Diffuse neutrino background from past core collapse supernovae.

Core collapse supernovae are among the most powerful explosions in the Universe, which emit thermal neutrinos that carry away most of the gravitational binding energy released. These neutrinos produce a diffuse supernova neutrino background (DSNB), which is one of the largest energy budgets among all radiation backgrounds. Detecting the DSNB is an important goal of modern high-energy astrophysics and particle physics, which provides valuable insights into core collapse modeling, neutrino physics, and cosmic supernova rate history. In this review, the key ingredients of DSNB calculation and what can be learned from future detections, including black hole formation and non-standard neutrino interactions are discussed. Moreover, an overview of the latest updates in neutrino experiments, which could lead to the detection of the DSNB in the next decade, is provided. With the promise of this breakthrough discovery on the horizon, the study of DSNB has great potential to further our understanding of the Universe.

Rationale, design and baseline characteristics of the effect of canagliflozin in patients with type 2 diabetes and microalbuminuria in the Japanese population: The CANPIONE study.

AIM: To evaluate the effect of canagliflozin, a sodium-glucose co-transporter-2 (SGLT2) inhibitor, on albuminuria and the decline of estimated glomerular filtration rate (eGFR) in participants with type 2 diabetes and microalbuminuria. METHODS: The CANPIONE study is a multicentre, randomized, parallel-group and open-labelled study consisting of a unique 24-week preintervention period, during which the rate of eGFR decline before intervention is estimated, followed by a 52-week intervention and a 4-week washout period. Participants with a geometric mean urinary albumin-to-creatinine ratio (UACR) of 50 and higher and less than 300 mg/g in two consecutive first-morning voids at two different time points, and an eGFR of 45 ml/min/1.73m2 or higher, are randomly assigned to receive canagliflozin 100 mg daily or to continue guideline-recommended treatment, except for SGLT2 inhibitors. The first primary outcome is the change in UACR, and the second primary outcome is the change in eGFR slope. RESULTS: A total of 258 participants were screened and 98 were randomized at 21 sites in Japan from August 2018 to May 2021. The mean baseline age was 61.4 years and 25.8% were female. The mean HbA1c was 7.9%, mean eGFR was 74.1 ml/min/1.73m2 and median UACR was 104.2 mg/g. CONCLUSIONS: The CANPIONE study will determine whether the SGLT2 inhibitor canagliflozin can reduce albuminuria and slow eGFR decline in participants with type 2 diabetes and microalbuminuria.

Novel Urinary Glycan Biomarkers Predict Cardiovascular Events in Patients With Type 2 Diabetes: A Multicenter Prospective Study With 5-Year Follow Up (U-CARE Study 2).

Background: Although various biomarkers predict cardiovascular event (CVE) in patients with diabetes, the relationship of urinary glycan profile with CVE in patients with diabetes remains unclear. Methods: Among 680 patients with type 2 diabetes, we examined the baseline urinary glycan signals binding to 45 lectins with different specificities. Primary outcome was defined as CVE including cardiovascular disease, stroke, and peripheral arterial disease. Results: During approximately a 5-year follow-up period, 62 patients reached the endpoint. Cox proportional hazards analysis revealed that urinary glycan signals binding to two lectins were significantly associated with the outcome after adjustment for known indicators of CVE and for false discovery rate, as well as increased model fitness. Hazard ratios for these lectins (+1 SD for the glycan index) were UDA (recognizing glycan: mixture of Man5 to Man9): 1.78 (95% CI: 1.24-2.55, P = 0.002) and Calsepa [High-Man (Man2-6)]: 1.56 (1.19-2.04, P = 0.001). Common glycan binding to these lectins was high-mannose type of N-glycans. Moreover, adding glycan index for UDA to a model including known confounders improved the outcome prediction [Difference of Harrel's C-index: 0.028 (95% CI: 0.001-0.055, P = 0.044), net reclassification improvement at 5-year risk increased by 0.368 (0.045-0.692, P = 0.026), and the Akaike information criterion and Bayesian information criterion decreased from 725.7 to 716.5, and 761.8 to 757.2, respectively]. Conclusion: The urinary excretion of high-mannose glycan may be a valuable biomarker for improving prediction of CVE in patients with type 2 diabetes, and provides the rationale to explore the mechanism underlying abnormal N-glycosylation occurring in patients with diabetes at higher risk of CVE. Trial Registration: This study was registered with the University Hospital Medical Information Network on June 26, 2012 (Clinical trial number: UMIN000011525, URL: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000013482).

Severe Visceral Obesity, Fatty Liver and Diabetes after Orchiectomy for Prostate Cancer.

A 79-year-old man without a history of diabetes underwent orchiectomy for prostate cancer. Eight months after the operation, he suffered severe deterioration of visceral fat deposition, fatty liver and diabetes. Treatment for diabetes with canagliflozin and dulaglutide resulted in improvement in his glycemic control, visceral fat and fatty liver. Visceral fat-dominant deposition, which differs from the typical course after androgen deprivation therapy, may have been associated with severe exacerbation of diabetes and fatty liver. Glycemic management with a sodium glucose cotransporter 2 (SGLT2) inhibitor and glucagon-like peptide (GLP)-1 receptor agonist may help improve the glucose metabolism, visceral fat deposition and fatty liver after orchiectomy.

Generating an agricultural risk map based on limited ecological information: A case study using Sicyos angulatus.

In this study, we propose a method for estimating the risk of agricultural damage caused by an invasive species when species-specific information is lacking. We defined the "risk" as the product of the invasion probability and the area of potentially damaged crop for production. As a case study, we estimated the risk imposed by an invasive weed, Sicyos angulatus, based on simple cellular simulations and governmental data on the area of crop that could potentially be damaged in Miyagi Prefecture, Japan. Simulation results revealed that the current distribution range was sufficiently accurate for practical purposes. Using these results and records of crop areas, we present risk maps for S. angulatus in agricultural fields. Managers will be able to use these maps to rapidly establish a management plan with minimal cost. Our approach will be valuable for establishing a management plan before or during the early stages of invasion.

Tomographic Constraints on High-Energy Neutrinos of Hadronuclear Origin.

Mounting evidence suggests that the TeV-PeV neutrino flux detected by the IceCube telescope has mainly an extragalactic origin. If such neutrinos are primarily produced by a single class of astrophysical sources via hadronuclear (pp) interactions, a similar flux of gamma-ray photons is expected. For the first time, we employ tomographic constraints to pinpoint the origin of the IceCube neutrino events by analyzing recent measurements of the cross correlation between the distribution of GeV gamma rays, detected by the Fermi satellite, and several galaxy catalogs in different redshift ranges. We find that the corresponding bounds on the neutrino luminosity density are up to 1 order of magnitude tighter than those obtained by using only the spectrum of the gamma-ray background, especially for sources with mild redshift evolution. In particular, our method excludes any hadronuclear source with a spectrum softer than E^{-2.1} as a main component of the neutrino background, if its evolution is slower than (1+z)^{3}. Starburst galaxies, if able to accelerate and confine cosmic rays efficiently, satisfy both spectral and tomographic constraints.

Testing the Dark Matter Scenario for PeV Neutrinos Observed in IceCube.

Late time decay of very heavy dark matter is considered as one of the possible explanations for diffuse PeV neutrinos observed in IceCube. We consider implications of multimessenger constraints, and show that proposed models are marginally consistent with the diffuse γ-ray background data. Critical tests are possible by a detailed analysis and identification of the sub-TeV isotropic diffuse γ-ray data observed by Fermi and future observations of sub-PeV γ rays by observatories like HAWC or Tibet AS+MD. In addition, with several-year observations by next-generation telescopes such as IceCube-Gen2, muon neutrino searches for nearby dark matter halos such as the Virgo cluster should allow us to rule out or support the dark matter models, independently of γ-ray and anisotropy tests.

Nonlinear evolution of anisotropic cosmological power.

There has been growing interest in the possibility of testing more precisely the assumption of statistical isotropy of primordial density perturbations. If it is to be tested with galaxy surveys at distance scales < or = 10 Mpc, then nonlinear evolution of anisotropic power must be understood. To this end, we calculate the angular dependence of the power spectrum to third order in perturbation theory for a primordial power spectrum with a quadrupole dependence on the wave vector direction. Our results suggest that primordial power anisotropies will be suppressed by < or = 7% in the quasilinear regime. We also show that the skewness in the statistically anisotropic theory differs by no more than 1% from that in the isotropic theory.

Psychosocial factors associated with smoking and drinking among Japanese early adolescent boys and girls: cross-sectional study.

BACKGROUND: Smoking and drinking alcohol among early adolescents are serious public health concerns, but few studies have been conducted in Japan to assess their prevalence and etiology. A regional survey was conducted in eight schools in two Japanese school districts to identify psychosocial factors associated with smoking and drinking behaviors for boys and girls. METHODS: Junior high school students from seventh to ninth grades (N = 2,923) completed a self-reported questionnaire between December 2002 and March 2003. Relationships between psychosocial variables (i.e., self-assertive efficacy to resist peer pressure, parental involvement, school adjustment, and deviant peer influence) and smoking and drinking were investigated using logistic regression analyses and path analyses. RESULTS: Smoking in the last six months was significantly more prevalent in boys (7.9%) than girls (5.1%). The prevalence of drinking in the last six months was similar in boys (23.7%) and girls (21.8%). Self-efficacy to resist peer pressure was negatively associated with both smoking and drinking among both boys and girls and provided both direct and indirect effects through deviant peer influence. Parental involvement showed indirect effects through school adjustment and/or deviant peer influence to both smoking among both boys and girls and drinking among girls, although parental involvement showed direct effects on smoking only for boys. School adjustment was negatively associated with smoking among both boys and girls and drinking among girls. CONCLUSION: These findings suggest that self-assertive efficacy to resist peer pressure, parental involvement, school adjustment and deviant peer influence are potentially important factors that could be addressed by programs to prevent smoking and/or drinking among early adolescent boys and girls in Japan.

A psychoeducational program to prevent aggressive behavior among Japanese early adolescents.

This study evaluates the impact of a school-based intervention program on aggressive behavior among junior high school students in Japan. One hundred and four seventh-graders were enrolled in the program and completed Time 1, Time 2, and Time 3 surveys. The program was implemented in two classes between Time 1 and Time 2 surveys (the first treatment group) and in two other classes between Time 2 and Time 3 surveys (the delayed treatment group). The program included four weekly lessons related to problem solving, stress management, and communication. The initial intervention group reported a significant increase in appropriate relationships with classmates. Aggressive behavior significantly decreased from Time 1 to Time 3 in both groups and from Time 2 to Time 3 in the delayed treatment group, but no treatment group effect was noted. Additional modification of the program may be needed to achieve decreases in aggressive behavior.

Thyroid hormone action at the cellular, genomic and target gene levels.

Thyroid hormone (TH) plays important roles in metabolism, growth and differentiation. Thyroid hormone receptors (TRs) are ligand-regulatable transcription factors that bind both TH and DNA enhancer sequences in the promoter region of target genes where they can interact with co-repressor and co-activator complexes. These interactons, in turn, have consequent effects on transcription. This review describes studies on TH action from our laboratory examining the cellular localization and motility of TRs using green fluorescent fusion proteins, gene expression profiles of TH in WT and TRalpha and TRbeta KO mice, as well as general transcription factor and co-activator recruitment on the promoters of target genes by TH in chromatin immunoprecipitation assays.

Detection of neutrinos from supernovae in nearby galaxies.

While existing detectors would see a burst of many neutrinos from a Milky Way supernova, the supernova rate is only a few per century. As an alternative, we propose the detection of approximately 1 neutrino per supernova from galaxies within 10 Mpc, in which there were at least 9 core-collapse supernovae since 2002. With a future 1 Mton scale detector, this could be a faster method for measuring the supernova neutrino spectrum, which is essential for calibrating numerical models and predicting the redshifted diffuse spectrum from distant supernovae. It would also allow a > or approximately 10(4) times more precise trigger time than optical data alone for high-energy neutrinos and gravitational waves.

Revealing the supernova-gamma-ray burst connection with TeV neutrinos.

Gamma-ray bursts (GRBs) are rare, powerful explosions displaying highly relativistic jets. It has been suggested that a significant fraction of the much more frequent core-collapse supernovae are accompanied by comparably energetic but mildly relativistic jets, which would indicate an underlying supernova-GRB connection. We calculate the neutrino spectra from the decays of pions and kaons produced in jets in supernovae, and show that the kaon contribution is dominant and provides a sharp break near 20 TeV, which is a sensitive probe of the conditions inside the jet. For a supernova at 10 Mpc, 30 events above 100 GeV are expected in a 10 s burst in the IceCube detector.

Can dark matter annihilation dominate the extragalactic gamma-ray background?

Annihilating dark matter (DM) has been discussed as a possible source of gamma rays from the galactic center and as a contribution to the extragalactic gamma-ray background. Assuming universality of the density profile of DM halos, we show that it is quite unlikely that DM annihilation is a main constituent of extragalactic gamma-ray background, without exceeding the observed gamma-ray flux from the galactic center. This argument becomes stronger when we include enhancement of the density profiles by supermassive black holes or baryon cooling. The presence of a substructure may loosen the constraint, but only if a very large cross section as well as the rather flat profile are realized.

Preliminary study of psychological factors affecting clinic attendance and glycemic control of Japanese patients with type 2 diabetes mellitus.

We studied 50 Japanese patients who were first diagnosed with type 2 diabetes mellitus. Psychological functioning was assessed by using the Rorschach test and the Yatabe-Guilford Personality test. Analysis indicated that patients who discontinued clinic attendance during the 2-yr. study period had more depression, lower general activity and less extraversion, more negative self-attitudes, and more concern about being helpless than those who continued having regular followups. This study also found that patients who had worse glycemic control 2 yr. after being first diagnosed reported more inferiority feelings, lower general activity, more need for closeness to others, and more emotional demands than those who had better glycemic control. In conclusion, understanding the psychological functioning would be helpful in the management of Japanese patients with type 2 diabetes mellitus.

p62, A TFIIH subunit, directly interacts with thyroid hormone receptor and enhances T3-mediated transcription.

Currently, little is known about the direct interactions of general transcription factors and nuclear hormone receptors. To investigate the potential role of the general transcription factor, TFIIH, in T3-mediated transcriptional activation, we examined thyroid hormone receptor (TR) interaction with individual TFIIH subunits in a yeast-two hybrid system. Among the nine subunits of TFIIH studied, only p62 subunit interacted with TRbeta in a ligand-dependent manner. Glutathione-S-transferase pull-down and in vivo coimmunoprecipitation studies also demonstrated direct TR/p62 interaction. Using chromatin immunoprecipitation assays, we showed that TFIIH subunits were corecruited on or near an endogenous thyroid hormone response element upon T3 addition. Cotransfection studies with TSA201 cells showed that p62 increased T3-mediated transcription, which could be further enhanced when p62 and another TFIIH subunit, p44, were cotransfected simultaneously. Taken together, these data suggest that TRs can interact directly with a subunit of TFIIH and may provide an alternative pathway for nuclear receptor communication with the general transcription machinery that circumvents coactivators.