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Moon, Su-Jeong. "Understanding of Duan Yu-Cai ’s Perspectives on Jiajie(假借)". Chinese Studies 50 (31 березня 2015): 237–56. http://dx.doi.org/10.14378/kacs.2015.50.50.237.
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Cosentino, Alessandro, and Vincent Russo. "Small sets of locally indistinguishable orthogonal maximally entangled states." Quantum Information and Computation 14, no. 13&14 (2014): 1098–106. http://dx.doi.org/10.26421/qic14.13-14-3.
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We study the problem of distinguishing quantum states using local operations and classical communication (LOCC). A question of fundamental interest is whether there exist sets of $k \leq d$ orthogonal maximally entangled states in $\complex^{d}\otimes\complex^{d}$ that are not perfectly distinguishable by LOCC. A recent result by Yu, Duan, and Ying [Phys. Rev. Lett. 109 020506 (2012)] gives an affirmative answer for the case $k = d$. We give, for the first time, a proof that such sets of states indeed exist even in the case $k < d$. Our result is constructive and holds for an even wider class of operations known as positive-partial-transpose measurements (PPT). The proof uses the characterization of the PPT-distinguishability problem as a semidefinite program.
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Yap, Cheah-Shen. "Preserving the Original Layout of Ancient Chinese Texts Using HTML5: Using Shuowen Jiezi as an Example." International Journal of Humanities and Arts Computing 7, supplement (2013): 111–19. http://dx.doi.org/10.3366/ijhac.2013.0064.
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We have developed a software platform for converting the Chinese classics into a digital format which the original layout is preserved. This method of conversion allows those that are not experts in classical Chinese literature, even those that do not understand Chinese, to partake in the proof-reading process. Since this kind of application involves complicated manipulation of 2D graphics, in the past, we have no choice but writing a native desktop program, with the introduction of CANVAS tag to the HTML 5 standards, we are able to move our code from desktop to browser without any plug-in or JAVA applet. The cost of cross-platform development and maintenance is greatly reduced. In order to clarify the various elements involved in the conversion and proof-reading process, we will use Duan Yu Cai's compilation of the Shuowen Jiezi 1 as an example throughout this paper.
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Zhang, Lin, Jingkun Qu, Yutao Qi, et al. "Abstract 2435: EZH2 engages TGFb signaling to promote breast cancer bone metastasis via Integrin b1-FAK activation." Cancer Research 82, no. 12_Supplement (2022): 2435. http://dx.doi.org/10.1158/1538-7445.am2022-2435.
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Abstract Bone metastasis is a frequent complication of breast cancer, occurring in about 50-70% of breast cancer patients with late-stage disease. The lack of effective therapy suggests that the precise molecular mechanisms underlying bone metastasis are still unclear. Enhancer of zeste homolog 2 (EZH2) is considered a breast cancer oncogene and its expression is correlated with metastasis of breast cancer, but its function in bone metastasis has not been well explored. Herein we report that EZH2 promotes osteolytic metastasis of breast cancer through regulating transforming growth factor beta (TGFβ) signaling, a key pathway in bone metastasis. Knocking down EZH2 decreases bone metastasis incidence and outgrowth in vivo. EZH2 induces cancer cell proliferation and osteoclast maturation, when breast cancer cells are co-cultured with osteoblasts and osteoclasts together in vitro. Mechanistically, EZH2 increases transcription of ITGB1, which encodes for integrin β1. Integrin β1 activates focal adhesion kinase (FAK), which phosphorylates TGFβ receptor type I (TGFβRI) at tyrosine 182, thus enhances the binding of TGFβRI to TGFβ receptor type II (TGFβRII), therefore activates Smad2 and increases parathyroid hormone-like hormone (PTHLH) expression. Clinically applicable FAK inhibitors but not EZH2 methyltransferase inhibitor effectively inhibits breast cancer bone metastasis in vivo. Overall, our data signify integrin β1-FAK as a new downstream effector of EZH2 in breast cancer cells, and EZH2-integrin β1-FAK axis cooperates with TGFβ signaling pathway to promote bone metastasis of breast cancer. Citation Format: Lin Zhang, Jingkun Qu, Yutao Qi, Yimin Duan, Yu-Wen Huang, Zhifen Zhou, Ping Li, Jun Yao, Beibei Huang, Shuxing Zhang, Dihua Yu. EZH2 engages TGFb signaling to promote breast cancer bone metastasis via Integrin b1-FAK activation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2435.
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Valdivieso Mora, E., M. Ivanisevic, and D. Johnson. "Community Engagement and Cognition in a Sample of Older Adults Residing in Costa Rica." Archives of Clinical Neuropsychology 34, no. 7 (2019): 1279. http://dx.doi.org/10.1093/arclin/acz029.46.
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Abstract Objective Costa Rica has the highest percentage of older adults (65+) of the Central American and Latin American region. In fact, Costa Rica has the highest life expectancy within an advanced healthcare system and socioeconomic infrastructure that differentiates it from neighboring countries in Central America. Previous research has shown that older adults who engage in higher social engagement show overall better cognitive functioning (Chen et al., 2018); however, limited research has examined the impact of socialization on cognition across rural and urban regions and furthermore no research to date has examined these factors in Costa Rican older adults. This study examined the effects of community engagement on cognition in urban and rural older adults residing in Costa Rica. Participants and Method Participants were neurotypical older adults residing in San Jose (urban region, n = 156) and Guanacaste (rural region, n = 69). Those with a history of neurological conditions and major psychiatric disorders were excluded. Results Older adults residing in an urban area (M = 55.43, SD = 23.26) participate more in social engagement within the community compared to those residing in the rural region (M = 46.30, SD = 28.50), p = 0.019. Furthermore, in the urban sample, those with higher social engagement showed better performance on learning and encoding (r = 30), verbal memory (r = 0.26), and executive functioning (r = .20). In older adults residing in the rural region, higher social engagement was only associated with better visuospatial abilities (r = 0.27). Conclusions Findings suggest that social engagement in the community for older adults in Costa Rica may serve as a protective factor for their cognitive health. However, there are significant differences on what cognitive processes serve as a protective factor as a function of location (rural versus urban). This study highlights the importance of examining the quality of social engagement when evaluating the cognition of Costa Rican older adults. References Chen, Ya-Mei, Tu, Yu-Kang, Yu, Hsiao-Wei, Chiu, Tzu-Ying, Chiang, Tung-Liang, Chen, Duan-Rung, & Chang, Ray-E. (2018). Leisure time activities as mediating variables in functional disability progression: An application of parallel latent growth curve modeling. PLoS ONE, 13(10).
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Zhang, Mengzhe. "POLYPHONIC GENRES IN PIANO CREATIVITY OF CHINESE COMPOSERS." Aspects of Historical Musicology 24, no. 24 (2021): 148–65. http://dx.doi.org/10.34064/khnum2-24.08.
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Statement of the problem. The twentieth century marked an increased interest in polyphonic music. The geography of polyphonic works for piano expanded significantly and a creative development of many Chinese composers, writing polyphonic piano pieces, took place. Today, polyphonic pieces make up a significant part of the piano repertoire in China, but they are little studied by musicologists and performers. The objective of this study – to reveal the contribution of Chinese composers to the creation of polyphonic piano repertoire of the XX – early XXI century. Analysis of the research and publications on the theme. А large number of modern authors study polyphony from the point of physical and mathematical research methods (Igarashi, Yu. & Ito, Masashi & Ito, Akinori, 2013; Weiwei, Zhang & Zhe, Chen, & Fuliang, Yin, 2016; Li, Xiaoquan et al. others, 2018). This approach does not reveal the factual musical component of polyphonic genres. In the 20th century, musicologists explored polyphony in musical folklore (Wiant, 1936; Fan Zuyin, 2004; Li Hong, 2015) and in professional Chinese composing (Sun Wei-bo, 2006, Winzenburg, 2018). The scientific novelty. This article studies the role of Chinese composers in the development of the world polyphonic piano repertoire of the XX – early XXI century. The methodological basis for the analysis of polyphonic works was the theoretical concepts of P. Hindemith, Peng Cheng, Fang Zuin, Li Hong, Sun Wei-bo. The results of the study. The research outcomes demonstrate the evolutionary development of the genre diversity of Chinese piano polyphony as well as those composers who created magnificent musical pieces. Conclusions. Chinese composers have fully mastered the art of modern counterpoint, represented by the genres of polyphonic program pieces (He Lu Ting), invention (Xiao Shu Xian, Du Qian, Sun Yun Yin, Chen Chen Quang), polyphonic suite (Ma Gui), large polyphonic cycle ( He Shao, Chen Hua Do, Xiao Shu Xian), fugue (Li Jun Yong, Yu Su Yan, Chen Gang, Tian Lei Lei, Duan Ping Tai, Zheng Zhong, Xiao Shu Xian) and small cycle “Prelude and Fugue” (Ding Shan Te, Chen Zhi Ming, Wang Li Shan). Creatively assimilating and rethinking the experience of Western polyphonists, Chinese composers have filled their polyphonic works with national features, firmly linking them with the origins of Chinese traditional and folk music. The polyphonic way of transmitting musical material becomes the most expressive at the moments of profound creativity and musical dramatization.
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Walters, Godfrey A., and Jezdimir Knezevic. "Discussion of “ Reliability‐Based Optimization Model for Water Distribution Systems ” by Yu‐Chun Su, Larry W. Mays, Ning Duan, and Kevin E. Lansey (December, 1987, Vol. 113, No. 12)." Journal of Hydraulic Engineering 115, no. 8 (1989): 1157–58. http://dx.doi.org/10.1061/(asce)0733-9429(1989)115:8(1157).
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Duan, Yimin, Yutao Qi, Lin Zhang, Xiangliang Yuan, and Dihua Yu. "Abstract 6370: Assessing the effect of blocking CCL2-CCR2 axis on breast cancer brain metastasis." Cancer Research 82, no. 12_Supplement (2022): 6370. http://dx.doi.org/10.1158/1538-7445.am2022-6370.
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Abstract Among the 300,000 newly diagnosed breast cancer patients every year, 5~20% of them will develop symptomatic brain metastasis, whose 1-year survival rate is lower than 20%. Our group previously reported that brain tumor microenvironment (TME)-mediated PTEN downregulation in brain metastatic tumor cells increases the secretion of the chemokine CCL2, which enhances the infiltration of CCR2+ bone marrow derived myeloid cells, eventually promoting brain metastasis outgrowth. However, the mechanism of CCL2-CCR2 axis promoting brain metastasis is not clear, and the efficacy of targeting either CCR2 or CCL2 remained to be assessed. Here we show that Ccr2 antagonism significantly blocked Ccr2high myeloid cells trafficking in the blood and infiltration into the brain TME. However, Ccr2 antagonism did not sufficiently impede breast cancer brain metastasis in multiple preclinical models. Nevertheless, knocking down CCL2 or targeting CCL2 exhibited significant inhibition of brain metastasis growth. Subsequent analysis of the brain TME through mass cytometry demonstrated dramatically decreased infiltration of both Ccr2high and Ccr2low myeloid cell populations in the CCL2 targeted group, implying that the Ccr2low myeloid cells are also involved in promoting brain metastasis growth. Our data highlights the differential responses between targeting CCR2 or CCL2 in multiple preclinical brain metastasis models, which direct us to explore the function of Ccr2low myeloid cells in regulating brain metastasis progression. Our findings also suggest that carefully choosing between CCR2 or CCL2 as a target to control brain metastasis is important in clinical practice. Citation Format: Yimin Duan, Yutao Qi, Lin Zhang, Xiangliang Yuan, Dihua Yu. Assessing the effect of blocking CCL2-CCR2 axis on breast cancer brain metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6370.
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Wan, Rui, Yi Fung Chau, Jun Zhao, et al. "Abstract CT055: Efficacy of YK-029A, a novel EGFR TKI, in advanced NSCLC patients with acquired T790M mutation." Cancer Research 84, no. 7_Supplement (2024): CT055. http://dx.doi.org/10.1158/1538-7445.am2024-ct055.
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Abstract In the multicenter, dose-escalation and dose-expansion phase 1 clinical trial (NCT05767866), we evaluated safety and tolerability of YK-029A in various EGFR mutated non-small-cell lung cancer (NSCLC). We have reported efficacy of YK-029A in untreated NSCLC with EGFR ex20ins mutation[1]. This time we report efficacy of YK-029A in patients with acquired EGFR T790M mutation after failure of first or second generation EGFR tyrosine kinase inhibitors (TKIs). Method: This dose-escalation and dose-expansion phase 1 trial recruited previously treated NSCLC patients with EGFR T790M mutation or patients with EGFR ex20ins or EGFR rare mutations. In dose-escalation phase, patients with EGFR T790M mutation were enrolled. YK-029A was given at doses of 50, 100, 150, 200 to 250 mg/day (3+3 design). In dose-expansion phase, patients with EGFR T790M, EGFR ex20ins, or EGFR rare mutations were enrolled. The primary objective was safety. Dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) were explored. Efficacy of YK-029A in EGFR T790M mutated NSCLC was assessed by the investigators. Results: A total of 114 patients were recruited into the study. Safety profile of the first 108 patients was reported previously[1]. By the cut-off date on Sep 12, 2023, 38 patients harbored EGFR T790M mutation were included in efficacy analysis. All these patients were previously treated with first or second generation EGFR-TKIs. The objective response rate (ORR; RECIST 1.1) was 65.8% (95%CI: 48.6%-80.4%) and disease control rate (DCR) was 84.2% (95%CI: 68.7%-94.0%). With a median follow-up time of 8.2 months,the median progression free survival (PFS) was 11.0 months (95%CI: 7.75-NR). The median overall survival (OS) was not reached. Among the 8 patients with measurable brain metastases, intracranial ORR was 75% (95%CI: 35.6%-95.6%) . Conclusions: YK-029A has promising activity in previously treated NSCLC patients harboring EGFR T790M mutation. Reference[1] DUAN J, WU L, YANG K, et al. Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of YK-029A in Treatment-Naive Patients With Advanced NSCLC Harboring EGFR Exon 20 Insertion Mutations: A Phase 1 Trial [J]. J Thorac Oncol, 2023. Citation Format: Rui Wan, Yi Fung Chau, Jun Zhao, Zhe Liu, Mingfang Zhao, Yanqiu Zhao, Xiumei Dai, Yueyin Pan, Zhihong Zhang, Yu Yao, Kunyu Yang, Lin Wu, Yanyan Xie, Bi Chen, Yixuan Yang, Yongqi Guo, Jie Wang, Jianchun Duan. Efficacy of YK-029A, a novel EGFR TKI, in advanced NSCLC patients with acquired T790M mutation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT055.
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Yang, Yongfei, Shuzhen Cao, Jing Zhang, et al. "Abstract 2907: 1C3, a Novel non-blocking anti-human TNFR2 antibody generated from RenMice, exhibits promising anti-tumor activity and safety in syngeneic tumor models in humanized TNFR2 mice." Cancer Research 82, no. 12_Supplement (2022): 2907. http://dx.doi.org/10.1158/1538-7445.am2022-2907.
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Abstract Regulatory T Cells (Treg) inhibit effector T cell (Teff) activity in the tumor microenvironment (TME). Therefore, depletion of regulatory T cells (Treg cells) is a promising therapeutic strategy for tumor immunotherapy. Tumor necrosis factor receptor-2 (TNFR2) is highly expressed on Treg cells and is a potential target for anti-tumor therapy. A TNFR2 non-blocking antibody (1C3) was generated from humanized IgG mice (RenMice), which is an effective platform for human antibody generation. 1C3 was selected from a large panel of antibody candidates through an unbiased, high-throughput in vivo efficacy screen in syngeneic tumor mouse models in humanized TNFR2 mice. Compared with other TNFR2 antagonistic antibodies, 1C3 effectively promoted the proliferation of CD8+ cytotoxic T cells in vitro, a population that is inhibited by Treg cells. To evaluate 1C3 efficacy and safety in vivo, syngeneic mouse tumor models were established. 1C3 monotherapy significantly inhibited tumor growth in a dose-dependent manner in syngeneic tumor mouse models in TNFR2 humanized mice. In combination with anti-human PD-1 or PD-L1 antibody, 1C3 also greatly increased antitumor activity compared to the monotherapy of each therapeutic agent. Mechanistically, 1C3 treatment significantly increased the ratio of Teff/Treg in the TME. In addition, 1C3 was well tolerated in TNFR2 humanized mice, and no side effects were observed even when the dose was increased to 100 mg/kg. Taken together, our data demonstrates that 1C3 is a novel anti-TNFR2 antibody for anti-tumor therapy and provides a great potential for the next generation of immunotherapy. Citation Format: Yongfei Yang, Shuzhen Cao, Jing Zhang, Zhe Shao, Xueyuan Jiang, Qingya Duan, Maopeng Tian, Sen Mei, Luke (Zhaoxue) Yu. 1C3, a Novel non-blocking anti-human TNFR2 antibody generated from RenMice, exhibits promising anti-tumor activity and safety in syngeneic tumor models in humanized TNFR2 mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2907.
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Zhang, Lin, Frank Lowery, Chenyu Zhang, et al. "Abstract 3161: PCTK1 driven glutamine metabolic adaptation in brain metastasis." Cancer Research 84, no. 6_Supplement (2024): 3161. http://dx.doi.org/10.1158/1538-7445.am2024-3161.
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Abstract Brain metastasis (BrM) is the most common malignancy of the central nervous system and the median survival time of patients with BrM is less than 1 year. Although recent impressive advances in targeted therapy and immunotherapy enable more effective control of the systemic diseases, the incidence of BrM upon disease recurrence is steadily increasing. Unfortunately, there is no effective treatments for BrM. To surmount this challenge, we have performed an in vivo human kinome screening to uncover novel kinases that promote breast cancer (BC) BrMs in mice and may serve as therapeutic targets. We identified &gt;20 different kinases enriched in BrM lesions of our mouse models and PCTK1 is one of the top “hits”. We transduced PCTK1 expression vector and the control vector into MDA-MB-231 human BC cells to generate 231.PCTK1 and 231.vector cells, respectively. Intra-carotid injection of the 231.PCTK1 cells into mice induced BrM significantly faster with shortened mouse survival than that of the control 231.vector cells, confirming PCTK1 as a BrM-promoting kinase. However, when 231.vector or 231.PCTK1 cells were injected into the mouse’ mammary glands, PCTK1 overexpression did not lead to enhanced primary tumor growth, suggesting that its pro-tumoral functions are BrM-specific. To uncover how PCTK1 promotes BrM but not primary tumor, we examined whether PCTK1 may confer growth advantage in BrM by utilizing the unique metabolic microenvironment of the brain. We analyzed the relationship between PCTK1 gene expression and gene expression of members of the glutamine metabolism pathway in TCGA database. We found that in the brain tumors, such as low-grade glioma, PCTK1 positively correlated with the expression of glutamine metabolizing genes, including glutaminase 1 and 2 (GLS and GLS2). To evaluate whether PCTK1-overexpressing cells can uptake glutamine from the media directly, we cultured 231.PCTK1 and 231.vector cells in low-nutrient BME media plus 5% d.FBS, with addition of different concentrations of glutamine. The PCTK1-overexpressing cells showed a clear growth advantage at glutamine concentrations ranging from 400 μM to 2 mM. Then, we knocked down PCTK1 in MDA-MB-231 cells by shRNAs and found that PCTK1 knocking down reduced the cell proliferation in 5% d.FBS.BME with 500 µM glutamine, a physiological glutamine level in the brain. We measured the expression of GLS, an enzyme that converts glutamine to glutamate, one of the key steps in the glutamine metabolism, and found that knockdown PCTK1 in MDA-MB-231 cells dramatically reduced the GLS expression, which indicates that PCTK1 can modulate glutamine metabolism in cancer cells. In summary, our data suggest that PCTK1 promotes BC BrM, at least partly, through increasing glutamine metabolism. Currently, we are exploring whether targeting PCTK1 or inhibiting glutamine metabolism can deter BrM progression. Our studies may reveal novel therapeutic targets for BrM inhibition. Citation Format: Lin Zhang, Frank Lowery, Chenyu Zhang, Yu-Wen Huang, Ya-Jing Jiang, Yimin Duan, Dihua Yu. PCTK1 driven glutamine metabolic adaptation in brain metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3161.
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Yang, Yongfei, Shuzhen Cao, Wenjiao Zhang, et al. "Abstract 6436: 1C3, a novel non-blocking anti-human TNFR2 antibody, promotes effector T cell responses and demonstrates potent anti-tumor activity." Cancer Research 83, no. 7_Supplement (2023): 6436. http://dx.doi.org/10.1158/1538-7445.am2023-6436.
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Abstract Regulatory T cells (Tregs) are a subset of immunosuppressive CD4+ T lymphocytes which can inhibit effector T cell activity in the tumor microenvironment (TME) and promote tumor growth. Depletion of Tregs is a promising immunotherapy strategy for treatment of cancers. Tumor necrosis factor receptor-2 (TNFR2) is highly expressed on both Tregs and many kinds of tumor cells, making it a potential candidate for tumor-targeted antibody therapy. A fully human, non-blocking agonist antibody to TNFR2, 1C3, was generated from RenMab™ mice, which contain the full human immunoglobulin variable domain. 1C3 was selected from a large panel of antibody candidates after unbiased, high-throughput efficacy screening conducted in syngeneic tumor mouse models established in humanized TNFR2 mice. In vitro, 1C3 effectively promoted proliferation of cytotoxic T cells. Subsequently, the in vivo anti-tumor efficacy and safety of 1C3 was evaluated in syngeneic tumor mouse models expressing human TNFR2. The results demonstrated that 1C3 monotherapy significantly inhibited tumor growth in a dose-dependent manner. In combination with anti-human PD-1 or PD-L1 antibodies, 1C3 also greatly potentiated anti-tumor responses compared to monotherapy of each agent. Analysis of tumor-infiltrating lymphocytes (TIL) demonstrated that 1C3 treatment significantly increased the ratio of effector T cells to Tregs in the TME. Moreover, 1C3 was well tolerated in mice, and no adverse effects were observed even at high doses (e.g. 100 mg/kg). In conclusion, these data demonstrate that 1C3 is a novel anti-human TNFR2 non-blocking agonist antibody with effective anti-tumor efficacy and favorable safety. 1C3 may exert these effects by regulating Treg and effector T cell activities. Citation Format: Yongfei Yang, Shuzhen Cao, Wenjiao Zhang, Jing Zhang, Zhe Shao, Xueyuan Jiang, Qingya Duan, Maopeng Tian, Sen Mei, Zhaoxue Yu. 1C3, a novel non-blocking anti-human TNFR2 antibody, promotes effector T cell responses and demonstrates potent anti-tumor activity [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 6436.
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Zheng, Chao, Dandan Ma, Linfeng Zhao, et al. "Abstract P4-03-31: Lifestyle factors are associated with breast cancer risk in women biopsied for benign breast diseases in China: 10-year results of a multi-center, hospital-based, case-control study." Cancer Research 83, no. 5_Supplement (2023): P4–03–31—P4–03–31. http://dx.doi.org/10.1158/1538-7445.sabcs22-p4-03-31.
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Abstract Objective: Benign breast disease (BBD), especially benign proliferative breast disease (BPBD), is related to increased breast cancer risk. However, few studies have examined whether conventional breast cancer risk factors influence risk of breast cancer among women with BBD. The aim of this study was to evaluate the associations of lifestyle factors with risk of breast cancer among women biopsied for BBD within a multi-center, hospital-based, case-control study in China, in order to provide scientific basis of health guidance for BBD patients and lay the foundation for primary prevention of breast cancer. Methods: A multi-center, hospital-based, case-control study was conducted. Patients with BPBD (n=608) and patients with non-proliferative breast disease (NPBD) (n=366) were collected from 23 hospitals in 11 provinces during April 2012 to April 2013. A face-to-face survey, baseline data and fasting blood was collected with all study subjects. Serum adiponectin levels were assayed using ELISA. After 10 years, the cumulative incidence rate of breast cancer in the two groups was counted through follow-up. Logistic regression analysis was used to obtain the association between specific factors and risk of breast cancer. Results: After 10 years’ follow-up, 388 BPBD and 240 NPBD cases were included in the final analysis (Table 1), of which 16 (4.12%) and 3 (1.25%) developed breast cancer, respectively. The cumulative incidence of breast cancer between the two groups was significant difference (P=0.041). Compared with women in the NPBD group, BPBD group were more likely to be central obesity (with higher waist-to-hip ratio (WHR)) (OR 24.98, 95% CI 1.845-336.203, P=0.015) and less likely to have physical activity (OR 0.626, 95% CI 0.416-0.943, P=0.025) and less often to eat carrots (OR 0.616, 95% CI 0.398-0.953, P=0.030) (Table 2). Subgroup analyze indicated that, physical activity, eat carrots and ham sausage, body weight, BMI, waist circumference and WHR were statistical differences in premenopausal BPBD patients, while only physical activity (OR 0.423, 95% CI 0.269-0.665 P &lt; 0.001) was the independent risk factors. Meanwhile, among the factors of Tea consumption, Glycemia, Body weight, BMI, Waist circumference, WHR and HMW/total adiponectin ratio in postmenopausal group, only HMW/total adiponectin ratio (OR 0.041, 95% CI 0.002-0.820 P=0.037) was statistically significant factor. These stratified multivariate logistic regression analysis results are shown in Table 3. Conclusion: In patients with BBD, physical activity may be the protect factor for breast cancer carcinogenesis in premenopausal women while lower HMW/total adiponectin ratio is a risk factor for postmenopausal women, which can provide direction for primary prevention of breast cancer. Table 1. Pathological types of all subjects. Table 2. The results of multivariate Logistic regression analysis. Table 3. Stratified multivariate Logistic regression analysis by menopause status. Citation Format: Chao Zheng, Dandan Ma, Linfeng Zhao, Maolin Guo, Shude Cui, Fuguo Tian, Zhimin Fan, Cuizhi Geng, Xuchen Cao, Zhenlin Yang, Xiang Wang, Hong Liang, Shu Wang, Hongchuan Jiang, Xuening Duan, Haibo Wang, Guolou Li, Qitang Wang, Jianguo Zhang, Feng Jin, Jinhai Tang, Liang Li, Shi-Guang Zhu, Wenshu Zuo, Fei Wang, Lixiang Yu, Fei Zhou, Yujuan Xiang, Mingming Guo, Yongjiu Wang, Wenzhong Zhou, Shuya Huang, Zhaohui Li, Yajie Zhou, Lijuan Hou, Xinyi Yang, Xuan Zhang, Liyuan Liu, Zhigang Yu. Lifestyle factors are associated with breast cancer risk in women biopsied for benign breast diseases in China: 10-year results of a multi-center, hospital-based, case-control study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-03-31.
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Yuan, Xiangliang, Hao-Nien Chen, Akosua Badu-Nkansah, Yimin Duan та Dihua Yu. "Abstract 673: p38γ MAPK remodels tumor microenvironment facilitating breast cancer progression and brain metastasis". Cancer Research 83, № 7_Supplement (2023): 673. http://dx.doi.org/10.1158/1538-7445.am2023-673.
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Abstract Major neoplastic diseases have high incidences of brain metastasis (BrM) which is a clinically dreadful consequence of advanced cancers with an abysmal prognosis. Unfortunately, our understanding of the biology and molecular mechanisms underlying BrM remains rudimentary. Improving our understanding of the pathogenesis of BrM will facilitate the rational development and prioritization of new therapeutic strategies. Mitogen-activated protein kinases (MAPKs) are a group of serine/threonine protein kinases that are key players in various intracellular signaling pathways controlling many cellular processes, e.g., growth, differentiation, stress responses, and immune defense which have a key role in cancer progression. However, little is known regarding the role of MAPKs in the pathogenesis of BrM. Here, we report that p38γ mitogen-activated protein kinase (MAPK12) is overexpressed in multiple tumor types and associated with aggressive breast cancer progression and a poor outcome in BrM patients. Interestingly, we found that the lack of p38γ did not impact the proliferation of tumor cells ex vivo, but significantly reduced both the primary tumor growth and BrM in EO771 and other mammary tumor-bearing immunocompetent mouse models. Our preclinical data indicated that p38γ promoted tumor progression and BrM through remodeling tumor microenvironments in vivo. We have mapped the immune landscape of BrM lesions of EO771-bearing mice using high-dimensional single-cell profiling. Clearly, cytometry by time-of-flight (CyTOF) analysis of the BrM immune infiltrates revealed reprogramming of the immunosuppressive brain microenvironment toward a proinflammatory and antitumoral state with tumor-intrinsic p38γ depletion, as indicated by highly enriched dendritic cell (DC) and cytolytic T cell (CTL) populations in BrM. To explore the impact of p38γ depletion in breast cancer cells, we performed RNA sequencing on EO771 cells having p38γ knocked down versus the control cells. We found that p38γ knocked down led to the upregulation of pathways related to immune cell movement, thereby leading to an increased accumulation of antitumor immune cells in BrM. Together, our findings uncover an important role for tumor-intrinsic p38γ in shaping the brain immune microenvironment and underscore the potential of specific p38γ blockade in enhancing antitumor immunity for the treatment of breast cancer BrM. Citation Format: Xiangliang Yuan, Hao-Nien Chen, Akosua Badu-Nkansah, Yimin Duan, Dihua Yu. p38γ MAPK remodels tumor microenvironment facilitating breast cancer progression and brain metastasis [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 673.
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Wang, Changhong. "(Digital Presentation) All-Solid-State Lithium Batteries: From Materials and Interface Design to Practical Pouch Cell Engineering." ECS Meeting Abstracts MA2022-01, no. 6 (2022): 2435. http://dx.doi.org/10.1149/ma2022-0162435mtgabs.
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All-solid-state lithium batteries (ASSLBs) have gained substantial attention because of their intrinsic safety and high energy density.1 However, the commercialization of ASSLBs has been stymied by insufficient ionic conductivity of solid-state electrolytes, significant interfacial challenges, as well as the large gap between fundamental research and practical engineering. Over the past several years, we have been dedicated to developing ASSLBs from solid electrolyte synthesis to interface design to engineering practical solid-state pouch cells. First, a wet-chemistry method with a low cost was proposed to produce solid-state electrolytes at the kilogram level with a high room-temperature ionic conductivity (> 1 mS.cm-1).2 Second, the interfacial challenges of ASSLBs have been well addressed via increasing the ionic conductivity of interfacial buffer layers,3 manipulating interfacial nanostructures,4, 5 using single-crystal cathodes,6 deciphering interfacial reaction mechanisms,7 and constructing artificial solid electrolyte interphases (SEI),8 which successfully boosted interfacial ion and electron transport kinetics.9 Resultantly, ASSLBs demonstrated superior electrochemical performance. Third, practical solid-state pouch cells with high energy density have been engineered. Recently, a solvent-free process was proposed to fabricate freestanding and ultrathin inorganic solid electrolyte membranes.10 Furthermore, a feasible solid-liquid transformable interface was devised to improve the solid-solid ionic contact and accommodate the significant volume change of solid-state pouch cells.11, 12 The resultant solid-state pouch cells successfully demonstrated high energy density and unparalleled safety. In summary, our research not only provides an in-depth understanding of solid electrolyte synthesis and rational interface design but also offers feasible strategies to commercialize ASSLBs with high energy density, low cost, and excellent safety. References C. Wang, J. Liang, Y. Zhao, M. Zheng, X. Li and X. Sun, Energy Environ. Sci., 2021, 14, 2577-2619. C. Wang, J. Liang, J. Luo, J. Liu, X. Li, F. Zhao, R. Li, H. Huang, S. Zhao, L. Zhang, J. Wang and X. Sun, Sci. Adv., 2021, 7, eabh1896. C. Wang, J. Liang, S. Hwang, X. Li, Y. Zhao, K. Adair, C. Zhao, X. Li, S. Deng, X. Lin, X. Yang, R. Li, H. Huang, L. Zhang, S. Lu, D. Su and X. Sun, Nano Energy, 2020, 72, 104686. C. Wang, X. Li, Y. Zhao, M. N. Banis, J. Liang, X. Li, Y. Sun, K. R. Adair, Q. Sun, Y. Liu, F. Zhao, S. Deng, X. Lin, R. Li, Y. Hu, T.-K. Sham, H. Huang, L. Zhang, R. Yang, S. Lu and X. Sun, Small Methods, 2019, 3, 1900261. C. Wang, J. Liang, M. Jiang, X. Li, S. Mukherjee, K. Adair, M. Zheng, Y. Zhao, F. Zhao, S. Zhang, R. Li, H. Huang, S. Zhao, L. Zhang, S. Lu, C. V. Singh and X. Sun, Nano Energy, 2020, 76, 105015. C. Wang, R. Yu, S. Hwang, J. Liang, X. Li, C. Zhao, Y. Sun, J. Wang, N. Holmes, R. Li, H. Huang, S. Zhao, L. Zhang, S. Lu, D. Su and X. Sun, Energy Storage Mater., 2020, 30, 98-103. C. Wang, S. Hwang, M. Jiang, J. Liang, Y. Sun, K. Adair, M. Zheng, S. Mukherjee, X. Li, R. Li, H. Huang, S. Zhao, L. Zhang, S. Lu, J. Wang, C. V. Singh, D. Su and X. Sun, Adv. Energy Mater., 2021, 11, 2100210. C. Wang, Y. Zhao, Q. Sun, X. Li, Y. Liu, J. Liang, X. Li, X. Lin, R. Li, K. R. Adair, L. Zhang, R. Yang, S. Lu and X. Sun, Nano Energy, 2018, 53, 168-174. C. Wang, K. Adair and X. Sun, Acc. Mater. Res., 2022, 3, 21-32. C. Wang, R. Yu, H. Duan, Q. Lu, Q. Li, K. R. Adair, D. Bao, Y. Liu, R. Yang, J. Wang, S. Zhao, H. Huang and X. Sun, ACS Energy Lett., 2022, DOI: 10.1021/acsenergylett.1c02261, 410-416. C. Wang, Q. Sun, Y. Liu, Y. Zhao, X. Li, X. Lin, M. N. Banis, M. Li, W. Li, K. R. Adair, D. Wang, J. Liang, R. Li, L. Zhang, R. Yang, S. Lu and X. Sun, Nano Energy, 2018, 48, 35-43. C. Wang, K. R. Adair, J. Liang, X. Li, Y. Sun, X. Li, J. Wang, Q. Sun, F. Zhao, X. Lin, R. Li, H. Huang, L. Zhang, R. Yang, S. Lu and X. Sun, Adv. Funct. Mater., 2019, 29, 1900392.
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Yang, Shao-Ping, Yimin Duan, Xiangliang Yuan, et al. "Abstract 4176: Histone deacetylase inhibitor Panobinostat enhances efficacy of immune checkpoint inhibitor via upregulating antigen presentation in breast cancer brain metastasis." Cancer Research 82, no. 12_Supplement (2022): 4176. http://dx.doi.org/10.1158/1538-7445.am2022-4176.
Full textAbstract:
Abstract Brain metastasis (BrM) affects millions of cancer patients and major cancer types, e.g., lung cancer, melanoma, and breast cancer, have high incidences of BrM. Symptomatic BrM patients have a less than 20% 1-year survival rate. The poor clinical outcome is due to lack of effective treatment for BrM as even immune checkpoint inhibition (ICI) only showed effects in 55% asymptomatic BrM in melanoma patients. Novel effective combination therapies are urgently needed to address metastasis in the unique brain immune microenvironment (BrIME). Interestingly, our RNA-seq data of patients treated at MD Anderson Cancer Center and immunohistochemistry (IHC) analysis of tumors of various mouse models showed that BrM express significantly lower major histocompatibility class I (MHC-I) and higher histone deacetylase (HDAC) 1 compares to extracranial tumors or metastasis. HDAC inhibitors (HDACi) have been reported to upregulate MHC-I in extracranial tumors. In this study, we tested whether HDACi, Panobinostat, can upregulate MHC-I expression in BrM and whether Panobinostat combined with ICI (e.g., anti-PD1) treatment in mouse models can impede BrM development. Clearly, our data showed that HDACi Panobinostat significantly increased MHC-I expression in brain-seeking human breast cancer cells (MDA-231, MDA-435) and mouse mammary tumor cells (4T1, EO771) with or without IFN-γ treatment. We then tested Panobinostat penetration of the blood-brain barrier (BBB) for treating BrM in vivo. C57BL/6 mice were treated with either 10 or 20mpk (i.p.) Panobinostat for three consecutive days. Mass spectrum analysis shows that Panobinostat can be detected in the brain at level of 10-8M after the treatment. We found that Panobinostat treatment increased both CD4+ and CD8+ T cell in the brain by FACS analysis. To test therapeutic efficacy of HDACi and ICI combination therapy in BrM, we induced BrM in C57BL/6 mice by intracarotid artery (ICA) injection of E0771-Luc.GFP tumor cells, then mice were divided to four groups and were treated with i) vehicle, ii) Panobinostat, iii) anti-PD1 and iv) Panobinostat +anti-PD1. We found that combination of Panobinostat with anti-PD1 more effectively inhibited BrM tumor outgrowth compares to either monotherapy and the vehicle control. Furthermore, Immunohistochemistry staining revealed upregulated MHC-I in BrM tumor cells and increased CD8+ T cell infiltration by Panobinostat treatment. In summary, our data indicated that HDACi Panobinostat can increase ICI efficacy in BrM by upregulating MHC-I for enhanced antigen presentation. Citation Format: Shao-Ping Yang, Yimin Duan, Xiangliang Yuan, Lin Zhang, Patrick Zhang, Jason T. Huse, Dihua Yu. Histone deacetylase inhibitor Panobinostat enhances efficacy of immune checkpoint inhibitor via upregulating antigen presentation in breast cancer brain metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 4176.
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Yang, Shao-Ping, Yimin Duan, Xiangliang Yuan, Lin Zhang, Patrick Zhang, and Dihua Yu. "Abstract 6427: Selective-HDAC inhibitor relieves the suppressive immune microenvironment in the brain to impede breast cancer brain metastasis." Cancer Research 83, no. 7_Supplement (2023): 6427. http://dx.doi.org/10.1158/1538-7445.am2023-6427.
Full textAbstract:
Abstract Brain metastasis (BrM) incidence is rising due to longer survival resulted from better systemic control of cancer, counting for approximately 20% of patients with cancers. Major cancer types, including lung, breast, and skin cancers, have a high rate to develop BrM with a 1-year survival rate of less than 20% for symptomatic patients. The overall response rate for immune checkpoint inhibitors (ICI) is merely 10-30% in patients with neurological symptoms. Developing novel combinatorial therapeutic strategies based on mechanistic understanding is urgently needed to further improve the efficacy of current immunotherapies in BrM patients. We recently found that BrMs in patients frequently have severe MHC-I loss. BrM patients' scRNA-seq data from available datasets show that MHC-I expression level is negatively correlated with HDAC level in breast cancer brain metastasis. On the other hand, HDAC inhibitors (HDACi) are epigenetic modulators which have been indicated to recover MHC-I expression loss that contributes to immune invasion. HDACi has been indicated to enhance ICI efficacy in primary tumors by reprogramming the tumor microenvironment (TME). However, the immunomodulatory effect of HDACi is unclear in the unique brain immune microenvironment (BrIME), which is characterized as immunosuppressive. Here, we report that although the selective-HDACi Entinostat has a relatively poor blood-brain barrier (BBB) penetration compared to pan-HDACi Panobinostat, Entinostat induced a comparable level of histone acetylation in the brain to that of Panobinostat. Furthermore, combinatorial treatment consisting of HDACi Entinostat/Panobinostat and anti-PD1 reduced BrM outgrowth of EO771 mammary tumor cell-induced BrM in synergetic mouse model. We explored the impact of HDACi on cell surface MHC-I expression by flow cytometry. Entinostat restored MHC-I expression levels on both brain-seeking human and murine breast and lung cancer cell lines, indicating a general epigenetic regulation on MHC-I expression by inhibition of HDACs. To dissect the impact of HDACi on the BrIME, immune profiling of BrM was performed by mass cytometry (CyTOF). Notably, Entinostat induced a dramatic increment of a specific antigen-presenting cell (APC) cluster in BrM-bearing BrIME with increased ratio of M1 proinflammatory macrophages: M2 tumor-associated macrophages (TAMs) and decreased Tregs. Our results suggest that Entinostat can upregulate MHC-I for more effective antigen presentation and enhance anti-tumor immunity in BrIME. Citation Format: Shao-Ping Yang, Yimin Duan, Xiangliang Yuan, Lin Zhang, Patrick Zhang, Dihua Yu. Selective-HDAC inhibitor relieves the suppressive immune microenvironment in the brain to impede breast cancer brain metastasis. [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 6427.
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Sadowska, Karolina, Paweł Awramiuk, Izabela Zgłobicka, Katarzyna Rećko, and Jacek Żmojda. "Quantum efficiency of europium doped LaPO4 phosphors for UV sensing applications." Photonics Letters of Poland 14, no. 2 (2022): 28. http://dx.doi.org/10.4302/plp.v14i2.1146.
Full textAbstract:
The radiation conversion phenomenon is used for UV sensing applications with rare earth doped phosphors. This paper presents the results of structural and optical measurements of undoped and europium doped LaPO4 phosphors. LaPO4 phosphors with 1% mol, 2% mol, and 5% mol of europium were fabricated by the co-precipitation method. The effect of Eu3+ concentrations on the luminescence characteristics under UV LED excitation was investigated. The maximum quantum efficiency of luminescence (c.a. 82%) was obtained in sampled doped with 5% of europium. Full Text: PDF ReferencesM. Runowski, "Nanotechnologia – nanomateriały, nanocząstki i wielofunkcyjne nanostruktury typu rdzeń/powłoka", Chemik 68, 9, 766-775 (2014). DirectLink J. Zhou, J.L. Leano Jr., Z. Liu, D. Jin, K.-L. Wong, R.S. Liu, et al., "Impact of Lanthanide Nanomaterials on Photonic Devices and Smart Applications", Small 14, 1801882 (2018). CrossRef Z. Li, Y. Zhang, G. Han, "Lanthanide-Doped Upconversion Nanoparticles for Imaging-Guided Drug Delivery and Therapy", Springer Series in Biomater. Sci. Eng. 6, 139-164, (2016). CrossRef M. Lin, Y. Zhao, S. Wang, M. Liu, Z. Duan, Y. Chen, et al., "Recent advances in synthesis and surface modification of lanthanide-doped upconversion nanoparticles for biomedical applications", Biotechnol. Adv. 30, 1551-1561 (2012). CrossRef H. Su, Y. Nie, H. Yang, D. Tang, K. Chen, T. Zhang, "Improving the thermal stability of phosphor in a white light-emitting diode (LED) by glass-ceramics: Effect of Al2O3 dopant", J. Eur. Ceram. Soc. 38, 2005-2009 (2018). CrossRef J. Huang, X. Hu, J. Shen, D. Wu, C. Yin, R. Xiang, et al., "Facile synthesis of a thermally stable Ce3+:Y3Al5O12 phosphor-in-glass for white LEDs", Cryst. Eng. Comm 17, 7079-7085 (2015). CrossRef R. Zhang, H. Lin, Y. Yu, D. Chen, J. Xu, Y. Wang, "A new-generation color converter for high-power white LED: transparent Ce3+:YAG phosphor-in-glass", Laser Photon. Rev. 8, 158-164 (2014). CrossRef B. Zheng, Y. Bai, H. Chen, H. Pan, W. Ji, X. Gong, et al., "Near-Infrared Light-Excited Upconverting Persistent Nanophosphors in Vivo for Imaging-Guided Cell Therapy", ACS Appl. Mater. Interfaces 10, 19514 (2018). CrossRef J. Qiao, G. Zhou, Y. Zhou, Q. Zhang, Z. Xia, "Divalent europium-doped near-infrared-emitting phosphor for light-emitting diodes", Nature Communications 10 (1), 5267 (2019). CrossRef V. Singh, A. Kumar, C. Mehare, H. Jeong, S. Dhoble, "UV/VUV excited photoluminescence of Tb3+ doped LaPO4 green emitting phosphors for PDP applications", Optik 206, 163733 (2020). CrossRef G. Han, Y. Wang, C. Wu, J. Zhang, "Hydrothermal synthesis and vacuum ultraviolet-excited luminescence properties of novel Dy3+-doped LaPO4 white light phosphors", Mat. Res. Bull. 44 (12), 2255-2257 (2009). CrossRef K. S. Gupta, P. S. Ghosh, M. Sahu, K. Bhattacharyya, R. Tewari, V. Natarajan, "Intense red emitting monoclinic LaPO4:Eu3+ nanoparticles: host–dopant energy transfer dynamics and photoluminescence properties", RSC Adv. 5, 58832-58842 (2015). CrossRef
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Chen, Hao-Nien, Xiangliang Yuan, Yimin Duan, Yi Xiao, Shao-Ping Yang, and DIhua Yu. "Abstract 5077: Engineering dendritic cell-derived exosomes forbrain metastases immunotherapy." Cancer Research 83, no. 7_Supplement (2023): 5077. http://dx.doi.org/10.1158/1538-7445.am2023-5077.
Full textAbstract:
Abstract Brain metastases (BrMs) represent an unmet challenge for the therapy of most aggressive cancers owing to the extremely poor survival and the limited efficacy of available therapies. Currently, NO curative therapy for breast cancer BrM (BCBrM) is available and we urgently need to develop new and effective therapies. Immune checkpoint therapies (ICT) have revolutionized cancer treatment, but are generally unsuccessful in treating BrMs, including BCBrM. A crucial reason for this is the unique brain immune microenvironment with low antigen exposure/presentation in BrMs and fewer antigen-specific T cells in the brain parenchyma. The priming and activation of antigen-specific T cells require professional antigen-presenting dendritic cells (DCs) for effective antigen presentation through multifaceted communication between DCs and T cells by direct intercellular contact and indirect distant communication via exosomes and other means. DC-derived exosomes (DCEXs) carry functional MHC-I/peptide complexes (pMHC-I) and costimulatory molecules, hence facilitating systemic T cell immune responses. DCEXs have been developed as immunotherapies which exhibit advantages over DC-based immunotherapies. However, DCEXs in ongoing clinical trials showed limited efficacy. We found that increased non-receptor protein tyrosine phosphatase SHP1, a DC-intrinsic inhibitory checkpoint, in monocyte-derived DCs (MoDCs) ex vivo led to DC exhaustion that limits DCEXs function resulting in poor systemic T cells stimulation in vivo. To improve DCEXs functions, we developed next-generation DCEXs by genetic knockout of SHP1 in DCs from which DCEXs (iSHP1-DCEXs) were isolated. Remarkably, the modified iSHP1-DCEXs exhibited significantly increased pMHC-I expression and more effectively improved T cell proliferation compared to control DCEXs, indicating a greater capacity of antigen presentation of engineered iSHP1-DCEXs. In the EO771-OVA mammary tumor cells-bearing mouse model, iSHP1-DCEXs treatment greatly increased tumor infiltration of OVA antigen-specific CD8+ T (OT-1) cells resulting in tumor inhibition and prolonged mouse survival, indicating that iSHP1-DCEXs elicited an effective and specific antitumor immunity in vivo. Moreover, combining iSHP1-DCEXs with anti-PD1 Ab yielded a strong syngenetic therapeutic response in mice bearing the anti-PD1-resistant EO771 tumors, as indicated by delayed tumor growth and prolonged survival. importantly, iSHP1-DCEXs also significantly increased tumor-infiltrating antigen-specific T cells and synergized with PD-1 Ab leading to tumors clearance in mice bearing the B16-GMCSF melanoma. To further test the iSHP1-DCEXs effect in BCBrM, we co-injected EO771-OVA and iSHP1-DCEXs into mice and found that iSHP1-DCEXs inhibited BrM. Together, the engineered iSHP1-DCEXs offer a promising option to generate a potent antigen-specific T cell immune response for BCBrM inhibition. Citation Format: Hao-Nien Chen, Xiangliang Yuan, Yimin Duan, Yi Xiao, Shao-Ping Yang, DIhua Yu. Engineering dendritic cell-derived exosomes forbrain metastases immunotherapy. [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 5077.
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Zheng, Hepeng, Zuhang Wu, Lifeng Zhang, Yanqiong Xie, and Hengchi Lei. "Improving Radar Rainfall Estimations with Scaled Raindrop Size Spectra in Mei-Yu Frontal Rainstorms." Sensors 20, no. 18 (2020): 5257. http://dx.doi.org/10.3390/s20185257.
Full textAbstract:
Hydrological calibration of raw weather radar rainfall estimation relies on in situ rainfall measurements. Raindrop size distribution (DSD) was collected during three typical Mei-Yu rainstorms in July 2014 using three particle size velocity (Parsivel) DSD sensors along the Mei-Yu front in Nanjing, Chuzhou, and the western Pacific, respectively. To improve the radar precipitation estimation in different parts of the Mei-Yu front, a scaling method was adopted to formulate the DSD model and further derive the Z–R relations. The results suggest a distinct variation of DSDs in different parts of the Mei-Yu front. Compared with statistical radar Z–ARb relations obtained by mathematical fitting techniques, the use of a DSD model fitting based on a scaling law formulation theoretically shows a significant improvement in both stratiform (33.9%) and convective (2.8%) rainfall estimations of the Mei-Yu frontal system, which indicates that using a scaling law can better reflect the DSD variations in different parts of the Mei-Yu front. Polarimetric radar has indisputable advantages with multiparameter detection ability. Several dual-polarization radar estimators are also established by DSD sensor data, and the R(ZH, ZDR) estimator is proven to be more accurate than traditional Z–R relations in Mei-Yu frontal rainfall, with potential applications for operational C-band polarimetric radar.
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Zheng, X. H., and J. X. Zheng. "Comment on “High-temperature superconductivity in transition metallic hydrides MH11 (M = Mo, W, Nb, and Ta) under high pressure” by M. Du, Z. Zhang, H. Song, H. Yu, T. Cui, V. Z. Kresinc and D. Duan, Phys. Chem. Chem. Phys., 2021, 23, 6717." Physical Chemistry Chemical Physics 24, no. 3 (2022): 1896–97. http://dx.doi.org/10.1039/d1cp01474a.
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In superconductors, scattered electrons cover the entire surface of the Fermi sphere (circle in the figure, valency = 3). In the MP scheme in the article concerned, the shaded wedge confines coverage, causing errors in results.
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Coelho Junior, Leconte De Lisle. "Um estudo sobre a violência em duas histórias gráficas." Journal of Human Growth and Development 15, no. 2 (2005): 55. http://dx.doi.org/10.7322/jhgd.19758.
Full textAbstract:
As histórias gráficas, também conhecidas como histórias em quadrinhos, são uma das formas mais antigas de expressão da humanidade. Elas refletem os valores da sociedade e podem servir como uma forma de educação. Esse estudo buscou reconhecer descritores da violência estilizada sob a forma de imagens agressivas e a intencionalidade de se cometer algum ato violento nas personagens de Fushigi Yûgi e Yu Yu Hakushô, que são histórias gráficas de origem japonesa denominadas 'mangás'. A análise estatística descritiva unida à análise semiológica permitiu reconhecer os principais componentes, acima apontados, das histórias. Verificou-se que estes recursos visuais contêm violência não somente explícita, mas também intencional, sendo a primeira forma a mais difundida, e que as personagens do gênero masculino são mais violentas que as de gênero feminino. Conclui-se também que estas histórias não podem ser tidas como as únicas e mais perigosas fontes de violência na sociedade.
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Mittova, Irina Ya, Boris V. Sladkopevtsev, Valentina O. Mittova та ін. "ФОРМИРОВАНИЕ ПЛЕНОК СИСТЕМЫ (Y2O3-Fe2O3) НАНОРАЗМЕРНОГО ДИАПАЗОНА ТОЛЩИНЫ НА МОНОКРИСТАЛЛИЧЕСКОМ InP". Kondensirovannye sredy i mezhfaznye granitsy = Condensed Matter and Interphases 21, № 3 (2019): 406–18. http://dx.doi.org/10.17308/kcmf.2019.21/1156.
Full textAbstract:
Методом центрифугирования сформированы пленки наноразмерного диапазона толщины (лазерная, спектральная эллипсометрия) системы Y2O3–Fe2O3 на монокристаллическом InP из нитратного раствора. Состав пленок, выращенных без отжига - YFe2O4; отожженных термически при 200 °С – YFe2O4, Fe2O3 с примесью Fe3O4; прошедших импульсную фотонную обработку (50 Дж/см2, 0.4 с) и термооксидирование (450–550 °С, время 10–60 мин) – YFe2O4 и YFeO3. Отжиг с последующим термооксидированием способствует уменьшению размера зерен на поверхности выращенной пленки, но увеличивает среднюю шероховатость. Импульсная фотонная обработка обусловливает повышенную неровность поверхности гетероструктуры.
 
 
 ИСТОЧНИК ФИНАНСИРОВАНИЯРабота выполнена при поддержке грантаРФФИ №18-03-00354 а.
 
 
 
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 Berezhnaya M. V., Mittova I. Y., Viryutina E. L., Perov N. S., Bessalova V. V., Al’myasheva O. V., Nguyen A. T., Mittova V. O. Production of zinc-doped yttrium ferrite nanopowders by the sol–gel method. Russian Journal of Inorganic Chemistry, 2018, v. 63(6), pp. 742−746. https://doi.org/10.1134/S0036023618060049
 Berezhnaya M. V., Perov N. S., Almjasheva O. V., Mittova V. O, Nguyen A. T., Mittova I. Ya., Druzhinina L. V., Alekhina Yu. A. Synthesis and magnetic properties of barium-doped nanocrystal lanthanum orthoferrite. Russian Journal of General Chemistry, 2018, v. 89(3), pp. 480−485. https://doi.org/10.1134/S1070363219030198
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Li, Ting, Pan Boan, Yuan Gao, Huang Xiaobo, Jiangbo Pu, and Chong Huang. "Noninvasive and Wearable Optical Monitoring of Brain Death with Aid of a Protocol at Differentiated Fractions of Oxygen Inspired." Blood 134, Supplement_1 (2019): 5808. http://dx.doi.org/10.1182/blood-2019-124448.
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Brain death is a permanent loss of all brain function [1]. Current clinical organ transplantations mostly depend on the organs from brain-dead patients [2]. And of note, a lot of blood deases are easy to cause cerebral haemorrhage, which is quite of danger and usually induce brain death if not detected and treated in time. Thus prompt evaluation of brain death is of great significance for saving medical resources and reducing economic burden of the patients' families. Current guide for diagnosing brain death required to perform a list of >30 hours neurological examninations, some of which are even invasive, not in time and easily hampered by many confounding factors. An ideal ancillary test to assess brain death is highlighted to be noninvasive, sensitive, universally available, timely, and easy to perform at the bedside. Near infrared spectroscopy ( NIRS ) is capable of monitoring hemodynamics in response to brain activity noninvasively, conveniently, continually, and relatively inexpensively, evidented by a series of clinical cerebral studies recently. Weigl et al newly reported to use a time resolved NIRS to detect the fluorescence photons excited in the indocyanine green ( ICG ) for cerebral perfusion detection. It provided a novel optical ancillary tool to assess brain death, while its accuracy was only 69.2%, which did not reach the level of brain death confirmation. Plus, it was invasive, requiring injection of optical contrast agent. We attempted to assess brain death completely in nonivasive way with just a custom wearable NIRS device developed in our lab [3] ( fig.1 a ). We novelly incororate a protocol at markedly but safely varied fractions of oxygen respiration. Firstly, Monte Carlo modeling were carried out to test the difference in photon transport within human brain at different oxygen concentrations induced by varied fractions of oxygen respiration ( FIO2 ) [4]. 18 healthy subjects ( 41 ± 11 years old ) and 17 brain dead patients were recruited from the intensive care unit (ICU) in Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital. No significant difference in age was found between patients and healthy groups ( p >0.413 ). These patients were finally clinically diagnosed by the international standards of brain death. Two protocols were used ( fig.1 b). One is consisted of 1 hour resting, 3-minute baseline measure, half-hour measurement at 60% FIO2 ( phase I, high oxygen ),a half hour measure at 40% FIO2 ( phase II, low oxygen ), and a half hour measure at 60% FIO2 ( phase III, high oxygen ). The other is low, high, and low. The Δ[Hb] and Δ[HbO2] time courses were recorded by NIRS in real time with related signal processing ( fig.1 c ). Statistical analysis were focus on the sensitivity and specificiy of our proposed methodology at combination of NIRS and above protocol, as well as which protocol act better. Fig.1 ( c right ) showed that the detected light signal profile dramatically differed among varied oxygen concentrations in human brain. Plus the hemodynamic responses varied clearly between two subject groups among varied FIO2 in both protocols ( fig1. d ). The ' II-III ' phase act more distinct in differing two groups than ' I-II ' phase. And the low-high-low protocol acted almost perfect in accessing brain death with highest sensitivity and specificity. Over all, the novel incorporation of NIRS and a low-high-low varied FIO2 protocol was shown to a be most sensitive, highly specific, noninvasive and real time way to assess brain death and promptly offer quality assured donor organs. [1] E. F. M. Wijdicks, P. N. Varelas, G. S. Gronseth, D. M. Greer, Evidence-based guideline update: Determining brain death in adults report of the quality standards subcommittee of the American Academy of Neurology, Neurology, vol. 74, no. 23, pp. 1911-1918, 2010 [2] K. Singbartl, R. Murugan, A. M. Kaynar, D. W. Crippen, S. A. Tisherman, K. Shutterly, S. A. Stuart, R. Simmons, Intensivist-led management of brain-dead donors is associated with an increase in organ recovery for transplantation, J. M. Darby, Am. J. Transplant., vol. 11, no. 7, pp. 1517-1521, 2011 [3] T. Li, M. Duan, Y. Zhao, G. Yu, Z. Ruan. Bedside monitoring of patients with shock using a portable spatially-resolved near-infrared spectroscopy. Biomed. Opt. Express, vol. 6, no. 9, pp. 3431-3436, 2015 [4] B. Pan, C. Huang, X. Fang, X. Huang, T. Li*, Noninvasive and Sensitive Optical Assessment of Brain Death, J. Biophotonics, vol. 12, no. 3, pp. e201800240, 2018 Disclosures No relevant conflicts of interest to declare.
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Chiromo, Humphrey, and Humphrey Chiromo. "Modified Metal Organic Frameworks Supported Ni Single Atom Catalyst for Enhanced Photocatalytic Hydrogen Evolution Reaction." ECS Meeting Abstracts MA2023-01, no. 17 (2023): 2800. http://dx.doi.org/10.1149/ma2023-01172800mtgabs.
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Abstract Downsizing metal nanoparticle catalysts to form single-atom catalysts (SACs) has proven to be one of the best ways to enhance the catalysts’ activity and selectivity1-2 due to their unique characteristics such as nearly 100% atom utilization and well-defined active sites.3 However, the broad application of SACs in catalytic reactions is limited by their poor stability as they possess high surface energy and thus tend to aggregate and form nanoclusters or nanoparticles.4 To address this challenge, various supports such as metal oxides, carbon materials, and porous materials are widely used to stabilize the SACs.5 Metal organic frameworks (MOFs), a class of porous crystalline materials, have proven to be an ideal candidate to support SACs owing to their high surface area, high porosity, and abundant potential anchoring sites.6 It has been shown that immobilizing SACs on MOFs, which forms MOF supported SACs, can integrate the unique properties of SACs and MOFs and led to remarkable catalytic activity, selectivity, and stability toward various catalytic reactions.6-8 Application of MOF supported SACs in photocatalysis, organic linkers of metal-organic frameworks act as photosensitive units,9 However most pristine metal-organic frameworks possesses poor light absorption properties due to wide band gap.9To enhance the light harvesting properties of the metal organic framework its organic linker is functionalized.10-11 In my poster presentation, I will present my work where post-synthetic modification of UiO-66-NH2 MOF linker with 3,4,9,10 perylene tetracarboxylic dianhydride (PDA) an organic molecule with broad absorption edge,12and immobilization of Ni single atom catalyst on the zirconium cluster of the MOF was done. This resulted in enhanced optical properties and charge separation efficiency which was proved by a combination of UV-visible spectroscopy (UV-Vis), photoelectrochemical techniques, and X-ray absorption spectroscopy (XAS). Observed photophysical effects posed by the modifications of the UiO-66-NH2 were evaluated by photocatalytic hydrogen generation. References Yan, J.; Kong, L.; Ji, Y.; White, J.; Li, Y.; Zhang, J.; An, P.; Liu, S.; Lee, S.-T.; Ma, T., Single atom tungsten doped ultrathin α-Ni (OH) 2 for enhanced electrocatalytic water oxidation. Nature communications 2019, 10 (1), 1-10. Jiao, L.; Jiang, H.-L., Metal-organic-framework-based single-atom catalysts for energy applications. Chem 2019, 5 (4), 786-804. Qiao, B.; Wang, A.; Yang, X.; Allard, L. F.; Jiang, Z.; Cui, Y.; Liu, J.; Li, J.; Zhang, T., Single-atom catalysis of CO oxidation using Pt1/FeO x. Nature chemistry 2011, 3 (8), 634-641. Xia, C.; Qiu, Y.; Xia, Y.; Zhu, P.; King, G.; Zhang, X.; Wu, Z.; Kim, J. Y.; Cullen, D. A.; Zheng, D., General synthesis of single-atom catalysts with high metal loading using graphene quantum dots. Nature chemistry 2021, 13 (9), 887-894. Wu, J.; Xiong, L.; Zhao, B.; Liu, M.; Huang, L., Densely populated single atom catalysts. Small Methods 2020, 4 (2), 1900540. Huang, H.; Shen, K.; Chen, F.; Li, Y., Metal–organic frameworks as a good platform for the fabrication of single-atom catalysts. ACS Catalysis 2020, 10 (12), 6579-6586. Qu, W.; Chen, C.; Tang, Z.; Wen, H.; Hu, L.; Xia, D.; Tian, S.; Zhao, H.; He, C.; Shu, D., Progress in metal-organic-framework-based single-atom catalysts for environmental remediation. Coordination Chemistry Reviews 2023, 474, 214855. Szilágyi, P.; Rogers, D.; Zaiser, I.; Callini, E.; Turner, S.; Borgschulte, A.; Züttel, A.; Geerlings, H.; Hirscher, M.; Dam, B., Functionalised metal–organic frameworks: a novel approach to stabilising single metal atoms. Journal of Materials Chemistry A 2017, 5 (30), 15559-15566. He, J.; Wang, J.; Chen, Y.; Zhang, J.; Duan, D.; Wang, Y.; Yan, Z., A dye-sensitized Pt@ UiO-66 (Zr) metal–organic framework for visible-light photocatalytic hydrogen production. Chemical communications 2014, 50 (53), 7063-7066. Elcheikh Mahmoud, M.; Audi, H.; Assoud, A.; Ghaddar, T. H.; Hmadeh, M., Metal–Organic Framework Photocatalyst Incorporating Bis(4′-(4-carboxyphenyl)-terpyridine)ruthenium(II) for Visible-Light-Driven Carbon Dioxide Reduction. Journal of the American Chemical Society 2019, 141 (17), 7115-7121. Hendrickx, K.; Joos, J. J.; De Vos, A.; Poelman, D.; Smet, P. F.; Van Speybroeck, V.; Van Der Voort, P.; Lejaeghere, K., Exploring lanthanide doping in UiO-66: a combined experimental and computational study of the electronic structure. Inorganic Chemistry 2018, 57 (9), 5463-5474. Yu, H.; Joo, P.; Lee, D.; Kim, B. S.; Oh, J. H., Photoinduced Charge‐Carrier Dynamics of Phototransistors Based on Perylene Diimide/Reduced Graphene Oxide Core/Shell p–n Junction Nanowires. Advanced Optical Materials 2015, 3 (2), 241-247.
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Zhang, Ning. "Qiaowu yu waijiao guanxi yanjiu: Zhongguo fangqi “shuangchong guoji” de huigu yu fansi Overseas Chinese Affairs and Diplomatic Relations: Retrospect on China's Abandoning of its Policy of “Dual Nationality”." Journal of Chinese Overseas 2, no. 1 (2006): 147–49. http://dx.doi.org/10.1163/179325406794756807.
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Tircunova, Svetlana. "THE PERIOD IN THE THEORY OF MUSICAL FORMS." Studiul artelor şi culturologie: istorie, teorie, practică, no. 1(42) (August 2022): 12–16. http://dx.doi.org/10.55383/amtap.2022.1.02.
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The article examines the main stages in the formation and development of the theory of the period: there is an analysis of the interpretation of this form in the works of A.B. Marx, G. Riemann, the Russian musicologists I. Sposodin, Yu. Tyulin, L. Mazel, V. Tsukerman and others. The dual nature of the period is characterized in connection with its simultaneous belonging to the syntactic and compositional levels of musical form. There are two approaches to understanding this structure – metro-tectonic and content-functional. It is concluded that the qualities of expositionality and completeness of the period are provided by its attraction to the periodicity of the structure, harmonic closure and functional balance of the constituent elements
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Stando, Grzegorz Jan, Paweł Stando, Pavel Chulkin, et al. "(Digital Presentation) Electrical Properties of Nanocarbon-Polyaniline Nanocomposites." ECS Meeting Abstracts MA2022-01, no. 9 (2022): 760. http://dx.doi.org/10.1149/ma2022-019760mtgabs.
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Macroscopic objects such as fibers and films formed from a combination of nanocarbon materials and polymers have promising electrical [1], thermal [2], thermoelectric [3], and mechanical [4] properties. In particular, composites of nanocarbon and conductive polymers revealed that they can constitute key parts of batteries [1] and thermoelectric generators [3]. In literature, it is possible to find many synthesis methods of this type of material. One of the most common approaches is electrochemical, wherein monomers are polymerized onto the nanocarbon surface due to its highly conducting nature [5]. Polyaniline (PANI) is the oldest and still one of the most popular conductive polymers used in this area. That is because PANI is relatively simple to manufacture at low cost and effort. Moreover, it has good mechanical strength and tunable electrical conductivity, which depend on the kind of PANI. This polymer has three forms: pernigraniline – fully oxidized (purpure/red), emeraldine – partially oxidized (blue/violet), and leucoemeraldine – fully reduced (black) [6]. Emeraldine achieves the highest conductivity when doped with Brøstead acids such as HCl, H2SO4, HBF4 [7]. The goal of this study was to exploit the phenomenon of the hydrophilic surface of carbon nanostructure caused by thermal annealing, described by us previously [8], to electropolymerize aniline onto free-standing films from nanocarbon. The films were manufactured by the wet method [8] using single-walled nanotubes (SWCNTs) exclusively and SWCNTs/graphene nanoplatelet composite. Electropolymerization was used to synthesize PANI on the surface of these materials. To establish the parameters of synthesis of different forms of PANI, voltage ranges between [(-1.6 V) – (1.6 V)] were investigated. The films were tested as a counter and a working electrode in this process. After the synthesis, the composites were investigated by optical and Scanning Electron Microscopy, Raman spectroscopy, Atomic Force Microscopy. Moreover, water contact angles, electrical conductivity values, and Seebeck coefficients were determined. Composites containing all three PANI forms have been synthesized and thoroughly analyzed to elucidate the structure-property relations. Consequently, correlations between the forms of PANI and the characteristics of nanocomposites were established. Depending on the amount and type of PANI on the surface, the character of the nanocarbon films was affected considerably. For example, coating of the material with emeraldine salts enhanced the electrical conductivity of the films by about 60% [9], while simultaneously making the material much stronger. [1] L. Xiao, Y.H. Sehlleier, S. Dobrowolny, F. Mahlendorf, A. Heinzel, C. Schulz, H. Wiggers, Novel Si-CNT/polyaniline nanocomposites as Lithium-ion battery anodes for improved cycling performance, Mater. Today Proc. 4 (2017) S263–S268. doi:10.1016/J.MATPR.2017.09.197. [2] Z. Duan, Y. Luo, Z. Luo, W. Yu, C. Liu, S. Fan, The influence of charging and discharging on the thermal properties of a carbon nanotube/polyaniline nanocomposite electrode, RSC Adv. 9 (2019) 7629–7634. doi:10.1039/C9RA00151D. [3] R. Wu, H. Yuan, C. Liu, J. Le Lan, X. Yang, Y.H. Lin, Flexible PANI/SWCNT thermoelectric films with ultrahigh electrical conductivity, RSC Adv. 8 (2018) 26011–26019. doi:10.1039/c8ra04863k. [4] M.R. Saeb, P. Zarrintaj, Polyaniline/graphene-based nanocomposites, Fundam. Emerg. Appl. Polyaniline. (2019) 165–175. doi:10.1016/B978-0-12-817915-4.00010-5. [5] C. Oueiny, S. Berlioz, F.X. Perrin, Carbon nanotube–polyaniline composites, Prog. Polym. Sci. 39 (2014) 707–748. doi:10.1016/J.PROGPOLYMSCI.2013.08.009. [6] S.C. Rasmussen, The Early History of Polyaniline: Discovery and Origins, An Int. J. Hist. Chem. Subst. 1 (2017) 99–109. doi:10.13128/substantia-30. [7] Q. Qin, Y. Guo, Preparation and characterization of nano-polyaniline film on ITO conductive glass by electrochemical polymerization, J. Nanomater. 2012 (2012). doi:10.1155/2012/519674. [8] D. Janas, G. Stando, Unexpectedly strong hydrophilic character of free-standing thin films from carbon nanotubes, Sci. Rep. 7 (2017) 12274. doi:10.1038/s41598-017-12443-y. [9] G.Stando, P. Stando, P. Chulkin, M. Salhman, M. Lundström, D. Janas, Electropolymerization of aniline onto hydrophilic nanocarbon films (in preparation) G.S. and P.S. would like to thank the Ministry of Science and Higher Education of Poland for financial support of research (under Diamond Grant, grant agreement 0036/DIA/201948). G.S. also would like to thank European Union for thanks for financing the costs of the conference (European Social Fund, grant nr POWR.03.05.00-00-Z305) and National Agency for Academic Exchange of Poland (under the Iwanowska program, grant agreement PPN/IWA/2019/1/00017/UO/00001) for financial support during the stay at the University of Pittsburgh in the USA. G.S. and H.L. acknowledge NSF (CBET-2028826) for partial support of this work. P. S. acknowledges the National Agency for Academic Exchange of Poland (under the Academic International Partnerships program, grant agreement PPI/APM/2018/1/00004) for supporting training in the Aalto University. G.S, P.S and D.J. would like to thank the National Centre for Research and Development, Poland (under the Leader program, grant agreement LIDER/0001/L-8/16/NCBR/2017).
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Kim, Han-Shin. "The Management and Implementation of Yu Seong-ryong’s Defense Plan in the Dual Wests during Imjin War." Journal of Korean History 192 (March 31, 2021): 39–89. http://dx.doi.org/10.31791/jkh.2021.03.192.39.
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Dirjayanto, Valerie Josephine, Jessica Audrey, and Daniel Martin Simadibrata. "Vonoprazan-amoxicillin dual regimen with Saccharomyces boulardii as a rescue therapy for Helicobacter pylori: Current perspectives and implications." World Journal of Gastroenterology 30, no. 10 (2024): 1280–86. http://dx.doi.org/10.3748/wjg.v30.i10.1280.
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Yu et al ’s study in the World Journal of Gastroenterology (2023) introduced a novel regimen of Vonoprazan-amoxicillin dual therapy combined with Saccharomyces boulardii (S. boulardii ) for the rescue therapy against Helicobacter pylori (H. pylori ), a pathogen responsible for peptic ulcers and gastric cancer. Vonoprazan is a potassium-competitive acid blocker renowned for its rapid and long-lasting acid suppression, which is minimally affected by mealtime. Compared to proton pump inhibitors, which bind irreversibly to cysteine residues in the H+/K+-ATPase pump, Vonoprazan competes with the K+ ions, prevents the ions from binding to the pump and blocks acid secretion. Concerns with increasing antibiotic resistance, effects on the gut microbiota, patient compliance, and side effects have led to the advent of a dual regimen for H. pylori . Previous studies suggested that S. boulardii plays a role in stabilizing the gut barrier which improves H. pylori eradication rate. With an acceptable safety profile, the dual-adjunct regimen was effective regardless of prior treatment failure and antibiotic resistance profile, thereby strengthening the applicability in clinical settings. Nonetheless, S. boulardii comes in various formulations and dosages, warranting further exploration into the optimal dosage for supplementation in rescue therapy. Additionally, larger, randomized, double-blinded controlled trials are warranted to confirm these promising results.
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Fintzen, Jessica, and Beth Romano. "Stable vectors in Moy–Prasad filtrations." Compositio Mathematica 153, no. 2 (2017): 358–72. http://dx.doi.org/10.1112/s0010437x16008228.
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Let $k$ be a finite extension of $\mathbb{Q}_{p}$, let ${\mathcal{G}}$ be an absolutely simple split reductive group over $k$, and let $K$ be a maximal unramified extension of $k$. To each point in the Bruhat–Tits building of ${\mathcal{G}}_{K}$, Moy and Prasad have attached a filtration of ${\mathcal{G}}(K)$ by bounded subgroups. In this paper we give necessary and sufficient conditions for the dual of the first Moy–Prasad filtration quotient to contain stable vectors for the action of the reductive quotient. Our work extends earlier results by Reeder and Yu, who gave a classification in the case when $p$ is sufficiently large. By passing to a finite unramified extension of $k$ if necessary, we obtain new supercuspidal representations of ${\mathcal{G}}(k)$.
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ZONG, Yao. "The Principal's Persistence to Confucianism under the spread of Western learning in the Late Qing Dynasty: A Case Study of Yu Yue's Activities in the GuJing Academy." Institute of Korean Cultural Studies Yeungnam University 82 (December 31, 2022): 163–85. http://dx.doi.org/10.15186/ikc.2022.12.31.08.
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In the late Qing Dynasty, under the changing circumstances of Western powers invading China, Western Learning were introduced into local education in order to save and strengthen the country. The introduction of Western learning not only updated the educational content, but also squeezed the living space of traditional Confucianism. Facing the assault of Western learning , Yuyue, the principal of the GuJing Academy, tried to break the predicament of Confucianism in development and inheritance through the academy. Before 1894, when the value of Confucianism in governing the country was still recognized, Yu Yue hoped to compete with Western learning for the territory of dissemination by revitalizing the practical functions of Confucianism in the academy. After 1894, When the Westernization Movement failed and the effect of Confucianism in saving the destiny of the country is basically denied, Yu Yue sought to retain the academy as a base for the continuation of Confucianism. Yu Yue’s behavior shows at the time of the collapse of the traditional political civilization order with “civilization throug h humanities” as the main social g overnance method, the principal g roup that had the dual responsibility of “defending the doctrine” and “spreading the doctrine”, explored and considered the future of Chinese national culture.
 
 청대 말기, 열강의 중국 침략이라는 위기의 국면 속에서 구국(救國) 자강(自 強)이라는 시대적 요청에 힘입어, 서양의 과학 기술과 문화 지식이 중국 교육에 편입되었다. 서학 도입은 청대 말기 교육 내용에 혁신을 일으킨 것과 동시에, 전통 유학이 설 자리를 압박하게 되었다. 서학의 충돌에 대면하여, 고경정사(詁經精舍)의 산장 유월(俞樾)은 서원을 통해 유학의 발전 및 전승이 어려워진 상황을 타파하고자 하였다. 갑오(甲午) 이전, 유학의 통치술(治術)로서의 가치가 여전히 인정받고 있었던 때, 유월은 서원의 ‘치용(致用)’ 기능을 회복하여서학과의 투쟁을 도모하였다. 갑오 이후, 양무운동의 실패와 더불어 유학의‘구세(救世)’라는 기대 효과는 부정당하고 말았고, 이에 유월은 서원을 유학 보존의 장소로 삼고자 하였다. 유월의 활동은 “도를 보위하고(衛道)”, “도를 전한다(傳道)”라는 이중적 임무를 짊어지고 있었던 청대 말기 서원 산장들의 실태를 드러낸다. 과거 ‘인문화성(人文化成)’을 주요 사회 통치 방식으로 삼았던전통 정교(政敎) 질서가 붕괴하던 당시, 유월의 활동은 민족 문화의 앞길에 대한 탐색과 고민을 보여준다.
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Dmitrovskaya, Maria. "Georgian Military Road: Constant Communication (the Structure of “A Hero of Our Time” by M. Yu. Lermontov)." Literatūra 62, no. 2 (2020): 171–84. http://dx.doi.org/10.15388/litera.2020.2.10.
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The article demonstrates the fact that the duality of human consciousness is connected by mutual projections with the topography of the Georgian Military Road and the model of the universe and also forms the system of narrators / characters and the structure of the novel as a whole, including the number of stories and the partition of the novel into two parts. The sources used by the writer in the formation of the narrative structure of the novel are reconstructed. The numerological code of the novel is considered, the language bases of the conceptual system are analyzed. The embeddedness in the conceptual system of the trinomial name of Mikhail Yuryevich Lermontov is demonstrated. The vertical and horizontal spatial orientation of the Georgian Military Road allows discovering the topographic connection of the road with the dual reality of Lermontov, in which the opposite poles of good and evil, divine and evil turn into one.
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Zhang, Jianbo, та Zhichang Lou. "Tradução das palavras com carga cultural no romance 活着 (huó zhe, Viver) a partir da perspectiva da eco-translatologia". Cadernos de Tradução 43, № 1 (2023): 1–22. http://dx.doi.org/10.5007/2175-7968.2023.e86532.
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O romance 活着 (huó zhe, Viver), do prestigiado escritor chinês Yu Hua, é considerado um dos romances mais influentes na história da literatura chinesa contemporânea e foi traduzido no Brasil (2008) e em Portugal (2019). Como o romance é marcado pela abundância de palavras com carga cultural, o presente trabalho tem como objeto a tradução das palavras com carga cultural nas duas referidas versões de tradução do romance à luz da eco-translatologia (proposta pelo teórico chinês Hu Gengshen), com uma análise qualitativa de caso sobre o grau de transformação tridimensional. O artigo fará o levantamento de todas as palavras com carga cultural no romance Viver, selecionará as palavras mais representativas, comparará as traduções destas palavras por dois tradutores e avaliará seus desempenhos em termos do grau de transformação tridimensional para enriquecer os resultados teóricos da eco-translatologia.
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Quan, Yu Hua, Kai Bao, Kyungsu Kim, et al. "Abstract 5975: Dual-channel near-infrared fluorescence imaging for simultaneous identification of lung cancer and intersegmental plane." Cancer Research 82, no. 12_Supplement (2022): 5975. http://dx.doi.org/10.1158/1538-7445.am2022-5975.
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Abstract Intraoperative delineation of the tumor with minimal negative margins is the holy grail of lung cancer surgery. Segmentectomy is a minimal resection surgery required for elderly patients or small sized early-stage lung cancer patients, in which accurate detection of tumor margins with simultaneous identification of the lung intersegment plane is the key to success. However, non-small cell lung cancer is difficult to detect intraoperatively, and the identification of intersegmental plane is challenging during minimal resection surgery. Here, we report dual-channel image-guided lung cancer surgery using renal clearable and physiochemically stable targeted fluorophores to visualize the tumor margins and intersegmental plane separately with different colors but simultaneously: cRGD-ZW800-PEG (800 nm channel) allows for tumor-specific targeting and ZW700-1C (700 nm channel) for discrimination of segmental planes. Armed with the dual-channel imaging, image-guided surgery enables complete tumor resection with minimal negative margins that can reduce the recurrence rate and increase the survival rate of lung cancer patients. Citation Format: Yu Hua Quan, Kai Bao, Kyungsu Kim, Haoran Wang, Shinya Yokomizo, G. Kate Park, Byeong Hyeon Choi, Jiyun Rho, Chungyeul Kim, Hak Soo Choi, Hyun Koo Kim. Dual-channel near-infrared fluorescence imaging for simultaneous identification of lung cancer and intersegmental plane [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5975.
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Wang, Yadong, Jian Zhang, Pao-Liang Chang, Carrie Langston, Brian Kaney, and Lin Tang. "Operational C-Band Dual-Polarization Radar QPE for the Subtropical Complex Terrain of Taiwan." Advances in Meteorology 2016 (2016): 1–15. http://dx.doi.org/10.1155/2016/4294271.
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Complex terrain poses significant challenges to the radar based quantitative precipitation estimation (QPE) because of blockages to the lower tilts of radar observations. The blockages often force the use of higher tilts data to estimate precipitation at the ground and result in errors due to vertical variations of the radar variables. To obtain accurate radar QPEs in the subtropical complex terrain of Taiwan, a vertically corrected composite algorithm (VCCA) was developed for two C-band polarimetric radars. The new algorithm corrects higher tilt radar variables with the vertical profile of reflectivity (VPR) or vertical profile of specific differential phase (VPSDP) and estimates rainfall rate at the ground through an automated combination ofR-ZandR-KDPrelations. The VCCA was assessed with three precipitation cases of different regimes including typhoon, mei-yu, and summer stratiform precipitation events. The results showed that a combination ofR-ZandR-KDPrelations provided more accurate QPEs than each alone becauseR-Zprovides better rainfall estimates for light rains andR-KDPrelation is more suitable for heavy rains. The vertical profile corrections for reflectivity and specific differential phase significantly reduced radar QPE errors caused by inadequate sampling of the orographic enhancement of precipitation near the ground.
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Liu, Ziqi, Min Hwan Lee, and ThomasJae Garcia. "3D Metal-Organic Framework Based Layered Double Hydroxide Core Shell Structure for Enhanced Oxygen Evolution Reaction." ECS Meeting Abstracts MA2022-02, no. 44 (2022): 1684. http://dx.doi.org/10.1149/ma2022-02441684mtgabs.
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Electrochemical water splitting, an effective approach of generating high purity hydrogen in a clean way, is composed of two half reactions: hydrogen evolution reaction (HER) and oxygen evolution reaction (OER).[1] OER is the main rate-limiting half reaction for water splitting due to its sluggish four-electron transfer process.[2] , [3] An efficient electrocatalyst is indispensable to minimize the activation barrier for the reaction and achieve a high efficiency. Recently, two-dimensional (2D) layered double hydroxides (LDHs) have shown promises as one of the most effective electrocatalysts towards OER. However, the confined nanostructure with poor electronic conductivity inhibits their further enhanced catalytic performance towards OER. Herein, a 3D core-shell LDH structure is synthesized through a facile one-step reaction strategy, in which the terephthalic acid and urea is employed as the organic ligand for the metal organic framework (MOF) precursor and surface coordination buffer between LDH and MOF. Benefiting from the hierarchical 3D microstructure with uniformly nanosheets grown on the surface, the as prepared electrocatalyst exhibits rich edge active sites and enormous electrochemical surface area. The representative sample (namely, CoNi-LDH@BDC) achieves an excellent OER activity with a low overpotential of 280 mV at 100 mA cm-2 and robust cyclic stability. In addition, quasi-operando studies using X-ray absorption and X-ray photoelectron spectroscopy further elucidate that the Co-Ni dual metal sites act as the main active site while Ni of high valence state is a favorable site to oxygen for the O-O bond formation. The prominent OER performance is also attributed to the synergistic effect between different transition metal atoms. References [1] L. Yu, H. Zhou, J. Sun, F. Qin, F. Yu, J. Bao, Y. Yu, S. Chen, Z. Ren, Energy Environ. Sci. 2017, 10, 1820. [2] Y. Wang, C. Xie, Z. Zhang, D. Liu, R. Chen, S. Wang, Adv. Funct. Mater. 2018, 28, 1703363. [3] L. Zhuang, L. Ge, Y. Yang, M. Li, Y. Jia, X. Yao, Z. Zhu, Adv. Mater. 2017, 29, 1606793. [4] R. Frydendal, E. A. Paoli, B. P. Knudsen, B. Wickman, P. Malacrida, I. E. L. Stephens, I. Chorkendorff, ChemElectroChem 2014, 1, 2075. [5] Y. Lee, J. Suntivich, K. J. May, E. E. Perry, Y. Shao-Horn, Synthesis and activities of rutile IrO 2 and RuO 2 nanoparticles for oxygen evolution in acid and alkaline solutions, Vol. 3, American Chemical Society, 2012, pp. 399–404. [6] M. Gao, W. Sheng, Z. Zhuang, Q. Fang, S. Gu, J. Jiang, Y. Yan, J. Am. Chem. Soc. 2014, 136, 7077.
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Sandoval, Gabriel J., Richard C. Centore, Sal Topal, et al. "Abstract A056: Treatment with dual BRG1/BRM (SMARCA4/2) inhibitor FHD-286 ablates tumor-associated androgen response elements (AREs) in prostate cancer." Molecular Cancer Therapeutics 22, no. 12_Supplement (2023): A056. http://dx.doi.org/10.1158/1535-7163.targ-23-a056.
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Abstract The Androgen Receptor (AR) cistrome is critical in the development of prostate cell identity while its misregulation promotes prostate cancer development. The pioneer transcription factor Forkhead box A1 (FOXA1) has been shown to be essential for the recruitment of AR to androgen response elements (AREs) allowing for reprogramming of the AR cistrome resulting in prostate cell transformation. FHD-286 is a BRM/BRG1 dual ATPase inhibitor currently in clinical trials for AML. Here, we show that treatment of prostate cancer cell lines with FHD-286 results in ablation of FOXA1 mediated AREs at tumor-associated AR binding sites (T-ARBS). Dual ATPase treatment subsequently reduces the expression level of various oncogenic AR target genes, leading to a decrease in tumor cell viability. Both patient derived organoid and In vivo studies provide further validation by showing a decrease in tumor growth. Strikingly, inhibition of BAF complex activity bypasses AR resistance mechanisms commonly seen after castration and Enzalutamide treatment as cell lines containing AR-V7 splice variants and neuroendocrine organoids display sensitivity. Taken together, our data illustrates a novel mechanism of treating AR mediated prostate cancer though the inhibition tumor associated AREs by treatment with FHD-286. Citation Format: Gabriel J Sandoval, Richard C Centore, Sal Topal, Dave Lahr, GiNell Elliott, Heena Gandevia, Ammar Adam, Jessica Piel, Holly M Nguyen, Eva Corey, Yu Chen, Steven Bellon, Murphy Hentemann. Treatment with dual BRG1/BRM (SMARCA4/2) inhibitor FHD-286 ablates tumor-associated androgen response elements (AREs) in prostate cancer [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr A056.
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Chu, Yu-Yi, Jianjun Gao, Dihua Yu, and Mien-Chie Hung. "Abstract 416: Phosphorylation of CDK9 transduces ALK signaling to promote resistance to PARP inhibitors via RNA Pol II activated homologous recombination repair." Cancer Research 83, no. 7_Supplement (2023): 416. http://dx.doi.org/10.1158/1538-7445.am2023-416.
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Abstract Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) are currently the most promising drugs to induce synthetic lethality in tumor with homologous recombination (HR) deficiency. However, development of resistance to PARPi is an almost universal occurrence in tumor despite initial sensitivity. Additionally, how to identify the right patients for PARPi monotherapy or in combination with other agents remains a substantial clinical challenge. Therefore, understanding the molecular underpinnings of PARPi resistance is critical to the development of rational combinatorial treatment strategies and identification of novel biomarkers which will in turn facilitate optimization of outcomes for patients receiving PARPi. By employing a screening procedure using phospho-RTK antibody array, our study identifies phosphorylated ALK (p-ALK) expression is higher in PARPi/platinum resistant cells relative to sensitive cells. We further demonstrate that p-ALK expression in human ovarian cancer tissue is associated with resistance to PARPi and platinum-based chemotherapy. Notably, FDA approved ALK inhibitors induce an HR-deficient phenotype and sensitize PARPi/platinum-resistant tumors to PARPi in vitro and in vivo. Mechanistically, ALK contributes to PARPi resistance by tyrosine phosphorylating CDK9 at Y19, thereby increasing the protein stability and kinase activity of CDK9 which in turn stabilizes positive transcriptional elongation factor b (P-TEFb) to activate RNA pol II and turn on HR repair genes transcription. Importantly, the phosphorylated counterparts of ALK/CDK9 complex (p-ALK/p-Y19 CDK9) can serve as a biomarker to identify patients with PARPi/platinum-resistant tumors which most likely to respond to dual PARP and ALK inhibition. Together, our findings identify p-ALK/p-Y19-CDK9 mediated stabilization of P-TEFb as a critical mechanism of PARPi resistance and supports a biomarker-guided therapeutic strategy combining ALKi and PARPi to induce synthetic lethality. Citation Format: Yu-Yi Chu, Jianjun Gao, Dihua Yu, Mien-Chie Hung. Phosphorylation of CDK9 transduces ALK signaling to promote resistance to PARP inhibitors via RNA Pol II activated homologous recombination repair [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 416.
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Chang, Yu, Jianzhang Yang, Jean Ching-Yi Tien, et al. "Abstract 3428: Discovery of a highly potent and selective dual PROTAC degrader of CDK12 and CDK13." Cancer Research 83, no. 7_Supplement (2023): 3428. http://dx.doi.org/10.1158/1538-7445.am2023-3428.
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Abstract Selective degradation of the cyclin-dependent kinases 12 and 13 (CDK12/13) presents a novel therapeutic opportunity for triple-negative breast cancer (TNBC), but there is still a lack of dual CDK12/13 degraders. Here, we report the discovery of the first series of highly potent and selective dual CDK12/13 degraders by employing the proteolysis-targeting chimera (PROTAC) technology. The optimal compound 7f effectively degraded CDK12 and CDK13 with DC50 values of 2.2 nM and 2.1 nM, respectively, in MDA-MB-231 breast cancer cells. Global proteomic profiling demonstrated the target selectivity of 7f. In vitro, 7f suppressed expression of core DNA damage response (DDR) genes in a time- and dose-dependent manner. Further, 7f markedly inhibited proliferation of multiple TNBC cell lines including MFM223, with an IC50 value of 47 nM. Importantly, 7f displayed a significantly improved anti-proliferative activity compared to the structurally similar inhibitor 4.The 2nd generation CDK12/13 degrader 9069 was further developed, which showed more potent degradation on both CDK12 and CDK13. Interestingly, multiple prostate cancer cell lines were sensitive to 9069, such as VCaP, 22RV1 and LAPC4 with IC50 values of 22.9, 90.3 and 152.1 nM, respectively. In vivo studies showed a potent tumor growth inhibition in both VCaP CRPC xenograft and PC310 PDX prostate cancer models. These results suggest the potential application of a CDK12/13 degrader for the treatment of TNBC and prostate cancer. Citation Format: Yu Chang, Jianzhang Yang, Jean Ching-Yi Tien, Zhen Wang, Yang Zhou, Pujuan Zhang, Weixue Huang, Josh Vo, Ingrid J. Apel, Cynthia Wang, Victoria Zhixuan Zeng, Yunhui Cheng, Shuqin Li, George Xiaoju Wang, Ke Ding, Arul M. Chinnaiyan. Discovery of a highly potent and selective dual PROTAC degrader of CDK12 and CDK13 [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 3428.
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Moriarty, Aidan, Oihana Iriondo, Desirae Mecenas, et al. "Abstract PO2-24-09: Prolonged Effects of Hypoxia in Luminal Breast Cancer Cells Promotes an Aggressive Phenotype." Cancer Research 84, no. 9_Supplement (2024): PO2–24–09—PO2–24–09. http://dx.doi.org/10.1158/1538-7445.sabcs23-po2-24-09.
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Abstract Aidan Moriarty Mentor: Dr. Min Yu Hypoxic Memory in Breast Cancer Cells Metastasis is the main cause of tumor-related mortality in breast cancer patients. Improving our understanding of the metastatic cascade is imperative to improve patient outcomes. Prior research indicates cancer cells with increased metastatic potential have acquired adaptive properties induced by factors in the tumor microenvironment (TME), including hypoxia. However, previous hypoxia research has been primarily focused on signaling changes that occur when cancer cells are in the hypoxic TME and does not account for long-term changes that may occur once cancer cells re-enter normoxia, such as when they metastasize. Our research in patient-derived circulating tumor cell (CTCs) lines and breast cancer cell lines has indicated that certain transcriptional changes are maintained after cells leave hypoxia, and that these post-hypoxic CTCs maintain a higher metastatic potential compared to cells not exposed to hypoxia. Taking an un-biased approach to define changes in hypoxia-exposed breast cancer cells upon reoxygenation, we performed bulk RNA-Seq on luminal breast cancer cell lines in various oxygen conditions over time. We found that a subset of genes that were differentially expressed in hypoxic conditions were maintained as up- or down-regulated after cells were reoxygenated, indicating a “hypoxic memory”. Additionally, a subset of genes were differentially expressed in the post-hypoxic cells compared to normoxia controls, demonstrating novel and prolonged gene expression changes induced by hypoxia exposure. We performed functional assays and observed that this post-hypoxic state is associated with a more aggressive phenotype in vitro. Current research in our lab is on-going to understand the epigenetic changes that may be responsible for this hypoxic memory to further understand the consequences of hypoxic memory in CTC biology and metastasis. Finally, we have designed a dual-reporter hypoxia-tracing system to validate our findings in vivo. This research will improve our understanding of the prolonged influence of hypoxia on metastatic potential in breast cancer cells and has the potential to inform future therapeutic strategies. Citation Format: Aidan Moriarty, Oihana Iriondo, Desirae Mecenas, Yilin Li, Yonatan Amzaleg, Remi Klotz, Min Yu. Prolonged Effects of Hypoxia in Luminal Breast Cancer Cells Promotes an Aggressive Phenotype [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-24-09.
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Jiang, Yunlong, Tingting Gu, Weiwei Yu, et al. "Abstract 5623: CD137 humanized mice for preclinical efficacy evaluation of therapeutic antibodies." Cancer Research 82, no. 12_Supplement (2022): 5623. http://dx.doi.org/10.1158/1538-7445.am2022-5623.
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Abstract CD137 (41-BB, tumor necrosis factor receptor superfamily 9), expressed on activated T cells and NK cells, has gained increased attention as an anti-tumor target because of remarkable clinical efficacy using either a single agent or in combination with other immune checkpoint inhibitors. We constructed CD137 humanized mice based on two different backgrounds, C57BL6 and BALB/c mice, as well as dual-target and triple-target mice crossbred with PD1/PDL1 humanized mice to create an ideal model to study CD137 target drugs. The normal immune cell population in peripheral blood were not affected in CD137 humanized mice, and hCD137 was expressed on T cells after the stimulation with a anti CD3 antibody. We verified the efficacy of anti-CD137 drugs in BALB/c-hCD137 mice inoculated with different cancer cell lines (i.e. CT26, EMT6 and 4T1). The drug Urelumab showed a dramatic response in the hCD137 mice model inoculated with CT26 and EMT6 but not with 4T1 cell line. In a rechallenge study, no tumors grew in tumor-free mice previously treated with Urelumab, with effector memory T cells increased in peripheral blood, indicating Urelumab has a relatively long-lasting anti-tumor effect. The combination of Urelumab and anti-PD1 has a stronger tumor growth inhibition effect than that of anti-CD137 or anti-PD1 monotherapy on dual-target or triple target mice. These data show that the humanized CD137 mouse is a suitable model for evaluating the monotherapies or combination therapies targeting CD137. Citation Format: Yunlong Jiang, Tingting Gu, Weiwei Yu, Hongyan Sun, Mingkun Zhang, Juan Liang, Shuai Li, Cunxiang Ju, Jing Zhao, Xiang Gao, Mark W. Moore. CD137 humanized mice for preclinical efficacy evaluation of therapeutic antibodies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5623.
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Zeng, Zhiqiao, Stoyan Bliznakov, Leonard J. Bonville, et al. "Large–Scale, High-Performance, Durable and Low-Cost Membrane Electrode Assemblies for Proton Exchange Membrane Water Electrolyzers." ECS Meeting Abstracts MA2022-02, no. 44 (2022): 1659. http://dx.doi.org/10.1149/ma2022-02441659mtgabs.
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Proton exchange membrane (PEM) water electrolyzers, designed to produce hydrogen from intermittent renewable energy, will play a key role in future sustainable energy systems.1 However, the widespread commercialization of PEM water electrolyzers is obstructed by their high cost, low durability, and safety concerns related to the hydrogen crossover. Currently, the production cost of green H2 is in the range of $3-8 kg-1. In order to boost the commercialization of this clean energy devices and lower the production cost of green H2, DOE implemented targets of $2 kg-1 by 2025 and $1 kg-1 hydrogen by 2030.2 In addition, the durability of all electrolyzer components has to be improved in order to increase the lifetime of a PEM water electrolyzer stack to the targeted 80,000 hours. These challenging targets inspired the researchers all over the world to work on development of novel catalyst and catalyst layers with decreased platinum group metal (PGM) loadings, invent new cost-effective methods for fabrication of membrane electrode assemblies (MEAs), develop innovative designs for the MEAs capable of decreasing the hydrogen crossover, and improve the corrosion resistance of the cell hardware and the other stack components to enhance their durability. In this work, the unique Reactive Spray Deposition Technology (RSDT) is used to fabricate a high-performance, durable, and low-cost MEAs with geometric area of 680 cm2. These large scale MEAs have one order of magnitude lower PGM loadings in their catalyst layers in comparison to the state-of-the-art (SOA) commercial MEAs. The RSDT is a flame-based method that combines the catalysts synthesis and electrodes deposition in one step and thus substantially reduces the time and cost for MEAs fabrication.3–5 As fabricated large-scale MEAs with 680 cm2 geometric area of their electrodes, have loadings of 0.2 mgPt/cm2 in the cathode and 0.3 mgIr/cm2 in the anode, which are 10 times lower than the loadings in the SOA MEAs. The MEAs of interest have been tested at steady-state conditions that are typical for an industrial hydrogen production system for over 1000 hours. The cell voltage transients, as well as the periodically measured polarization curves during the test, clearly show that as fabricated MEAs have excellent activity and durability performance. Furthermore, the RSDT fabricated MEAs have integrated dual recombination layers that effectively reduce the hydrogen crossover to below 10 % LFL at all measured current densities (from 0.58 to 1.8 A/cm2). In addition, the MEA was subjected to comprehensive post-test analysis to study the degradation mechanisms governing the performance loss during the long-term durability test, and the results obtained will be presented and discussed in this presentation. Reference 1. C. Van Pham, D. Escalera-López, K. Mayrhofer, S. Cherevko, and S. Thiele, Adv. Energy Mater., 11 (2021). 2. https://www.energy.gov/eere/fuelcells/hydrogen-shot-summit-proceedings-panel-session-1-electrolysis 3. H. Yu, N. Danilovic, Y. Wang, W. Willis, A. Poozhikunnath, L. Bonville, C. Capuano, K. Ayers, and R. Maric, Appl. Catal. B Environ., 239, 133–146 (2018). 4. G. Mirshekari, R. Ouimet, Z. Zeng, H. Yu, S. Bliznakov, L. Bonville, A. Niedzwiecki, C. Capuano, K. Ayers, and R. Mari, Int. J. Hydrogen Energy, 46, 1526–1539 (2021). 5. H. Yu, L. Bonville, J. Jankovic, and R. Maric, Appl. Catal. B Environ., 260, 118194 (2020).
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Wang, Chung-Chieh, Yu-Han Chen, Yu-Yao Lan, and Wei-Yu Chang. "An Evaluation of Simulated Cloud Microphysical Characteristics of Three Mei-Yu Rainfall Systems in Taiwan by a Cloud-Resolving Model Using Dual-Polarimetric Radar Observations." Remote Sensing 15, no. 19 (2023): 4651. http://dx.doi.org/10.3390/rs15194651.
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This study selected three heavy-rainfall events of different types in Taiwan’s Mei-yu season for high-resolution simulations at a grid size of 1 km and assessed the model’s capability to reproduce their morphology and characteristics. The three cases include a pre-frontal squall line, a mesoscale convective system (MCS) embedded in southwesterly flow, and a local convection near the front in southern Taiwan during the South-West Monsoon Experiment (SoWMEX) in 2008, chosen mainly because of the availability of the S-band polarimetric (S-Pol) radar observations, and especially the particle identification results. The simulations using the Cloud-Resolving Storm Simulator (CReSS) could reproduce all three corresponding rainfall systems at roughly the correct time and location, including their kinematic structures such as system-relative flows with minor differences, although the cells appeared to be coarser and wider than the S-Pol observations. The double-moment cold-rain microphysics scheme of the model could also capture the general distributions of hydrometeors, such as heavy rainfall below the updraft core with lighter rainfall farther away below the melting level, and graupel and mixed-phase particles in the upper part of the updraft with snow and ice crystals in stratiform areas between updrafts above the melting level. Near the melting level, the coexistence of rain and snow corresponds to wet snow in the observations. Differences in cloud characteristics in the events are also reflected in the model results to some extent. Overall, the model’s performance in the simulation of hydrometeors exhibits good agreement with the observation and appears reasonable.
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Lowery, Frank, Sri Krishna, Rami Yoseph, et al. "651 Molecular signature of neoantigen-reactive CD4+ and CD8+ T cells from metastatic human cancers enables prospective antitumor TCR prediction." Journal for ImmunoTherapy of Cancer 9, Suppl 2 (2021): A680. http://dx.doi.org/10.1136/jitc-2021-sitc2021.651.
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BackgroundAutologous patient T cells engineered to express antitumor T cell receptors (TCRs) and chimeric antigen receptors (CARs) have been effective for the treatment of certain cancer types,1–4 and tumor neoantigens encoded by cancer-specific mutations have emerged as major targets of CD4+ and CD8+ T cells in immune checkpoint blockade (ICB) and in adoptive cell therapy (ACT).5–9 However, only a minority of intratumoral T cells are reactive to cancer antigens while the majority represent bystander cells.10–12 Conventional approaches to isolate tumor-reactive T cells and identify their TCRs from tumors rely on T cell function and can be impaired due to T cell exhaustion and dysfunction.13 14MethodsWe performed single-cell RNA and T cell receptor (TCR) sequencing (scRNA/TCR-seq) on over 46,000 T cells isolated from eleven archival metastatic tumor samples whose primary cancer types included colon, rectal, breast, anal, and melanoma. From these samples, 15 CD8+ and 17 CD4+ neoantigen-reactive TCR clonotypes (NeoTCRs) were known. We then performed transcriptomic clustering of these cells and mapped known NeoTCR clonotypes onto the transcriptomic map. Subsequently we predicted NeoTCRs from prospective metastatic colon cancer samples based on their presence within clusters sharing gene expression with NeoTCR+ clusters in the archival samples.ResultsProjecting known NeoTCRs onto the TIL transcriptomic map, we observed 325 total T cells bearing these NeoTCRs, and the majority (>80%) of NeoTCRs were expressed by T cells within 2 clusters, one CD4+ and one CD8+, that included by expression of CXCL13, ENTPD1 (CD39), TOX, TIGIT, LAG3, and PDCD1 (PD-1), indicating a dysfunctional state. Reasoning that T cells sharing phenotypes with those within the NeoTCR clusters could be novel NeoTCRs, we developed gene signatures (NeoTCR4 and NeoTCR8) of CD4 and CD8 NeoTCR+ cells, respectively, and four prospective patients' TIL were analyzed by scRNA/TCR-seq and scored according to NeoTCR signatures. We expressed predicted NeoTCRs in healthy donor PBL and screened them with antigen presenting cells (APCs) expressing candidate neoantigens. 33/73 predicted NeoTCRs (including both CD4 and CD8) were reactive against patients' tumors or candidate neoantigens.ConclusionsThis study enabled successful detection of tumor-specific NeoTCRs in the sequenced TIL of 14/14 patients for whom reactivity was studied. Deconvolution of NeoTCRs from bystander TCRs within the tumor-immune microenvironment represents an important step in the development of personalized immunotherapeutics, and prospective NeoTCR isolation based on TIL transcriptional phenotypes will allow for rapid development of personalized immunotherapy in the form of lymphocytes expressing these tumor-specific TCRs.AcknowledgementsWe thank the Surgery Branch TIL Laboratory and clinical team for generating TIL, and patients enrolled in our clinical protocols. Support from CCR Single Cell Analysis Facility was funded by FNLCR Contract HHSN261200800001E. This work utilized the computational resources of the NIH HPC Biowulf cluster (http://hpc.nih.gov). We also thank NIDAP for providing additional computational support and the CCR Genomics Core for next-generation sequencing supportReferencesRobbins PF, Morgan RA, Feldman SA, Yang JC, Sherry RM, Dudley ME, Wunderlich JR, Nahvi AV, Helman LJ, Mackall CL, Kammula US, Hughes MS, Restifo NP, Raffeld M, Lee CCR, Levy CL, Li YF, El-Gamil M, Schwarz SL, Laurencot C, Rosenberg SA.Tumor regression in patients with metastatic synovial cell sarcoma and melanoma using genetically engineered lymphocytes reactive with NY-ESO-1. J Clin Oncol 2011;29:917–924.Morgan RA, Dudley ME, Wunderlich JR, Hughes MS, Yang JC, Sherry RM, Royal RE, Topalian SL, Kammula US, Restifo NP, Zheng Z, Nahvi A, de Vries CR, Rogers-Freezer LJ, Mavroukakis SA, Rosenberg SA. Cancer regression in patients after transfer of genetically engineered lymphocytes. Science 2006;314:126–129.June CH, Sadelain M. Chimeric Antigen Receptor Therapy. N Engl J Med 2018;379:64–73.Kochenderfer JN, Yu Z, Frasheri D, Restifo NP, Rosenberg SA. Adoptive transfer of syngeneic T cells transduced with a chimeric antigen receptor that recognizes murine CD19 can eradicate lymphoma and normal B cells. Blood 2010;116:3875–3886.Tran E, Robbins PF, Rosenberg SA, “Final common pathway” of human cancer immunotherapy: targeting random somatic mutations. Nat Immunol 2017;18:255–262.Robbins PF, Lu YC, El-Gamil M, Li YF, Gross C, Gartner J, Lin JC, Teer JK, Cliften P, Tycksen E, Samuels Y, Rosenberg SA, Mining exomic sequencing data to identify mutated antigens recognized by adoptively transferred tumor-reactive T cells. Nat Med 2013;19:747–752.Parkhurst MR, Robbins PF, Tran E, Prickett TD, Gartner JJ, Jia L, Ivey G, Li YF, El-Gamil M, Lalani A, Crystal JS, Sachs A, Groh E, Ray S, Ngo LT, Kivitz S, Pasetto A, Yossef R, Lowery FJ, Goff SL, Lo W, Cafri G, Deniger DC, Malekzadeh P, Ahmadzadeh M, Wunderlich JR, Somerville RPT, Rosenberg SA. Unique Neoantigens Arise from Somatic Mutations in Patients with Gastrointestinal Cancers. Cancer Discov 2019;9:1022–1035.Gubin MM, Zhang X, Schuster H, Caron E, Ward JP, Noguchi T, Ivanova Y, Hundal J, Arthur CD, Krebber WJ, Mulder GE, Toebes M, Vesely MD, Lam SSK, Korman AJ, Allison JP, Freeman GJ, Sharpe AH, Pearce EL, Schumacher TN, Aebersold R, Rammensee HG, Melief CJM, Mardis ER, Gillanders WE, Artyomov MN, Schreiber RD. Checkpoint blockade cancer immunotherapy targets tumour-specific mutant antigens. Nature 2014;515:577–581.van Rooij N, van Buuren MM, Philips D, Velds A, Toebes M, Heemskerk B, van Dijk LJA, Behjati S, Hilkmann H, el Atmioui D, Nieuwland M, Stratton MR, Kerkhoven RM, Keşmir C, Haanen JB, Kvistborg P, Schumacher TN. Tumor Exome Analysis Reveals Neoantigen-Specific T-Cell Reactivity in an Ipilimumab-Responsive Melanoma. Journal of Clinical Oncology 2013;31:e439–e442.Duhen T, Duhen R, Montler R, Moses J, Moudgil T, de Miranda NF, Goodall CP, Blair TC, Fox BA, McDermott JE, Chang SC, Grunkemeier G, Leidner R, Bell RB, Weinberg AD. Co-expression of CD39 and CD103 identifies tumor-reactive CD8 T cells in human solid tumors. Nat Commun 2018;9:2724.Simoni Y, Becht E, Fehlings M, Loh CY, Koo SL, Teng KWW, Yeong JPS, Nahar R, Zhang T, Kared H, Duan K, Ang N, Poidinger M, Lee YY, Larbi A, Khng AJ, Tan E, Fu C, Mathew R, Teo M, Lim WT, Toh CK, Ong BH, Koh T, Hillmer AM, Takano A, Lim TKH, Tan EH, Zhai W, Tan DSW, Tan IB, Newell EW, Bystander CD8 T cells are abundant and phenotypically distinct in human tumour infiltrates. Nature 2018;557:575–579.Scheper W, Kelderman S, Fanchi LF, Linnemann C, Bendle G, de Rooij MAJ, Hirt C, Mezzadra R, Slagter M, Dijkstra K, Kluin RJC, Snaebjornsson P, Milne K, Nelson BH, Zijlmans H, Kenter G, Voest EE, Haanen JBAG, Schumacher TN. Low and variable tumor reactivity of the intratumoral TCR repertoire in human cancers. 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Yu, Jindan. "Abstract IA002: Genomic and epigenomic regulation during prostate cancer progression." Cancer Research 83, no. 11_Supplement (2023): IA002. http://dx.doi.org/10.1158/1538-7445.prca2023-ia002.
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Abstract Prostate cancer (PCa) development and progression are controlled by aberrant expression, mutation, and function of essential transcriptional factors and epigenetic modifiers. Over the years, our work has delineated the molecular mechanisms by which androgen receptor (AR) and Polycomb Repressive Complex 2 (PRC2) protein EZH2 regulate PCa progression in concert with other key transcriptional factors such as TMPRSS2-ERG and FOXA1. We recently found that HOXB13, a homeodomain transcription factor primarily known as a pioneering factor of AR, plays an AR-independent role in inhibiting cancer metabolism and tumor metastasis. An important function that is mediated by its interaction with the HDAC3-NCoR corepressor complex, which is disrupted by the PCa risk-associated HOXB13 G84E mutation. On the other hand, we characterize the unique roles of PALI1, a newly identified PRC2-accessory protein, in mediating molecular crosstalk between PRC2 and G9A proteins to catalyze dual H3K27 and H3K9 methylation at target loci. Thus, PALI1 enforces strong repression of differentiation genes, rendering cell stemness and cancer progression. Our findings laid the foundations for the development of several new therapeutic strategies for the treatment of advanced PCa. Citation Format: Jindan Yu. Genomic and epigenomic regulation during prostate cancer progression [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr IA002.
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Jiang, Vivian Changying, Lingzhi Li, Alexa Jordan, et al. "Abstract 3955: Targeting transcription elongation via CDK9 in mantle cell lymphoma patients with dual resistance to BTK inhibition and CAR T therapy." Cancer Research 82, no. 12_Supplement (2022): 3955. http://dx.doi.org/10.1158/1538-7445.am2022-3955.
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Abstract Introduction Clinical relapse following CD19 CAR T therapy after failure to BTK inhibitors (BTKi) is a novel and fast growing medical challenge in treating patients with mantle cell lymphoma (MCL). Thus, developing a novel therapy to overcome this BTKi-CAR T dual resistance (Dual-R) is an urgent need. Our unpublished data revealed MYC targets and cyclin-dependent kinase 9 (CDK9) are highly upregulated in the Dual-R compared to BTKi-R samples. CDK9 is a critical component of the positive transcription elongation factor b (P-TEFb) complex. Its inhibition induces acute decline of short-lived mRNA and proteins, especially MYC and MCL-1, in acute myeloid leukemia and diffuse large B-cell lymphoma. Therefore, we hypothesize that targeting CDK9 may turn off MYC-driven tumor survival and drug resistance. BAY-1251152 is a novel selective CDK9 inhibitor with nanomolar potency. However, whether it has the potential to overcome BTKi-CAR T dual resistance has not been assessed. Methods To validate the correlation of MYC and CDK9 with drug resistance and clinical outcome, we performed whole transcriptomic profiling using primary patient samples. To assess the in vitro efficacy of BAY-1251152, we performed cell viability assay and cell apoptosis assay using MCL cell lines and primary patient samples and followed up with functional studies. furthermore, we assessed its in vivo efficacy using patient-derived xenograft (PDX) models derived from MCL patients including one with Dual-R. Results The expression of MYC oncogene associates with ibrutinib resistance and Dual-R, and poor clinical outcome. CDK9 expression does not correlates with ibrutinib resistance but it does associate with Dual-R and poor clinical outcome in CAR T-relapsed patients. CDK9 inhibition by BAY-1251152 is highly potent in anti-MCL activity in MCL cell lines with low nanomolar range of IC50 (59.6-172.3 nM) by inducing robust cell apoptosis. BAY-1251152 induces dose and time-dependent CDK9 inhibition. A rapid decline of phosphorylation of RNA polymerase II, MYC, MCL-1, and Cyclin D1 can be observed as early as 2 hours. Furthermore, BAY-1251152 (10mg/kg, QW) significantly inhibited tumor growth (p = 0.000003) in a PDX model derived from a Dual-R patient without causing apparent toxicity in NSG mice. In addition, BAY-1251152 also significantly suppressed tumor growth in the PDX models derived from a BTKi-R patient (p=0.00015) and a BTKi-venetoclax dual-resistant patient (p=0.009). Conclusion Our findings showed that targeting CDK9 by its specific inhibitor BAY-1251152 led to potent in vitro anti-MCL activity. BAY-1251152 induces fast CDK9 inhibition and rapid decline of MYC, MCL-1 and Cyclin D1 to induce robust cell death. BAY-1251152 is also potent in inhibiting tumor growth in PDX models. These data support that CDK9 is a promising target to overcome BTKi-CAR T dual resistance in MCL, which is in urgent need. Citation Format: Vivian Changying Jiang, Lingzhi Li, Alexa Jordan, Yu Xue, Fangfang Yan, Joseph McIntosh, Yang Liu, Yuxuan Che, Yijing Li, Qingsong Cai, Angela Leeming, Lukas Simon, Zhongming Zhao, Jia Zhou, Michael Wang. Targeting transcription elongation via CDK9 in mantle cell lymphoma patients with dual resistance to BTK inhibition and CAR T therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3955.
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Moreira, Rita de Cássia Teixeira, Margarete Magalhães Souza, Cláusio Antonio Ferreira de Melo, Abelmon Silva Gesteira, and Gonçalo Santos Silva. "Análises citogenéticas em espécies, cultivares e híbridos do gênero Citrus." Semina: Ciências Biológicas e da Saúde 38, no. 1supl (2018): 92. http://dx.doi.org/10.5433/1679-0367.2017v38n1suplp92.
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O gênero Citrus L. é composto de grande variedade de cultivares e híbridos que em campo podem apresentar características fenotípicas semelhantes, inclusive, entre cultivares poliploides e diploides. O objetivo deste trabalho foi caracterizar cariotípicamente cultivares e híbridos do gênero Citrus através do bandamento CMA3/DAPI, da localização in situ de sequências repetitivas Foram analisadas as espécies C. limon (L.) Burm. F., C. sunki Hort. ex Tanaka, C. volkameriana V. Tem & Pasq., C. latifólia Yu. Tanaka (IAC-05), assim como os híbridos Thaiti-03 e Thaiti-08. O número cromossômico diplóide 2n = 18 foi observado nas espécies C. limon, C. sunki, C. volkameriana e também no híbrido Thaiti-08. No híbrido Thaiti-03, foi identificado 2n = 3x = 27, como também a espécie C. latifólia (IAC-5), triploide (2n=3x= 27), corroborando com análises divulgadas da cultivar. O bandamento CMA3+/DAPI- realizado em C. volkameriana revelou nove cromossomos com um bloco terminal e um cromossomo com dois blocos, bem como um terminal e um pericentromérico. As espécies C. limon e C. sunki, apresentaram nove cromossomos com um bloco terminal e um cromossomo com dois blocos CMA3+/DAPI- terminais. Em C. latifólia foram observados treze cromossomos com blocos terminais e um cromossomo com dois blocos terminais. A análise molecular de alguns dos genótipos por Hibridação in situ Fluorescente (FISH), demonstrou em C. sunki, duas marcas dos sítios 45S e 5S localizadas próximas no mesmo par cromossômico. A espécie C. limon apresentou duas marcas dos sítios 45S e 5S, em que um dos cromossomos apresenta os dois sítios. Na cultivar, triploide, C. latifólia (IAC-05), foram identificados seis sítios 45S e dois sítios 5S. Foram utilizadas sequência para DNA repetitivo de Citrus obtidas do NCBI (National Center for Biotechnology Information) para o desenho de primers no Primer 3 Plus e posterior localização in situ. A hibridação das sequências repetidas não expressas revelou que os as duas sequências investigadas estão co-localizadas no genoma das espécies e híbridos analisados com ao menos quinze sítios para as sondas satélites em C. latifólia e oito sítios em C. limon. O DNA repetitivo não expresso pode ser utilizado como excelente marcador citológico para ploidia e compatibilização cromossômica no melhoramento de Citrus.Agradecimentos: UESC, EMBRAPA e CAPES.
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Zeng, Zhiqiao, Stoyan Bliznakov, Leonard J. Bonville, et al. "(Digital Presentation) Large–Scale High-Performance Low Catalyst Loaded Membrane Electrode Assemblies for Advanced Proton Exchange Membrane Water Electrolyzers." ECS Meeting Abstracts MA2022-01, no. 35 (2022): 1520. http://dx.doi.org/10.1149/ma2022-01351520mtgabs.
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Hydrogen is regarded as the next-generation energy carriers for the future hydrogen economy.1 Among the hydrogen production technologies, proton exchange membrane (PEM) water electrolyzers is considered the favored approach for the implementation of the global hydrogen energy transformation due to its several benefits including high power density operation, low ohmic losses and differential pressure operation. However, (i) high cost mainly from the high platinum group metals (PGM) loading in the catalysts layers; (ii) low durability due to instability of the catalysts layers and membrane; and (iii) poor safety because of hydrogen crossover of PEM water electrolyzers have jeopardized their widespread commercialization. Currently, a new Department of Energy Consortium (H2NEW) has targeted hydrogen production from electrolysis, especially PEM water electrolysis, for use as a clean, sustainable fuel, which can achieve $2/kg hydrogen production cost by 2025.2 This requires a balance between the performance, durability and scale-up cost of membrane electrode assemblies (MEAs) for PEM water electrolyzers. In this work, we demonstrate the capability to fabricate large scale MEAs by the unique Reactive Spray Deposition Technology (RSDT), that have one order of magnitude lower PGM loadings in the catalyst layer than the state-of-the-art (SOA) designs, and activity and durability performance comparable to the SOA commercial MEAs. RSDT is a flame-based method that combines the catalysts synthesis and electrodes deposition processes into one step and thus substantially reduces the time and cost for their fabrication.3–5 The RSDT fabricated MEA with 680 cm2 geometric area electrodes, and loadings of 0.2 mgPt/cm2 in the cathode and 0.3 mgIr/cm2 in the anode has been tested at current density of 1.8 A cm-2, 50 oC, and 400 psi differential hydrogen pressure. The initial steady-state test for over 250 hours, clearly shows excellent activity and stability. In addition, the RSDT fabricated MEA has integrated dual recombination layers that effectively reduce the hydrogen crossover to below 10 %LFL at all current densities from 0.58 to 1.8 A/cm2. Reference 1. M. Carmo, D. L. Fritz, J. Mergel, and D. Stolten, Int. J. Hydrogen Energy, 38, 4901–4934 (2013). 2. https://www.energy.gov/sites/default/files/2021-09/h2-shot-summit-panel1-lte-status.pdf 3. H. Yu et al., Appl. Catal. B Environ., 239, 133–146 (2018) https://doi.org/10.1016/j.apcatb.2018.07.064. 4. H. Yu et al., Electrochim. Acta, 247, 1155–1168 (2017) http://dx.doi.org/10.1016/j.electacta.2017.07.093. 5. G. Mirshekari et al., Int. J. Hydrogen Energy, 46, 1526–1539 (2021) https://doi.org/10.1016/j.ijhydene.2020.10.112.
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Shusse, Yukari, and Kazuhisa Tsuboki. "Dimension Characteristics and Precipitation Efficiency of Cumulonimbus Clouds in the Region Far South from the Mei-Yu Front over the Eastern Asian Continent." Monthly Weather Review 134, no. 7 (2006): 1942–53. http://dx.doi.org/10.1175/mwr3159.1.
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Abstract Dimension characteristics in precipitation properties of cumulonimbus clouds are basic parameters in understanding the vertical transport of water vapor in the atmosphere. In this study, the dimension characteristics and precipitation efficiency of cumulonimbus clouds observed in the Global Energy and Water Cycle Experiment (GEWEX) Asian Monsoon Experiment (GAME) Huaihe River Basin Experiment (HUBEX) are studied using data from X-band Doppler radars and upper-air soundings. The maximum echo area (EAmax) of the cumulonimbus clouds ranged from 0.5 to 470 km2, and the maximum echo top (ETmax) ranged from 2 to 19 km. The total number of cells (TNC) within the cumulonimbus clouds over their lifetime was from 1 to 25. The ETmax, TNC, area time integral (ATI), and total rainfall amount (Rtot) strongly correlate with the EAmax of the cumulonimbus clouds. The cell-averaged ATI (ATIcell = ATI/TNC), maximum rainfall intensity (RImax), and cell-averaged rainfall amount (Rcell = Rtot/TNC) increase when the EAmax is smaller than 100 km2. On the other hand, they are almost constant when the EAmax is larger than 100 km2. The rain productivity of small clouds (&lt;100 km2 in EAmax) increases not only by the increase of the TNC but also by the intensification of cells, while that of large cumulonimbus clouds (&gt;100 km2 in EAmax) increases by the increase of the TNC rather than by the intensification of cells. In the present study, precipitation efficiency (ɛp) is defined as the ratio of the total rainfall amount (Rtot) to the total water vapor amount ingested into the cloud through the cloud base (Vtot). The ɛp was calculated for six clouds whose vertical velocity data at the cloud-base level were deduced by dual-Doppler analysis throughout their lifetime. The ɛp ranged from 0.03% to 9.31% and exhibited a strong positive correlation with the EAmax. This indicates that more than 90% of the water vapor that enters the clouds through the cloud base is consumed to moisten the atmosphere and less than 10% is converted to precipitation and returned to the ground. The cumulonimbus clouds in the region far south from the mei-yu front over the eastern Asian continent efficiently transport water vertically and humidify the upper troposphere.