Search

Since Parkinson's disease (PD) is a heterogeneous disorder with symptoms, such as tremors, gait and speech disturbances, or memory loss, individualized diagnostics are needed to optimize treatment. In their current form, the typical paper-pencil methods traditionally used to track disease progression are too coarse to capture the subtleties of clinical phenomena. For this reason, digital biomarkers that capture, for example, motor function, cognition, and behavior using apps, wearables, and tracking systems are becoming increasingly established. However, given the high prevalence of cognitive impairment in PD, digital cognitive biomarkers to predict mental progression are important in clinical practice. This pilot study aimed to identify those components of our digital version of the TMT (dTMT) that allow discrimination between PD patients with and without cognitive deficits. A total of 30 healthy control (age 66.3 ± 8.61) and 30 participants with PD (age 68.3 ± 9.66) performed the dTMT using a touch-sensitive tablet to capture enhanced performance metrics, such as the speed between and inside circles. The decomposition of cognitive abilities based on integrating additional variables in the dTMT revealed that the Parkinson's disease group was significantly more sensitive to parameters of inhibitory control. In contrast, the mild cognitive impairment group was sensitive to parameters of cognitive flexibility and working memory. The dTMT allows objective, ecologically valid, and long-term cognitive and fine-motor performance tracking, suggesting its potential as a digital biomarker in neurodegenerative disorders.

Studies on the effects of acute exercises on cognitive functions vary greatly and depend on the duration and intensity of exercise and the type of cognitive tasks. This study aimed to investigate the neural correlates that underpin the acute effects of high-intensity interval (HIIE) versus moderate-intensity continuous exercise (MCE) on fine motor-cognitive performance while walking (dual-task, DT) in healthy young adults. Twenty-nine healthy right-handers (mean age: 25.1 years ± 4.04; 7 female) performed the digital trail-making-test (dTMT) while walking (5 km/h) before and after acute exercise. During task performance, the hemodynamic activation of the frontopolar area (FPA), dorsolateral prefrontal (DLPFC), and motor cortex (M1) was recorded using functional near-infrared spectroscopy (fNIRS). Both HIIE and MCE resulted in improved dTMT performance, as reflected by an increase in the number of completed circles and a reduction in the time within and between circuits (reflecting improvements in working memory, inhibition, and decision making). Notably, HIIE evoked higher cortical activity on all brain areas measured in the present study than the MCE group. To our knowledge, these results provide the first empirical evidence using a mobile neuroimaging approach that both HIIE and MCE improve executive function during walking, likely mediated by increased activation of the task-related area of the prefrontal cortex and the ability to effectively use, among other things, high fitness levels as neural enrichment resources.

This paper proposes an extended time uncertainty analysis approach in Level 2 human reliability analysis (HRA) considering severe accident management (SAM) strategies. The method is a time-based model that classifies two time distribution functions—time required and time available—to calculate human failure probabilities from delayed action when implementing SAM strategies. The time required function can be obtained by the combination of four time factors: 1) time for diagnosis and decision by the technical support center (TSC) for a given strategy, 2) time for strategy implementation mainly by the local emergency response organization (ERO), 3) time to verify the effectiveness of the strategy and 4) time for portable equipment transport and installation. This function can vary depending on the given scenario and includes a summation of lognormal distributions and a choice regarding shifting the distribution. The time available function can be obtained via thermal-hydraulic code simulation (MAAP 5.03). The proposed approach was applied to assess SAM strategies that use portable equipment and safety depressurization system valves in a total loss of component cooling water event that could cause reactor vessel failure. The results from the proposed method are more realistic (i.e., not conservative) than other existing methods in evaluating SAM strategies involving the use of portable equipment.

One of the key challenges in assessing cognitive performance is to detect not only apparent impairment but to also pick up on subtle differences. Computerized tests benefit especially from the acquisition of fine-grained outcome measures. However, the equivalency of paper-based and computerized tests cannot be assumed. The Trail-Making-Test is a paper-pencil cognitive assessment tool (ppTMT) that has been used in many research studies to evaluate visuomotor abilities and mental flexibility. A digital version of the extended TMT (including a condition measuring fine motor speed) called the dTMT has been developed. This study aims to test (1) reliability, (2) equivalence, and (3) agreement of the ppTMT and dTMT. A total of 53 healthy individuals aged 19 to 82 years of age (22 men, 31 women; mean age 42.2, SD = 22.8) completed three trials per ppTMT and dTMT condition. Part M involves following a predefined path, Part A links numbers randomly distributed in space, in ascending order, and Part B alternates between linking numbers and letters. dTMT scores were highly reproducible, correlated strongly with paper-pencil administered durations, and discriminated young from older adults. Measures of reliability, sensitivity, and clinical meaning for dTMT scores were favorable compared with ppTMT-based testing. Our findings support the comparability of TMT-indices in computerized assessments. While many digital biomarker efforts are in progress (e.g., neurodegenerative disorders), the dTMT sets itself apart through its high sensitivity, the alternate forms, and the additional component measures. In this light, it could serve as a starting point for an early diagnostic tool.

The interactions between the microbes and the surface of an anode play an important role in capturing the respiratory electrons from bacteria in a microbial fuel cell (MFC). The chemical and electrochemical characteristics of the carbon material affect biofilm growth and direct electron transfer in MFCs. This study examined the electrodeposition of polydopamine (PDA) and polypyrrole (PPY) on graphite felt electrode (GF). The MFC with the modified PDA/PPY-GF reached 920 mW/m

Although an extensive body of literature is trying to verify the acute effects of exercise, findings are highly contradictory due to many different study protocols. The number of studies using an intermittent exercise (IE) protocol is limited, especially with regard to comparison across the life span. We examined whether the effects of a HIIE protocol on performance in a perceptual-cognitive task (NeuroTracker® (NT)) differed between children, young adults, and older adults to address this gap.A total of 36 participants participated in the present study: 12 children (CH, 6 females, 9.83 ± 1.19 years), 12 young adults (YA, 6 females, 23.5 ± 3.55 years), and 12 older adults (OA, 4 females, 66.92 ± 4.08 years). The IE treadmill protocol used in the present study consisted of eleven 30-second intervals at 90% VO2max, interspersed with 2-minute active recovery periods at 50% VO2max. Before and during this exercise protocol, three series of the NeuroTracker® task were performed after 5, 15, and 25 minutes.We observed a significant main effect time and a significant main effect group regarding absolute NT scores and progression during IE. YA had significantly higher absolute NT scores than CH and OA. The normalized perceptual-cognitive task progression was observed in OA and YA but not in CH. YA, in particular, showed progression in the NT performance during IE.The present study confirmed previous findings on age-related differences in NT performance. Based on these findings, the effects of different exercise protocols (e.g., continuous vs. intermittent) seem to be a worthwhile subject for future investigations. Normalized speed thresholds should best capture improvement differences between groups to compare results across studies better, as pre-test values are taken as the baseline.

Several studies have shown that acute exercise has a small positive effect on cognitive performance. However, it is still unclear what type of exercise has a sustained impact on cognitive performance during post-exercise recovery. Therefore, the purpose of our study was to investigate cognitive performance at the behavioral level, and their neural correlates after a 10-minute post-exercise recovery period with two different types of exercise intervention (high-intensity interval exercise (HIIE) vs. Moderate-intensity continuous exercise (MCE)).A total of 29 healthy young adults (7 women) between the ages of 19 and 33 with fair to good cardiovascular fitness were submitted to two different exercise protocols and a recovery session. Cognitive function was assessed using a digital Trail-Making-Test (dTMT). Cortical activity in the prefrontal and the motor cortex using functional near-infrared spectroscopy (fNIRS) was measured before, after acute exercise, and during recovery. The statistical analysis of fNIRS data was performed by comparing the slope and mean of the hemodynamic response.High levels of hemodynamic responses were observed in the prefrontal and motor cortex on the brain during performing the dTMT while walking from pre- to post-exercise and decreased again in post-recovery, accompanied by improvement and maintenance of cognitive performance. Notably, a high hemodynamic response in the left motor area of the brain was maintained by HIIE in post-recovery compared with MCE.The high cortical activation in the left motor area from post-exercise to recovery for the HIIE group may be due to the additional availability of neural resources for fine motor and postural control by high-intensity exercise-induced fatigue. Additionally, the improved cognitive performance may have effectively utilized the available neural resources in the frontal lobe, depending on the condition (sitting and walking) and the two types of exercise protocol (HIIE and MCE).

The customer of massage chair is expanding day by day from middle age to all ages. In 2018, the market size was 700 billion KRW, an increase of 30 times over 10 years. However, most related SMEs suffer from excessive competition by the market monopoly of some major companies. In this situation, in order for a related company to survive, it is necessary to steadily research and develop new products. Founded in 2009, company L produces massage chairs for health and relaxation of customers. L’s products use a sound wave vibration module that is favorable for human body, unlike other products that use vibration motor type. However, frequent breakdowns of massage chair due to the vulnerability of plate (leaf) springs, which play an important role in sound wave vibration modules, made sap its competitiveness. In this paper, we propose a method to design desirable plate spring structure by sequentially experimenting with five different plate springs. The results of this study are expected to contribute to improve the quality of plate spring and the reliability of sound wave vibration module. In the future, it is necessary to find a way to use it in the development of foot massage or scalp management device as well as continuous research to find optimal plate spring structure through various analysis.

Gene therapy is a suitable alternative to chemotherapy due to the complications of drug resistance and toxicity of drugs, and is also known to reduce the occurrence of cellular mutation through the use of gene carriers. In this study, gene carrier nanoparticles with minimal toxicity and high transfection efficiency were fabricated from a biocompatible and biodegradable polymer, l-tyrosine polyurethane (LTU), which was polymerized from presynthesized desaminotyrosyl tyrosine hexyl ester (DTH) and polyethylene glycol (PEG), by using double emulsion and solvent evaporation techniques, resulting in the formation of porous nanoparticles, and then used to evaluate their potential biological activities through molecular controlled release and transfection studies. To assess cellular uptake and transfection efficiency, two model drugs, fluorescently labeled bovine serum albumin (FITC-BSA) and plasmid DNA-linear polyethylenimine (LPEI) complex, were successfully encapsulated in nanoparticles, and their transfection properties and cytotoxicities were evaluated in LX2 as a normal cell and in HepG2 and MCF7 as cancer cells. The morphology and average diameter of the LTU nanoparticles were confirmed using light microscopy, transmission electron microscopy, and dynamic light scattering, while confocal microscopy was used to validate the cellular uptake of FITC-BSA-encapsulated LTU nanoparticles. Moreover, the successful cellular uptake of LTU nanoparticles encapsulated with pDNA-LPEI and the high transfection efficiency, confirmed by gel electrophoresis and X-gal assay transfection, indicated that LTU nanoparticles had excellent cell adsorption ability, facilitated gene encapsulation, and showed the sustained release tendency of genes through transfection experiments, with an optimal concentration ratio of pDNA and LPEI of 1:10. All the above characteristics are ideal for gene carriers designed to transport and release drugs into the cytoplasm, thus facilitating effective gene therapy.

Biodegradable triblock copolymers based on poly(ε-caprolactone) (PCL) and poly(lactic acid) (PLA) were synthesized via ring-opening polymerization of L-lactide followed by reversible addition–fragmentation chain-transfer (RAFT) polymerization of poly(methyl vinyl ketone) (PMVK) as a photodegradable block, and characterized by FT-IR and 1H NMR spectroscopy for structural analyses, and by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) for their thermal properties. Porous, biodegradable PCL-b-PLA microspheres were fabricated via the oil/water (O/W) emulsion evaporation method, followed by photodegradation of PMVK blocks by UV irradiation. The macro-chain transfer agent (CTA) synthesized by reacting a carboxylic-acid-terminated CTA—S-1-dodecyl-S′-(a,a′-dimethyl-a′′-acetic acid)trithiocarbonate (DDMAT)—with a hydroxyl-terminated PCL-b-PLA block copolymer was used to synthesize well-defined triblock copolymers with methyl vinyl ketone via RAFT polymerization with controlled molecular weights and narrow polydispersity. Gel permeation chromatography traces indicated that the molecular weight of the triblock copolymer decreased with UV irradiation time because of the photodegradation of the PMVK blocks. The morphology of the microspheres before and after UV irradiation was investigated using SEM and videos of three-dimensional confocal laser microscopy, showing a change in their surface texture from smooth to rough, with high porosity owing to the photodegradation of the PMVK blocks to become porous templates.

Butyl rubber/hydrophobized graphene oxide (HG) nanocomposites were prepared by solution mixing followed by compression molding process, and evaluated their properties using scanning electron microscope (SEM), oscillating disc rheometer (ODR), universal testing machine (UTM), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC). The hydrophilic graphene oxide (GO) obtained through the oxidation of graphite (GP) was first hydrophobized with octadecylamine. The HG exhibit excellent dispersibility in toluene and stable under stationary condition for over 30 days. The chemical structure and functionality of HG was analyzed by fourier transform infrared (FTIR), raman spectroscopies, and wide-angle X-ray diffraction (WAXD) patterns. HG was successfully dispersed within BR matrix and result in significant reduction of curing time (around 30%), enhanced tensile strength (around 35%) as compared to the pristine butyl rubber. The air permeability of the hydrophobized graphene oxide composites was also significantly reduced by 75% compared to unfilled butyl rubber.

Recently, automobile manufacturing companies, which are major customers of them, are requiring IATF 16949 (ISO/TS 16949) certification as a mandatory requirement to secure product quality. In particular, IATF 16949 : 2016, revised in October 2016, was reinforced product traceability requirements for production information management by lot in the production process. Therefore, small and medium-sized precision parts processing companies in the automobile industry are very difficult to survive due to quality and price competition for customers satisfaction.MES (Manufacturing Execution System) is required to solve this problem. However, small and medium sized precision parts processing enterprises are reluctant to introduce the MES which is not suitable for the manufacturing environment of them such as high cost and low utilization. Even if the system is introduced, it is difficult to operate and maintain the system because the lack of computer manpower.In this paper, we propose a method for building a lot tracking system for small and medium precision parts processing companies by reviewing relevant literature and analyzing cases. In addition, by managing the production history for each lot of the final product in the system, we will grasp the effect of reducing the quality failure cost obtained by minimizing the range of defect selection.

Domestic SMEs play a key role in production and employment, accounting for 98.9% of total enterprises, 74.4% of employment, 50.8% of production, and 49.0% of value added (as of 2016). However, they are faced with difficulties of survival because of continuous decrease in profitability, shortage of funds and manpower, insufficient accumulation of technology, minimum wage increase, and 52-hour workweek. In order for SMEs to continue to develop in such a difficult environment, we must constantly innovate our organization by making full use of our knowledge, information, experience and ability. To do this, CEO (management) leadership is very important to ensure that the best people are focused on the organizational innovation and management performance without moving the company. In this study, we wanted to establish empirically how the newly emerging compassionate rationalism leadership of SMEs business managers affected the innovation activities and management performance of companies. Research has shown that management’s compassionate rationalism leadership has a positive and significant causal relationship with the innovation activities and management performance of the enterprise. Therefore, SMEs managers need to learn the bottom eight strategic factors of compassionate rationalism leadership and use them strategically to make efforts to create positive emotions for the organization so that members can be immersed in innovative activities and management performance creation.

The population of domestic companion animals is estimated to be about 10 million now. In recent years, the domestic pet market has been launching a wide range of products and services for high quality, smart and well-being. As a result, the market size will increase from 900 billion won in 2012 to 2.3 trillion won in 2016, which has more than doubled in five years. The industry expects to reach 6 trillion won by 2020, expecting 3 trillion won this year. In particular, domestic dogs and cats market is estimated at 275.5 billion won, accounting for 19% of the domestic animal market and 1.425 billion won for the world market. However, despite the growing market for companion animals products, unfortunately the import dependence on related industrial goods is still high and the quality of service is very low. Unlike Europe and the United States, 90% of companion animals are housed in apartments, often causing problems in the health and safety of companions and companions. The purpose of this study is to develop a smart house for companion animals with environmental friendliness and AI function that can be won in competition with products of developed countries. The results of this study are expected to contribute to the creation of a new value - added base for the related industries through the strengthening of the competitiveness of the related SMEs and further the effect of employment increase and import substitution.

Being poor solubility and degradation at relatively higher pH present in the small intestine, it is very essential to develop gastro-retentive dosages for the release of curcumin. In this paper, the halloysite nanotubes (HNTs) was modified with aminopropyl trimethoxy silane (APTES) in order to increase the buoyancy of the hybrid beads through holding CO2 molecules within the pores of the beads, followed by the encapsulation of curcumin into the lumen of the HNTs. Highly porous pectin based hybrid beads were fabricated by incorporating various compositions of curcumin loaded amino silanized halloysite nanotube (MHNT) and sodium bicarbonate as CO2 generating agent. Finally, hybrid beads were crosslinked by ionotropic gelation method using calcium chloride and used to gastro retentive delivery of curcumin in sustained manner. The amino salinization of halloysite and curcumin loading into the modified halloysite were characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), thermogravimetric analysis (TGA) and transmission electron microscopy (TEM). The highly porous nature of cross-linked hybrid beads has been confirmed with scanning electron microscopy (SEM) studies. In vitro release studies in simulated gastric fluid indicate that these new hybrid floating carriers are suitable for gastro retentive controlled release applications.

Small enterprises in the root industry are currently experiencing difficulties in fulfilling their deadlines due to the recent increase in the minimum wage, shortened working hours, and low productivity. Therefore, it is very important to establish a Manufacturing Execution System (MES) that can increase production and process efficiency with minimum manpower.

New antitumor active polyrotaxanes, presynthesized from β-cyclodextrin and polypropylene glycol, were first end capped with antitumor active drug, 5-fluorouracil, and further conjugated with 5-fluo...

Generation of autologous human motor neurons holds great promise for cell replacement therapy to treat spinal cord injury (SCI). Direct conversion allows generation of target cells from somatic cells, however, current protocols are not practicable for therapeutic purposes since converted cells are post-mitotic that are not scalable. Therefore, therapeutic effects of directly converted neurons have not been elucidated yet. Here, we show that human fibroblasts can be converted into induced motor neurons (iMNs) by sequentially inducing POU5F1(OCT4) and LHX3. Our strategy enables scalable production of pure iMNs because of the transient acquisition of proliferative iMN-intermediate cell stage which is distinct from neural progenitors. iMNs exhibited hallmarks of spinal motor neurons including transcriptional profiles, electrophysiological property, synaptic activity, and neuromuscular junction formation. Remarkably, transplantation of iMNs showed therapeutic effects, promoting locomotor functional recovery in rodent SCI model. Together, our advanced strategy will provide tools to acquire sufficient human iMNs that may represent a promising cell source for personalized cell therapy.

Alzheimer&rsquo, s disease (AD) is a complex, age-related neurodegenerative disease that is the most common form of dementia. However, the cure for AD has not yet been founded. The accumulation of amyloid beta (A&beta, ) is considered to be a hallmark of AD. Beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), also known as beta secretase is the initiating enzyme in the amyloidogenic pathway. Blocking BACE1 could reduce the amount of A&beta, but this would also prohibit the other functions of BACE1 in brain physiological activity. SPONDIN1 (SPON1) is known to bind to the BACE1 binding site of the amyloid precursor protein (APP) and blocks the initiating amyloidogenesis. Here, we show the effect of SPON1 in A&beta, reduction in vitro in neural cells and in an in vivo AD mouse model. We engineered mouse induced neural stem cells (iNSCs) to express Spon1. iNSCs harboring mouse Spon1 secreted SPON1 protein and reduced the quantity of A&beta, when co-cultured with A&beta, secreting Neuro 2a cells. The human SPON1 gene itself also reduced A&beta, in HEK 293T cells expressing the human APP transgene with AD-linked mutations through lentiviral-mediated delivery. We also demonstrated that injecting SPON1 reduced the amount of A&beta, and ameliorated cognitive dysfunction and memory impairment in 5xFAD mice expressing human APP and PSEN1 transgenes with five AD-linked mutations.

Objective: Vascular progenitor cells (VPCs), which are able to differentiate into both endothelial cells and smooth muscle cells, have the potential for treatment of ischemic diseases. Generated by pluripotent stem cells, VPCs carry the risk of tumorigenicity in clinical application. This issue could be resolved by direct lineage conversion, the induction of functional cells from another lineage by using only lineage-restricted transcription factors. Here, we show that induced VPCs (iVPCs) can be generated from fibroblasts by ETS (E-twenty six) transcription factors, Etv2 and Fli1 . Approach and Results: Mouse fibroblasts were infected with lentivirus encoding Etv2 and Fli1 . Cell colonies appeared in Fli1 - and Etv2/Fli1 -infected groups and were mechanically picked. The identity of cell colonies was confirmed by proliferation assay and reverse-transcription polymerase chain reaction with vascular markers . Etv2/Fli1 - infected cell colonies were sorted by CD144 (also known as CDH5, VE-cadherin). We defined that CD144-positive iVPCs maintained its own population and expanded stably at multiple passages. iVPCs could differentiate into functional endothelial cells and smooth muscle cells by a defined medium. The functionalities of iVPC-derived endothelial cells and smooth muscle cells were confirmed by analyzing LDL (low-density lipoprotein) uptake, carbachol-induced contraction, and tube formation in vitro. Transplantation of iVPCs into the ischemic hindlimb model enhanced blood flow without tumor formation in vivo. Human iVPCs were generated by human ETS transcription factors ETV2 and FLI1 . Conclusions: We demonstrate that ischemic disease curable iVPCs, which have self-renewal and bipotency, can be generated from mouse fibroblasts by enforced ETS family transcription factors, Etv2 and Fli1 expression. Our simple strategy opens insights into stem cell–based ischemic disease therapy.

A short-term station blackout (STSBO) accident has been considered as one of risk dominant sequences for nuclear power plants (NPPs). Unless appropriate mitigation actions are not taken, a rapid damage of the reactor core and thereby a severe accident may result in. This paper presents best practice analysis results on the evolution of the severe accident sequences and fission product (FP) source terms expected during the STSBO accident of a reference pressurized water reactor. In addition, this study aims to analyze the impact of dedicated severe accident mitigation/management actions on the results of interest through the established modeling approach. As the modeling and simulation tools for the analysis, MELCOR2.2 and MAAP5.05, were used to compare the analysis results of interest such as the integrities of the reactor coolant system (RCS) pressure boundary and the reactor/containment building, the generation of flammable gases (such as hydrogen and carbon monoxide), and the environmental release of the FP cesium. As a key finding, this study demonstrated that both codes similarly predicted the environmental release of the FP cesium as well as the general trend of the evolution of the severe accident sequences and plant responses. Of particular interest was the substantial difference in predicting the generation of the flammable gases by the two codes. Relevant insights are summarized in terms of particular points of interest.

Mitochondrial dynamics are associated with the development of porcine embryos. However, little is known about the effects of mitochondrial dynamics-related genes (Drp1 and pDrp1-Ser616) on early porcine embryo development. Here, we investigated the effect of Drp1-dependent mitochondrial fission signaling on the development of porcine embryos using the mitochondrial fission inducer, tyrphostin A9 (TA9). We determined that TA9 (1μM) treated embryos were increased the mitochondrial functions, blastocyst development rate and quality, as well as decreased mitochondria-specific superoxide and mitochondrial apoptosis. Thus, TA9-induced appropriate mitochondrial fission improved the developmental competence via maintenance of a balance in mitochondrial dynamics in porcine embryo.

The objective of this study is to present a rare case of an invaginated inferior vena cava (IVC) aneurysm in the lumbar intradiscal space. A 73-year-old woman with lower back pain and bilateral lower extremity swelling presented to the clinic. She had undergone spinal surgery performed thrice at the same site (L4–L5) in another hospital and a separate posterolateral fusion surgery procedure 3 years previously. On plain radiography, pseudarthrosis was observed at L4–L5 segment. Contrast computed tomography (CT) imaging revealed a dilatation of the IVC in the intradiscal space of L4–L5. On the anterior side, anterior discectomy was performed. Following insertion of the allograft bone chip and cage, the invaginated IVC aneurysm was repositioned. Implant removal and screw fixation were performed posteriorly. Post-surgery, the patient’s lower back pain improved, and the start of anticoagulation treatment after vascular evaluation was planned. Although there have been numerous case reports of patients with intradiscal cysts or gas requiring surgical treatment, there have not yet been any reports of those with invaginated IVC in an intradiscal space. It is important to provide the appropriate treatment based on a thorough prior understanding of the patient’s anatomy.

Direct conversion from fibroblasts to generate hepatocyte like-cells (iHeps) bypassing the pluripotent state has been described in previous reports as an attractive method acquiring hepatocytes for cell-based therapy. The limited proliferation of iHeps, however, has hampered it uses in cell-based therapy. Since hepatic stem cells (HepSCs) possess self-renewal and bipotency with the capacity to differentiate into both hepatocytes and cholangiocytes, they have therapeutic potential for treating liver disease. Here, we investigated the therapeutic effects of induced HepSCs (iHepSCs) on a carbon tetrachloride (CCl4)-induced liver fibrosis model. We demonstrate that Oct4 and Hnf4a are sufficient to convert fibroblasts into expandable iHepSCs. Hepatocyte-like cells derived from iHepSCs (iHepSC-HEPs) exhibit the typical morphology of hepatocytes and hepatic functions, including glycogen storage, low-density lipoprotein (LDL) uptake, Indocyanine green (ICG) detoxification, drug metabolism, urea production, and albumin secretion. iHepSCs-derived cholangiocyte-like cells (iHepSC-CLCs) expressed cholangiocyte-specific markers and formed cysts and tubule-like structures with apical-basal polarity and secretory function in three-dimensional culture condition. Furthermore, iHepSCs showed anti-inflammatory and anti-fibrotic effects in CCl4-induced liver fibrosis. This study demonstrates that Oct4 and Hnf4α-induced HepSCs show typical hepatic and biliary functionality in vitro. It also presents the therapeutic effect of iHepSCs in liver fibrosis. Therefore, directly converting iHepSCs from somatic cells may facilitate the development of patient-specific cell-based therapy for chronic liver damage.

Bisphenol A (BPA) is synthetic organic compound that exhibits estrogen-like properties and it induces mitochondrial superoxide production. Melatonin (Mela) protects against BPA-mediated cell damage and apoptosis. However, the antioxidative effects of Mela against BPA-induced superoxide production in porcine oocytes are still not known. In this study, we investigated the antioxidative effects of Mela against BPA-derived superoxide on oocyte maturation in pigs. To investigate the effects of the superoxide specific scavenger, Mito-TEMPO, on porcine oocyte maturation in response to BPA exposure apoptosis proteins, we treated the oocytes with Mito-TEMPO (0.1 &micro, M) after pre-treating them with BPA (75 &micro, M) for 22 h. As expected, the reduction in meiotic maturation and cumulus cell expansion of cumulus-oocyte-complexes (COCs) in the BPA (75 &micro, M) treated group was recovered (p &lt, 0.01) by treatment with Mito-TEMPO (0.1 &micro, M). An increase in the levels of mitochondrial apoptotic proteins (AIF, cleaved Cas 3 and cleaved Parp1) in response to BPA-induced damage was also reduced by Mito-TEMPO treatment in porcine COCs. Interestingly, we confirmed the positive effects of Mela with respect to superoxide production upon BPA exposure during oocyte maturation and also confirmed the reduction in mitochondrial apoptosis in Mela (0.1 &micro, M)-treated porcine COCs. These results provide evidence for the first time that antioxidative effects of Mela on BPA-derived superoxide improve porcine oocyte maturation.

Gangliosides exist in glycosphingolipid-enriched domains on the cell membrane and regulate various functions such as adhesion, differentiation, and receptor signaling. Ganglioside GM3 by ST3GAL5 enzyme provides an essential function in the biosynthesis of more complex ganglio-series gangliosides. However, the role of gangliosides GM3 in porcine oocytes during in vitro maturation and early embryo development stage has not yet understood clear. Therefore, we examined ganglioside GM3 expression patterns under apoptosis stress during maturation and preimplantation development of porcine oocytes and embryos. First, porcine oocytes cultured in the NCSU-23 medium for 44 h after H2O2 treated groups (0.01, 0.1, 1 mM). After completion of meiotic maturation, the proportion MII (44 h) was significantly different among control and the H2O2 treated groups (76.8±0.3 vs 69.1±0.4; 0.01 mM, 55.7±1.0; 0.1 mM, 38.2±1.6%; 1 mM, P

Biodegradable polyfumarateurethane (PFU) for use as a bupivacaine delivery vehicle, synthesized using di-(2-hydroxypropyl fumarate) (DHPF), polyethylene glycol (PEG) and 1,6-hexamethylene diisocyanate (HMDI), was designed to be degradable through the hydrolysis and enzymatic degradation of the ester bonds in its polymer backbone. Using a water-in-oil-in-water double emulsion techniques, nanoparticles encapsulating water or fluorescein isothiocyanate (FITC) were fabricated to avoid the immune system owing to the presence of PEG on their surface. The morphologies of these nanoparticles were characterized by DLS, TEM, FE-SEM, and fluorescent microscopies. The present study explored the encapsulation, loading efficiency and in vitro drug release of bupivacaine encapsulated with biodegradable PFU nanoparticles for the treatment of local anesthesia. Various concentrations of bupivacaine were encapsulated into nanoparticles and their encapsulation efficiencies and drug loading were investigated. Encapsulation efficiency was highest when 2.5% bupivacaine was encapsulated. Drug release behavior from the bupivacaine-loaded PFU nanoparticles followed a sustained release profile.

Mitochondria are highly dynamic organelles that undergo constant fusion/fission as well as activities orchestrated by large dynamin-related GTPases. These dynamic mitochondrial processes influence mitochondrial morphology, size and function. Therefore, this study was conducted to evaluate the effects of mitochondrial fission inhibitor, mdivi-1, on developmental competence and mitochondrial function of porcine embryos and primary cells. Presumptive porcine embryos were cultured in PZM-3 medium supplemented with mdivi-1 (0, 10 and 50 μM) for 6 days. Porcine fibroblast cells were cultured in growth medium with mdivi-1 (0 and 50 μM) for 2 days. Our results showed that the rate of blastocyst production and cell growth in the mdivi-1 (50 μM) treated group was lower than that of the control group (P < 0.05). Moreover, loss of mitochondrial membrane potential in the mdivi-1 (50 μM) treated group was increased relative to the control group (P < 0.05). Subsequent evaluation revealed that the intracellular levels of reactive oxygen species (ROS) and the apoptotic index were increased by mdivi-1 (50 μM) treatment (P < 0.05). Finally, the expression of mitochondrial fission-related protein (Drp 1) was lower in the embryos and cells in the mdivi-1-treated group than the control group. Taken together, these results indicate that mdivi-1 treatment may inhibit developmental competence and mitochondrial function in porcine embryos and primary cells.

In Korea, pressurized heavy water-cooled reactors (PHWR) account for 17% of operating units and have taken an important role in providing national energy supply. The recent biggest issue in domestic PHWR community was the continued operation of the Wolsong-1 CANada Deuterium Uranium (CANDU) plant, which has recently been approved to operate for 10 more years after a 30 year design life. In relation to this issue, various actions from both post-Fukushima lessons and Wolsong-1 (WS1) stress test results are being taken. In KAERI R&D, the following topics are studied to support the basis for these actions. First, PHWR severe accident issues such as (1) primary heat transport system (PHTS) overpressure protection capability, (2) containment overpressure protection capability, and (3) bypass source term are evaluated. Second, a computer tool (called MAAP–ISAAC) has been modified and updated to support analyzing Wolsong severe accident issues. Third, a decision supporting tool, called Severe Accident Management Expert (SAMEX)–CANDU, has been developed to aid emergency response experts under severe accident conditions.

Bovine somatic cell nuclear transfer (SCNT) is an important and powerful tool for basic research and biomedical and agricultural applications, however, the efficiency of SCNT has remained extremely low. In this study, we investigated the effects of cathepsin B inhibitor (E-64) supplementation of culture medium on in vitro development of bovine SCNT embryos. We initially used three concentrations of E-64 (0.1, 0.5, 1.0 μm), among which 0.5 μm resulted in the highest rate of blastocysts production after in vitro fertilization (IVF), and was therefore used for further experiments. Blastocyst development of SCNT embryos in the E-64 treatment group also increased relative to the control. Moreover, the cryosurvival rates of IVF and SCNT blastocysts were increased in E-64 treatment groups when compared with the control. On the other hand, we found that IVF and SCNT blastocysts derived from E-64-treated groups had increased total cell numbers and decreased apoptotic nuclei. Furthermore, assessment of the expression of apoptosis-related genes (Bax and Bcl-xL) in bovine IVF and SCNT blastocysts treated with E-64 by real-time RT-PCR analysis revealed suppressed expression of the pro-apoptotic gene Bax and stimulated expression of the anti-apoptotic gene Bcl-xL. Taken together, these finding indicate that addition of E-64 to embryo culture medium may have important implications for improving developmental competence and preimplantation quality in bovine IVF and SCNT embryos.