RANDOM PERTURBATIONS OF NON-SINGULAR TRANSFORMATIONS ON [0; 1]

We consider random perturbations of non-singular measur-\ud able transformations S on [0; 1]. By using the spectral decomposition\ud theorem of Komornik and Lasota, we prove that the existence of the\ud invariant densities for random perturbations of S. Moreover the densi-\ud ties for random perturbations with small noise strongly converges to the\ud deinsity for Perron-Frobenius operator corresponding to S with respect\ud to L1([0; 1])-norm

Classification of Imbalanced Data Represented as Binary Features

Typically, classification is conducted on a dataset that consists of numerical features and target classes. For instance, a grayscale image, which is usually represented as a matrix of integers varying from 0 to 255, enables one to apply various classification algorithms to image classification tasks. However, datasets represented as binary features cannot use many standard machine learning algorithms optimally, yet their amount is not negligible. On the other hand, oversampling algorithms such as synthetic minority oversampling technique (SMOTE) and its variants are often used if the dataset for classification is imbalanced. However, since SMOTE and its variants synthesize new minority samples based on the original samples, the diversity of the samples synthesized from binary features is highly limited due to the poor representation of original features. To solve this problem, a preprocessing approach is studied. By converting binary features into numerical ones using feature extraction methods, succeeding oversampling methods can fully display their potential in improving the classifiers’ performances. Through comprehensive experiments using benchmark datasets and real medical datasets, it was observed that a converted dataset consisting of numerical features is better for oversampling methods (maximum improvements of accuracy and F1-score were 35.11% and 42.17%, respectively). In addition, it is confirmed that feature extraction and oversampling synergistically contribute to the improvement of classification performance

Structure of SARS-CoV-2 membrane protein essential for virus assembly

新型コロナウイルスのウイルス形成に必須の膜タンパク質の構造を解明. 京都大学プレスリリース. 2022-08-08.The coronavirus membrane protein (M) is the most abundant viral structural protein and plays a central role in virus assembly and morphogenesis. However, the process of M protein-driven virus assembly are largely unknown. Here, we report the cryo-electron microscopy structure of the SARS-CoV-2 M protein in two different conformations. M protein forms a mushroom-shaped dimer, composed of two transmembrane domain-swapped three-helix bundles and two intravirion domains. M protein further assembles into higher-order oligomers. A highly conserved hinge region is key for conformational changes. The M protein dimer is unexpectedly similar to SARS-CoV-2 ORF3a, a viral ion channel. Moreover, the interaction analyses of M protein with nucleocapsid protein (N) and RNA suggest that the M protein mediates the concerted recruitment of these components through the positively charged intravirion domain. Our data shed light on the M protein-driven virus assembly mechanism and provide a structural basis for therapeutic intervention targeting M protein

22367 Influence pf steel rod sizes at a connection in Sustainable building structural sysetem

研究報告書ページ(161)-(162

Time definition of reintubation most relevant to patient outcomes in critically ill patients: a multicenter cohort study

Background: Reintubation is a common complication in critically ill patients requiring mechanical ventilation. Although reintubation has been demonstrated to be associated with patient outcomes, its time definition varies widely among guidelines and in the literature. This study aimed to determine the association between reintubation and patient outcomes as well as the consequences of the time elapsed between extubation and reintubation on patient outcomes. Methods: This was a multicenter retrospective cohort study of critically ill patients conducted between April 2015 and March 2021. Adult patients who underwent mechanical ventilation and extubation in intensive care units (ICUs) were investigated utilizing the Japanese Intensive Care PAtient Database. The primary and secondary outcomes were in-hospital and ICU mortality. The association between reintubation and clinical outcomes was studied using Cox proportional hazards analysis. Among the patients who underwent reintubation, a Cox proportional hazard analysis was conducted to evaluate patient outcomes according to the number of days from extubation to reintubation. Results: Overall, 184,705 patients in 75 ICUs were screened, and 1849 patients underwent reintubation among 48,082 extubated patients. After adjustment for potential confounders, multivariable analysis revealed a significant association between reintubation and increased in-hospital and ICU mortality (adjusted hazard ratio [HR] 1.520, 95% confidence interval [CI] 1.359–1.700, and adjusted HR 1.325, 95% CI 1.076–1.633, respectively). Among the reintubated patients, 1037 (56.1%) were reintubated within 24 h after extubation, 418 (22.6%) at 24–48 h, 198 (10.7%) at 48–72 h, 111 (6.0%) at 72–96 h, and 85 (4.6%) at 96–120 h. Multivariable Cox proportional hazard analysis showed that in-hospital and ICU mortality was highest in patients reintubated at 72–96 h (adjusted HR 1.528, 95% CI 1.062–2.197, and adjusted HR 1.334, 95% CI 0.756–2.352, respectively; referenced to reintubation within 24 h). Conclusions: Reintubation was associated with a significant increase in in-hospital and ICU mortality. The highest mortality rates were observed in patients who were reintubated between 72 and 96 h after extubation. Further studies are warranted for the optimal observation of extubated patients in clinical practice and to strengthen the evidence for mechanical ventilation.Tanaka A., Shimomura Y., Uchiyama A., et al. Time definition of reintubation most relevant to patient outcomes in critically ill patients: a multicenter cohort study. Critical Care 27, 378 (2023); https://doi.org/10.1186/s13054-023-04668-3

Decreased serum pyridoxal levels in schizophrenia : meta-analysis and Mendelian randomization analysis

Background: Alterations in one-carbon metabolism have been associated with schizophrenia, and vitamin B6 is one of the key components in this pathway. Methods: We first conducted a case–control study of serum pyridoxal levels and schizophrenia in a large Japanese cohort (n = 1276). Subsequently, we conducted a meta-analysis of association studies (n = 2125). Second, we investigated whether rs4654748, which was identified in a genome-wide association study as a vitamin B6-related single nucleotide polymorphism, was genetically implicated in patients with schizophrenia in the Japanese population (n = 10 689). Finally, we assessed the effect of serum pyridoxal levels on schizophrenia risk using a Mendelian randomization (MR) approach. Results: Serum pyridoxal levels were significantly lower in patients with schizophrenia than in controls, not only in our cohort, but also in the pooled data set of the meta-analysis of association studies (standardized mean difference –0.48, 95% confidence interval [CI] –0.57 to –0.39, p = 9.8 × 10–24). We failed to find a significant association between rs4654748 and schizophrenia. Furthermore, an MR analysis failed to find a causal relationship between pyridoxal levels and schizophrenia risk (odds ratio 0.99, 95% CI 0.65–1.51, p = 0.96). Limitations: Food consumption and medications may have affected serum pyridoxal levels in our cross-sectional study. Sample size, number of instrumental variables and substantial heterogeneity among patients with schizophrenia are limitations of an MR analysis. Conclusion: We found decreased serum pyridoxal levels in patients with schizophrenia in this observational study. However, we failed to obtain data supporting a causal relationship between pyridoxal levels and schizophrenia risk using the MR approach

Treatment with buckwheat bran extract prevents the elevation of serum triglyceride levels and fatty liver in KK-Ay mice.

Buckwheat powder or protein has been shown to decrease the total serum cholesterol level in non-diabetic mice or rats. However, the lipid-lowering effect of buckwheat bran extract (BBE) in diabetic mice has not been fully elucidated. KK-Ay mice that received six-week treatment with BBE showed decreased body weight and liver weight compared to those of control (vehicle) mice. However, there was no significant difference in food intake. BBE treatments prevented liver triglyceride accumulation and decreased the serum level of triglycerides. In addition, mRNA expression levels lipogenic enzyme genes, fatty acid synthase, acetyl-coenzyme a oxidase and stearyl-coenzyme a desaturase 1, but not those of β-oxidized enzyme genes, were decreased in BBE-treated mice. Level of transcription factors ChREBP and SREBP1c, transcripts of lipogenic genes, were also decreased in BBE-treated mice. These results suggest that chronic treatment with BBE derivatives could have beneficial effects on hypertriglycemia in patients with type 2 diabetes mellitus

Lack of impact of the ALDH2 rs671 variant on breast cancer development in Japanese BRCA1/2‐mutation carriers

The aldehyde degrading function of the ALDH2 enzyme is impaired by Glu504Lys polymorphisms (rs671, termed A allele), which causes alcohol flushing in east Asians, and elevates the risk of esophageal cancer among habitual drinkers. Recent studies suggested that the ALDH2 variant may lead to higher levels of DNA damage caused by endogenously generated aldehydes. This can be a threat to genome stability and/or cell viability in a synthetic manner in DNA repair-defective settings such as Fanconi anemia (FA). FA is an inherited bone marrow failure syndrome caused by defects in any one of so far identified 22 FANC genes including hereditary breast and ovarian cancer (HBOC) genes BRCA1 and BRCA2. We have previously reported that the progression of FA phenotypes is accelerated with the ALDH2 rs671 genotype. Individuals with HBOC are heterozygously mutated in either BRCA1 or BRCA2, and the cancer-initiating cells in these patients usually undergo loss of the wild-type BRCA1/2 allele, leading to homologous recombination defects. Therefore, we hypothesized that the ALDH2 genotypes may impact breast cancer development in BRCA1/2 mutant carriers. We genotyped ALDH2 in 103 HBOC patients recruited from multiple cancer centers in Japan. However, we were not able to detect any significant differences in clinical stages, histopathological classification, or age at clinical diagnosis across the ALDH2 genotypes. Unlike the effects in hematopoietic cells of FA, our current data suggest that there is no impact of the loss of ALDH2 function in cancer initiation and development in breast epithelium of HBOC patients