Kant on Radical Evil

The purpose of this thesis is to propose an interpretation of Kant’s claim that the human being’s evil nature is the effect of the free power of choice. I suggest that if his concept of free choice is properly understood, Kant’s claim should be interpreted as follows: the human being’s radical evil is the effect of a failure to use freely the power of choice that determines its fundamental disposition, a failure that is to be presupposed as universal for all human agents. According to this reading, we are evil by nature since evil lies in our fundamental disposition. Still, our evil nature can be thought of as acquired, since we could constitute our fundamental disposition as morally good through freedom of choice. In the end, it turn out that for Kant, the concepts of free choice and of evil nature are closely connected

Modeling the Capacity of Left-Turn and Through Movement Considering Left-Turn Blockage and Spillback at Signalized Intersection with Short Left-Turn Bay

This research presents more realistic models for left-turn and through volume capacity by taking into account the probabilistic nature of the left-turn bay blockages and spillbacks at a signalized intersection under the leading phasing scheme with a short left-turn bay. Generally, the left-turn bay spillback situation has been overlooked in the leading left-turn signal because much attention has been given to the more common problem of left-turn blockage under the leading left signal. The left-turn spillback situation, however, might happen because the ratio of left-turning vehicle tends to be relatively high in the traffic after the occurrence of left-turn bay blockage. That is, left-turn bay blockage, spillback situations, left-turn capacity, and through capacity are closely connected with one another. Hence, this research estimates more precisely the capacity for through and left-turn movement by considering the left-turn bay blockage and spillback situations associated with left-turn bay under leading left-turn signal operations. In order to find general agreement between the results from this proposed model and a real-world situation, the developed capacity model is validated with the results from CORSIM simulations of a real-world signalized intersection. The binomial distribution is applied as the arrival distribution for through movement considering the characteristics of expected arrivals under heavy flow conditions. Finally, since left-turn bay blockage and spillback situation seem to have adverse impacts on each other, this research investigates if there are any dependent relationships between left-turn bay blockage and spillback. Here, this study confirmed that close relationships between left-turn bay blockage and spillback situations obviously exists

Peroxisome Proliferators-Activated Receptor (PPAR) Modulators and Metabolic Disorders

Overweight and obesity lead to an increased risk for metabolic disorders such as impaired glucose regulation/insulin resistance, dyslipidemia, and hypertension. Several molecular drug targets with potential to prevent or treat metabolic disorders have been revealed. Interestingly, the activation of peroxisome proliferator-activated receptor (PPAR), which belongs to the nuclear receptor superfamily, has many beneficial clinical effects. PPAR directly modulates gene expression by binding to a specific ligand. All PPAR subtypes (α, γ, and σ) are involved in glucose metabolism, lipid metabolism, and energy balance. PPAR agonists play an important role in therapeutic aspects of metabolic disorders. However, undesired effects of the existing PPAR agonists have been reported. A great deal of recent research has focused on the discovery of new PPAR modulators with more beneficial effects and more safety without producing undesired side effects. Herein, we briefly review the roles of PPAR in metabolic disorders, the effects of PPAR modulators in metabolic disorders, and the technologies with which to discover new PPAR modulators

Bacterial community analysis of sediment seep in Kagoshima Bay, Japan

1902-1906Microorganisms in the deep-sea environments such as hydrothermal vent and cold-seep regions are primary energy producers and an important community in these ecosystems. We have used 454-Pyrosequencing and 16S rDNA clone library methods to determine the diversity of bacteria in the sediment of the seep regions around the vestimentiferan tubeworm habitat at Kagoshima Bay. Taxonomic composition from both libraries suggested that 454-Pyrosequencing methods can represent more diverse groups than the conventional clone library methods. Most abundant taxa with higher folds were Proteobacteria and Bacteroidetes found in both methods. Through the 454-Pyrosequencing method, we were able to detect underrepresented taxa as well as non-detectable taxa. This analyses and comparison provide bacterial taxonomic group detection efficiency of both library types and emphasize the different uses and utilities for exploring the unknown microbial domain

A microfluidic chip for screening individual cancer cells via eavesdropping on autophagyinducing crosstalk in the stroma niche

Autophagy is a cellular homeostatic mechanism where proteins and organelles are digested and recycled to provide an alternative source of building blocks and energy to cells. The role of autophagy in cancer microenvironment is still poorly understood. Here, we present a microfluidic system allowing monitoring of the crosstalk between single cells. We used this system to study how tumor cells induced autophagy in the stromal niche. Firstly, we could confirm that transforming growth factor beta 1 (TGF beta 1) secreted from breast tumor cells is a paracrine mediator of tumor-stroma interaction leading to the activation of autophagy in the stroma component fibroblasts. Through proof of concept experiments using TGF beta 1 as a model factor, we could demonstrate real time monitoring of autophagy induction in fibroblasts by single tumor cells. Retrieval of individual tumor cells from the microfluidic system and their subsequent genomic analysis was possible, allowing us to determine the nature of the factor mediating tumor-stroma interactions. Therefore, our microfluidic platform might be used as a promising tool for quantitative investigation of tumor-stroma interactions, especially for and high-throughput screening of paracrine factors that are secreted from heterogeneous tumor cell populations

Mechanical Adaptations of Epithelial Cells on Various Protruded Convex Geometries

The shape of epithelial tissue supports physiological functions of organs such as intestinal villi and corneal epithelium. Despite the mounting evidence showing the importance of geometry in tissue microenvironments, the current understanding on how it affects biophysical behaviors of cells is still elusive. Here, we cultured cells on various protruded convex structure such as triangle, square, and circle shape fabricated using two-photon laser lithography and quantitatively analyzed individual cells. Morphological data indicates that epithelial cells can sense the sharpness of the corner by showing the characteristic cell alignments, which was caused by actin contractility. Cell area was mainly influenced by surface convexity, and Rho-activation increased cell area on circle shape. Moreover, we found that intermediate filaments, vimentin, and cytokeratin 8/18, play important roles in growth and adaptation of epithelial cells by enhancing expression level on convex structure depending on the shape. In addition, microtubule building blocks, alpha-tubulin, was also responded on geometric structure, which indicates that intermediate filaments and microtubule can cooperatively secure mechanical stability of epithelial cells on convex surface. Altogether, the current study will expand our understanding of mechanical adaptations of cells on out-of-plane geometry

The association of serum irisin with anthropometric, metabolic, and bone parameters in obese children and adolescents

BackgroundIrisin is an adipomyokine secreted by muscle and adipose cells, and it plays a role in glucose, fat, and bone metabolism. This study aimed to determine the correlation of serum irisin levels with anthropometric, metabolic, and bone parameters in obese children and adolescents.MethodsThis single-center study included 103 Korean children and adolescents: 54 (52.4%) obese participants with a body mass index (BMI) ≥95th percentile and 49 (47.6%) healthy controls with BMI within the 15th to 85th percentile. Various parameters were measured, including fasting blood glucose, fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), triglyceride and glucose (TyG) index, lipid profile, alkaline phosphatase (ALP), osteocalcin, and 25(OH)-Vitamin D levels. Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry (DEXA) in 33 healthy subjects.ResultsSerum irisin was significantly higher in the obese group than in the control group (mean 18.1 ± 3.5 vs. 16.2 ± 2.0 ng/mL; p = 0.001). Serum irisin level was positively correlated with chronological age (r = 0.28; p = 0.004), height SDS (r = 0.24; p = 0.02), BMI SDS (r = 0.37; p < 0. 001), fasting glucose (r = 0.27; p = 0.007), fasting insulin (r = 0.23; p = 0.03), HOMA-IR (r = 0.21; p = 0.04), osteocalcin (r = 0.27; p = 0.006) and negatively correlated with HDL cholesterol (r = -0.29; p = 0.005). All these correlations were evident in obese subjects but not in healthy subjects. ALP and 25(OH)-Vitamin D were unrelated to irisin levels. Among 33 healthy subjects, total body-less head (TBLH) BMD Z-score was positively correlated with serum irisin (r = 0.39; p = 0.03), osteocalcin (r = 0.40; p = 0.02), fasting insulin (r = 0.39; p = 0.04), and HOMA-IR (r = 0.38; p = 0.047).ConclusionThis study demonstrated an association between irisin levels and glucose, lipid, and bone parameters in children and adolescents. Our findings suggest that irisin has a potential role in metabolic disorders and bone health in obese children and adolescents

Factors affecting height velocity in normal prepubertal children

Purpose To analyze the effects of clinical and laboratory factors, including insulin-like growth factor (IGF) levels, on the height velocity of normal prepubertal children. Methods Ninety-five healthy prepubertal children (33 boys, 62 girls) were enrolled. The mean chronological age was 6.3±1.4 years, with a height standard deviation score (SDS) of -0.88±0.70. IGF-1, IGF binding protein-3 (IGFBP-3), SDS for anthropometric measurements, and changes in SDS for anthropometric measurements were analyzed for 1 year, and their associations with 1-year height velocity were investigated. Results The group of children with a 1-year height velocity of ≥6 cm were chronologically younger than the group with a 1-year height velocity of <6 cm (5.9±1.3 years vs. 6.7±1.3 years, P=0.004), with a lesser increase of SDS for body mass index (BMI) over 1 year (-0.18±0.68 vs. 0.13±0.53, P=0.014). There were no differences between the 2 groups in IGF-1 SDS and IGFBP-3 SDS. Multiple linear regression showed that baseline chronological age (r=0.243, P=0.026) and height SDS (r=0.236, P=0.030) were positively associated with IGF-1 SDS. Binomial logistic regression showed that an older chronologic age at referral (odds ratio [OR], 0.68; 95% confidence interval [CI], 0.47–0.99) and an increase of BMI SDS over 1 year (OR, 0.41; 95% CI, 0.18–0.89) were associated with a decreased growth possibility of an above-average height velocity (≥6 cm/yr). Conclusions Height velocity of normal prepubertal children is affected by an increase of BMI SDS and chronological age. Prepubertal IGF-1 SDS reflects height SDS at the time of measurement but is not associated with subsequent height velocity

Genomic characterization of Nocardia seriolae strains isolated from diseased fish

Members of the genus Nocardia are widespread in diverse environments; a wide range of Nocardia species are known to cause nocardiosis in several animals, including cat, dog, fish, and humans. Of the pathogenic Nocardia species, N. seriolae is known to cause disease in cultured fish, resulting in major economic loss. We isolated two N. seriolae strains, CK‐14008 and EM15050, from diseased fish and sequenced their genomes using the PacBio sequencing platform. To identify their genomic features, we compared their genomes with those of other Nocardia species. Phylogenetic analysis showed that N. seriolae shares a common ancestor with a putative human pathogenic Nocardia species. Moreover, N. seriolae strains were phylogenetically divided into four clusters according to host fish families. Through genome comparison, we observed that the putative pathogenic Nocardia strains had additional genes for iron acquisition. Dozens of antibiotic resistance genes were detected in the genomes of N. seriolae strains; most of the antibiotics were involved in the inhibition of the biosynthesis of proteins or cell walls. Our results demonstrated the virulence features and antibiotic resistance of fish pathogenic N. seriolae strains at the genomic level. These results may be useful to develop strategies for the prevention of fish nocardiosis.