A Criticality Analysis of the GBC-32 Dry Storage Cask with Hanbit Nuclear Power Plant Unit 3 Fuel Assemblies from the Viewpoint of Burnup Credit

AbstractNuclear criticality safety analyses (NCSAs) considering burnup credit were performed for the GBC-32 cask. The used nuclear fuel assemblies (UNFAs) discharged from Hanbit Nuclear Power Plant Unit 3 Cycle 6 were loaded into the cask. Their axial burnup distributions and average discharge burnups were evaluated using the DeCART and Multi-purpose Analyzer for Static and Transient Effects of Reactors (MASTER) codes, and NCSAs were performed using SCALE 6.1/STandardized Analysis of Reactivity for Burnup Credit using SCALE (STARBUCS) and Monte Carlo N-Particle transport code, version 6 (MCNP 6). The axial burnup distributions were determined for 20 UNFAs with various initial enrichments and burnups, which were applied to the criticality analysis for the cask system. The UNFAs for 20- and 30-year cooling times were assumed to be stored in the cask. The criticality analyses indicated that keff values for UNFAs with nonuniform axial burnup distributions were larger than those with a uniform distribution, that is, the end effects were positive but much smaller than those with the reference distribution. The axial burnup distributions for 20 UNFAs had shapes that were more symmetrical with a less steep gradient in the upper region than the reference ones of the United States Department of Energy. These differences in the axial burnup distributions resulted in a significant reduction in end effects compared with the reference

Isolation of human Dna2 endonuclease and characterization of its enzymatic properties

In eukaryotes, the creation of ligatable nicks in DNA from flap structures generated by DNA polymerase δ-catalyzed displacement DNA synthesis during Okazaki fragment processing depends on the combined action of Fen1 and Dna2. These two enzymes contain partially overlapping but distinct endonuclease activities. Dna2 is well-suited to process long flaps, which are converted to nicks by the subsequent action of Fen1. In this report, we purified human Dna2 as a recombinant protein from human cells transfected with the cDNA of the human homologue of Saccharomyces cerevisiae Dna2. We demonstrated that the purified human Dna2 enzyme contains intrinsic endonuclease and DNA-dependent ATPase activities, but is devoid of detectable DNA helicase activity. We determined a number of enzymatic properties of human Dna2 including its substrate specificity. When both 5′ and 3′ tailed ssDNAs were present in a substrate, such as a forked-structured one, both single-stranded regions were cleaved by human Dna2 (hDna2) with equal efficiency. Based on this and other properties of hDna2, it is likely that this enzyme facilitates the removal of 5′ and 3′ regions in equilibrating flaps that are likely to arise during the processing of Okazaki fragments in human cells

The susceptibility of Anopheles lesteri to infection with Korean strain of Plasmodium vivax

<p>Abstract</p> <p>Background</p> <p>Following its recent re-emergence, malaria has gained renewed attention as a serious infectious disease in Korea. Three species of the Hyrcanusgroup, <it>Anopheles lesteri, Anopheles sinensis </it>and <it>Anopheles pullus</it>, have long been suspected malaria vectors. However, opinions about their vector ability are controversial. The present study was designed with the aim of determining the susceptibility of these mosquitoes to a Korean isolate of <it>Plasmodium vivax</it>. Also, <it>An. sinensis </it>is primarily suspected to be vector of malaria in Korea, but in Thailand, the same species is described to have less medical importance. Therefore, comparative susceptibility of Thai and Korean strains of <it>An. sinensis </it>with Thai strain of <it>P. vivax </it>may be helpful to understand whether these geographically different strains exhibit differences in their susceptibility or not.</p> <p>Methods</p> <p>The comparative susceptibility of <it>An. lesteri</it>, <it>An. sinensis </it>and <it>An. pullus </it>was studied by feeding laboratory-reared mosquitoes on blood from patients carrying gametocytes from Korea and Thailand.</p> <p>Results</p> <p>In experimental feeding with Korean strain of <it>P. vivax</it>, oocysts developed in <it>An. lesteri</it>, <it>An. sinensis </it>and <it>An. pullus</it>. Salivary gland sporozoites were detected only in <it>An. lesteri </it>and <it>An. sinensis </it>but not in <it>An. pullus</it>. Large differences were found in the number of sporozoites in the salivary glands, with <it>An. lesteri </it>carrying much higher densities, up to 2,105 sporozoites in a single microscope field of 750 × 560 μM, whereas a maximum of 14 sporozoites were found in any individual salivary gland of <it>An. sinensis</it>. Similar results were obtained from a susceptibility test of two different strains of <it>An. sinensis </it>to Thai isolate of <it>P. vivax</it>, and differences in vector susceptibility according to geographical variation were not detected.</p> <p>Conclusion</p> <p>The high sporozoite rate and sporozoite loads of <it>An. lesteri </it>indicate that this species is highly susceptible to infection with <it>P. vivax</it>. <it>Anopheles sinensis </it>appears to have a markedly reduced ability to develop salivary gland infection, whilst in <it>An. pullus</it>, no sporozoites were found in the salivary glands. Provided that the survival rate of <it>An. lesteri </it>is sufficiently high in the field, it would be a highly competent vector of vivax malaria.</p

Intra- and inter-hemispheric effective connectivity in the human somatosensory cortex during pressure stimulation

Background: Slow-adapting type I (SA-I) afferents deliver sensory signals to the somatosensory cortex during low-frequency (or static) mechanical stimulation. It has been reported that the somatosensory projection from SA-I afferents is effective and reliable for object grasping and manipulation. Despite a large number of neuroimaging studies on cortical activation responding to tactile stimuli mediated by SA-I afferents, how sensory information of such tactile stimuli flows over the somatosensory cortex remains poorly understood. In this study, we investigated tactile information processing of pressure stimuli between the primary (SI) and secondary (SII) somatosensory cortices by measuring effective connectivity using dynamic causal modeling (DCM). We applied pressure stimuli for 3 s to the right index fingertip of healthy participants and acquired functional magnetic resonance imaging (fMRI) data using a 3T MRI system. Results: DCM analysis revealed intra-hemispheric effective connectivity between the contralateral SI (cSI) and SII (cSII) characterized by both parallel (signal inputs to both cSI and cSII) and serial (signal transmission from cSI to cSII) pathways during pressure stimulation. DCM analysis also revealed inter-hemispheric effective connectivity among cSI, cSII, and the ipsilateral SII (iSII) characterized by serial (from cSI to cSII) and SII-level (from cSII to iSII) pathways during pressure stimulation. Conclusions: Our results support a hierarchical somatosensory network that underlies processing of low-frequency tactile information. The network consists of parallel inputs to both cSI and cSII (intra-hemispheric), followed by serial pathways from cSI to cSII (intra-hemispheric) and from cSII to iSII (inter-hemispheric). Importantly, our results suggest that both serial and parallel processing take place in tactile information processing of static mechanical stimuli as well as highlighting the contribution of callosal transfer to bilateral neuronal interactions in SII.open1

Synthetic biology for evolutionary engineering: from perturbation of genotype to acquisition of desired phenotype

With the increased attention on bio-based industry, demands for techniques that enable fast and effective strain improvement have been dramatically increased. Evolutionary engineering, which is less dependent on biological information, has been applied to strain improvement. Currently, synthetic biology has made great innovations in evolutionary engineering, particularly in the development of synthetic tools for phenotypic perturbation. Furthermore, discovering biological parts with regulatory roles and devising novel genetic circuits have promoted high-throughput screening and selection. In this review, we first briefly explain basics of synthetic biology tools for mutagenesis and screening of improved variants, and then describe how these strategies have been improved and applied to phenotypic engineering. Evolutionary engineering using advanced synthetic biology tools will enable further innovation in phenotypic engineering through the development of novel genetic parts and assembly into well-designed logic circuits that perform complex tasks.This work was supported by the Bio & Medical Technology Development Program (NRF-2018M3A9H3020459) and the C1 Gas Refnery Program (NRF2016M3D3A1A01913561) through the National Research Foundation (NRF) funded by Ministry of Science and ICT (MSIT). JY was partially supported by Basic Science Research Program (NRF-2018R1C1B6005764) through the National Research Foundation (NRF) funded by MSIT and SWS was partially supported by Creative-Pioneering Researchers Program through Seoul National University (SNU)

In vivo and in vitro studies of Mgs1 suggest a link between genome instability and Okazaki fragment processing

The non-essential MGS1 gene of Saccharomyces cerevisiae is highly conserved in eukaryotes and encodes an enzyme containing both DNA-dependent ATPase and DNA annealing activities. MGS1 appears to function in post-replicational repair processes that contribute to genome stability. In this study, we identified MGS1 as a multicopy suppressor of the temperature-sensitive dna2Δ405N mutation, a DNA2 allele lacking the N-terminal 405 amino acid residues. Mgs1 stimulates the structure-specific nuclease activity of Rad27 (yeast Fen1 or yFen1) in an ATP-dependent manner. ATP binding but not hydrolysis was sufficient for the stimulatory effect of Mgs1, since non-hydrolyzable ATP analogs are as effective as ATP. Suppression of the temperature-sensitive growth defect of dna2Δ405N required the presence of a functional copy of RAD27, indicating that Mgs1 suppressed the dna2Δ405N mutation by increasing the activity of yFen1 (Rad27) in vivo. Our results provide in vivo and in vitro evidence that Mgs1 is involved in Okazaki fragment processing by modulating Fen1 activity. The data presented raise the possibility that the absence of MGS1 may impair the processing of Okazaki fragments, leading to genomic instability

A Protein Profile of Visceral Adipose Tissues Linked to Early Pathogenesis of Type 2 Diabetes Mellitus

Adipose tissue is increasingly recognized as an endocrine organ playing important pathophysiological roles in metabolic abnormalities, such as obesity, cardiovascular disease, and type 2 diabetes mellitus (T2DM). In particular, visceral adipose tissue (VAT), as opposed to subcutaneous adipose tissue, is closely linked to the pathogenesis of insulin resistance and T2DM. Despite the importance of VAT, its molecular signatures related to the pathogenesis of T2DM have not been systematically explored. Here, we present comprehensive proteomic analysis of VATs in drug-naïve early T2DM patients and subjects with normal glucose tolerance. A total of 4,707 proteins were identified in LC-MS/MS experiments. Among them, 444 increased in abundance in T2DM and 328 decreased. They are involved in T2DM-related processes including inflammatory responses, peroxisome proliferator-activated receptor signaling, oxidative phosphorylation, fatty acid oxidation, and glucose metabolism. Of these proteins, we selected 11 VAT proteins that can represent alteration in early T2DM patients. Among them, up-regulation of FABP4, C1QA, S100A8, and SORBS1 and down-regulation of ACADL and PLIN4 were confirmed in VAT samples of independent early T2DM patients using Western blot. In summary, our profiling provided a comprehensive basis for understanding the link of a protein profile of VAT to early pathogenesis of T2DM. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.1

Activation of the EGFR-PI3K-CaM pathway by PRL-1-overexpressing placenta-derived mesenchymal stem cells ameliorates liver cirrhosis via ER stress-dependent calcium

Background Cholesterol accumulation and calcium depletion induce hepatic injury via the endoplasmic reticulum (ER) stress response. ER stress regulates the calcium imbalance between the ER and mitochondria. We previously reported that phosphatase of regenerating liver-1 (PRL-1)-overexpressing placenta-derived mesenchymal stem cells (PD-MSCsPRL−1) promoted liver regeneration via mitochondrial dynamics in a cirrhotic rat model. However, the role of PRL-1 in ER stress-dependent calcium is not clear. Therefore, we demonstrated that PD-MSCsPRL−1 improved hepatic functions by regulating ER stress and calcium channels in a rat model of bile duct ligation (BDL). Methods Liver cirrhosis was induced in Sprague–Dawley (SD) rats using surgically induced BDL for 10 days. PD-MSCs and PD-MSCsPRL−1 (2 × 106 cells) were intravenously administered to animals, and their therapeutic effects were analyzed. WB-F344 cells exposed to thapsigargin (TG) were cocultured with PD-MSCs or PD-MSCsPRL−1. Results ER stress markers, e.g., eukaryotic translation initiation factor 2α (eIF2α), activating transcription factor 4 (ATF4), and C/EBP homologous protein (CHOP), were increased in the nontransplantation group (NTx) compared to the control group. PD-MSCsPRL−1 significantly decreased ER stress markers compared to NTx and induced dynamic changes in calcium channel markers, e.g., sarco/endoplasmic reticulum Ca2+ -ATPase 2b (SERCA2b), inositol 1,4,5-trisphosphate receptor (IP3R), mitochondrial calcium uniporter (MCU), and voltage-dependent anion channel 1 (VDAC1) (*p < 0.05). Cocultivation of TG-treated WB-F344 cells with PD-MSCsPRL−1 decreased cytosolic calmodulin (CaM) expression and cytosolic and mitochondrial Ca2+ concentrations. However, the ER Ca2+ concentration was increased compared to PD-MSCs (*p  < 0.05). PRL-1 activated phosphatidylinositol-3-kinase (PI3K) signaling via epidermal growth factor receptor (EGFR), which resulted in calcium increase via CaM expression. Conclusions These findings suggest that PD-MSCsPRL−1 improved hepatic functions via calcium changes and attenuated ER stress in a BDL-injured rat model. Therefore, these results provide useful data for the development of next-generation MSC-based stem cell therapy for regenerative medicine in chronic liver disease.This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI17C1050) and Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2020M3A9B302618221)