non-coding RNA, that promote translation of partially overlapping sense protein-coding mRNAs with no effects on their mRNA levels. By synthesizing a SINEUP targeting Gdnf mRNA, we were able to increase endogenous GDNF protein levels by about 2-fold. Adeno-associated virus (AAV)9-mediated delivery in the striatum of wild-type (WT) mice led to an increase of endogenous GDNF protein for at least 6 months and the potentiation of the DA system’s functions while showing no side effects. Furthermore, SINEUP-GDNF was able to ameliorate motor deficits and neurodegeneration of DA neurons in a PD neurochemical mouse model. Our data indicate that SINEUP-GDNF could represent a new strategy to increase endogenous GDNF protein levels in a more physiological manner for therapeutic treatments of PD.
Espinoza and colleagues demonstrate that a SINEUP non-coding RNA targeting GDNF mRNA can increase GDNF protein levels in vivo for several months after viral delivery. They also show that SINEUP-GDNF ameliorates motor deficits and neurodegeneration of dopamine neurons in a mouse model of Parkinson’s disease.
The CUORE and CUORE-0 experiments at LNGS D’Addabbo, A.; Alduino, C.; Alfonso, K. ...
EPJ Web of Conferences,
01/2017, Letnik:
164
Journal Article, Conference Proceeding
Recenzirano
Odprti dostop
The Cryogenic Underground Observatory for Rare Events (CUORE) is a 1-ton scale bolometric experiment devoted to the search of the neutrinoless double-beta decay (0νββ) in 130Te. The CUORE detector ...consists of an array of 988 TeO2 crystals operated at 10 mK. CUORE-0 is the CUORE demonstrator: it has been built to test the performance of the upcoming CUORE experiment and represents the largest 130Te bolometric setup ever operated. CUORE-0 has been running at Laboratori Nazionali del Gran Sasso (Italy) from 2013 to 2015. The final CUORE-0 analysis on 0νββ and the corresponding detector performance are presented. The present status of the CUORE experiment, now in its final construction and commissioning phase, are discussed. The results from assembly of the detector and the commissioning of the cryostat are reported.
The CDF plug upgrade electromagnetic calorimeter: test beam results Albrow, M.; Aota, S.; Apollinari, G. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
03/2002, Letnik:
480, Številka:
2
Journal Article
Recenzirano
Odprti dostop
The CDF Plug Upgrade calorimeter, which fully exploits the tile–fiber technique, was tested at the Fermilab meson beamline. The calorimeter was exposed to positron, positively charged pion and ...positive muon beams with energies in the range of 5–
230
GeV
. The energy resolution of the electromagnetic calorimeter to the positron beam is consistent with the design value of
16%/
E
⊕1%
, where E is the energy in units of GeV and ⊕ represents sum in quadrature. The non-linearity for positrons is studied in an energy range of 11–
181
GeV
. It is important to incorporate the response of the preshower detector, the first layer of the electromagnetic calorimeter which is readout separately, into that of the calorimeter to reduce the non-linearity to 1% or less. The energy scale is about
1.46
pC/
GeV
with HAMAMATSU R4125 operated typically at a gain of 2.5×10
4. The response non-uniformity over the surface of a tower of the electromagnetic calorimeter is found to be about 2% with
57
GeV
positrons. Studies of several detailed detector characteristics are also presented.
A search for a long-lived scalar particle χ is performed, looking for the decay B+→K+χ with χ→μ+μ− in pp collision data corresponding to an integrated luminosity of 3 fb−1, collected by the LHCb ...experiment at center-of-mass energies of s=7 and 8 TeV. This new scalar particle, predicted by hidden sector models, is assumed to have a narrow width. The signal would manifest itself as an excess in the dimuon invariant mass distribution over the Standard Model background. No significant excess is observed in the accessible ranges of mass 250<m(χ)<4700 MeV/c2 and lifetime 0.1<τ(χ)<1000 ps. Upper limits on the branching fraction B(B+→K+χ(μ+μ−)) at 95% confidence level are set as a function of m(χ) and τ(χ), varying between 2×10−10 and 10−7. These are the most stringent limits to date. The limits are interpreted in the context of a model with a light inflaton particle.
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