Search for Periodic Time Variations of the Solar

We report a search for time variations of the solar ^{8}B neutrino flux using 5804 live days of Super-Kamiokande data collected between May 31, 1996, and May 30, 2018. Super-Kamiokande measured the precise time of each solar neutrino interaction over 22 calendar years to search for solar neutrino flux modulations with unprecedented precision. Periodic modulations are searched for in a dataset comprising five-day interval solar neutrino flux measurements with a maximum likelihood method. We also applied the Lomb-Scargle method to this dataset to compare it with previous reports. The only significant modulation found is due to the elliptic orbit of the Earth around the Sun. The observed modulation is consistent with astronomical data: we measured an eccentricity of (1.53±0.35)%, and a perihelion shift of (-1.5±13.5) days.

Search for Electron Antineutrino Appearance in a Long-Baseline Muon Antineutrino Beam.

Electron antineutrino appearance is measured by the T2K experiment in an accelerator-produced antineutrino beam, using additional neutrino beam operation to constrain parameters of the Pontecorvo-Maki-Nakagawa-Sakata (PMNS) mixing matrix. T2K observes 15 candidate electron antineutrino events with a background expectation of 9.3 events. Including information from the kinematic distribution of observed events, the hypothesis of no electron antineutrino appearance is disfavored with a significance of 2.40σ and no discrepancy between data and PMNS predictions is found. A complementary analysis that introduces an additional free parameter which allows non-PMNS values of electron neutrino and antineutrino appearance also finds no discrepancy between data and PMNS predictions.

Search for Boosted Dark Matter Interacting with Electrons in Super-Kamiokande.

A search for boosted dark matter using 161.9 kt yr of Super-Kamiokande IV data is presented. We search for an excess of elastically scattered electrons above the atmospheric neutrino background, with a visible energy between 100 MeV and 1 TeV, pointing back to the Galactic center or the Sun. No such excess is observed. Limits on boosted dark matter event rates in multiple angular cones around the Galactic center and Sun are calculated. Limits are also calculated for a baseline model of boosted dark matter produced from cold dark matter annihilation or decay. This is the first experimental search for boosted dark matter from the Galactic center or the Sun interacting in a terrestrial detector.

Search for CP Violation in Neutrino and Antineutrino Oscillations by the T2K Experiment with 2.2×10

The T2K experiment measures muon neutrino disappearance and electron neutrino appearance in accelerator-produced neutrino and antineutrino beams. With an exposure of 14.7(7.6)×10^{20} protons on target in the neutrino (antineutrino) mode, 89 ν_{e} candidates and seven anti-ν_{e} candidates are observed, while 67.5 and 9.0 are expected for δ_{CP}=0 and normal mass ordering. The obtained 2σ confidence interval for the CP-violating phase, δ_{CP}, does not include the CP-conserving cases (δ_{CP}=0, π). The best-fit values of other parameters are sin^{2}θ_{23}=0.526_{-0.036}^{+0.032} and Δm_{32}^{2}=2.463_{-0.070}^{+0.071}×10^{-3} eV^{2}/c^{4}.

Combined Analysis of Neutrino and Antineutrino Oscillations at T2K.

T2K reports its first results in the search for CP violation in neutrino oscillations using appearance and disappearance channels for neutrino- and antineutrino-mode beams. The data include all runs from January 2010 to May 2016 and comprise 7.482×10^{20} protons on target in neutrino mode, which yielded in the far detector 32 e-like and 135 µ-like events, and 7.471×10^{20} protons on target in antineutrino mode, which yielded 4 e-like and 66 µ-like events. Reactor measurements of sin^{2}2θ_{13} have been used as an additional constraint. The one-dimensional confidence interval at 90% for the phase δ_{CP} spans the range (-3.13, -0.39) for normal mass ordering. The CP conservation hypothesis (δ_{CP}=0, π) is excluded at 90% C.L.

Measurement of Muon Antineutrino Oscillations with an Accelerator-Produced Off-Axis Beam.

T2K reports its first measurements of the parameters governing the disappearance of ν[over ¯]_{µ} in an off-axis beam due to flavor change induced by neutrino oscillations. The quasimonochromatic ν[over ¯]_{µ} beam, produced with a peak energy of 0.6 GeV at J-PARC, is observed at the far detector Super-Kamiokande, 295 km away, where the ν[over ¯]_{µ} survival probability is expected to be minimal. Using a data set corresponding to 4.01×10^{20} protons on target, 34 fully contained µ-like events were observed. The best-fit oscillation parameters are sin^{2}(θ[over ¯]_{23})=0.45 and |Δm[over ¯]_{32}^{2}|=2.51×10^{-3} eV^{2} with 68% confidence intervals of 0.38-0.64 and 2.26-2.80×10^{-3} eV^{2}, respectively. These results are in agreement with existing antineutrino parameter measurements and also with the ν_{µ} disappearance parameters measured by T2K.

Measurement of Coherent π

We report the first measurement of the flux-averaged cross section for charged current coherent π^{+} production on carbon for neutrino energies less than 1.5 GeV, and with a restriction on the final state phase space volume in the T2K near detector, ND280. Comparisons are made with predictions from the Rein-Sehgal coherent production model and the model by Alvarez-Ruso et al., the latter representing the first implementation of an instance of the new class of microscopic coherent models in a neutrino interaction Monte Carlo event generator. We observe a clear event excess above background, disagreeing with the null results reported by K2K and SciBooNE in a similar neutrino energy region. The measured flux-averaged cross sections are below those predicted by both the Rein-Sehgal and Alvarez-Ruso et al.

Precise measurement of the neutrino mixing parameter θ23 from muon neutrino disappearance in an off-axis beam.

New data from the T2K neutrino oscillation experiment produce the most precise measurement of the neutrino mixing parameter θ23. Using an off-axis neutrino beam with a peak energy of 0.6 GeV and a data set corresponding to 6.57×10(20) protons on target, T2K has fit the energy-dependent νµ oscillation probability to determine oscillation parameters. The 68% confidence limit on sin(2)(θ23) is 0.514(-0.056)(+0.055) (0.511±0.055), assuming normal (inverted) mass hierarchy. The best-fit mass-squared splitting for normal hierarchy is Δm32(2)=(2.51±0.10)×10(-3) eV(2)/c(4) (inverted hierarchy: Δm13(2)=(2.48±0.10)×10(-3) eV(2)/c(4)). Adding a model of multinucleon interactions that affect neutrino energy reconstruction is found to produce only small biases in neutrino oscillation parameter extraction at current levels of statistical uncertainty.

Observation of electron neutrino appearance in a muon neutrino beam.

The T2K experiment has observed electron neutrino appearance in a muon neutrino beam produced 295 km from the Super-Kamiokande detector with a peak energy of 0.6 GeV. A total of 28 electron neutrino events were detected with an energy distribution consistent with an appearance signal, corresponding to a significance of 7.3σ when compared to 4.92±0.55 expected background events. In the Pontecorvo-Maki-Nakagawa-Sakata mixing model, the electron neutrino appearance signal depends on several parameters including three mixing angles θ12, θ23, θ13, a mass difference Δm(32)(2) and a CP violating phase δ(CP). In this neutrino oscillation scenario, assuming |Δm(32)(2)|=2.4×10(-3) eV(2), sin(2)θ(23)=0.5, and Δm322>0 (Δm(32)(2)<0), a best-fit value of sin(2)2θ(13)=0.140(-0.032)(+0.038) (0.170(-0.037)(+0.045)) is obtained at δ(CP)=0. When combining the result with the current best knowledge of oscillation parameters including the world average value of θ(13) from reactor experiments, some values of δ(CP) are disfavored at the 90% C.L.

Measurement of the inclusive electron neutrino charged current cross section on carbon with the T2K near detector.

The T2K off-axis near detector ND280 is used to make the first differential cross-section measurements of electron neutrino charged current interactions at energies ∼1 GeV as a function of electron momentum, electron scattering angle, and four-momentum transfer of the interaction. The total flux-averaged ν(e) charged current cross section on carbon is measured to be ⟨σ⟩(ϕ)=1.11±0.10(stat)±0.18(syst)×10⁻³8 cm²/nucleon. The differential and total cross-section measurements agree with the predictions of two leading neutrino interaction generators, NEUT and GENIE. The NEUT prediction is 1.23×10⁻³8 cm²/nucleon and the GENIE prediction is 1.08×10⁻³8 cm²/nucleon. The total ν(e) charged current cross-section result is also in agreement with data from the Gargamelle experiment.

Measurement of neutrino oscillation parameters from muon neutrino disappearance with an off-axis beam.

The T2K Collaboration reports a precision measurement of muon neutrino disappearance with an off-axis neutrino beam with a peak energy of 0.6 GeV. Near detector measurements are used to constrain the neutrino flux and cross section parameters. The Super-Kamiokande far detector, which is 295 km downstream of the neutrino production target, collected data corresponding to 3.01×10(20) protons on target. In the absence of neutrino oscillations, 205±17 (syst) events are expected to be detected while only 58 muon neutrino event candidates are observed. A fit to the neutrino rate and energy spectrum, assuming three neutrino flavors and normal mass hierarchy yields a best-fit mixing angle sin2(θ23)=0.514±0.082 and mass splitting |Δm(32)(2)|=2.44(-0.15)(+0.17)×10(-3) eV2/c4. Our result corresponds to the maximal oscillation disappearance probability.

Involvement of mouse Mlh1 in DNA mismatch repair and meiotic crossing over.

Mice that are deficient in either the Pms2 or Msh2 DNA mismatch repair genes have microsatellite instability and a predisposition to tumours. Interestingly, Pms2-deficient males display sterility associated with abnormal chromosome pairing in meiosis. Here mice deficient in another mismatch repair gene, Mlh1, possess not only microsatellite instability but are also infertile (both males and females). Mlh1-deficient spermatocytes exhibit high levels of prematurely separated chromosomes and arrest in first division meiosis. We also show that Mlh1 appears to localize to sites of crossing over on meiotic chromosomes. Together these findings suggest that Mlh1 is involved in DNA mismatch repair and meiotic crossing over.

Tumour susceptibility and spontaneous mutation in mice deficient in Mlh1, Pms1 and Pms2 DNA mismatch repair.

Germline mutations in the human MSH2, MLH1, PMS2 and PMS1 DNA mismatch repair (MMR) gene homologues appear to be responsible for most cases of hereditary non-polyposis colorectal cancer (HNPCC; refs 1-5). An important role for DNA replication errors in colorectal tumorigenesis has been suggested by the finding of frequent alterations in the length of specific mononucleotide tracts within genes controlling cell growth, including TGF-beta receptor type II (ref. 6), BAX (ref. 7) and APC (ref. 8). A broader role for MMR deficiency in human tumorigenesis is implicated by microsatellite instability in a fraction of sporadic tumours, including gastric, endometrial and colorectal malignancies. To better define the role of individual MMR genes in cancer susceptibility and MMR functions, we have generated mice deficient for the murine homologues of the human genes MLH1, PMS1 and PMS2. Surprisingly, we find that these mice show different tumour susceptibilities, most notably, to intestinal adenomas and adenocarcinomas, and different mutational spectra. Our results suggest that a general increase in replication errors may not be sufficient for intestinal tumour formation and that these genes share overlapping, but not identical functions.

Measurements of neutrino oscillation parameters from the T2K experiment using 3.6×1021 protons on target.

The T2K experiment presents new measurements of neutrino oscillation parameters using 19.7(16.3)×1020 protons on target (POT) in (anti-)neutrino mode at the far detector (FD). Compared to the previous analysis, an additional 4.7×1020 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 sin2θ13 and the impact of priors on the δCP measurement. Both analyses prefer the normal mass ordering and upper octant of sin2θ23 with a nearly maximally CP-violating phase. Assuming the normal ordering and using the constraint on sin2θ13 from reactors, sin2θ23=0.561-0.032+0.021 using Feldman-Cousins corrected intervals, and Δm322=2.494-0.058+0.041×10-3eV2 using constant Δχ2 intervals. The CP-violating phase is constrained to δCP=-1.97-0.70+0.97 using Feldman-Cousins corrected intervals, and δCP=0,π is excluded at more than 90% confidence level. A Jarlskog invariant of zero is excluded at more than 2σ credible level using a flat prior in δCP, and just below 2σ using a flat prior in sinδCP. When the external constraint on sin2θ13 is removed, sin2θ13=28.0-6.5+2.8×10-3, in agreement with measurements from reactor experiments. These results are consistent with previous T2K analyses.

Ultrafast exciton population, relaxation, and decay dynamics in thin oligothiophene films.

Femtosecond time-resolved two-photon photoemission spectroscopy is utilized to determine the electronically excited states dynamics at the α-sexithiophene (6T)/Au(111) interface and within the 6T film. We found that a photoinduced transition between the highest occupied molecular orbital and lowest unoccupied molecular orbital is essential in order to observe exciton population, which occurs within 100 fs. In thin 6T films, the exciton exhibits a lifetime of 650 fs. On a time scale of 400 fs, an energetic stabilization is observed leading to the formation of a polaron or electron trapping at defect states. The lifetime of this state is 6.3 ps. Coverage-dependent measurements show that apart from the excited state decay within the film, a substrate-mediated relaxation channel is operative. The present study demonstrates that two-photon photoemission spectroscopy is a powerful tool to investigate the whole life cycle from creation to decay of excitons in an organic semiconductor.

Indication of electron neutrino appearance from an accelerator-produced off-axis muon neutrino beam.

The T2K experiment observes indications of ν(µ) → ν(e) appearance in data accumulated with 1.43×10(20) protons on target. Six events pass all selection criteria at the far detector. In a three-flavor neutrino oscillation scenario with |Δm(23)(2)| = 2.4×10(-3) eV(2), sin(2)2θ(23) = 1 and sin(2)2θ(13) = 0, the expected number of such events is 1.5±0.3(syst). Under this hypothesis, the probability to observe six or more candidate events is 7×10(-3), equivalent to 2.5σ significance. At 90% C.L., the data are consistent with 0.03(0.04) < sin(2)2θ(13) < 0.28(0.34) for δ(CP) = 0 and a normal (inverted) hierarchy.

A kinesin motor in a force-producing conformation.

BACKGROUND: Kinesin motors hydrolyze ATP to produce force and move along microtubules, converting chemical energy into work by a mechanism that is only poorly understood. Key transitions and intermediate states in the process are still structurally uncharacterized, and remain outstanding questions in the field. Perturbing the motor by introducing point mutations could stabilize transitional or unstable states, providing critical information about these rarer states. RESULTS: Here we show that mutation of a single residue in the kinesin-14 Ncd causes the motor to release ADP and hydrolyze ATP faster than wild type, but move more slowly along microtubules in gliding assays, uncoupling nucleotide hydrolysis from force generation. A crystal structure of the motor shows a large rotation of the stalk, a conformation representing a force-producing stroke of Ncd. Three C-terminal residues of Ncd, visible for the first time, interact with the central beta-sheet and dock onto the motor core, forming a structure resembling the kinesin-1 neck linker, which has been proposed to be the primary force-generating mechanical element of kinesin-1. CONCLUSIONS: Force generation by minus-end Ncd involves docking of the C-terminus, which forms a structure resembling the kinesin-1 neck linker. The mechanism by which the plus- and minus-end motors produce force to move to opposite ends of the microtubule appears to involve the same conformational changes, but distinct structural linkers. Unstable ADP binding may destabilize the motor-ADP state, triggering Ncd stalk rotation and C-terminus docking, producing a working stroke of the motor.

ICBP90, a novel human CCAAT binding protein, involved in the regulation of topoisomerase IIalpha expression.

The one-hybrid system with an inverted CCAAT box as the DNA target sequence was used to identify proteins acting on key DNA sequences of the promoter of the topoisomerase IIalpha gene. Screening of cDNA libraries from the leukemia Jurkat cell line and from the adult human thymus resulted in the isolation of a novel protein of 793 amino acids (89,758 Da). This protein has in vitro CCAAT binding properties and has been called ICBP90. Adult thymus, fetal thymus, fetal liver, and bone marrow, known as active tissues in terms of cell proliferation, are the tissues richest in ICBP90 mRNA. In contrast, highly differentiated tissues and cells such as the central nervous system and peripheral leukocytes are free of ICBP90 mRNA. Western blotting experiments showed a simultaneous expression of topoisomerase IIalpha and ICBP90 in proliferating human lung fibroblasts. Simultaneous expression of both proteins has also been observed in HeLa cells, but in both proliferating and confluent cells. Overexpression of ICBP90 in COS-1-transfected cells induced an enhanced expression of endogenous topoisomerase IIalpha. Immunohistochemistry experiments showed that topoisomerase IIalpha and ICBP90 were coexpressed in proliferating areas of paraffin-embedded human appendix tissues and in high-grade breast carcinoma tissues. We have identified ICBP90, which is a novel CCAAT binding protein, and our results suggest that it may be involved in topoisomerase IIalpha expression. ICBP90 may also be useful as a new proliferation marker for cancer tissues.

Enhanced intestinal adenomatous polyp formation in Pms2-/-;Min mice.

Analysis of two human familial cancer syndromes, hereditary nonpolyposis colorectal cancer and familial adenomatous polyposis, indicates that mutations in either one of four DNA mismatch repair gene homologues or the adenomatous polyposis coli (APC) gene, respectively, are important for the development of colorectal cancer. To further investigate the role of DNA mismatch repair in intestinal tumorigenesis, we generated mice with mutations in both Apc and the DNA mismatch repair gene, Pms2. Whereas Pms2-deficient mice do not develop intestinal tumors, mice deficient in Pms2 and heterozygous for Min, an allele of Apc, develop approximately three times the number of small intestinal adenomas and four times the number of colon adenomas relative to Min and Pms2+/-;Min mice. Although Pms2 deficiency clearly increases adenoma formation in the Min background, histological analysis indicated no clear evidence for progression to carcinoma.

Role of DNA mismatch repair in the cytotoxicity of ionizing radiation.

The DNA mismatch repair (MMR) system in mammalian cells not only serves to correct base mispairs and other replication errors, but it also influences the cellular response to certain forms of DNA damage. Cells that are deficient in MMR are relatively resistant to alkylation damage because, in wild-type cells, the MMR system is thought to promote toxicity via futile repair of alkylated mispairs. Conversely, MMR-deficient cells are sensitive to UV light, possibly due to the requirement for MMR factors in transcription-coupled repair of active genes. MMR deficiency has been associated with familial and sporadic carcinomas of the colon and other sites, and so, we sought to determine the influence of MMR status on cellular response to ionizing radiation, an agent commonly used for cancer therapy. Fibroblast cell lines were established from transgenic mice carrying targeted disruptions of one of three MMR genes in mammalian cells: Pms2, Mlh1, or Msh2. In comparison to wild-type cell lines from related mice, the Pms2-, Mlh1-, or Msh2-nullizygous cell lines were found to exhibit higher levels of clonogenic survival following exposure to ionizing radiation. Because ionizing radiation generates a variety of lesions in DNA, the differences in survival may reflect a role for MMR in processing a subset of these lesions, such as damaged bases. These results both identify a new class of DNA-damaging agents whose effects are modulated by the MMR system and may help to elucidate pathways of radiation response in cancer cells.