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BACKGROUND AND PURPOSE: Noninvasive perfusion-weighted imaging with short scanning time could be advantageous in order to determine presumed penumbral regions and subsequent treatment strategy for acute ischemic stroke (AIS). Our aim was to evaluate interobserver agreement and the clinical utility of intravoxel incoherent motion MR imaging in patients with acute ischemic stroke. MATERIALS AND METHODS: We retrospectively studied 29 patients with AIS (17 men, 12 women; mean age, 75.2 [SD, 12.0 ] years; median, 77 years). Each patient underwent intravoxel incoherent motion MR imaging using a 1.5T MR imaging scanner. Diffusion-sensitizing gradients were applied sequentially in the x, y, and z directions with 6 different b-values (0, 50, 100, 150, 200, and 1000 seconds/mm(2)). From the intravoxel incoherent motion MR imaging data, diffusion coefficient, perfusion fraction, and pseudodiffusion coefficient maps were obtained using a 2-step fitting algorithm based on the Levenberg-Marquardt method. The presence of decreases in the intravoxel incoherent motion perfusion fraction and pseudodiffusion coefficient values compared with the contralateral normal-appearing brain was graded on a 2-point scale by 2 independent neuroradiologists. Interobserver agreement on the rating scale was evaluated using the κ statistic. Clinical characteristics of patients with a nondecreased intravoxel incoherent motion perfusion fraction and/or pseudodiffusion coefficient rated by the 2 observers were also assessed. RESULTS: Interobserver agreement was shown for the intravoxel incoherent motion perfusion fraction (κ = 0.854) and pseudodiffusion coefficient (κ = 0.789) maps, which indicated almost perfect and substantial agreement, respectively. Patients with a nondecreased intravoxel incoherent motion perfusion fraction tended to show recanalization of the occluded intracranial arteries more frequently than patients with a decreased intravoxel incoherent motion perfusion fraction. CONCLUSIONS: Intravoxel incoherent motion MR imaging could be performed in

Carbonaceous chondrites are considered to have originated from C-type asteroids and represent some of the most primitive material in our solar system. Furthermore, since carbonaceous chondrites can contain significant quantities of volatile elements, they may have played a crucial role in supplying volatiles and organic material to Earth and other inner solar system bodies. However, a major challenge of unravelling the volatile composition of chondritic meteorites is distinguishing between which features were inherited from the parent body, and what may be a secondary feature attributable to terrestrial weathering. In December 2020, the Hayabusa2 mission of the Japan Aerospace Exploration Agency (JAXA) successfully returned surface material from the C-type asteroid (162173) Ryugu to Earth. This material has now been classified as closely resembling CI-type chondrites, which are the most chemically pristine meteorites. The analysis of material from the surface of Ryugu therefore provides a unique opportunity to analyse the volatile composition of material that originated from a CI-type asteroid without the complications arising from terrestrial contamination. Given their highly volatile nature, the noble gas and nitrogen inventories of chondrites are highly sensitive to different alteration processes on the asteroid parent body, and to terrestrial contamination. Here, we investigate the nitrogen and noble gas signature of two pelletized grains collected from the first and second touchdown sites (Okazaki et al., 2022a), to provide an insight into the formation and alteration history of Ryugu. The concentration of trapped noble gas in the Ryugu samples is greater than the average composition of previously measured CI chondrites and are primarily derived from phase Q, although a significant contribution of presolar nanodiamond Xe-HL is noted. The large noble gas concentrations coupled with a significant contribution of presolar nanodiamonds suggests that the Ryugu samples may represent some of the most primitive unprocessed material from the early solar system. In contrast to the noble gases, the abundance of nitrogen and δ15N composition of the two Ryugu pellets are lower than the average CI chondrite value. We attribute the lower nitrogen abundances and δ15N measured in this study to the preferential loss of a 15N-rich phase from our samples during aqueous alteration on the parent planetesimal. The analyses of other grains returned from Ryugu have shown large variations in nitrogen concentrations and δ15N indicating that alteration fluids heterogeneously interacted with material now present on the surface of Ryugu. Finally, the ratio of trapped noble gases to nitrogen is higher than CI chondrites, and is closer to refractory phase Q and nanodiamonds. This indicates that Ryugu experienced aqueous alteration that led to the significant and variable loss of nitrogen, likely from soluble organic matter, without modification of the noble gas budget, which is primarily hosted in insoluble organic matter and presolar diamonds and is therefore more resistant to aqueous alteration., Geochimica et Cosmochimica Acta, 345, ISSN:0016-7037, ISSN:1872-9533

Introduction: Erythropoietin (EPO), produced in the kidney in a hypoxia responsive manner, is required for red blood cell production. In non-erythroid tissue, EPO increases endothelial cell production of nitric oxide (NO) and endothelial nitric oxide synthase (eNOS) that regulates vascular tone to improve oxygen delivery. This contributes to EPO cardioprotective activity in mouse models. Nitric oxide treatment in mice shifts hematopoiesis toward the erythroid lineage, increases red blood cell production and total hemoglobin. In erythroid cells, nitric oxide can also be generated by hydroxyurea metabolism that may contribute to hydroxyurea induction of fetal hemoglobin. We find that during erythroid differentiation, EPO induces neuronal nitric oxide synthase (nNOS) and that neuronal nitric oxide synthase is required for normal erythropoietic response.Methods: Wild type (WT) mice and mice with targeted deletion of nNOS (nNOS−/−) and eNOS (eNOS−/−) were assessed for EPO stimulated erythropoietic response. Bone marrow erythropoietic activity was assessed in culture by EPO dependent erythroid colony assay and in vivo by bone marrow transplantation into recipient WT mice. Contribution of nNOS to EPO stimulated cell proliferation was assessed in EPO dependent erythroid cells and in primary human erythroid progenitor cell cultures.Results: EPO treatment increased hematocrit similarly in WT and eNOS−/− mice and showed a lower increase in hematocrit nNOS−/− mice. Erythroid colony assays from bone marrow cells were comparable in number from wild type, eNOS−/− and nNOS−/− mice at low EPO concentration. Colony number increased at high EPO concentration is seen only in cultures from bone marrow cells of wild type and eNOS−/− mice but not from nNOS−/− mice. Colony size with high EPO treatment also exhibited a marked increase in erythroid cultures from wild type and eNOS−/− mice but not from nNOS−/− mice. Bone marrow transplant from nNOS−/− mice into immunodeficient mice showed engraftment at comparable levels to WT bone marrow transplant. With EPO treatment, the increase in hematocrit was blunted in recipient mice that received with nNOS−/− donor marrow compared with recipient mice that received WT donor marrow. In erythroid cell cultures, addition of nNOS inhibitor resulted in decreased EPO dependent proliferation mediated in part by decreased EPO receptor expression, and decreased proliferation of hemin induced differentiating erythroid cells.Discussion: EPO treatment in mice and in corresponding cultures of bone marrow erythropoiesis suggest an intrinsic defect in erythropoietic response of nNOS−/− mice to high EPO stimulation. Transplantation of bone marrow from donor WT or nNOS−/− mice into recipient WT mice showed that EPO treatment post-transplant recapitulated the response of donor mice. Culture studies suggest nNOS regulation of EPO dependent erythroid cell proliferation, expression of EPO receptor and cell cycle associated genes, and AKT activation. These data provide evidence that nitric oxide modulates EPO dose dependent erythropoietic response.

Objectives The aim of this AFIRE (Atrial Fibrillation and Ischemic Events With Rivaroxaban in Patients With Stable Coronary Artery Disease) trial subgroup analysis was to examine rivaroxaban monotherapy benefits and their relation to the time between stenting and enrollment among patients after coronary stenting. Background Of 2,215 patients with atrial fibrillation and stable coronary artery disease in the AFIRE trial, rivaroxaban monotherapy was noninferior to rivaroxaban plus antiplatelet therapy (combination therapy) in terms of efficacy and superior for safety endpoints. However, thrombotic risk after antiplatelet therapy cessation remained a concern among 1,444 patients who had undergone coronary stenting >1 year before enrollment. Methods The benefits of rivaroxaban monotherapy in coronary stenting subgroups were assessed for efficacy (a composite of stroke, systemic embolism, myocardial infarction, unstable angina requiring revascularization, or death of any cause), safety (major bleeding defined according to International Society on Thrombosis and Haemostasis criteria), ischemic endpoints, net adverse clinical event, and time between stenting and enrollment. Results Efficacy and safety endpoints for monotherapy were superior to combination therapy, with HRs of 0.70 for efficacy (95% CI: 0.50-0.98; P = 0.036) and 0.55 for safety (95% CI: 0.33-0.92; P = 0.019). For ischemic endpoints, the HR was 0.82 (95% CI: 0.58-1.15; P = 0.240). The HR became smaller with longer time between stenting and enrollment (efficacy, P for interaction = 0.158; safety, P = 0.097). Conclusions In patients with atrial fibrillation after coronary stenting, the benefits of rivaroxaban monotherapy for efficacy and safety endpoints were consistent with those in the whole AFIRE trial population. The benefits became apparent with longer time between stenting and enrollment. (Atrial Fibrillation and Ischemic Events With Rivaroxaban in Patients With Stable Coronary Artery Disease Study [AFIRE]; UMIN000016612 , NCT02642419 )

Background Cardiogenic shock (CS) in patients with AMI presents worse cardiovascular outcomes, which suggests the need for better risk stratification and management. The Society for Cardiovascular Angiography and Intervention (SCAI) has recently proposed CS classification scheme, which stratifies CS into 5 groups according to hypotension and hypoperfusion. While stage A and B exhibits CS without hypotension and/or hypoperfusion, their clinical condition could rapidly deteriorate into stage C-E. However, clinical characteristics and in-hospital outcomes of CS exhibiting its deterioration remains uncertain. Purpose To characterize AMI patients who deteriorated their CS status from stage A and B into stage C-E. Methods This single-center observational study included 326 consecutive AMI patients receiving primary PCI who presented CS stage A and B on arrival (2019.09.01–2021.09.30). Deterioration of CS (D-CS) was defined as the progression from stage A and B on arrival to stage C-E after primary PCI. Clinical characteristics and outcomes were compared in those with and without D-CS. Results D-CS was identified in 16.0% of entire subjects (=52/326). Of these, 94.2 and 5.8% of them exhibited stage C and E, respectively (Figure). Patients with D-CS more likely presented STEMI (84.6 vs. 67.9%, p=0.01) with a lower systolic BP (sBP) level (130±31 vs. 148±26mmHg, p Conclusion 16.0% of AMI without any hypotension/hypoperfusion on arrival exhibited deterioration of CS status on SCAI classification. The combination of sBP, LVEF and pre-TIMI flow grade could help to identify AMI subjects with a risk of D-CS, who may benefit from early adoption of intensified management including MCS prior to PCI. Funding Acknowledgement Type of funding sources: None.

Introduction The International Atherosclerosis Society (IAS) has proposed “severe familial hypercholesterolemia” (FH) as a phenotype with the highest cardiovascular risk. LDL-C Purpose To determine whether achieving LDL-C Methods A total of 148 severe FH subjects without any history of ASCVD were analyzed. Severe FH was defined as untreated LDL-C >10.3 mmol/l, LDL-C >8.0 mmol/l+ 1 high-risk feature, LDL-C >4.9 mmol/l + 2 high-risk features according to IAS proposed statement. The occurrence of ASCVD (all-cause death, CAD, ischemic stroke and lower extremity artery disease (LEAD)) were compared in those with on-treatment LDL-C < and ≥1.8 mmol/L. Results 10.1% (=15/148) of study subjects achieved on-treatment LDL-C Conclusions A significantly lower frequency of ASCVD was observed in severe FH who achieved LDL-C Funding Acknowledgement Type of funding sources: None.

Background Recent clinical trials are testing strategies for short (1–3 months) dual antiplatelet therapy (DAPT) following newer-generation drug-eluting stent (DES) placement. However, the safety of short DAPT regimens is not supported by biological evidence in humans. Purpose We sought to evaluate early pathologic responses to newer-generation DES by comparing abluminal biodegradable polymer-coated DES (BP-DES) with circumferential durable polymer-coated DES (DP-DES) in human autopsy cases. Methods The study included a total of 37 coronary lesions with thin strut newer-generation DES (DP-DES=23 [XIENCE=18, Resolute Integrity=5] and BP-DES=14 [SYNERGY=9, Ultimaster=5]) with duration of implantation Results Duration of implantation was similar in lesions with DP-DES and those with BP-DES (median=20 vs. 17 days). A total of 1986 struts (DP-DES=1261, BP-DES=725) were pathologically analyzed. Focal grade 2 coverage was observed as early as 5 days after the implantation in both stents. Multilevel mixed-effects ordered logistic regression model demonstrated that BP-DES exhibited greater strut coverage compared with DP-DES (odds ratio; 3.50, 95% CI; 1.31–9.41, P=0.013), which remained significant after adjustment for duration of implantation and underlying tissue characteristics (odds ratio; 2.64, 95% CI; 1.04–6.68, P=0.040). The time course of vessel healing assessed as predictive probability of strut coverage (grade 0–3) stratified by duration of implantation is shown in Figure 2. Predictive probability of grade 2 and 3 coverage was comparably limited at 30 days (DP-DES=17.7% vs. BP-DES=29.0%) and increased at 90 days (DP-DES=76.1% vs. BP-DES=85.9%). Both stents showed few inflammation and similar degree of fibrin deposition. Conclusions The current first pathologic study on early biological responses to newer-generation DES in humans demonstrated that single-layered endothelial coverage begins in days following the stent placement, and abluminal BP-DES potentially exhibit faster strut coverage with smooth muscle cell infiltration than circumferential DP-DES. Nevertheless, vessel healing remains suboptimal at 30 days in both DP- and BP-DES, which progresses with time to become substantial at 90 days. Our results suggest that very short duration of DAPT for 1 month should be applied with caution, taking into account the trade-off between bleeding and thrombotic risks. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Grant-in-Aid for Scientific Research (C) from the Japan Society for the Promotion of Science

Samples of the carbonaceous asteroid Ryugu were brought to Earth by the Hayabusa2 spacecraft. We analyzed 17 Ryugu samples measuring 1 to 8 millimeters. Carbon dioxide–bearing water inclusions are present within a pyrrhotite crystal, indicating that Ryugu’s parent asteroid formed in the outer Solar System. The samples contain low abundances of materials that formed at high temperatures, such as chondrules and calcium- and aluminum-rich inclusions. The samples are rich in phyllosilicates and carbonates, which formed through aqueous alteration reactions at low temperature, high pH, and water/rock ratios of

EPO receptor (EPOR) expression in white adipose tissue (WAT) mediates EPO metabolic activity and mitochondrial biogenesis. Mice that lack EPOR in adipose tissue have increase fat mass accumulation, increased susceptibility to diet induced obesity and decreased WAT mitochondrial activity. Here we assess the potential for EPO to promote a metabolic response in liver, brown adipose tissue and skeletal muscle by assessing the extent of EPOR expression using the EpoR-dtTomato-Cre mouse. We quantified EPOR in liver, brown adipose tissue and soleus muscle compared with EPOR expression in subcutaneous and epididymal WAT and found the highest level in WAT by mRNA, protein and immunohistochemical analyses. Elevated EPO by intraperitoneal injection or by transgene over expression resulted in tissue specific changes in gene expression. In liver, EPO decreased expression of genes involved in gluconeogenesis and triglyceride secretion. In brown adipose tissue, EPO increased expression of thermogenic genes. In subcutaneous WAT, EPO decreased genes involved in lipogenesis. In soleus muscle, EPO decreased expression of lipolytic genes. These findings indicate that increased EPO decreases lipogenesis gene LPI, ACC1, ACC2 and Fas expression in the BAT, skeletal muscle, ScWAT, liver and eWAT and increases lipolysis gene Atgl and Hsl expression in the BAT, ScWAT, skeletal muscle, and Atgl expression in the liver and eWAT. Measurements of energy metabolism did not detect any changes associated with EPO treatment in energy expenditure, respiratory exchange ratio, locomotor activity and total activity. However, as observed in WAT, we also find that EPO promotes mitochondria activity in liver, brown adipose tissue and skeletal muscle indicated by elevated gene expression of CytC, Idh3α, Cpt1, Pgc-1α and Cox7a1. Together, these data support the hypothesis that EPO promotes lipolysis and inhibits fat synthesis to regulate body weight and fat mass. In addition, EPO may regulate glucose metabolism via inhibition of gluconeogenesis. Disclosure W. Yin: None. H. Rogers: None. P. K. Rajvanshi: None. X. An: None. M. Gassmann: None.

Endogenous Erythropoietin (EPO) provides protection against obesity and heart function. Mice with EPO receptor restricted to erythroid tissue (ΔEPORE mice) become obese, glucose intolerant and insulin resistant. In male mice at 4 months of age, after three weeks of high fat diet feeding, ΔEPORE mice showed an increase in fat mass from to 13 grams compared to fat mass in wild type mice that more than doubled from 4 to grams. EPO treatment (i.p. 3000 U/kg, 3 times/week for three weeks) during high fat diet feeding in wild type mice reduced the increase in fat mass to 3 grams and had a minimal effect on fat mass in ΔEPORE mice. The EPO stimulated increase in hematocrit was comparable in wild type and ΔEPORE mice. Using echocardiography to measure cardiac systolic function and cardiac output after high fat diet feeding, without EPO treatment ejection fraction (%) and fractional shortening (%) of left ventricular contractility were decreased in ΔEPORE mice compared with wild type mice, suggesting that endogenous EPO provided a cardioprotective effect mediated by EPO receptor expression in non-erythroid cells. EPO treatment in wild type mice decreased peak velocity and left ventricular outflow tract velocity but there were no significant changes in ΔEPORE mice, indicating that the decreases in these parameters with EPO administration are independent of EPO stimulated erythropoiesis and mediated by EPO receptor in non-erythroid cells. EPO treatment also decreased ejection fraction and fractional shortening in wild type mice and had no further significant effect in ΔEPORE mice. These data provide evidence that while endogenous EPO may be protective for heart function, high dose EPO administration during high fat diet feeding in wild type mice compromises cardiac function. EPO modulation of heart function requires EPO receptor expression beyond erythroid cells and is distinct from EPO stimulated erythropoiesis. Disclosure J.Lee: None. H.Rogers: None. C.T.Noguchi: None.

Although characteristic, Salmonella is a rare cause of osteomyelitis, especially in healthy individuals. A 25-year old primigravida at 29 weeks' gestation noticed pain and swelling in her right wrist. Her leukocyte count was normal, but her C-reactive protein level was slightly elevated, at 1.1 mg dL−1 (normal range,  mg dL−1). Plain radiography showed an osteolytic lesion in the distal radius, and magnetic resonance imaging (MRI) showed an extraosseous fluid collection with bone edema in addition to the osseous lesion. After a needle biopsy was performed, the skin overlying the lesion became ulcerated at the site of the needle tract. We drained whitish pus from the site; both this pus and the original biopsy specimen grew Salmonella on culture. We diagnosed Salmonella osteomyelitis and began intravenous antibiotic therapy, avoiding oral quinolones to prevent fetotoxicity. Her symptoms resolved, as did the bone edema and fluid collection. Ossification occurred at the site of osteolysis, with localized abnormal signal intensity persisting on MRI. This rare case of Salmonella osteomyelitis was treated without surgery; the patient's pregnancy influenced the treatment course.

Introduction Recent studies have demonstrated favourable modification of lipidic plaque materials under achieving LDL-C Purpose To clarify the frequency, clinical demographics and factors associated with residual lipid-rich plaques under LDL-C Methods The REASSURE-NIRS registry is an on-going multi-center registry to enroll CAD subjects receiving NIRS/intravascular ultrasound-guided PCI. The current analysis included 133 statin-treated stable CAD patients with on-treatment LDL-C Results In the current study, 45% (=58/128) of study subjects exhibited maxLCBI4mm ≥400 at culprit lesions under on-treatment LDL-C Conclusion Almost half of CAD subjects who achieved LDL-C level Funding Acknowledgement Type of funding sources: None.

Introduction Type 2 diabetic patients more likely exhibit a lower high-density lipoprotein (HDL) level. Given a greater glycation and oxidative stress in diabetic subjects, these atherogenic characteristics could cause dysfunctional HDL including a reduced cholesterol efflux capacity (CEC), which may account for an increased risk of diabetic macrovascular disease including acute coronary syndrome (ACS). However, it remains to be fully elucidated characteristics of HDL-mediated CEC in type 2 diabetic patients, in association with clinical presentation of coronary artery disease (CAD). Purpose To characterize CEC in CAD subjects with type 2 diabetes mellitus. Methods The current study prospectively analyzed 87 statin-naive patients with CAD. CEC was measured by using the collected apolipoprotein B-depleted serum. Liquid scintillation counting (Perkin-Elmer Analytical Sciences, MA, US) was used to quantify the efflux of radioactive cholesterol from J774 cells. Clinical characteristics and CEC were compared in diabetic and non-diabetic subjects. Results The averaged HbA1c in diabetic patients was 6.7±1.2, and 66.7% of them achieved HbA1c Conclusions A lower CEC level was observed in subjects with type 2 diabetes mellitus. In particular, this HDL functionality was profoundly diminished in those presenting ACS. Our findings suggest functionality of HDL as a potential therapeutic target in diabetic patients experiencing ACS. Funding Acknowledgement Type of funding sources: None. Table 1Figure 1

In the transitional mass range (~8–10 solar masses) between white dwarf formation and iron core-collapse supernovae, stars are expected to produce an electron-capture supernova. Theoretically, these progenitors are thought to be super-asymptotic giant branch stars with a degenerate O + Ne + Mg core, and electron capture onto Ne and Mg nuclei should initiate core collapse1–4. However, no supernovae have unequivocally been identified from an electron-capture origin, partly because of uncertainty in theoretical predictions. Here we present six indicators of electron-capture supernovae and show that supernova 2018zd is the only known supernova with strong evidence for or consistent with all six: progenitor identification, circumstellar material, chemical composition5–7, explosion energy, light curve and nucleosynthesis8–12. For supernova 2018zd, we infer a super-asymptotic giant branch progenitor based on the faint candidate in the pre-explosion images and the chemically enriched circumstellar material revealed by the early ultraviolet colours and flash spectroscopy. The light-curve morphology and nebular emission lines can be explained by the low explosion energy and neutron-rich nucleosynthesis produced in an electron-capture supernova. This identification provides insights into the complex stellar evolution, supernova physics, cosmic nucleosynthesis and remnant populations in the transitional mass range. Electron-capture supernovae are thought to come from progenitors with a narrow range of masses, and thus they are rare. Here the authors present six indicators of an electron-capture supernova origin, and find that supernova 2018zd fulfils all six criteria., Instituto de Astrofísica de La Plata, Facultad de Ciencias Astronómicas y Geofísicas

Three-dimensional thermal convection in a cubic cavity heated from one wall and chilled from its opposite wall in the terrestrial-gravity and zero-gravity fields with and without a sinusoidal modulation is investigated numerically. The gravity and its modulation are parallel to the temperature gradient. An incompressible fluid with Prandtl number Pr = 7.1 (water) is considered and hence the Boussinesq approximation is used. The gravity-modulation parameters are a vibrational Rayleigh number Raη and a non-dimentional gravity-modulation frequency ω. Here the authors report a novel ‘trident’ flow structure in laminar and steady thermal convection, which consists of a point-symmetric pair of three-pronged flows, namely, three ascending streams and three descending streams in the cube. This flow structure is stable and persistent in the sense that it is observed in all three situations: a stationary cube under the terrestrial gravity, an oscillating cube under the terrestrial gravity, and an oscillating cube under zero gravity. A POD analysis confirmed this observation. Tested parameters are Rayleigh number Ra = 8.0 × 104 in the terrestrial-gravity field without the gravity modulation or Ra = 1.0 × 104; and the gravity modulation in the terrestrial-gravity field Raη = 1.0 × 105 and ω = 5.0 in the terrestrial-gravity field and Raη = 1.1 × 105 and ω = 5.0 in the zero-gravity field.

The 3M Cavilon barrier is a no-sting film which acts as a physical barrier to protect the skin from friction and contamination.The 3M Cavilon barrier prevents erasure of surgical skin markings with removal of povidone iodine adhesive draping.

We attempt to develop the algorithm that identify the trajectory of the air strings from the image data. As a result, we reveal the behaviour of the vortex. Furthermore, we extract the air string with the longest life, and reveal its trajectory with poor regularity. In some cases, the air string tends to turn back and to attract to the pipe. But in some cases, the air string tends to move linearly and to have the trajectory that moves away from the pipe. In addition, the air string sometimes takes the trajectory that wraps around the wake along the pipe.

An important parameter of Josephson junctions (JJs) is the product of normal state resistance (R n) and critical current (I c) for designing superconductor analogue devices or digital circuits. Determination of R n and I c from voltage–current (U–I) characteristic curves often faces difficulties; in particular I c is considerably reduced by intrinsic thermal or extrinsic electrical noises. Here, we propose a standard measurement method of R n and intrinsic critical current (I ci) for high-T c superconductor (HTS) grain boundary JJs operated in liquid nitrogen and low-T c superconductor (LTS) multilayer superconductor/normal-conductor/superconductor (SNS) JJs in liquid helium. The applicable condition of this method is that both HTS and LTS JJs have U–I curves compatible with resistively-shunted junction (RSJ) model. Both R n and I ci values are extracted by combining a geometric mean criterion to select a data set and a least-squares fitting method with the RSJ model, eliminating two distortion effects on U–I curves: noise-rounding and self-heating. The combined method ensures relative standard uncertainty values of 1.9% for R n and 8% for I ci or better, when the users follow the standard protocol. It is demonstrated that the combined method is valid for d-wave HTS JJs near 77 K, regardless of peculiarities such as 0–π junction transition in d-wave superconductors at lower temperatures, and s-wave LTS SNS JJs with a wide range of junction parameters. This work is the first step to facilitate standardization for superconductor electronics with JJs.

This paper describes the kinetic and microstructural mechanism of electromigration (EM) failure found in low-profile solder joints where EM and intermetallic phase formation compete for the same volume of Sn. The low-profile solder joint used in our study was made of 20-25um thick solder situated in between a Cu pillar and a Ni coated Cu lead frame (LF). The samples were EM tested in a temperature range of 140-170oC with the current densities varying between 35-45 KA/cm2 in an oil bath to induce failure without Joule Heat induced artifacts. Our studies on EM failure kinetics and microstructural mechanism have produced two key findings. The first finding suggests that the EM diffusivity (Z*D) of diffusing species (Sn, Ni, Cu) in the solder matrix can be uniquely ranked from microstructural analysis, and it is estimated to be (Z*D) Cu> (Z*D) Sn>(Z*D) Ni. This difference in EM diffusivity causes Cu-Sn and Ni-Sn intermetallic compounds (IMC) to develop in distinctively different manners under EM, leading to different EM failure mechanisms. The second finding is that EM in low-profile solder joints consists of multiple failure stages: a) with EM-related voiding in Sn dominating at lower temperatures; while b) thermally-induced IMC growth and invasion competes with EM-induced Sn voiding at high temperatures leading to the complete failure of each joint.

The sudden decrease in stratospheric water vapor at around the year 2000 to 2001 is relatively well accepted in spite of the difficulty to quantify the long-term variations. This stepwise change is studied by examining the entry value of water to the stratosphere ([H2O]e) and some Lagrangian diagnostics of dehydration taking place in the tropical tropopause layer (TTL). The analysis is made using the backward kinematic trajectories initialized every ∼ 10 days from January 1997 to December 2002 at 400 K potential temperature surface in the tropics. The [H2O]e is estimated by the ensemble mean value of the water saturation mixing ratio (SMR) at the Lagrangian cold point (LCP) where SMR becomes minimum (SMRmin) in the TTL before reaching the 400 K surface. The drop in [H2O]e is identified to have occurred in September 2000. The horizontal projection of September trajectories, tightly trapped by anticyclonic circulation around the Tibetan high, shows eastward expansion since the year 2000. Associated changes are measured by three-dimensional bins, each having the dimension of 10° longitude by 10° latitude within the TTL. The probability distribution of LCPs shows an appreciable change exhibiting a composite pattern of two components: (i) the dipole structure consisting of the decrease over the Bay of Bengal and Malay Peninsula and the increase over the northern subtropical western Pacific and (ii) the patterns of the decrease over the equatorial western Pacific and the increase over the central Pacific that are almost symmetric with respect to the Equator. The SMRmin shows a general decrease in the tropics with some enhancement in the central Pacific. The expectation values, defined by the multiple of the probability of LCP events and the ensemble mean values of SMRmin, are calculated on each bin for both periods prior and posterior to the drop. These values are the spatial projection of [H2O]e on an individual bin. The results indicate that the drop is brought about by the decrease in water transport borne by the air parcels that have experienced the LCP over the Bay of Bengal and the western tropical Pacific. The former is related to the eastward expansion of the anticyclonic circulation around the weakened Tibetan high, while the latter would be linked to the eastward expansion of western tropical warm water to the central Pacific. This oceanic surface forcing may be responsible also for the modulation of dehydration efficiency in the successive northern winter. The drop in September 2000 and the sustained low values thereafter of [H2O]e are thus interpreted as being driven by the changes in thermal forcing from the continental and oceanic bottom boundaries.

We evaluated the surgical outcomes in 16 patients with long-standing dislocation of the temporomandibular joint (TMJ): eight men and eight women, mean (range) age 72 (21-94) years. They all had multiple underlying diseases, either dementia or a mental disorder, and the joint had been dislocated for four weeks or longer. Manual reduction had been ineffective. They were operated on after assessments by the Department of Geriatric Medicine. The procedures were successful in 14 of the 16 patients: eminectomy (n = 5), eminectomy and discectomy or condylectomy (n = 2), eminectomy, discectomy, and condylectomy (n = 3), release of the lateral pterygoid muscle (n = 3), and curettage of a fibrotic scar in the mandibular fossa (n = 1). Reduction was “easy” (n = 4), “moderately difficult” (n = 3), or “very difficult” (n = 9). Complete reduction could not be achieved for two of the “very difficult” patients. After reduction, three patients had the mandibular condyle tethered to the mandibular fossa. Operation was successful in 12 of the 16 patients. Two patients died, one of cardiopulmonary arrest, and one of chronic pulmonary insufficiency, while reduction was incomplete in two. There were no recurrences. The difficulty of reducing the joint in most of our patients suggests that detailed preoperative surgical planning is essential, patients at risk should be carefully selected, and indications for techniques to prevent recurrence should be carefully evaluated.

Myeloproliferative neoplasms (MPNs) are developing resistance to therapy by JAK1/2 inhibitor ruxolitinib. To explore the mechanism of ruxolitinib’s limited effect, we examined the JAK1/2 mediated induction of proliferation related ERK1/2 and AKT signaling by proinflammatory interleukin-6 (IL-6) in MPN granulocytes and JAK2V617F mutated human erythroleukemia (HEL) cells. We found that JAK1/2 or JAK2 inhibition prevented the IL-6 activation of STAT3 and AKT pathways in polycythemia vera and HEL cells. Further, we showed that these inhibitors also blocked the IL-6 activation of the AKT pathway in primary myelofibrosis (PMF). Only JAK1/2 inhibitor ruxolitinib largely activated ERK1/2 signaling in essential thrombocythemia and PMF (up to 4.6 fold), with a more prominent activation in JAK2V617F positive granulocytes. Regarding a cell cycle, we found that IL-6 reduction of HEL cells percentage in G2M phase was reversed by ruxolitinib (2.6 fold). Moreover, ruxolitinib potentiated apoptosis of PMF granulocytes (1.6 fold). Regarding DNA replication, we found that ruxolitinib prevented the IL-6 augmentation of MPN granulocytes frequency in the S phase of the cell cycle (up to 2.9 fold). The inflammatory stimulation induces a cross-talk between the proliferation linked pathways, where JAK1/2 inhibition is compensated by the activation of the ERK1/2 pathway during IL-6 stimulation of DNA replication.

The ALMA telescope has been producing ground-breaking science since 2011, but it is mostly based on front-end and back-end technology from the 2000s. In order to keep ALMA competitive in the coming decade, timely updates are necessary in order to further improve the science output of the telescope. In NAOJ, we have been doing research leading to technological developments which aim to increase the field-of-view of the telescope, and the RF and instantaneous bandwidth for more efficient and accurate spectral surveys. In this contribution, we will describe the most important technical achievements by our group in recent years.

著者人数: 153名（所属. 宇宙航空研究開発機構宇宙科学研究所(JAXA)(ISAS): 堂谷, 忠靖; 羽澄, 昌史; 今田, 大皓; 満田, 和久; 坂井, 真一郎; Tomida, T.; 辻本, 匡弘; Yamamoto, R.; 山崎, 典子）, Accepted: 2018-04-30, 資料番号: SA1180210000

We have developed a technique for fabrication of a field emitter array (FEA) of carbon nanotubes (CNTs) to obtain a high emission current along with a high current density. The FEA was prepared with many small equidistant circular emitters of randomly oriented multiwall carbon nanotubes. The fabrication of a FEA substrate followed with deposition of titanium nitride (TiN) film on a tantalum (Ta) substrate and circular titanium (Ti) islands on the TiN coated Ta substrate in a DC magnetron sputtering coater. CNTs were dispersed on the substrate and rooted into the circular Ti islands at a high temperature to prepare an array of circular emitters of CNTs. The TiN film was applied on a Ta substrate to make a reaction barrier between the Ta substrate and CNTs in order to root CNTs only into the Ti islands without a reaction with the Ta substrate at the high temperature. A high emission current of 31.7 mA with an effective current density of 34.5 A/cm2 was drawn at 6.5 V/μm from a FEA having 130 circular emitters in a diameter of 50 μm and with a pitch of 200 μm. The high emission current was ascribed to the good quality rooting of CNTs into the Ti islands and an edge effect, in which a high emission current was expected from the peripheries of the circular emitters.

In October 2014, the Architectural Institute of Japan established and published the Recommendation for Mix Design, Production and Construction Practice of Concrete with Recycled Concrete Aggregate. This Recommendation specifies the inspection methods for the reinforced concrete buildings that are the raw material source for recycled aggregate, the recommended recycled aggregate production methods and quality control methods, the types of recycled concrete aggregate whose use is recommended according to which part of the building and which member, as well as the recommended mix design methods, production methods, transportation methods, construction methods, and quality control methods for concrete with recycled aggregate. Further, the Appendix provides a list of all the recycled aggregates and concretes with recycled aggregate that have earned JIS certifications or ministerial certification thus far, and an overview of typical cases of the application of these aggregates and concretes to buildings.年10月，日本建築学会は「再生骨材を用いるコンクリートの設計・製造・施工指針（案）」を制定・出版した。同指針には，再生骨材の原料起源である鉄筋コンクリート造建築物の調査方法や再生骨材の製造方法・品質管理方法のあるべき姿が示されるとともに，建築物の部位・部材の条件に応じて利用が推奨される再生骨材コンクリートの種類が示されており，その調合方法，製造方法，運搬方法，施工方法，品質管理方法などが規定されている。また，付録には，これまでにJIS認証および大臣認定を取得した再生骨材および再生骨材コンクリートのリストが掲載され，それらの建築物への代表的な適用事例が概説されている。

Erythropoietin (EPO), known primarily for its erythropoietic activity, is commonly used clinically to treat anemia of chronic kidney disease. However, the expression of EPO receptor (EpoR) beyond erythroid tissue provides for potential extrahematopoietic effects of EPO, including EPO regulation of metabolic homeostasis (Zhang et al., 2014). Small clinical studies have shown that EPO treatment in patients with end-stage renal disease improved glycemic control and insulin sensitivity. Studies in animal models have shown that EPO regulation of metabolism is mainly attributed to its response in fat, and the hypothalamus-pituitary axis (Dey et al., 2016; Dey, Scullen,Noguchi, 2015; Teng, Gavrilova, et al., 2011; Wang et al., 2013) and is not dependent on its hematopoietic activity. EpoR expression in the hypothalamus is localized to the neurons expressing proopiomelanocortin (POMC) in the arcuate nucleus region, the most important site in the brain for the regulation of physiological energy expenditure. EPO treatment increases POMC production in anorexigenic POMC neurons in the hypothalamus. In the pituitary, EPO modulates the secretion of the POMC-derived peptide, adrenocorticotropic hormone (ACTH) that regulates physiological and metabolic stress response. With EPO produced by cells in the brain, such as astrocytes, and with EPO-stimulated POMC expression in the hypothalamus and EPO-inhibited ACTH secretion in the pituitary, EPO signaling contributes to the hypothalamic-pituitary axis as a major regulator of glucose metabolism and energy homeostasis.