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Global emissions of the ozone depleting gas 1,1-dichloro-1-fluoroethane (HCFC-141b, CH3CCl2F), derived from measurements of atmospheric mole fractions, have been rising between 2017–2021 despite a fall in reported production and consumption for dispersive uses. This study evaluates the possible drivers behind this renewed rise in emissions. HCFC-141b is a controlled substance under the Montreal Protocol, and its phase-out is currently underway, after a peak in reported consumption and production in developing countries (Article 5) in 2013. If reported production and consumption are correct, it suggests that the 2017–2021 rise is due to an increase in emissions from the bank when HCFC-141b containing appliances reach the end of their life, or from production of HCFC-141b not reported for dispersive uses. Regional emissions have been estimated between 2017–2020 for all regions where measurements have sufficient sensitivity to emissions. This includes the regions of northwestern Europe, east Asia, the USA and Australia, where emissions decreased by a total of 1.6 ± 3.9 Gg yr−1, compared to a mean global increase of 3.0 ± 1.2 Gg yr−1 over the same period. Collectively these regions only account for around a third of global emissions in 2020. Therefore we are not able to pinpoint the source regions or specific activities responsible for the recent global emission rise.

Trifluoromethane (CHF3, HFC-23), one of the most potent greenhouse gases among HFCs, is mainly emitted to the atmosphere as a by-product in the production of the ozone depleting legacy refrigerant and chemical feedstock chlorodifluoromethane (CHClF2, HCFC-22). A recent study on global HFC-23 emissions (Stanley et al., 2020) showed significant discrepancies over 2014–2017 between the increase in the observation-derived (top-down) emissions and the 87 % emission reduction expected from capture and destruction processes of HFC-23 at HCFC-22 production facilities mandated by national phase-out plans (bottom-up). However, the actual sources of the increased emissions were not identified. Here, we estimate the regional top-down emissions of HFC-23 for East Asia based on in situ measurements at Gosan, South Korea, and show that the HFC-23 emissions from eastern China have increased from 5.0 ± 0.4 Gg yr-1 in 2008 to 9.5 ± 1.0 Gg yr-1 in 2019. The continuous rise was contrary to the large emissions reduction reported since 2015 under the Chinese hydrochlorofluorocarbons production phase-out management plan (HPPMP). The magnitude of the mismatch between top-down and bottom-up estimates for 2015–2019 in eastern China was ~23.7 ± 3.6 Gg, which accounts for 47 ± 11 % of the global mismatch. Given the location of HCFC-22 production plants in eastern China and the fraction of regional to global HCFC-22 production capacities, the HFC-23 emissions rise in eastern China is most likely associated with known HCFC-22 production facilities and thus, observed discrepancies between top-down and bottom-up emissions could be attributed to unsuccessful factory level HFC-23 abatement and inaccurate quantification of emission reductions.

Angiogenesis plays an important role in damaged organ or tissue and cell regeneration and ovarian development and function. Primary ovarian insufficiency (POI) is a prevalent pathology in women under 40. Conventional treatment for POI involves hormone therapy. However, due to its side effects, an alternative approach is desirable. Human mesenchymal stem cells (MSCs) from various sources restore ovarian function; however, they have many limitations as stem cell sources. Therefore, it is desirable to study the efficacy of placenta-derived MSCs (PD-MSCs), which possess many advantages over other MSCs, in a rat model of ovarian dysfunction. Here, we investigated the restorative effect of PD-MSCs on injured ovaries in ovariectomized (OVX) rats and the ability of intravenous transplantation (Tx) of PD-MSCs (5 × 105) to enhance ovarian vasculature and follicular development. ELISA analysis of serum revealed that compared to the non-transplantation (NTx) group, the Tx group showed significantly increased levels of anti-Müllerian hormone, follicle stimulating hormone, and estradiol (E2) (*P, Vascular endothelial growth factor secreted by placenta-derived mesenchymal stem cells (PD-MSCs) promotes follicular development and ovarian function after ovariectomy through vascular remodeling. These results provide fundamental data for understanding the therapeutic mechanisms of stem cell therapy based on placenta-derived mesenchymal stem cells PD-MSCs and provide a theoretical foundation for their application for obstetrical and gynecological diseases, including infertility and menopause.

Mesenchymal stem cell (MSC)-based therapy using gene delivery systems has been suggested for degenerative diseases. Although MSC-based clinical applications are effective and safe, the mode of action remains unclear. Researchers have commonly applied viral-based gene modification because this system has efficient vehicles. While viral transfection carries many risks, such as oncogenes and chromosomal integration, nonviral gene delivery techniques are less expensive, easier to handle, and safe, although they are less efficient. The electroporation method, which uses Nucleofection technology, provides critical opportunities for hard-to-transfect primary cell lines, including MSCs. Therefore, to improve the therapeutic efficacy using genetically modified MSCs, researchers must determine the optimal conditions for the introduction of the Nucleofection technique in MSCs. Here, we suggest optimal methods for gene modification in PD-MSCs using an electroporation gene delivery system for clinical application.

This study explores how peer learning and teaching interactions in undergraduate STEM courses occurred through the “Peer-Learning Assistant” (PLA) model. This is one of the active learning strategi...

New psychoactive substance (NPS) opioids have proliferated within the international drug market. While synthetic opioids are traditionally composed of fentanyl analogues, benzimidazole-derived isotonitazene and its derivatives are the current NPS opioids of concern. Hence, in this study, we implement immunopharmacotherapy wherein antibodies are produced with high titers and nanomolar affinity to multiple benzimidazole-derived NPS opioids (BNO). Notably, these antibodies blunt psychoactive and physiological repercussions from BNO exposure, which was observed through antinociception, whole-body plethysmography, and blood-brain biodistribution studies. Moreover, we detail previously unreported pharmacokinetics of these drugs, which explains the struggle of traditional pharmaceutical opioid antagonists against BNO substances. These findings provide further insight into the

Background: Vascular abnormalities in the ovary cause infertility accompanied by ovarian insufficiency due to a microenvironment of barren ovarian tissues. placenta-derived mesenchymal stem cells (PD-MSCs, Naïve) treatment in ovarian dysfunction shows angiogenic effect, however, the therapeutic mechanism between ovarian function and vascular remodeling still unclear. Therefore, we examined whether by phosphatase regenerating liver -1 (PRL-1), which is correlated with angiogenesis in reproductive systems, overexpressed PD-MSCs could maximize the angiogenic effects in an ovarian tissues injured of rat model with partial ovariectomy and their therapeutic mechanism by enhanced vascular function via PDGF signaling.Methods: PD-MSCsPRL-1 (PRL-1) were generated by nonviral AMAXA gene delivery system and analyzed the vascular remodeling and follicular development in ovary. One week after Sprague-Dawley (SD) rats ovariectomy, Naïve and PRL-1 was transplanted. The animals were sacrificed at 1, 3 and 5 weeks after transplantation and vascular remodeling and follicular development were analyzed. Also, human umbilical vein endothelial cells (HUVECs) and ovarian explantation culture were performed to prove the specific effects and mechanism of PRL-1.Results: Vascular structures in ovarian tissues (e.g., number of vessels, thickness and lumen area) showed changes in the Naïve and PRL-1-overexpressed PD-MSC (PRL-1) transplantation (Tx) groups compared to the nontransplantation (NTx) group. Especially, PRL-1 induce to increase the expression of platelet-derived growth factor (PDGF), which plays a role in vascular remodeling as well as follicular development, compared to the NTx. Also, the expression of genes related to pericyte and vascular permeability in arteries was significantly enhanced in the PRL-1 compared to the NTx (pConclusions: Our results show that PRL-1 restored ovarian function by enhanced vascular function via PDGF signaling pathway. These findings offer new insight into the effects of functionally enhanced stem cell therapy for reproductive systems and should provide new avenues to develop more efficient therapies in degenerative medicine.

Background Vascular abnormalities in the ovary cause infertility accompanied by ovarian insufficiency due to a microenvironment of barren ovarian tissues. Placenta-derived mesenchymal stem cells (PD-MSCs, Naïve) treatment in ovarian dysfunction shows angiogenic effect, however, the therapeutic mechanism between ovarian function and vascular remodeling still unclear. Therefore, we examined whether by phosphatase regenerating liver-1 (PRL-1), which is correlated with angiogenesis in reproductive systems, overexpressed PD-MSCs could maximize the angiogenic effects in an ovarian tissues injured of rat model with partial ovariectomy and their therapeutic mechanism by enhanced vascular function via PDGF signaling. Methods PD-MSCsPRL-1 (PRL-1) were generated by nonviral AMAXA gene delivery system and analyzed the vascular remodeling and follicular development in ovary. One week after Sprague–Dawley (SD) rats ovariectomy, Naïve and PRL-1 was transplanted. The animals were sacrificed at 1, 3 and 5 weeks after transplantation and vascular remodeling and follicular development were analyzed. Also, human umbilical vein endothelial cells (HUVECs) and ovarian explantation culture were performed to prove the specific effects and mechanism of PRL-1. Results Vascular structures in ovarian tissues (e.g., number of vessels, thickness and lumen area) showed changes in the Naïve and PRL-1-overexpressed PD-MSC (PRL-1) transplantation (Tx) groups compared to the nontransplantation (NTx) group. Especially, PRL-1 induce to increase the expression of platelet-derived growth factor (PDGF), which plays a role in vascular remodeling as well as follicular development, compared to the NTx. Also, the expression of genes related to pericyte and vascular permeability in arteries was significantly enhanced in the PRL-1 compared to the NTx (p Conclusions Our results show that PRL-1 restored ovarian function by enhanced vascular function via PDGF signaling pathway. These findings offer new insight into the effects of functionally enhanced stem cell therapy for reproductive systems and should provide new avenues to develop more efficient therapies in degenerative medicine.

Unintentional overdose deaths related to opioids and psychostimulants have increased in prevalence due to the adulteration of these drugs with fentanyl. Synergistic effects between illicit compounds and fentanyl cause aggravated respiratory depression, leading to inadvertent fatalities. Traditional small-molecule therapies implemented in the expanding opioid epidemic present numerous problems since they interact with the same opioid receptors in the brain as the abused drugs. In this study, we report an optimized dual hapten for use as an immunopharmacotherapeutic tool in order to develop antibodies capable of binding to fentanyl-contaminated heroin in the periphery, thus impeding the drugs’ psychoactive effects on the central nervous system. This vaccine produced antibodies with nanomolar affinities and effectively blocked opioid analgesic effects elicited by adulterated heroin. These findings provide further insight into the development of chemically contiguous haptens for broad-spectrum immunopharmacotherapies against opioid use disorders.

The perfluorocarbons (PFCs), tetrafluoromethane (CF

Trade-related issues such as market access and tariff elimination or reduction have been the main concerns of free trade agreements or FTAs since the early 2000s. With more attention recently given to the concept of sustainable development, however, a growing number of countries start to share a common understanding that global and concerted efforts for environmental and labour protection are crucial for sustainable growth. In this context more of the recent FTAs focus on non-trade concerns such as protection of the environment and workers. A leading example is the FTA between Korea and the EU. Ever since the Korea-EU FTA, the EU has included a chapter on “Trade and Sustainable Development” or “TSD” to extensively provide for environment and labour obligations in its bilateral trade agreements. Further, it is noteworthy that the U.S. and the EU have resorted to dispute settlement and enforcement mechanisms within their FTAs to ensure that their trade partners effectively implement environment and labour obligations at the domestic level. For instance, on December 17, 2018, the European Commission requested a consultation to Korea under the Korea-EU FTA on the grounds that the Korean government had not shown sufficient efforts in ratifying the remaining four of the eight fundamental ILO Conventions and thus acted inconsistently with the TSD Chapter of the same FTA. This is the first case that the EU has ever initiated a dispute settlement procedure under a TSD chapter. The Panel of Experts was composed on December 30, 2019, and the final report was recently published on January 25th, 2021. Against this background, for consideration by the Korean government this Brief discusses the emerging trends of environmental and labour provisions in U.S. and EU trade agreements (with a special emphasis on the USMCA), particularly focusing on the aspect of ‘enforceability’ of such obligations.

[Image: see text] In addition to the risk of developing opioid use disorder (OUD), known side-effects of long-term opioid use include chronic inflammation and hyperalgesia, which may arise from immune responses induced following chronic opioid use. To investigate this hypothesis, blood samples were obtained from individuals with chronic back pain who were either chronically taking prescription opioids or had minimal recent opioid exposure. Patient samples were analyzed using an enzyme-linked immunosorbent assay (ELISA) against hydrocodone- or oxycodone-hapten conjugates to assess the levels of antibodies present in the samples. While no specific response was seen in opioid-naïve subjects, we observed varying levels of anti-opioid IgM antibodies in the exposed subjects. In these subjects, antibody formation was found to be weakly correlated with current reported daily opioid dose. Other drugs of abuse found to elicit an immune response have been shown to generate advanced glycation end-products (AGEs) through reaction with glucose and subsequent modification of self-proteins. Investigations into this potential mechanism of anti-opioid antibody production identified reduced the formation of reactive intermediate species upon norhydrocodone reaction with glucose in comparison with nornicotine, thus identifying potentially important differences in hapten processing to yield the observed adaptive immune response.

We report a 40-year history of SF6 atmospheric mole fractions measured at the Advanced Global Atmospheric Gases Experiment (AGAGE) monitoring sites, combined with archived air samples to determine emission estimates from 1978–2018. Previously we reported a global emission rate of 7.3 ± 0.6 Gigagrams (Gg) yr−1 in 2008 and over the past decade emissions have continued to increase by about 24 % to 9.04 ± 0.35 Gg yr−1 in 2018. We show that changing patterns in SF6 consumption from developed (Kyoto Protocol Annex-1) to developing countries (non-Annex-1) and the rapid global expansion of the electric power industry, mainly in Asia, have increased the demand for SF6-insulated switchgear, circuit breakers and transformers. The large bank of SF6 sequestered in this electrical equipment provides a substantial source of emissions from maintenance, replacement and continuous leakage. Other emissive sources of SF6 occur from the magnesium, aluminium, electronics industries and more minor industrial applications. More recently, reported emissions, including those from electrical equipment and metal industries, primarily in the Annex-1 countries, have steadily declined through substitution of alternative blanketing gases and technological improvements in less emissive equipment and more efficient industrial practices. Conversely, in the non-Annex-1 countries SF6 emissions have increased due to an expansion in the growth of the electrical power, metal and electronics industries to support their development. There is an annual difference of 2.5–5 Gg yr−1 (1990–2018) between our modelled top-down emissions and the UNFCCC reported bottom-up emissions, which we attempt to reconcile through analysis of the potential contribution of emissions from the various industrial applications which use SF6. We also investigate regional emissions in East Asia (China, S. Korea) and Western Europe and their respective contributions to the global atmospheric SF6 inventory. On an average annual basis, our estimated emissions from the whole of China are approximately 10 times greater than emissions from Western Europe. In 2018, our modelled Chinese and Western European emissions accounted for ~ 36 % and 3.1 %, respectively, of our global SF6 emissions estimate.

NF00659B1 is a novel α-pyrone diterpenoid natural product with potent anti-colon cancer activity. A stereoselective approach to the 2,2-dimethyl oxepanol core of NF00659B1 is described enlisting a sequence of olefinic ester ring-closing metathesis, epoxidation, and Grignard addition. This strategy paves the way to a total synthesis of NF00659B1 for further biological studies.

The existence of cancer stem cells (CSCs) is the main reason for failure of cancer treatment caused by drug resistance. Therefore, eradicating cancers by targeting CSCs remains a significant challenge. In the present study, because of the important role of BMI-1 proto-oncogene, polycomb ring finger (BMI-1) and C-terminal Mucin1 (MUC1-C) in tumor growth and maintenance of CSCs, we aimed to confirm that microRNA miR-128, as an inhibitor of BMI-1 and MUC1-C, could effectively suppress paclitaxel (PTX)-resistant lung cancer stem cells. We showed that CSCs have significantly higher expression levels of BMI-1, MUC1-C, stemness proteins, signaling factors, and higher malignancy compared with normal tumor cells. After transfection with miR-128, the BMI-1 and MUC1-C levels in CSCs were suppressed. When miR-128 was stably expressed in PTX-resistant lung cancer stem cells, the cells showed decreased proliferation, metastasis, self-renewal, migration, invasive ability, clonogenicity, and tumorigenicity in vitro and in vivo and increased apoptosis compared with miR-NC (negative control) CSCs. Furthermore, miR-128 effectively decreased the levels of β-catenin and intracellular signaling pathway-related factors in CSCs. MiR-128 also decreased the luciferase activity of MUC1 reporter constructs and reduced the levels of transmembrane MUC1-C and BMI-1. These results suggested miR-128 as an attractive therapeutic strategy for PTX-resistant lung cancer via inhibition of BMI-1 and MUC1-C.

Autoimmune diseases are chronic inflammatory diseases associated with high morbidity and mortality. Treatment options for autoimmune diseases have increased over the past several decades, but they are, in general, limited in their clinical efficacy due to high toxicity and lack of selectivity. Thus, efforts must be made to identify new immunomodulatory agents that are effective through a novel mechanism to circumvent existing side effects. To define the structural requirements of subglutinols for immunomodulatory activity and to provide guiding principles on future therapeutic development, we prepared and evaluated several subglutinol analogs for their immunomodulatory activities. Our efforts identified a subglutinol analog with reduced structural complexity as a potential lead compound for future autoimmune drug development. Our study will provide an important framework for the design of potent and nontoxic immunomodulating agents derived from subglutinols.

Rhodojaponin III is a grayanane-type diterpenoid natural product with a novel chemical scaffold. It shows potent antinociceptive activity and may represent a new class of natural non-opioid analgesics with a novel mode of action. We explored the Au(I)-catalyzed Conia-ene cyclization and the Mn(III)-mediated radical cyclization of alkynyl ketones for the synthesis of the bicyclo[3.2.1]octane fragment of rhodojaponin III. These strategies will be applicable in the synthesis of rhodojaponin III and analogs for future biological studies.

5-HT7 receptor (5-HT7R) agonists and antagonists have been reported to be used for treatment of neuropathic pain and depression, respectively. In this study, as a novel scaffold for 5-HT7R modulators, we designed and prepared a series of biphenyl-3-yl-methanamine derivatives with various amino groups. Evaluation of functional activities as well as binding affinities of the title compounds identified partial agonists (EC50 = 0.55–3.2 μM) and full antagonists (IC50 = 5.57–23.1 μM) depending on the amino substituents. Molecular docking study suggested that the ligand-based switch in functional activity from agonist to antagonist results from the size of the amino groups and thereby different binding modes to 5-HT7R. In particular, interaction of the ligand with Arg367 of 5-HT7R is shown to differentiate agonists and antagonists. In the pharmacophore model study, two distinct pharmacophore models can tell whether a ligand is an agonist or an antagonist. Taken together, this study provides valuable information for designing novel compounds with selective agonistic or antagonistic properties against 5-HT7R.

The prediction of creative performance from ideation has shown promise, but questions remain. In this study, the relationship of ideational behavior and the creative performance of elementary school children (N = 255) was examined across 6 domains of creative performance: science, mathematics, technology, fine arts, music, and writing. Importantly, the potential confounding of grade and gender were controlled and creative self-efficacy tested as a moderator. Results indicated that ideational behavior explained a unique portion of variance in creative performance, above and beyond the potential confounding factors. The moderating effect of creative self-efficacy was confirmed, but only in the domain of science. Interestingly, ideation was more strongly related to creative activity than was creative self-efficacy in every domain except art and writing. Limitations and future research are discussed.

Korean Abstract: 최근 보호무역주의의 확산과 함께 WTO로 대표되는 다자무역체제가 위협받고 있다. 그럼에도 불구하고 지난 수년간 자유무역협정은 꾸준히 확대되어 왔으며 특히 협정이 포함하는 구성요소와 이를 규율하는 조항이 복잡·다양해졌다. 이에 본 연구는 Worldbank(2017) 데이터베이스를 활용하여 전 세계와 한국의 자유무역협정 구성요소 현황을 조사하고 자유무역협정의 수준 및 구성요소가 교역에 미치는 영향을 분석하였다. English Abstract: Recently, the global trade system is deteriorating and the basis for world free trade is being threatened by a rise in trade protectionism. The multilateral trade system represented by the WTO has shown its limitations in efficiently reflecting the rapidly changing global trade environment. In the meantime, free trade agreements have continued to increase up to recently, not only in terms of their numbers but also the scope they cover. While free trade agrements in the past focused on tariff reduction, more recent free trade agrements include complex provisions on issues such as non-tariff barriers, services, investment, digital trade, and intellectual property rights. This study reviews the contents of free trade agreements and investigates their effects on trade using data from Worldbank (2017). First, more recent free trade agreements appear to contain more contents or provisions. We also find that Korea tends to sign more comprehensive free trade agreements, containing an average of 26 provisions, which is higher than the world average of 18. Second, we find that establishing such comprehensive free trade agreements has greater positive effects on trade. In particular, free trade agreements including more WTO-X provisions promote trade flows more effectively. Third, we also investigate the effect of each type of provision on trade. Empirical results are as follow. Market access provisions increased trade significantly. However, service provisions appear to have a negative effect on trade. Investment provisions also have a negative effect on trade, mainly negative for export from advanced countries to both advanced and developing countries. We also find that intellectual property rights provisions play a restrictive role on trade between developing countries while public procurement provisions have a positive effect on export to developing countries. Finally, while standard provisions have a negative effect on exports from developing countries to advanced countries, they appear to promote trade between developing countries. As mentioned above, the effects of provisions on trade are heterogeneous by the level of a country’s economy. Moreover, these might vary depending on how they are implemented, so further research is needed for an accurate interpretation of the results.

To cope with hypoxia, tumor cells have developed a number of adaptive mechanisms mediated by hypoxia-inducible factor 1 (HIF-1) to promote angiogenesis and cell survival. Due to significant roles of HIF-1 in the initiation, progression, metastasis, and resistance to treatment of most solid tumors, a considerable amount of effort has been made to identify HIF-1 inhibitors for treatment of cancer. Isolated from Saururus cernuus, manassantins A (1) and B (2) are potent inhibitors of HIF-1 activity. To define the structural requirements of manassantins for HIF-1 inhibition, we prepared and evaluated a series of manassantin analogues. Our SAR studies examined key regions of manassantin’s structure in order to understand the impact of these regions on biological activity and to define modifications that can lead to improved performance and drug-like properties. Our efforts identified several manassantin analogues with reduced structural complexity as potential lead compounds for further development. Analogues MA04, MA07, and MA11 down-regulated hypoxia-induced expression of the HIF-1α protein and reduced the levels of HIF-1 target genes, including cyclin-dependent kinase 6 (Cdk6) and vascular endothelial growth factor (VEGF). These findings provide an important framework to design potent and selective HIF-1α inhibitors, which is necessary to aid translation of manassantin-derived natural products to the clinic as novel therapeutics for cancers.

NF00659B(1) is a novel α-pyrone diterpenoid natural product with potent anti-colon cancer activity. A stereoselective approach to the 2,2-dimethyl oxepanol core of NF00659B(1) is described enlisting a sequence of olefinic ester ring-closing metathesis, epoxidation, and Grignard addition. This strategy paves the way to a total synthesis of NF00659B(1) for further biological studies.

Given Reacting to the Past’s (RTTP’s) tremendous growth since its earliest iteration in the mid-1990s, students and faculty alike have come to view RTTP as a transformative experience. This chapter assesses both sides of the RTTP classroom by presenting the results of two national surveys. The surveys illuminate students’ and faculty’s perceptions of both the pedagogy and its high-impact elements. Through the lenses of social cohesion theory and the relationship-driven teaching model, the authors evaluate students’ views of the impact(s) of RTTP on their learning within RTTP course(s), as well as how the pedagogy influenced their study habits, appreciation of course content, and sense of autonomy as learners. Additionally, the faculty survey provides key insights into how RTTP implementation, its successes and challenges, influences faculty decisions on teaching and instruction beyond their RTTP-based classes and how they perceive improvements in student performance when compared to non-RTTP courses.

To develop novel, selective, and reversible MAO-B inhibitors for safer treatment of Parkinson’s disease, benzothiazole and benzoxazole derivatives with indole moiety were designed and synthesized. Most of the synthesized compounds showed inhibitory activities against MAO-B and selectivity over MAO-A. The most active compound was compound 5b, 6-fluoro-2-(1-methyl-1H-indol-5-yl)benzo[d]thiazole with an IC50 value of 28 nM with no apparent effect on MAO-A activity at 10 μM. Based on the reversibility assay, compound 5b turned out to be fully reversible with over 95% of recovery of enzyme activity after washout of the compound. Compound 5b showed a reasonable stability in human liver microsomes and did not affect the activities of CYP isozymes, suggesting an absence of high-risk drug–drug interaction. In an in vivo MPTP-induced animal model of Parkinson’s disease, oral administration of compound 5b showed neuroprotection of nigrostriatal dopaminergic neurons as revealed by tyrosine hydroxylase staining and pr...

Korean Abstract: 2017년 피터슨 연구소의 보고서는 반덤핑, 상계관세, 세이프가드, 국가안보에 근거하여 미국이 현재 조사 중인 수입규제가 현실화될 경우 적용대상이 되는 한국의 대미 수출품이 7.9%에서 12.2%로 늘어나 중국을 제치고 한국이 가장 큰 피해를 보는 국가가 될 것이라고 예상하고 있다. 본 연구는 무역구제조치의 경제적 영향 분석 시 기존의 부분균형 접근방식으로부터 탈피하여 일반균형 관점에서 새롭게 무역구제조치의 경제적 효과를 분석하였다. 아울러 무역구제조치와 관련된 최근 데이터를 업데이트하여 현황을 정리하고 특징을 분석하였으며, 제도적 관점에서 최근 미국을 중심으로 두드러지는 무역구제조치의 특징을 살펴보았다. 또한, 무역구제조치에 의한 관세상당치를 추정하여 본 연구의 여러 가지 시나리오 분석에서 활용하였다. 우리나라의 중장기 통상정책 및 무역구제조치에 대한 대응방안 수립에 참고할 수 있는 유용한 기초자료로서 사용되기를 바란다. English Abstract: This study aims to investigate the economic impact of trade remedy in a general equilibrium model with world input-output linkage by quantifying the trade and welfare effects from trade remedy measures. Before examining the economic impact of trade remedy, we investigate the impact of anti-dumping initiations on trade cost by focusing on the steel industry for the last five years. We conduct the fixed-effect as well as PPML estimation in a panel dataset constructed with anti-dumping initiation records, HS 6-digit product-level trade data among 15 countries for the last five years, tariff-lines, usual control variables used in gravity model provided by CEPII, and other relevant variables. We find that anti-dumping initiation in previous year has a negative impact on trade volume in current year. This key result provides a rationale of the study assuming that strengthening trade remedy measures increases trade cost.

Korean Abstract: 글로벌 금융위기 이후 세계 경제의 저성장 기조가 지속되는 가운데 보호무역주의 확산에 대한 우려가 커지고 있다. 특히 각국 정부는 WTO 등 국제기구를 통해 모니터링이 용이한 관세 대신 비관세조치를 일자리 창출이나 국내 산업 보호를 목적으로 하는 보호무역주의 정책의 수단으로 이용하는 경향이 나타나고 있다. 이에 본 보고서에서는 최근 나타나고 있는 신보호무역주의 동향을 살펴보고, UNCTAD 비관세조치 데이터베이스를 이용하여 주요국의 비관세조치 현황 및 비관세조치가 무역에 미치는 영향을 분석하였다. English Abstract: This study revisits and investigates the effects of non-tariff measures on trade flows from a theoretical and empirical viewpoint. First, the theoretical framework provided in the paper shows that the changes of trade patterns with regard to introduction of non-tariff measures by the importing country depend on the relative changes of compliance costs between importing and exporting countries. In particular, it is suggested that the introduction of high standards in developed countries may impose higher compliance costs on producers in developing countries than those in developed countries. In such a case, imports of developed countries from developing countries will decrease. The corresponding empirical analysis investigates the effects of non-tariff measures, primarily SPS and TBT, on imports in eight industries – agriculture/fisheries, mining, textile/garments/other, chemical, metal/non-metallic minerals, transport equipment, electronics and machinery, using the UNCTAD non-tariff measures database. The results are as follows. The effect of SPS measures on imports is significantly restrictive in the agriculture/fisheries and textile/garment/other industries. TBT measures are also trade-restrictive in most industries except for electronics. Further analysis to explain why the electronics industry poses such an exception shows that while TBT measures in electronics play a restrictive role in imports of developed countries from developing countries, they perform a promoting role the other way around. Such results are in line with theoretical predictions and imply with caveat that not all non-tariff measures in certain industries serve as barriers.

© 2019 Elsevier Inc. Intrinsic and acquired drug resistance and induction of secondary malignancies limit successful chemotherapy. Because mutagenic translesion synthesis (TLS) contributes to chemoresistance as well as treatment-induced mutations, targeting TLS is an attractive avenue for improving chemotherapeutics. However, development of small molecules with high specificity and in vivo efficacy for mutagenic TLS has been challenging. Here, we report the discovery of a small-molecule inhibitor, JH-RE-06, that disrupts mutagenic TLS by preventing recruitment of mutagenic POL ζ. Remarkably, JH-RE-06 targets a nearly featureless surface of REV1 that interacts with the REV7 subunit of POL ζ. Binding of JH-RE-06 induces REV1 dimerization, which blocks the REV1-REV7 interaction and POL ζ recruitment. JH-RE-06 inhibits mutagenic TLS and enhances cisplatin-induced toxicity in cultured human and mouse cell lines. Co-administration of JH-RE-06 with cisplatin suppresses the growth of xenograft human melanomas in mice, establishing a framework for developing TLS inhibitors as a novel class of chemotherapy adjuvants. A small molecule specifically targeting the mutagenic branch of translesion synthesis binds a nearly featureless surface of REV1 to induce dimerization and block recruitment of POL ζ.

Structure–activity relationship (SAR) calculations were used to find monoamine oxidase-B (MAO-B) inhibitors by identifying pharmacophores exhibiting high inhibitory activities. Several such chromenylchalcones were designed and synthesized accordingly. Their inhibitory effects on MAO-B were determined using an HPLC-based method and an MAO-B enzyme assay kit. (E)-3-(6-Methoxy-2H-chromen-3-yl)-1-(2-methoxyphenyl)prop-2-en-1-one exhibited a half-maximal inhibitory concentration of 320 nM. Its molecular-level binding mode with the three-dimensional structure of MAO-B was elucidated using an in silico docking study. The chromenylchalcone scaffold, which is derived from natural products including isoflavonoids and chalcones, had not been previously reported as an MAO-B inhibitor.

Korean Abstract: 본 연구에서는 한국의 수입구조에 대한 이해를 높이기 위하여 수입구조를 수출 및 해외투자와의 상호작용 속에서 파악하고, 수입이 기업의 퇴출과 구성요소별 생산성을 통해 기업의 분포구조에 미치는 영향을 분석하였다. 이를 토대로 수출 및 투자와 연동된 새로운 수입통계 시스템 도입, 무역조정 지원제도의 개선, 유형별 수입을 고려한 맞춤형 대책수립을 제안하였다. English Abstract: Recently, our trades have been declining for the second year in a row, due to the maturity of the global value chain and the delay in the recovery of the world economy. In particular, imports decline more than exports, but trade surplus is rather expanding. Policy makers and experts expressed concern about the decline in exports, but did not show interest in decreased imports. Behind these responses, there is dichotomy that the increase in exports is positive but the increase in imports is negative. More importantly, there is still a lack of clear understanding of Korea's import structure. In this paper, we analyze determinants of Korea's imports in the context of the interaction between exports and foreign investments, and investigate the effects of imports on firms' exit and productivity in order to understand Korea's import structure and distributional influences of imports. Since 1988, Korea's overall imports have increased substantially, except for the currency crisis and the period of the global financial crisis, but it has recorded a continuous declining trend due to recent sharp drop in imports of raw materials. Major importing countries have changed from developed countries in the past to resource-abundant countries and developing countries. By type, intermediate goods account for about 50% of imports, raw materials and capital goods account for 20% respectively, and consumption goods account for around 10%. In order to analyze determinants of imports by type, we constructed theoretical model and found two propositions. First, regardless of types, imports will increase as the economic sizes of importing countries become larger, and will decrease as the transaction cost with the importing partner increases. Second, while imports of consumption goods increase as the income level and market size of importing countries increases, imports of intermediate goods and raw materials used as production inputs increases as the outputs and exports of industries increase. The results of the empirical analysis based on the theoretical model are summarized as follows. First, as the export becomes more active, imports of intermediate goods and raw materials used as production input factors will increase, while imports of consumer goods will decrease. Second, imports of intermediate goods and raw materials are positively related with inward foreign direct investment (FDI), but imports of consumption goods are negatively affected by inward FDI. Third, the more industries spend R&D investments, the more the industries import intermediate goods and raw materials. Fourth, the effects of import liberalization are different for each type of import. The influence of the tariff rate was limited for raw materials and capital goods imports. According to the analysis of Korea's import structure, imports of consumption goods declined by 0.137%, and imports of intermediate materials and raw materials were analyzed to increase by 0.235% and 0.193%, respectively when exports increased by 1%. When inward FDI increased by 1%, imports of consumption goods and capital goods decreased by 0.02% and 0.017% respectively, but imports of raw materials were expected to increase by 0.071%. The main results of analyzing the effects of imports on probability of firms’ exit are as follows. First, the increase in total imports increase the probability of a firm's exit but the firm size, capital stocks, productivity decrease the probability. Second, imports of raw materials and intermediate goods decrease the probability. Third, whether firms are exporting or not does not significantly affect the relationship between import penetration and firms' exit. Fourth, the magnitude of the effects of imports on firms' exit varied from industry to industry. The results of effects of imports on productivity structure are summarized as follows. First, the total import penetration rates have an inverse U-shaped relationship with total factor productivity. Second, these nonlinear relationships between import penetration rate and total factor productivity are very different for each type of imports by industry. In order to investigate the effects of imports on the distribution of productivity within the industry, we decompose changes in the productivity into within firm effects, between firm effects, and exit and entry effects. Second, when imports increase, within firms effects are significant in food, iron, transportation industries and between firms effects are significant in oil and iron industries. Only in the transportation industry, exit and entry effects turn out significant. Third, the total import penetration rates have a positive impact on the growth rate of productivity by economies of scale, whereas the penetration rates of intermediate goods imports increase productivity through technological progress. Based on this, three policy proposals were derived. The first is the introduction of a new statistical system for imports linked with export and investment. Also, the new system should contain statistics for e-commerce imports in order to analyze the current situation of import of consumption goods. The second is improvement of the trade adjustment assistant (TAA) program. An increase in imports will increase the competitiveness of the domestic market and induce the exit of companies with low productivity, but these impacts were analyzed to be somewhat different depending on type and industry. In addition, a nonlinear relationship between imports and productivity was also considered. Third one is customized policies taking into account effects of imports by type. As the FTA tariff elimination schedule goes forward, the effects of imports are expected to continue to expand. To introduce customized policy for imports by type, it is necessary to raise the understanding of Korea’s import structure.

In this study, as a bioisosteric alternative scaffold of the antiviral aryl diketoacids (ADKs), we used 5-hydroxychromone on which two arylmethyloxy substituents were installed. The 5-hydroxychromones (5b–5g) thus prepared showed anti-HCV activity and, depending on the aromatic substituents on the 2-arylmethyloxy moiety, some of the derivatives (5b–5f) were also active against SCV. In addition, unlike the ADKs which showed selective inhibition against the helicase activity of the SCV NTPase/helicase, the 5-hydroxychromones (5b–5f) were active against both NTPase and helicase activities of the target enzyme. Among those, 3-iodobenzyloxy-substituted derivative 5e showed the most potent activity against HCV (EC50 = 4 μM) as well as SCV (IC50 = 4 μM for ATPase activity, 11 μM for helicase activity) and this might be used as a platform structure for future development of the multi-target or broad-spectrum antivirals., Graphical abstract The 2,6-bis-arylmethyloxy-5-hydroxychromones were identified to have antiviral activity against both hepatitis C virus (HCV) and SARS-associated coronavirus (SCV). Highlights ► Investigation of bioisosteric alternative scaffold of antiviral arylmethyloxy-ADKs. ► 2,6-Bis-arylmethyloxy-5-hydroxychromones active against both HCV and SCV. ► Antiviral activity against HCV (EC50 = 4 μM). ► Inhibition of SCV NTPase (IC50 = 4 μM) as well as ATPase activity (IC50 = 11 μM). ► Potential platform structure for multi-target or broad-spectrum antivirals.

Anti-HCV activity of aryl diketoacid (ADK) has been characterized by its two pharmacophoric elements, α,β-diketo acid moiety and substituted aryl ring. In this study, as a part of our ongoing efforts to discover a novel anti-HCV compound mimicking the ADK scaffold, we designed 2-arylmethylaminomethyl-5,6-dihydroxychromone derivatives of which the dihydroxychromone moiety as well as the arylmethylaminomethyl substituent (R-PhCH 2 NHCH 2 –) were anticipated in exact match with the pharmacophore model of the ADK. The dihydroxychromone derivatives ( 3a – 3u ), thus prepared, showed biological activity in a substituent-dependent fashion, thereby leading to selective anti-HCV effect (EC 50 = 2.0–14.0 μM, CC 50 >100 μM) with the substituent groups such as Cl, Br, I, and Me specifically at the 3-position of the aromatic ring.

It is well known that economic growth and services have a positive association. In particular, the more developed an economy is, the higher the share of the services sector. While most research has focused on service output, this study also examines services as input. Recently, the need for taking services a separate input in the production function has come to the fore. Therefore, the OECD productivity manual generalizes the KLEM model to KLEMS (capital-labor-energy-materials-services) model by including the services as an input. We use KLEMS data in this study. In addition, we augmented the standard production function with other variables such as the inventory to sales ratio, R&D to sales ratio, education expenditure to sales ratio, and the debt to sales ratio. The findings are encouraging and lead us to formulate some important conclusions; for example, after the 1998 Financial Crisis, the Korean economy has increased in efficiency and this is partly due to an increased importance of services as both output and input.