The moment magnitude (M(w)) = 9.0 2011 Tohoku-Oki mega-thrust earthquake occurred off the coast of northeastern Japan. Combining Global Positioning System (GPS) and acoustic data, we detected very ...large sea-floor movements associated with this event directly above the focal region. An area with more than 20 meters of horizontal displacement, that is, four times larger than those detected on land, stretches several tens of kilometers long along the trench; the largest amount reaches about 24 meters toward east-southeast just above the hypocenter. Furthermore, nearly 3 meters of vertical uplift occurred, contrary to observed terrestrial subsidence.
Patients with type 2 diabetes mellitus (T2DM) are reaching an explosive number. Pancreatic β cell dysfunction is the characteristic feature of the progression of T2DM and there is an increasing need ...for agents to improve its function. GPR119 is a G protein-coupled receptor (GPCR) expressed both in pancreatic β cells and enteroendocrine cells and has garnered significant interest as a promising target for the next generation of T2DM drug. In vitro studies indicate that GPR119 agonists increase intracellular cAMP levels leading to enhanced glucose-induced insulin release and enhanced incretin hormone glucagon-like peptide 1 (GLP-1) secretion. In T2DM rodent models, GPR119 agonists are shown to decrease blood glucose level and preserve pancreatic β cell function.
This review summarizes the function of GPR119 and the progresses made in the discovery of GPR119 agonists reported since 2002 in literatures. The importance of GPR119 agonists in glycemic control is discussed.
GPR119 agonists with glucose-dependent insulin release and increased insulin promoter activity is expected to preserve pancreatic β cell function, thereby providing great clinical benefits for T2DM patients. Both the preclinical and clinical data suggest that GPR119 agonist will be a promising anti-diabetic drug.
Abstract
Transient sources such as supernovae (SNe) and tidal disruption events are candidates of high-energy neutrino sources. However, SNe commonly occur in the universe and a chance coincidence of ...their detection with a neutrino signal cannot be avoided, which may lead to a challenge of claiming their association with neutrino emission. In order to overcome this difficulty, we propose a search for ∼10–100 TeV multiple neutrino events within a timescale of ∼30 days coming from the same direction, called neutrino multiplets. We show that demanding multiplet detection by a ∼1 km
3
neutrino telescope limits the distances of detectable neutrino sources, which enables us to identify source counterparts by multiwavelength observations owing to the substantially reduced rate of the chance coincidence detection of transients. We apply our results by constructing a feasible strategy for optical follow-up observations and demonstrate that wide-field optical telescopes with a ≳4 m dish should be capable of identifying a transient associated with a neutrino multiplet. We also present the resultant sensitivity of multiplet neutrino detection as a function of the released energy of neutrinos and burst rate density. A model of neutrino transient sources with an emission energy greater than a few × 10
51
erg and a burst rate rarer than a few ×10
−8
Mpc
−3
yr
−1
is constrained by the null detection of multiplets by a ∼1 km
3
scale neutrino telescope. This already disfavors the canonical high-luminosity gamma-ray bursts and jetted tidal disruption events as major sources in the TeV-energy neutrino sky.
Recently, Research and development activity of HTS (High Temperature Superconducting) power application is very progressive worldwide. Especially, HTS cable system and HTSFCL (HTS Fault current ...limiter) system are proceeding to practical stages. In such system and equipment, cryogenic cooling system, which makes HTS equipment cooled lower than critical temperature, is one of crucial components. In this article, cryogenic cooling system for HTS application, mainly cable, is reviewed. Cryogenic cooling system can be categorized into conduction cooling system and immersion cooling system. In practical HTS power application area, immersion cooling system with sub-cooled liquid nitrogen is preferred. The immersion cooling system is besides grouped into open cycle system and closed cycle system. Turbo-Brayton refrigerator is a key component for closed cycle system. Those two cooling systems are focused in this article. And, each design and component of the cooling system is explained.
This is a review of compact liquefaction/recondensation equipment with cryocoolers, namely, GM-coolers and pulse tube cryocoolers. The improvement of liquefaction performance is remarkable since the ...advent of the 4-K pulse tube cryocooler. This article describes a brief history about 4-K cryocoolers and their liquefaction performance. Additionally, commercialized helium gas liquefaction/recondensation systems with cryocoolers are introduced and those specifications are shown.
Weight gain during interpregnancy period is related to hypertensive disorders of pregnancy (HDP). However, in interpregnancy care/counseling, the unpredictability of the timing of the next conception ...and the difficulties in preventing age-related body weight gain must be considered while setting weight management goals. Therefore, we suggest considering the annual change in the body mass index (BMI). This study aimed to clarify the association between annual BMI changes during the interpregnancy period and HDP risk in subsequent pregnancies. A multicenter retrospective study of data from 2009 to 2019 examined the adjusted odds ratio (aOR) of HDP in subsequent pregnancies. The aORs in several annual BMI change categories were also calculated in the subgroups classified by HDP occurrence in the index pregnancy. This study included 1,746 pregnant women. A history of HDP (aOR, 16.76; 95% confidence interval CI, 9.62 - 29.22), and annual BMI gain (aOR, 2.30; 95% CI, 1.76 - 3.01) were independent risk factors for HDP in subsequent pregnancies. An annual BMI increase of ≥ 1.0 kg/m
/year was related to HDP development in subsequent pregnancies for women without a history of HDP. This study provides data as a basis for interpregnancy care/counseling, but further research is necessary to validate our findings and confirm this relationship.
Postpartum depression (PPD) is as a major public health issue and clinical priority worldwide. This study aimed to investigate the association between pre-pregnancy sleep duration and PPD. A ...multicenter retrospective study was conducted using clinical data of women who delivered at term between 2014 and 2018 at 12 maternity care hospitals in Japan. A total of 15,314 women were stratified into five groups according to their pre-pregnancy sleep duration: < 6, 6–7, 7–8, 8–9, and ≥ 9 h. Univariate and multivariate regression analyses were conducted to determine whether pre-pregnancy sleep duration affects the Edinburgh Postnatal Depression Scale (EPDS) scores at 1 month postpartum. We also evaluated whether the risk for PPD differs between primipara and multipara women classified according to pre-pregnancy sleep duration. The adjusted odds ratio for high EPDS scores (≥ 9) among women who slept for < 6 h and 6–7 h was 2.08 (95% confidence interval CI: 1.60–2.70) and 1.41 (95% CI: 1.18–1.68), respectively, relative to that in women with 7–8 h of sleep as the reference group. A 1-h increase in sleep duration was associated with an approximately 14% reduction in the risk for high EPDS scores. The association between short sleep duration and high EPDS scores was more remarkable in multipara women than in primipara women. Short pre-pregnancy sleep duration is associated with high EPDS scores, and this association is more significant in multipara women than in primipara women. Our findings emphasize the importance of collecting information on pre-pregnancy sleep duration to identify women at a high risk for PPD.
Highlights • NaC expression is associated with LWC during development in mice. • NaC is expressed in AEC II and PMVECs in mouse lung. • Elevation of Na+ o increased Na+ i in the alveolar wall in the ...presence of amiloride.
Objectives
We recently demonstrated that the cerebral sodium‐glucose transporter (SGLT) is involved in postischaemic hyperglycaemia‐induced exacerbation of cerebral ischaemia. However, the associated ...SGLT‐mediated mechanisms remain unclear. Thus, we examined the involvement of cerebral SGLT‐induced excessive sodium ion influx in the development of cerebral ischaemic neuronal damage.
Methods
Na+i was estimated according to sodium‐binding benzofuran isophthalate fluorescence. In the in vitro study, primary cortical neurons were prepared from fetuses of ddY mice. Primary cortical neurons were cultured for 5 days before each treatment with reagents, and these survival rates were assessed using biochemical assays. In in vivo study, a mouse model of focal ischaemia was generated using middle cerebral artery occlusion (MCAO).
Key findings
In these experiments, treatment with high concentrations of glucose induced increment in Na+i, and this phenomenon was suppressed by the SGLT‐specific inhibitor phlorizin. SGLT‐specific sodium ion influx was induced using a‐methyl‐D‐glucopyranoside (a‐MG) treatments, which led to significant concentration‐dependent declines in neuronal survival rates and exacerbated hydrogen peroxide‐induced neuronal cell death. Moreover, phlorizin ameliorated these effects. Finally, intracerebroventricular administration of a‐MG exacerbated the development of neuronal damage induced by MCAO, and these effects were ameliorated by the administration of phlorizin.
Conclusions
Hence, excessive influx of sodium ions into neuronal cells through cerebral SGLT may exacerbate the development of cerebral ischaemic neuronal damage.
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