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Parkinson’s disease (PD), characterized by degeneration of dopaminergic neurons, share pathogenic features with obesity, including mitochondrial dysfunction and oxidative stress. Paraoxonase 2 (PON2) is an inner mitochondrial membrane protein that is highly expressed in dopaminergic neurons and is involved in the regulation of mitochondrial oxidative stress. However, no drug targeting PON2 has ever been developed for the treatment of PD. Here, we show that vutiglabridin, a clinical phase 2-stage drug for the treatment of obesity, has therapeutic effects in PD models, targeting mitochondrial PON2. Vutiglabridin penetrates into the brain, binds to PON2, and restores 1-methyl-4-phenylpyridinium (MPP+)-induced mitochondrial dysfunction in SH-SY5Y neuroblastoma cells. Knockdown of PON2 by lentiviral shRNA infection abolished the effects of vutiglabridin on mitochondria. In mice, vutiglabridin significantly alleviated motor impairments and damage to dopaminergic neurons in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model, and these effects were also abolished in PON2-knockdown mice, suggesting that vutiglabridin is neuroprotective via PON2. Extensive in vitro and in vivo assessment of potential neurotoxicity showed vutiglabridin to be safe. Overall, these findings provide support for the clinical development of vutiglabridin as a novel PON2 modulator for the treatment of PD.One Sentence SummaryTargeting paraoxonase-2 by a clinical-stage compound vutiglabridin provides neuroprotective effects in preclinical models of Parkinson’s disease.

Bezoar without gastrointestinal surgical history occurring simultaneously in the gastric and duodenal lumen is very rare. We report a case of acute pancreatitis due to duodenal obstruction caused by two large bezoars. Two large bezoars were detected in the gastric and duodenal lumen, respectively, on abdominal computed tomography (CT) scan and oesophagogastroduodenoscopy images. Bezoars were crushed and removed using endoscopic devices such as trapezoid basket and lithotripsy handle. After removal of bezoars, blood tests and CT follow-up tests confirmed improvement. In the case of bezoar, which causes duodenal obstruction, it is difficult to administer coke for dissolution, and if it is difficult to perform surgical approach due to old age, an endoscopic treatment using mechanical lithotripsy devices can be an alternative option.

This paper proposes an effective numerical method to predict welding distortion for large welded structures. To predict welding distortions, inherent strain-based methods are computationally efficient and widely used in engineering fields. However, there are some drawbacks such as the generation of undesirable longitudinal forces and the use of vector-type input variables. Equivalent loads are derived through finite element formulation considering orthotropic thermal expansion conditions. Unlike previous methods, the proposed method predicts transverse shrinkage and angular distortion accurately, removing the undesirable longitudinal forces. In addition, scalar-type input variables are employed, which results in a convenient design procedure. The performance of the proposed method is verified through various examples including complex and large welded structures.

Dollar spot, caused by Clarireedia spp. (formerly Sclerotinia homoeocarpa F.T. Bennett), is the most economically important turfgrass disease causing considerable damage on golf courses. While cultural practices are available for reducing dollar spot infection, chemical fungicide use is often necessary for maintaining optimal turf quality. Since the release of boscalid in 2003, the succinate dehydrogenase inhibitor (SDHI) class has become an invaluable tool for managing dollar spot. However, resistance to this class has recently been reported in Clarireedia spp. and many other plant pathogenic fungi. After SDHI field failure on four golf courses and one university research plot, a total of six unique SDH mutations conferring differential in vitro sensitivities to SDHIs have been identified in Clarireedia spp. In 2018 and 2019, turf research plots were inoculated with sensitive, non-mutated isolates of Clarireedia spp., as well as resistant isolates harboring each unique identified mutation. Fungicide efficacy trials were conducted on inoculated plots to assess differential sensitivity to five SDHI active ingredients (boscalid, fluxapyroxad, isofetamid, fluopyram, and pydiflumetofen) across mutations under field conditions. Results indicate unique mutations are associated with distinct SDHI field efficacy profiles as shown in in-vitro sensitivity assays. Isolate populations with B subunit mutations (H267Y/R) were more sensitive to fluopyram, whereas isolate populations with C subunit mutations (C-G91R, C-G150R) showed resistance to all SDHIs tested. Mutation-associated differential sensitivity observed under field conditions indicates a need for a nation-wide survey and frequent monitoring of SDHI sensitivity of dollar spot populations on golf courses in the USA. Further, the information gained from this study will be useful in providing sustainable management recommendations for controlling site-specific resistant populations of Clarireedia spp.

Aptamers are short single-stranded DNA or RNA oligonucleotides capable of binding with high affinity and specificity to target molecules. Because of their durability and ease of synthesis, aptamers are used in a wide range of biomedical fields, including the diagnosis of diseases and targeted delivery of therapeutic agents. The aptamers were selected using a process called systematic evolution of ligands by exponential enrichment (SELEX), which has been improved for various research purposes since its development in 1990. In this protocol, we describe a modified SELEX method that rapidly produces high aptamer screening yields using two types of magnetic beads. Using this method, we isolated an aptamer that specifically binds to an antimicrobial peptide. We suggest that by conjugating a small therapeutic-specific aptamer to a gold nanoparticle-based delivery system, which enhances the stability and intracellular delivery of peptides, aptamers selected by our method can be used for the development of therapeutic agents utilizing small therapeutic peptides.

The database was established by conducting field surveys and water quality analysis of 877 water samples based on the national-scale various water sources, including 167 sampling sites from historically well-known hot springs, mineral waters, and spring waters (from August 2017 to June 2020). Spatial analysis using Kriging interpolation was performed to create a distribution map for 14 mineral components. The distribution maps were prepared with 50 m spatial resolution in raster type, and provided by Geo Bigdata Open Platform service of KIGAM. The spatial distribution of each mineral component showed some relationships with geological (lithology and fault) and regional characteristics, and could be used for drinking water and beverage industry (beverages, alcoholic beverages, teas, coffee, etc.) by providing the various information on the occurrence of natural Good-Water. We plan to continuously update information on Good-Water source to increase spatial resolution and secure its representativeness at each location.

Despite the promise of pyrenetetrone derivatives as insoluble organic cathode compounds for lithium-ion batteries, there is limited information on their electrochemical characteristics. Herein, a highly reliable computational protocol is employed to systematically explore the redox properties and theoretical performances of pyrenetetrone derivatives. This comprehensive analysis reveals that the electrochemical redox properties of pyrenetetrone derivatives at fully charged states are determined by complementary contributions from key factors, such as dopant electronegativity, electrostatic potential of the central backbone, and interatomic electronic flow. In contrast, dopant electronegativity becomes a dominant factor for tuning the redox behaviors of these organic compounds during the Li-involved discharging process, indicating the potential of boron-doped compounds for high-performance cathodes. Further investigation highlights that the entire discharging process can be summarized as Li-induced continuous reduction in electron affinity terminated by a sudden increase in solvation energy (depending on dopant electronegativity), which emphasizes the importance of solvation energy in determining cathodic deactivation.

Dollar spot, caused by the ascomycete fungus Clarireedia (formerly Sclerotinia), is one of the most resource-demanding diseases on amenity turfgrasses in North America. Differential resistance to the succinate dehydrogenase inhibitor (SDHI) fungicide class, conferred by singular point mutations on the SdhB, SdhC, and SdhD subunits of the succinate dehydrogenase enzyme (SDH), has been reported in dollar spot as well as many other plant-pathogenic fungal diseases. Four unique mutations were previously reported from Clarireedia field isolates collected from two different cool-season golf courses in Japan and Rhode Island: an amino acid substitution H267Y and a silent mutation (CTT to CTC) at codon 181 on the SdhB subunit gene, and amino acid substitutions G91R and G150R on the SdhC subunit gene. To properly diagnose and monitor SDHI resistance in the field, a rapid detection system for known mutations is crucial. As part of this study, additional SDHI-resistant Clarireedia isolates were collected from Rutgers University research plots and in vitro sensitivity to four SDHI active ingredients was assessed. SdhB, SdhC, and SdhD subunits of these isolates were sequenced to reveal an additional mutation on the SdhB subunit gene, H267R, not previously observed in Clarireedia. Cleaved amplified polymorphic sequence (CAPS) and derived CAPS molecular markers were developed to detect five mutations conferring SDHI resistance in Clarireedia isolates and validated using samples from two additional golf courses in Connecticut and Wisconsin experiencing SDHI field failure. This PCR-based molecular detection system will be useful for continued monitoring, assessment, and delay of SDHI resistance in the field.

Recent trade agreements contain new norms on SOEs which set forth detailed provisions to regulate a wide range of activities of contracting parties’ governments and their SOEs. Given the increasing global attention to the operation of SOEs in international trade and investment, and their significant influence, the new norms provide important legal guidance and a useful platform for future discussions in this area. These new norms include: restriction of governmental support for SOEs, restriction of SOEs’ support for other SOEs, and prevention of anti-competitive activities of SOEs, among others. While arguably offering a first stride in the right direction, the new norms also include critical ambiguities and uncertainties as regards key concepts and principles, which could potentially render full implementation of the norms elusive and complex. In particular, these new norms contain provisions that could lead to significant circumvention due to its critical “ASCM-minus” approach. This loophole is arguably capable of undermining the basic objectives of the new SOE norms. This approach should be reconsidered in future formulation of SOE norms in trade agreements including a prospective new agreement on this issue at the WTO.

The new countervailing duty proceeding rule of the United States on exchange rates aims to address currency undervaluation through a subsidy tool under the Agreement on Subsidies and Countervailing Measures. As there is no prohibition in the Agreement on Subsidies and Countervailing Measures (ASCM) making macro-economic policies off-limits from the reach of subsidy norms, exchange rates can be subject to countervailing duty proceedings. However, there are specific requirements to be met under the ASCM and World Trade Organization jurisprudence. Most notably, the new countervailing duty proceeding rule arguably fails to meet the ‘benefit’ analysis requirements. It takes into account the effect that negatively weighs on foreign exporters subject to a countervailing duty proceeding while ignoring the one that positively weighs. This skewed benefit analysis of selective nature is difficult to sustain under the ASCM and its jurisprudence. A more detailed and thorough benefit analysis is needed to make this new scheme work in a World Trade Organization (WTO)–consistent manner. The new countervailing duty rule showcases structural problems addressing macro-economic policies through a subsidy framework.

PURPOSE The implant-enhanced latissimus dorsi (LD) flap, or a hybrid LD flap, is widely used in certain indications, even though abdominal-based flaps are now considered the gold standard of autologous breast reconstruction. However, few articles distinguish the hybrid LD flap from traditional LD flaps, and not many articles have compared the surgical outcomes, with the abdominal-based flap procedure, especially in the area of immediate breast reconstruction. In addition, it is often overlooked that the reported esthetic comparisons are based on different populations and contralateral balancing procedures (CBPs). Thus, this study aimed to review the reconstruction outcomes and to compare the variable-matched esthetic outcomes between 2 groups. METHODS A retrospective review of patients who underwent immediate breast reconstruction with either a hybrid LD flap or an abdominal-based free flap and had completed at least 2 years of follow-up visits was carried out. The patient demographics, oncologic data, breast parameters, and postoperative outcomes were compared across the entire patient group. The body mass index (BMI)- and CBP-matched cohort was randomly selected and assessed using the Aesthetic Outcome parameter of the Aesthetic Item Scale. RESULT Thirty-eight hybrid LD flap and 51 abdominal-based free flap procedures were included. The hybrid LD group showed a shorter operation time (330 ± 260 minutes vs 550 ± 480 minutes, respectively; P < 0.01), and fewer patients in the hybrid LD group underwent additional revision surgeries (7 [18.4%] vs 20 [39.2%], respectively; P < 0.01). Other complication rates were not significantly different between groups. A BMI- and CBP-matched esthetic analysis revealed that the hybrid LD group showed superior results in symmetry (Mann-Whitney U test, P = 0.047). CONCLUSIONS The LD flap in combination with an implant remains a viable option in immediate breast reconstruction and had a similar complication profile while having a shorter operative time compared with the abdominal-based autologous breast reconstruction procedure. If properly used in certain populations, hybrid LD flaps may offer superior results regarding symmetry over the abdominal-based flap procedure.

In this letter, we formulate a novel Markov Decision Process (MDP) for safe and data-efficient learning for humanoid locomotion aided by a dynamic balancing model. In our previous studies of biped locomotion, we relied on a low-dimensional robot model, commonly used in high-level Walking Pattern Generators (WPGs). However, a low-level feedback controller cannot precisely track desired footstep locations due to the discrepancies between the full order model and the simplified model. In this study, we propose mitigating this problem by complementing a WPG with reinforcement learning. More specifically, we propose a structured footstep control method consisting of a WPG, a neural network, and a safety controller. The WPG provides an analytical method that promotes efficient learning while the neural network maximizes long-term rewards, and the safety controller encourages safe exploration based on step capturability and the use of control-barrier functions. Our contributions include the following (1) a structured learning control method for locomotion, (2) a data-efficient and safe learning process to improve walking using a physics-based model, and (3) the scalability of the procedure to various types of humanoid robots and walking., Comment: 8 pages, 7 figures

The purpose of this study was to empirically investigate the relationship among fashion brand experience, brand loyalty, relationship quality, and repurchase intention. The 420 survey questionnaires were distributed among the consumers in their 30s and 40s who had experience buy fashion brands products through convenience sampling in Seoul. Due to the reliability of data, 120 samples were discarded and 300 samples were put to actual analysis. By using SAS 9.4, data were analyzed for frequency analysis, reliability analysis, correlation analysis. The results of the study are as follows. First, the fashion brand experience which is consist of sensory, affective, behavioral and intellectual experience had positive effects on brand satisfaction and brand trust. Second, brand trust and brand commitment and the relationship quality of brand satisfaction, only satisfaction and commitment affects brand loyalty significantly. Lastly, brand loyalty had significantly effect on repurchase intention. It presented the potential to use the brand as a strategic tool to build strong brand assets, along with providing specific ways to secure differentiated competitiveness in the fashion brand market. It is also thought to be meaningful in that we presented a practical strategy to build and strengthen a lasting bond with consumers by looking at the impact on the quality of the relationship.

As deep inferior epigastric artery perforator (DIEP) flap surgery is gaining popularity, more patients including BRCA-positive patients need simultaneous laparoscopic surgery. We share our experience on a patient who underwent concurrent laparoscopic hysterectomy during flap elevation with a novel method. A patient diagnosed with a right breast cancer also required laparoscopic hysterectomy due to multiple uterine myoma. After perforator mapping was performed, flap elevation through external oblique fascia level was carried out first, sparing the periumbilical perforator and superficial inferior epigastric vein. Three ports were inserted for laparoscopy on posterior fascia level in the periumbilical area, left upper quadrant area and suprapubic area. The surgery was completed without any complication, gas leaks or vascular injury with the advantage of reduced risk of vascular damage and less surgical incision.

The blood exhibits a dynamic flux of proteins that are secreted by the tissues and cells of the body. To identify novel aging-related circulating proteins, we compared the plasma proteomic profiles of young and old mice using tandem mass spectrometry. The expression of 134 proteins differed between young and old mice. We selected seven proteins that were expressed at higher levels in young mice, and confirmed their plasma expression in immunoassays. The plasma levels of anthrax toxin receptor 2 (ANTXR2), cadherin-13 (CDH-13), scavenger receptor cysteine-rich type 1 protein M130 (CD163), cartilage oligomeric matrix protein (COMP), Dickkopf-related protein 3 (DKK3), periostin, and secretogranin-1 were all confirmed to decrease with age. We then investigated whether any of the secreted proteins influenced bone metabolism and found that CDH-13 inhibited osteoclast differentiation. CDH 13 treatment suppressed the receptor activator of NF-κB ligand (RANKL) signaling pathway in bone marrow-derived macrophages, and intraperitoneal administration of CDH-13 delayed age-related bone loss in the femurs of aged mice. These findings suggest that low plasma CDH-13 expression in aged mice promotes aging-associated osteopenia by facilitating excessive osteoclast formation. Thus, CDH-13 could have therapeutic potential as a protein drug for the prevention of osteopenia.

In this study, we evaluated the possibility of replacing existing perfluorocarbon gas with C7F14, which can be recovered in its liquid state from room-temperature air. We performed plasma etching of SiON films using the CF4 + X + O2 mixed gas, where X = CHF3, C4F8, or C7F14, and examined the etching characteristics of the films (e.g., etching rate, etching profile, and selectivity over Si). Using contact angle goniometry, atomic force microscopy, and X-ray photoelectron spectroscopy, we analyzed the physicochemical changes in the etched SiON film surface. Moreover, optical emission spectroscopy and double Langmuir probe measurements were carried out for plasma diagnosis. Compared with the conventional CHF3 and C4F8 mixed plasma, the C7F14 mixed plasma exhibited a more perpendicular etching profile with higher SiON/Si selectivity and a smoother surface.

PurposeThe purpose of this paper is to empirically examine the inequality perpetuated through social categories in accessing the social capital generated through the microfinance interventions in India as the country has pronounced economic inequality by social categories like many developing stratified societies.Design/methodology/approachThe study uses survey data collected from 75 villages in rural India and tests whether the formation and maximization of social capital through self-help groups (SHGs) is dominated by social categories, e.g. high-caste groups, males and superior occupation classes. Using logistic regression framework, the study assesses the formation and maximization of social capital through multiple SHG membership.FindingsThe paper finds that the microfinance approach of empowering weaker sections is considerably limited in its success, in the sense that it provides them with the opportunity to the credit access and support through SHGs. But, the empirical model further indicates that social capital in form of these SHGs may fall prey to the dominant social categories, and thus, these institutions may potentially enhance inequality.Research limitations/implicationsThe paper is derived from the secondary data set, so it is unable to comment field reality qualitatively.Practical implicationsMicrofinance policy makers will have an improved understanding of inherent social inequalities while implementing group-based programs in socially stratified societies.Originality/valueSocial capital, if treated as an outcome accumulated in form of groups, provides with an important framework to assess the unequal access through the microfinance interventions. Overlooking the inherent unequal access will deceive the purpose of social justice in the group-based interventions. The microfinance and other welfare policies engaged in group formation and generating the social capital need to be more sensitive to the disadvantageous sections while focusing on multiple group access by disadvantaged social groups.

Selective periarterial sympathectomy in Raynaud phenomenon (RP) has not been adequately studied as there was no reliable method to evaluate outcomes. However, dynamic Doppler ultrasonography may have clinical value in the management and follow-up of patients with RP; but few reports describe using the device to assess surgical outcomes. Here, we report a case of successful digital sympathectomy in a single digit and the postoperative evaluation using ultrasonography. A 23-year-old patient with secondary RP underwent surgery targeting both common digital artery (ulnar side) and the proper digital artery (radial side). The procedure yielded immediate pain relief and the improvement of recurrent fingertip ulceration. The 1-year postoperative assessment with dynamic Doppler ultrasonography using a hockey-stick probe was performed with a cold provocation test and revealed peak systolic velocity improvement comparable to the nontreated ulnar side but prominent fibrosis on the radial aspect. We anticipate that Doppler ultrasonography may be an effective tool for the postoperative assessment of patients who underwent digital sympathectomy for treatment of RP.

Whilst copper and silver are the conductors of choice for myriad current and emerging applications, patterning these metals is a slow and costly process. We report the remarkable finding that an extremely thin (∼10 nm) printed layer of specific organofluorine compounds enables selective deposition of copper and silver vapour, with metal condensing only where the organofluorine layer is not. This unconventional approach is fast, inexpensive, avoids metal waste and the use of harmful chemical etchants, and leaves the metal surface uncontaminated. We have used this approach to fabricate thin films of these metals with 6 million apertures cm−2 and grids of ∼1 μm lines, through to 10 cm diameter apertures. We have also fabricated semi-transparent organic solar cells in which the top silver electrode is patterned with a dense array of 2 μm diameter apertures, which cannot be achieved by any other scalable means directly on an organic electronic device.

Three conjugated polymers (CPs) were synthesized to obtain CPs with the same backbone but with different compositions of repeat units (phenylene and benzoselenadiazole (BSD)). The dominant composition of phenylene units and a smaller amount of BSD in the CP backbone enabled the CPs to emit different fluorescence colors according to their condition (solution or solid), which was caused by the difference in intermolecular electron transfer between CP backbones. Inspired by this, we fabricated polymer dots (Pdots) with various sizes using the CPs to control the number of CP chains within a spherical Pdot. This implied that smaller Pdots, where the chance of intermolecular electron transfer would be at a minimum, would accommodate fewer polymer chains than larger ones. The minimum chance for intermolecular electron transfer resulted in a short-wavelength emission, which was the identical emission color encountered in liquid CP solution. A more frequent intermolecular electron transfer was expected in larger Pdots, exhibiting long-wavelength emission, which was the same as observed in solid CPs. White-light-emitting Pdots that showed Commission Internationale de 1'Eclairage (CIE) coordinates of (0.34, 0.31) were fabricated simply by controlling the Pdot size.

Since the coronavirus disease 2019 (COVID-19) pandemic, most professional sports events have been held without spectators. It is generally believed that home teams deprived of enthusiastic support from their home fans experience reduced benefits of playing on their home fields, thus becoming less likely to win. This study attempts to confirm if this belief is true in four major European football leagues through statistical analysis. This study proposes a Bayesian hierarchical Poisson model to estimate parameters reflecting the home advantage and the change in such advantage. These parameters are used to improve the performance of machine-learning-based prediction models for football matches played after the COVID-19 break. The study describes the statistical analysis on the impact of the COVID-19 pandemic on football match results in terms of the expected score and goal difference. It also shows that estimated parameters from the proposed model reflect the changed home advantage. Finally, the study verifies that these parameters, when included as additional features, enhance the performance of various football match prediction models. The home advantage in European football matches has changed because of the behind-closed-doors policy implemented due to the COVID-19 pandemic. Using parameters reflecting the pandemic’s impact, it is possible to predict more precise results of spectator-free matches after the COVID-19 break.

Smoke detection is very important for fire detection, because smoke usually occurs before a fire breaks out. Smoke has a variety of characteristics, such as color, shape, texture, and so on. Using these characteristics, there has been a lot of research on smoke detection based on image processing. However, smoke detection is still difficult, because these characteristics can change due to environmental factors, such as wind and lighting changes. So, in this paper, a new smoke detection method based on fire-starting regions is presented to reduce sensitivity to environmental factors. The proposed method consists of three main parts: i) generating a candidate smoke region, ii) fire starting?region detection, and iii) detecting smoke based on fire-starting regions and predicting the direction of smoke movement. As a result, the proposed smoke detection method is less sensitive to the motion of non-smoke objects (humans, shadows, vehicles, etc.) and can detect smoke quickly by determining the fire-starting region where the smoke is generated. The proposed detection method can be applied to a video surveillance system and a fire- and smoke-analysis system.