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The purpose of this study is to identify the factors affecting the job stress of commercial sports center workers on organizational commitment and turnover intention. The causal relationship between their demographic characteristics and job stress was investigated for 261 out of 300 workers working at commercial sports centers in Seoul, Incheon, and Gyeonggi province. There was a difference by work type, and it was found that there was a difference between regular and contract workers. Role-related and interpersonal relationships had a negative influence relationship in terms of tenure commitment, normative commitment, and affective commitment. Job characteristics, role-related, interpersonal relationship, and compensation system had an influence on turnover intention. In other words, it was found that role-related and interpersonal relationships had a positive effect on turnover intention, and job characteristics and compensation system had a negative effect on turnover intention. It was found that job stress affects both organizational commitment and turnover intention. The results of this study indicate that job stress, organizational commitment, and turnover intention should be dealt with mainly in order to reduce turnover intention of commercial sports center workers. In other words, clearer guidelines on the role of commercial sports center workers and various welfare programs for improving human relationships should be provided. Therefore, commercial sports centers should continuously research and develop ways to maximize job satisfaction from the perspective of workers in order to reduce job stress and induce positive organizational commitment.

Triple-negative breast cancer (TNBC) has a poor clinical outcome, due to a lack of actionable therapeutic targets. Herein we define lysosomal acid lipase A (LIPA) as a viable molecular target in TNBC and identify a stereospecific small molecule (ERX-41) that binds LIPA. ERX-41 induces endoplasmic reticulum (ER) stress resulting in cell death, and this effect is on target as evidenced by specific LIPA mutations providing resistance. Importantly, we demonstrate that ERX-41 activity is independent of LIPA lipase function but dependent on its ER localization. Mechanistically, ERX-41 binding of LIPA decreases expression of multiple ER-resident proteins involved in protein folding. This targeted vulnerability has a large therapeutic window, with no adverse effects either on normal mammary epithelial cells or in mice. Our study implicates a targeted strategy for solid tumors, including breast, brain, pancreatic and ovarian, whereby small, orally bioavailable molecules targeting LIPA block protein folding, induce ER stress and result in tumor cell death.

In this study, we propose a new capacity estimation scheme for various aging states of lithium-ion batteries based on an inverted bottleneck network (IBN) that learns electrochemical knowledge. Most existing capacity estimation schemes that employ simple models have limitations in accuracy because they cannot reflect the complex aging states inside the batteries. An electrochemical model is sufficiently sophisticated to estimate the capacity of lithium-ion batteries accurately; however, it is computationally expensive. Therefore, we transfer the knowledge of an electrochemical model that deals with the physico-chemical behavior of the batteries to a small-sized IBN. Then, the proposed neural network that learns both the synthetic and experimental data can estimate the capacity of different aging states accurately with a lower computational time. Further, the specific structure of the IBN allows the neural network to extract visible information, called an attention map, which represents the decision basis of the neural network when estimating capacity. We propose an estimation score for determining the reliability of the capacity estimation result by analyzing the attention map and input voltage data. We measured capacity data from 12 real 37 Ah-standard batteries with different aging states to validate the efficacy of the proposed approach. The resulting estimation errors were about 0.445 Ah, which correspond to only 1.202 % errors based on the 37 Ah capacity.

The advancement of electrolyte systems has enabled the development of high-performance Li metal batteries (LMBs), which have tackled intractable dendritic Li growth and irreversible Li plating/stripping. In particular, the robust electrode–electrolyte interfaces created by electrolyte additives inhibit the deterioration of the cathode and the Li metal anode during repeated cycles. This paper reports the application of electrode–electrolyte interface modifiers, namely lithium nitrate (LiNO3) and lithium difluoro(bisoxalato) phosphate (LiDFBP) as a N donor and F donor, respectively. LiDFBP and LiNO3 with different electron-accepting abilities construct a mechanically robust, LiF-rich inner solid electrolyte interphase (SEI) and ion-permeable, Li3N-containing outer SEI layers on the Li metal anode, respectively. A well-structured dual-layer SEI capable of transporting Li+ ions is formed on the Li metal anode, while the cathode–electrolyte interface (CEI) on the LiNi0.8Co0.1Mn0.1O2 (NCM811) cathode is strengthened. Ether-based electrolytes containing LiDFBP and LiNO3 lead to a long cycle life (600 cycles) of Li|NCM811 full cells at C/2 with 80.9% capacity retention and a high Coulombic efficiency (CE) of 99.94%. Structural optimization of the SEI and CEI provides an opportunity for advancing the practical uses of LMBs.

Improvements to perovskite solar cells (PSCs) have focused on increasing their power conversion efficiency (PCE) and operational stability and maintaining high performance upon scale-up to module sizes. We report that replacing the commonly used mesoporous–titanium dioxide electron transport layer (ETL) with a thin layer of polyacrylic acid–stabilized tin(IV) oxide quantum dots (paa-QD-SnO 2 ) on the compact–titanium dioxide enhanced light capture and largely suppressed nonradiative recombination at the ETL–perovskite interface. The use of paa-QD-SnO 2 as electron-selective contact enabled PSCs (0.08 square centimeters) with a PCE of 25.7% (certified 25.4%) and high operational stability and facilitated the scale-up of the PSCs to larger areas. PCEs of 23.3, 21.7, and 20.6% were achieved for PSCs with active areas of 1, 20, and 64 square centimeters, respectively.

The prevalence of obesity has been continuously increasing, especially in rural areas of South Korea. Therefore, it is important to examine various genetic, behavioral, and environmental factors associated with obesity in these rural areas. The Korean Society for the Study of Obesity commenced a community-based prospective cohort study of the Gangwon area called the Gangwon Obesity and Metabolic Syndrome (GOMS) study to investigate longitudinal changes in the status of obesity and its related factors.A total of 317 adults 40-69 years of age were recruited from Hongcheon and Inje districts, Gangwon province, as part of the first wave of this cohort study. Information on participants' demographic, behavioral, psychological, dietary, and environmental factors and past medical histories were collected by self-administered questionnaires and interviewer-administered questionnaires. Anthropometric measurements, blood tests, and a hand grip strength test were performed, and skin keratin and stool samples were collected. Among the 317 enrolled subjects, two participants who did not have anthropometric data were excluded from the data analyses, resulting in an inclusion of a total of 315 participants.The mean age of the 315 participants in the GOMS initial baseline survey was 58.5 years old, 87 of them were men, and the mean body mass index was 24.7±3.7 kg/mThe first baseline survey of the GOMS study was initiated, and a more detailed analysis of respondents' data is expected to be continued. Further follow-up and additional recruitment will allow the investigation of risk factors and the etiology of obesity and its comorbidities in rural areas of Gangwon province.

NMDA receptor (NMDAR) and GABA neuronal dysfunctions are observed in animal models of autism spectrum disorders, but how these dysfunctions impair social cognition and behavior remains unclear. We report here that NMDARs in cortical parvalbumin (Pv)-positive interneurons cooperate with gap junctions to promote high-frequency (>80 Hz) Pv neuronal burst firing and social cognition. Shank2–/– mice, displaying improved sociability upon NMDAR activation, show impaired cortical social representation and inhibitory neuronal burst firing. Cortical Shank2–/– Pv neurons show decreased NMDAR activity, which suppresses the cooperation between NMDARs and gap junctions (GJs) for normal burst firing. Shank2–/– Pv neurons show compensatory increases in GJ activity that are not sufficient for social rescue. However, optogenetic boosting of Pv neuronal bursts, requiring GJs, rescues cortical social cognition in Shank2–/– mice, similar to the NMDAR-dependent social rescue. Therefore, NMDARs and gap junctions cooperate to promote cortical Pv neuronal bursts and social cognition., How NMDAR and GABA neuronal dysfunctions result in impaired social behaviour is unclear. Here, the authors show that NMDARs and gap junctions in cortical PV interneurons modulate burst firing, affecting social behaviour.

Microscale lasers efficiently deliver coherent photons into small volumes for intracellular biosensors and all-photonic microprocessors. Such technologies have given rise to a compelling pursuit of ever-smaller and ever-more-efficient microlasers. Upconversion microlasers have great potential owing to their large anti-Stokes shifts but have lagged behind other microlasers due to their high pump power requirement for population inversion of multiphoton-excited states. Here, we demonstrate continuous-wave upconversion lasing at an ultralow lasing threshold (4.7 W cm−2) by adopting monolithic whispering-gallery-mode microspheres synthesized by laser-induced liquefaction of upconversion nanoparticles and subsequent rapid quenching (“liquid-quenching”). Liquid-quenching completely integrates upconversion nanoparticles to provide high pump-to-gain interaction with low intracavity losses for efficient lasing. Atomic-scale disorder in the liquid-quenched host matrix suppresses phonon-assisted energy back transfer to achieve efficient population inversion. Narrow laser lines were spectrally tuned by up to 3.56 nm by injection pump power and operation temperature adjustments. Our low-threshold, wavelength-tunable, and continuous-wave upconversion microlaser with a narrow linewidth represents the anti-Stokes-shift microlaser that is competitive against state-of-the-art Stokes-shift microlasers, which paves the way for high-resolution atomic spectroscopy, biomedical quantitative phase imaging, and high-speed optical communication via wavelength-division-multiplexing., Upconversion microlasers present a lot of advantages but also require high pumping powers. Here the authors present a high-performing microlaser based on anti-Stokes-shift in upconversion nanoparticles synthesized using a technique of liquid quenching.

Crystalline silicon solar cells are considered mainstream products in the photovoltaic market. To further improve their performance, it is important to maintain good contact between metal electrodes and the Si surface because the state of the metal–Si interface affects the saturation current density J0.metal and open-circuit voltage. Moreover, the large saturation current density strongly attributes to the performance degradation of solar cells. Therefore, the interfacial structure formed by the metal electrodes and Si surface must be examined to minimize the J0.metal value. In this study, we investigated the formation mechanism of Ag crystallites on the surface of Si emitter layer in screen-printed Ag paste. Interestingly, J0.metal was minimized by Ag epitaxial growth, which was verified using an atomic-scale approach. Furthermore, the effect of P doping on the Ag–Si interfacial structure reduced J0.metal. Our study can provide new insights into the origin of J0.metal for realizing high-performance solar cells.

Neural prostheses are systems that interact with the human nervous system to recover function lost as a result of disease by recording or stimulating neural signals. Neural implants have a variety of components, but among them, designing highly efficient wireless power transmission systems is particularly important. However, there is a problem that it is difficult to design a wireless power transmission system with high transmission efficiency because power transmission efficiency is affected by various coil parameters. In addition, nerve implants are mainly designed based on polymer substrates, but studies have not been conducted on the process of manufacturing coils based on polymer substrates. In this study, to overcome the mentioned problems, an easy and fast manufacturing process was proposed before designing a precise coil on a polymer substrate. Coil was made by manually winding the 200um copper wire, and the coil was packaged using COC. The coil feasibility test was conducted after fabrication to evaluate the performance of fabrication process. It did not fit the expected frequency because the wire was manually wound to make a small size coil. However, the wire wound coil is expected to be more efficient than the coil made through the PCB process, and if the sophistication is supplemented, it can be used as a highly efficient coil for wireless power transmission.

BACKGROUND: Ovarian cancer (OCa) is the deadliest of all gynecologic cancers in the United States. Currently approved therapies have improved OCa survival for clinically localized disease, however, the majority (~90%) of patients with high-grade serous OCa (HGSOC) experience relapse with incurable metastases. There is a dire need for new therapeutic approaches. We hypothesized that the high basal endoplasmic reticulum stress (ERS) in OCa represents a critical and targetable vulnerability and may overcome the tumor heterogeneity. The objective of this project is to exploit increased ERS in ovarian cancer cells by engaging the novel target LIPA using the unique compound ERX-41. METHODS: The utility of ERX-41 as a new therapy was evaluated using MTT and CellTiter-Glo Cell Viability Assays. We used multiple established and patient derived OCa cell lines. The effect of ERX-41 on the Cell viability of patient-derived organoids (PDO) was measured using CellTiter-Glo 3D Assay. Long term effects of ERX-41 on cell survival were measured using colony formation assays. Apoptosis was measured using Annexin V and Caspase-Glo® 3/7 Assays. Cell cycle analysis was analyzed by Flow Cytometry. Mechanistic studies were done using LIPA knockout (KO) cells, RT-qPCR, and western blotting. Status of LIPA in OCa was determined using TNMplot database. In vivo efficacy of ERX-41 was tested using both cell line derived (CDX) and patient derived (PDXs) xenografts. RESULTS: TNM plot results showed that LIPA is highly expressed in OCa tumors compared to normal tissues and LIPA expression correlated with clinical grade. Kaplan-Meier plotter analyses of TCGA data revealed that LIPA expression is negatively correlated with overall survival in OCa patients. MTT and CellTitre-Glo assay results showed that ERX-41 significantly reduced the cell viability of both established and primary OCa cells, and PDO’s with an IC50 of ~500nM. ERX-41 treatment also significantly reduced the cell survival, increased S-phase arrest, and promoted apoptosis of OCa cells. A time course study revealed a robust and consistent induction of ERS markers (CHOP and sXBP1) in OCa cells by ERX-41 within 4h. Western blotting analyses also confirmed increased expression of ERS markers including CHOP, elF2α, PERK, and ATF4 upon ERX-41 treatment confirming that ERX-41 induces ERS. In xenograft studies, ERX-41 treatment resulted in ~66% reduction of tumor volume measured by Xenogen-IVIS. Further, in studies using PDX tumors, treatment with ERX-41 resulted in a significant reduction (~60%) of tumor volume and tumor weight. CONCLUSION: Collectively, our results suggest that ERX-41 is a novel therapeutic agent that targets the LIPA with a unique mechanism of action and implicate ERX-41 binding to LIPA induces ER stress, and apoptosis of OCa cells. Further molecular characterization of how ERX-41 binding to LIPA induces ER stress in OCa cells is ongoing. Citation Format: Alexia B. Collier, Suryavathi Viswanadhapalli, Tae-Kyung Lee, Kara Kassees, Karla Parra, Gaurav Sharma, Tanner Reese, Michael Hsieh, Xihui Liu, Xue Yang, Behnam Ebrahimi, Uday P. Pratap, Rahul Gopalam, Chia Yuan Chen, Scott Terry Elmore, Gangadhara Reddy Sareddy, Edward R. Kost, Jung-Mo Ahn, Ganesh V. Raj, Ratna K. Vadlamudi. Novel LIPA targeted therapy for treating ovarian cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3986.

Background: Ovarian cancer (OCa) is the deadliest of all gynecologic cancers in the United States. Despite initial response to chemotherapy, most OCa patients become chemo resistant and progress to metastatic disease. Here, we tested the hypothesis that the high basal level of endoplasmic reticulum stress (ERS) in OCa represents a critical vulnerability and drugs that further aggravate this already engaged system in OCa may exhaust its protective features and contribute to apoptosis induction. The objective of this proposal is to identify a hit compound that enhances ERS in OCa and to conduct mechanistic studies. Methods: We synthesized a small library of >200 chemically distinct oligobenzamide analogs with maintenance of the chemical backbone but altered R groups of ERX-11. We performed the primary screening of this library to evaluate the induction of mRNA levels of two canonical ERS/UPR (unfolded protein response) genes- sXBP1 and CHOP. Biological activity of ERX-208 was validated using multiple OCa cells. Mechanistic studies were conducted using CRISPR/Cas9 KO, Western blotting, reporter gene assays, IHC and RNA-seq analysis. PK (pharmacokinetics) and toxicity studies were done using C57BL/6 mice. Cell line-derived xenografts (CDXs), patient-derived xenografts (PDXs), patient-derived explants (PDEs), and patient-derived organoids (PDO) were used for preclinical evaluation. Results: From a screen of a curated ERX-11 derived oligobenzamide library, we identified a hit compound, ERX-208 that potently (IC50~100nM) induces ERS/UPR and apoptosis in multiple OCa cells in vitro. CRISPR KO screen identified the lysosomal acid lipase A (LIPA) protein as the critical target of ERX-208. LIPA KO abrogates response to ERX-208, while reconstitution of LIPA restores ERX-208 response. The time course studies showed a robust and consistent induction (>15-fold CHOP, and >10-fold sXBP1) by ERX-208 treatment within 24h. We confirmed induction of classic UPR components peIF2α, CHOP and LC3B using Western blotting in multiple OCa cells. Functionally, ERX-208 causes growth inhibition of OCa cells, as noted by MTT cell viability assays using 15 OCa cells with an IC50 of ~50-100nM. The activity of ERX-208 is distinct among oligobenzamides as ERX-11 has limited/no activity against OCa cells. RNA-seq analysis confirmed that ERX-208 induces significant ERS, UPR, and apoptosis. Further, ERX-208 reduced the growth of OCa PDO’s in vitro, PDEs ex vivo and CDXs and PDXs in vivo. ERX-208 treatment did not show any signs of toxicity and body weight of mice was not affected. IHC analyses showed increased activation of ERS/UPR markers such as GRP78, p-PERK and decreased proliferation measured by Ki67. Conclusions: Collectively, our results demonstrated the utility of ERX-208 and will establish a novel therapeutic paradigm in OCa that overcomes tumor heterogeneity by targeting LIPA and enhancing ERS leading to apoptosis. Citation Format: Suryavathi Viswanadhapalli, Tae-Kyung Lee, Kara Kassees, Gaurav Sharma, Rahul Gopalam, Karla Parra, Tanner Reese, Michael Hsieh, Uday P. Pratap, Xue Yang, Behnam Ebrahimi, Chia Yuan Chen, Scott Terry Elmore, Christian Cervantes, Zhenming Xu, Edward Kost, Gangadhara Reddy Sareddy, Rajeshwar Rao Tekmal, Jung-Mo Ann, Ganesh V. Raj, Ratna K. Vadlamudi. ERX-208 as a novel therapeutic for treating ovarian cancer by enhancing endoplasmic reticulum stress. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4813.

Introduction: Estrogen receptor gene (ESR1) drives approximately 70-80% of breast cancer cases, which are primarily treated with endocrine therapies. Mutations in the ESR1 exclusively occur in the ligand binding domain (LBD) and are significantly enriched following endocrine therapy. These mutations retain the estrogen receptor (ER) expression thus conferring ligand-independent growth, which is a paramount contributor to endocrine therapy resistant disease. Worse progression-free survival is consistently associated with ESR1 mutation status; therefore, there is an unmet need for therapies against these mutations. To this end, we recently developed TX-245, a bis-benzamide molecule that hampers the function of the two most common ESR1 mutations - Y537S and D538G. Methods: TX-245 was evaluated in vitro using MTT cell proliferation assay and colony formation assay carried out in multiple ER+ breast cancer cells harboring wild type (WT) ESR1 or mutant (MT) ESR1. Approaches such as tumor spheroid cultures were also implemented to study the effect of TX-245 compared to selected SERDs/SERMs via CellTiter-Glo 3D viability assay. Mechanistic insights were obtained performing TR-FRET assay, fluorescence polarization assay, RNA-seq, ChIP-seq, western blot, and qRT-PCR. The therapeutic efficacy in vivo was evaluated using cell xenografts, patient derived xenografts (PDX), patient derived explants (PDE), and metastatic mouse models of MT-ER breast cancer. Results: TX-245 demonstrated greater anti-proliferative dose-dependent activity in models harboring WT and MT ESR1, including those resistant to fulvestrant and tamoxifen, when compared to other SERDs/SERMs. RNAseq data suggests that TX-245 dramatically alters the transcription of ERα-regulated genes, with repression of canonical estradiol-upregulated and induction of estradiol-repressed genes. TX-245 was able to antagonize ER-chromatin interaction and ER-transcriptional signaling in breast cancer cells driven by ESR1 mutation. TX-245 treatment downregulated ER protein expression and decreased expression of ER targeted genes (i.e., GREB and PGR) in multiple ER+ cell lines. TX-245 treatment as a single agent or in combination with palbociclib resulted in tumor regression in xenografts expressing WT, Y537S or D538G ESR1 mutation. PDX and PDE models consistently exhibited substantial tumor growth inhibition as well as decreased proliferation (Ki67 staining). Metastases studies using intracardiac and intratibial injection demonstrated that TX-245 inhibited the progression of established metastatic niches in mice injected with Y537S or D538G ER+ breast cancer cells. Conclusion: Our results indicate that TX-245 inhibits cell proliferation in cell lines that express WT or mutant ESR1, induce ER degradation, suppress ER-mediated signaling and reduce tumor burden in mouse models. These studies highlight the utility of TX-245 in targeting mutations in the ER-LBD. Citation Format: Karla Parra, Suryavathi Viswanadhapalli, Tanner Reese, Xihui Liu, JunHao Liu, Zexuan Liu, Tae-Kyung Lee, Chia Yuan Chen, Kara Kassees, Jung-Mo Ahn, Ratna Vadlamudi, Ganesh Raj, Carlos Roggero. Targeting the mutant estrogen receptor in metastatic breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3440.

The use of role-assigned ionic additives with different adsorption energies and distinct electron-accepting abilities enables the construction of a multilayer solid electrolyte interphase (SEI) wit...

Neuroinflammation is a primary characteristic of the aging brain. During normal aging, macrophage inflammatory protein‑3α (MIP‑3α) and its receptor C‑C chemokine receptor type 6 (CCR6) serve pivotal roles in the neuroinflammatory process in the brain. The aim of the present study was to investigate age‑dependent alterations in the immunoreactivity of MIP‑3α and CCR6 in the gerbil hippocampus at postnatal month (PM) 1, 6, 12 and 24 via immunohistochemistry. In the PM 1 group, both MIP‑3α and CCR6 immunoreactivity were observed primarily in the stratum pyramidale in the hippocampus proper and in the granule cell layer in the dentate gyrus. In the PM 6 and PM 12 groups, MIP‑3α in the stratum pyramidale and granule cell layer was decreased compared with the PM 1 group, and CCR6 immunoreactivity in both layers was faint. In the PM 24 group, MIP‑3α expression in the stratum pyramidale and granule cell layer was higher than that in the PM 1 group, and CCR6 immunoreactivity in both layers was increased compared with the PM 12 group; however, it was decreased compared with the PM 1 group. In conclusion, MIP‑3α and CCR6 immunoreactivity were altered in the hippocampus during normal aging. The results of the current study suggested that age‑dependent alterations of MIP‑3α and CCR6 may be associated with age‑related neuroinflammation in the hippocampus.

Panax ginseng CA Meyer has a variety of biological effects, including antioxidant and antidiabetic activities. Ginseng requires long-term cultivation, but this can be shortened using hydroponic systems to facilitate the commercial development of ginseng as a functional food. However, the characteristics of short-term-cultured (

The effect of cationic chlorides has been studied to achieve high quality perovskite films, for high performance perovskite solar cells. However, the role of cationic chloride additives which form mixed-cations on the perovskite structure is still unclear. Investigating the crystal morphology and stability of perovskite films for various sizes or concentrations of cationic chlorides is an essential part of the optoelectronic perovskite study. This paper investigates how cationic chlorides GuCl, FACl, CsCl, RbCl, and KCl, with different cationic sizes and concentrations, affected FAPbI3 perovskite. By forming mixed-cations by the addition of cationic chlorides with appropriate cation size and concentration, based on the tolerance factor, the crystallinity of the perovskite film was improved, achieving a lifetime 2.50 times longer, and a grain size 2.44 times larger. As a result, the efficiency of the perovskite solar cells is increased to 23.28%, and certified as 22.65% at Newport with optimized cationic chlorides. To understand the effect of the cation size and concentration of the cationic chlorides, theoretical analysis of the mechanism by which the cationic chlorides increased the crystallinity was performed using density functional theory calculations. The results revealed the effect of the various cationic chlorides on perovskite phase structures and matched the experimental results.

Background: ESR1 mutations are acquired following ERα targeted therapies and are a major determinant of therapy-resistance. These ESR1 mutations maintain ESR1 signaling, albeit in a ligand-independent manner. Effective drugs targeting these mutant (MT) ERα proteins represent a significant unmet clinical need. We had previously shown that ERX-11, an ESR1-coregulator binding inhibitor, could block the function of these MT ERα proteins. In this study, we sought to leverage recently published structures of MT ERα to develop more potent analogues of ERX-11. Methods: Virtual screening of >250,000 derivatives of ERX-11 was performed with simulated docking on the MT ERα to identify and design analogues of ERX-11. Several hundred analogues were synthesized and tested in vitro using multiple BC model cells that express wild type (WT) ESR1 or mutant (MT) ESR1 (Y537S or D538G). Mechanistic studies were performed using RNA-Seq, Western blotting, qRT-PCR and reporter gene assays. The in vivo efficacy of the most potent ERX-11 analogue ERX-245 was examined using xenograft, PDX and metastatic models of MT-ER driven BC. Results: From our virtual and functional screen, we identified an ERX-11 analogue, ERX-245 as the most potent hit to target MT-ERα. Docking studies modeled a better fit of ERX-245 into the ligand binding domain of both the Y537S and D538G MT-ERα. ERX-245 potently reduced (IC50 ~250 nM) the cell viability of both WT-ERα and MT-ERα driven BC cells but not ERα negative BC cells. ERX-245 significantly reduced the growth (colony formation, clonogenic and mammosphere assays) of MT-ERα BC cells. ERX-245 exhibited synergistic activity in combination with CDK4/6 inhibitors. In distinction to classic SERDs like fulvestrant (which degrade ERα with in 4h), ERX-245 treatment decreased MT-ERα protein levels over 24 hours. PK studies indicated that ERX-245 is more polar and has better solubility and pharmacokinetic properties than ERX-11. ERX-245 reduced tumor growth of subcutaneous xenograft and PDX models driven by MT-ERα as well as the proliferation of xenograft derived MT-ERα explant models. ERX-245 significantly reduced the invasive capability of MT-ERα BC cells in vitro and inhibited both the metastatic capability and growth of metastatic tumors derived from MT-ERα BC cells injected by intracardiac or intratibial routes. Conclusions: Taken together, these results indicate that ERX-245 is a potent and pharmacologically translatable analog of ERX-11, with activity against both primary and metastatic tumors driven by MT-ERα. Citation Format: Ganesh V Raj, Suryavathi Viswanadhapalli, Karla Parra, Shihong Ma, Tae-Kyung Lee, Xihui Liu, Kara Kassees, Weiwei Tang, Junhao Liu, Zexuan Liu, Uday P Pratap, Behnam Ebrahimi, Rajeshwar Rao Tekmal, Jung-Mo Ann, Ratna K Vadlamudi. Development of a potent mutant-ESR1 targeted agent, ERX-245, for treating metastatic therapy-resistant breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS17-09.

Modern H2-based energy storage and conversion devices require a polymer electrolyte membrane (PEM) fuel cell–based integrated power system with synergistic heat integration. The key issue in integrated power systems is developing a PEM that can operate at 200–300 °C. However, currently used phosphoric-acid-based high-temperature PEM fuel cells limited stability at higher operating temperatures. Herein, we introduce a cerium hydrogen phosphate (CeHP) PEM that conducts protons above 200 °C through a self-assembled network (SAN). The SAN-CeHP-PBI reached maximum power densities of 2.4 W cm-2 and operate stably for over 7000 minute without any voltage decay at 250 ℃ under H2/O2 and anhydrous conditions. The developed fuel cell can be combined with an external hydrogen generator that uses a liquid hydrogen carrier such as N-ethylcarbazole and methanol as fuel, thus achieving a high energy efficiency. The thermal stability and fuel flexibility of these SAN-CeHP-PBI demonstrate potential for commercial applications.

Summary One of the most effective methods to achieve high-performance perovskite solar cells has been to include additives that serve as dopants, crystallization agents, or passivate defect sites. Cl-based additives are among the most prevalent in literature, yet their exact role is still uncertain. In this work, we systematically study the function of methylammonium chloride (MACl) additive in formamidinium lead iodide (FAPbI3)-based perovskite. Using density functional theory, we provide a theoretical framework for understanding the interaction of MACl with a perovskite. We show that MACl successfully induces an intermediate to the pure FAPbI3 α-phase without annealing. The formation energy is related to the amount of incorporated MACl. By tuning the incorporation of MACl, the perovskite film quality can be significantly improved, exhibiting a 6× increase in grain size, a 3× increase in phase crystallinity, and a 4.3× increase in photoluminescence lifetime. The optimized solar cells achieved a certified efficiency of 23.48%.

Natural gas has been suggested as an alternative fuel for compression ignition (CI) engines because it generates significantly less pollutants and has a smaller carbon footprint, while maintaining the cycle efficiency. However, the high auto-ignition temperature of natural gas typically requires the use of a quasi-compression ignition method such as homogenous charge compression ignition (HCCI) or a dual-fuel mode. Yet, methods such as these are unable to realize the full potential of high efficiency and low emissions. This motivated us to evaluate the applicability of a high-pressure direct-injected natural gas jet for a pure CI engine under various engine load, injection timing, and injection pressure conditions using a single cylinder CI engine with a compression ratio of 15.5. The intake temperature was raised to 400 °C to achieve the auto-ignition temperature of methane after compression and a multi-hole GDI injector capable of operating at a pressure of 400 bar was used for fuel injection. As a result, CI operation was possible, but ignition occurred after the end of the injection in the form of a partially premixed flame rather than a diffusion flame for all conditions under which the engine was operated. A sufficient equivalence ratio of 0.8 was achieved at an injection pressure of 300 bar and injection duration of 1.6 ms with the multi-hole GDI injector, and the GMEP value varied from 2 bar to 5.5 bar according to the equivalence ratio. However, at an equivalence ratio of 0.7 or higher, the combustion efficiency decreased drastically because of the limit of the volume fraction of the piston bowl at TDC and the narrow nozzle distribution of the GDI injector. Measurement of the pollutants indicated that the total number of particles from methane CI operation exceeded that of diesel at an equivalence ratio of 0.74 in the same engine setup because of incomplete combustion; however, the total mass of the particulate matter (PM) was approximately 15% of the diesel because the average particle size from methane CI was approximately one third smaller than that of diesel. However, the high post-compression temperature for the auto-ignition of methane gas resulted in a high peak temperature, which resulted in the production of approximately 2000 ppm NOx under all test conditions. The results of the parametric study showed that, as the injection timing retarded, the ignition timing was almost equally retarded, thus the combustion was still observed in the form of a diffusion flame. As the injection pressure increased, the ignition delay became shorter and the emission of PM could be further reduced, but the NOx emission increased.

Practical electronic device applications using graphene-based materials dictate that their band gap must be tunable. The synthesis of hydrogenated graphene has received much attention due to the de...