Development of a Reporter System for In Vivo Monitoring of gamma-Secretase Activity in Drosophila

The gamma-secretase complex represents an evolutionarily conserved family of transmembrane aspartyl proteases that cleave numerous type-I membrane proteins, including the beta-amyloid precursor protein (APP) and the receptor Notch. All known rare mutations in APP and the gamma-secretase catalytic component, presenilin, which lead to increased amyloid betapeptide production, are responsible for early-onset familial Alzheimer\u27s disease. beta-amyloid protein precursor-like (APPL) is the Drosophila ortholog of human APP. Here, we created Notch- and APPL-based Drosophila reporter systems for in vivo monitoring of gamma-secretase activity. Ectopic expression of the Notch- and APPL-based chimeric reporters in wings results in vein truncation phenotypes. Reporter-mediated vein truncation phenotypes are enhanced by the Notch gain-of-function allele and suppressed by RNAi-mediated knockdown of presenilin. Furthermore, we find that apoptosis partly contributes to the vein truncation phenotypes of the APPL-based reporter, but not to the vein truncation phenotypes of the Notch-based reporter. Taken together, these results suggest that both in vivo reporter systems provide a powerful genetic tool to identify genes that modulate gamma-secretase activity and/or APPL metabolism

Competition between B-Z and B-L transitions in a single DNA molecule: Computational studies

Under negative torsion, DNA adopts left-handed helical forms, such as Z-DNA and L-DNA. Using the random copolymer model developed for a wormlike chain, we represent a single DNA molecule with structural heterogeneity as a helical chain consisting of monomers which can be characterized by different helical senses and pitches. By Monte Carlo simulation, where we take into account bending and twist fluctuations explicitly, we study sequence dependence of B-Z transitions under torsional stress and tension focusing on the interaction with B-L transitions. We consider core sequences, (GC)(n) repeats or (TG)(n) repeats, which can interconvert between the right-handed B form and the left-handed Z form, imbedded in a random sequence, which can convert to left-handed L form with different (tension dependent) helical pitch. We show that Z-DNA formation from the (GC)(n) sequence is always supported by unwinding torsional stress but Z-DNA formation from the (TG)(n) sequence, which are more costly to convert but numerous, can be strongly influenced by the quenched disorder in the surrounding random sequence.National Research Foundation NRF-2012 R1A1A3013044 NRF-2014R1A1A2055681NRF-2012R1A1A2021736IBS-R023-D1NRF-2015R1A2A2A01005916Chemistr

Experimental Study on the Fire Spreading between Vehicles Using a Real Scale Fire Test

Extended Abstract With increasing vehicle, the vehicle fire is considered one of the dangerous disaster. Because vehicles have the many inflammable materials as like gasoline engine oil, plastic and leather etc. Especially, when the vehicle fire is occurred in underground parking lot, the fire can easily spread around the vehicles due to the narrow parking space. [1] Thus, the vehicle fire can be developed to the large fire. In order to prevent the fire spreading, the fire extinguishing systems are installed in underground parking lot. However, these extinguishing systems are designed initial fire suppression, thus it is difficult to extinguish the large fire due to the fire spreading. [2] Therefore, fire spread between vehicles should be considered to improve extinguishing performance. In this study, experimental studies are performed to analyse the fire spread characteristics between vehicles using a real scale fire tests. The fire spread characteristics is analysed by using the temperature measured in various part of the vehicle. The fire is occurred at passenger seat by using the gasoline. Also, the vehicles used in the experiments are the fourwheel sedan. The vehicle is divided into four regions according to the characteristics of the inflammable materials (seat, engine room, fuel tank and bumper

Timing of intravenous immunoglobulin treatment and outcome in Guillain-Barré syndrome: is time nerve?

Introduction/Aims: Despite treatment, a considerable proportion of patients with Guillain–Barré syndrome (GBS) experience poor recovery, highlighting a therapeutic need. There is a lack of evidence that treatment timing affects recovery. This study aims to investigate the effects of intravenous immunoglobulin (IVIg) timing on disability and speed of recovery in GBS. Methods: We performed a retrospective study of 136 IVIg-treated GBS patients admitted to two Korean centers between 2010 and 2021. We analyzed the effect of time to IVIg on the GBS disability scale (GBS-DS) and the degree of improvement from nadir (∆GBS-DS) at 1, 3, 6, and 12 months, as well as the time to regain the ability to walk or run unaided. Time to IVIg was treated either as a continuous variable or categorized into 1-week intervals to explore critical time windows. Known prognostic factors, the modified Erasmus GBS Outcome Scores on admission and pre-treatment serum albumin levels were adjusted as covariates. Results: Shorter time to IVIg was independently associated with better GBS-DS, greater ∆GBS-DS, and shorter time to walk or run unaided at all time points. The therapeutic effect of IVIg was notably diminished when administered beyond the first 2 weeks of onset. Discussion: Our study highlights the timing of IVIg as a modifiable prognostic factor in GBS. The earlier IVIg is initiated, the better the outcomes, with the ideal time window being within the first 2 weeks. These findings underscore the importance of prompt diagnosis and early intervention to optimize recovery in GBS patients

Risk stratification of symptomatic brain metastases by clinical and FDG PET parameters for selective use of prophylactic cranial irradiation in patients with extensive disease of small cell lung cancer

Purpose: To identify risk factors for developing symptomatic brain metastases and evaluate the impact of prophylactic cranial irradiation (PCI) on brain metastasis-free survival (BMFS) and overall survival (OS) in extensive disease small cell lung cancer (ED-SCLC). Materials and methods: Among 190 patients diagnosed with ED-SCLC who underwent FDG PET/CT and brain Magnetic Resonance Imaging (MRI) prior to treatment, 53 (27.9%) received PCI while 137 (72.1%) did not. Prognostic index predicting a high risk of symptomatic brain metastases was calculated for the group without receiving PCI (observation group, n = 137) with Cox regression model. Results: Median follow-up time was 10.6 months. Multivariate Cox regression showed that the following three factors were associated with a high risk of symptomatic brain metastases: the presence of extrathoracic metastases (p = 0.004), hypermetabolism of bone marrow or spleen on FDG PET (p < 0.001), and high neutrophil-to-lymphocyte ratio (p = 0.018). PCI significantly improved BMFS in high-risk patients (1-year rate: 94.7% vs. 62.1%, p = 0.001), but not in low-risk patients (1-year rate: 100.0% vs. 87.7%, p = 0.943). However, PCI did not improve OS in patients at high risk for symptomatic brain metastases (1-year rate: 65.2% vs. 50.0%, p = 0.123). Conclusion: Three prognostic factors (the presence of extrathoracic metastases, hypermetabolism of bone marrow or spleen on FDG PET, and high neutrophil-to-lymphocyte ratio) were associated with a high risk of symptomatic brain metastases in ED-SCLC. PCI was beneficial for patients at a high risk of symptomatic brain metastases in terms of BMFS, but not OS. Thus, selective use of PCI in ED-SCLC according to the risk stratification is recommended. (C) 2020 Elsevier B.V. All rights reserved.

B Cell Immunophenotyping and Transcriptional Profiles of Memory B Cells in Patients with Myasthenia Gravis

Myasthenia gravis (MG) is an autoimmune neuromuscular junction disorders mediated by various autoantibodies. Although most patients with MG require chronic immunosuppressive treatment to control disease activity, appropriate surveillance biomarkers that monitor disease activity or potential toxicity of immunosuppressants are yet to be developed. Herein, we investigated quantitative distribution of peripheral blood B cell subsets and transcriptional profiles of memory B cells (CD19+ CD27+) in several subgroups of MG patients classified according to the Myasthenia Gravis Foundation of America (MGFA) Clinical Classification. This study suggests potential immunologic B-cell markers that may guide treatment decision in future clinical settings.N

Intravascular Papillary Endothelial Hyperplasia (Masson's Hemangioma) of the Liver: A New Hepatic Lesion

Intravascular papillary endothelial hyperplasia (Masson's hemangioma) is a disease characterized by exuberant endothelial proliferation within the lumen of medium-sized veins. In 1923, Masson regarded this disease as a neoplasm inducing endothelial proliferation, however, now it is considered to be a reactive vascular proliferation following traumatic vascular stasis. The lesion has a propensity to occur in the head, neck, fingers, and trunk. Occurrence within the abdominal cavity is known to be very rare, and especially in the liver, there has been no reported case up to date. The authors have experienced intravascular papillary endothelial hyperplasia of the liver in a 69-yr-old woman, and report the case with a review of the literature

A Radiation Analysis of 500W RTPV System having Cylindrical Sources

In this work, the radiation shielding analysis for a RTPV (Radioisotope Thermo-Photo-Voltaic) device using 238PuO2 was performed to estimate the radiation dose distribution over source region and radiation doses in a specified tally zone. The radiation source intensities and spectra were evaluated with ORIGEN-S and the detailed shielding analyses were performed with MCNP6 and MONACO/MAVRIC (in SCALE 6.1). In particular, comparative shielding analysis using two different types of RTPV (cubic homogeneous source type and cylindrical heterogeneous source type) were performed to show their relative performances. The results show that the RTPV device using the heterogeneous cylindrical source type has lower dose values by 5~11% depending on the packing factor at the measurement cell than the one using the homogeneous cubic source type. The additional thermal analysis using COMSOL shows that the temperature distribution of the heterogeneous cylindrical source type is more flat than that of a homogeneous cubic source type