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Key message: Segmental introgression and advanced backcross lines were developed and validated as important tools for improving agronomically important traits in pepper, offering improved sensitivity in detecting quantitative trait loci for breeding. Segmental introgression lines (SILs) and advanced backcross lines (ABs) can accelerate genetics and genomics research and breeding in crop plants. This study presents the development of a complete collection of SILs and ABs in pepper using Capsicum annuum cv. ‘CM334’ as the recipient parent and Capsicum baccatum ‘PBC81’, which displays various agronomically important traits including powdery mildew and anthracnose resistance, as donor parent. Using embryo rescue to overcome abortion in interspecific crosses, and marker-assisted selection with genotyping-in-thousands by sequencing (GT-seq) to develop SILs and ABs containing different segments of the C. baccatum genome, we obtained 63 SILs and 44 ABs, covering 94.8% of the C. baccatum genome. We characterized them for traits including powdery mildew resistance, anthracnose resistance, anthocyanin accumulation, trichome density, plant architecture, and fruit morphology. We validated previously known loci for these traits and discovered new sources of variation and quantitative trait loci (QTLs). A total of 15 QTLs were identified, including four for anthracnose resistance with three novel loci, seven for plant architecture, and four for fruit morphology. This is the first complete collection of pepper SILs and ABs validated for agronomic traits and will enhance QTL detection and serve as valuable breeding resources. Further, these SILs and ABs will be useful for comparative genomics and to better understand the genetic mechanisms underlying important agronomic traits in pepper, ultimately leading to improved crop productivity and sustainability. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to evaluate the possibility of attic cholesteatomas concealed within a tiny retraction of the pars flaccida (classification of Tos and Poulsen type I or II attic retraction) in patients with an intact pars tensa of the tympanic membrane. Methods: The clinical records of patients with a tiny retraction of the pars flaccida and an intact pars tensa of the tympanic membrane who presented to the ear clinic of a tertiary care medical center for the first time between March 2012 and February 2015 were retrospectively reviewed. All patients who had an abnormal pars flaccida of the tympanic membrane were recommended to undergo temporal bone computed tomography (CT) scans. In cases of a soft tissue density lesion within Prussak's space, an exploratory operation was recommended. Results: Among 1320 adult patients, 146 patients (n = 168 ears) who had a tiny attic retraction with a normal pars tensa in unilateral or bilateral ears underwent temporal bone CT scans, and 18 ears had a soft tissue density lesion within Prussak's space. Among the ears with a tiny retraction of the pars flaccida and a normal pars tensa, an attic cholesteatoma was suspected in 10.7% (n = 18 ears) of cases based on the CT scans. After exploratory operations, 2% of patients who underwent CT scans (3 out of 146 patients) and 23% of patients who had a soft tissue density lesion within Prussak's space on CT scans (3 out of 13 operations) had an attic cholesteatoma. Conclusion: All attic retractions which are even in cases of Tos type I or II should be examined closely using endoscopy, microscopy, and, if necessary, temporal bone CT scan. [ABSTRACT FROM AUTHOR]

Interferon (IFN) stimulates a whole repertoire of cellular genes, collectively referred to as ISGs (Interferon-stimulated genes). ISG20, a 3´-5´ exonuclease enzyme, has been previously shown to bind and degrade hepatitis B Virus (HBV) transcripts. Here, we show that the N6-methyladenosine (m6A)-modified HBV transcripts are selectively recognized and processed for degradation by ISG20. Moreover, this effect of ISG20 is critically regulated by m6A reader protein, YTHDF2. Previously, we identified a unique m6A site within HBV transcripts and confirmed that methylation at nucleotide A1907 regulates HBV lifecycle. In this report, we now show that the methylation at A1907 is a critical regulator of IFN-α mediated decay of HBV RNA. We observed that the HBV RNAs become less sensitive to ISG20 mediated degradation when methyltransferase enzymes or m6A reader protein YTHDF2 are silenced in HBV expressing cells. By using an enzymatically inactive form ISG20D94G, we further demonstrated that ISG20 forms a complex with m6A modified HBV RNA and YTHDF2 protein. Due to terminal redundancy, HBV genomic nucleotide A1907 position is acquired two times by pregenomic RNA (pgRNA) during transcription and therefore the sites of methylation are encoded within 5´ and 3´ epsilon stem loops. We generated HBV mutants that lack m6A site at either one (5´ or 3´) or both the termini (5´& 3´). Using these mutants, we demonstrated that m6A modified HBV RNAs are subjected to ISG20-mediated decay and propose sequence of events, in which ISG20 binds with YTHDF2 and recognizes m6A-modified HBV transcripts to carry out the ribonuclease activity. This is the first study, which identifies a hitherto unknown role of m6A modification of RNA in IFN-α induced viral RNA degradation and proposes a new role of YTHDF2 protein as a cofactor required for IFN-α mediated viral RNA degradation. Author summary: Hepatitis B Virus (HBV) is a DNA virus but replicates through a transitional pregenomic RNA (pgRNA) synthesized by reverse transcription. Interferon stimulated antiviral RNase, ISG20 selectively binds to the lower epsilon stem loop of HBV RNA and causes their degradation. Surprisingly this ISG20 binding site is chemically modified by N6-methyladenosine addition to A1907 residue, which resides in the lower region of the epsilon stem loop. This single m6A site occurs twice in due to terminal redundancy of sequences in the pgRNA. We demonstrated herein that IFN-α-induced ISG20 can selectively degrade m6A modified HBV RNA. Using a combined strategy of silencing cellular methyltransferases, m6A binding protein YTHDF2 and the m6A sites mutants, we show that HBV transcripts are resistant to either IFN-α treatment or ectopically introduced ISG20 mediated degradation. YTHDF2 is an m6A binding protein which makes the HBV RNAs unstable. YTHDF2 protein forms a complex with IFN-α stimulated ISG20 and executes the nuclease digestion of the recruited m6A modified transcripts. Absence of cellular m6A machinery (methyltransferases or m6A reader proteins) makes the HBV RNA unresponsive to ISG20 mediated decay. This study provides molecular explanation of IFN-α mediated degradation of m6A modified HBV RNAs. [ABSTRACT FROM AUTHOR]

The Visual Internet of Things has received much attention in recent years due to its ability to get the object location via image information of the scene, attach the visual label to the object, and then return information of scene objects to the network. In particular, face recognition is one of the most suitable means to Visual IoT because face feature is inherent label for human being. However, current state-of-the-art face recognition methods based on huge deep neural networks are difficult to apply in the embedded platform for Visual IoT due to the lack of computational resources. To solve this problem, we present compact deep neural network-based face recognition method for Visual Internet of Things. The proposed method has a low model complexity to operate in an embedded environment while using deep neural networks, which is strong against posture and illumination changes. We show competitive accuracy and performance results for the LFW verification benchmark and the collected mobile face recognition dataset. Additionally, we demonstrate that the implementation of the proposed system can be run in real time on the Android-based mobile embedded platform. [ABSTRACT FROM AUTHOR]

Abstract In a tokamak reactor, plasma facing components (PFCs) can be damaged under high heat flux conditions caused by plasma instabilities. In these conditions, material phase change including melting and evaporation may occur, which can degrade the thermal and structural integrity of PFCs. Effective heat capacity method (EHCM) is one of the numerical techniques used to simulate the melting phenomenon, modifying the heat capacity using the latent heat of the material. However, it has some disadvantages in convergence on mesh sizes resulting in distortion of the prediction result under rapid transient events. In this study, a mesh adaptation technique is implemented to a phase change calculation module based on the EHCM to simulate the melting of the first wall in a tokamak blanket efficiently and to improve the calculation capability under plasma disruption. Mesh adaptation procedure consists of adopting an appropriate monitoring function for tracking melting front of the blanket first wall and reconstructing the mesh near it at each time step. As the mesh adaptation technique is applied to the EHCM, its numerical efficiency is improved in the proposed phase change calculation module. Then, the phase change simulation module was used to analyze the thermal-hydraulic behavior of the water-cooled breeding blanket for the high heat flux conditions coupled with the nuclear reactor safety analysis code, MARS. [ABSTRACT FROM AUTHOR]

Plasma facing components of tokamak reactors such as ITER or the Korean fusion demonstration reactor (K-DEMO) can be subjected to damage by plasma instabilities. Plasma disruptions like vertical displacement event (VDE) with high heat flux, can cause melting and vaporization of plasma facing materials and burnout of coolant channels. In this study, to simulate melting and vaporization of the first wall in a water-cooled breeding blanket under VDE, one-dimensional heat equations were solved numerically by using an in-house first wall module, including phase change models, effective heat capacity method, and evaporation model. For thermal-hydraulics, the in-house first wall analysis module was coupled with the nuclear reactor safety analysis code, MARS, to take advantage of its prediction capability for two-phase flow and critical heat flux (CHF) occurrence. The first wall was proposed for simulation according to the conceptual design of the K-DEMO, and the heat flux of plasma disruption with a value of 600 MW/m 2 for 0.1 s was applied. The phase change simulation results were analyzed in terms of the melting and evaporation thicknesses and the occurrence of CHF. The thermal integrity of the blanket first wall is discussed to confirm whether the structural material melts for the given conditions. [ABSTRACT FROM AUTHOR]

The liver-specific microRNA miR-122, which has essential roles in liver development and metabolism, is a key proviral factor for hepatitis C virus (HCV). Despite its crucial role in the liver and HCV life cycle, little is known about the molecular mechanism of miR-122 expression regulation by HCV infection. Here, we show that the HCV core protein downregulates the abundance of miR-122 by promoting its destabilization via the inhibition of GLD-2, a non-canonical cytoplasmic poly(A) polymerase. The decrease in miR-122 expression resulted in the dysregulation of the known functions of miR-122, including its proviral activity for HCV. By high-throughput sequencing of small RNAs from human liver biopsies, we found that the 22-nucleotide (nt) prototype miR-122 is modified at its 3′ end by 3′-terminal non-templated and templated nucleotide additions. Remarkably, the proportion of miR-122 isomers bearing a single nucleotide tail of any ribonucleotide decreased in liver specimens from patients with HCV. We found that these single-nucleotide-tailed miR-122 isomers display increased miRNA activity and stability over the 22-nt prototype miR-122 and that the 3′-terminal extension is catalyzed by the unique terminal nucleotidyl transferase activity of GLD-2, which is capable of adding any single ribonucleotide without preference of adenylate to the miR-122 3′ end. The HCV core protein specifically inhibited GLD-2, and its interaction with GLD-2 in the cytoplasm was found to be responsible for miR-122 downregulation. Collectively, our results provide new insights into the regulatory role of the HCV core protein in controlling viral RNA abundance and miR-122 functions through miR-122 stability modulation. [ABSTRACT FROM AUTHOR]

According to the conceptual design of the fusion DEMO reactor proposed by the National Fusion Research Institute of Korea, the water-cooled breeding blanket system incorporates a total of 736 blanket modules. The heat flux and neutron wall loading to each blanket module vary along their poloidal direction, and hence, thermal analysis for at least one blanket sector is required to confirm that the temperature limitations of the materials are satisfied in all the blanket modules. The present paper proposes a methodology of thermal analysis for multiple modules of the blanket system using a nuclear reactor thermal-hydraulic analysis code, MARS-KS. In order to overcome the limitations of the code, caused by the restriction on the number of computational nodes, a supervisor program was devised, which handles each blanket module separately at first, and then corrects the flow rate, considering pressure drops that occur in each module. For a feasibility test of the proposed methodology, 46 blankets in a single sector were simulated; the calculation results of the parameters, such as mass flow, pressure drops, and temperature distribution in the multiple blanket modules showed that the multi-module analysis method can be used for efficient thermal-hydraulic analysis of the fusion DEMO reactor. [ABSTRACT FROM AUTHOR]

Background: Adjuvant Online (AOL) is web-accessible risk-assessment model that predicts the mortality and the benefits of adjuvant therapy (www.newadjuvantonline.com). AOL has never been validated for Asian colon cancer patients. Methods: Using the Yonsei Tumor Registry database, patients who were treated within the Yonsei University Health System between 1990 and 2005 for T1-4, N0-2, and M0 colon cancer were included in the calculations for survival. Observed and predicted 5-year overall survival was compared for each patient. Results: The median age of the study population of 1431 patients was 60 years (range, 15–87 years), and the median follow-up duration was 7.9 years (range, 0.06–19.8 years). The predicted 5-year overall survival rate (77.7%) and observed survival (79.5%) was not statistically different (95% Confidential interval, 76.3–81.5) in all patients. Predicted outcomes were within 95% confidential interval of observed survival in both stage II and III disease, including most demographic and pathologic subgroups. Moreover, AOL more accurately predicted OS for patients with stage II than stage III. Conclusions: AOL tended to offer reliable prediction for 5-year overall survival and could be used as a decision making tool for adjuvant treatment in Korean colon cancer patients whose prognosis is similar to other Asian patients. [ABSTRACT FROM AUTHOR]

• A critical heat flux (CHF) experiment was performed on a heater rod under inclined and rolling conditions. • The CHF is enhanced under inclination for most conditions. • For rolling, the precursor of CHF existed under most experimental conditions. • The effect of inclination of the CHF is weakened by rolling motion. • The results may be useful for the safety analysis of marine reactors. Offshore floating nuclear power plants have been developed to supply power to remote regions. Since they are operated in an ocean environment, the thermal–hydraulic phenomena in the reactor core may be different from those in the land-based reactors. However, the experimental study on critical heat flux (CHF) under ocean condition is limited and its mechanism is unclear. In this study, an experiment was performed to measure CHF in a single heater rod under inclined and rolling conditions. To create the required environment to simulate the conditions of inclination and rolling, a rolling platform was designed and constructed. It could provide an inclination of up to 45° and rolling of up to 45° with a minimum period of 6 s. In the CHF test loop, the experimental conditions were set up to correspond to pressurized water reactor conditions, using the fluid-to-fluid scaling method. The working fluid used was R134a. The test section was a concentric annular channel composed of a heater rod and an unheated tube housing. The result of the inclination experiment suggested that in the most cases, the CHF was enhanced when compared with the vertical condition. In a limited number of cases of low-pressure and high-flow conditions, the CHF was degraded as compared to the vertical condition. These variations were proportional to the inclination angle and inversely proportional to the mass flux. From the results of the rolling experiment, a precursor of CHF was observed with a large fluctuation in temperature before the CHF, and its trigger was related to the CHF value of the inclined case. Based on this observation, the overall relations between the vertical, inclined, and rolling CHF values were derived. It was concluded that the rolling motion weakened the CHF enhancement and degradation effects of the inclination. [ABSTRACT FROM AUTHOR]

Pulmonary manifestations of benign metastasizing leiomyoma (BML) usually include multiple well-defined, round, bilateral nodules. Low-grade endometrial stromal sarcoma (LG-ESS) is a rare uterine tumor. A 70-year-old woman visited the clinic complaining of acute cough and dyspnea in April 2017. Chest computed tomography (CT) revealed pneumothorax and multiple pulmonary nodules. She had a history of hysterectomy for uterine leiomyoma 23 years ago. Biopsy revealed that the pulmonary masses were consistent with BML. However, the patient had two subsequent episodes of acute, recurrent respiratory distress, accompanied by massive pleural effusions and hydropneumothorax over the next two years. A chest CT performed for acute dyspnea revealed large and multiple hydropneumothoraces. The size and distribution of pulmonary masses were aggravated along with cystic changes and bilateral pleural effusions. Given this aggressive feature, additional immunohistochemical findings and gynecologic pathologist review confirmed the correct diagnosis to be LG-ESS. After initiating anti-estrogen therapy, the patient achieved a partial response, without recurrence of symptoms, for 28 months. Metastatic LG-ESS responds well to anti-hormonal therapy. If the clinical pattern of a disease is different than expected, the possibility of a correction in the diagnosis should be considered. [ABSTRACT FROM AUTHOR]

• Scaling analysis was performed under single-phase natural circulation under motion. • The inclination angle can be preserved or reduced in the scaled-down model. • Simplified test loops of prototype and model were simulated using a system code. • Natural circulation similarity criteria under motion were verified with MARS-KS. In designing a thermal–hydraulic facility simulating a floating nuclear power plant, the scaling of dynamic motion is necessary. As natural circulation under motion is a significant phenomenon in floating nuclear reactors, a scaling analysis for single-phase natural circulation was performed, and similarity criteria were derived for inclination, frame acceleration, and rotational motion conditions. The inclination angle can be reduced or maintained in the scaled model with adjustments to the hydraulic diameter and volumetric heat generation. In addition, the amplitudes of acceleration and angle should be maintained in the model under motion, and their periods follow the time scale. Thereafter, the similarity criteria were verified using a system analysis code to simulate virtual test loops of the prototype and scaled-down models for a one-dimensional single-phase natural circulation under various motion conditions. In result, this similarity criteria can be used to design a scaled-down single-phase natural circulation facility under motion conditions. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and coronavirus disease 2019 (COVID-19) are emerging zoonotic diseases caused by coronavirus (CoV) infections. The viral RNA-dependent RNA polymerase (RdRp) has been suggested as a valuable target for antiviral therapeutics because the sequence homology of CoV RdRp is highly conserved. We established a cell-based reporter assay for MERS-CoV RdRp activity to test viral polymerase inhibitors. The cell-based reporter system was composed of the bicistronic reporter construct and the MERS-CoV nsp12 plasmid construct. Among the tested nine viral polymerase inhibitors, ribavirin, sofosbuvir, favipiravir, lamivudine, zidovudine, valacyclovir, vidarabine, dasabuvir, and remdesivir, only remdesivir exhibited a dose-dependent inhibition. Meanwhile, the Z-factor and Z′-factor of this assay for screening inhibitors of MERS-CoV RdRp activity were 0.778 and 0.782, respectively. Ribavirin and favipiravir did not inhibit the MERS-CoV RdRp activity, and non-nucleoside HCV RdRp inhibitor, dasabuvir, partially inhibited MERS-CoV RdRp activity. Taken together, the cell-based reporter assay for MERS-CoV RdRp activity confirmed remdesivir as a direct inhibitor of MERS-CoV RdRp in cells. A cell-based MERS-CoV RdRp activity reporter assay is reliable and accurate for screening MERS-CoV RdRp-specific inhibitors. It may provide a valuable platform for developing antiviral drugs for emerging CoV infections. [ABSTRACT FROM AUTHOR]

AbstractThis study experimentally investigated the flow boiling critical heat flux (CHF) under heaving conditions pertinent to floating nuclear power plants (FNPPs). Experiments were conducted using R134a to simulate the operational pressure of pressurized water reactors, extending the CHF database to a pressure range of 5 to 18 MPa. The tested heaving motion reached up to 0.6 g of maximum acceleration, with a period that varied from 3 to 5.3 s. A parametric trend involving mass flux, critical quality, and motion conditions was analyzed through extensive tests encompassing static and heaving conditions.The results showed that CHF reduction was observed due to the effect of heaving acceleration, even in the absence of oscillations in other thermal-hydraulic factors. The CHF reduction was up to 9% in the present experimental conditions. The heaving motion effect was prominent under two specific thermal-hydraulic conditions: when the critical quality was close to zero and when it exceeded the value of 0.6. Furthermore, an examination of wall temperature responses suggested that a longer period of heaving motion can lead to an earlier occurrence of CHF. This fundamental effort was conducted to enhance the understanding of the CHF mechanism under motion conditions, with the aim of contributing to the safe and efficient design of FNPPs. [ABSTRACT FROM AUTHOR]

BACKGROUND: Chronic stroke can impair cardiopulmonary function, mobility, and daily activities. This study assessed the impact of robot-assisted gait training (RAGT) on such impairments. OBJECTIVE: To investigate the effects of robot-assisted gait training on cardiopulmonary function, walking ability, lower extremity function and strength, activities of daily living (ADLs), and blood test results among individuals with chronic stroke. METHODS: A multicenter, prospective, single-blinded, randomized controlled trial with 22 chronic stroke participants compared RAGT against a control exercise regimen. RAGT involved three days weekly sessions of high-intensity interval training for 8 weeks (24 sessions) with a Morning Walk® device. The control group also performed home exercises. (24 sessions) Measures included VO2max, Functional Ambulatory Category, 2-minute walk test, 10-meter walk test, Motricity Index-Lower, Korean version of the Fugl-Meyer Assessment Scale, Modified Barthel Index, Berg Balance Scale, muscle strength, InBody body composition, and blood tests (cholesterol, lipid, glucose). RESULTS: RAGT significantly improved VO2max, gait, balance, and lower limb strength compared with controls, with significant improvements in 2-minute walk test, 10-meter walk test, Motricity Index-Lower, and Fugl-Meyer Assessment outcomes. No changes were seen in muscle mass or blood markers. CONCLUSION: RAGT enhances cardiopulmonary function and ambulatory capacity in chronic stroke patients, underscoring its potential in stroke rehabilitation. [ABSTRACT FROM AUTHOR]

SUMMARY: Fruit color is one of the most important traits in peppers due to its esthetic value and nutritional benefits and is determined by carotenoid composition, resulting from diverse mutations of carotenoid biosynthetic genes. The EMS204 line, derived from an EMS mutant population, presents bright‐red color, compared with the wild type Yuwolcho cultivar. HPLC analysis indicates that EMS204 fruit contains more zeaxanthin and less capsanthin and capsorubin than Yuwolcho. MutMap was used to reveal the color variation of EMS204 using an F3 population derived from a cross of EMS204 and Yuwolcho, and the locus was mapped to a 2.5‐Mbp region on chromosome 2. Among the genes in the region, a missense mutation was found in ZEP (zeaxanthin epoxidase) that results in an amino acid sequence alteration (V291 → I). A color complementation experiment with Escherichia coli and ZEP in vitro assay using thylakoid membranes revealed decreased enzymatic activity of EMS204 ZEP. Analysis of endogenous plant hormones revealed a significant reduction in abscisic acid content in EMS204. Germination assays and salinity stress experiments corroborated the lower ABA levels in the seeds. Virus‐induced gene silencing showed that ZEP silencing also results in bright‐red fruit containing less capsanthin but more zeaxanthin than control. A germplasm survey of red color accessions revealed no similar carotenoid profiles to EMS204. However, a breeding line containing a ZEP mutation showed a very similar carotenoid profile to EMS204. Our results provide a novel breeding strategy to develop red pepper cultivars containing high zeaxanthin contents using ZEP mutations. Significance Statement: Despite health benefits, such as macular protection and antioxidant effects, most crops contain low levels of zeaxanthin. Orange pepper is an important source of zeaxanthin which is scarce in our diet. We demonstrated that a leaky mutation in zeaxanthin epoxidase leads to the development of bright‐red fruit, elevated zeaxanthin levels, and affects endogenous plant hormones in pepper. Our findings suggest a novel breeding strategy for developing red pepper cultivars with high levels of zeaxanthin. [ABSTRACT FROM AUTHOR]

Background: Anthracnose is a fungal disease caused by Colletotrichum spp. that has a significant impact on worldwide pepper production. Colletotrichum scovillei is the most common pathogenic anthracnose-causing species in the Republic of Korea. Results: The resistances of 197 pepper (Capsicum chinense) accessions deposited in Korea's National Agrobiodiversity Center were evaluated for their response against the virulent pathogens Colletotrichum acutatum isolate 'KSCa-1' and C. scovillei isolate 'Hana') in the field and in vitro methods for three consecutive years (2018 to 2020). The severity of the disease was recorded and compared between inoculation methods. Six phenotypically resistant pepper accessions were selected based on three years of disease data. All of the selected resistant pepper accessions outperformed the control resistant pepper in terms of resistance (PI 594,137). A genome-wide association study (GWAS) was carried out to identify single nucleotide polymorphisms (SNPs) associated with anthracnose resistance. An association analysis was performed using 53,518 SNPs and the disease score of the 2020 field and in vitro experiment results. Both field and in vitro experiments revealed 25 and 32 significantly associated SNPs, respectively. These SNPs were found on all chromosomes except Ch06 and Ch07 in the field experiment, whereas in the in vitro experiment they were found on all chromosomes except Ch04 and Ch11. Conclusion: In this study, six resistant C. chinense accessions were selected. Additionally, in this study, significantly associated SNPs were found in a gene that codes for a protein kinase receptor, such as serine/threonine-protein kinase, and other genes that are known to be involved in disease resistance. This may strengthen the role of these genes in the development of anthracnose resistance in Capsicum spp. As a result, the SNPs discovered to be strongly linked in this study can be used to identify a potential marker for selecting pepper material resistant to anthracnose, which will assist in the development of resistant varieties. [ABSTRACT FROM AUTHOR]

The thermal design of a breeding blanket for the Korean Fusion DEMOnstration reactor (K-DEMO) is evaluated using the Multidimensional Analysis of Reactor Safety (MARS-KS) code in this study. The MARS-KS code has advantages in simulating transient two-phase flow over computational fluid dynamics (CFD) codes. In order to confirm the prediction capability of the code for the present blanket system, the calculation results were compared with the CFD prediction. The results of MARS-KS calculation and CFD prediction are in good agreement. Afterwards, a transient simulation for a conceptual problem was carried out so as to show the applicability of MARS-KS for a transient or accident condition. Finally, a methodology to simulate the multiple blanket modules is proposed. [ABSTRACT FROM AUTHOR]

The research and development efforts are underway to utilize nuclear power across various fields with the aim of carbon neutrality. As part of these efforts, floating nuclear power plants have been proposed. These systems require a compact reactor design due to spatial and weight constraints. Therefore, there is potential for the use of helical-shaped fuel, which offers various advantages in designing high-power-density reactors. However, the effect of non-circular fuel shapes on Critical Heat Flux (CHF) under ocean conditions is not well understood. In this study, the CHF on a helical finned rod heater was experimentally examined under rolling conditions. The experimental results showed that the CHF during rolling conditions varied compared to vertical and inclined CHF. The local wall temperature behavior leading rolling CHF was analyzed for each CHF regime. Commonly, significant heat transfer degradation was observed when reaching the maximum roll angle. As a result, it was found that rolling CHF was decreased compared to inclined CHF due to the influence of tangential force, and the degree of decrease was greater with shorter periods. The CHF database and insights gained from this research can contribute to the design of a nuclear reactor using helical-shaped fuel under ocean conditions. [ABSTRACT FROM AUTHOR]

• A critical heat flux (CHF) experiment was conducted with a helical finned rod under heaving conditions. • Effects of oscillatory acceleration and heater geometry on CHF were confirmed. • CHF decreased around the critical quality of 0 and above 0.8 due to reduced gravity. • CHF increased around the critical quality of −0.2 due to helical fin structure. Floating nuclear power plants (FNPPs) have garnered attention as a promising solution to provide clean energy and seawater desalination, addressing the energy needs of remote areas without access to the power grid. However, the oceanic environment can introduce variations in thermal-hydraulic phenomena, particularly affecting Critical Heat Flux (CHF). While few experimental studies have explored CHF under rolling and heaving motions, there is a need to expand the experimental database to encompass various test section geometries. This is necessary to elucidate the motion effect on the CHF mechanism and evaluate the applicability of helical finned fuel rods for FNPPs. Hence, the present study conducted experiments to assess the heaving motion effect on the flow boiling CHF of a helical finned rod. To simulate the heaving motion of ocean environments, the tests were performed on a heaving motion platform with a maximum acceleration of 0.6 g and periods ranging from 3 to 6 s. The CHF test loop utilized refrigerant R134a as the working fluid, with test conditions representative of pressurized water reactor operations. The test section featured a helical finned heater rod inside an annulus channel. CHF tests were conducted in conditions of both static and heaving motion to examine the CHF variation due to the oscillatory acceleration field. The results revealed that CHF could exhibit decreases of up to 5% or increases of up to 3%, depending on the specific thermal-hydraulic and motion conditions in the present test configuration. Notably, similar to previous experiments involving a bare heater rod, CHF reduction due to heaving motion was prominent in two specific areas: one where the critical quality neared zero and another where it exceeded 0.8. Additionally, an increase in CHF was observed around the critical quality of -0.2, a phenomenon not observed in bare rod tests. This suggests a unique mechanism associated with the helical fin structure. This study proposed CHF variation mechanisms for each region based on the experimental observations. [ABSTRACT FROM AUTHOR]

Objectives Hepatitis C virus (HCV) infection causes chronic liver disease and is a major public health problem worldwide. The aim of this study was to evaluate the potential of Monascus pigment derivatives, which were derived from a microbial secondary metabolite synthesized from polyketides by Monascus spp., as HCV antiviral agents. Methods We performed an in vitro RNA-dependent RNA polymerase (RdRp) assay to screen for HCV RdRp inhibitors. The anti-HCV activity of RdRp inhibitors in HCV-replicating cells was evaluated by quantification of the RNA viral genome. Molecular docking analysis was performed to predict the binding sites of the selected RdRp inhibitors. Results We have identified a Monascus pigment and its derivatives as inhibitors of the HCV NS5B RdRp. A group of Monascus orange pigment (MOP) amino acid derivatives, in which the reactive oxygen moiety was changed to amino acids, significantly inhibited HCV replication. Further, combination of the MOP derivatives (Phe, Val or Leu conjugates) with interferon (IFN)-α inhibited HCV replication more than IFN-α treatment alone. Lastly, molecular docking studies indicate the inhibitors may bind to a thumb subdomain allosteric site of NS5B. The antiviral activity of the MOP derivatives was related to a modulation of the mevalonate pathway, since the mevalonate-induced increase in HCV replication was suppressed by the MOP compounds. Conclusions Our results identify amino acid derivatives of MOP as potential anti-HCV agents and suggest that their combination with IFN-α might offer an alternative strategy for the control of HCV replication. [ABSTRACT FROM PUBLISHER]

• Bacterial wilt (BW) resistance in pepper is difficult to study due to its complex oligogenic inheritance in pepper. • Combined bi-parental quantitative trait loci (QTL) mapping and a genome-wide association study (GWAS) were used to map BW-resistant loci in pepper. • The combined mapping approaches revealed five BW-resistant loci-associated SNPs on chromosome 4, 5, and 8 and found 13 candidate genes for BW resistance in pepper. Ralstonia solanacearum is responsible for causing bacterial wilt (BW) disease in solanaceous crops, leading to significant crop losses. The challenge in controlling this disease lies in its soil-borne nature and the complex genetic architecture of R. solanacearum. Moreover, the complex oligogenic nature of resistance genes makes breeding resistant cultivars in peppers difficult. In this study, we combined bi-parental quantitative trait loci (QTL) mapping and a genome-wide association study (GWAS) to map loci associated with BW resistance. An F 5:7 recombinant inbred lines were subjected to genotyping by sequencing (GBS) and the GWAS panel was genotyped using an Illumina PepperSNP 16 K array genotyping platform. A significant QTL (QTL.Bw5) was identified on the telomeric region of chromosome 5. GWAS analysis also identified four loci associated with BW resistance (GWAS.Bw.4, GWAS.Bw.5, GWAS.Bw.8.1 , and GWAS.Bw.8.2) on chromosomes 4, 5, and 8. Our study revealed 13 candidate genes within QTL regions and in the vicinity of GWAS single-nucleotide polymorphisms (SNPs) based on their biological gene functions. A majority of these candidate genes were associated with plant stress, defense, or hormone signaling pathways. The QTLs and GWAS-SNPs related to BW resistance will provide valuable information for further characterizing resistance genes and developing markers to facilitate the breeding of resistant pepper cultivars. [ABSTRACT FROM AUTHOR]

Subspecies of Brassica rapa are morphologically and genetically diverse, and include a variety of fresh vegetables grown worldwide. Among them, turnip (B. rapa subsp. rapa) produces a large bulbous taproot, and thus is primarily consumed as a root vegetable in Europe and Asia. In comparison to Chinese cabbage (B. rapa subsp. pekinensis), however, genetic analysis and breeding of turnip is hampered in practice due in part to scarcity of useful genetic resources. In this study, we produced a doubled haploid (DH) line of Ganghwa turnip, an heirloom specialty crop in Korea that is usually propagated by open pollination. Microspores were isolated from young flower buds of Ganghwa turnip, and shoots and roots were sequentially regenerated in vitro. Chromosome doubling was induced with the colchicine treatment, and verified by flow cytometry analysis. The G14 DH line displayed uniformity in overall morphology compared to heterogeneous commercial Ganghwa turnips. The whole genome of G14 was sequenced on an Illumina HiSeq 4000 platform, and the reads mapped onto the B. rapa reference genome identified 1,163,399 SNPs and 779,700 indels. Despite high similarity in overall genome sequence, turnips and Chinese cabbage have different compositions of transposable elements (TEs). In particular, long terminal repeat (LTR) retrotransposons are more enriched in turnips than in Chinese cabbage genomes, in which the gypsy elements are classified as major LTR sequences in the turnip genome. These findings suggest that subspecies-specific TE divergence is in part responsible for huge phenotypic variations observed within the same species. [ABSTRACT FROM AUTHOR]

Finding the same individual across cameras in disjoint views at different locations and times, which is known as person re-identification (re-id), is an important but difficult task in intelligent visual surveillance. However, to build a practical re-id system for large-scale and crowdsourced environments, the existing approaches are largely unsuitable because of their high model complexity. In this paper, we present a deep feature learning framework for automated large-scale person re-id with low computational cost and memory usage. The experimental results show that the proposed framework is comparable to the state-of-the-art methods while having low model complexity. [ABSTRACT FROM AUTHOR]

• CHF on a helical finned rod under vertical and inclined conditions was studied. • The helical fin effect on CHF is determined by the CHF regime. • In DNB regime, the helical fin lowered the inclined CHF compared to the vertical CHF on average 2%. • In dryout regime, inclined CHF is larger than vertical CHF on average 7% due to gravity being dominant. Recently, diverse marine applications of nuclear power are being considered to meet the carbon reduction goals in the maritime industries. One of the distinctive characteristics of marine nuclear reactors is the limit in space and it requires high power density. To address this problem, tight lattice bundle with a helical shaped non-circular fuel rods can be employed. However, the critical heat flux (CHF) mechanisms for such alternative fuel rods have not been adequately investigated experimentally. In particular, no open-access CHF experiment under inclined and motion conditions in accordance with marine conditions has yet been reported. Thus, in this study, the CHF on a helical-finned heater was measured under static vertical and inclined conditions. Considering the reactor operating conditions, a high-pressure experiment was performed using refrigerant R134a. The fin and inclination effects were evaluated based on a comparison between the results of this study and the CHF data for a bare-rod under inclined condition obtained from a previous study. In addition, the inclination effect was analyzed phenomenologically based on the wall temperature behavior. The findings in this work can contribute to designing a marine nuclear reactor core by quantifying the effects of inclination on the CHF. [ABSTRACT FROM AUTHOR]

The hepatitis C virus (HCV) internal ribosome entry site (IRES) that directs cap-independent viral translation is a primary target for small interfering RNA (siRNA)-based HCV antiviral therapy. However, identification of potent siRNAs against HCV IRES by bioinformatics-based siRNA design is a challenging task given the complexity of HCV IRES secondary and tertiary structures and association with multiple proteins, which can also dynamically change the structure of this cis-acting RNA element. In this work, we utilized siRNA tiling approach whereby siRNAs were tiled with overlapping sequences that were shifted by one or two nucleotides over the HCV IRES stem-loop structures III and IV spanning nucleotides (nts) 277–343. Based on their antiviral activity, we mapped a druggable region (nts 313–343) where the targets of potent siRNAs were enriched. siIE22, which showed the greatest anti-HCV potency, targeted a highly conserved sequence across diverse HCV genotypes, locating within the IRES subdomain IIIf involved in pseudoknot formation. Stepwise target shifting toward the 5′ or 3′ direction by 1 or 2 nucleotides reduced the antiviral potency of siIE22, demonstrating the importance of siRNA accessibility to this highly structured and sequence-conserved region of HCV IRES for RNA interference. Nanoparticle-mediated systemic delivery of the stability-improved siIE22 derivative gs_PS1 siIE22, which contains a single phosphorothioate linkage on the guide strand, reduced the serum HCV genome titer by more than 4 log10 in a xenograft mouse model for HCV replication without generation of resistant variants. Our results provide a strategy for identifying potent siRNA species against a highly structured RNA target and offer a potential pan-HCV genotypic siRNA therapy that might be beneficial for patients resistant to current treatment regimens. [ABSTRACT FROM AUTHOR]

Background and Purpose: Hepatitis C virus (HCV) infection is responsible for various chronic inflammatory liver diseases. Here, we have identified a naturally occurring compound with anti-HCV activity and have elucidated its mode of antiviral action.Experimental Approach: Luciferase reporter and real-time RT-PCR assays were used to measure HCV replication. Western blot, fluorescence-labelled HCV replicons and infectious clones were employed to quantitate expression levels of viral proteins. Resistant HCV mutant mapping, in vitro NS3 protease, helicase, NS5B polymerase and drug affinity responsive target stability assays were also used to study the antiviral mechanism.Key Results: A resveratrol tetramer, vitisin B from grapevine root extract showed high potency against HCV replication (EC50 = 6 nM) with relatively low cytotoxicity (EC50 >10 μM). Combined treatment of vitisin B with an NS5B polymerase inhibitor (sofosbuvir) exhibited a synergistic or at least additive antiviral activity. Analysis of a number of vitisin B-resistant HCV variants suggested an NS3 helicase as its potential target. We confirmed a direct binding between vitisin B and a purified NS3 helicase in vitro. Vitisin B was a potent inhibitor of a HCV NS3 helicase (IC50 = 3 nM). In vivo, Finally, we observed a preferred tissue distribution of vitisin B in the liver after i.p. injection in rats, at clinically attainable concentrations. Conclusion and Implications Vitisin B is one of the most potent HCV helicase inhibitors identified so far. Vitisin B is thus a prime candidate to be developed as the first HCV drug derived from natural products. [ABSTRACT FROM AUTHOR]

Abstract: In order to identify the inhibitors of hepatitis C virus (HCV) replication with a novel scaffold via a mechanistically unbiased approach, we screened our in-house library composed of ∼6000 compounds with various chemical structures by using the renilla luciferase-linked genotype 2a reporter virus, and we identified a series of compounds containing an indole moiety that were active against HCV replication. Based on this result, we further synthesized three groups of indole derivatives and evaluated their inhibitory effects on HCV replication. In the present structure–activity relationship study of these indole derivatives, we discovered that compound 12e was the most potent inhibitor of HCV replication with minimal cytotoxicity (EC50 = 1.1 μM, EC90 = 2.1 μM, and CC50 = 61.8 μM). We also confirmed that compound 12e caused a dose- and time-dependent reduction of viral RNA as well as viral protein levels in both genotype 2a J6/JFH1 RNA-transfected cells and genotype 1b Bart79I subgenomic replicon cells. Finally, a genetic mapping study of mutant viruses resistant to compound 12e revealed that NS5B RNA polymerase was the potential target. This finding was further validated by demonstration of inhibition of NS5B RNA polymerase in vitro by compound 12e (IC50 = 292 nM). Compound 12e may serve as a valuable candidate for the development of a new class of HCV NS5B RNA polymerase inhibitors in the future. [Copyright &y& Elsevier]

Abstract: The hepatitis C virus (HCV) core protein is the primary protein component of the nucleocapsid that encapsidates the viral RNA genome. Besides its role as a viral structural protein, the core protein is implicated in HCV chronic infection-associated liver diseases by induction of reactive oxygen species (ROS) production and modulation of apoptosis. Here, we show that interaction of the core protein, through its N-terminal domain (amino acids 1–75), with heat shock protein (Hsp60) is critical for the induction of ROS production, leading to sensitization of core protein-expressing cells to apoptosis induced by tumor necrosis factor-α (TNF-α). Moreover, overexpression of Hsp60 rescued the core protein-expressing cells from cell death by reducing ROS production. Collectively, our results suggest that impairment of Hsp60 function through binding of HCV core protein contributes to HCV viral pathogenesis by ROS generation and amplification of the apoptotic effect of TNF-α. [Copyright &y& Elsevier]

Recent outbreaks of zoonotic coronaviruses, such as Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have caused tremendous casualties and great economic shock. Although some repurposed drugs have shown potential therapeutic efficacy in clinical trials, specific therapeutic agents targeting coronaviruses have not yet been developed. During coronavirus replication, a replicase gene cluster, including RNA-dependent RNA polymerase (RdRp), is alternatively translated via a process called -1 programmed ribosomal frameshift (−1 PRF) by an RNA pseudoknot structure encoded in viral RNAs. The coronavirus frameshifting has been identified previously as a target for antiviral therapy. In this study, the frameshifting efficiencies of MERS-CoV, SARS-CoV and SARS-CoV-2 were determined using an in vitro −1 PRF assay system. Our group has searched approximately 9689 small molecules to identify potential −1 PRF inhibitors. Herein, we found that a novel compound, 2-(5-acetylthiophen-2yl)furo[2,3-b]quinoline (KCB261770), inhibits the frameshifting of MERS-CoV and effectively suppresses viral propagation in MERS-CoV-infected cells. The inhibitory effects of 87 derivatives of furo[2,3-b]quinolines were also examined showing less prominent inhibitory effect when compared to compound KCB261770. We demonstrated that KCB261770 inhibits the frameshifting without suppressing cap-dependent translation. Furthermore, this compound was able to inhibit the frameshifting, to some extent, of SARS-CoV and SARS-CoV-2. Therefore, the novel compound 2-(5-acetylthiophen-2yl)furo[2,3-b]quinoline may serve as a promising drug candidate to interfere with pan-coronavirus frameshifting. [ABSTRACT FROM AUTHOR]

The kinase C-related kinase 2 (PRK2), which phosphorylates hepatitis C virus (HCV) RNA polymerase, is a proviral factor enhancing HCV replication. Here, we report on the in vivo anti-HCV efficacy of HA1077, which inhibits viral genome replication by targeting PRK2 and displays viral entry inhibitory activity by targeting Rho-associated kinase. HA1077 showed synergistic antiviral activity selectively with nonstructural protein 5 A (NS5A) inhibitors including daclatasvir (DCV). HA1077 oral administration substantially reduced serum viral loads in mice bearing HCV genotype 2a-replicating Huh7 xenografts. When administered with DCV, HA1077 potentiated the antiviral efficacy of DCV and suppressed the generation of DCV resistance-associated variants (RAVs). By deep-sequencing analysis, we uncovered an unprecedented DCV-induced polymorphism at the poly-proline motif (PxxPxxP) of NS5A. Coadministration of HA1077 reduced such a polymorphism. Overall, our results demonstrate the potential therapeutic benefit of combination therapy with HA1077 plus DCV for HCV patients carrying emerging or pre-existing RAVs toward NS5A inhibitors. [ABSTRACT FROM AUTHOR]