Determination of the point resolution of high-resolution transmission electron microscope using the through-focus technique.

From the viewpoint of evaluating the instrumental performance of high-resolution electron microscopy (HREM), the Scherzer condition was investigated using information theory. As a result, the optimum defocus amount Δf can be expressed based on [Formula: see text] , and the formula [Formula: see text] is obtained. Furthermore, a procedure for measuring point resolution using the through-focus technique is developed, and a new method for determining the spherical aberration coefficient using the variance of Δf is introduced in the procedure.

Renal sinus fat is associated with intrarenal hemodynamic abnormalities independent of visceral fat in patients with chronic kidney disease.

OBJECTIVE: Obesity is a risk factor of chronic kidney disease (CKD), contributing to the rising incidence of cardiometabolic diseases. Renal sinus fat (RSF) is an ectopic fat depot located at the renal cavity that could impair renal function and hemodynamic through compression of renal structures. The major purpose of this study was to explore the relationship between RSF accumulation and renal dysfunction in CKD patients. METHODS: We evaluated the associations between computed tomography measured RSF volume and key clinical and histologic parameters involved in renal function and hemodynamics in 132 well-characterized CKD patients who underwent renal biopsy (median age: 62 years; 63.6% men). RESULTS: RSF volume normalized by renal volume (RSF%) positively correlated with obesity-related traits such body mass index and visceral fat volume (VFV) (all P < 0.001) whereas it negatively correlated with estimated glomerular filtration rate (eGFR) (ρ = -0.42, P < 0.001) and 24-h urinary creatinine clearance (CCr) (ρ = -0.34, P < 0.001). Notably, we found robust positive correlations between RSF% and renal resistive index (RRI) measured by the Doppler ultrasound (ρ = 0.40, P < 0.001), and the histological severity of global glomerular sclerosis (ρ = 0.48, P < 0.001) and interstitial fibrosis and tubular atrophy (IFTA) (ρ = 0.35, P < 0.001). In the multivariate linear regression models, after accounting for potential confounders including VFV, RSF% remained significantly associated with CCr (ß = -0.26, P < 0.001), RRI (ß = 0.17, P = 0.022), global glomerular sclerosis (ß = 0.21, P = 0.002), and IFTA (ß = 0.17, P = 0.012). CONCLUSION: RSF accumulation is associated with renal dysfunction and hemodynamic abnormalities independent of visceral adiposity. Our results suggest that RSF may have a potential unique role in the pathogenesis of CKD.

Combined effect of interstitial-substitutional elements on dislocation dynamics in nitrogen-added austenitic stainless steels.

Combined addition of interstitial-substitutional elements has been acknowledged to contribute to the increase in the strengths of steels. For further improvements in mechanical properties, their atomic-scale interaction mechanisms with dislocations are required to be examined. In this study, both high-resolution transmission electron microscopy and atom-probe tomography were used to correlate interstitial-substitutional elements with dislocation characteristics in austenitic stainless steels. Three types of dislocation core structures are identified and associated with their strain fields as well as N and Cr atoms in the N-added steels. It is revealed that N atoms interact elastically with the dislocations, followed by the segregation of Cr atoms via the chemical interaction between N and Cr atoms. This insight significantly improves the understanding of the multiple alloying mechanism in metallic materials such as interstitial alloys and high-entropy alloys.

Association Between Renal Sinus Fat and Cardiometabolic and Renin-Angiotensin System Parameters in Primary Aldosteronism.

Context: Renal sinus fat (RSF) accumulation is associated with cardiometabolic diseases, such as obesity, diabetes, hypertension, and chronic kidney disease. However, clinical implications of RSF in primary aldosteronism (PA) remain unclear. Objective: We aimed to investigate relationships between RSF volume and key cardiometabolic and renin-angiotensin system (RAS) parameters in PA patients and clarify the differences in these relationships between unilateral and bilateral subtypes. Methods: We analyzed data obtained from well-characterized PA patients that involved 45 unilateral (median age: 52 years; 42.2% men) and 92 bilateral patients (51 years; 42.4% men). Results: RSF volume normalized by renal volume (RSF%) was greater in the unilateral group than in the bilateral group (P < .05). RSF% was greater in men than in women (P < .05). RSF% positively correlated with parameters related to cardiometabolic risk, including age, body mass index, visceral fat volume, creatinine, triglycerides/high-density lipoprotein cholesterol ratio, uric acid, fasting glucose, and C-reactive protein regardless of PA subtypes (all P < .05). Intriguingly, RSF% positively correlated with plasma aldosterone concentration (PAC), aldosterone-to-renin ratio, and intact parathyroid hormone (iPTH) (all P < .05) in bilateral patients but did not correlate with RAS parameters and even showed an opposite trend in unilateral patients. In subgroup analyses by sex, these distinctions became more evident in women. After adjustment for potential confounders, RSF% remained positively correlated with PAC and iPTH in bilateral patients. Conclusion: Our results indicate that RSF accumulation is involved in cardiometabolic dysfunction associated with PA. However, there were distinct correlations between RSF volume and RAS parameters according to sex and PA subtypes.

Antineutrophil cytoplasmic antibody-associated vasculitis predominantly manifesting tubulointerstitial nephritis: A case report.

The common histopathology of antineutrophil cytoplasmic antibody-associated vasculitis comprises pauci-immune crescentic glomerulonephritis with concomitant tubulointerstitial nephritis. Tubulointerstitial nephritis in the absence of glomerular involvement in patients with antineutrophil cytoplasmic antibody-associated vasculitis is uncommon. We report a case of antineutrophil cytoplasmic antibody-associated vasculitis-associated acute kidney injury manifesting as tubulointerstitial nephritis without glomerulonephritis. A 75-year-old woman with fever, cough, and myalgia developed kidney dysfunction with inflammatory reactions and tubular-type proteinuria, without glomerular hematuria. A kidney biopsy revealed tubulointerstitial nephritis with arteritis. We ruled out important underlying etiologies of tubulointerstitial nephritis, including infection, drug reactions, and autoimmune diseases. Since chest high-resolution computed tomography demonstrated mild interstitial pneumonia in bilateral lower lung fields, myeloperoxidase antineutrophil cytoplasmic antibody was measured and found to be positive. Therefore, we diagnosed the patient with antineutrophil cytoplasmic antibody-associated vasculitis-associated tubulointerstitial nephritis but not glomerulonephritis, and interstitial pneumonia. The patient's kidney function and symptoms markedly improved with prednisolone treatment. Clinicians should maintain high-level vigilance for antineutrophil cytoplasmic antibody-associated vasculitis as a possible underlying component of tubulointerstitial nephritis, particularly when kidney function deteriorates with tubulointerstitial injuries without glomerular features.

Adipocyte NMNAT1 expression is essential for nuclear NAD+ biosynthesis but dispensable for regulating thermogenesis and whole-body energy metabolism.

Nicotinamide adenine dinucleotide (NAD+) functions as an essential cofactor regulating a variety of biological processes. The purpose of the present study was to determine the role of nuclear NAD+ biosynthesis, mediated by nicotinamide mononucleotide adenylyltransferase 1 (NMNAT1), in thermogenesis and whole-body energy metabolism. We first evaluated the relationship between NMNAT1 expression and thermogenic activity in brown adipose tissue (BAT), a key organ for non-shivering thermogenesis. We found that reduced BAT NMNAT1expression was associated with inactivation of thermogenic gene program induced by obesity and thermoneutrality. Next, we generated and characterized adiponectin-Cre-driven adipocyte-specific Nmnat1 knockout (ANMT1KO) mice. Loss of NMNAT1 markedly reduced nuclear NAD+ concentration by approximately 70% in BAT. Nonetheless, adipocyte-specific Nmnat1 deletion had no impact on thermogenic (rectal temperature, BAT temperature and whole-body oxygen consumption) responses to ß-adrenergic ligand norepinephrine administration and acute cold exposure, adrenergic-mediated lipolytic activity, and metabolic responses to obesogenic high-fat diet feeding. In addition, loss of NMNAT1 did not affect nuclear lysine acetylation or thermogenic gene program in BAT. These results demonstrate that adipocyte NMNAT1 expression is required for maintaining nuclear NAD+ concentration, but not for regulating BAT thermogenesis or whole-body energy homeostasis.

Three-dimensional electron tomography and recent expansion of its applications in materials science.

Electron tomography (ET) is a powerful tool for elucidating the properties and functionalities of materials. The innovative development of aberration-corrected electron microscopy in the early 21st century and the remarkable progress in the development of detectors, equipment and devices related to ET have resulted in substantial improvements in resolution. However, not only advances in hardware but also remarkable developments in reconstruction algorithms and related three-dimensional (3D) analysis methods have contributed to the resolution improvements. ET has its own problems, including the missing-wedge problem due to the limited tilt-angle range and the need to acquire numerous specimen-tilt images, the latter of which is time-consuming and can potentially damage the specimen. This review paper aims to (i) describe the established basic theories and definitions regarding 3D resolution of ET and practical 3D resolution measurement methods, (ii) discuss various reconstruction algorithms that effectively overcome the aforementioned problems and (iii) describe recent progress in the core of ET applications in materials science with respect to atomic ET, analytical ET and in-situ ET. The aforementioned ET problems have been addressed with each method developed in each field of application. Notably, in terms of aim (ii), recently developed reconstruction algorithms can reduce the number of projection images (specimen-tilt images) needed to attain a certain resolution without violating the Nyquist criterion. This approach is interpreted as a novel non-linear sampling theorem.

Development of Alveolar Hemorrhage After Pfizer-BioNTech COVID-19 mRNA Vaccination in a Patient With Renal-Limited Anti-neutrophil Cytoplasmic Antibody-Associated Vasculitis: A Case Report.

Since the coronavirus disease 2019 (COVID-19) pandemic continues and a new variant of the virus has emerged, the COVID-19 vaccination campaign has progressed. Rare but severe adverse outcomes of COVID-19 vaccination such as anaphylaxis and myocarditis have begun to be noticed. Of note, several cases of new-onset antineutrophil cytoplasmic antibody-associated vasculitis (AAV) after COVID-19 mRNA vaccination have been reported. However, relapse of AAV in remission has not been recognized enough as an adverse outcome of COVID-19 vaccination. We report, to our knowledge, a first case of renal-limited AAV in remission using every 6-month rituximab administration that relapsed with pulmonary hemorrhage, but not glomerulonephritis, following the first dose of the Pfizer-BioNTech COVID-19 vaccine. The patient received the COVID-19 vaccine more than 6 months after the last dose of rituximab according to the recommendations. However, his CD19+ B cell counts were found to be increased after admission, indicating that our case might have been prone to relapse after COVID-19 vaccination. Although our case cannot establish causality between AAV relapse and COVID-19 mRNA vaccination, a high level of clinical vigilance for relapse of AAV especially in patients undergoing rituximab maintenance therapy following COVID-19 vaccination should be maintained. Furthermore, elapsed time between rituximab administration and COVID-19 mRNA vaccination should be carefully adjusted based on AAV disease-activity.

Assessment of coastal anthropo-ecological system dynamics in response to a tsunami catastrophe of an unprecedented magnitude encountered in Japan.

On 11 March 2011, a catastrophic earthquake and subsequent tsunami hit the Pacific coast of northern Japan, devastating many of the towns, villages and coastal ecosystems located along the shoreline. To assess the impacts of the disaster, we investigated temporal dynamics of fish and epibenthic megafaunal community structure in relation to changes in a range of physical, biological and anthropogenic variables between 2007 and 2018 in Onagawa Bay. Commercially important fish such as greenlings, Japanese anchovy, flatfishes, rockfishes were consistently abundant in both larval and adult fish assemblages. While abundance, species richness, and Shannon index H' for adult fish and epibenthic megafaunal assemblages increased significantly soon after the disaster to peak values towards the end of the study period, the same metrics did not change accordingly for larval fish assemblages. Temporal dynamics of larval fish community clearly demonstrated significant seasonal variation along with changes in large-scale environmental conditions such as temperature and nutrients. However, anthropogenic components such as decline in human population, reduction in fishing pressure and the recovery of aquaculture operations significantly explained the observed post-disaster change in adult fish and epibenthic megafaunal communities. The pelagic and benthic components of Onagawa Bay appeared to have responded to the 2011 disaster very differently, and this study suggests the post-disaster recovery and dynamics of the coastal ecosystems may be regulated by how human societies respond to the impacts of a tsunami catastrophe through their influences on benthic habitat of ecosystems.

Active Extraction of Experience of Adverse Drug Reactions in Children.

OBJECTIVE: Safety information regarding the use of medication, over-the-counter drugs, and supplements for Japanese children is scarce. The aim of this study was to clarify adverse drug reaction (ADR) experiences in children and consider the method to collect ADRs efficiently. METHODS: We conducted a questionnaire survey regarding the ADR experiences of 20,412 children who were attending a preschool or kindergarten in the cities of Warabi and Toda, Saitama Prefecture, in May 2013. RESULTS: Responses were received from the guardians of 15,076 children (49.5% girls; 8.2 ± 3.5 yr). A total of 196 guardians (1.3%) responded that their children had experienced ADRs. Among them, a total of 243 suspected drugs and 284 ADRs were reported. Of the 243 suspected drugs, 2.5% were associated with a vaccine. The most frequently reported medication, reaction, and "medication-reaction pair" were antibacterials for systemic use, rash, and "antibacterials for systemic use and rash," respectively. CONCLUSIONS: In this study, we clarified that there were many potential ADRs among children, but all "medication-reaction pairs" reported were consistent with adverse events reported in the clinical trials available in the prescribing information of each medication. This study provides data respective to the frequency of these adverse events in the general pediatric population. Additional education is needed to enlighten guardians of the importance to report ADRs through the Direct Patient Reporting System.

Novel nonlinear reconstruction method with grey-level quantisation units for electron tomography.

We report a new computed tomography reconstruction method, named quantisation units reconstruction technique (QURT), applicable to electron and other fields of tomography. Conventional electron tomography methods such as filtered back projection, weighted back projection, simultaneous iterative reconstructed technique, etc. suffer from the 'missing wedge' problem due to the limited tilt-angle range. QURT demonstrates improvements to solve this problem by recovering a structural image blurred due to the missing wedge and substantially reconstructs the structure even if the number of projection images is small. QURT reconstructs a cross-section image by arranging grey-level quantisation units (QU pieces) in three-dimensional image space via unique discrete processing. Its viability is confirmed by model simulations and experimental results. An important difference from recently developed methods such as discrete algebraic reconstruction technique (DART), total variation regularisation-DART, and compressed sensing is that prior knowledge of the conditions regarding the specimen or the expected cross-section image is not necessary.

A NiRhS fuel cell catalyst - lessons from hydrogenase.

We present a novel fuel cell heterogeneous catalyst based on rhodium, nickel and sulfur with power densities 5-28% that of platinum. The NiRhS heterogeneous catalyst was developed via a homogeneous model complex of the [NiFe]hydrogenases (H2ases) and can act as both the cathode and anode of a fuel cell.

Plan-view characterization of intergranular precipitates on grain boundaries by combination of FIB lift out method and TEM analyses: A case study in austenitic stainless steel.

A new characterization method is proposed to study intergranular precipitates of polycrystalline material in the planar manner. A dual beam focused ion beam (FIB) - scanning electron microscopy (SEM) was applied to fabricate thin FIB lamella with a grain boundary parallel to the lamella to investigate for transmission electron microscopy (TEM). Distributions, microstructures and compositions of intergranular precipitates of austenitic stainless steel were then examined by TEM, scanning transmission electron microscopy (STEM), and energy dispersive X-ray spectroscopy (EDS). This plan-view microstructural characterization methods would play important roles in the case of materials where the intergranular precipitates play key roles for their physical and chemical properties.

Short-term effectiveness of biologics in patients with moderate-to-severe plaque psoriasis: A systematic review and network meta-analysis.

BACKGROUND: Complete lesion clearance is important to patients with psoriasis. OBJECTIVE: To conduct a network meta-analysis of randomized controlled trials of biologic agents available for psoriasis in Japan, using mixed-treatment comparisons. METHODS: MEDLINE and EMBASE were searched to identify randomized clinical trials (placebo-controlled or head-to-head) of infliximab, adalimumab, ustekinumab, secukinumab, ixekizumab, brodalumab, risankizumab or guselkumab in adult patients with moderate-to-severe plaque psoriasis published in English between 01 January 2000 and 31 August 2019. We assessed the proportion of patients who achieved a 100 %, 90 % and 75 % reduction in their Psoriasis Area and Severity Index (PASI) score (PASI100, PASI90 and PASI75) at 10, 12 or 16 weeks after starting biologic treatment, using contrast-based network meta-analysis methods and risk difference (RD). Probabilities of rank and surface under the cumulative ranking (SUCRA) were also estimated. RESULTS: Data were pooled from 41 trials in 19,248 patients. All biologics were significantly more effective than placebo for PASI100, PASI90 and PASI75. The RD for PASI100 for brodalumab vs ixekizumab was 0.05 (95 % Confidence intervals [CI] -0.02, 0.11), brodalumab vs risankizumab was 0.04 (95 %CI -0.03, 0.11), and risankizumab vs ixekizumab was -0.01 (95 %CI -0.08, 0.06). The SUCRA for PASI100 and PASI90 achievement was 96.8 % and 86.8 %, respectively, for brodalumab, 82.6 % and 90.3 %, respectively for risankizumab, and 78.3 %, 80.9 %, respectively, for ixekizumab. CONCLUSION: Of the biologics assessed, brodalumab, ixekizumab and risankizumab were the greatest rates of PASI90 and PASI100 achievement, and a higher probability of being most effective in the induction phase, compared with the other biologics.

Analysis of environmental and microbiological changes in Onagawa Bay immediately after the tsunami of the Great East Japan Earthquake based on sediment cores.

We investigated two sediment cores to understand whether a tsunami in Onagawa Bay, Japan caused environmental changes. The value of δ13C ranged from -21.9‰ to -24.3‰ and of δ15N ranged from 5.1 to 5.9‰. We conclude that the source of the sediment in the present study area was mainly oceanic and not terrestrial. The chlorophyll concentration ranged from 1.8 to 4.0 µg/g ww, and did not vary greatly between surface and bottom layers. We inferred that all layers were deposited after the tsunami. The major phytoplankton taxa in sediments were diatoms from DNA sequencing. The presence of harmful dinoflagellates was minor. The concentrations of several heavy metals decreased slightly after the tsunami. We inferred that heavy metals in sediments were diluted by the tsunami disturbance. The land in Onagawa suffered serious damage, but disturbance of the seabed was much less evident.

Nanoscopic Porous Iridium/Iridium Dioxide Superstructures (15†nm): Synthesis and Thermal Conversion by In†Situ Transmission Electron Microscopy.

Porous particle superstructures of about 15 nm diameter, consisting of ultrasmall nanoparticles of iridium and iridium dioxide, are prepared through the reduction of sodium hexachloridoiridate(+IV) with sodium citrate/sodium borohydride in water. The water-dispersible porous particles contain about 20 wt % poly(N-vinylpyrrolidone) (PVP), which was added for colloidal stabilization. High-resolution transmission electron microscopy confirms the presence of both iridium and iridium dioxide primary particles (1-2 nm) in each porous superstructure. The internal porosity (≈58 vol%) is demonstrated by electron tomography. In situ transmission electron microscopy up to 1000 °C under oxygen, nitrogen, argon/hydrogen (all at 1 bar), and vacuum shows that the porous particles undergo sintering and subsequent compaction upon heating, a process that starts at around 250 °C and is completed at around 800 °C. Finally, well-crystalline iridium dioxide is obtained under all four environments. The catalytic activity of the as-prepared porous superstructures in electrochemical water splitting (oxygen evolution reaction; OER) is reduced considerably upon heating owing to sintering of the pores and loss of internal surface area.

Structural and compositional study of precipitates in under-aged Cu-added Al-Mg-Si alloy.

Atomic scale characterization of fine precipitates in an under-aged Cu added Al-Mg-Si alloy was carried out by combination of atomically-resolved annular dark-field scanning transmission electron microscopy and energy dispersive X-ray spectroscopy. Two types of precipitates were observed in the alloy. In the case of ordered ß" precipitates, ß" was proposed as Mg5-xAl2+xSi4 (x ≈ 1) with solute Cu atoms replacing Al site of ß" precipitate. In the case of disordered precipitates, the precipitates were found to consist of ß" sub-unit cells, three-fold symmetric structure without Cu atoms, Cu containing structures termed as "Cu sub-unit cluster", and Q' sub-unit cells. Among these structures, the morphologies of three-fold symmetric structure without Cu atoms, Cu sub-unit cluster, and Q' sub-unit cell were almost the same, so that these structures should be the clusters of Q' phase. Since the areal density, length and diameter of precipitates were almost equal between Cu free Al-Mg-Si alloy and Cu added Al-Mg-Si alloy, the increase of hardness by Cu addition should be due to the precipitation of Cu related precipitates, such as Cu sub-unit clusters and Q' sub-unit cells.

Scalable faceted voids with luminescent enhanced edges in WS2 monolayers.

A scalable approach is needed in the formation of atomically flat edges with specific terminations to enhance local properties for optoelectronic, nanophotonic and energy applications. We demonstrate point defect clustering-driven faceted void formations with luminescent enhanced edges in WS2 monolayers during large-scale CVD growth and controlled annealing. With the aid of aberration-corrected scanning transmission electron microscopy (AC-STEM) high angle annular dark field (HAADF) imaging, we probed atomic terminations of S and W to explain observed luminescence enhancement in alternate edges. Faceted void formation in monolayer WS2 was found to be sensitive to annealing temperature, time, gas environment and precursor supply. Our observations of areal coverage evolution over time revealed competition between monolayer WS2 growth and void formation at 850 °C. While the initial stage was dominated by monolayer growth, defect generation and void growth dominated at later stages and provided an optimum processing window for monolayer WS2 as well as faceted void growth. Growth of faceted voids not only followed the geometry of monolayer facets but also showed similar atomic terminations at the edges and thus enabled local manipulation of photoluminescence enhancement with an order of magnitude increase in intensity. The developed CVD processing enabled multi-fold increase in the luminescent active edge length through the formation of faceted voids within the WS2 monolayer.