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Background: Acquired idiopathic generalized anhidrosis (AIGA) leads to heat intolerance due to the loss or reduction in thermoregulatory sweating over an extensive area of the body. The pathomechanism of AIGA is still unclear but is believed to be autoimmune. Objectives: We investigated the clinical and pathological features of inflammatory AIGA (InfAIGA) and noninflammatory AIGA (non‐InfAIGA) within the skin. Methods: We compared anhidrotic and normohidrotic skin samples from 30 patients with InfAIGA and non‐InfAIGA, as well as skin samples of melanocytic nevus as a negative control. We conducted morphometric analysis and immunohistochemical analysis of cell types and expression of inflammatory molecules (TIA1, CXCR3 and MxA). MxA expression was used as a proxy for type 1 interferon activity. Results: We found that tissue samples from patients with InfAIGA exhibited inflammation within the sweat duct and atrophy of the sweat coil, whereas patients with non‐InfAIGA exhibited only atrophy of the sweat coil. Cytotoxic T lymphocyte infiltration and MxA expression were only observed in the sweat ducts of patients with InfAIGA. Conclusions: InfAIGA is associated with increased sweat duct inflammation and sweat coil atrophy, whereas non‐InfAIGA is only associated with sweat coil atrophy. These data suggest that inflammation leads to epithelial destruction of sweat ducts associated with the sweat coil atrophy and subsequent loss of function. Non‐InfAIGA may be regarded as a postinflammatory state of InfAIGA. These observations indicate the contribution of both type 1 and type 2 interferons to sweat gland injury. The mechanism involved is similar to the pathomechanism of alopecia areata (AA). [ABSTRACT FROM AUTHOR]

We present near-infrared spectroscopy of the z ≃ 3.2 quasar SDSS J1707+6443, obtained with MOIRCS on the Subaru Telescope. This quasar is classified as a "nitrogen-loud" quasar because of the fairly strong N III] and N IV] semi-forbidden emission lines from the broad-line region (BLR) observed in its rest-frame UV spectrum. However, our rest-frame optical spectrum from MOIRCS shows strong [O III] emission from the narrow-line region (NLR), suggesting that, at variance with the BLR, NLR gas is not metal-rich. To reconcile these contradictory results, there may be two alternative possibilities: (1) the strong nitrogen lines from the BLR are simply caused by a very high relative abundance of nitrogen and not by a very high BLR metallicity, or (2) the BLR metallicity is not representative of the metallicity of the host galaxy, which is better traced by the NLR. In either case, the strong broad nitrogen lines in the UV spectrum are ot indication of a chemically enriched host galaxy. We estimated the black hole mass and Eddington ratio of this quasar from the velocity width of both C iv and Hβ, which results in log (MBH/M⊙) = 9.50 and log (Lbol/LEdd) = -0.34. The relatively high Eddington ratio is consistent with our earlier result that strong nitrogen emission from BLRs is associated with high Eddington ratios. Finally, we detected significant [Ne iii] emission from the NLR, implying a quite high gas density of ne ~ 106 cm-3 and suggesting a strong coupling between quasar activity and dense interstellar clouds in the host galaxy. [ABSTRACT FROM AUTHOR]

We present near-infrared spectroscopy of the z ≈ 3.2 quasar SDSS J1707+6443, obtained with MOIRCS on the Subaru Telescope. This quasar is classified as a "nitrogen-loud" quasar because of the fairly strong N iii] and N iv] semi-forbidden emission lines from the broad-line region (BLR) observed in its rest-frame UV spectrum. However, our rest-frame optical spectrum from MOIRCS shows strong [O iii] emission from the narrow-line region (NLR), suggesting that, at variance with the BLR, NLR gas is not metal-rich. To reconcile these contradictory results, there may be two alternative possibilities: (1) the strong nitrogen lines from the BLR are simply caused by a very high relative abundance of nitrogen and not by a very high BLR metallicity, or (2) the BLR metallicity is not representative of the metallicity of the host galaxy, which is better traced by the NLR. In either case, the strong broad nitrogen lines in the UV spectrum are ot indication of a chemically enriched host galaxy. We estimated the black hole mass and Eddington ratio of this quasar from the velocity width of both C iv and Hβ, which results in log(MBH/M☉) = 9.50 and log(Lbol/LEdd) = -0.34. The relatively high Eddington ratio is consistent with our earlier result that strong nitrogen emission from BLRs is associated with high Eddington ratios. Finally, we detected significant [Ne iii] emission from the NLR, implying a quite high gas density of ne ∼ 106 cm-3 and suggesting a strong coupling between quasar activity and dense interstellar clouds in the host galaxy. [ABSTRACT FROM AUTHOR]

Abstract: Recent studies have suggested that noncoding RNA (ncRNA) molecules could play an important role in the regulatory architecture of eukaryotic cells. This new RNA-based regulation might indicate the existence of a hidden layer in the central dogma. In spite of its importance, the large-scale structure as well as the local interaction pattern of the ncRNA regulatory network has not been investigated. In this work, we collected regulatory interactions between ncRNA molecules and their regulated protein targets. We then constructed the ncRNA–protein interaction network corresponding to six model organisms, including Homo sapiens. The large-scale network analysis of ncRNA–protein interactions revealed a high degree of similarity for the degree distribution to that of the transcription regulatory network. Moreover, characterization of the local interaction structure of these networks based on motifs abundance also reveals significant similarities between ncRNA–protein and TFs–gene regulatory networks. Based on the identified motif abundance, we propose an evolutionary model that rebuilds the degree distribution and predicts the observed degree exponent. Taken together, our findings offer insights into the noncoding RNA-mediated regulation and provide knowledge about its structure and evolutionary mechanisms. [Copyright &y& Elsevier]

1. The aims were to attest whether HepG2-GS-3A4, a cell line into which the human CYP3A4 gene was introduced, can be used for a screening of chemicals that will inhibit CYP3A4 activity. 2. The capacity of the cells for metabolizing CYP3A4 substrates in vitro was evaluated. Also determined was the effect of CYP3A4 inhibitors and non-inhibitors on nifedipine hydroxylation. Western blot, immunohistochemostry and determination of β-nicotinamide adenine dinucleotide phosphate (NADPH)-reductase activity were performed. 3. HepG2-GS-3A4 selectively metabolized substrates of CYP3A4 (diazepam, nordiazepam, lidocaine, atorvastatin, and nifedipine) to a greater degree than control. The metabolites were easily detected in the culture medium. Values of Vmax of HepG2-GS-3A4 were about 30- to 100-fold higher than those of the control, while values of Km were comparable. Pre-incubation of cimetidine and ketoconazole significantly inhibited nifedipine hydroxylation, while addition of inhibitors specific to other isoforms of CYPs had no substantial effect. The HepG2-GS-3A4 expressed a higher amount of CYP3A4 protein and mRNA than control. Most NADPH reductase activity was detected in microsomal fractions. 4 In conclusion, HepG2-GS-3A4 sufficiently and selectively metabolize substrates of CYP3A4, and inhibitors of CYP3A4 reduced the metabolism. Because the metabolites were easily detected in the culture medium, this cell might be useful for the new and easy screening of new drugs for the evaluation of CYP3A4-inhibiting activity in vitro. [ABSTRACT FROM AUTHOR]

To study the relationship between antibodies detected in patients’ and/or donors’ sera and the clinical features of acute non-haemolytic transfusion reactions (ANHTRs), and to determine any gender-related difference. ANHTRs range from urticaria to transfusion-related acute lung injury (TRALI). Antibodies to human leukocyte antigen (HLA), granulocytes, platelets, and/or plasma proteins are implicated in some of the ANHTRs. A higher antibody positivity is expected for females than for males. A comparative study of ANHTRs for antibody positivity and their clinical features between females and males for both patients and donors is helpful for characterizing ANHTRs including TRALI more clearly, but such studies are few and outdated. Two hundred and twenty-three ANHTR cases reported by 45 hospitals between October 2000 and July 2005 were analysed. The patients and 196 donors of suspect blood products were screened for antibodies to HLA Class I, HLA Class II, granulocytes, and platelets. The patients were also screened for anti-plasma protein antibodies. The types and severity of ANHTR did not differ significantly between female and male patients. The frequency of the anti-HLA antibodies, but not that of the non-HLA antibodies, was significantly higher in females. Non-HLA antibodies were significantly associated with severe reactions in females. All the TRALI cases had predisposing risk factors for acute lung injury, and 60% of the cases showed anti-leucocyte antibodies. Although the anti-HLA antibodies were detected more frequently in females than males, no significant association of ANHTRs including TRALI with gender, not only for patients, but also for donors, could be shown in this study. [ABSTRACT FROM AUTHOR]

Abstract: The origin of piezoelectricity for langasite stated by a previous article has been clarified from the crystal structure under high pressure. The crystal structure of langasite with trigonal symmetry has the special empty-spaces located between A- and B-sites which are two large cation sites. The empty-space works for piezoelectricity. When a force is applied to the [100] direction, piezoelectricity was produced by the formation of polarity due to the shift of the A-cation in the [100] direction towards empty-space and deformation of the A-decahedron in the [−100] direction. In spite of the deformation of the A-site, the atomic distance between A- and B-ions is not changed due to the electrostatic repulsion. The empty-space plays a role keeping of the A–B adjacent atomic distance and decreasing the B–A atomic distance throughout the empty-space. Under high pressure, it was clarified that the linear compressibility of the a-direction including the empty-space is larger than that of the c-direction. This shows the empty-space is contributing to the piezoelectricity. Also, it was clarified that the compressibility of the bond distance between A- and B-cations is smaller than that of the bond distance between A- and B-cations over the empty-space. [Copyright &y& Elsevier]

The transcription level of amoA mRNA encoding a subunit of ammonia monooxygenase (AMO) in ammonia-oxidizing bacteria (AOB) was quantified by reverse transcription-polymerase chain reaction (RT-PCR) methods in combination with real-time PCR technology. The effects of ammonia concentration and dissolved oxygen (DO) on the transcription levels of amoA mRNA and 16S rRNA in AOB were evaluated in batch experiments with nitrifying sludge taken from a lab-scale reactor treating artificial wastewater. A batch incubation without ammonia resulted in a rapid decrease, within four hours, in the transcription level of amoA mRNA to as low as 1/10 of that at the beginning of the experiment, while the 16S rRNA level in AOB was almost constant. After subsequent incubation with 3 mM ammonia for eight hours, a small increase in the transcription level of amoA mRNA occurred, but ammonia oxidation proceeded in the interim. Copy numbers of amoA mRNA showed an almost fixed value for over eight hours in the absence of dissolved oxygen. [ABSTRACT FROM AUTHOR]

Prolonged incubation of proteins with reducing sugar produces advanced glycation end products (AGEs), which are implicated as factors for aging and diabetic complications. We previously demonstrated the presence of N(epsilon)-(carboxymethyl)lysine (CML), one of the main AGE structures, in human and animal tissues using a monoclonal anti-CML antibody (6D12). These findings suggest that CML structures present in vivo could serve as immunogens to generate autoantibodies. This suggestion was tested in the present study. First, plasma samples from diabetic rats reacted positively with AGE bovine serum albumin (BSA). These reactivities increased with the duration of diabetic states and were inhibited specifically by CML-BSA. Second, a fraction purified from plasma of diabetic patients, which bound to AGE-BSA, showed a positive reaction to CML-BSA and furthermore also to human lens proteins, which are known to undergo CML modification in vivo. Finally, patients with renal failure caused by diabetes or nondiabetic pathologies had a higher autoantibody activity against CML structure than that in normal subjects or diabetic patients without renal failure. These results indicate that CML accumulated in vivo serves as an immunological epitope to generate an autoantibody specific for CML that might be used as a potential marker for diabetic nephropathy or chronic renal failure. [ABSTRACT FROM AUTHOR]

The changes in physical properties and microbial activities were investigated during initial biofilm formation in lab-scale anaerobic fluidized bed reactors. Four different upflow velocities, i.e., 4, 7, 14 and 25 m·hr-1 were applied to four respective reactors of an equal size. The upflow velocities caused a prominent difference in the pattern of initial biofilm formation. The biofilm thickness attained eventually approximately 100 µm after 100 days of operation, independent of upflow velocity. On the contrary the biofilm density varied from 4.4 to 24.1 mg-VSS·cm-3 with an increase in the upflow velocity imposed. The activity of acetoclastic methane production increased remarkably 15 to 30 fold of seed sludge, regardless of upflow velocity. Microbial activities with respect to acetate production, H2-utilizing methanogenesis and acetate-utilizing methanogenesis increased finally up to 3-4 times as large as those of suspended grown sludge in a chemostat. [ABSTRACT FROM AUTHOR]

Recently, a shift from Au bonding wire to Cu bonding wire is expected for automotive application. Palladium coated copper (PCC) wire is strong candidate since it is widely used in LSI packages owing to its high performance and low cost. In order to apply PCC wire to automotive devices, long-term reliability specific to automobiles including stable operation under harsh environment with high temperature and humidity is required. However, pitting corrosion at the wedge bond portion was reported with PCC wire under high temperature storage life (HTSL) test. Depending on the surrounding environment such as mold compound, it is difficult for conventional PCC wire to achieve the target of automotive application. A newly developed PCC wire (EX1R) has thus developed. By using additive element in Cu core, halide induced interface corrosion and also pitting corrosion can be prevented successfully. In this paper, effect of additive element on the corrosion resistance will be discussed. The result shows that additive element forms protective passivation layer on the intermetallic compound (IMC) and Cu surface. Thereby, EX1R improves bond reliability even under severe reliability test condition. • Effects of alloying elements in copper wire material • Performance of bond reliability under high temperature environment • Enhancing Cu wire bond reliability using alloying elements [ABSTRACT FROM AUTHOR]

A magnetic levitation system that has a vibration suppressing electromagnet which use only the velocity of the levitated object for the control has been studied. The proposed system has advantages of the stable levitation of a flexible steel plate which moves with time under the fixed electromagnets. The simulation of levitated plate's response using finite element method and the magnetic levitation experiments using such a vibration suppressing magnet were carried out. The results show the vibration suppressing magnet is able to control the low frequency natural vibration effectively, and a notch filter is able to avoid the excitation of the high frequency natural vibration. [ABSTRACT FROM PUBLISHER]

Although palliative radiotherapy for gastric cancer may improve some symptoms, it may also have a negative impact due to its toxicity. We investigated whether symptoms improved after radiotherapy with adjustment for the Palliative Prognostic Index (PPI) considering that patients with limited survival tend to experience deterioration of symptoms. This study was an exploratory analysis of the Japanese Radiation Oncology Study Group study (JROSG 17-3). We assessed six symptom scores (nausea, anorexia, fatigue, shortness of breath, pain at the irradiated area and distress) at registration and 2, 4 and 8 weeks thereafter. We tested whether symptoms linearly improved after adjusting for the baseline PPI. Shared parameter models were used to adjust for potential bias in missing data. The present study analysed all 55 patients enrolled in JROSG 17-3. With time from registration as the only explanatory variable in the model, a significant linear decrease was observed in shortness of breath, pain and distress (slopes, −0.26, −0.22 and −0.19, respectively). Given that the interaction terms (i.e. PPI × time) were not significantly associated with symptom scores in any of the six symptoms, only PPI was included as the main effect in the final multivariable models. After adjusting for the PPI, shortness of breath, pain and distress significantly improved (slope, −0.25, −0.19 and −0.17; P < 0.001, 0.002 and 0.047, respectively). An improvement in fatigue and distress was observed only in patients treated with a biologically effective dose ≤14.4 Gy. Shortness of breath, pain and distress improved after radiotherapy. Moreover, a higher PPI was significantly associated with higher symptom scores at all time points, including baseline. In contrast, PPI did not seem to influence the improvement of these symptoms. Regardless of the expected survival, patients receiving radiotherapy for gastric cancer can expect an improvement in shortness of breath, pain and distress over 8 weeks. Multiple-fraction radiotherapy might hamper the improvement in fatigue and distress by its toxicity or treatment burden. • Patients receiving radiotherapy for gastric cancer can expect improvement of symptoms. • Shortness of breath, pain and distress improved after radiotherapy. • Palliative Prognostic Index did not seem to influence the improvement of symptoms. • Multiple-fraction radiotherapy might hamper the improvement in fatigue and distress. [ABSTRACT FROM AUTHOR]

Fluorescence in-situ hybridization (FISH) and DO microelectrodes were applied to biofilms developed in a novel reactor named DHS (downflow hanging sponge-cubes), to investigate the mechanisms of simultaneous carbon removal and nitrification. The DHS reactor was employed as an aerobic post-treatment process after an UASB anaerobic pre-treatment process receiving a municipal sewage. The presence ratio of Nitrosomonas and Nitrobacter cells to total cells of the DHS biomass was estimated by FISH technique to be 1.4% and 0.18%, respectively. Cell concentrations of both nitrifying bacteria were in good agreement with the magnitudes of ammonia-oxidizing and nitrite-oxidizing activities evaluated from batch tests. The habitats of both nitrifiers were the interior space of sponge-cubes, rather than within the biofilms attached onto sponge-cube surfaces. DO microelectrodes verify that the sponge-cubes insides were kept aerobically throughout the whole reactor height excluding the inlet vicinity portion. [ABSTRACT FROM AUTHOR]

To investigate the real-world data on overall survival (OS) in patients with stage III non-small cell lung cancer (NSCLC) treated with concurrent chemoradiotherapy (CCRT) with or without consolidation durvalumab, and to perform an exploratory analysis on effective radiation dose to the immune cells (EDIC). In our multi-institutional retrospective study, patients who received CCRT between July 2018 and July 2019 for stage III NSCLC in Japan were investigated. EDIC was estimated using mean lung dose, mean heart dose, body volume, body mean dose, and body weight, as reported in the secondary analysis of RTOG 0617. The cut-off value of EDIC was calculated using the maximally selected log-rank statistics. One hundred and seventy-eight patients were eligible for the analysis (136 patients, CCRT with consolidation durvalumab [CCRT+D] cohort; 42 patients, CCRT cohort). The median follow-up period was 42.5 months. Three-year OS rates were 59.8% in the overall cohort: 60.5% in the CCRT+D cohort, and 58.0% in the CCRT cohort with no significant difference (hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.45–1.27; P = 0.29). Univariate analysis showed that ECOG-PS, smoking history, histology, EGFR mutational status, gross tumor volume and EDIC were significantly associated with OS. Multivariate analysis showed that ECOG-PS 2, gross tumor volume ≥ 57 cm3 and EDIC ≥ 4.4 Gy were associated with poor OS. Among 21 EGFR-mutated patients, 3 year-OS rates were 64.7% in the CCRT+D cohort and 100% in the CCRT cohort, while 3 year-OS rates were 68.8% and 58.7% among 90 EGFR wild-type patients. Three-year OS rates were 64.6% and 47.6% for EDIC < 4.4 Gy and EDIC ≥ 4.4 Gy in the overall cohort (HR, 1.82; 95% CI, 1.14–2.90; P = 0.015). In the subgroup analysis, 66.3% vs. 44.4% in the CCRT+D cohort (HR, 2.01; 95% CI, 1.17–3.47; P = 0.016), and 59.0% vs. 56.1% in the CCRT cohort (HR, 1.20; 95% CI, 0.48–3.01; P = 0.70), respectively. Our real-world data in Japan showed that there was no significant difference in OS between the CCRT+D cohort and the CCRT cohort. High EDIC could be a risk for poor OS in patients treated with CCRT and consolidation durvalumab compared with those treated with CCRT. [ABSTRACT FROM AUTHOR]

Aurora A mitotic kinase is frequently overexpressed in various human cancers and is widely considered to be an oncoprotein. However, the cellular contexts in which Aurora A induces malignancy in vivo are still unclear. We previously reported a mouse model in which overexpression of human Aurora A in the mammary gland leads to small hyperplastic changes but not malignancy because of the induction of p53-dependent apoptosis. To study the additional factors required for Aurora A-associated tumorigenesis, we generated a new Aurora A overexpression mouse model that lacks p53. We present evidence here that Aurora A overexpression in primary mouse embryonic fibroblasts (MEFs) that lack p53 overrides postmitotic checkpoint and leads to the formation of multinucleated polyploid cells. Induction of Aurora A overexpression in the mammary glands of p53-deficient mice resulted in development of precancerous lesions that were histologically similar to atypical ductal hyperplasia in human mammary tissue and showed increased cellular senescence and p16 expression. We further observed DNA damage in p53-deficient primary MEFs after Aurora A overexpression. Our results suggest that Aurora A overexpression in mammary glands is insufficient for the development of malignant tumors in p53-deficient mice because of the induction of cellular senescence. Both p53 and p16 are critical in preventing mammary gland tumorigenesis in the Aurora A overexpression mouse model.Oncogene (2008) 27, 4305–4314; doi:10.1038/onc.2008.76; published online 31 March 2008 [ABSTRACT FROM AUTHOR]

Although palliative radiotherapy for gastric cancer may improve some symptoms, it may also have negative impact due to its toxicity. We investigated whether symptoms improved after radiotherapy with adjustment for the Palliative Prognostic Index (PPI) considering that patients with limited survival tend to experience deterioration of symptoms. This study was an exploratory analysis of a multicenter prospective observational trial (Japanese Radiation Oncology Study Group [JROSG] 17-3). We assessed six symptom scores (nausea, lack of appetite, fatigue, shortness of breath, pain at the irradiated area, and distress) based on the M. D. Anderson Symptom Inventory at registration and 2, 4, and 8 weeks thereafter. PPI prediction model contains five independent indicators: palliative performance scale, intake, edema, dyspnea at rest, and delirium. A higher PPI score means worse survival. We tested whether symptoms linearly improved after adjusting for the baseline PPI. Shared parameter models were used to account for potential bias in missing data. The present study analyzed all 55 patients enrolled in JROSG 17-3. The median age was 73 years (range, 50–93 years). The average PPI was 2.9 (95% confidence interval: 2.2–3.6). The median 20 Gy (range, 8–45 Gy) total radiation dose was delivered in a median of 5 fractions. At registration, 27 (49%), 36 (65%), 44 (80%), 38 (69%), 29 (53%) and 44 patients (80%) had nausea, lack of appetite, fatigue, shortness of breath, pain, and distress, respectively. All six symptoms were evaluable for 48 (87%), 36 (65%), and 28 (51%) patients at 2, 4, and 8 weeks, respectively. With time from registration as the only explanatory variable in the model, a significant linear decrease was observed in shortness of breath, pain, and distress (slopes, −0.26, −0.22, and −0.19, respectively). Given that the interaction terms (i.e., PPI × time) were not significantly associated with symptom scores in any of the six symptoms, only PPI was included as the main effect in the final multivariable models. After adjusting for the PPI, shortness of breath, pain, and distress significantly improved (slope, −0.25, −0.19, and −0.17; p < 0.001, 0.002, and 0.047, respectively). Higher PPI scores were associated with higher symptom scores in all six symptoms. Shortness of breath, pain, and distress significantly improved after radiotherapy. Moreover, a higher PPI was significantly associated with higher symptom scores at all time points, including baseline. In contrast, PPI did not seem to influence the improvement of these symptoms. Regardless of the expected survival, patients receiving radiotherapy for gastric cancer can expect improvement in shortness of breath, pain, and distress over 8 weeks. [ABSTRACT FROM AUTHOR]

Background Acquired idiopathic generalized anhidrosis (AIGA) is characterized by anhidrosis/hypohidrosis without other autonomic and neurological dysfunctions. Pathologically, AIGA is considered to usually present no significant morphological alterations in eccrine glands, the secretory portion which consists of clear cells, dark cells, and myoepithelial cells. AIGA patients recently have been reported to show high serum concentrations of carcinoembryonic antigen (CEA). Objective Our aim is to reveal morphological abnormalities of dark cells and investigate their relationship with serum CEA. Methods We performed comparative analysis of eccrine glands between sweat-preserved and non-sweating skin in four AIGA patients. Serum CEA concentrations in 22 cases with AIGA were measured with healthy volunteers. Furthermore, we semiquantitatively investigated dermcidin, FoxA1 and CEA expression in eccrine glands of 12 cases with AIGA and 5 cases with non-AIGA. Results Marked degranulation and shrinkage of dark cells consistently occurred in AIGA. Furthermore, high serum CEA concentrations were found in 14 of 22 AIGA patients (over 60%), but serum CEA levels were not correlated with CEA expression in eccrine glands. Dermcidin expression in dark cells apparently decreased in AIGA patients, severely in those with high serum CEA and moderately in those with low serum CEA, while well-preserved expression was found in non-AIGA subjects. Conclusion Our study suggests morphological damage and molecular dysregulation of dark cells, leading to impairment of their functions in AIGA patients. Severely damaged dark cells correspond to high serum CEA. Accordingly, these pathological changes in eccrine dark cells may be involved in anhidrosis/hypohidrosis of AIGA. [ABSTRACT FROM AUTHOR]

Purpose/objective(s): In the largest prospective study to date, we examined the effectiveness of palliative radiation therapy for bleeding gastric cancer, and the association of the biologically effective dose (BED) with survival, bleeding response, or re-bleeding.Materials/methods: We recruited patients with incurable gastric cancer for whom palliative radiation therapy was planned. Eligibility criteria included blood transfusion or hemoglobin levels < 8.0 g/dL. The primary endpoint was the intention-to-treat (ITT) response rate at four weeks. Response entailed all of the following criteria: 1) hemoglobin levels ≥ 8.0 g/dL, 2) seven consecutive days from enrollment to blood sampling without blood transfusion, and 3) no salvage treatment (surgery, endoscopic treatment, transcatheter embolization, or reirradiation) for bleeding gastric cancer. Re-bleeding was defined as the need for blood transfusion or salvage treatment. Response was assessed at 2, 4, and 8 weeks after enrollment; re-bleeding was assessed monthly during the 6-month follow-up. Sample size was designed with the probability of obtaining a 90% confidence interval (CI) ≤ ± 15% being set at 0.8, assuming a per-protocol (PP) response rate of 70% at 4 weeks.Results: We enrolled 55 patients from 15 institutions. A median total radiation dose of 20 Gy (range, 8-45 Gy) was delivered in a median of five fractions. Of the 55 patients, 38 responded to treatment; of the 38 responders, 19 (50%) died and 12 (32%) experienced re-bleeding. The ITT response rates were 47%, 53% (95% CI, 39%-66%), and 49% at 2, 4, and 8 weeks, respectively. The PP response rates were 55%, 78%, and 90% at 2, 4, and 8 weeks, respectively. Restricted mean response and re-bleeding time up to 8 months were 2.3 months and 0.8 months, respectively. The median overall survival was 3.8 months (median follow-up, 12.1 months). The multivariable Cox model showed that neither response (a time-dependent covariate) (hazard ratio [HR], 1.04; 95% CI, 0.44-2.48) nor BED (alpha/beta = 10) (HR, 0.98; 95% CI, 0.95-1.02) were significant predictors of overall survival. The multivariable Fine-Gray model showed that BED was not a significant predictor of response (subdistribution HR, 1.02; 95% CI, 0.99-1.06). The univariable Cox model on transition hazard from response to re-bleeding showed that BED was not significantly associated with re-bleeding (HR, 0.98; 95% CI, 0.92-1.04). Grade 1, 2, 3, and ≥ 4 radiation-related adverse events were reported in 11, 9, 1, and 0 patients, respectively.Conclusion: The PP bleeding response rate increased to 90% during the 8-week follow-up period. The frequent occurrence of death from shortly after enrollment lowered the ITT response rate and shortened the duration of response. BED was not significantly associated with survival, bleeding response, or re-bleeding. [ABSTRACT FROM AUTHOR]

Dysferlin is a sarcolemmal protein that is defective in Miyoshi myopathy and LGMD2B, and is involved in sarcolemmal repair. Proteomics analyses have identified multiple dysferlin-binding partners including cytoskeletal proteins. Affixin, a binding partner of dysferlin, regulates cytoskeletal actin. We reported that affixin, β- and γ-actin accumulated at the sarcolemmal injury site of wild-type mice in response to membrane rapture. α-tubulin and microtubule-associated proteins have been reported as dysferlin binding partners, however, their involvement in sarcolemmal repair remains unclear. The purpose of this study is to examine involvement of microtubule in sarcolemmal repair. To clarify molecular behavior of α-tubulin in sarcolemmal repair, GFP2-tagged human α-tubulin was expressed in mouse FDB muscle (C57BL/6J and dysferlin-deficient SJL) by electroporation. Membrane wound-repair assay of single myofiber was performed using confocal microscope equipped two-photon laser. GFP2-α-tubulin expressed in wild-type mice was localized at sarcolemma and T-tubule, and observed as a striated pattern. This striation pattern of GFP2-α-tubulin was slightly disorganized in SJL mice. After sarcolemmal injury, GFP2-α-tubulin in wild-type mice was disassembled and accumulates slower compared to GFP-β- and γ-actin. In SJL mice, GFP2-α-tubulin around the injury site was depolymerized, however, accumulation of GFP2-α-tubulin was not observed. α-Tubulin may also have a role in sarcolemmal repair. [Copyright &y& Elsevier]

The article focuses on the study on sporadic diffuse leukoencephalopathy with spheroids (SDLS). It relates the case of 56-year-old woman with forgetfulness and an inability to count and 35-year-old man with mutism. It mentions that the clinicopathological features of SDLS show no mutations in genes like colony stimulating factor 1 receptor (CSF1R), TYROBP and TREM2.

In this study, continuous operation of a pilot-scale upflow anaerobic sludge blanket (UASB) reactor for sewage treatment was conducted for 630 days to investigate the physical and microbial characteristics of the retained sludge. The UASB reactor with a working volume of 20.2 m³ was operated at ambient temperature (16-29 °C) and seeded with digested sludge. After 180 days of operation, when the sewage temperature had dropped to 20 °C or lower, the removal efficiency of both total suspended solids (TSS) and total biochemical oxygen demand (BOD) deteriorated due to washout of retained sludge. At low temperature, the cellulose concentration of the UASB sludge increased owing to the rate limitation of the hydrolytic reaction of suspended solids in the sewage. However, after an improvement in sludge retention (settleability and concentration) in the UASB reactor, the process performance stabilized and gave sufficient results (68% of TSS removal, 75% of total BOD removal) at an hydraulic retention time (HRT) of 9.7 h. The methanogenic activity of the retained sludge significantly increased after day 246 due to the accumulation of Methanosaeta and Methanobacterium following the improvement in sludge retention in the UASB reactor. Acid-forming bacteria from phylum Bacteroidetes were detected at high frequency; thus, these bacteria may have an important role in suspended solids degradation. [ABSTRACT FROM AUTHOR]

To evaluate the specific reactivity of HLA Class I antibodies (HLA-I Abs) in acute non-hemolytic transfusion reactions (ANHTRs) using solid phase assays (SPAs) and conventional complement-dependent lymphocyte cytotoxicity test (LCT). ANHTRs are major issues in transfusion medicine. Anti-leukocyte antibodies have been implicated as one of the causative agents of transfusion-related acute lung injury (TRALI) and febrile reaction. Antibodies to HLA Class I and/or Class II (HLA Abs) have been intensively studied using SPAs for TRALI, but not for febrile reaction. About 107 patients and 186 donors associated with ANHTRs were screened for HLA Abs by SPAs such as enzyme-linked immunosorbent assay (ELISA) and the Luminex method. When HLA-I Ab was detected, its specific reactivity was evaluated by comparing its specificity identified by the Luminex method using recombinant HLA molecules and cognate HLA antigens (Ags), as well as LCT with or without anti-human globulin (AHG). The incidences of HLA Abs were as high as 32·7% of patients' serum samples and 16% of donors' serum samples. The incidence of HLA-I Abs did not differ significantly between cases of febrile and allergic reactions. However, HLA-I Abs associated with febrile reaction showed a significantly higher rate of possessing specific reactivity to cognate HLA Ags than those associated with allergic reactions. In addition, the Luminex method enabled the detection of HLA-I Abs much earlier than AHG-LCT in serum samples from a patient with febrile reaction and platelet transfusion refractoriness (PTR). SPAs seem more useful than AHG-LCT for evaluating reactivity of antibodies in ANHTR cases. [ABSTRACT FROM AUTHOR]

The imaging discrimination between neurofibroma (NF) and malignant peripheral nerve sheath tumor (MPNST) is clinically very important. The purpose of this study is to define the criteria for the differential diagnosis between NF and MPNST on MRI in neurofibromatosis 1 (NF1). A total of 37 patients with NF1, 18 NFs and 19 MPNSTs were evaluated by MRI at 1.5 T. Magnetic resonance imaging (MRI) findings were compared using univariate and multivariate analyses. The MRI findings characteristic of MPNST ( p < 0.05) were an irregular tumor shape (15/19 in MPNST vs. 5/18 in NF), unclear margin (13/19 in MPNST vs. 6/18 in NF), intra-tumoral lobulation (12/19 in MPNST vs. 3/18 in NF), presence of high signal-intensity area on T1-weighted images (T1WI) (12/19 in MPNST vs. 1/18 in NF), no target sign (0/19 in MPNST vs. 12/18 in NF), inhomogeneous enhancement on contract-enhanced T1WI (17/18 in MPNST vs. 9/16 in NF) and a lower rate of enhanced area (54% in MPNST vs. 87% in NF) were critical indicators to differentiate MPNST from NF. A multivariate analysis showed that intra-tumoral lobulation and the presence of a high signal-intensity area on T1WI were considered to be diagnostic indicators of MPNST. The sensitivity and specificity for these two items were 63.2, 83.3, 63.2 and 87.5%, respectively. MRI shows features which were helpful for differentiating MPNST from NF. [ABSTRACT FROM AUTHOR]

Abstract: This paper, under the NEDO project, aims at technology development of high-quality, n-type multicrystalline Si wafers. The targets of the technology development are to realize a high minority-carrier lifetime of 1ms and to apply for a commercial solidification furnace. In particular, real-time observation of the unidirectional solidification process, the effect of quartz crucible quality on the ingots, the quality improvement of n-type Si wafers and evolution to a commercial furnace will be described. [Copyright &y& Elsevier]

In this study, a lab scale EGSB reactor was operated for 400 days to investigate the influence of temperature-decrease on the microbial characteristic of retained sludge. The EGSB reactor was started-up at 15°C seeding with 20°C-grown granular sludge. The influent COD of synthetic wastewater was set at 0.6-0.8 gCOD/L. The process-temperature was stepwise reduced from 15°C to 5°C during 400 days operation. Decrease of temperature of the reactor from 15°C to 10°C caused the decline of COD removal efficiency. However, continuous operation of the EGSB reactor led the efficient treatment of wastewater (70% of COD removal, 50% of methane recovery) at 10°C. We confirmed that the both acetate-fed and hydrogen-fed methanogenic activities of retained sludge clearly increased under 15 to 20°C. Changes of microbial profiles of methanogenic bacteria were analyzed by 16S rDNA-targeted DGGE analysis and cloning. It shows that genus Methanospirillum as hydrogen-utilizing methanogen proliferated due to low temperature operation of the reactor. On the other hand, genus Methanosaeta presented in abundance as acetoclastic-methanogen throughout the experiment. [ABSTRACT FROM AUTHOR]

We have undertaken investigations of the crystal structures and microwave dielectric properties of the Ba6−3xR8+2xTi18O54 solid solutions. The dielectric constant is affected by the volumes of cation polyhedra in which ions are located: octahedral B-site for Ti ion; rhombic A1-site mainly for R ions, deformed from cuboctahedron in perovskite structure; pentagonal A2-site for Ba ions and trigonal C-site for small ions. In the more precise crystal structure, the A1- and A2-sites separate into five and two independent positions, respectively. In this study, the configurations and coordination numbers of the cation polyhedra are presented. The dielectric constant is also discussed based on the volume of these polyhedra. [Copyright &y& Elsevier]

Abstract: Dysferlin is a sarcolemmal protein that is defective in Miyoshi myopathy and LGMD2B. In the presence of Ca2+, dysferlin accumulates around the damaged membrane site and is suggested to mediate sarcolemmal repair. We previously reported that affixin is a dysferlin-binding protein and co-localizes with dysferlin at the sarcolemma of normal human skeletal muscle. The association of dysferlin with affixin was confirmed by immunoprecipitation study using normal human skeletal muscles and COS-7 transfectants. The immunoreactivity of affixin was reduced in sarcolemma of dysferlinopathy muscles. We also reported that affixin activates Rac1 via GDP/GTP nucleotide exchange factor (GEF) and regulates the reorganization of cytoskeletal actin. The purpose of this study is to examine the effect of calcium on the association of dysferlin with affixin and to test the possibility that affixin is involved in sarcolemmal repair. The calcium-dependency of dysferlin–affixin association was examined by pull-down assay using lysates from COS-7 transfectants expressing human dysferlin and bacterially expressed affixin CH1 domain. To clarify molecular behavior of affixin in sarcolemmal repair, mCherry-tagged human affixin was expressed in FDB of mice (C57BL/6J and dysferlin-deficient A/J) by electroporation. Membrane wound-repair assay of single myofiber was performed using confocal microscope equipped two-photon laser. Pull-down assay revealed that dysferlin associates with affixin in a calcium-dependent manner. However, the association of dysferlin and caveolin-3 was not affected in different calcium concentrations. mCherry–affixin accumulates at the wounded site in C57BL/6J mice, however accumulation of affixin was not observed in A/J mice. These results suggest affixin involvement in sarcolemmal repair. We are analyzing movement of mCherry–affixin and dysferlin–GFP during sarcolemmal repair. [Copyright &y& Elsevier]

The article presents a case report about a man with a history of cluster headache, who had developed early morning hemifacial spasm. The hemifacial spasm without headache can be explained by a difference in the activation threshholds for trigeminal afferents and for facial motoneurons. The patient is diagnosed to have a subtype of the cluster headache syndrome.