5,084 research outputs found

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    Amyotrophic lateral sclerosis (ALS) is a progressively paralytic neurodegenerative disease that can be caused by mutations in Cu/Zn-superoxide dismutase 1 (SOD1). Transgenic mice that overexpress mutant SOD1 develop paralysis and accumulate aggregates of mutant protein in the brainstem and spinal cord. Bee venom (BV), which is also known as apitoxin, is extracted from honeybees and is commonly used in oriental medicine for the treatment of chronic rheumatoid arthritis and osteoarthritis. The purpose of the present study was to determine whether BV affects misfolded protein aggregates such as alpha-synuclein, which is a known pathological marker in Parkinson disease, and ubiquitin-proteasomal activity in hSOD1G93A mutant mice. BV was bilaterally administered into a 98-day-old hSOD1G93A animal model. We found that BV-treated hSOD1G93A transgenic mice showed reduced detergent-insoluble polymerization and phosphorylation of α-synuclein. Furthermore, phosphorylated or nitrated α-synuclein was significantly reduced in the spinal cords and brainstems of BV-treated hSOD1G93A mice and reduced proteasomal activity was revealed in the brainstems of BV-treated symptomatic hSOD1G93A. From these findings, we suggest that BV treatment attenuates the dysfunction of the ubiquitin-proteasomal system in a symptomatic hSOD1G93A ALS model and may help to slow motor neuron loss caused by misfolded protein aggregates in ALS models

    Methodology of Estimating Socioeconomic Burden of Disease Using National Health Insurance (NHI) Data

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    The cost-of-illness (COI) studies convert the burdens associated with certain illnesses into economic and monetary values so as to measure the socioeconomic costs that are inevitably incurred by a given society in association with certain illnesses. The estimated costs provided by COI studies provide an important basis for estimating the amounts of public health resources spent and productivity losses incurred and thereby make it possible to quantify the socioeconomic burdens that illnesses impose on society in general. In this chapter, we review the diverse methodologies and techniques for estimating the socioeconomic burden of disease, which is widely used in the established literature all over the world, and compare the pros and cons of each. This chapter introduces the existing COI studies in terms of their research designs, data selection and value assessment processes, applied perspectives, and chosen components of costs. Furthermore, this chapter introduces a real-world example of estimating the national economic burden of disease by using the National Health Insurance (NHI) data. We hope that this chapter will help readers better understand and use the COI study

    Flow Characteristics Around Step-Up Street Canyons with Various Building Aspect Ratios

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    We investigate the flow characteristics around step-up street canyons with various building aspect ratios (ratio of along-canyon building length to street-canyon width, and upwind building height to downwind building height) using a computational fluid dynamics (CFD) model. Simulated results are validated against experimental wind-tunnel results, with the CFD simulations conducted under the same building configurations as those in the wind-tunnel experiments. The CFD model reproduces the measured in-canyon vortex, rooftop recirculation zone above the downwind building, and stagnation point position reasonably well. We analyze the flow characteristics, focusing on the structural change of the in-canyon flows and the interaction between the in- and around-canyon flows with the increase of building-length ratio. The in-canyon flows undergo development and mature stages as the building-length ratio increases. In the development stage (i.e., small building-length ratios), the position of the primary vortex wanders, and the incoming flow closely follows both the upstream and downstream building sidewalls. As a result, increasing momentum transfer from the upper layer contributes to a momentum increase in the in-canyon region, and the vorticity in the in-canyon region also increases. In the mature stage (i.e., large building-length ratios), the primary vortex stabilizes in position, and the incoming flow no longer follows the building sidewalls. This causes momentum loss through the street-canyon lateral boundaries. As the building-length ratio increases, momentum transfer from the upper layer slightly decreases, and the reverse flow, updraft, and streamwise flow in the in-canyon region also slightly decrease, resulting in vorticity reduction

    Growth of superconducting MgB2 thin films via postannealing techniques

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    We report the effect of annealing on the superconductivity of MgB2 thin films as functions of the postannealing temperature in the range from 700 C to 950 C and of the postannealing time in the range from 30 min to 120 min. On annealing at 900 C for 30 min, we obtained the best-quality MgB2 films with a transition temperature of 39 K and a critical current density of ~ 10^7 A/cm^2. Using the scanning electron microscopy, we also investigated the film growth mechanism. The samples annealed at higher temperatures showed the larger grain sizes, well-aligned crystal structures with preferential orientations along the c-axis, and smooth surface morphologies. However, a longer annealing time prevented the alignment of grains and reduced the superconductivity, indicating a strong interfacial reaction between the substrate and the MgB2 film.Comment: 7 pages, 4 figures include

    Acute Oral Toxicity and Kinetic Behaviors of Inorganic Layered Nanoparticles

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    Layered double hydroxide (LDH) nanoparticles, also known as anionic clays, have attracted a great deal of interest for their potential as delivery carriers. Recent studies showed that LDH nanoparticles can efficiently deliver drugs or bioactive molecules into cells, which are highly related to their endocytic pathway. However, the efficient cell permeation capacity of LDH may also raise concern about their toxicity potential. In this study, the acute oral toxicity of LDH nanoparticles was assessed, and their kinetic behaviors, such as plasma concentration-time curve, tissue distribution, and excretion, were also evaluated in mice. No significant effects of oral LDH nanoparticles on behaviors, body weight gain, survival rate, and organosomatic index were observed up to the dose of 2000 mg/kg for 14 days. Serum biochemical parameters did not significantly increase, indicating that LDH nanoparticles did not cause acute liver or kidney injury. Plasma concentration of LDH nanoparticles rapidly decreased within 30 min depending on exposure doses, but they did not accumulate in any specific organ. Their excretion via urine and feces was observed within 24 h. These findings suggest that LDH nanoparticles do not exhibit acute oral toxicity and favorable kinetic behaviors in mice and, therefore, will be promising candidates for biological and pharmaceutical applications

    Hull-form optimization of a 66,000 dwt bulk carrier in irregular wave condition

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    This paper deploys optimization techniques to obtain the optimum hull form of a 66,000 DWT bulk carrier in calm water and in irregular head waves at sea state 6. Parametric modification functions for the bow hull-form variation are SAC shape, section shape (U-V type, DLWL type). Multi-objective functions are applied to minimize the values of wave-making resistance in calm water and mean added resistance in waves. WAVIS version 1.3 is used to obtain wave-making resistance in calm water condition. The modified Fujii and Takahashi's formula is applied to obtain the added resistance in short waves. The added resistance in long wave is obtained from the potential-flow solver based on the 3-D panel method. And the mean added resistance in irregular head waves is obtained by linear superposition of the wave spectrum and the response function. The PSO (Particle swarm optimization) algorithm is employed for the optimization technique. The resistance and motion characteristics in calm water, in regular head waves and in irregular head waves of the two hull forms are compared. It has been shown that the optimal brings 6.8% reduction in the mean added resistance at sea state 6
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