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Asymmetric ENSO teleconnections in a symmetric CO2 concentration pathway
No full textEl Ni & ntilde;o-Southern Oscillation (ENSO) is the strongest interannual phenomenon occurring in the tropical Pacific, significantly affecting the entire world. The ENSO response to increasing CO2 concentrations have been extensively studied, but the reverse scenario is still not well understood. Here, we investigate the hysteresis of ENSO teleconnections in a CO2 removal simulation of an earth system model. During the ramp-up period of CO2 concentrations, Pacific-North American and Pacific-South American patterns are intensified, with the eastward shift of their poles, which are even further intensified during the ramp-down period. This ENSO teleconnection hysteresis is closely linked to the tropical-origin hysteresis, in which, during the ramp-down periods, the prevalence of the eastern-Pacific type El Ni & ntilde;o leads to the hysteresis in the eastern Hemispheric ENSO teleconnections and the enhanced ENSO skewness and the eastward shift of ENSO-induced tropical atmospheric convection do to that in the western Hemispheric ENSO teleconnection. The alterations by the tropical origin are predominantly associated with intensified southward migration of the Intertropical Convergence Zone, along with a stronger El Ni & ntilde;o-like warming trend. We also demonstrate that the hysteretic change in the mid-latitude mean state over the North Pacific region could lead to hysteresis of the ENSO teleconnection without invoking a tropical origin.Y
Characteristics of Convectively Induced Turbulence in East Asia Using Geostationary Korea Multi-Purpose Satellite-2A (GK-2A) and In Situ Aircraft Data
No full textDeep convection and its vicinity are important areas of turbulence encountered in cruising aircraft, called convectively induced turbulence (CIT). In this study, deep convection area (DCA) in East Asia is identified using the infrared channel of Geostationary Korea Multi-Purpose Satellite-2A (GK-2A) over 49 months (from August 2019 to August 2023), and CIT is determined by using in situ aircraft data adjacent to the DCA. Based on the satellite-based CIT algorithm, the results indicate that 13.85%, 15.65%, and 18.23% of the total turbulence cases are classified as CIT over the Korean Peninsula, East Asia, and the full-disk area, respectively, which are consistent with those in the previous studies. In East Asia, the CIT ratio is the highest in summer primarily due to the East Asian summer monsoon, and surprisingly, it is the second highest in winter. In winter, DCA occurs along the storm tracks accompanied by Aleutian Low, which provides favorable conditions for flights to encounter CIT in the North Pacific Ocean. The CIT intensity decreases rapidly as the horizontal distance between the DCA boundary and CIT location increases. However, at a distance exceeding 40 km from the DCA boundary, the intensity of turbulence gradually increases, which is most significant in winter. This trend is more likely related to the broader areas of DCA in the winter season than those in summer mainly due to the stronger upper-level jet and its interaction with a storm system. Eventually, this algorithm can provide better information of avoidance guidance for CIT over the ocean.Y
Imlunestrant, an Oral Selective Estrogen Receptor Degrader, as Monotherapy and in Combination With Targeted Therapy in Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: Phase Ia/Ib EMBER Study
No full textPURPOSEImlunestrant is a next-generation oral selective estrogen receptor (ER) degrader designed to deliver continuous ER target inhibition, including in ESR1-mutant breast cancer. This phase Ia/b trial determined the recommended phase II dose (RP2D), safety, pharmacokinetics, and efficacy of imlunestrant, as monotherapy and in combination with targeted therapy, in ER-positive (ER+) advanced breast cancer (ABC) and endometrial endometrioid cancer. The ER+/human epidermal growth factor receptor 2-negative (HER2-) ABC experience is reported here.METHODSAn i3+3 dose-escalation design was used, followed by dose expansions of imlunestrant as monotherapy or in combination with abemaciclib with or without aromatase inhibitor (AI), everolimus, or alpelisib. Imlunestrant was administered orally once daily and with the combination partner per label.RESULTSOverall, 262 patients with ER+/HER2- ABC were treated (phase Ia, n = 74; phase Ib, n = 188). Among patients who received imlunestrant monotherapy (n = 114), no dose-limiting toxicities or discontinuations occurred. At the RP2D (400 mg once daily), patients (n = 51) reported grade 1-2 nausea (39.2%), fatigue (39.2%), and diarrhea (29.4%). Patients at RP2D had received previous cyclin-dependent kinase 4/6 inhibitor (CDK4/6i; 92.2%), fulvestrant (41.2%), and chemotherapy (29.4%) for ABC and achieved a median progression-free survival (mPFS) of 7.2 months (95% CI, 3.7 to 8.3). Among patients who received imlunestrant + abemaciclib (n = 42) and imlunestrant + abemaciclib + AI (n = 43), most (69.4%) were treatment-na & iuml;ve for ABC; all were CDK4/6i-na & iuml;ve. Patients treated with imlunestrant + everolimus (n = 42)/alpelisib (n = 21) had received previous CDK4/6i (100%), fulvestrant (34.9%), and chemotherapy (17.5%) for ABC. No new safety signals or interactions with partnered drugs were observed. The mPFS was 19.2 months (95% CI, 13.8 to not available) for imlunestrant + abemaciclib and was not reached for imlunestrant + abemaciclib + AI. The mPFS with imlunestrant + everolimus/alpelisib was 15.9 months (95% CI, 11.3 to 19.1)/9.2 months (95% CI, 3.7 to 11.1). Antitumor activity was evident regardless of ESR1 mutation status.CONCLUSIONImlunestrant, as monotherapy or in combination with targeted therapy, had a manageable safety profile with evidence of preliminary antitumor activity in ER+/HER2- ABC.N
Discovery of Spirosnuolides A-D, Type I/III Hybrid Polyketide Spiro-Macrolides for a Chemotherapeutic Lead against Lung Cancer
No full textFour new macrolides, spirosnuolides A-D (1-4, respectively), were discovered from the termite nest-derived Kitasatospora sp. INHA29. Spirosnuolides A-D are 18-membered macrolides sharing an embedded [6,6]-spiroketal functionality inside the macrocycle and are conjugated with structurally uncommon side chains featuring cyclopentenone, 1,4-benzoquinone, hydroxyfuroic acid, or butenolide moieties. Structure elucidation was achieved using a combination of spectroscopic analyses, multiple chemical derivatizations (methylation, methanolysis, Luche reduction, and Mosher's reaction), X-ray diffraction analysis, and computational ECD calculations. Interestingly, genome sequencing analysis suggests that spirosnuolides were biosynthesized through a rare type I/III hybrid polyketide synthase. Importantly, spirosnuolide B displayed potent antiproliferative effects against various cancer cell lines at nanomolar concentrations, particularly against HCC827 cells, an EGFR mutant non-small-cell lung cancer (NSCLC) cell line, with a high safety index value. Based on in vitro studies, the antiproliferative mechanism of spirosnuolide B involved the activation of AMPK signaling, leading to cell cycle arrest and apoptosis in HCC827 cells. Its potent efficacy was also proven in vivo by the effective inhibition of tumor growth in mouse xenograft studies. Moreover, cotreatment with spirosnuolide B and gefitinib, synergistically enhanced the antiproliferative activity and apoptosis, suggesting a potential strategy to overcome gefitinib resistance in EGFR mutant NSCLC.Y
Exploring the intersection of disasters and science education with preservice science teachers through a disaster case study
No full textModern society is under increasing threats of natural and technological disasters, which involve complex interactions among science, technology and social structures. Although a scientific understanding of disasters is an immediate global issue, there is limited discussion about how disasters can relate to science education. To address this gap, we report findings from a research study to support preservice science teachers' learning about disasters and its relevance to science education. Fifteen preservice science teachers participated in a six-hour workshop focused on the scientific and sociotechnical aspects of the humidifier disinfectant disaster, which caused severe lung injuries to half a million people in South Korea. The study aim was to identify preservice science teachers' perceptions about how disasters can be incorporated into science teaching. The participants were engaged in a series of group activities using the official investigation report, followed by a discussion on the aspects of science, technology, and society that unfolded in the disaster. Our analysis suggested that the participants were able to discover important aspects of the mutual relationship between science and disasters, and propose various cognitive, attitudinal, and functional aims that could be pursued by embedding disasters in science lessons. The lesson plans showed that the participants were able to suggest how to use disasters in science lessons and leverage diverse teaching methods to achieve their lesson goals. However, the shift in their perceptions before and after the workshop was limited. We argue that support is necessary for preservice science teachers to incorporate disasters into the science classroom, by providing more time and resources and lowering the barriers related to the political and traumatic aspects of disasters.Y
Assessment of the efficacy of bacterial inactivation by combination treatment with peracetic acid and UVC light-emitting diode and elucidation of the bactericidal mechanism
No full textThis study was conducted to investigate the bactericidal effects of combination treatment with an ultraviolet C light-emitting diode (UVC LED) and peracetic acid (PAA) on three major foodborne pathogens (Escherichia coli O157:H7, Salmonella Typhimurium, and Listeria monocytogenes). Pathogen-inoculated peptone water (5 ml) was treated with UVC LED and PAA individually or simultaneously. Following combination treatment, a 6.5-log inactivation was observed at 60 s for E. coli O157:H7 and 5.9-log and 3.9-log inactivation were observed at 90 s for S. Typhimurium and L. monocytogenes, respectively. The possibility of reusing the PAA-solution was evaluated to determine the effectiveness of the system in repetitive treatments, which showed that combination treatment could ensure sufficient microbial safety up to 5 treatments. The microbicidal mechanism and role of putative molecules were investigated to elucidate the synergistic of combination treatment. Using reactive oxygen species (ROS) scavengers, center dot O-2(-) was confirmed as the major ROS generated by the combination system, and enhanced cell membrane damage and inhibition of enzymatic activity were observed following combination treatment compared with individual treatments. This study demonstrated that combination treatment with UVC LED and PAA could be used as an innovative non-thermal technology for washing minimally processed fresh produce.N
Changes in Curtain Wall Details of Kimm Jong Soungs Architecture Amid Industrial and Technological Growth From the 1970s to 1990s
No full textThis study examines the evolution of curtain wall details in Kimm Jong Soung's architecture, focusing on high-rise buildings from the 1970s to the 1990s. It emphasizes the profound influence of Mies van der Rohes design principles on Kimms work, focusing on the similarities between Kimms curtain wall details and those of Mies. Initially, Kimm followed Miess formal principles, but he later reinterpreted and developed these details to fit Koreas industrial and architectural context, establishing his own curtain wall design philosophy. The study explores how Kimm overcame the technological and industrial limitations of Korea at the time to apply these design principles. Despite restricted materials and construction technologies, Kimm creatively reinterpreted Miess ideas through meticulous attention to curtain wall details. His curtain wall designs go beyond simple facade treatments, serving as visual records of the evolution of Korean architecture. This re-evaluation of Kimms approach to curtain walls holds significant meaning in Korean architectural history, as it highlights his achievement in integrating structural and aesthetic elements.N
How to run a successful internship programme
No full textFive researchers from around the world share advice for helping students and their mentors benefit from short-term internships.N
Techno-economic analysis of combined photovoltaic cells and hydrogen energy systems for data center energy consumption
No full textThe future energy consumption of data centers is expected to be significant worldwide. From the perspective of carbon neutrality, designing 100 % renewable energy systems with distributed energy resources that can reliably supply energy to data centers is necessary. However, renewables' intrinsic uncontrollable characteristics make the stable energy supply challenging. Herein, we designed a 100 % renewable energy system by combining abundant but uncontrollable solar energy (e.g., photovoltaic (PV) cells) and controllable hydrogen (H2) energy systems (e.g., hydrogen microturbine and fuel cells) for a stable energy supply to an actual data center in South Korea. The hybrid system with on-site hydrogen production would be favorable after 2030 because of the expected decrease in green hydrogen prices and increase in carbon tax. Also, from sensitivity analyses, we found that the total NPC decreased by 75.2 % (/kg to 3 $/kg.N
Elimination of olfactory sensory neurons by zinc sulfate inoculation prevents SARS-CoV-2 infection of the brain in K18-hACE2 transgenic mice
No full textCoronavirus disease-2019 (COVID-19), attributed to the severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2), has posed global health challenges since it first emerged in 2019, and its impact continues to persist. The neurotropic nature of SARS-CoV-2 remains undisclosed, though researchers are proposing hypotheses on how the virus is transmitted to the central nervous system. One of the prevailing hypotheses is that SARS-CoV-2 travels through the olfactory nerve system via the olfactory epithelium (OE). Using a K18-human angiotensin converting-enzyme 2 (hACE2) transgenic mouse model with impaired olfactory sensory neurons (OSNs) induced by zinc sulfate, we examined the role of the olfactory nerve in the brain invasion by SARS-CoV-2. Mice lacking OSNs exhibited reduced levels of viral transmission to the brain, leading to significantly improved outcomes following SARS-CoV-2 infection. Moreover, a positive correlation was observed between viral persistence in the OE and brain infection. These results indicate that early inhibition of the olfactory nerve pathway effectively prevents viral invasion of the brain in K18-hACE2 mice. Our study underscores the significance of the olfactory nerve pathway in the transmission of SARS-CoV-2 to the brain.Y