A Study on Real Time IGBT Junction Temperature Estimation Using the NTC and Calculation of Power Losses in the Automotive Inverter System.

This paper proposes a junction temperature estimation algorithm for the insulated gate bipolar transistor (IGBT) based on a power loss calculation and a thermal impedance model for inverter systems. The Simulink model was designed to calculate the power losses of power semiconductor devices and to estimate the junction temperature with a simplified thermal impedance model. This model can estimate the junction temperature up to the transient state, including the steady state. The parameters used to calculate the power losses, the thermal resistance, and the thermal capacitance were optimized for a given inverter to be tested for improving the accuracy. The simulation results and experimental measurement data were compared to verify the proposed junction temperature estimation algorithm. Finally, the algorithm was installed on the inverter controller, and the performance was verified by comparing the real time estimation result with the measured temperature.

Anti-aging treatments slow propagation of synucleinopathy by restoring lysosomal function.

Aging is the major risk factor for neurodegenerative diseases that are also associated with impaired proteostasis, resulting in abnormal accumulation of protein aggregates. However, the role of aging in development and progression of disease remains elusive. Here, we used Caenorhabditis elegans models to show that aging-promoting genetic variations accelerated the rate of cell-to-cell transmission of SNCA/α-synuclein aggregates, hallmarks of Parkinson disease, and the progression of disease phenotypes, such as nerve degeneration, behavioral deficits, and reduced life span. Genetic and pharmacological anti-aging manipulations slowed the spread of aggregates and the associated phenotypes. Lysosomal degradation was significantly impaired in aging models, while anti-aging treatments reduced the impairment. Transgenic expression of hlh-30p::hlh-30, the master controller of lysosomal biogenesis, alleviated intercellular transmission of aggregates in the aging model. Our results demonstrate that the rate of aging closely correlates with the rate of aggregate propagation and that general anti-aging treatments can slow aggregate propagation and associated disease progression by restoring lysosomal function.

Modulation of Melanogenesis by Heme Oxygenase-1 via p53 in Normal Human Melanocytes.

As a key regulator of melanogenesis, p53 controls microphthalmia-associated transcription factor (MITF) and tyrosinase expression. The anti-oxidant enzyme heme oxygenase-1 (HO-1) is induced by various forms of cellular stress and diverse oxidative stimuli. However, few studies have examined the role of HO-1 in melanogenesis. Therefore, the aim of this study was to determine the role of HO-1 in melanogenesis and the mechanism underlying this relationship. Cultures of normal human melanocytes were treated with the HO-1 inducer cobalt protoporphyrin (CoPP) or the HO-1 inhibitor zinc protoporphyrin (ZnPP). We then measured the melanin content of the cells. Additional analyses consisted of Western blotting and RT-PCR. The results showed that the cellular melanin content was increased by CoPP and decreased by ZnPP. The Western blot and RT-PCR analyses showed that CoPP increased p53, MITF and tyrosinase levels, and ZnPP reduced all of them. The knockdown of p53 by siRNA transfection was followed by large decreases in the expression levels of p53, MITF and tyrosinase at 3 h of transfection. The presence of CoPP or ZnPP had no significant increased or decreased effects on MITF and tyrosinase levels from 15 h in the siRNA transfectants. Our results suggest that HO-1 modulates melanogenesis in human melanocytes via a p53-dependent pathway.

Antimicrobial efficacy of granulysin-derived synthetic peptides in acne vulgaris.

BACKGROUND: Antimicrobial peptides are considered as a potential alternative to antibiotic treatment in acne vulgaris because the development of a resistant strain of Propionibacterium acnes is problematic. Granulysin can be regarded as an ideal substance with which to treat acne because it has antimicrobial and anti-inflammatory effects. OBJECTIVES: This study was performed to explore the effectiveness of granulysin-derived peptides (GDPs) in killing P. acnes in vitro under a standard microbiologic assay and to evaluate their potential use in a topical agent for the treatment of acne vulgaris. METHODS: Twenty different peptides based on the known sequence of a GDP were synthesized and tested in vitro for antimicrobial activity. Thirty patients with facial acne vulgaris were instructed to apply a topical formulation containing synthetic GDP to acne lesions twice per day for 12 weeks. RESULTS: A newly synthesized peptide in which aspartic acid was substituted with arginine, and methionine was substituted with cysteine, showed the highest antimicrobial activity against P. acnes. Moreover, it was effective against both Gram-positive and Gram-negative bacteria in vitro. After treatment with the topical formulation containing 50 ppm of synthetic peptide for 12 weeks, a significant reduction in the number of pustules was observed, regardless of the increase in the number of comedones. In addition, a significant reduction in the clinical grade of acne based on the Korean Acne Grading System (KAGS) was evident. CONCLUSIONS: Synthesized GDP shows strong antimicrobial activity against P. acnes in vitro. The clinical improvement observed suggests a topical formulation containing the GDP has therapeutic potential for the improvement of inflammatory-type acne vulgaris by its antimicrobial activity.

Transcriptional and post-translational regulation of Bim is essential for TGF-ß and TNF-α-induced apoptosis of gastric cancer cell.

BACKGROUND: Tumor necrosis factor-α (TNF-α) and transforming growth factor-ß (TGF-ß) are well known as central signaling molecules in natural antitumor mechanisms. However, some cancer cells are resistant to TNF-α or TGF-ß-induced death signaling. Herein, we investigated synergistic activities of TGF-ß and TNF-α and molecular mechanisms involved in apoptosis of gastric cancer cells. METHODS: SNU620, a human gastric carcinoma cell line was tested for cell viability by treatment of TGF-ß in combination with TNF-α. Cell apoptosis, proliferation, caspase activation and gene expression were tested using flow cytometry, Western blot, MTT assay, luciferase assay and real-time qRT-PCR analysis. Knockdown of target genes were performed using lentiviral shRNA system. RESULTS: TGF-ß sensitizes SNU620 cells undergoing TNF-α-induced caspase-dependent apoptosis. TNF-α and TGF-ß synergistically induced the degradation of poly(ADP-ribose) polymerase (PARP) and caspase cascade activation. We also confirmed that c-Jun NH2-terminal kinase (JNK) and Smad3 play critical roles in the apoptotic pathway. In addition, a pro-apoptotic protein Bim was critical for apoptosis and was regulated by TGF-ß and TNF-α at the transcriptional and post-translational levels. Expression of Bim was induced at the transcriptional level by Smad3 while Bim protein stability was maintained by a JNK-mediated pathway. CONCLUSION: By understanding the synergistic activation of TGF-ß and TNF-α in apoptosis, we may have a chance to identify good therapeutic approaches for the treatment of cancers that are resistant to death signals. GENERAL SIGNIFICANCE: Our results indicate that TGF-ß and TNF-α act in concert to activate apoptosis in gastric cancer cell through crosstalk between Smad and JNK signaling pathways.

Protein aggregate spreading in neurodegenerative diseases: problems and perspectives.

Progressive accumulation of specific protein aggregates is a defining feature of many major neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, fronto-temporal dementia, Huntington's disease, and Creutzfeldt-Jakob disease (CJD). Findings from several recent studies have suggested that aggregation-prone proteins, such as tau, α-synuclein, polyglutamine-containing proteins, and amyloid-ß, can spread to other cells and brain regions, a phenomenon considered unique to prion disorders, such as CJD and bovine spongiform encephalopathy. Cell-to-cell propagation of protein aggregates may be the general underlying principle for progressive deterioration of neurodegenerative diseases. This may also have significant implications in cell replacement therapies, as evidenced by the propagation of α-synuclein aggregates from host to grafted cells in long-term transplants in Parkinson's patients. Here, we review recent progress in protein aggregate propagation in experimental model systems and discuss outstanding questions and future perspectives. Understanding the mechanisms of this pathological spreading may open the way to unique opportunities for development of diagnostic techniques and novel therapies for protein misfolding-associated neurodegenerative diseases.