Search

The kidney plays a central role in regulating the salt sensitivity of blood pressure (BP) by governing sodium excretion and reabsorption via renal sodium transporters. We hypothesized that sodium-glucose cotransporter 2 (SGLT2) inhibition and angiotensin II type 1 receptor (AT1R) blockade can synergistically reduce renal sodium reabsorption by beneficially effects on these transporters, leading to lower BP and ameliorating renal and cardiac damage.Dahl salt-sensitive rats were treated orally for 8weeks with a normal salt diet (0.3% NaCl), a high-salt diet (8% NaCl), high-salt diet with ipragliflozin (0.04%), high-salt diet with losartan (0.05%) or high-salt diet with a combination of ipragliflozin and losartan. The combination treatment significantly reduced BP and increased daily urine sodium excretion compared with losartan or ipragliflozin monotherapy, leading to greater improvement in BP salt sensitivity than ipragliflozin monotherapy. The combination treatment significantly ameliorated glomerulosclerosis and reduced cardiomyocyte hypertrophy compared with losartan or ipragliflozin monotherapy. The protein expression levels of Na+/H+ exchanger isoform 3 (NHE3) and Na+-K+-CI- cotransporter 2 (NKCC2) in the kidney were significantly decreased with losartan monotherapy and combination treatment, but not with ipragliflozin monotherapy.Inhibition of SGLT2 in combination with an angiotensin II receptor blocker effectively improved BP salt sensitivity by reducing renal expression levels of sodium transporters including NHE3 and NKCC2, which eventually led to improvement of BP salt sensitivity and cardiorenal protection.

Aortic valve stenosis (AS) leads to increased cardiovascular mortality and morbidity, and recent studies reported that even mild-to-moderate AS was associated with poor prognosis in the general population. This study investigated the prognostic impact of mild or moderate AS, defined as 2.0 m/s ≤ peak aortic jet velocity (Vmax) ≤3.9 m/s using echocardiography in acute myocardial infarction (AMI) patients.Methods and Results: This study enrolled 3,049 AMI patients using data from the Mie ACS registry. Patients were divided into 2 groups according to Vmax: Group 1: Vmax2.0 m/s and/or visually intact aortic valve in which all 3 leaflets are fully and evenly open; Group 2: 2.0 m/s ≤ Vmax ≤ 3.9 m/s. There were 2,976 patients in Group 1and 73 patients in Group 2. The Group 2 patients were older, had a higher percentage of males and had lower body mass index and Killip ≥2 than the Group 1 patients. Angiographic data, door-to-balloon time, and mechanical support were not different between the 2 groups. The Group 2 patients demonstrated a significantly higher all-cause mortality rate (P0.01) and composite of cardiovascular death and heart failure hospitalization (P0.01), and Kaplan-Meier analysis showed the same tendency in propensity score-matched patients.The present study revealed that mild or moderate AS based on Vmax is associated with poor prognosis following AMI.

Pulmonary arterial hypertension (PAH) is a fatal disease, which is characterized by occlusive pulmonary vascular disease (PVD) in small pulmonary arteries. It remains unknown whether perinatal insults aggravate occlusive PVD later in life. We tested the hypothesis that perinatal hypoxia aggravates PVD and survival in rats. PVD was induced in rats with/without perinatal hypoxia ( embryonic day 14 to postnatal day 3) by injecting SU5416 at 7 wk of age and subsequent exposure to hypoxia for 3 wk (SU5416/hypoxia). Hemodynamic and morphological analyses were performed in rats with/without perinatal hypoxia at 7 wk of age (baseline rats, n = 12) and at 15 wk of age in 4 groups of rats: SU5416/hypoxia or control rats with/without perinatal hypoxia ( n = 40). Pulmonary artery smooth muscle cells (PASMCs) from the baseline rats with/without perinatal hypoxia were used to assess cell proliferation, inflammation, and genomic DNA methylation profile. Although perinatal hypoxia alone did not affect survival, physiological, or pathological parameters at baseline or at the end of the experimental period in controls, perinatal hypoxia decreased weight gain and survival rate and increased right ventricular systolic pressure, right ventricular hypertrophy, and indices of PVD in SU5416/hypoxia rats. Perinatal hypoxia alone accelerated the proliferation and inflammation of cultured PASMCs from baseline rats, which was associated with DNA methylation. In conclusion, we established the first fatal animal model of PAH with worsening hemodynamics and occlusive PVD elicited by perinatal hypoxia, which was associated with hyperproliferative, proinflammatory, and epigenetic changes in cultured PASMCs. These findings provide insights into the treatment and prevention of occlusive PVD.

Background Kidney plays a central role in regulating salt-sensitivity of blood pressure (BP) to governs sodium excretion via several mechanisms including pressure natriuresis and the actions of renal sodium transporters. Purpose We clarified the effects of combination treatment of sodium-glucose cotransporter 2 (SGLT2) inhibitor and angiotensin receptor blocker (ARB) on BP and the pathogenesis of renocardiac injuries, and elucidated underlying molecular mechanisms involved in the regulation of renal sodium handling in the development of salt-sensitivity by comparing with each monotreatment in Dahl salt-sensitive (DSS) hypertensive rats. Methods DSS rats were treated orally for 8-weeks with normal salt diet (0.3% NaCl) (NS/Cont group), high salt diet (8% NaCl) (HS/Cont group), high salt diet with ipragliflozin (0.04%) (HS/Ipra group), high salt diet with losartan (0.05%) (HS/Los group), or high salt diet with combination of ipragliflozin and losartan (HS/Ipra+Los group). Results The combination group significantly reduced systolic BP compared with either high salt diet control group, losartan or ipragliflozin monotreatment groups (HS/Ipra+Los: 182.5±18.4mmHg vs HS/Cont: 227.7±26.1; HS/Ipra: 216.6±26.9; HS/Los: 208.6±21.6, at 8-weeks of treatment, P Conclusions The dual inhibition of SGLT2 and AT1R effectively improved salt-sensitivity via reducing renal expression levels of the sodium transporters, which eventually lead to renocardiac protection. Thus, the combination treatment could be a novel and useful therapeutic strategy for treating salt-sensitive hypertension and renal injury in non-diabetic patients. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Grant-in-Aid for Scientific Research

We experimentally demonstrate that the photovoltaic responsivity in an InP-based dual-grating-gate HEMT plasmonic THz detector with the gate-readout configuration is significantly enhanced by a positive gate bias application due to the nonlinear rectification effect at the InGaAs/InAlAs heterobarrier.

The photonic carrier frequency downconverter is an active device that directly converts digital coherent optical data signals to the digital coherent wireless data signals and furthermore to the intermediate frequency (IF) signals, too. Its key functionality is called photonic double-mixing, consisting of a photomixing of an optical data signal with an optical subcarrier signal to generate a down-converted terahertz (THz) wireless data signal and an rf-mixing of the generated THz data signal and a local (LO) signal to generate an IF signal. It also works to mix the THz wireless data signal with a LO signal generated by photomixing two optical subcarrier signals to generate an IF signal. At the present, various photomixers as well as several photonic carrier frequency downconverters have been developed [1] - [2] . However, their operation frequency range is limited by the electron transit time effect. In this study, we demonstrate the 1-THz band photonic double-mixing operation by using plasmonic technology. Plasmons, the quanta of the collective oscillation of electrons, are expected to overcome the electron transit time limitation [3] .

The regulation of muscle contraction is a critical function in the cardiovascular system, and abnormalities may be life-threatening or cause illness. The common basic mechanism in muscle contraction is the interaction between the protein filaments myosin and actin. Although this interaction is primarily regulated by intracellular Ca2+, the primary targets and intracellular signaling pathways differ in vascular smooth muscle and cardiac muscle. Phosphorylation of the myosin regulatory light chain (RLC) is a primary molecular switch for smooth muscle contraction. The equilibrium between phosphorylated and unphosphorylated RLC is dynamically achieved through two enzymes, myosin light chain kinase, a Ca2+-dependent enzyme, and myosin phosphatase, which modifies the Ca2+ sensitivity of contractions. In cardiac muscle, the primary target protein for Ca2+ is troponin C on thin filaments; however, RLC phosphorylation also plays a modulatory role in contraction. This review summarizes recent advances in our understanding of the regulation, physiological function, and pathophysiological involvement of RLC phosphorylation in smooth and cardiac muscles.

Background: Chronic total occlusion (CTO) in a non-infarct-related artery (IRA) in patients with acute coronary syndrome (ACS) is associated with a poor prognosis. However, whether the prognostic impact of non-IRA CTO differs according to left ventricular ejection fraction (LVEF) is unclear. Methods and results: A total of 2060 consecutive acute myocardial infarction (AMI) patients who underwent primary percutaneous coronary intervention (PCI) were classified into 2 groups according to their LVEF (reduced EF: LVEF < 50%, preserved EF: LVEF ≥ 50%) and further subdivided according to the presence of concomitant non-IRA CTO. In the reduced EF group, patients with CTO had a higher 1-year all-cause death rate (20.3% vs. 34.3%, P = 0.001) and major adverse cardiac event rate (MACE: 19.6% vs. 39.6%, P

We experimentally demonstrate the photovoltage from an InGaAs-channel dual-grating-gate HEMT THz detector in the gate-readout configuration is significantly enhanced by the positive gate bias application due to the nonlinear rectification effect at the InGaAs/InAlAs heterobarrier.

We propose the use of the gate electrode as a readout port of photovoltage of a grating-gate plasmonic THz detector. We fabricate the device and experimentally demonstrate the scaling of the photovoltage with the size of active area for the gate-readout and an excellent impedance matching to a 50-Ω interconnection system, both of which are impossible for the drain-readout.

We identified eight nonlinear crystals enabling THz emission from quadratic phase-matched Difference-Frequency-Generation: YCOB, BNA, LBO, CSP, AGS, CdSe, ZnO and GaP. For all these crystals, we performed Time-Domain Spectroscopy in the same conditions to determine their absorption spectra in polarized light as well as their principal refractive indices as a function of wavelength in the 0.5-2.0 THz range. By combining previous data with the Sellmeier equations valid in their visible and infrared transparency ranges, we calculated the coherence length of Difference-Frequency-Generation associated to all possible configurations of polarization and found interesting and complementary phase-matching conditions in the eight studied crystals.

Using terahertz time-domain spectroscopy, we report the principal values of absorption coefficients and refractive indices as a function of wavelength between 0.5 and 2.0 THz of eight attractive nonlinear crystals: YCOB, BNA, LBO, CSP, AGS, CdSe, ZnO and GaP. From these data, we calculated the coherence length and phase-matching conditions associated to the emission of a THz wave from a second-order difference-frequency generation.

Background Aortic valve stenosis (AS) is associated with the presence and severity of coronary artery disease independently of clinical risk factors, which leads to increased cardiovascular mortality. However, the prevalence of AS and its prognostic value among patients with acute myocardial infarction (AMI) remain unknown. Purpose The purpose of this study was to investigate the prevalence and prognostic impact of AS in AMI patients. Methods We studied 2,803 AMI patients using data from Mie ACS registry, a prospective and multicenter registry. Patients were divided into subgroups according to the presence and severity of AS based on maximal aortic flow rate by Doppler echocardiography before hospital discharge: non-AS Results AS was detected in 79 patients (2.8%) including 49 mild AS, 23 moderate AS and 6 severe AS. AS patients were significantly older (79.9±9.8 versus 68.3±12.6 years), and higher killip classification than non-AS patients (P Cox hazard regression analysis Hazard ratio 95% Confidential interval P-value Severity of aortic valve stenosis 1.71 1.30–2.24 All cause mortality Conclusions The presence of AS of any severity contributes to worsening of patients' prognosis following AMI independently of other known risk factors. Acknowledgement/Funding None

We experimentally demonstrate that the introduction of the 2D diffraction grating to a grating-gate plasmonic THz detector enables the coupling between incident THz waves with lateral polarization and 2D plasmons oscillating perpendicular to it, which in turn results in the alteration of polarization characteristic of the detector.

International audience

Measurements of the phase-matching conditions from second-harmonic and sum-frequency generation allowed us to refine the Sellmeier equations of BNA up to the near-infrared and to improve the tuning curve of THz emission from difference-frequency generation.

Cases of hepatitis E have been caused by infection with hepatitis E virus (HEV) due to consumption of raw or undercooked game meats and liver of wild boars or deer in various countries. We investigated HEV prevalence in wild boar and deer in Okazaki City and its outskirts, Aichi, Japan, using liver samples (439 boar; 185 deer) collected between April 2010 and November 2014. HEV RNA was detected in 49 (11.2%)of 439 and 0 of 185 samples of wild boar and deer, respectively. The positive rate (13.0%, 28/216) of HEV RNA from the wild boar with estimated body weight of less than 40 kg was significantly higher than that (2.7%, 3/111) in animals with estimated body weight of more than 40 kg. The 49 HEV strains were typed as genotype 4 (G4) by phylogenetic analysis. They clustered with Aichi/Shizuoka strains and 48 of the 49 strains subclustered together (Okazaki strains).

Asymmetric-dual-grating-gate high-electron-mobility-transistors (ADGG-HEMTs) are expected for on-chip, sensitive, room-temperature operating, high-speed THz detectors. In this paper, we experimentally verify the high-speed response of an ADGG-HEMT by measuring its response to THz pulse generated from an injection-seeded THz-wave parametric generator (is-TPG). From the pulse response waveform of the output photovoltage signal, it is demonstrated that the response time of the detector at least as fast as 100 ps.

We analyzed the Suzaku data of M86 and its adjacent regions to study the extended emission around it. The M86 core, the plume, and the tail extending toward the northwest were clearly detected, as well as the extended halo around them. From the position angle $\sim45\deg$ to $\sim275\deg$, the surface brightness distribution of the core and the extended halo was represented relatively well with a single $\beta$-model of $\beta\sim0.5$ up to 15'-20'. The X-ray spectra of the core was represented with a two-temperature model of $kT\sim 0.9$ keV and $\sim0.6$ keV. The temperatures of the core and the halo have a positive gradient in the center, and reach the maximum of $kT\sim1.0$ keV at $r\sim7'$, indicating that the halo gas is located in a larger scale potential structure than that of the galaxy. The temperatures of the plume and the tail were $0.86\pm0.01$ keV and $1.00\pm0.01$ keV. We succeeded in determining the abundances of $\alpha$-element separately, for the core, the plume, the tail, and the halo for the first time. Abundance ratios with respect to Fe were consistent with the solar ratios everywhere, except for Ne. The abundance of Fe was $\sim0.7$ in the core and in the plume, while that in the tail was $\sim1.0$, but the difference was not significant considering the uncertainties of the ICM. The abundance of the halo was almost the same up to $r\sim10'$, and then it becomes significantly smaller (0.2-0.3) at $r\gtrsim10'$, indicating the gas with low metal abundance still remains in the outer halo. From the surface brightness distribution, we estimated the gas mass ($\sim3\times10^{10}M_\odot$) and the dynamical mass ($\sim3\times10^{12}M_\odot$) in $r, Comment: 17 pages, 14 figures, 7 tables

THz imaging was performed in 2 s intervals with 1 mm resolution on a 3 in., 0.42 mm thick, as-cut n-type Silicon Carbide wafer. Carrier density, relaxation time, mobility, and resistivity obtained from imaging results are 0.91 × 1018 cm-3, 4.36 × 10-14 s, 218 cm2V-1s-1, and 3.14 × 10-2 Ωcm, respectively. Compared with the standard values provided by the manufacturers, the results suggest that THz imaging has reliable precision and accuracy.

We report on ultrahigh sensitive, broadband terahertz (THz) detectors based on asymmetric dual-grating-gate (A-DGG) high electron mobility transistors, demonstrating a record responsivity of 2.2 kV/W at 1 THz with a superior low noise equivalent power of 15 pW/√Hz using InGaAs/InAlAs/InP material systems. When THz radiation is absorbed strong THz photocurrent is first generated by the nonlinearity of the plasmon modes resonantly excited in undepleted portions of the 2D electron channel under the high-biased sub-grating of the A-DGG (as a quadratic nature of the product of local carrier density and velocity perturbations), then the THz photovoltaic response is read out at high-impedance parts of 2D channel under the other sub-grating biased at the level close to the threshold. Extraordinary enhancement by more than two orders of magnitude of the responsivity is verified with respect to that for a symmetric DGG structure.

This paper presents a model for integrated production and transportation scheduling in order to develop a low-carbon supply chain. A genetic algorithm and heuristic rules are applied to production scheduling problems, and beam search technique is used for transportation scheduling problems in consideration of both the tardiness of products and the amount of carbon dioxide emitted in manufacturing and transportation processes. A simulation system is developed to verify the effectiveness of the model.

We examine array configuration and silicon-lens integration of asymmetric-dual-grating-gate high-electron-mobility transistors (A-DGG HEMTs) as plasmonic terahertz detectors in order to enhance their external coupling efficiencies. We demonstrate 4-fold enhancement of the efficiency by an array of four series-connected detectors and 6-fold enhancement by the hyper-hemispherical silicon-lens integration. Those preliminary results indicate a possibility of enhancing external responsivities of A-DGG HEMTs up to their intrinsic values.

The reflectance around the longitudinal optical (LO) phonon frequency in the terahertz region changes with the carrier density of silicon carbide (SiC), while the reflectance around the transverse optical (TO) phonon frequency remains constantly high. The relative reflectance obtained from the reflectance at the two frequencies related to the TO and LO phonon was evaluated as a function of the carrier density of SiC. Two waves around these phonon frequencies can be generated easily using a tunable terahertz source. Nondestructive imaging of the carrier density of cubic SiC (3C-SiC) at the rate of 1 s per point was carried out successfully using this tunable terahertz source.

Rapid imaging of the carrier density of n-type silicon (Si) was carried out at the rate of 2 s per point using a terahertz wave of 4.4 THz generated from a tunable terahertz source. Reflectance of 4.4 THz as a function of carrier density was calculated using a simple Drude model. The carrier densities obtained from the terahertz imaging were 1 × 1018 cm−3 and 3 × 1018 cm−3, respectively.

A new nondestructive method using terahertz waves for determining the carrier density of GaAs is proposed. The reflectance around the longitudinal optical (LO) phonon frequency changes with carrier density, whereas the reflectance around the transverse optical (TO) phonon frequency is constant. The relative reflectance, which is evaluated from the reflectance at the two frequencies related to the TO and LO phonon, as a function of the carrier density of GaAs was calculated from the dielectric function. A broadband tunable terahertz source is convenient for producing two waves around these phonon frequencies. Imaging of n-type GaAs wafer using this new terahertz method is described.

We perform the dispersion-corrected first-principles calculations of vibrational absorption and the far-infrared (terahertz) spectroscopic experiments at different temperature to examine the effect of weak-hydrogen-bond network on the low-frequency vibrations of solid-state salicylic acid. By dispersion correction, calculated frequencies improve especially in the intermonomer torsion and interdimer translational modes which are closely related to the weak hydrogen bonds. The calculated frequencies and their relative intensities reproduce the observed spectrum in the accuracy of 10 cm −1 or less. Weak-hydrogen-bond network causes a large frequency shift of out-of-plane intermonomer modes and enhances interdimer translational modes accompanied by the O⋯H stretching vibrations.

We have developed widely tunable terahertz (THz)-wave sources using nonlinear optical crystals. In the 1–3 THz region, a frequency-agile THz-wave parametric oscillator in a ring-cavity configuration has been realized using MgO-doped LiNbO3 as the nonlinear crystal. An organic 4-dimethylamino-N-methyl-4-stilbazolium tosylate (DAST) crystal is promising for THz-wave generation in an ultra-wide range 1–40 THz. Difference-frequency generation from DAST, pumped using a dual-wavelength KTiOPO4 (KTP) optical parametric oscillator, is demonstrated. Additionally, THz-wave detection, with high sensitivity, fast response-time and room-temperature operation, is achieved by nonlinear up-conversion. Water concentration mapping of biological tissue samples and carrier density mapping of semiconductor wafers using frequency-agile THz-wave sources are demonstrated.

We performed the direct measurement of second harmonic generation and sum frequency generation phase-matching directions in the organic N-benzyl-2-methyl-4-nitroaniline crystal over its visible and near-infrared transparency range. The fit of these data allowed us to refine the Sellmeier equations of the three principal refractive indices in this range. With these equations, we improved the calculated tuning curves of terahertz emission from a phase-matched difference frequency process. We also determined the absolute magnitude of the d24 nonlinear coefficient.