The transmembrane protein CD5, expressed on all T cells and the B1 subset of B cells, modulates antigen receptor-mediated activation. We used the yeast two-hybrid system to identify proteins that ...interact with its cytoplasmic domain and play a role in CD5 proximal signaling events. We found that the beta subunit of the serine/threonine kinase casein kinase 2 (CK2) interacts specifically with the cytoplasmic domain of CD5. Co-immunoprecipitation experiments showed activation-independent association of CK2 with CD5 in human and murine B and T cell lines and murine splenocytes. The interaction of CK2 holoenzyme with CD5 is mediated by the amino terminus of the regulatory subunit beta. CK2 binds and phosphorylates CD5 at the CK2 motifs flanked by Ser459 and Ser461. Cross-linking of CD5 leads to the activation of CD5-associated CK2 in a murine B-lymphoma cell line and a human T-leukemia cell line and is independent of net recruitment of CK2 to CD5. In contrast, CK2 is not activated following cross-linking of the B cell receptor complex or the T cell receptor complex. This direct regulation of CK2 by a cell surface receptor provides a novel pathway for control of cell activation that could play a significant role in regulation of CD5-dependent antigen receptor activation in T and B cells.
We present the results of a search in the Super-Kamiokande (SK) detector for excesses of neutrinos with energies above a few GeV that are in the direction of the track events reported in IceCube. ...Data from all SK phases (SK-I through SK-IV) were used, spanning a period from 1996 April to 2016 April and corresponding to an exposure of 225 kiloton-years. We considered the 14 IceCube track events from a data set with 1347 livetime days taken from 2010 to 2014. We use Poisson counting to determine if there is an excess of neutrinos detected in SK in a 10° search cone (5° for the highest energy data set) around the reconstructed direction of the IceCube event. No significant excess was found in any of the search directions we examined. We also looked for coincidences with a recently reported IceCube multiplet event. No events were detected within a 500 s time window around the first detected event, and no significant excess was seen from that direction over the lifetime of SK.
Background: Germline mutations in the CDKN2A gene have been linked to melanoma incidence in many families with multiple cases of the disease. Previous studies of multiple-case families have indicated ...that the lifetime risk (i.e., penetrance) of melanoma in CDKN2A mutation carriers is very high, ranging from 58% in Europe to 91% in Australia by age 80 years. In this study, we examined lifetime melanoma risk among CDKN2A mutation carriers using carriers who were identified in a population-based study of melanoma. Methods: Probands for the study were incident case patients with either first or subsequent melanoma who were identified in nine geographic regions in Australia, Canada, the United States, and Italy. A total of 3626 probands (53% participation rate) with adequate DNA for analysis were recruited and genotyped for CDKN2A mutations. From the 3550 probands whose DNA could be amplified by polymerase chain reaction of CDKN2A exons 1α, 2, and 3 and surrounding regions, 65 mutation carriers were identified. Melanoma histories in first-degree relatives of these probands were used to calculate the lifetime risk in CDKN2A mutation carriers using the kin–cohort method. Results: The risk of melanoma in CDKN2A mutation carriers was approximately 14% (95% CI = 8% to 22%) by age 50 years, 24% (95% CI = 15% to 34%) by age 70 years, and 28% (95% CI = 18% to 40%) by age 80 years. Eighteen probands had three or more first-degree relatives with melanoma, but only one was a carrier of a CDKN2A mutation. Conclusions: CDKN2A mutation carriers in the general population have a much lower risk of melanoma than that suggested by estimates obtained from multiple-case families. The preponderance of familial clustering of melanoma occurs in families without identifiable mutations in CDKN2A.
The rate of high energy cosmic ray muons as measured underground is shown to be strongly correlated with upper‐air temperatures during short‐term atmospheric (10‐day) events. The effects are seen by ...correlating data from the MINOS underground detector and temperatures from the European Centre for Medium Range Weather Forecasts during the winter periods from 2003–2007. This effect provides an independent technique for the measurement of meteorological conditions and presents a unique opportunity to measure both short and long‐term changes in this important part of the atmosphere.
MINOS is a long baseline neutrino oscillation experiment that uses two detectors separated by 734
km. The readout systems used for the two detectors are different and have to be independently ...calibrated. To verify and make a direct comparison of the calibrated response of the two readout systems, test beam data were acquired using a smaller calibration detector. This detector was simultaneously instrumented with both readout systems and exposed to the CERN PS T7 test beam. Differences in the calibrated response of the two systems are shown to arise from differences in response non-linearity, photomultiplier tube crosstalk, and threshold effects at the few percent level. These differences are reproduced by the Monte Carlo (MC) simulation to better than 1% and a scheme that corrects for these differences by calibrating the MC to match the data in each detector separately is presented. The overall difference in calorimetric response between the two readout systems is shown to be consistent with zero to a precision of 1.3% in data and 0.3% in MC with no significant energy dependence.
Abstract
We report a measurement of the flux-integrated $\nu_{\mu}$ charged-current cross sections on water, hydrocarbon, and iron in the T2K on-axis neutrino beam with a mean neutrino energy of 1.5 ...GeV. The measured cross sections on water, hydrocarbon, and iron are $\sigma^{\rm{H_{2}O}}_{\rm{CC}} = (0.840\pm 0.010(\mathrm{stat.})^{+0.10}_{-0.08}(\mathrm{syst.}))\times10^{-38}\,\mathrm{cm}^2$/nucleon, $\sigma^{\rm{CH}}_{\rm{CC}} = (0.817\pm 0.007(\mathrm{stat.})^{+0.11}_{-0.08}(\mathrm{syst.}))\times10^{-38}\,\mathrm{cm}^2$/nucleon, and $\sigma^{\rm{Fe}}_{\rm{CC}} = (0.859\pm 0.003(\mathrm{stat.})^{+0.12}_{-0.10}(\mathrm{syst.}))\times10^{-38}\,\mathrm{cm}^2$/nucleon, respectively, for a restricted phase space of induced muons: $\theta_{\mu}<45^{\circ}$ and $p_{\mu}>$0.4 GeV/$c$ in the laboratory frame. The measured cross section ratios are ${\sigma^{\rm{H_{2}O}}_{\rm{CC}}}/{\sigma^{\rm{CH}}_{\rm{CC}}} = 1.028\pm 0.016(\mathrm{stat.})\pm 0.053(\mathrm{syst.})$, ${\sigma^{\rm{Fe}}_{\rm{CC}}}/{\sigma^{\rm{H_{2}O}}_{\rm{CC}}} = 1.023\pm 0.012(\mathrm{stat.})\pm 0.058(\mathrm{syst.})$, and ${\sigma^{\rm{Fe}}_{\rm{CC}}}/{\sigma^{\rm{CH}}_{\rm{CC}}} = 1.049\pm 0.010(\mathrm{stat.})\pm 0.043(\mathrm{syst.})$. These results, with an unprecedented precision for the measurements of neutrino cross sections on water in the studied energy region, show good agreement with the current neutrino interaction models used in the T2K oscillation analyses.
Abstract The T2K experiment presents new measurements of neutrino oscillation parameters using $$19.7(16.3)\times 10^{20}$$ 19.7 ( 16.3 ) × 10 20 protons on target (POT) in (anti-)neutrino mode at ...the far detector (FD). Compared to the previous analysis, an additional $$4.7\times 10^{20}$$ 4.7 × 10 20 POT neutrino data was collected at the FD. Significant improvements were made to the analysis methodology, with the near-detector analysis introducing new selections and using more than double the data. Additionally, this is the first T2K oscillation analysis to use NA61/SHINE data on a replica of the T2K target to tune the neutrino flux model, and the neutrino interaction model was improved to include new nuclear effects and calculations. Frequentist and Bayesian analyses are presented, including results on $$\sin ^2\theta _{13}$$ sin 2 θ 13 and the impact of priors on the $$\delta _{\textrm{CP}}$$ δ CP measurement. Both analyses prefer the normal mass ordering and upper octant of $$\sin ^2\theta _{23}$$ sin 2 θ 23 with a nearly maximally CP-violating phase. Assuming the normal ordering and using the constraint on $$\sin ^2\theta _{13}$$ sin 2 θ 13 from reactors, $$\sin ^2\theta _{23}=0.561^{+0.021}_{-0.032}$$ sin 2 θ 23 = 0 . 561 - 0.032 + 0.021 using Feldman–Cousins corrected intervals, and $$\varDelta {}m^2_{32}=2.494_{-0.058}^{+0.041}\times 10^{-3}~\text {eV}^2$$ Δ m 32 2 = 2 . 494 - 0.058 + 0.041 × 10 - 3 eV 2 using constant $$\varDelta \chi ^{2}$$ Δ χ 2 intervals. The CP-violating phase is constrained to $$\delta _{\textrm{CP}}=-1.97_{-0.70}^{+0.97}$$ δ CP = - 1 . 97 - 0.70 + 0.97 using Feldman–Cousins corrected intervals, and $$\delta _{\textrm{CP}}=0,\pi $$ δ CP = 0 , π is excluded at more than 90% confidence level. A Jarlskog invariant of zero is excluded at more than $$2\sigma $$ 2 σ credible level using a flat prior in $$\delta _{\textrm{CP}},$$ δ CP , and just below $$2\sigma $$ 2 σ using a flat prior in $$\sin \delta _{\textrm{CP}}.$$ sin δ CP . When the external constraint on $$\sin ^2\theta _{13}$$ sin 2 θ 13 is removed, $$\sin ^2\theta _{13}=28.0^{+2.8}_{-6.5}\times 10^{-3},$$ sin 2 θ 13 = 28 . 0 - 6.5 + 2.8 × 10 - 3 , in agreement with measurements from reactor experiments. These results are consistent with previous T2K analyses.
Purpose To prospectively evaluate the safety and effectiveness of arthroscopic acellular human dermal matrix augmentation of large rotator cuff tear repairs. Methods A prospective, institutional ...review board–approved, multicenter series of patients undergoing arthroscopic repair of 2-tendon rotator cuff tears measuring greater than 3 cm were randomized by sealed envelopes opened at the time of surgery to arthroscopic single-row rotator cuff repair with GraftJacket acellular human dermal matrix (Wright Medical Technology, Arlington, TN) augmentation (group 1) or without augmentation (group 2). Preoperative and postoperative functional outcome assessments were obtained by use of the American Shoulder and Elbow Surgeons (ASES), Constant, and University of California, Los Angeles scales. Gadolinium-enhanced magnetic resonance imaging (MRI) evaluation of these repairs was obtained at a mean of 14.5 months (range, 12 to 24 months). Adverse events were recorded. Results There were 22 patients in group 1 and 20 in group 2 with a mean age of 56 years. The mean follow-up was 24 months (range, 12 to 38 months). The ASES score improved from 48.5 to 98.9 in group 1 and from 46.0 to 94.8 in group 2. The scores in group 1 were statistically better than those in group 2 ( P = .035). The Constant score improved from 41.0 to 91.9 in group 1 and from 45.8 to 85.3 in group 2. The scores in group 1 were statistically better than those in group 2 ( P = .008). The University of California, Los Angeles score improved from 13.3 to 28.2 in group 1 and from 15.9 to 28.3 in group 2 ( P = .43). Gadolinium-enhanced MRI scans showed intact cuffs in 85% of repairs in group 1 and 40% in group 2 ( P < .01). No adverse events were attributed to the presence of the matrix grafts. Conclusions Acellular human dermal matrix augmentation of large (>3 cm) cuff tears involving 2 tendons showed better ASES and Constant scores and more frequent intact cuffs as determined by gadolinium-enhanced MRI. Intact repairs were found in 85% of the augmented group and 40% of the nonaugmented group ( P < .01). No adverse events related to the acellular human dermal matrix were observed. Level of Evidence Level II, lesser-quality randomized controlled trial.
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 and 735 km, using a ...combined MINOS and MINOS+ exposure of 16.36×10^{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}θ_{24} for most values of the sterile neutrino mass splitting Δm_{41}^{2}>10^{-4} eV^{2}.
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