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Podocyte injury leading to albuminuria is a characteristic feature of diabetic nephropathy (DN). Hyperglycemia and advanced glycation end products (AGEs) are major determinants of DN. However, the underlying mechanisms of podocyte injury remain poorly understood. The cytosolic protein TNFAIP2/M-Sec is required for tunneling nanotubes (TNTs) formation, which are membrane channels that transiently connect cells, allowing organelle transfer. Podocytes express TNFAIP2 and form TNTs, but the potential relevance of the TNFAIP2-TNT system in DN is unknown. We studied TNFAIP2 expression in both human and experimental DN and the renal effect of tnfaip2 deletion in streptozotocin-induced DN. Moreover, we explored the role of the TNFAIP2-TNT system in podocytes exposed to diabetes-related insults. TNFAIP2 was overexpressed by podocytes in both human and experimental DN and exposre of podocytes to high glucose and AGEs induced the TNFAIP2-TNT system. In diabetic mice, tnfaip2 deletion exacerbated albuminuria, renal function loss, podocyte injury, and mesangial expansion. Moreover, blockade of the autophagic flux due to lysosomal dysfunction was observed in diabetes-injured podocytes both in vitro and in vivo and exacerbated by tnfaip2 deletion. TNTs allowed autophagosome and lysosome exchange between podocytes, thereby ameliorating AGE-induced lysosomal dysfunction and apoptosis. This protective effect was abolished by tnfaip2 deletion, TNT inhibition, and donor cell lysosome damage. By contrast, Tnfaip2 overexpression enhanced TNT-mediated transfer and prevented AGE-induced autophagy and lysosome dysfunction and apoptosis. In conclusion, TNFAIP2 plays an important protective role in podocytes in the context of DN by allowing TNT-mediated autophagosome and lysosome exchange and may represent a novel druggable target. Abbreviations: AGEs: advanced glycation end products; AKT1: AKT serine/threonine kinase 1; AO: acridine orange; ALs: autolysosomes; APs: autophagosomes; BM: bone marrow; BSA: bovine serum albumin; CTSD: cathepsin D; DIC: differential interference contrast; DN: diabetic nephropathy; FSGS: focal segmental glomerulosclerosis; HG: high glucose; KO: knockout; LAMP1: lysosomal-associated membrane protein 1; LMP: lysosomal membrane permeabilization; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; PI3K: phosphoinositide 3-kinase; STZ: streptozotocin; TNF: tumor necrosis factor; TNFAIP2: tumor necrosis factor, alpha-induced protein 2; TNTs: tunneling nanotubes; WT: wild type.

Recently, pretreatment with immune checkpoint inhibitors (ICIs) has been shown to enhance the therapeutic effects of the combination therapy of ramucirumab (RAM) and docetaxel (DTX); however, its influence on the drug's side effects remains unclear. This study investigated the influence of pretreatment with ICIs on the incidence of neutropenia caused by RAM + DTX therapy in patients with non-small cell lung cancer (NSCLC). Patients with NSCLC who received RAM + DTX therapy at Gifu Prefectural General Medical Center between April 2016 and December 2020 were enrolled. Retrospective data regarding age, sex, performance status and detailed treatment history, among others, at treatment initiation were collected from the patients' electronic medical records. Additionally, data on the course number of RAM + DTX therapy, supportive therapy and blood biochemical parameters, including leukocyte and neutrocyte counts, during the treatment period were collected. We identified 41 patients receiving RAM + DTX therapy. Among the more than grade 3 adverse events caused by this therapy, neutropenia was the most common (78.1%). Despite the fact that all previous risk factors influencing this incidence rate had corresponded, the only factor influencing the incidence rate of neutropenia more than grade 3 was ICI treatment history. A difference in the incidence of neutropenia more than grade 3 in the Kaplan-Meier curve was observed between patients with and without ICI pretreatment history (

Aerosols significantly affect Earth's radiation budget, thus influencing global climate. In the Arctic, sulfate aerosols are thought to have reduced the warming during the twentieth century. However, trends in past sulfate aerosols are poorly known, especially the aerosol sizes and compositions. Here, we analyze a high-resolution ice core from southeastern Greenland, comparing the seasonal deposition flux of large sulfate salt particles and small sulfur compounds, including non-neutralized sulfuric acid, between the anthropogenic sulfate maximum (1973-1975) and after sulfur emissions control (2010-2012). Between these periods, we find that the large-diameter (>0.4 mu m) flux remains roughly unchanged, yet the small-diameter (

We present continuum extrapolated results of charmonium and bottomonium correlators in the vector channel at several temperatures below and above $T_c$. The continuum extrapolation jointly performed with the interpolations to have physical values of $J/\psi$ and $\Upsilon$ masses in the confined phase is based on calculations on several large quenched isotropic lattices using clover-improved Wilson valence fermions carrying different quark masses. The extrapolated lattice correlators are confronted with perturbation theory results incorporating resummed thermal effects around the threshold from pNRQCD and vacuum asymptotics above the threshold. An additional transport peak is modelled below the threshold allowing for an estimate of the diffusion coefficients for charm and bottom quarks. We find that charmonium correlators in the vector channel can be well reproduced by perturbative spectral functions above $T_c$ where no resonance peaks for $J/\psi$ are needed at and above 1.1 $T_c$, while for bottomonium correlators a resonance peak for $\Upsilon$ is still needed up to 1.5 $T_c$. By analyzing the transport contribution to the correlators we find that the drag coefficient of a charm quark is larger than that of a bottom quark., Comment: published version

For the first time, we demonstrated 55 nm-CMOS/ spin-orbit-torque-device hybrid magnetic random-access memory (SOT-MRAM) cell with magnetic field free writing. For field free writing, we developed canted SOT device under 300 mm BEOL process full compatible with 400°C thermal tolerance. Moreover, we developed its advanced process as follows; SOT channel layer PVD process for high spin Hall angle under 400°C thermal tolerance, low damage RIE technology of MTJ for high TMR/thermal stability factor (Δ) and ultra-smooth surface metal via process under SOT channel to reduce contact resistance.By above developed technologies, our canted SOT devices fabricated under a 400°C thermal tolerance successfully achieved fast write speed of 0.35 ns without an external magnetic field, a large enough Δ of 70 for non-volatile memory (retention time is over 10 years), and a high TMR ratio of 167%, for the first time. Moreover, we successfully demonstrated field free SOT-MRAM performance.

The Hiroshima torrential rain and sediment disaster that occurred from 19 to 20 August 2014, brought a huge disaster to the private house on the alluvial cone. It was conducted a debris flow disaster focusing on this alluvial cone. In this survey, it was found that in the hornfels distribution area, there are many stones and gravels and the matrix content is small, so the alluvial cone becomes steep and the debris flow does not reach relatively far. In other words, from the viewpoint of disaster prevention and disaster prevention, it is important to think about land use while keeping in mind that the slope of the alluvial cone in the range where the debris flow in the upper part of the alluvial azimuth falls directly differs from geology. Although prediction analysis has been tried from such a disaster case, it has not yet been reflected in the design. It is desirable to predict highly accurate predictive analysis, but first of all, it was calculated by a simple calculation method as much as possible.

The development of the magnetic tunnel junctions with perpendicular easy axis using interfacial anisotropy [1–4] (p-MTJs) has been intensively advanced toward realization of high performance spin-transfer-torque magnetoresistive random access memories (STT-MRAMs). The p-MTJs used in the STT-MRAMs are required to withstand 400°C annealing to be compatible with CMOS back-end-of-line-process. Although we have demonstrated the thermal tolerance against 400°C annealing for the free layer in the CoFeB/MgO-based p-MTJs [5], we also found variation of properties in synthetic ferrimagnetic (SyF) reference layer. We revealed that the variation was caused by the diffusion of Fe in the CoFeB reference layer toward the bottom Co/Pt pinned layer after annealing [6]. We simultaneously observed degradation of perpendicular anisotropy of the Co/Pt multi layer. Perpendicular anisotropy of Co/Pt is influenced by the Co/Pt thickness ratio, buffer layer material, and roughness [7]. In this study, we focus on modification of the buffer layer and reveal that degradation can be suppressed by employing a surface modification treatment (SMT) of the Pt buffer layer. MTJ stacks from the substrate side, Ta /Pt buffer layer/with or without SMT/ [Co/Pt] 4 /Co /Ru/ [Co /Pt] 2 /Co /Ta /CoFeB /MgO barrier/free layer/top electrode, were deposited on a 300-mm $\Phi $ thermally oxidized Si wafer using a DC/RF magnetron sputtering system at room temperature (Fig.1(a)). In the SMT process, the Pt buffer layer was exposed to an ion plasma. The upper layers on the Pt buffer layer were deposited without breaking the vacuum. After deposition, samples were annealed at 350 °C for 2 h or 400 °C for 1 h in vacuum without applying magnetic field. The out-of-plane magnetic moment per unit area versus magnetic field (m-H) curves of the blanket films were measured by a vibrating sample magnetometer, and the film structures were investigated by energy dispersive x-ray spectroscopy (EDX) and high-resolution X-ray diffraction (HRXRD) using Cu Ka radiation. As shown in Fig. 1(b) and 1(c), perpendicular anisotropy of the SyF reference layer without SMT degraded after 400 °C annealing, while that of the SyF reference layer with SMT hardly changed. Interestingly, after annealing at 400 °C, magnetic moment variation in the top and bottom parts of the reference layer is observed in the stack without SMT due to Fe diffusion from the CoFeB reference layer toward the bottom Co/Pt layer, as we previously reported [6]. In contrast, the magnetic moments of the top and bottom parts of the reference layer in the stack with SMT are almost the same. This indicates that Fe diffusion in the reference layer is suppressed by the SMT of the Pt buffer layer. In order to verify this hypothesis, we performed cross-sectional EDX line analysis (Fig. 2). In the stack without SMT, Fe element in the CoFeB reference layer is observed in the other layers such as the top and bottom Co/Pt multilayers after annealing at 400 °C Fig. 2(a)), which indicates that Fe diffused toward the bottom Co/Pt layer. In contrast, in the stack with SMT, Fe element is observed only in the CoFeB layer in the as-deposited state and after annealing at 400 °C Fig. 2(b)). These results are consistent with the variation of magnetic properties shown in Fig. 1(b) and 1(c). In order to clarify the reason for the suppression of perpendicular anisotropy degradation of the Co/Pt multilayer after 400 °C annealing by SMT, we evaluated the crystal structure of the Co/Pt multilayer using HRXRD. X-ray diffraction analysis revealed that the ions penetrated the Pt buffer layer, expanding the Pt lattice constant and enhancing Co/Pt grain growth, which well oriented to the fcc (111) closed-packed plane parallel to the substrate surface. This caused larger perpendicular anisotropy in the Co/Pt multilayer and higher thermal tolerance. In addition, this may suppress Fe diffusion from the CoFeB reference layer toward the bottom Co/Pt layer. This work is supported by CIES’s Industrial Affiliation on STT MRAM program, and JST ACCEL Grant Number JPMJAC1301, Japan, and JST-OPERA.

The BL28XU beamline, dedicated to rechargeable battery analysis, is described., The newly installed BL28XU beamline at SPring-8 is dedicated to in situ structural and electronic analysis of rechargeable batteries. It supports the time range (1 ms to 100 s) and spatial range (1 µm to 1 mm) needed for battery analysis. Electrochemical apparatus for battery charging and discharging are available in experimental hutches and in a preparation room. Battery analysis can be carried out efficiently and effectively using X-ray diffraction, X-ray absorption fine-structure analysis and hard X-ray photoelectron spectroscopy. Here, the design and performance of the beamline are described, and preliminary results are presented.

A new VLSI CAD environment considering stochastic behavior of MTJ devices is proposed for the evaluation of not only the performance but also the reliability of MTJ/MOS-hybrid logic LSI. The proposed simulator allows users to support the design of MTJ/MOS-hybrid LSI by RTL/gate-level hardware description, whose simulation considering stochastic switching behavior of MTJ device can be done by analog-mixed-signal simulation with de-facto standard EDA tools. Through the design of a nonvolatile logic LSI based on a general purpose 32-bit microprocessor, the impact of the proposed design flow is demonstrated.

In order to simulate the effects of burnable poison doping on the fission fragment damage of UO2 nuclear fuels, Er2O3-doped CeO2 pellets were irradiated with 200 MeV Xe14+ ions. The irradiation effect was measured by means of X-ray diffraction (XRD). The expansion of lattice and the disordering of atomic arrangement due to the irradiation become more remarkable with increasing the concentration of the Er2O3 dopant.

In order to simulate the effects of high energy fission products on high-burnup UO 2 nuclear fuel pellets, CeO 2 thin films and bulk specimens were irradiated with 200 MeV Xe ions. Effects of the irradiation were studied by using Extended X-ray Absorption Fine Structure (EXAFS) measurement and X-ray photoelectron spectroscopy (XPS) at synchrotron radiation facilities. The EXAFS spectra for the irradiated thin films near the Ce K-edge show the formation of the oxygen deficiency around Ce ions. XPS Spectra show that the valence state of Ce atoms is changed from intrinsic Ce 4+ to Ce 3+ state by the irradiation. As such irradiation effects appear even for low fluence irradiation, the experimental result suggests that the oxygen deficiency and the change in Ce valence state are due to high-density electronic excitation induced by the 200 MeV Xe ions.

Background and Objectives Our previous study demonstrated using an oral gavage model that Porphyromonas gingivalis could induce various inflammatory changes linked to periodontitis-associated systemic diseases by altering gut microbiota. A ligature-induced periodontitis model is similar to human periodontitis in various aspects: in both cases, alveolar bone resorption depends on oral bacterial load, and gingival tissue becomes infiltrated with inflammatory cells. Therefore, this model may be suitable for the analysis of bacterial burden and gingival tissue inflammation with changes related to systemic diseases. Material and Methods Periodontal tissue destruction was induced by a 2 wk ligature placement around the bilateral maxillary second molar. We analyzed the expression profile of various genes in several tissues, levels of systemic inflammatory markers and induction of insulin resistance. In addition, we studied changes in gut microbiota composition and bacterial load in the oral cavity. Results Two weeks after ligature placement gingival inflammation was significantly induced with a disrupted gingival epithelial barrier and alveolar bone resorption accompanied by increased bacterial burden in the oral cavity. Gene expression analysis of the gingival tissue of ligated mice demonstrated that interleukin (Il)1b was significantly elevated and Il6 and Il17a tended to be higher in ligated mice than in untreated mice. Although serum IL-6 was significantly elevated and serum amyloid A tended to be higher in ligated compared to untreated mice, endotoxin levels did not differ between the two groups. Among the genes whose expressions are closely related to glucose and lipid metabolisms, only phosphoenolpyruvate carboxykinase 1 (Pck1) and acetyl-coenzyme A carboxylase alpha (Acaca) showed significant changes following ligature placement in the liver, with the former upregulated and the latter downregulated. However, insulin sensitivity did not change following ligature placement. Furthermore, ligature placement weakly affected the composition of gut microbiota and gene expression in the intestines. Conclusion The results suggest that increased oral commensals and gingival inflammation have limited roles in the pathological changes to adipose and liver tissues, which are important organs whose dysfunctions contribute to the development of periodontitis-related systemic diseases.

A headspace gas chromatography/mass spectrometry method was developed for the simultaneous determination of vinylidene chloride and 1-chlorobutane in foods packaged with polyvinylidene chloride casing films. The solid foodstuff was homogenized with an equal mass of distilled water. The homogenate was incubated for 1 h at 90 degrees C in a sealed headspace vial, and the headspace gas was then analysed by gas chromatography/mass spectrometry in selected ion-monitoring mode using a bonded porous polymer-coated capillary column. The recovery rates of vinylidene chloride and 1-chlorobutane in foodstuffs were 94.5-103.9 and 85.8-120.3%, respectively. Among 13 samples tested, vinylidene chloride was detected at 0.001-0.020 microg g(-1) in 11 foodstuffs, and 1-chlorobutane was detected at 0.004-0.040 microg g(-1) in all 13 foodstuffs. Furthermore, vinylidene chloride was detected at 0.04 microg g(-1) in one casing film, and 1-chlorobutane was detected in all casing films. The results indicate that these compounds migrated from the casing films into the foodstuffs.

Despite the semi-routine use of color Doppler sonography for evaluating portal circulation abnormalities, there is a relative paucity of detailed color Doppler findings of portal systemic (P-S) shunt through the renal vein (P-SR shunt). We reviewed the color Doppler findings of 18 patients with P-SR shunt to determine its clinical significance and appropriate scanning techniques for diagnosing accurately P-SR shunt. The splenorenal shunt was imaged as a highly tortuous vessel at the splenic hilum, which then coursed backward behind the spleen. Splenic vein flow was reversed or very slow. The gastrorenal shunt originated from the splenic vein, coursed backward, and joined the left renal vein. Flow direction in the splenic vein was always hepatopetal. The P-S shunt through the right renal vein originated from duodenal or jejunal varices, coursed posterolaterally, and joined the right renal vein at the renal hilum. Familiarity with these color Doppler findings will help increase the diagnostic confidence of P-SR shunt by color Doppler sonography.

We have fabricated the light-emitting Si-rich and oxygen-rich amorphous SiO 2 (a-SiO 2 ) films using the neutral cluster deposition (NCD) method without and with oxygen gas admitted, respectively, and demonstrate for the first time that these films show a photoluminescent feature. The Si thin films were observed by atomic force microscopy and high-resolution transmission electron microscopy, and analyzed by means of X-ray photoelectron spectroscopy, photoluminescence (PL) and FTIR-attenuated total reflection measurements. All of the PL spectra show mountainous distribution with a peak around 620 nm. It is found that the increase in the oxygen termination in the a-SiO 2 films evidently makes the PL intensity increase. It is demonstrated that NCD technique is one of the hopeful methods to fabricate light-emitting Si thin films.