Denudation Process of Crystalline Nappes in a Continental Collision Zone Constrained by Inversion of Fission‐Track Data and Thermokinematic Forward Modeling: An Example From Eastern Nepalese Himalaya

Thermochronological methods were applied to the Higher Himalayan Crystalline (HHC) nappe and the underlying Lesser Himalayan Sequences (LHS) to elucidate the denudation process for the middle- and upper-crust of eastern Nepal over millions of years. Thermochronological inverse modeling was undertaken for new results of fission-track (FT) age and FT length data of zircon and apatite in order to reconstruct the time-temperature (t-T) paths in the temperature range of 60–350°C. Eight t-T paths calculated along the across-strike section show that the cooling process of the HHC nappe in this study area is characterized by the following three aspects: (a) gradual cooling followed by rapid cooling and subsequent gradual cooling, (b) northward-younging of the timing of the rapid cooling, and (c) gradual cooling followed by <2 Myr rapid cooling in the frontmost part of the HHC nappe. The observed FT ages and t-T paths were then compared with those predicted by forwarding thermokinematic modeling. The results of the thermokinematic modeling for the “Flat-Ramp-Flat MHT model”, in which the HHC and the underlying LHS are denudated in direct proportion to the uplift of rocks transported along the Main Himalayan Thrust (MHT), reproduced the observed t-T paths and FT ages in eastern Nepal. This indicates that the observed FT ages and t-T paths reflect a denudation process driven by the movement of the MHT with a flat-ramp-flat geometry and that the denudation rate and its spatial distribution have roughly been constant in eastern Nepal since ca. 9 Ma

The Evaluation for Alterations of DOM Components from Upstream to Downstream Flow of Rivers in Toyama (Japan) Using Three-Dimensional Excitation-Emission Matrix Fluorescence Spectroscopy

The dissolved organic matter (DOM) is one of the important factors for controlling water quality. The behavior and constitutions of DOM is related to the risk of human health because it is able to directly or indirectly affect the behavior, speciation and toxicity of various environmental pollutants. However, it is not easy to know the contents of DOM components without using various complicated and time consuming analytical methods because DOM is a complex mixture and usually exists at low concentration. Here, we describe the fluorescence properties of DOM components in water samples collected from four rivers in Toyama, Japan by means of the three-dimensional excitation-emission matrix (3DEEM) fluorescence spectroscopy. In order to evaluate the alterations of DOM components in each of the river during the flow from upstream to downstream, the patterns of relative fluorescence intensity (RFI) at six peaks which are originated from fluorophores including humic-like and protein-like components were investigated. The changes in the patterns of RFI values at each of the peak and the concentration of dissolved organic carbon (DOC) for each river water sample were discussed in connection with the differences of land use managements and basic water quality parameters, such as pH, EC, turbidity, Fe3+, T-N, NO3-N, T-P, PO4-P, chlorophyll a, DOC and N/P ratio. The DOC concentrations in the water samples collected from these rivers were relatively low (0.63–1.16 mg/L). Two main peaks which have a strong RFI value expressed a positive correlation with the DOC concentration (r = 0.557, 0.535). However, the correlations between the RFI values for other four peaks and the DOC concentration were below 0.287. The alterations of DOM components during the flow of a river from upstream to downstream were investigated from the changes in the patterns of RFI values for six fluorescent peaks. It was clarified that the great increase of RFI values in peak A and peak T from river water located in urban area showed high concentration of PO4-P and Fe3+, and low N/P ratio due to the high biological activities. The values of fluorescence index (FIX) and biological index (BIX) were as high as 1.60 and 0.72, respectively

A new heterozygous compound mutation in the CTSA gene in galactosialidosis

Galactosialidosis is an autosomal recessive lysosomal storage disease caused by the combined deficiency of lysosomal β-galactosidase and neuraminidase due to a defect in the protective protein/cathepsin A. Patients present with various clinical manifestations and are classified into three types according to the age of onset: the early infantile type, the late infantile type, and the juvenile/adult type. We report a Japanese female case of juvenile/adult type galactosialidosis. Clinically, she presented with short stature, coarse facies, angiokeratoma, remarkable action myoclonus, and cerebellar ataxia. The patient was diagnosed with galactosialidosis with confirmation of impaired β-galactosidase and neuraminidase function in cultured skin fibroblasts. Sanger sequencing for CTSA identified a compound heterozygous mutation consisting of NM_00308.3(CTSA):c.746 + 3A>G and c.655-1G>A. Additional analysis of her mother’s DNA sequence indicated that the former mutation originated from her mother, and therefore the latter was estimated to be from the father or was a de novo mutation. Both mutations are considered pathogenic owing to possible splicing abnormalities. One of them (c.655-1G>A) is novel because it has never been reported previously

Minority-carrier diffusion length, minority-carrier lifetime, and photoresponsivity of β-FeSi2 layers grown by molecular-beam epitaxy

We have epitaxially grown undoped β-FeSi2 films on Si(111) substrates via atomic-hydrogen-assisted molecular-beam epitaxy. β-FeSi2 films grown without atomic hydrogen exhibited p-type conduction with a hole density of over 1019 cm−3 at room temperature (RT). In contrast, those prepared with atomic hydrogen showed n-type conduction and had a residual electron density that was more than two orders of magnitude lower than the hole density of films grown without atomic hydrogen (of the order of 1016 cm−3 at RT). The minority-carrier diffusion length was estimated to be approximately 16 μm using an electron-beam-induced current technique; this value is twice as large as that for β-FeSi2 prepared without atomic hydrogen. This result could be well explained in terms of the minority-carrier lifetimes measured by a microwave photoconductance decay technique. The 1/e decay time using a 904 nm laser pulse was approximately 17 μs, which is much longer than that for β-FeSi2 prepared without atomic hydrogen (3 μs). The photoresponsivity reached 13 mA/W at 1.31 μm, which is the highest value ever reported for β-FeSi2 films

Metalorganic chemical vapor deposition of β-FeSi2 on β-FeSi2 seed crystals formed on Si substrates

We have fabricated a β-FeSi2 film by metalorganic chemical vapor deposition on a Si(001) substrate with β-FeSi2 seed crystals grown by molecular beam epitaxy, and investigated the crystallinity, surface morphology and temperature dependence of photoresponse properties of the β-FeSi2 film. The surface of the grown β-FeSi2 film was atomically flat, and step-and-terrace structure was clearly observed. Multi-domain structure of β-FeSi2 whose average size was approximately 200 nm however was revealed. The photoresponse was obtained in an infrared light region (~ 0.95 eV) at temperatures below 200 K. The external quantum efficiency reached a maximum, being as large as 25% at 100 K when a bias voltage was 2.0 V

Long-term efficacy of intravenously administered immunoglobulin in a case of polymyositis with limited application of steroid therapy.

A 72-year-old man who had been diagnosed with polymyositis (PM) was admitted to our hospital for pneumonia with exacerbation of muscle weakness, elevation of muscle enzymes, and positive magnetic resonance imaging findings. The patient had been refractory to cyclosporine A or azathioprine and hoped to avoid administration of high-dose steroids; IV immunoglobulin (IVIG) was therefore administered after improvement of the pneumonia. Two weeks after the IVIG therapy, muscle test scores, activities of daily living, and muscle enzymes were drastically improved. Twenty months after IVIG, no relapse of PM was observed

Low magnetic field promotes recombinant human BMP-2-induced bone formation and influences orientation of trabeculae and bone marrow-derived stromal cells

Effects of high magnetic fields [MFs, ≥ 1 T (T)] on osteoblastic differentiation and the orientation of cells or matrix proteins have been reported. However, the effect of low MFs (< 1 T) on the orientation of bone formation is not well known. This study was performed to verify the effects of low MFs on osteoblastic differentiation, bone formation, and orientation of both cells and newly formed bone. An apparatus was prepared with two magnets (190 mT) aligned in parallel to generate a parallel MF. In vitro, bone marrow-derived stromal cells of rats were used to assess the effects of low MFs on cell orientation, osteoblastic differentiation, and mineralization. A bone morphogenetic protein (BMP)-2-induced ectopic bone model was used to elucidate the effect of low MFs on microstructural indices, trabecula orientation, and the apatite c-axis orientation of newly formed bone. Low MFs resulted in an increased ratio of cells oriented perpendicular to the direction of the MF and promoted osteoblastic differentiation in vitro. Moreover, in vivo analysis demonstrated that low MFs promoted bone formation and changed the orientation of trabeculae and apatite crystal in a direction perpendicular to the MF. These changes led to an increase in the mechanical strength of rhBMP-2-induced bone. These results suggest that the application of low MFs has potential to facilitate the regeneration of bone with sufficient mechanical strength by controlling the orientation of newly formed bone.Okada R., Yamato K., Kawakami M., et al. Low magnetic field promotes recombinant human BMP-2-induced bone formation and influences orientation of trabeculae and bone marrow-derived stromal cells. Bone Reports, 14, 100757. https://doi.org/10.1016/j.bonr.2021.100757

A modified application of the luciferase immunoprecipitation systems for detecting antibodies to the G protein-coupled receptors

Background:　When multipass transmembrane molecules are located on the cell surface, there may be interaction with notonly bioactive molecules but also pathogenic molecules in areas protruding outside the cell. In antibody-mediated autoimmunedisorders, it has been found that the autoantibodies occasionally attack membrane molecules on the cell surface, thus causingthe disease such as myasthenia gravis. In such cases, highly sensitive autoantibody detection technology is required for earlydiagnosis. However, autoantibody analysis technology that is specialized for membrane molecules is still under development.Here we demonstrate a novel method for detecting of antibodies against the extracellular portions of multipass transmembranemolecules.Methods:　Antibodies for muscarinic acetylcholine receptor type3 (M3R) were detected with two kinds of luciferase immunoprecipitaionsystems (LIPS), conventional LIPS (cLIPS) and its modified application, termed modified LIPS (mLIPS). In mLIPS, antibodiesagainst extracellular portions of membrane molecules could be preferentially detected.Results:　An antibody to the amino-terminal portion of human M3R was detected with modified LIPS with a high sensitivity. Incontrast, an antibody to the carboxyl-terminal portion was not detected with mLIPS, because it did not interact with intracellularportions of M3R in living cells. We also found antibodies for M3R in a patient serum with Sjogren’s syndrome.Conclusion:　Our technology has a promising future, and we hope that it will be applied in the analysis of antibodies against adiverse range of multipass transmembrane molecules, including GPCRs

Incidence and Risk Factors for Infections Requiring Hospitalization, Including Pneumocystis Pneumonia, in Japanese Patients with Rheumatoid Arthritis

Objective. Rheumatoid arthritis (RA) may be complicated by different infections, but risk factors for these are not fully elucidated. Here, we assessed the incidence of and risk factors for infections requiring hospitalization (IRH) including pneumocystis pneumonia (PCP) in patients with RA. Methods. We retrospectively surveyed all RA patients treated at our hospital from 2009 to 2013, for whom data were available on demographic features, medications, comorbidities, and severity of RA. Multivariate logistic regression analysis was applied to calculate adjusted odds ratios (ORs) for factors associated with the occurrence of IRH. Results. In a total of 9210 patient-years (2688 patients), there were 373 IRH (3.7/100 patient-years). Respiratory tract infections were most frequent (, and additionally 16 PCP), followed by urinary tract infections (). Significant factors for PCP included higher age (≥70 years; OR 3.5), male sex (6.6), underlying lung disease (3.0), use of corticosteroids (4.8), and use of biologics (5.4). Use of methotrexate (5.7) was positively associated with PCP but negatively with total infections (0.7). Additionally, functional disorders and higher RA disease activity were also related to total infections. Conclusions. Risk factors for infection should be taken into account when deciding treatment for the individual RA patient

Abnormal Liver Function in Patients with Sjogren\u27s Syndrome

We measured the liver function tests of 145 patients with Sjogren\u27s syndrome (SjS) (75 patients with primary SjS, 70 patients with secondary SjS), and characterized the SjS patients with abnormal liver function tests from several points of view : 1, the incidence of them in the primary SjS comparing with that in secondary SjS. 2, the staining pattern of anti-nuclear antibodies, and 3, the existence of antihepatitis C virus (HCV) antibody, hepatitis B surface (HBs) antigen, and antibody against human T-lymphotropic virus type I (HTLV-I). Abnormal liver function tests were detected in 38 out of 145 patients (26.2%) with SjS. Fifteen of the 38 patients (20.0%) had primary SjS while the remaining patients (32.9%) had secondary SjS. Histopathological examination identified primary biliary cirrhosis (PBC) in 2 patients, autoimmune hepatitis in 4 patients, and autoimmune cholangitis in a single patient with SjS. No significant difference in the presence of antinuclear antibody (ANA) was found between SjS patients with and without abnormal liver function tests. However, the incidence of discrete speckled pattern was significantly higher in SjS patients with abnormal liver function than in the patients with normal liver function. Two sera showing cytoplasmic pattern of ANA were also positive for anti-mitochondrial M2 antibody, allowing the diagnosis of PBC. All 11 sera exhibiting discrete speckled pattern contained significant amounts of anti-centromere antibody. Abnormal liver function tests were detected in 8 of 11 sera with these antibodies, 2 patients with PBC, 2 patients with autoimmune hepatitis, one patient with autoimmune cholangitis, one patient with chronic hepatitis B and 2 other patients with unconfirmed diagnosis. The percentages of anti-HCV antibody-positive, HBs-Agpositive and anti-HTLV-I antibody-positive in sera of patients were higher than those of blood donors from the same geographical area. However, no significant difference was seen of these percentages in sera between the patients with and without abnormal liver function. Taken together, present study indicated that SjS patients with anti-centromere antibody may have some susceptibility for acquiring autoimmune liver disease