15 research outputs found
Functional characterization of the neuron-restrictive silencer element in the human trytophan hydroxylase 2 gene expression
No full textTryptophan hydroxylase 2 (TPH2) is the key enzyme in the synthesis of neuronal serotonin. Although previous studies suggest that TPH2 neuron-restrictive silencer element (NRSE) functions as a negative regulator dependent on neuron-restrictive silencer factor (NRSF) activity, the underlying mechanisms are yet to be fully elucidated. Here, we show a detailed analysis of the NRSE-mediated repression of the human TPH2 (hTPH2) promoter activity in RN46A cells, a cell line derived from rat raphe neurons. Quantitative real-timeRT-PCRanalysis revealed the expression of serotonergic marker genes (Mash1, Nkx2.2, Gata2, Gata3, Lmx1b, Pet-1, 5-Htt, and Vmat2) and Nrsf gene in RN46A cells. Tph1 mRNA is the prevalent form expressed in RN46A cells; Tph2 mRNA is also expressed but at a lower level. Electrophoreticmobility shift assays and reporter assays showed that hTPH2 NRSE is necessary for the efficient DNA binding of NRSF and for the NRSF-dependent repression of the hTPH2 promoter activity. The hTPH2 promoter activity was increased by knockdown of NRSF, or over-expression of the engineered NRSF (a dominant-negative mutant or a DNA-binding domain and activation domain fusion protein). MS-275, a class I histone deacetylase (HDAC) inhibitor, was found to be more potent than MC-1568, a class II HDAC inhibitor, in enhancing the hTPH2 promoter activity. Furthermore, treatment with the ubiquitin-specific protease 7 deubiquitinase inhibitors, P-22077 or HBX 41108, increased the hTPH2 promoter activity. Collectively, our data demonstrate that the hTPH2 NRSE-mediated promoter repression viaNRSFinvolves class IHDACsand ismodulated by the ubiquitin-specific protease 7-mediated deubiquitination and stabilization of NRSF
Growth Curve Model with Bilinear Random Coefficients
No full textIn the present paper, we derive a new multivariate model to fit correlated data, representing a general model class. Our model is an extension of the Growth Curve model (also called generalized multivariate analysis of variance model) by additionally assuming randomness of regression coefficients like in linear mixed models. Each random coefficient has a linear or a bilinear form with respect to explanatory variables. In our model, the covariance matrices of the random coefficients is allowed to be singular. This yields flexible covariance structures of response data but the parameter space includes a boundary, and thus maximum likelihood estimators (MLEs) of the unknown parameters have more complicated forms than the ordinary Growth Curve model. We derive the MLEs in the proposed model by solving an optimization problem, and derive sufficient conditions for consistency of the MLEs. Through simulation studies, we confirmed performance of the MLEs when the sample size and the size of the response variable are large.</p
On model selection consistency using a kick-one-out method for selecting response variables in high-dimensional multivariate linear regression
No full textThis article deals with the selection of non redundant response variables in normality-assumed multivariate linear regression, where the redundancy of the response variables is defined by conditional expectation. A sufficient condition for model selection consistency is obtained using a kick-one-out method based on the generalized information criterion under a high-dimensional asymptotic framework such that the sample size tends to infinity and the number of response variables and explanatory variables does not exceed the sample size but may tend to infinity. A consistent kick-one-out method using the obtained condition is proposed. Simulation results show that the proposed method has a high probability of selecting true, non redundant variables
Asymptotic null and non-null distributions of test statistics for redundancy in high-dimensional canonical correlation analysis
No full text In this paper, we derive asymptotic null and non-null distributions of three test statistics, namely, the likelihood ratio criterion, the Lawley–Hotelling criterion, and the Bartlett–Nanda–Pillai criterion, for tests of redundancy in high-dimensional (HD) canonical correlation analysis. Since our setting is that the dimension of one of two observation vectors may be large but does not exceed the sample size, we use a HD asymptotic framework such that the sample size and the dimension divided by the sample size tend to [Formula: see text] and a positive constant within [0,1), respectively, for evaluating asymptotic distributions. Through simulation experiments, it is shown that our proposed HD approximations are more accurate than those under the classical asymptotic framework, i.e. only the sample size tends to [Formula: see text]. </jats:p
High-dimensional asymptotic behavior of the difference between the log-determinants of two Wishart matrices
No full textA Clinical Trial Evaluating the Efficacy of Deep Learning-Based Facial Recognition for Patient Identification in Diverse Hospital Settings
No full textBackground: Facial recognition systems utilizing deep learning techniques can improve the accuracy of facial recognition technology. However, it remains unclear whether these systems should be available for patient identification in a hospital setting. Methods: We evaluated a facial recognition system using deep learning and the built-in camera of an iPad to identify patients. We tested the system under different conditions to assess its authentication scores (AS) and determine its efficacy. Our evaluation included 100 patients in four postures: sitting, supine, and lateral positions, with and without masks, and under nighttime sleeping conditions. Results: Our results show that the unmasked certification rate of 99.7% was significantly higher than the masked rate of 90.8% (p < 0.0001). In addition, we found that the authentication rate exceeded 99% even during nighttime sleeping. Furthermore, the facial recognition system was safe and acceptable for patient identification within a hospital environment. Even for patients wearing masks, we achieved a 100% success rate for authentication regardless of illumination if they were sitting with their eyes open. Conclusions: This is the first systematical study to evaluate facial recognition among hospitalized patients under different situations. The facial recognition system using deep learning for patient identification shows promising results, proving its safety and acceptability, especially in hospital settings where accurate patient identification is crucial
Heterologous complementation systems verify the mosaic distribution of three distinct protoporphyrinogen IX oxidase in the cyanobacterial phylum
No full textThe pathways for synthesizing tetrapyrroles, including heme and chlorophyll, are well-conserved among organisms, despite the divergence of several enzymes in these pathways. Protoporphyrinogen IX oxidase (PPOX), which catalyzes the last common step of the heme and chlorophyll biosynthesis pathways, is encoded by three phylogenetically-unrelated genes, hemY, hemG and hemJ. All three types of homologues are present in the cyanobacterial phylum, showing a mosaic phylogenetic distribution. Moreover, a few cyanobacteria appear to contain two types of PPOX homologues. Among the three types of cyanobacterial PPOX homologues, only a hemJ homologue has been experimentally verified for its functionality. An objective of this study is to provide experimental evidence for the functionality of the cyanobacterial PPOX homologues by using two heterologous complementation systems. First, we introduced hemY and hemJ homologues from Gloeobacter violaceus PCC7421, hemY homologue from Trichodesmium erythraeum, and hemG homologue from Prochlorococcus marinus MIT9515 into a Delta hemG strain of E. coli. hemY homologues from G. violaceus and T. erythraeum, and the hemG homologue of P. marinus complimented the E. coli strain. Subsequently, we attempted to replace the endogenous hemJ gene of the cyanobacterium Synechocystis sp. PCC6803 with the four PPOX homologues mentioned above. Except for hemG from P. marinus, the other PPOX homologues substituted the function of hemJ in Synechocystis. These results show that all four homologues encode functional PPOX. The transformation of Synechocystis with G. violaceus hemY homologue rendered the cells sensitive to an inhibitor of the HemY-type PPOX, acifluorfen, indicating that the hemY homologue is sensitive to this inhibitor, while the wild-type G. violaceus was tolerant to it, most likely due to the presence of HemJ protein. These results provide an additional level of evidence that G. violaceus contains two types of functional PPOX
Aldo-keto reductase 1 family B7 is the gene induced in response to oxidative stress in the livers of Long-Evans Cinnamon rats
No full textThe Long-Evans Cinnamon (LEC) rat strain (Atp7b m/m), which accumulates copper in the liver due to mutations in the Atp7b gene, is a useful model for investigating the relationship between oxidative stress and hepatocarcinogenesis. To determine the effect of this mutation on oxidative stress marker genes, we performed oligonucleotide array analysis (Affymetrix), and compared the results in Atp7b m/m rats with those of a sibling line with the Atp7b w/w genotype. We focused our studies on the expression of the aldo-keto reductase I family B7 (AKR1B7)-like protein gene, since this gene codes for reductase enzymes involved in the detoxification of oxidizing compounds (e.g., aldehydes) and was differentially expressed in Atp7b m/m and Atp7b w/w rat liver. Akr1B7 mRNA expression was significantly increased in comparison with the expression of 4 other known oxidative stress responsive genes, haem-oxygenase-1 (HO-1), thioredoxin (Trx), aldehyde reductase (AKR1A1), and glucose-6-phosphate dehydrogenase (G6PDH). By searching binding motifs, five nuclear factor kappa B (NF-KB) binding sites were located in the 5'-upstream region of the Akr1b7 gene. Transient co-transfection with both I-kBa and the Akr1b7 6 kb promoter (p6.0-AKR-Luc) inhibited luciferase activity of p6.0-AKR-Luc in HepG2 cells. Cuprous ion however did not affect the transcription activity induced by p6.0-AKR-Luc. Gel-shift assay showed that the DNA binding activity of NF-KB increased in the livers of LEC rats, suggesting that the oxidative stress is mediated through NF-KB. The results indicate conclusively that in LEC rat liver, Akr1b7 might be up-regulated by oxidative stress mediated through NF-KB, but not that mediated directly by copper.OncologySCI(E)13ARTICLE4829-8382
Comparison of clinical outcomes of polyetheretherketone and hybrid resin crowns placed on molars for over two years
No full textAbstract This study aimed to compare the 2-year clinical outcomes of polyetheretherketone (PEEK) and hybrid resin crowns placed on molars. Patients who received PEEK (P-Cr) and hybrid resin (H-Cr) crowns at Hiroshima University Hospital between 2016 and 2021 were evaluated in 2024 for crown conditions, including loss, fractures, and occlusal wear. No cases of crown debonding or fracture were observed in the P-Cr group. In contrast, the H-Cr group had 10 cases of loss and 4 cases of fractures. The P-Cr group demonstrated significantly fewer cases of crown debonding than the H-Cr group. Occlusal wear was observed in most crowns in the P-Cr group. Compared to the hybrid resin crowns, the PEEK crowns had a lower risk of fracture and debonding and retained long-term functionality; however, surface roughness and color changes were observed, suggesting that they may not be ideal for patients with particularly high esthetic demands. Nevertheless, physiological occlusal relationships and functionality were preserved, indicating that PEEK crowns could be a viable option for restoring molar defects
