A sample of 1.53 x 10 super(9) cosmic-ray-induced single muon events has been recorded at 225 m water equivalent using the MINOS near detector. The underground muon rate is observed to be highly ...correlated with the effective atmospheric temperature. The coefficient alpha sub(T), relating the change in the muon rate to the change in the vertical effective temperature, is determined to be 0.428 + or - 0.003(stat.) + or - 0.059(syst.). An alternative description is provided by the weighted effective temperature, introduced to account for the differences in the temperature profile and muon flux as a function of zenith angle. Using the latter estimation of temperature, the coefficient is determined to be 0.352 + or - 0.003(stat.) + or - 0.046(syst.).
A search for mixing between active neutrinos and light sterile neutrinos has been performed by looking for muon neutrino disappearance in two detectors at baselines of 1.04 km and 735 km, using a ...combined MINOS and MINOS+ exposure of \(16.36\times10^{20}\) protons-on-target. A simultaneous fit to the charged-current muon neutrino and neutral-current neutrino energy spectra in the two detectors yields no evidence for sterile neutrino mixing using a 3+1 model. The most stringent limit to date is set on the mixing parameter \(\sin^2\theta_{24}\) for most values of the sterile neutrino mass-splitting \(\Delta m^2_{41} > 10^{-4}\) eV\(^2\).
Spalt-like proteins are Zinc finger transcription factors from Caenorhabditis elegans to vertebrates, with critical roles in development. In vertebrates, four paralogues have been identified ...(SALL1-4), and SALL2 is the family's most dissimilar member. SALL2 is required during brain and eye development. It is downregulated in cancer and acts as a tumor suppressor, promoting cell cycle arrest and cell death. Despite its critical functions, information about SALL2 regulation is scarce. Public data indicate that SALL2 is ubiquitinated and phosphorylated in several residues along the protein, but the mechanisms, biological consequences, and enzymes responsible for these modifications remain unknown. Bioinformatic analyses identified several putative phosphorylation sites for Casein Kinase II (CK2) located within a highly conserved C-terminal PEST degradation motif of SALL2. CK2 is a serine/threonine kinase that promotes cell proliferation and survival and is often hyperactivated in cancer. We demonstrated that CK2 phosphorylates SALL2 residues S763, T778, S802, and S806 and promotes SALL2 degradation by the proteasome. Accordingly, pharmacological inhibition of CK2 with Silmitasertib (CX-4945) restored endogenous SALL2 protein levels in SALL2-deficient breast MDA-MB-231, lung H1299, and colon SW480 cancer cells. Silmitasertib induced a methuosis-like phenotype and cell death in SW480 cells. However, the phenotype was significantly attenuated in CRISPr/Cas9-mediated SALL2 knockout SW480 cells. Similarly, Sall2-deficient tumor organoids were more resistant to Silmitasertib-induced cell death, confirming that SALL2 sensitizes cancer cells to CK2 inhibition. We identified a novel CK2-dependent mechanism for SALL2 regulation and provided new insights into the interplay between these two proteins and their role in cell survival and proliferation.
We modelled the utility of applying a personalised screening approach for colorectal cancer (CRC) when compared with standard age-based screening. In this personalised screening approach, eligibility ...is determined by absolute risk which is calculated from age and polygenic risk score (PRS), where the PRS is relative risk attributable to common genetic variation. In contrast, eligibility in age-based screening is determined only by age.
We calculated absolute risks of CRC from UK population age structure, incidence and mortality rate data, and a PRS distribution which we derived for the 37 known CRC susceptibility variants. We compared the number of CRC cases potentially detectable by personalised and age-based screening. Using Genome-Wide Complex Trait Analysis to calculate the heritability attributable to common variation, we repeated the analysis assuming all common CRC risk variants were known.
Based on the known CRC variants, individuals with a PRS in the top 1% have a 2.9-fold increased CRC risk over the population median. Compared with age-based screening (aged 60: 10-year absolute risk 1.96% in men, 1.19% in women, as per the UK NHS National Bowel Screening Programme), personalised screening of individuals aged 55–69 at the same risk would lead to 16% fewer men and 17% fewer women being eligible for screening with 10% and 8%, respectively, fewer screen-detected cases. If all susceptibility variants were known, individuals with a PRS in the top 1% would have an estimated 7.7-fold increased risk. Personalised screening would then result in 26% fewer men and women being eligible for screening with 7% and 5% fewer screen-detected cases.
Personalised screening using PRS has the potential to optimise population screening for CRC and to define those likely to maximally benefit from chemoprevention. There are however significant technical and operational details to be addressed before any such programme is introduced.
The Royal College of Surgeons rat provides a valuable animal model for examining the ontogeny of inherited or acquired photoreceptor degeneration and for assessing various treatment paradigms. Here ...we describe a sequence of events in which photoreceptor loss induces secondary changes that ultimately result in a progressive loss of retinal ganglion cells. The functional consequences of photoreceptor loss are described and compared with those observed in dystrophic animals that received grafts of pigment epithelial cells at an early stage in the degenerative process. The results of this work suggest that transplantation might slow or halt the progress of photoreceptor loss in certain human retinal degenerative conditions, provided suitable safeguards have been put in place.
We report the first observation of seasonal modulations in the rates of cosmic ray multiple-muon events at two underground sites, the MINOS Near Detector with an overburden of 225 mwe, and the MINOS ...Far Detector site at 2100 mwe. At the deeper site, multiple-muon events with muons separated by more than 8 m exhibit a seasonal rate that peaks during the summer, similar to that of single-muon events. In contrast and unexpectedly, the rate of multiple-muon events with muons separated by less than 5-8 m, and the rate of multiple-muon events in the smaller, shallower Near Detector, exhibit a seasonal rate modulation that peaks in the winter.
Beam and experiments: summary Blondel, A.; Bueno, A.; Campanelli, M. ...
Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment,
2000, Letnik:
451, Številka:
1
Journal Article, Conference Proceeding
Recenzirano
Odprti dostop
The discovery of neutrino oscillations marks a major milestone in the history of neutrino physics, and opens a new window to the still mysterious origin of masses and flavour mixing. Many current and ...forthcoming experiments will answer open questions; however, a major step forward, up to and possibly including CP violation in the neutrino-mixing matrix, requires the neutrino beams from a neutrino factory. The neutrino factory is a new concept for producing neutrino beams of unprecedented quality in terms of intensity, flavour composition, and precision of the beam parameters. Most importantly, the neutrino factory is the only known way to generate a high-intensity beam of electron neutrinos of high energy. The neutrino beam from a neutrino factory, in particular the electron–neutrino beam, enables the exploration of otherwise inaccessible domains in neutrino oscillation physics by exploiting baselines of planetary dimensions. Suitable detectors pose formidable challenges but seem within reach with only moderate extrapolations from existing technologies. Although the main physics attraction of the neutrino factory is in the area of neutrino oscillations, an interesting spectrum of further opportunities ranging from high-precision, high-rate neutrino scattering to physics with high-intensity stopped muons comes with it.
The objective of this study was to assess international trends in antipsychotic use, using a standardised methodology. A repeated cross-sectional design was applied to data extracts from the years ...2005 to 2014 from 16 countries worldwide. During the study period, the overall prevalence of antipsychotic use increased in 10 of the 16 studied countries. In 2014, the overall prevalence of antipsychotic use was highest in Taiwan (78.2/1000 persons), and lowest in Colombia (3.2/1000). In children and adolescents (0–19 years), antipsychotic use ranged from 0.5/1000 (Lithuania) to 30.8/1000 (Taiwan). In adults (20–64 years), the range was 2.8/1000 (Colombia) to 78.9/1000 (publicly insured US population), and in older adults (65+ years), antipsychotic use ranged from 19.0/1000 (Colombia) to 149.0/1000 (Taiwan). Atypical antipsychotic use increased in all populations (range of atypical/typical ratio: 0.7 (Taiwan) to 6.1 (New Zealand, Australia)). Quetiapine, risperidone, and olanzapine were most frequently prescribed. Prevalence and patterns of antipsychotic use varied markedly between countries. In the majority of populations, antipsychotic utilisation and especially the use of atypical antipsychotics increased over time. The high rates of antipsychotic prescriptions in older adults and in youths in some countries merit further investigation and systematic pharmacoepidemiologic monitoring.
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