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1
Grant, Beata. "Thirty Years of Dream-Wandering: Zhang Ruzhao (1900-1969) and the Making of a Buddhist Laywoman." Nan Nü 19, no. 1 (August 4, 2017): 28–63. http://dx.doi.org/10.1163/15685268-00191p02.
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Zhang Ruzhao (1900-69), also known as Zhang Shenghui, was ordained as a Buddhist nun, with the title Tiantai Master Benkong. In early life, Zhang established a reputation as a poet, and was actively engaged in many of the political and feminist movements of the 1920s. Disillusioned both politically and personally, she turned to Buddhism and reinvented herself as China’s premier female lay Buddhist scholar, writer and educator during the 1930s and 40s. From 1949, she took ordination as a Buddhist nun and was officially designated a lineage holder in the Tiantai lineage. She was persecuted severely during the early years of Cultural Revolution, and died in 1969. This study offers a historical overview of the life of this relatively unstudied twentieth-century Buddhist woman, with a special focus on a selection of autobiographical writings published in the early 1930s in which Zhang reflects, in both poetry and prose, on her first three decades of personal and emotional turmoil, and how they contributed to her decision to dedicate the second half of her life to the practice and propagation of Buddhism.
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Rubets, Maria Vladimirovna. "Zhang Dongsun`s epistemological theory." Orientalistica 4, no. 3 (October 12, 2021): 704–19. http://dx.doi.org/10.31696/2618-7043-2021-4-3-704-719.
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The article is a study on Zhang Dongsun’s “theory of epistemological pluralism” based on his book called “The Theory of Knowledge” (认识论). Zhang Dongsun was one of the first Chinese philosophers of the 20th century to create a holistic epistemological theory, and also one of the first intercultural philosophers. In the Russian scholarly literature, Zhang Dongsun’s “theory of epistemological pluralism” is under-researched. The article aims to give a detailed account of the epistemological theory of Zhang Dongsun as comes from his book “The Theory of Knowledge”. The article, which uses comparative and systematic approaches is also supported by a significant number of specialist works written both by Russian and foreign scholars. The author outlines the Zhang Dongsun theory regarding epistemological pluralism and his views on cosmology and the evolution theory. Equally, she presents the Zhang Dongsun views on the impact of culture on the phenomenon of knowledge. The author also considers the Western philosophical categories, which could have influenced the formation of Zhang Dongsun’s theory of epistemological pluralism.
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Moshchenko, Irina A. "The concept of “love” in the early works of Zhang Ailing (张爱玲 1920–1995)." Philological Sciences. Scientific Essays of Higher Education, no. 3 (May 2021): 59–67. http://dx.doi.org/10.20339/phs.3-21.059.
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This article presents a study designed to analyse the concept of love in the early work of chinese writer Zhang Ailing. The research reveals conceptual binary oppositions which are formed arround the core of the concept of love that is: ai (爱), qing (情) and lian (恋). The oppositions are the following: absurdity — conciseness; frivolous / pretense — serious / sincerity; material — spiritual / sacred; isolation — openness; selfishness — generosity; cowardice — courage; overseas — traditional. This ambiguity of the concept is the key to understanding how early works of Zhang Ailing differs from the previous literature tradition, which understands love as а supreme good. The research shows the transformation of the concept of love in the early work of Zhang Ailing. The writer confronts the tradition, she tries to destroy the romantic-sentimental attitude to love that was formed in Chinese literature in the first decades of the twentieth century. Breaking with the conventional image of “love above all” (恋爱之上), Zhang Ailing begins to build up her own world of love. She starts from the denying of romantic love and attachment, and only then tries to fit love into the social structure, to turn ordinary love into a social value equal to success in work, financial well-being, etc.
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Agenosov, Vladimir V. "Chinese associates of Y. Zamyatin: Zhang Tianyi and Lao She." Neophilology, no. 4 (2022): 759–71. http://dx.doi.org/10.20310/2587-6953-2022-8-4-759-771.
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We explore the dystopian novels of the 1930s by Chinese novelists Zhang Tianyi “Ghostland Diary” (1931) and Lao She “Cat Country” (1932). We give brief information about the specifics of the work of Chinese writers who are not known to a wide range of modern domestic readers and literary critics. We reveal the typological proximity of these works to the dystopian novel by Y.I. Zamyatin “We”. We identify the literary predecessors of the analyzed novels, the connection with the works of Russian, Chinese, and world literature. We note the role of criticism in the fate of authors and their creations. We designate traditional and innovative genre and style features of books. We analyze in detail the plot-compositional structure, figurative system, and ideological content of the novels. We consider an ironic description of various spheres of life: the party system, elections, the education system, wars, and the creative activity of decadent poets. The features of narration associated with the artistic functions of narrators are studied in detail. The synthetic nature of the novels, combining elements of several literary genres, is noted. We reveal that the form of hyperbolic generalization of modern realities, elements of satire and irony in the depiction of society gave the works a timeless and extraspatial character, taking them beyond the limits of Chinese reality. We form an idea of the genre-typological community of Zhang Tianyi and Lao She’s warning novels, exposing myths about the ideal society of the 20th century.
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Wang, Wenrong. "The Transformation of Chinese Women’s Identity in Hollywood Films—The Role of Zhang Ziyi as an Example." Art and Society 2, no. 1 (February 2023): 1–6. http://dx.doi.org/10.56397/as.2023.02.01.
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This article examines and compares Zhang Ziyi’s star identity and image in China and the West by using several films in which she acted that enjoyed fame on the international stage, such as Crouching Tiger, Hidden Dragon and Memoirs of a Geisha, as case studies. The evolution of her Asian female identity in American cinema is further analyzed by combing through her career development in Hollywood. At the same time, it is useful to describe her as a symbol of the Asian consumer market by examining how her cosmopolitan identity, described as a “modern woman”, is represented in advertisements or magazines for brands she represents. This paper seeks to reveal the development of Chinese female identity as revealed by the character of Zhang in Hollywood films. It finds that Zhang has shaped the Western perception of Chinese female immigrants with her outstanding performance through comparing her perceptions in the West and China. Moreover, her remarkable influence and identity symbol promote the localization of overseas brands in Asian markets.
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Lambert, Thomas E. "Short-Term Versus Long-Term Effects of the Louisville Enterprise Zone Incentives: A Response to Sumei Zhang." Economic Development Quarterly 34, no. 3 (June 6, 2020): 294–98. http://dx.doi.org/10.1177/0891242420929422.
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Zhang wrote that the Louisville enterprise zone (EZ) was more successful than what previous research showed and that variations in research design have led to conflicting or mixed reviews of many local economic development policies that are based on the EZ concept. She mentions a study and an article on the Louisville, Kentucky EZ and implies the time horizon used to evaluate it was too short. This Forum/Letter to the Editor points out that the Louisville EZ went through multiple transformations and expansions over its history from 1983 to 2003, and as noted in the first of two studies, the original zone showed virtually no progress from 1983 to 1990. Several other unpublished papers pointed out the same results when the original EZ and other parts of the expanded EZ were analyzed up to the last years of the 20th century. Finally, this Forum/Letter to the Editor argues that and provides reasons for the methodology employed by Lambert and Coomes as a superior way of analyzing the Louisville EZ when compared with the methods employed by Zhang. The main reason why Zhang showed success in the EZ is because she mostly evaluates it in its final form in the late 1990s after it had annexed many sections of Jefferson County, which were not as nearly economically disadvantaged as the original Louisville EZ established in 1983.
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Chang, Eileen. "Chinese Translation: A Vehicle of Cultural Influence." PMLA/Publications of the Modern Language Association of America 130, no. 2 (March 2015): 488–99. http://dx.doi.org/10.1632/pmla.2015.130.2.488.
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Translation played a central role in the life of Eileen Chang (Zhang Ailing, 1920-95). One of the most iconic figures in twentieth-century Chinese literature, Chang also wrote extensively in English throughout her career, which began in the early 1940s in Japanese-occupied Shanghai. She achieved fame quickly but fell into obscurity after the war ended in 1945. Chang stayed in Shanghai through the 1949 Communist revolution and in 1952 moved to Hong Kong, where she worked as a freelance translator and writer for the United States Information Service and wrote two anti-Communist novels in English and Chinese, The Rice-Sprout Song (1955) and Naked Earth (1956).
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Zhang, Ying. "Religion and Prison Art in Ming China (1368–1644)." Brill Research Perspectives in Religion and the Arts 3, no. 3 (April 23, 2020): 1–102. http://dx.doi.org/10.1163/24688878-12340009.
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Abstract Approaching the prison as a creative environment and imprisoned officials as creative subjects in Ming China (1368–1644), Ying Zhang introduces a few important themes at the intersection of premodern Chinese religion, poetry, and visual and material culture. The Ming is known for its extraordinary cultural and economic accomplishments in the increasingly globalized early modern world. For scholars of Chinese religion and art, this era crystallizes the essential and enduring characteristics in these two spheres. Drawing on scholarship on Chinese philosophy, religion, aesthetics, poetry, music, and visual and material culture, Zhang illustrates how the prisoners understood their environment as creative and engaged it creatively. She then offers a literature survey on the characteristics of premodern Chinese religion and art that helps situate the questions of “creative environment” and “creative subject” within multiple fields of scholarship.
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SHEN, David Ta-Chun. "PF Merger would Do, too: A Reply to Zhang (1997)." Acta Linguistica Asiatica 1, no. 2 (October 20, 2011): 9–24. http://dx.doi.org/10.4312/ala.1.2.9-24.
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The analysis for the phenomenon that prepositions may or may not undergo the third tone sandhi in Mandarin in Zhang (1997) is reviewed. She considers that this phenomenon is short of sound coverage and couches her analysis in the framework of Optimality Theory (OT). However, upon scrutiny, Zhang’s analysis invites unnecessary questions. The postulation of two “constituent strength” constraints is with no foundation. It is difficult to grab the idea behind the constituent-strength concept even till now. Related to the concept, the non-specification of a prepositional phrase is not clear. Instead, the syntactic feature manifestation could mark a preposition’s uniqueness. In addition, the misuse of the Generalized Alignment and stipulations toward the evaluations in OT are spotted, too. My synthetic approach, based on the extant and developing knowledge about constituency, PF merger, and Shih’s (1997) foot formation, shows that for this phenomenon, no new device is needed.
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Yetty, Yetty, and Rosemary Rosemary. "Analysis Zhang Ailing’s Novel (Red Rose And White Rose) Image Of The Characters And Story Plot." Lingua Cultura 5, no. 1 (May 31, 2011): 47. http://dx.doi.org/10.21512/lc.v5i1.374.
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Zhang Ailing is a heterogeneous novel writer in China literature’s history. Almost of her life, she already wrote so many literature’s works. One of her famous novel is (Red Rose and White Rose). The story is describe the image of main figure’s character and his emotional. Writer wants use the characterization, complexity of personality and story plot these three aspect to analysis the novel’s figure looks, figure character and the story. This novel story is a complication relationship between the man and two women, red roses as her lover and white rose as her wife. About a man that in his standard life and emotional condition occur some contradiction. Writer use reference material and theory of novel writing to analysis Zhang Ailing (Red Rose and White Rose)‘s novel. The result of this analisys are the most important part in novel’s story is not only about the story plot but also the describtion of figure looks and characterization. Zhang Ailing in (Red rose and white rose) descbribtion is very spesific, the story become so interesting because of the Complementary of the figure looks, figure characterization and story plot, embraced each other, fully reflects the fictional reality of compromise and frustration.
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Yang, Chen. "On the "Return" and "No Return"." International Journal of Education and Humanities 3, no. 2 (June 24, 2022): 1–3. http://dx.doi.org/10.54097/ijeh.v3i2.595.
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The movie "Return" is based on Yan Geling's novel "Lu Gang Yan Zhi" by director Zhang Yimou. It tells the love story between the hero and heroine in an ordinary family in the context of the "Cultural Revolution" period. Most of the colors used in the whole film are black, white and gray as the base, and the overall atmosphere is dark and depressing. The film is based on the heroine Feng Wanyu waiting for the return of her husband Lu Yanzhi without hindrance as a clue, but in the end, Jun Yi returns without knowing it, and until the end of the film, she is also in an infinite waiting to return. Throughout the film, director Zhang Yimou shows us the "return" of different people, but under the "return" of these characters, it is hidden that the "non-return" of the ordinary public's spiritual and spiritual trauma in the context of the times is hidden.
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Xiao, Jiwei. "Can She Say No to Zhang Ailing? Detail, idealism and woman in Wang Anyi's fiction." Journal of Contemporary China 17, no. 56 (June 19, 2008): 513–28. http://dx.doi.org/10.1080/10670560802000308.
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SMITH, NORMAN. "‘Only Women can Change this World into Heaven’ Mei Niang, Male Chauvinist Society, and the Japanese Cultural Agenda in North China, 1939–1941." Modern Asian Studies 40, no. 1 (February 2006): 81–107. http://dx.doi.org/10.1017/s0026749x06001831.
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From 1939 to 1941, Mei Niang (b. 1920) penned three of her most famous novellas, Bang (Clam)(1939), Yu (Fish)(1941), and Xie (Crabs)(1941). Each of these works sheds light on the struggle of Chinese feminists in Japanese-occupied north China to realize ideals that stood in stark contrast to the conservative constructs of ‘good wives, wise mothers’ (xianqi liangmu) favoured by colonial officials. The contemporary appeal of Mei Niang's work is attested to by a catch-phrase, coined in 1942, that linked her with one of the most celebrated Chinese women writers of the twentieth century, Zhang Ailing (1920–1995): ‘the south has Zhang Ailing, the north has Mei Niang’ (Nan Ling, Bei Mei). Both women attained great fame in Japanese-occupied territories, only to have their achievements tempered by condemnation of the environments in which they forged their early careers. The Chinese civil war that followed the collapse of the Japanese empire propelled the two writers along divergent trajectories: Zhang Ailing moved to Hong Kong and the United States, where she achieved iconic status, while Mei Niang remained in the People's Republic of China, to be vilified. As one of the pre-eminent ‘writers of the enemy occupation’ (lunxian zuojia), Mei Niang was persecuted by a Maoist regime (1949–1976) dedicated to the refutation of the Japanese colonial order in its entirety.
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Milburn, Olivia. "Spring Colors in the Han Palace: A Late Qing Reappraisal of the Life of Empress Zhang (202-163 BCE)." NAN NÜ 24, no. 1 (June 9, 2022): 70–94. http://dx.doi.org/10.1163/15685268-02410037.
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Abstract At the very end of the Qing dynasty, Xue Fucheng (1838-1894) and his circle produced a series of writings about empresses and imperial consorts of previous dynasties, in which they constructed a sympathetic discourse about elite women who had suffered exploitation and abuse. This paper analyzes a single text, Spring Colors in the Han Palace (Hangong chunse), and argues that this collection of short stories was written to explore new perspectives on the life of Empress Zhang (202-163 BCE) and reconfigure her as a symbol of patriarchal oppression. The empress is described as a paragon of virtue, who has fully internalized traditional Confucian models of how a woman should behave; a process which has left her so mentally and emotionally crippled that she is unable to deal with the challenges she faces during her lifetime. In these tales, Empress Zhang’s biography is reappraised in the light of late Qing progressive discourses about social norms, as well as tackling such controversial issues as women’s chastity and footbinding.
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Tan, Mei Ah. "Decoding the Ambiguous Narrative Voice in the “Tale of Yingying”: Ritual Propriety as Key." NAN Nü 21, no. 1 (June 25, 2019): 38–75. http://dx.doi.org/10.1163/15685268-00211p02.
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Abstract Yuan Zhen’s “Tale of Yingying” has long been known for its ambiguous narrative voice. This article argues that what we perceive as a conflict in the narrative voice, did not exist for readers of the Tang dynasty (618-907). The tale was composed to emphasize the essential nature of ritual propriety for both men and women; both the male protagonist Zhang and the female character Yingying are targets of criticism. Unearthing the resonances and allusions of the discourse, and analyzing the social and political background of the mid-Tang, this study proposes that the tale may be read at two levels, using ritual propriety as key. From the literary point of view, this tale presents a regrettable love story, one that does not yield its fruit, due to the tide of passion – passion is the crucial element in romance, but in the end, it is also passion that drives the two lovers apart. From the didactic point of view, the author condemns Yingying not in self-justification, as those who support the autobiographical reading often presume, but because she is a fallen woman and a potentially dangerous femme fatale. Zhang is ridiculed for initiating the ritual transgression, and in failing to behave as a junzi (gentleman). This tale is an educational inquiry into self-cultivation and politics. By incorporating two points of view, that of Zhang and that of Yingying, the tale provokes reflection on the nature of romance and its possible effects on men and women, and ultimately, the indispensability of propriety.
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Wang, Lingzhen. "Zhang Nuanxin and Social Commitment in 1980s Chinese Women’s Experimental Cinema." Camera Obscura: Feminism, Culture, and Media Studies 34, no. 3 (December 1, 2019): 1–29. http://dx.doi.org/10.1215/02705346-7772363.
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In December 1978, the Chinese government formally laid out its economic reform policy, thereby marking the beginning of a new post-Mao era. As economic reform deepened around the mid-1980s, the state began to openly retreat from its former socialist commitments—including the institutionalized practice of class and gender equality—and new mainstream discourses began to endorse a universal modernity, disregarding sociopolitical consequences of the market. Zhang Nuanxin (张暖忻, 1941–95) emerged as a pioneer in both the theory and practice of early post-Mao new experimental cinema, but she was dismissed as nonessential to the advancement of post-Mao new cinema in the late 1980s. Post-Mao feminist film scholars have since expressed their disappointment with Zhang’s films due to their incomplete break from the socialist mainstream cinema of the Mao era. This article closely studies Zhang’s most representative film, Sacrificed Youth (青春祭, 1985), exploring its complicated negotiation with the socialist legacy and new post-Mao discourses. With a highly subjective and documentary experimental style, the film articulates a double critique of political and cultural uniformity during the Cultural Revolution (1966–76) and the socially detached and universal individualism, naturalized sexual difference, and essentialized female consciousness newly mainstreamed around the mid-1980s in China. The article argues that the dismissal of Zhang toward the end of the 1980s reveals both the transformation of Chinese culture into a depoliticized and male-centered masculine practice and Zhang’s insistence on sociopolitically engaged filmmaking as China moved toward a market economy.
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Ehrlich, Melanie. "Risks and rewards of big-data in epigenomics research: an interview with Melanie Ehrlich." Epigenomics 14, no. 6 (March 2022): 351–58. http://dx.doi.org/10.2217/epi-2022-0056.
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Melanie Ehrlich, PhD, is a professor in the Tulane Cancer Center, the Tulane Center for Medical Bioinformatics and Genomics and the Hayward Human Genetics Program at Tulane Medical School, New Orleans, LA. She obtained her PhD in molecular biology in 1971 from the State University of New York at Stony Brook and completed postdoctoral research at Albert Einstein College of Medicine in 1972. She has been working on various aspects of epigenetics, starting with DNA methylation, since 1973. Her group made many first findings about DNA methylation (see below). For example, in 1982 and 1983, in collaboration with Charles Gehrke at the University of Missouri, she was the first to report tissue-specific and cancer-specific differences in overall DNA methylation in humans. In 1985, Xian-Yang Zhang and Richard Wang in her lab discovered a class of human DNA sequences specifically hypomethylated in sperm. In 1998, her group was the first to describe extensive losses of DNA methylation in pericentromeric and centromeric DNA repeats in human cancer. Her lab's many publications on the prevalence of both DNA hypermethylation and hypomethylation in the same cancers brought needed balance to our understanding of the epigenetics of cancer and to its clinical implications [ 1 ]. Besides working on cancer epigenetics, her research group has helped elucidate cytogenetic and gene expression abnormalities in the immunodeficiency, centromeric and facial anomalies (ICF) syndrome, a rare recessive disease often caused by mutations in DNMT3B. Her group also studied the epigenetics and transcriptomics of facioscapulohumeral muscular dystrophy (FSHD), whose disease locus is a tandem 3.3-kb repeat at subtelomeric 4q (that happens to be hypomethylated in ICF DNA [ 2 ]). Her study of FSHD has taken her in the direction of muscle (skeletal muscle, heart and aorta) epigenetics [ 3–6 ]. Recently, she has led research that applies epigenetics much more rigorously than usual to the evaluation of genetic variants from genome-wide association studies (GWAS) of osteoporosis and obesity. In continued collaboration with Sriharsa Pradhan at New England Biolabs and Michelle Lacey at Tulane University, she has compared 5-hydroxymethylcytosine and 5-methylcytosine clustering in various human tissues [ 7 ] and is studying myoblast methylomes that they generated by a new high-resolution enzymatic technique (enzymatic methyl-seq).
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Ball, E., D. Okane, C. Mccourt, M. Mccarron, and C. Riddell. "AB0767 SEVERE BREAST ULCERATION IN BEHÇET’S DISEASE TREATED WITH CYCLOPHOSPHAMIDE: A CASE REPORT." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 1410.1–1410. http://dx.doi.org/10.1136/annrheumdis-2021-eular.1639.
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Background:Behcet’s disease is a systemic autoimmune vasculitis that typically involves mucocutaneous surfaces, the eyes and the skin with varying manifestations. Skin ulceration often secondary to pathergy is a common feature.Objectives:To raise awareness of breast ulceration as a clinical manifestation in Behcet’s disease.Methods:We report a case of complex Bechet’s disease associated with severe refractory breast ulceration successfully treated with cyclophosphamide.Results:A 27 year old female patient presented to the rheumatology department with a non-healing lesion on her face secondary to a cat scratch. She reported previous episodes of ulceration usually as a result of minor trauma such as IV cannulation, as well as a two year history of severe oral and genital ulceration. She had also been diagnosed with ‘colitis’ requiring iliocaecal resection two years prior to presentation. Previous treatments for her bowel included azathioprine, infliximab, adalimumab and vedolizumab. Over the next three years she developed recurrent eye involvement in the form of scleritis with ongoing oral and genital ulceration. Further treatment under our care included ustekinumab, entanercept, benepali, certolizumab and tacrolimus with background prednisolone. She then developed a small area of broken skin on her left breast which continued to extend and ulcerate despite treatment with IV steroids. Tissue biopsy showed deep focal vasculitis with intravascular thrombi. Anticoagulation was commenced and she was treated with tocilizumab IV for 3 months with no clinical improvement. Involvement extended to include 80 percent of the breast surface and the nipple self-amputated. Due to the severity and extent of the ulceration which was extremely painful and distressing, she was given 3 months of IV cyclophosphamide at a dose of 15mg/kg every 2-3 weeks. The ulceration showed rapid clinical improvement (see Figure 1).Figure 1.Breast ulceration before and after 3 months of cyclophosphamide treatmentConclusion:Involvement of the breast in systemic vasculitides (such as GPA or PAN) has been reported, although usually manifesting as a palpable mass with diagnosis on biopsy 1. Similar presentations in Behcet’s disease have been recognised 2, although much less commonly. Our case demonstrates that severe breast ulceration can be a clinical manifestation of this condition and can be refractory to usual therapies.References:[1]Ren J, Liu J, Su J, Zhang J, Zhao J. Systemic vasculitis involving the breast: a case report and literature review. Rheumatol Int. 2019 Aug;39(8):1447-1455[2]Soleto MJ, Marcos L. Behçet’s disease involving the breast. Eur Radiol. 2002 Dec;12 Suppl 3:S98-S100. doi: 10.1007/s00330-002-1420-4.Disclosure of Interests:None declared
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Lim, Jonea, Katherine O’neal, Jeffrey Henderson, and Joanne Skaggs. "ODP227 Nivolumab Induced Type 1 Diabetes." Journal of the Endocrine Society 6, Supplement_1 (November 1, 2022): A327. http://dx.doi.org/10.1210/jendso/bvac150.678.
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Abstract Introduction Nivolumab is a treatment option used for renal cell carcinoma (RCC). It is reported to have high response rate to renal cancer cells with rare adverse events to the endocrine system including type 1 diabetes mellitus (DM1). Our case reports the use of nivolumab and ipilimumab in a patient with RCC with timeline of hyperglycemia following initiation of the regimen. Clinical Case A 71-year-old woman with RCC metastasized to the lungs experienced adverse effects leading discontinued sunitinib therapy. Her imaging showed increased pulmonary nodules with tumor extension into left superior and inferior pulmonary veins. Therapy with Ipilimumab 56 mg plus nivolumab 169 mg initiated shortly. Pre-treatment labs were within normal limits. Labs remained within normal limits (plasma glucose 82 mg/dL) before second treatment. Less than a week following 2 nd treatment, she presented with generalized rash and was sent to the emergency room (ER). She was treated with one dose IV and a course of PO steroids for total 5 days. Infusions were put on hold. Despite rash resolving, she continued to have low-grade fever (99.1°F). She also reported 10 lbs. weight loss and polydipsia. Three weeks follow-up lab noted plasma glucose level of 559 mg/dL. She was instructed to go to the ER. ER labs: HbA1c: 9.1%,, plasma glucose 525 mg/dL, B-hydroxybutyrate 10.47 mmol/L; UA 3+ glucose; 2+ ketones. She met criteria for diabetes ketoacidosis (DKA). She was admitted, started and later discharged on insulin therapy with referral to see outpatient diabetes providers. Labs obtained during outpatient follow up include: C-peptide 0.3 ng/ml & paired plasma glucose of 246 mg/dl. Nivolumab monotherapy re-initiated later. With insulin therapy, HbA1c improved with most recent HbA1c at 7.7%. Clinical Lesson: There is evidence of anti-PD-1-monoclonal-antibody-induced diabetes mellitus throughreduced activity of PD-1 which is common to both traditional onset type 1 diabetes or antiPD-1 therapy-related diabetes. PD-1 reduction may cause inappropriate activation of T cells causing autoimmune response against pancreatic beta cells. Clotman et al reports 42 cases of PD-1 inhibitor–induced DM1. Half of tested case subjects (22/39 or 56%) had detectable diabetes-related autoantibodies; however, no clear pattern of diabetes-related autoantibodies. Additionally, median interval from immunotherapy initiation to diagnosis of diabetes was 5 weeks in GADA-positive subjects vs 9 weeks in GADA negative subjects. Li Zhang et al reports 735 cases of immune checkpoint inhibitors (ICI) DM: 25% presented fulminant DM1; 45% presented in DKA. Of these, 25% had severe case and 5.5% resulted in deaths. Because immunotherapy use will continue to increase, raising awareness of ICI DM induced by anti–PD-1 therapy is essential. Although incident is rare, missing or delaying diagnosis can not only significantly impact a patient's life but be potentially life-threatening. Presentation: No date and time listed
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Pimentel, G., A. Cruz, M. Loureiro, S. Fernandes, C. Baixinho, and A. Marques. "AB1565-HPR REHABILITATION NURSES KNOWLEDGE ABOUT OSTEOPOROSIS AND FRAGILITY FRACTURES IN PORTUGAL." Annals of the Rheumatic Diseases 81, Suppl 1 (May 23, 2022): 1882.1–1882. http://dx.doi.org/10.1136/annrheumdis-2022-eular.3205.
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BackgroundScientific evidence reveals gaps in health professionals’ knowledge about osteoporosis and fragility fractures, which impairs and influences the quality of care, namely in preventive actions.ObjectivesTo analyse knowledge of Rehabilitation Nurses about osteoporosis and fragility fractures to identify training needs of Rehabilitation Nurses.MethodsA cross-sectional study, integrated in a larger project, using an adapted questionnaire, made available online and disseminated by mailing list of “Ordem dos Enfermeiros” (Royal Colleague of Nursings) to all Portuguese Rehabilitation Nurses.ResultsThere were include 452 participants(10.3% of the 4 397 Rehabilitation Nurses), 17% perform functions in orthopaedics and traumatology service, 4.5% physical medicine and rehabilitation and 78.6% in other services, majority, 74.6% women. On average, 69.6% correct answers were identified regarding osteoporosis and fragility fractures. Results reveal that the main areas of knowledge deficit, in this study, are related to the concept and epidemiology of osteoporosis and fragility fractures and about the most appropriate diet. Nurses with higher academic degree (master’s degree) revealed more knowledge (p=0.01).ConclusionThis study reveals that the knowledge about osteoporosis and fragility fractures is low (<70% correct answers), thus there is an opportunity to improve the knowledge related to osteoporosis and fragility fractures among Specialist Nurses in Rehabilitation Nursing.References[1]Peng, L., Reynolds, N., He, A., Liu, M., Yang, J., She, P., & Zhang, Y. (2020). Osteoporosis knowledge and related factors among orthopedic nurses in Hunan province of China. International journal of orthopaedic and trauma nursing, 36, 100714. https://doi.org/10.1016/j.ijotn.2019.100714Disclosure of InterestsNone declared
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Nokhbehzaeim, Mahrokh, Lloyd Panjirkaran, and Terri Washington. "Rituximab as an Alternative Treatment for Refractory Granulomatous Hypophysitis." Journal of the Endocrine Society 5, Supplement_1 (May 1, 2021): A608. http://dx.doi.org/10.1210/jendso/bvab048.1239.
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Abstract Background: Although glucocorticoids have been adopted as the main stay treatment for granulomatous hypophysitis, refractory cases have been treated by infliximab with success in multiple reported case.[1,2,3] Given the low prevalence, incidence of granulomatous hypophysitis[4] and the advent of biologics, evidence of rituximab’s efficacy are largely based on a handful of case reports[1,2,3] and needs more evidence to label its utility. We describe a case of recurrent primary granulomatous hypophysitis in a 48-year-old female who had significant treatment challenge until there was good response after initiation of rituximab. Clinical Case: Patient was a known case of granulomatous hypophysitis and had undergone total hypophysectomy. Despite this approximately a year after her surgery she had become symptomatic and had MRI changes. She was started on a succession of immunosuppressive agents and high dose steroids to control recurrent symptoms. Due to treatment failure and very high steroid dose, patient was eventually started on Rituximab and patient had significant improvement of her symptoms as well as resolution of the MRI changes. Conclusion: Although there is a lack of prospective, double blind and controlled studies this case study highlights the utility of Rituximab as a potent alternative treatment for refractory given the adverse effect associated with the steroids and other immunosuppressive agents. Reference statement: 1. Schreckinger M, Francis T, Rajah G, Jagannathan J, Guthikonda M, Mittal S. Novel strategy to treat a case of recurrent lymphocytic hypophysitis using rituximab. J Neurosurg. 2012 Jun;116(6):1318-23. doi: 10.3171/2012.2.JNS111456. Epub 2012 Mar 23. PMID: 22443503. 2. Xu C, Ricciuti A, Caturegli P, Keene CD, Kargi AY. Autoimmune lymphocytic hypophysitis in association with autoimmune eye disease and sequential treatment with infliximab and rituximab. Pituitary. 2015 Aug;18(4):441-7. doi: 10.1007/s11102-014-0592-7. PMID: 25224140. 3. Gu WJ, Zhang Q, Zhu J, Li J, Wei SH, Mu YM. Rituximab was used to treat recurrent IgG4-related hypophysitis with ophthalmopathy as the initial presentation: A case report and literature review. Medicine (Baltimore). 2017 Jun;96(24):e6934. doi: 10.1097/MD.0000000000006934. PMID: 28614220; PMCID: PMC5478305. 4. Angelousi A, Alexandraki K, Tsoli M, Kaltsas G, Kassi E. Hypophysitis (Including IgG4 and Immunotherapy). Neuroendocrinology. 2020;110(9-10):822-835. doi: 10.1159/000506903. Epub 2020 Mar 4. PMID: 32126548
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Fahmi, A. "New approach to quantum key distribution via quantum encryption." Quantum Information and Computation 9, no. 9&10 (September 2009): 879–98. http://dx.doi.org/10.26421/qic9.9-10-9.
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Recently, Zhang, Li and Guo (ZLG) suggested a new approach to quantum key distribution by using a shared Bell state which acts as quantum key in order to encode and decode classical information. Subsequently, others extended ZLG protocol to d-dimensional systems and to quantum secret sharing based on reusable GHZ states. However, Gao et al. have shown that if Eve employs a special strategy to attack, these protocols become insecure. Afterwards, they repair ZLG protocol so that their eavesdropping strategy becomes inefficient. In this paper, we investigate the security of ZLG quantum key distribution protocol and show that it is not secure against Eve's attacks and with probability of one half she gets all of the keys without being detected by the two parties. In this eavesdropping strategy, Eve transforms the previously shared Bell state between Alice and Bob to two Bell states among herself and the parties. Moreover, we briefly show that ZLG's repairing by Gao et al's is not efficient against of our attack and Eve can choose an appropriate rotation angle and measurement bases which help her to do eavesdropping. Afterwards, we discuss generalization of ZLG protocol to d-dimensional systems and show that with probability 1/d, Eve gets all of keys. We show that quantum secret sharing based on reusable GHZ states is also not secure and with probability one half, Eve gets all of keys. We repair them by going to higher dimensional shared EPR or GHZ states. Finally, we compare ZLG protocol with ours and show that the ZLG protocol and its extensions are less robust against the channel noise with respect to ours.
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Loganathan, Archana, Govinda Ghimire, Dambar Hamal, Osama Awadallah, and Bilal El-Zahab. "Metal Sulfide Artificial Solid-Electrolyte Interface for Improved Lithium Anode Stability." ECS Meeting Abstracts MA2022-02, no. 2 (October 9, 2022): 162. http://dx.doi.org/10.1149/ma2022-022162mtgabs.
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In the last decade, lithium metal has burgeoned into a potential anode material from Li-ion battery to next generation battery systems because of the low redox potential (-3.040 V vs SHE.) and high gravimetric energy density [1-3]. Unlike conventional batteries, the major challenges to be addressed in lithium metal anodes are the dendritic growth, continuous lithium depletion, rapid capacity loss and low Columbic efficiency [4]. These challenges can be averted using electrolyte additives or creating artificial solid electrolyte (SEI) interphases [5]. In the present work, nanostructured transition metal sulfide (MS) and lithium transition metal sulfide (LMS) are used as artificial SEI on lithium metal anode by modifying the lithium metal/electrolyte interfaces and homogenous lithium deposition. The nanostructured transition metal sulfide and lithium transition metal sulfide were synthesized by a simple wet chemical route at relatively low temperatures (150-200 °C). The synthesized LMS were typically of high purity and were filtered, washed, ball-milled, and calcined prior to use in the battery. The microstructure, structure and chemical analysis of the synthesized metal sulfide was characterized by scanning electron microscope (SEM), X-ray diffraction (XRD), energy-dispersive X-ray spectroscopy (EDS) and X-ray photoelectron spectroscopy (XPS). Figure 1(a) shows the morphology of the ball-milled LMS as a layered structure with varying sizes of 10 µm to 100 nm. The EDS analysis of the ball-milled powder majorly showed an M/S ratio of 1:1 and 1:2. The LSM was deposited on Li metal substrate by sputtering technique from a LSM target in Ar atmosphere. This film deposition was carried out at different sputtering time (10 sec -100 sec) and processing pressures. Homogeneous deposition of this LSM of few tens of nanometers thickness was successfully achieved. The electrochemical performance of the LSM artificial SEI was investigated in symmetric cells of two coated Li electrodes and compared to bare Li (Figure 1(b)). At different current densities of 0.5 and 1 mA/cm2, repeated Li plating and stripping revealed an enhanced cycling performance of metal sulfide coated Li compared to bare Li electrode. To better understand the interfacial stability, electrochemical impedance spectroscopy (EIS) studies were performed at different stages of cycling. The cycling performance of coated and bare Li anode was performed in a full cell containing NMC811 as cathode. After cycling, the microstructural changes in lithium metal anode were explored using SEM. Figure 1: (a) SEM image of the ball-milled layered lithium metal sulfide and (b) Time-voltage profiles of the symmetric cells with Li anode and coated Li anode at the current density of 0.5 mA/cm2 References [1] D. Lin, Y. Liu, Y.Cui, “Reviving the Lithium Metal Anode for High-Energy Batteries”, Nature Nanotechnology, 12 (2017), 194-206. [2] D. Aurbach, B.D. McCloskey, L.F. Nazar, P.G. Bruce, “Advances in Understanding the Mechanisms Underpinning Lithium-air Batteries”, Nature Energy, 1 (2016) 16128. [3] W. Xu, J. Wang, F. Ding, X.Chen, E. Nasybulin, Y. Zhang, J.G. Zhang, “Lithium metal Anodes for Rechargeable Batteries”, Energy and Environmental Science, 7 (2014) 513-537. [4]J. Liu, Z. Bao, Y. Cui, E.J. Dufek, J.B. Goodenough, P. Khalifah, Q. Li, B.Y. Liaw, P. Liu, A. Manthiram, Y.S. Meng, V.R. Subramanian, M.F. Toney, V.V. Viswanathan, M.S. Whittingham, J. Xia, W. Xu, J. Yang, X.Q. Yang, J.G. Zhang, "Pathways for Practical High-Energy Long Cycling Lithium Metal Batteries", Nature Energy, 4 (2019) 180-186. [5] K Kim, M. Balaish, M. Wadaguchi, L. Kong, J. Rupp, “Solid State Batteries: Solid-State Li-metal Batteries: Challenges and Horizons of Oxide and Sulfide Solid Electrolytes and their Interfaces”, Advanced Energy Materials, 11 (2021) 2170002 Figure 1
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Ip Lau, Regina Suk-yee. "The challenges facing the next Chief Executive of Hong Kong in 2022: managing growth, conflict, change and continuity." Public Administration and Policy 24, no. 2 (August 10, 2021): 117–24. http://dx.doi.org/10.1108/pap-07-2021-0037.
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PurposeThis article outlines the challenges faced by the next Chief Executive of the Hong Kong Special Administrative Region (HKSAR) in 2022 – the need to address economic problems resulting from Hong Kong’s slow growth; its inability to restructure its economy to broaden job opportunities and improve upward mobility for young people; and the government’s belated attempt to deploy innovation and technology.Design/methodology/approachThis article is based on the author’s in-depth analysis of the current situation and insights on the challenges faced by the next Chief Executive.FindingsTensions are inherent in the concept of “One Country, Two Systems”. Back in November 2012, Deputy Director of the Hong Kong and Macao Office Zhang Xiaoming already reminded Hong Kong of the need to manage well three sets of relationships: (1) maintaining the “One Country” principle while preserving the SARs’ “separate systems”; (2) upholding Central Authority while preserving the SARs’ “high degree of autonomy”; and (3) unleashing the economic potential of mainland China while raising the competitiveness of the SARs. These three sets of relationships represent three fundamental difficulties in implementing “One Country, Two Systems”. However, Hong Kong kept ignoring Beijing’s advice and failed to resolve the tension between the mainland and Hong Kong SAR, culminating in the riotous events of 2019, which morphed into a dangerous, anti-China insurgency.Originality/valueThe next Chief Executive needs to mediate between the constitutional requirements of the Central Authority while preserving Hong Kong SAR’s “high degree of autonomy”, its unique character and lifestyle. He or she also needs to deal with continuity and change. Hong Kong cannot stand still, and should not allow itself to be lulled by the “50 years no change” mantra into overlooking the need to move with the times. Much reform needs to be implemented by the next Chief Executive to give people hope, faith in “One Country, Two Systems” and true love of the country.
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Xue, Kaiming, and Denis Yu. "(Digital Presentation) A 2.8V Reversible Sn-Li Battery." ECS Meeting Abstracts MA2022-01, no. 1 (July 7, 2022): 80. http://dx.doi.org/10.1149/ma2022-01180mtgabs.
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Tin (Sn) is a metal that is commonly used in our daily life. With the rapid development of lithium-ion battery in the past decades, Sn and its alloy, such as Sn-Cu[1], and Sn-Ni[2], Sn-Co[3] and Sn-Fe[4] have been used as anode for lithium-ion battery because they can undergo alloying/dealloying process with lithium ions and exhibit high capacity and suitable working voltage of about 0.4 V vs. Li/Li+. Sn can also undergo an oxidation reaction to Sn2+, with an electrode potential of about -0.14 V vs. SHE. It is therefore possible to also use Sn as a cathode material. Herein, we are first to demonstrate a metal-metal battery made up of Sn metal as the cathode and Li metal as the anode in organic electrolyte (see Fig. a). Sn foil and Li foil are simply assembled with 3M LiTFSI in dimethoxyethane/propylene carbonate (DME/PC) electrolyte in an Ar-filled glove box to form a pouch cell. During charging, Sn will give out two electrons and dissolves into the electrolyte as Sn2+, while during discharging, the metal ions will be re-deposited onto the cathode. Thus, the energy is stored in the form of Sn2+ in the electrolyte. The charge-discharge curves in Fig. b show that the operating voltage of the battery is about 2.8 V. Since Sn2+ that is dissolved into the electrolyte from the cathode has higher potential than the Li metal anode, any Sn2+ ions cross-over to the anode will be spontaneously reduced, decreasing the efficiency of the battery. To suppress such self-discharge process, an anion exchange membrane based on poly(ionic liquid) polymer coated on common polypropylene separator is adopted. The Sn-Li battery with the modified separator tested in a current rate of 0.2 mA cm-2 with a capacity limitation of 0.1 mAh cm-2 gives an average Coulombic efficiency about 99.5% and can be cycled for more than 1500 cycles(See Fig. c). We found that the stripping/deposition of Sn on the cathode, and its polarization depend strongly on the type of electrolyte used. With 3M LiTFSI in DME/PC electrolyte, the discharge voltage is lowered by about 0.05 V when the current density is increased from 0.2 mA cm-2 to 1 mA cm-2. More results on the factors affecting the charge-discharge performance of Sn-Li batteries will be discussed at the meeting. [1]X. F. Tan, S. D. McDonald, Q. Gu, Y. Hu, L. Wang, S. Matsumura, T. Nishimura, K. Nogita, Journal of Power Sources 2019, 415, 50. [2]H. Zhang, T. Shi, D. J. Wetzel, R. G. Nuzzo, P. V. Braun, Advanced Materials 2016, 28, 742. [3]J. Yang, J. Zhang, X. Zhou, Y. Ren, M. Jiang, J. Tang, ACS Applied Materials & Interfaces 2018, 10, 35216. [4]Z. Lin, X. Lan, X. Xiong, R. Hu, Materials Chemistry Frontiers 2021, 5, 1185. Figure 1
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Ikezawa, Atsunori, Tadaaki Nishizawa, Yukinori Koyama, and Hajime Arai. "Development of MoO3-Based Proton Batteries." ECS Meeting Abstracts MA2022-02, no. 1 (October 9, 2022): 17. http://dx.doi.org/10.1149/ma2022-02117mtgabs.
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Aqueous rocking chair batteries have attracted attention as highly safe and inexpensive secondary batteries. Lithium and sodium ions have mostly been used as the mobile ions, whereas proton systems with potentially the highest mobility have rarely been reported. Recently, research on proton batteries has been conducted using concentrated sulfuric acid solutions as the electrolyte that can assist high-rate performance.[1] Stability under concentrated acidic conditions is required for the electrode materials, as well as the capability of proton accommodation. MoO3 has been reported as a stable negative electrode material for aqueous proton batteries,[2] while few positive electrode materials are known except for bulky organic[3] and Prussian-blue materials[4]. For achieving high energy density and long life, oxide positive electrode materials are desirable. Here we propose the application of MoO3 as the positive electrode material by optimizing the operating composition range. The potential values shown below are all shown versus SHE (actually measured with Ag/AgCl). MoO3 showed a discharge profile at around 0.5 V with the maximum capacity of ca. 100 mAh g-1, as shown in the figure. This potential is sufficiently more positive than the redox potential of protonated MoO3 of around -0.3 V as the negative electrode. With the aid of operando X-ray diffraction analysis, it turned out that the discharge regions at 0.5 V and 0.4 V are respectively associated with a biphasic transition of MoO3/phase I (ca. 0 < x < 0.3 in H x MoO3) and a single-phase reaction of phase I (ca. 0.3 < x < 0.5 in H x MoO3). Deep discharging beyond this range results in the coexistence of phase I and phase III (ca. 0.5 < x < 1.5 in H x MoO3) and the proton extraction from phase III leads to the formation of phase II or phase IIa with its discharging potential of 0.0 V. Structural calculation based on the density function theory is employed to clarify the origin of this irreversible phase transition behavior. Different proton sites between these phases seem to be responsible. An aqueous proton battery with a 7 mol dm–3 sulfuric acid electrolyte was constructed with H-inserted MoO3 and MoO3as the negative and positive electrodes, respectively, and was successfully discharged and charged repeatedly, with the operating voltage of ca. 0.6 V, indicating the launch of aqueous proton battery composed of oxide active materials. Reference s : [1] J. Li, H. Yan, C. Xu, Y. Liu, X. Zhang, M. Xia, L. Zhang, J. Shu, Nano Energy, 89 (2021) 106400. [2] X. Wang, Y. Xie, K. Tang, C. Wang, C. Yan, Angew. Chem. Int. Ed., 57 (2018) 11569. [3] X. Wang, J. Zhou, W. Tang, Energy Storage Mater., 36 (2021) 1. [4] X. Wu, J. J. Hong, W. Shin, L. Ma, T. Liu, X. Bi, Y. Yuan, Y. Qi, T. W. Surta, W. Huang, J. Neuefeind, T. Wu, P. A. Greaney, J. Lu, X. Ji, Nat. Energy, 4 (2019) 123. Figure 1
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Zheng, Zijian. "(Invited) Textile Composite Electrodes for Wearable Batteries and Beyond." ECS Meeting Abstracts MA2022-02, no. 5 (October 9, 2022): 572. http://dx.doi.org/10.1149/ma2022-025572mtgabs.
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Abstract Wearable energy storage devices are indispensable corner stones for future wearable electronics. Current energy storage technologies are based on materials and devices that are rigid, bulky, and heavy, making them difficult to wear. On the other hand, fibers are flexible and lightweight materials that can be assembled into different textiles and have been worn by human beings thousands of years. Different from conventional two-dimensional thin films and foils, the three-dimensional fibre and textile structures not only provide superior wearing ability, but also much larger surface areas. This talk will introduce how our research group makes use of the attributes of fibres for high-performance wearable energy storage devices. We will demonstrate the strategies and discuss the perspectives to modify fibers and textiles for making wearable capacitators and batteries with excellent mechanical durability, electrochemical stability, and high energy/power density. We will also show that the fibrous materials can significantly enhance the stability and energy density of battery for wearable applications and others such as Na battery. References [1] Q. Huang, D. Wang, Z. J. Zheng*, Adv. Energy Mater. 2016, 6, 1600783. [2] Y. Gao, C. Xie, Z. J. Zheng*, Adv. Energy Mater. 2020, 2002838 [3] L. Liu, Y. Yu, C. Yan, K. Li, Z. J. Zheng*, Nat. Commun. 2015, 6, 7260. [4] Y. Yu, C. Yan, Z. J. Zheng*, Adv. Mater. 2014, 26, 55085516. [5] Y. Yang, Q. Huang, L. Niu, D. Wang, C. Yan, Y. She, Z. J. Zheng*, Adv. Mater. 2017, 160667. [6] J. Chang, Z.J.Zheng* et al., Nat. Commun. 2018, 2018, 9, 4480. [7] J. Chang, Q. Huang, and Z. J. Zheng*, Joule 2020, 4, 7, 1346 [8] J. Chang, Q. Huang, Y. Gao, Z. J. Zheng*, Adv. Mater. 2021, 202004419. [9] Y. Gao, H. Hu, J. Chang, Q. Huang, Q. Zhuang, P. Li, Z. J. Zheng*, Adv. Energy Mater. 2021, 2101809. [10] L. Wang, J. Shang, Q. Huang, H. Hu, Y. Zhang, C. Xie, Y. Luo, Y. Gao, H. Wang, Z. J. Zheng*, Adv. Mater. 2021, 2102802.
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Minehan, Bridie Andrews. "Zhang Daqing. Zhongguo jin dai ji bing she hui shi [A Social History of Diseases in Modern China (1912–1937)]. (Zhongguo jin xian dai ke xue ji shu shi yan jiu cong shu.) iv + 229 pp., illus., tables, bibl., index. Jinan: Shandong jiao yu chu ban she [Shandong Education Press], 2006. (Paper.)." Isis 100, no. 1 (March 2009): 192–93. http://dx.doi.org/10.1086/599688.
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Shen, Grace Y. "Zhang Jiuchen . Di zhi xue yu Minguo she hui: 1916–1950 [Geology and Society: A Study in Chinese National Geological Survey]. (Zhongguo jin xian dai ke xue ji shu shi yan jiu cong shu.). 286 pp., bibl., index. Jinan: Shandong jiao yu chu ban she [Shandong Education Press], 2005. π⃑ 33 (paper)." Isis 99, no. 3 (September 2008): 634–35. http://dx.doi.org/10.1086/593257.
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Liu, F., H. Zhang, X. Wang, J. Feng, Y. Cao, Y. Su, M. Wada, Y. Ma, and Y. Ma. "THU0036 FIRST-IN-HUMAN TRIAL OF BCMA-CD19 COMPOUND CAR IN THE TREATMENT OF AUTOANTIBODY MEDIATED DISORDERS." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 231.1–231. http://dx.doi.org/10.1136/annrheumdis-2020-eular.4065.
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Background:Donor-specific anti-HLA antibodies (DSAs) are antibodies in the recipient directed against donor class I/II HLA antigens. The existence of DSAs before allogenic hematopoietic stem cell transplantation (AHSCT) are known to cause primary graft failure. Currently there’s no established method of DSA desensitization due to the long half-life of plasma cells.Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease involving in multiple organ systems mediated by numerous autoantibodies. Recent results have shown that depletion of B cells by CD19 CAR-T cells effectively reversed some manifestations in two SLE mouse models. However, plasma cells could be spared with single CD19 CAR-T cells, and peripheral circulating anti-DNA IgG and IgM autoantibodies remain elevated or increased in treated mice.Objectives:We present the efficacy of BCMA-CD19 compound CAR (cCAR), which target on antibody- producing “root”, both B cells and plasma cells in preclinical study and in our first-in-human phase 1 clinical trial.Methods:We constructed a BCMA-CD19 cCAR composed of a complete BCMA-CAR fused to a complete CD19 CAR, separated by a self-cleaving P2A peptide. We assessed the functional activity of cCAR in co-culture assay with multiple cell lines. We also verified cCAR efficacy with two mouse models, injected with either BCMA-expressing MM.1S cells or CD19-expressing REH cells. In our phase 1 clinical trial, we enrolled patients with hematologic malignancies with antibody mediated disorders.Results:BCMA-CD19 cCAR exhibited robust cytotoxic activity against the K562 cells engineered to express either CD19 or BCMA in co-culture assays, indicating the ability of each complete CAR domain to specifically lyse target cells. In mouse model study, cCAR-T cells were able to eliminate tumor cells in mice injected with MM.1S cells and REH cells, indicating that both BCMA and CD19 are specifically and equally lysing B cells and plasma cells in vivo, making BCMA-CD19 cCAR a candidate for clinical use.In our first-in-human clinical trial, the first case is a 48-year-old female patient having resistant B-ALL with high DSA titers. She exhibited complete remission of B-ALL at day 14 post-CAR T treatment. MFI of DSA dropped from 7800 to 1400 at 8 weeks post cCAR treatment, the reduction percentage was approximately 80% (Figure 1). The patient had no CRS, and no neurotoxicity was observed.Figure 1.1. A) MFI of DSA and other HLA antibodies before and at different time points after cCAR T infusion. B) the percent reduction post-transfusion of cCAR T cells at different time points.The second case is a 41-year-old female patient having a refractory diffuse large B cell lymphoma with bone marrow (BM) involvement. Furthermore, she has a 20 years of SLE, with manifestation of fever dependent of corticosteroids. On day 28 after cCAR treatment, PET/CT scan showed CR, and BM turned negative. In addition, she is independent of steroids, has no fever and other manifestations, C3/C4 are within normal ranges, and all the ANA dropped significantly, especially the nuclear type ANA, which turned from> 1:1000 to be negative at day 64. She had Grade 1 CRS but with no neurotoxicity observed. The absence of B cells and plasma cells persisted more than 5 months post CAR therapy.Conclusion:Our first in human clinical trial on BCMA-CD19 cCAR demonstrated profound efficacy in reducing DSA levels in an AHSCT candidate and ANA titer in a SLE patient. There was strong clinical evidence of depletion of antibody-producing roots, B-cells and plasma cells in both patients. Our results further suggested that BCMA-CD19 cCAR has the potential to benefit patients receiving solid organ transplants or those with other antibody-mediated diseases.Figure 2.Reduction of different type of ANA titer at different time points.Acknowledgments:patients and their familiesDisclosure of Interests:Fang liu: None declared, Hongyu Zhang: None declared, Xiao Wang: None declared, Jia Feng: None declared, Yuanzhen cao Employee of: Employee of iCell Gene Therapeutics LLC, Yi Su: None declared, Masayuki Wada Employee of: employee of iCell Gene Therapeutics LLC, Yu Ma Employee of: employee of iCAR Bio Therapeutics Ltd, Yupo Ma Shareholder of: shareholder of iCell Gene Therapeutics LLC
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Jethwa, Rajesh, Dominic Hey, Rachel Kerber, Dominic S. Wright, and Clare P. Grey. "An Exploration of Nitrogen-Rich Fused Heteroaromatic Quinones for Redox Flow Battery Applications." ECS Meeting Abstracts MA2022-01, no. 48 (July 7, 2022): 2013. http://dx.doi.org/10.1149/ma2022-01482013mtgabs.
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The growing need to transition from fossil fuels to renewable energy sources will require innovative development of grid-level electrochemical energy storage.1 Suitable grid-level storage must provide a high cycle number durability, long calendar life, high efficiency, low cost and fast response time.2–4 Redox flow batteries (RFBs) are one potential solution boasting a decoupled power and capacity scaling.1,4,5 However, the low energy density1,6,7 and high capital costs6,7 of current systems preclude wide-scale deployment of this technology. Increasing energy density can be achieved in various ways: expanding the voltage window or by minimising the mass and/or volume per electron transferred.8 These offer potential strategies for electrolyte exploration but the challenge is to minimise the cost while providing as much electrical energy storage as possible. Current electrolyte systems for RFBs rely on a variety of metal-based systems (vanadium,9 iron,10 chromium10)1,11 and a range of organic molecules (nitroxide radicals,12 phenazines,12–14 viologens,15 and quinones16–18).4,5 Quinones offer fast kinetics, high tunability and low cost.5 Of these, higher order quinones offer increased chemical and electrochemical stability.5 In this work, an exploration of nitrogen-rich fused heteroaromatic quinones was carried out to investigate new avenues for electrolyte development. The electrolytes were screened using electrochemical techniques and the most promising candidate was tested in a lab-scale flow battery as an anolyte under aqueous conditions. Sitting at -0.7 V(SHE), a capacity fade rate of 0.004%.cycle-1 was found in symmetric cycling. In situ UV-Vis, NMR19,20 and EPR19 spectroscopy were used to investigate the electrochemical stability and nature of the charged species involved during operation, complemented by density functional theory modelling. These studies indicate that fused systems of this type may be promising candidates for aqueous RFBs. Alotto, P., Guarnieri, M. & Moro, F. Redox flow batteries for the storage of renewable energy: A review. Renew. Sustain. Energy Rev. 29, 325–335 (2014). Weber, A. Z. et al. Redox flow batteries: A review. J. Appl. Electrochem. 41, 1137–1164 (2011). Gyuk, I. et al. Grid Energy Storage. (2013). Cao, J., Tian, J., Xu, J. & Wang, Y. Organic Flow Batteries: Recent Progress and Perspectives. Energy and Fuels 34, 13384–13411 (2020). Ding, Y., Zhang, C., Zhang, L., Zhou, Y. & Yu, G. Molecular engineering of organic electroactive materials for redox flow batteries. Chem. Soc. Rev. 47, 69–103 (2018). Potash, R. A., McKone, J. R., Conte, S. & Abruña, H. D. On the Benefits of a Symmetric Redox Flow Battery. J. Electrochem. Soc. 163, A338–A344 (2016). Wang, W. et al. Recent progress in redox flow battery research and development. Adv. Funct. Mater. 23, 970–986 (2013). Armand, M. & Tarascon, J. M. Building better batteries. Nature 451, 652–657 (2008). Ulaganathan, M. et al. Recent Advancements in All-Vanadium Redox Flow Batteries. Adv. Mater. Interfaces 3, (2016). Sun, C. & Zhang, H. A review of the development of the first‐generation redox flow battery : iron chromium system. ChemSusChem (2021). doi:10.1002/CSSC.202101798 Noack, J., Roznyatovskaya, N., Herr, T. & Fischer, P. The Chemistry of Redox-Flow Batteries. Angew. Chemie - Int. Ed. 54, 9776–9809 (2015). Winsberg, J. et al. Aqueous 2,2,6,6-Tetramethylpiperidine-N-oxyl Catholytes for a High-Capacity and High Current Density Oxygen-Insensitive Hybrid-Flow Battery. ACS Energy Lett. 2, 411–416 (2017). Kwon, G. et al. Multi-redox Molecule for High-Energy Redox Flow Batteries. Joule 2, 1771–1782 (2018). Romadina, E. I., Komarov, D. S., Stevenson, K. J. & Troshin, P. A. New phenazine based anolyte material for high voltage organic redox flow batteries. Chem. Commun. 57, 2986–2989 (2021). Hu, S. et al. Phenylene-Bridged Bispyridinium with High Capacity and Stability for Aqueous Flow Batteries. Adv. Mater. 33, 2005839 (2021). Suo, L. et al. Advanced High-Voltage Aqueous Lithium-Ion Battery Enabled by “Water-in-Bisalt” Electrolyte. Angew. Chemie - Int. Ed. 55, 7136–7141 (2016). Shimizu, A. et al. Liquid Quinones for Solvent-Free Redox Flow Batteries. Adv. Mater. 29, 1606592 (2017). Yang, Z. et al. Alkaline Benzoquinone Aqueous Flow Battery for Large-Scale Storage of Electrical Energy. Adv. Energy Mater. 8, 1702056 (2018). Zhao, E. W. et al. Coupled in Situ NMR and EPR Studies Reveal the Electron Transfer Rate and Electrolyte Decomposition in Redox Flow Batteries. J. Am. Chem. Soc. 143, 1885–1895 (2021). Zhao, E. W. et al. In situ NMR metrology reveals reaction mechanisms in redox flow batteries. Nature 579, 224–228 (2020). Figure 1
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Wang, Zuoyue. "Jian Zhang. Ke xue she tuan zai jin dai Zhongguo de ming yun: yi Zhongguo ke xue she wei zhong xin [The Science Association and the Change of Society in Modern China: A Study on the Science Society of China]. (Zhongguo jin xian dai ke xue ji shu shi yan jiu cong shu.). 460 pp., tables, bibl., index. Jinan: Shandong jiao yu chu ban she [Shandong Education Press], 2005. ¥49 (paper)." Isis 99, no. 2 (June 2008): 437–38. http://dx.doi.org/10.1086/591376.
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Fujiwara, Mariana Tazima, Karla Borges Daniel, Marília Bortolotto Felippe Trentin, Murilo Oliveira Cerci, and Heraldo Mendes Garmes. "Pituitary Hyperplasia Secondary to Primary Hypothyroidism Mimicking a Macroadenoma With Optical Chiasm Compression." Journal of the Endocrine Society 5, Supplement_1 (May 1, 2021): A599—A600. http://dx.doi.org/10.1210/jendso/bvab048.1222.
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Abstract Background: A long term untreated primary hypothyroidism can stimulate thyrotropes proliferation, leading to pituitary hyperplasia. This condition is known as pituitary hyperplasia secondary to primary hypothyroidism (PHPH). It is a rare condition that mimics pituitary adenoma and can achieve large proportions with optic chiasm compression. A misdiagnosis may be catastrophic, and a pituitary resection wrongly performed. Clinical Case: A 25-year-old woman with a medical history of delayed neuro psychomotor development and epilepsy due to congenital CNS malformation had a Brain MRI performed for epilepsy follow-up three years earlier. At that time, neuroimaging had shown a pituitary enlargement, and laboratory data were diagnostic of severe primary hypothyroidism with TSH of 290.6 uUI/mL (normal range 0.4 to 4.5 uUI/mL) and T4L <0.23 ng/dL (normal range: 0.9 to 1.8 ng/dL). She then had received a 75 mcg levothyroxine prescription. However, the patient missed medical follow-up and returned three years later, when sella turcica MRI showed a 0.9x1.0x1,4 cm pituitary lesion, consistent with a macroadenoma with suprasellar extent near the optic chiasm. Because of the cognitive impairment, the patient was not able to complete the visual field test. Neurology service referred the patient to endocrinology evaluation for surgical treatment. Hypothyroidism was still uncontrolled with TSH 157.1 uUI/mL and T4L 0.28 ng/dL. We had adjusted the levothyroxine dose to 125 mcg and advised adherence. Subsequent thyroid function tests had shown TSH 6.91 uUI/mL and T4L 1.15 ng/dL. After thyroid function stabilization, the patient performed a new sella turcica MRI, which had not evidenced pituitary lesion. Pituitary hyperplasia secondary to primary hypothyroidism was her final diagnosis. Conclusion: This case report illustrates the importance of the correct diagnosis and treatment of PHPH. Levothyroxine replacement, with TSH normalization, reverses the gland hyperplasia within 2 to 4 months. References: 1. Cao J, Lei T, Chen F, Zhang C, Ma C, Huang H. Primary hypothyroidism in a child leads to pituitary hyperplasia: A case report and literature review. Medicine (Baltimore). 2018 Oct;97(42):e12703.2. Shivaprasad KS, Siddardha K. Pituitary Hyperplasia from Primary Hypothyroidism. N Engl J Med. 2019 Feb 21;380(8):e9.
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GOLOB, Nina. "Foreword." Acta Linguistica Asiatica 6, no. 1 (June 29, 2016): 5–6. http://dx.doi.org/10.4312/ala.6.1.5-6.
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Just before summer, when the air around university is filled with students' adrenalin due to numerous tests, we are pleased to announce our summer ALA issue. It was compiled bearing in mind that the outcome of such efforts is mainly students' of course, however, ours also; the outcome of teachers and researchers. In a very broad sense, this issue places importance on a successful second language pedagogical process, be it readability, pronunciation, generalization and application of grammatical rules, or their methodological issues. It supports the idea that reciprocal improvements on students' as well as teachers' and researchers' sides undoubtedly deliver best results in the language pedagogy as well as in linguistic research. Improvements that build upon expertise and considerable amount of real-life data. Improvements aspired to.Kristina HMELJAK SANGAWA in her article analized a collection of Japanese texts which had been linguistically simplified for learners of Japanese as a foreign language, and compared them to their original versions. The main aim of such analysis was to uncover different strategies that are used to make texts more accessible to learners. The author, however, makes some further steps and discusses the application of such strategies to assessing, selecting, and devising texts in a language classroom. Zuzana POSPĚCHOVÁ offers a detailed introduction to the method of prosodic transcription (PTR) for Standard Chinese established by phonetician Oldřich Švarný. The PTR method has taken several decades to form and it is nowadays a well established way of teaching Chinese prosody in the language courses around the Czech Republic. The article offers a short sample text, students' opinion on PTR, and an outline of the use of PTR in academic research. It concludes with the suggestion that PTR could be an international system of transcription capturing prosodic features worldwide. The idea in Mateja PETROVČIČ’s article also emerged from her experience with students of Chinese as a second language and their problems in the learning process. She highlights the so called liheci, a special type of Chinese polymorphemic verbs. Such verbs are known to sometimes accept one or more elements to infuse in between their morphemes, however, the author points out that word sketches such as Sketch Engine hardly offer any information on the behaviour of such words. She gives suggestions on how to include them.Liulin ZHANG offers a discussion on the two commonly recognized imperfective aspect markers in Mandarin Chinese zai and着zhe, and argues their qualifications as imperfective aspect markers based on the differences in their origins, historical evolutions, and corpus data. Alexander AKULOV is critical towards the methods in comparative linguistics that base on the characteristics of lexems of the compared languages. He points out that such methods do not suppose verification and therefore allow different, even opposing conclusions. In his article he suggests the comparison of grammars of the languages involved, and by using Prefixation Ability Index (PAI) and Verbal Grammar Correlation Index (VGCI) tackles the problem of Buyeo language group. His findings prove that Japanese and Korean belong to the same language group, and not just to the same language family. Finally, Pankaj DWIVEDI and Somdev KAR contributed a survey article on a Hindi dialect called Kanauji. The article exposes problems researchers have to deal with on the field when monitoring and documenting spoken language of a certain area, and fitting the findings into concepts such as a language and a dialect.
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Manjum, Marjanul, Saheed Adewale Lateef, Hunter Addison McRay, William Earl Mustain, and Golareh Jalilvand. "Low-Cost Processing of Highly Durable (>1000 cycles) Sulfur Cathodes for Li-S Batteries." ECS Meeting Abstracts MA2022-02, no. 6 (October 9, 2022): 588. http://dx.doi.org/10.1149/ma2022-026588mtgabs.
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Lithium-sulfur (Li-S) batteries are one of the promising alternatives to modern Lithium-ion Battery (LIB) technology due to their superior specific energy density, which can satisfy the emerging needs of advanced energy storage applications such as electric vehicles and grid-scale energy storage and delivery. However, achieving this high specific energy density is hampered by several challenges inherent to the properties of sulfur and its discharge products. One major issue is related to the insulating nature of S and its fully discharged product (Li2S), which often leads to low utilization of the active material and poor rate capability. The poor electronic conductivity of these species can be overcome by utilizing conductive hosts, though they are dilutive and decrease the energy density, meaning that their mass ratio to the active material should be as low as possible [1]. Another crucial issue relates to the undesired solubility of certain sulfur discharge products, so-called long-chain Li polysulfides (LiPSs), in the conventional ether-based liquid electrolyte. The solubility of long-chain LiPSs promotes their free back-and-forth transport between the positive and negative electrodes, which results in poor cyclability and capacity decay [2, 3]. Despite the efforts to engineer and control the undesired LiPSs shuttling effect, advances have been mostly limited to a small number of cycles (100-200), or the need for complex and often expensive synthesis that has limited the rational development of new sulfur cathodes. At present, a large majority of the sulfur cathode research has focused on nano-architectured electrodes using 2D and 3D host materials for sulfur, such as carbon nanotubes, graphene, conductive scaffolds, yolk-shell structures, and the like, to increase the conductivity and alleviate the LiPSs shuttling [4]. Although these approaches have helped to increase the achievable capacity, and sometimes the cyclability, their synthesis methods have been highly complex, meaning that their manufacturing cost will be high. Also, in operating cells, it is highly unlikely that these complex structures can be effectively reproduced upon many charge-discharge cycles – meaning that capacity loss is essentially inevitable. Thus, developing novel, yet affordable and scalable, cathode architectures that can enhance the rapid transport of Li-ions to active sites for electrode reactions, accommodate discharge-induced volume expansion, and minimize the shuttling mechanism by sulfur encapsulation are still in great need. In this work, we present a low-cost and scalable processing method for highly durable sulfur cathodes containing commercial sulfur, carbon black, and polyvinylidene fluoride (PVDF). The sulfur cathode slurry was prepared through a simple and scalable recipe where the degree of binder dissolution into the solvent was controlled before electrode deposition. Variables such as the solvent:binder ratio, dissolution time, and agitation will be discussed. The microstructure of the sulfur cathodes was characterized using scanning electron microscopy. Through controlled dissolution of binder, a porous, swollen network of binder was achieved that adhered the sulfur and carbon particles while providing a highly porous structure that can accommodate the sulfur volume expansion during discharge and impede dissolution of the discharge products into the electrolyte by physically trapping them. The cycling performance of the sulfur cathodes prepared through the present novel processing was tested at C/10 and compared with those prepared through the conventional production techniques. The sulfur cathodes prepared with this novel electrode processing offered impressive capacity retention of 80% after 1000 cycles suggesting a considerable improvement in the shuttling effect and active material preservation. These results are expected to help move the production and manufacturing of Li-S batteries forward. References -J. Lee, T.-H. Kang, H.-Y. Lee, J. S. Samdani, Y. Jung, C. Zhang, Z. Yu, G.-L. Xu, L. Cheng, S. Byun et al., Advanced Energy Materials, vol. 10, no. 22, p. 1903934, 2020. Yang, G. Zheng, and Y. Cui, Chemical Society Reviews, vol. 42, no. 7, pp. 3018–3032, 2013. She, Y. Sun, Q. Zhang, and Y. Cui., Chemical society reviews, vol. 45, no. 20, pp. 5605-5634, 2016. Zhou, D. L. Danilov, R.-A. Eichel, and P. H. L. Notten, Advanced Energy Materials, vol. 1, p. 2001304, 2020.
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Pannu, Danish Kaur, Stephan N. Steinmann, Carine Michel, Theodorus de Bruin, Carlos Nieto-Draghi, and Gentien Thorner. "Computational Study of Thermodynamic Overpotentials of Quinone Reduction on Carbon Electrodes to Accelerate Organic Redox Flow Battery Research." ECS Meeting Abstracts MA2022-01, no. 48 (July 7, 2022): 2015. http://dx.doi.org/10.1149/ma2022-01482015mtgabs.
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Redox flow batteries (RFBs) offer advantages as compared to conventional batteries, such as the possibility of decoupling the energy density (volume and concentration of the electrolyte) and the power density (surface contact between electrode and electrolyte) of the battery. Organic redox flow batteries (ORFBs) have gained attention recently because they promise to be more eco-friendly and cheaper than their inorganic counterparts. Particularly, organic molecules are highly tunable in terms of both solubility and redox potential. Many families of organic molecules have been reported for this purpose, with quinones being particularly promising [Symons, 2021]. However, ORFBs are limited in terms of their cell potential and stability. To discover optimal molecules for ORFBs, many research groups have employed molecular modelling methods [Er et al., 2015]. These studies using density functional theory (DFT) in implicit solvents only compute the Nernst potential [Zhang et al., 2020] of the one-step coupled e- and H+ redox reaction (see Figure 1(a)), ignoring the overpotential of the reaction. Our study addresses two aspects going beyond this state of the art: 1) considering the intermediate, semiquinone, of the reaction (see Figure 1(b)) and thus the thermodynamic overpotential; and 2) incorporating the effects of the electrode/electrolyte interface, where the actual electrochemical processes take place (see Figure 1(c)). Since the exact atomic structure of the carbon felt is unknown, we use different model carbon morphologies to calculate the thermodynamic overpotential of the given reaction. Grand-canonical DFT in combination with the linearized Poisson–Boltzmann implicit solvent model [Abidi et al., 2020] was used to calculate the overpotential (versus SHE) of the two-step reduction reaction of non-substituted p-benzoquinone (BQ) on 6 different models for carbon surfaces - graphite basal plane (0001), and edges (1100), (1000), zigzag nanotube, armchair nanotube and Buckyball. The overpotential on these surfaces was found to be between 0.2-0.5 V. The solution-phase overpotential due to the intermediate was 0.3 V for non substituted quinone, and 0.5 V for both the substituted quinones that we studied (R=CN and R=OMe). At the graphite basal plane, while for the non-substituted quinone, the overpotential negligibly increased, for the substituted ones, the overpotential reduced by ~0.2 V each (see Figure 1(d)). This showed an interesting relationship between the substituents of the quinone and the electrode surface. Extending our study further, we explored the effect of defects in the graphite basal plane: substitutional B or N doping, and the Stone-Wales (SW) defect. We found that the overpotential of the BQ reduction reaction did not change for the SW defect, and it increased by 0.1 V if a C-atom was substituted by a B-atom and decreased by 0.1 V, for N-atom substitution. The N-doped surface had the least overpotential (0.25 V), which suggests that doping the electrode with nitrogen would make better electrodes. From these results, we concluded that the atomic-level morphology of the surface does not affect the overpotential of the reaction as much as the dopants in the surface do. In summary, our results demonstrate that grand-canonical DFT leads to detailed insights on the chemistry of ORFB at the electrode. From an electrochemical viewpoint, we show that estimating the overpotential of ORFB requires the consideration of the intermediate in the reduction reaction, and that substituting the quinones with CN or OMe decreases the overpotential on the electrode surface. Finally, the effect of the atomic-level morphology of the electrode does not significantly affect the overpotential, while substitutional N-doping lowers the overpotential. References: Abidi, N., Lim, K. R. G., Seh, Z. W., & Steinmann, S. N. (2020). WIREs Computational Molecular Science, 11(3), e1499. Er, S., Suh, C., Marshak, M. P., & Aspuru-Guzik, A. (2015).Chemical Science, 6(2), 885 - 893. Symons, P. (2021). Current Opinion in Electrochemistry, 29, 100759. Zhang, Q., Khetan, A., & Er, S. (2020). Scientific Reports, 10(1), 22149. Figure 1: (a) One-step coupled 2e-,2H+ reduction reaction of benzoquinone (Q) into hydroquinone (HQ); (b) Two-step e-,H+ coupled reduction reaction via the intermediate, semiquinone (SQ); (c) Two-step e-,H+ transfer reduction reaction at the interface of carbon electrode and electrolyte; For substituted quinones, we used model examples of electron withdrawing substituents Ri={1,2,3,4}=CN and electron donating sbstituents Ri={1,3}=OMe (d) Overpotential of reduction reaction of different quinones in solution phase (blue) and at the graphite basal plane (0001) (red) is compared. While for non-substituted quinone, the overpotential only slightly increases due to the surface, for the substituted cases, the overpotential due to the surface decreases by 0.2 V. Figure 1
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Zhang, Xu Hannah, Vu N. Ngo, Natalie Sandoval, Qi Cui, Yanhong Shi, Jasmine M. Zain, Christiane Querfeld, Chao Guo, Xiwei Wu, and Steven T. Rosen. "Role of p38γ - NFATc4 - IL17A Pathway As a Potential Therapeutic Target in Cutaneous T Cell Lymphoma." Blood 128, no. 22 (December 2, 2016): 2725. http://dx.doi.org/10.1182/blood.v128.22.2725.2725.
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Abstract Cutaneous T cell lymphoma (CTCL) is an incurable skin homing T cell malignancy. We have previously reported p38 as therapeutic targets for CTCL.1 However, the mechanism underlying p38 signaling is not completely understood. To further investigate p38 and its downstream signaling components, we examined public database of gene expression and found that p38γ is overexpressed in CTCL as compared to normal T cells. In addition, p38γ has negligible expression in normal lymphoid tissues, with the exception of high level expressed in smooth and cardiac muscle cells. We have demonstrated that p38γ over-expression increases cell proliferation and knockdown of p38γ causes Hut78 cell death. p38γ plays an important role in inflammation-associated tumorigenesis3 and inhibition of its activity has emerged as a strategy to treat a spectrum of cancers.4 The transcription factor, NFATc4, downstream of p38γ, is also significantly up-regulated in CTCL cells by microarray analysis, and it is at non-detectable level in normal T cells.1We have demonstrated that shRNA-mediated knockdown of p38γ reduced NFATc4 mRNA levels in Hut78 cells, and that inhibition of NFATc4 by siRNA reduces the proliferation of CTCL cells. We also found that the cytokine IL17A functions downstream of p38γ and NFATc4, as knockdown of either p38γ or NFATc4 significantly reduced IL17A mRNA levels in Hut78 cells. This result suggests that IL17A is a target for transcriptionally activated NFATc4. Previously we have shown that IL17A rescues Hut78 cells from apoptosis induced by combined inhibition of NFAT and NFkB (treated with curcumin and Ly2228820). This implicates IL17A as a key mediator for CTCL survival. Therefore, we propose a novel p38γ - NFATc4 - IL17A signaling pathway in malignant T cells that promotes the survival of CTCL which provides potential therapeutic target against this disease. To further define the role of p38 and identify targets that increase the antitumor efficacy of p38 inhibition, we performed a synthetic lethal RNA interference (RNAi) screen in Hut78 cells treated with 10 µM of the p38 MAPK inhibitor Ly2228820. We transduced control and Ly2228820-treated Hut78 cells with a pooled retroviral RNAi library consisting of 4290 shRNAs that targeted more than 1000 genes involved in human cancers. If a shRNA from the library is not toxic to the control cells, but causes cell death in Ly2228820-treated cells, the gene targeted by this shRNA would be identified by the screen as synthetically lethal to p38 inhibition. Among many hits identified from the screen, we selected UCHL5 for further analysis. UCHL5encodes a deubiquitin enzyme that cleaves K48-linked polyubiquitin chains and plays an important role in the regulation of protein stability. Interestingly, combination of Ly2228820 and b-AP15, a small molecule inhibitor of UCHL5, significantly reduced the protein levels of NFATc4 isoform but not other NFAT isoforms. NFATc4 protein levels are known to be regulated by ubiquitin-proteasome pathway.2 Our finding thus suggests UCHL5 as a potential new regulator that stabilizes NFATc4 protein. Further studies are needed to confirm this prediction. More importantly, combination of Ly2228820 and b-AP15 enhanced apoptosis in CTCL cell lines (HH and Hut78) and primary Sézary cells, but was not toxic in normal PBMC cells. In summary, our findings suggest that the p38γ - NFATc4 - IL17A signaling pathway plays an important role in the survival of CTCL. In addition, improving the efficacy of targeting this pathway via p38 may also benefit from combined inhibition of UCHL5, a potentially important regulator of NFATc4 that needs further characterization. Reference: 1 Bliss-Moreau M, Coarfa C, Gunaratne PH, Guitart J, Krett NL, Rosen ST (2015). Identification of p38beta as a therapeutic target for the treatment of Sezary syndrome. The Journal of investigative dermatology135:599-608. 2 Fan Y, Xie P, Zhang T, Zhang H, Gu D, She M et al (2008). Regulation of the stability and transcriptional activity of NFATc4 by ubiquitination. FEBS letters582:4008-4014. 3 Qi X, Yin N, Ma S, Lepp A, Tang J, Jing W et al (2015). p38gamma MAPK Is a Therapeutic Target for Triple-Negative Breast Cancer by Stimulation of Cancer Stem-Like Cell Expansion. Stem cells33:2738-2747. 4 Yin N, Qi X, Tsai S, Lu Y, Basir Z, Oshima K et al (2015). p38gamma MAPK is required for inflammation-associated colon tumorigenesis. Oncogene. Disclosures Querfeld: Actelion: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.
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Rao, V. Koneti, Susan Price, Morgan Similuk, Julie Niemela, Joshua D. Milner, and Sergio Rosenzweig. "Clinical Spectrum of Autoimmune Lymphoproliferative Syndrome Associated with Caspase10 Mutations (ALPS-CASP10)." Blood 128, no. 22 (December 2, 2016): 1335. http://dx.doi.org/10.1182/blood.v128.22.1335.1335.
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Abstract Autoimmune lymphoproliferative syndrome (ALPS) is a rare disorder of the immune system due to defective Fas-mediated apoptosis which usually presents in childhood with lymphadenopathy, hypersplenism, hypergammaglobulinemia and multilineage cytopenias. Heterozygous germline mutations in FAS (TNFRSF6) gene commonly cause what is known as ALPS-FAS. Patients with genetic defect in Caspase 10 are classified as ALPS-CASP10. We have identified 16 individuals from 11 families with caspase 10 mutations. However six individuals were noted to have recognized caspase 10 polymorphisms. Here we are describing the clinical spectrum of a cohort of 10 patients from 8 families seen in our institution during the last 20 years with features suggestive of ALPS due to Caspase 10 mutations. There were 5 males and 5 females. Their median age at presentation was 7 years (Range 1-32yrs). Lymphadenopathy (n=8) was noted in most and splenomegaly in 5/10. The immunophenotypic signature of ALPS, "double negative" TCR-__+ T lymphocytes (DNTs) that lack both CD4 and CD8 markers were expanded in 6/8 patients. One patient (#132.1) had significant autoimmune kidney disease (glomerulonephritis) in addition to AIHA and ITP requiring renal transplantation. Patient #11.1 had acquired factor VIII inhibitor, hematuria, joint effusions and needed long term immunosuppression including weekly methotrexate. She is currently off all immunosuppressive medications and without any clinically significant autoimmune problems. More details of the clinical spectrum seen in this cohort of patients are presented in Table 1. During follow up we noted significant hypogammaglobulinemia requiring IVIG associated with infiltrative lung lesions and arthropathies in two siblings from family #171. Their unique evolving clinical phenotype led to diagnosis of a second genetic defect (STAT3 gain of function defect: 2141C>T; p.P714L) in them. The Caspase 10 mutation seen in this family(pI406L) was also noted following EXOME sequencing in another child with congenital neurological findings and her healthy parent as well as healthy sibling. Hence we are attributing the more recent clinical findings of hypogammaglobulinemia, diffuse lymphocytic lung disease and pulmonary fibrosis in patients 171.1.and 171.4 to the recently described STAT3 GOF mutation (Reference). Lesson learnt from this one family we wish to share is that if evolving clinical phenotype in a patient does not fit the working diagnosis of a known monogenic disorder, it is worthwhile to expand the search for other coexisting genetic defects using extended genetic testing methods currently in vogue. Reference: Milner JD, Vogel TP, Forbes L, Ma CA, Stray-Pedersen A, Niemela JE, Lyons JJ, Engelhardt KR, Zhang Y, Topcagic N, Roberson ED, Matthews H, Verbsky JW, Dasu T, Vargas-Hernandez A, Varghese N, McClain KL, Karam LB, Nahmod K, Makedonas G, Mace EM, Sorte HS, Perminow G, Rao VK, O'Connell MP, Price S, Su HC, Butrick M, McElwee J, Hughes J, Willet J, Swan D, Xu Y, Santibanez-Koref M, Slowik V, Dinwiddie DL, Ciaccio CE, Saunders CJ, Septer S, Kingsmore SF, White AJ, Cant AJ, Hambleton S, Cooper MA. Early-onset lymphoproliferation and autoimmunity caused by germline STAT3 gain-of-function mutations. Blood. 2014 Oct 30.PMID: 25359994. Disclosures No relevant conflicts of interest to declare.
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Zhang, Wenhui, Heather Becker, and Alexa Stuifbergen. "Comparing Health Promotion and Quality of Life in People with Progressive Versus Nonprogressive Multiple Sclerosis." International Journal of MS Care 22, no. 5 (September 1, 2020): 239–46. http://dx.doi.org/10.7224/1537-2073.2020-040.
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CME/CNE Information Activity Available Online: To access the article, post-test, and evaluation online, go to http://www.cmscscholar.org. Target Audience: The target audience for this activity is physicians, physician assistants, nursing professionals, and other health care providers involved in the management of patients with multiple sclerosis (MS). Learning Objectives: 1) Describe factors associated with health and well-being among people with progressive and nonprogressive MS. 2) Identify differences in health-related variables between those with progressive MS and those with nonprogressive MS. Accreditation Statement: In support of improving patient care, this activity has been planned and implemented by the Consortium of Multiple Sclerosis Centers (CMSC) and Delaware Media Group. The CMSC is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team. Physician Credit: The CMSC designates this journal-based activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Nurse Credit: The CMSC designates this enduring material for 1.0 contact hour (none in the area of pharmacology). Disclosures: Francois Bethoux, MD, Editor in Chief of the International Journal of MS Care (IJMSC), has served as Physician Planner for this activity. He has disclosed relationships with Springer Publishing (royalty), Qr8 (receipt of intellectual property rights/patent holder), Biogen (receipt of intellectual property rights/patent holder, speakers’ bureau), GW Pharma (consulting fee), MedRhythms (consulting fee, contracted research), and Adamas Pharmaceuticals (contracted research). Mary Alissa Willis, MD, Associate Editor of IJMSC, has disclosed relationships with Greenwich Biosciences (consulting fee), Biogen (speakers’ bureau), Genentech (speakers’ bureau), and Alexion (contracted research). Laurie Scudder, DNP, NP, has served as Reviewer for this activity. She has disclosed no relevant financial relationships. Wenhui Zhang, PhD, MS, RN, has disclosed no relevant financial relationships. Heather Becker, PhD, has disclosed no relevant financial relationships. Alexa Stuifbergen, PhD, RN, FAAN, has disclosed no relevant financial relationships. The peer reviewers for IJMSC have disclosed no relevant financial relationships. The staff at IJMSC, CMSC, and Delaware Media Group who are in a position to influence content have disclosed no relevant financial relationships. Note: Financial relationships may have changed in the interval between listing these disclosures and publication of the article. Method of Participation: Release Date: October 1, 2020 Valid for Credit Through: October 1, 2021 In order to receive CME/CNE credit, participants must: 1) Review the continuing education information, including learning objectives and author disclosures.2) Study the educational content.3) Complete the post-test and evaluation, which are available at http://www.cmscscholar.org Statements of Credit are awarded upon successful completion of the post-test with a passing score of >70% and the evaluation. There is no fee to participate in this activity. Disclosure of Unlabeled Use: This educational activity may contain discussion of published and/or investigational uses of agents that are not approved by the FDA. The CMSC and Delaware Media Group do not recommend the use of any agent outside of the labeled indications. The opinions expressed in the educational activity are those of the faculty and do not necessarily represent the views of the CMSC or Delaware Media Group. Disclaimer: Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information presented in this activity is not meant to serve as a guideline for patient management. Any medications, diagnostic procedures, or treatments discussed in this publication should not be used by clinicians or other health care professionals without first evaluating their patients’ conditions, considering possible contraindications or risks, reviewing any applicable manufacturer’s product information, and comparing any therapeutic approach with the recommendations of other authorities.
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Schroeder, Thomas, Christian Saure, Ingmar Bruns, Fabian Zohren, Akos G. Czibere, Nelly Nancy Safaian, Roland Fenk, Rainer Haas, and Guido Kobbe. "Clinical Efficacy of Sorafenib in Patients with Acute Myeloid Leukemia (AML) and Activating FLT3-Mutations." Blood 114, no. 22 (November 20, 2009): 2057. http://dx.doi.org/10.1182/blood.v114.22.2057.2057.
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Abstract Abstract 2057 Poster Board II-34 Introduction: Patients with acute myeloid leukemia (AML) and activating mutations in the Fms-like tyrosine-3 (FLT3) gene have an abysmal prognosis. Together with other groups we have recently demonstrated the clinical activity of the multikinase and FLT3 inhibitor sorafenib in patients with FLT3+ AML (Safaian et al., 2008; Zhang et al., 2008; Metzelder et al., 2009). We here present clinical results of 8 AML FLT3+ patients treated with sorafenib either prior or after allogeneic stem cell transplantation (allo-SCT) on an off-label basis. Patients, Treatment and Response Evaluation: Between February 2007 to August 2009 eight patients with AML (7 female, 1 male, median age: 47 years, range 23-63 years) were treated with sorafenib 800 mg daily (dose range 400-800 mg daily) for a median duration of 37 days (range 5-225 days). Six patients had an internal tandem duplication mutation (ITD), while 2 patients carried a tyrosine kinase domain (TKD) mutation. One patient received sorafenib at diagnosis before remission induction while all other patients had relapsed and/or refractory disease. Response and toxicity were evaluated regularly and defined according to established criteria. Results: Two of four patients who received sorafenib for refractory relapse after allo-SCT (median time to relapse 78 days, range 59-84 days) achieved complete remission (CR) (1 CR, 1 complete molecular remission (CMR) with disappearance of extramedullary chloromas) and survived 164 and 594 days, respectively. One of these patients died after another systemic relapse, while the other died as result of a CNS-chloroma being still in CMR in bone marrow (BM). In the 2 other patients sorafenib induced a hematological response (HR) and these patients survived 188 and 329 days before they died of progressive disease. Of the 4 patients treated prior allo-SCT, 2 had relapsed during consolidation after a previous CR, 1 had refractory disease and 1 was treated at diagnosis. Both patients with relapse showed response to sorafenib treatment thereby permitting allo-SCT. While one achieved HR, the other had regression of multiple isolated cutaneous relapse manifestations. Both patients are still alive at day +81 and day +16 in CMR and CR, respectively. The patient, who was primary refractory to double induction and high-dose cytarabine had a reduction of BM-blasts. She discontinued sorafenib because of neurotoxicity after 13 days. This patient reached a CR after allo-SCT, but died on day + 379 of another relapse. At the time of AML diagnosis the fourth patients had a WBC of 377.000/ul. Despite treatment with hydroxyurea, cytarabine and leukapheresis WBC could not be lowered <100.000/ul within 5 days and the patient developed pulmonary leukostasis syndrome. At this point of time FLT3 TKD mutation was detected and sorafenib was started promptly. Within the next 5 days WBC (peripheral blasts %) declined from 119.700/μl (98%) to 5.300/μl (28%) without tumor lysis syndrome facilitating induction therapy with cytarabine, daunorubicin and etoposide. Sorafenib therapy was continued in parallel and led to a CMR without increased toxicity. In general, sorafenib treatment was well tolerated. Besides neurotoxicity in one patient extrahematological side effects were almost limited to transient dermatological symptoms in two patients, which resolved after discontinuitation of sorafenib. Four Patients developed neutropenia grade IV and thrombopenia grade IV, which was not exclusively attributable to sorafenib, but also to the underlying AML. Conclusion: Our results add to the growing evidence that sorafenib is highly active in patients with FLT3+ AML. In view of the clinical course of our patients we suggest that sorafenib can achieve temporary disease control, but should be integrated into induction and consolidation regimens to achieve curative treatment. Recent data on synergistic effects between sorafenib and cytarabine and the CXCR4 inhibitor AMD3100 suggest these combinations for new clinical trials. Disclosures: Off Label Use: individual treatment approach of patients with refractory FLT3+ AML with multikinase inhibitor sorafenib, which is approved by EMEA + FDA for renal cell carcinoma.
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Zhu, Yuelin. "Li Zhang. Xin Zhongguo yu xin ke xue: gao fen zi xue zai xian dai Zhongguo de jian li [New Science for a New China: Institutionalization of Polymer Science in the P. R. China]. (Zhongguo jin xian dai ke xue ji shu shi yan jiu cong shu.). 340 pp., tables, bibl., index. Jinan: Shandong jiao yu chu ban she [Shandong Education Press], 2005. ¥37.50 (paper)." Isis 99, no. 2 (June 2008): 446–47. http://dx.doi.org/10.1086/591385.
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Zhang, Ziye. "Comparing online and professional restaurant reviews: What can we learn?" Hospitality Insights 1, no. 1 (October 25, 2017): 11–12. http://dx.doi.org/10.24135/hi.v1i1.9.
Full textAbstract:
Social media and review websites such as Trip Advisor are emerging as important platforms for restaurant reviews. The tendency of consumers to seek out electronic word of mouth before deciding where to dine has increased rapidly, with online content being shown to significantly impact purchasing decisions. Practitioners have indicated they are keenly aware of the importance of online reviews, but there is almost no research that looks at this phenomenon in the New Zealand context, and no research that compares traditional, print-based reviews with online content. In order to address this gap, a recent Auckland University of Technology master’s thesis applied content analysis to compare online and published restaurant reviews of restaurants in Auckland, New Zealand. Three hundred reviews from TripAdvisor website, Cuisine Magazine and the New Zealand Herald newspaper were analysed, and some results are presented here.
Traditional print reviews (Cuisine and the Herald) tend towards a more ‘specialist’ approach, including detailed information about the chefs, the owners and the restaurants’ histories. They also use more ‘fancy’ language in their food descriptions, including very detailed menu ingredients. TripAdvisor reviews, by contrast, tend towards non-specialist, ‘plain language’ reviews, with simple menu descriptor words and little attention on ingredients. When discussing price, print reviews take an ‘objective’ stance, listing the price but rarely making a personal judgement about value; whereas the online reviews feature prominent personal judgements about value for money. In addition, online reviews emphasise the social aspects of dining (who they are dining with, the social nature of the event, e.g. birthday, interactions throughout the meal), often spending as much time discussing their companions as the products and service involved in the experience. By contrast, print reviews tend to focus more on the ‘physical’ aspects of dining (the wine, the food, the decor). Finally, both platforms strongly emphasise food and service as the main criteria for judgement, accounting for almost half the word counts in both styles of reviews.
What can the practitioner take from this research? Firstly, the fact that food and service are the predominant criteria for both online and professional reviewers serves as a reminder for restaurant operators that, no matter how exquisite or stylish the restaurant is, well-cooked food and attentive service are significantly emphasised as the primary criteria by reviewers. Moreover, both review formats stress that the reliability of the booking system and efficiency of the service staff tended to enhance all reviewers’ satisfaction.
However, there are clear differences in the review styles that represent the different audiences they are addressing. Each format attempts to recognise the perceived social identity of their audience, with the print reviews taking the ‘insider expert’ voice and appearing to speak to a more sophisticated upmarket, product-focussed audience. The print reviews also assume their readers are less sensitive to price, rarely discussing the perceived value of the meal. By contrast, the online reviews are more ‘plain language’, discuss value directly and are socially driven. By being aware of these differences in reviewing approaches, restaurant operators’ can finesse their marketing strategies. By reading and reflecting on the link between the contrasting review styles and the social identity of the respective readers, practitioners can consider how their offering ‘fits’ with their target markets. Finally, as online review platforms become increasingly important, practitioners should engage with the content they find there, ensuring they take time for reading, reflecting and responding.
If you would like to read the original thesis this article is based on, please email: david.williamson@aut.ac.nz
Corresponding author
Ziye is an emerging researcher in the field of hospitality management. She received her bachelor’s degree from Beijing Union University in 2015 and her master’s degree from Auckland University of Technology in 2017, majoring in international hospitality management. Her research focusses on user-generated content in restaurant reviews, a relatively new data source for analysis in this area. Ziye also researches electronic word-of-mouth, online restaurant reviews and writers’ criteria for restaurant measurement.
Ziye Zhang can be contacted at: ziye0927@outlook.com
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Manjum, Marjanul, Saheed Adewale Lateef, William Earl Mustain, and Golareh Jalilvand. "Cycle-Induced Structural Evolution of Sulfur Cathodes in Lithium-Sulfur Batteries." ECS Meeting Abstracts MA2022-02, no. 2 (October 9, 2022): 136. http://dx.doi.org/10.1149/ma2022-022136mtgabs.
Full textAbstract:
Lithium (Li) ion batteries (LIBs) have been the predominant and fastest growing energy storage technology over the past few decades. A significant amount of LIB research has been carried out and remarkable improvements in the technology have been achieved. As a result, state-of-the-art LIBs offer superior cyclability, high efficiency, and high specific energy relative to competitors [1]. However, the desire for long-range electric vehicles (EVs) and grid-level energy storage and delivery is increasing the demands for batteries with very high gravimetric energy density (e.g. > 500 Wh/kg) [2]. This is simply much higher than what LIB electrode materials can practically offer (~ 260 Wh/kg). Therefore, alternative chemistries are needed at both electrodes. One material that has received significant attention recently as a replacement cathode material in Li-based batteries is sulfur (S). S has 5 times the theoretical specific energy than conventional LIB cathodes and can offer a practical energy density of > 500 Wh/kg when coupled with commercially available lithiated graphite or Li metal anodes [3]. S is also non-toxic, low-cost, and has high natural abundance. These properties make S a promising candidate for next-generation cathodes in Li battery systems. Yet, the path to achieving near theoretical capacity and long cycle life for S cathodes has proven difficult due to numerous unsolved scientific and technical issues including: i) the insulating nature of Sulfur (S8) and its discharged product (Li2S); ii) undesired solubility of the S products in the liquid electrolyte, resulting in the degrading so-called Li polysulfides “shuttling”, and iii) structural change of the S cathode during charge and discharge due to the large volume variation between the fully charged and discharged products [4]. Several approaches have been reported to address these challenges and improve the Li-S battery performance and durability. Despite these efforts, the advances have been mostly limited to a small number of cycles, or the need for complex structures and that would lead to expensive synthesis costs at the manufacturing scale. In fact, it is not truly known if such complex structures are even necessary as the literature lacks a truly systematic investigation into i) the influence of the S structure on its behavior; and ii) how the S structure evolves as a result of charging and discharging the cell. It is also likely that complex structures would not be reformed upon deep charging/discharging – making their possible advantages only temporary. Hence, there are a limited number of truly practical S cathodes that can be rationally developed [3, 4]. In this work, new insights are presented regarding the structural evolution of S cathodes throughout cycling. The structural changes experienced by the S cathodes were investigated by scanning electron microscopy (SEM) during charge and discharge (at C/10) over the lifetime of the cell (10’s to 100’s of cycles) for multiple cells. Cycling was done with Li-S coin cells that were made using a Li metal anode and a S cathode. The S cathode was prepared using commercially available S powder, a through low-cost, simple, and scalable electrode recipe and production techniques. Drastic microstructural and compositional transformations were observed in the S cathodes as a consequence of charging and discharging. Results suggest that there was a reversible swelling transfiguration of the support structure (conductive carbon plus binder) during each discharge and charge step. It was also observed that the location and distribution of S was changed, and new structures were formed. These results are expected to cast light on a fairly unknown area in the Li-S battery technology, which can help with future scale-up and manufacturing of these cells. References [1] G. E. Blomgren, “The development and future of lithium ion batteries,” Journal of The Electrochemical Society, vol. 164, no. 1, p. A5019, 2016. [2] B. Zhu, X. Wang, P. Yao, J. Li, and J. Zhu, “Towards high energy density lithium battery anodes: silicon and lithium,” Chemical science, vol. 10, no. 30, pp. 7132–7148, 2019. [3] Z. Lin and C. Liang, “Lithium–sulfur batteries: from liquid to solid cells,” Journal of Materials Chemistry A, vol. 3, no. 3, pp. 936–958, 2015. [4] ZW. She, Y. Sun, Q. Zhang, and Y. Cui. “Designing high-energy lithium–sulfur batteries” Chemical society reviews, vol. 45, no. 20, pp. 5605-5634, 2016.
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Suthers, Amy N., Hsuan Su, Sarah M. Anand, Jonathan C. Poe, Jeremy J. Rose, Frances T. Hakim, Steven Z. Pavletic, et al. "Increased TLR7 Signaling of BCR-Activated B Cells in Chronic Graft-Versus Host Disease (cGVHD)." Blood 130, Suppl_1 (December 7, 2017): 75. http://dx.doi.org/10.1182/blood.v130.suppl_1.75.75.
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Abstract After hematopoietic allogeneic stem cell transplantation (HCT), B cells reconstitute in the presence of alloantigen in a nucleic acid (NA)-rich environment. Ongoing tissue and cellular damage results in release of endogenous NA that may serve as ligand for endosomal Toll-Like Receptors (TLRs). Alloantibodies and autoantibodies, including NA-binding antibodies, have been associated with the presence of cGVHD manifestations. In patients after HCT, B cells are constitutively activated via key proximal B Cell Receptor (BCR) signaling molecules, Syk and BLNK (Allen JL et al Blood 2014, Flynn R et al Blood 2015) . In mouse models of autoimmunity, TLR7 or TLR9 can operate in conjunction with the BCR to mediate autoantibody production (Suthers A et al. Front Immunol. 2017). Whether TLR7/9-BCR signaling contributes to cGVHD remains unknown. We studied responses by TLR9 and TLR7 in B cells from patients >12 months post-HCT who had active, inactive or no cGVHD at the time of sample acquisition and were not receiving high dose steroid. In contrast to a previous study (She K et al. BBMT 2007) and consistent with findings by others (de Masson A et al Blood 2015), we did not find a consistent increase in B cell response to TLR9 agonist. Instead we found significantly higher TLR7 transcript expression in B cells from patients with active cGVHD (n=7) compared to no/inactive cGVHD patient B cells (n=11, p=0.042). TLR7 over-expression in mice leads to anti-RNA antibody production by immature B cells (Giltiay NV et al JEM 2013). We employed ELISA to measure antibodies to a known RNA-containing autoantigen, Ro-52 in a group of 66 plasma samples. We found that significantly more patients with active cGVHD (n=32) had anti-Ro-52 antibody compared to inactive cGVHD patients (n=22) or patients without cGVHD (n=12) (Fisher exact test for both comparisons = p<0.0001). This suggests potential opposing roles for TLR9 and TLR7 in cGVHD (Sharma et al, J.Immunol. 2015), and allowed us to hypothesize that B cells in cGVHD were aberrantly activated via TLR7. To determine if TLR7 activation was increased in cGVHD B cells, we measured IL-6 production. Without ex vivo stimulation, cGVHD patient B cells produced significantly more IL-6 (p=0.039) (Fig.1A). After TLR7 stimulation with R848, B cells from patients with active cGVHD had significantly increased IL-6 production compared those from patients without (p= 0.008) or those with inactive cGVHD (p=0.017) (Fig.1A). We next investigated the influence of the BCR-activated state in cGVHD on TLR7 responses and signaling. Using flow cytometry, we measured Ki-67 expression as a marker of activation after ex vivo stimulation with both low level surrogate BCR antigen and R848. We found that B cells from active cGVHD patients were significantly more responsive compared to no cGVHD patients (p=0.015) and healthy donors (p=0.045), revealing increased synergistic BCR-TLR7 signaling in cGVHD B cells (Fig.1B). To further investigate this, we employed qPCR to measure levels of the proximal BCR signaling molecule, Lyn, known to negatively regulate anti-NA antibody production (Lamagna et al. J. Immunol. 2014). We found that Lyn expression was significantly decreased in B cells from active cGVHD patients compared to healthy donor (p=0.001), inactive (p=0.042) or no (p=0.007) cGVHD patients (Fig.1C). Lyn can also negatively regulate TLR7/9 activation by directly associating with Interferon Regulatory Factor 5 (IRF5), which is important for pro-inflammatory cytokine production, including IL-6 (Ban et al, J.Immunol. 2016). Consistent with a role for Lyn in TLR7 activation, we found that IRF5 was significantly increased in active cGVHD patient B cells compared to all other groups (healthy donor, p=0.035; inactive cGVHD, p=0.011; no cGVHD, p=0.006) (Fig.1D). Notably, no difference in expression was found in downstream TLR7 transcription factors, IRF3 and IRF7 . Using a mouse model (Zhang C et al Blood 2006), we found significantly higher IRF5 expression in splenic B cells in animals with cGVHD manifestations (p=0.005). Ongoing mouse work will ascertain mechanistic roles for Lyn and IRF5 in TLR7 signaling by cGVHD B cells. Together data support a potentially pathogenic role of TLR7 signaling in cGVHD B cells. Development of agents that block this newly elucidated TLR7-BCR signaling axis in cGVHD is warranted. This work was supported by National Institutes of Health grant R01 HL129061 Figure 1 Figure 1. Disclosures Rizzieri: Erytech: Research Funding; Shire: Research Funding.
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Romio, Martina, Yuri Surace, Nicolas Eshraghi, Benedikt Herzog, Bruno Eckmann, Damian Marlon Cupid, Johannes Hoffmann, and Marcus Jahn. "Advanced Investigation of the Electrolyte-Mg Anode Interphase for the Development of Mg-Ion Batteries." ECS Meeting Abstracts MA2022-02, no. 4 (October 9, 2022): 465. http://dx.doi.org/10.1149/ma2022-024465mtgabs.
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Magnesium-ion batteries (MIBs) represent a promising chemistry to potentially substitute lithium-ion technologies in the e-mobility and stationary energy storage applications. This is due to the favourable properties of metallic Mg, such as: abundancy, non-toxic nature, high recycling rate1, low redox potential (-2.37 vs SHE), safety (smooth Mg2+ electrodeposition), as well as divalent character of Mg2+ cations which leads to higher theoretical volumetric capacity (3833 mAh/cm3) than Li (2046 mAh/cm3) and commercial graphite (760 mAh/cm3).2 However, the major obstacle in the further development of MIBs is the incompatibility of Mg metal anode with conventional electrolyte solutions, which are formed by mixing simple Mg-based salts (e.g Mg(TFSI)2, Mg(ClO4)2, etc.) and polar aprotic solvents (e.g. acetonitrile, carbonates, etc.). These solutions decompose at the surface of metallic Mg forming an electronic and ionic insulating layer, leading to the passivation of the Mg anode and poor performance of the overall cell. Conversely, organoborate (Mg-tetrakis(hexafluorosisopropyloxy)borate in monoglyme, MgBOR)3 or organoaluminate (1:2 AlCl3:PhMgCl in THF, APC)4 ethereal solutions are known to prevent the passivation of the Mg metal anode, allowing the reversible electrochemical Mg2+ electrodeposition onto its surface. Despite a great effort has been done in the development of MIB,5 very little is known about the formation, evolution and degradation of the solid electrolyte interphase (SEI) formed at the interface between metallic Mg and electrolyte. This work, therefore, aims to investigate the interactions between Mg metal and passivating (Mg(TFSI)2 in monoglyme:diglyme) and non-passivating (MgBOR and APC) electrolytes combining ex-situ and in-situ spectroscopic and microscopic techniques with electrochemical testing. The properties of the SEIs will be evaluated at different states of charge (ex-situ) and during cell cycling (in-situ). Raman, Fourier transformed infrared (FTIR) and X-ray photoelectron (XPS) spectroscopies are used to identify the composition of the electrolyte interphases, as well as monitor their changes upon cell discharge-charge cycles. Scanning electron microscopy (SEM) is performed to analyse the interphase morphologies, whereas scanning microwave microscopy (SMM)6,7 locally probes the impedance of the SEI layer. Atomic force microscopy (AFM) is also employed to evaluate the roughness of the Mg metal electrodes. Cyclic voltammetry (CV) and galvanostatic cycling with potential limitation (GCPL) are carried out in order to determine the electrochemical performance of bare Mg metal or covered with SEI layers. Furthermore, electrochemical impedance spectroscopy (EIS) is employed to probe the Mg2+ diffusion coefficients through the SEI layers at different state of charge (e.g. open circuit voltage, etc.) and determine charge transfer evolution with cycling time of the Mg metal anode. As the first step, a successful polishing method was developed to remove the native oxide layer form the surface of Mg discs allowing to expose a bare Mg metal to the electrolyte solutions and to evaluate their interactions. The polishing method also enabled to perform SMM imaging of the Mg metal since a roughness between 1-2.5 µm was achieved. The Mg discs were then immersed in the electrolyte solutions and an initial deposition of interfacial species (few nanometre thickness) was observed by SEM when Mg(TFSI)2 in monoglyme:diglyme was used, whereas a smooth surface was detected with MgBOR and APC electrolytes. This resulted in different electrochemical behaviours. In fact, symmetric cells (Mg||Mg) with MgBOR electrolyte showed a significantly higher cycling stability (> 250 h) than those with Mg(TFSI)2 in monoglyme:diglyme solution. In addition, when the latter electrolyte was used, fluorinated by-products were identified by XPS. In order to study the SEI formation and growth further, in-situ spectroscopic techniques (e.g. Raman and SMM) were employed to establish a correlation between the chemical composition of the electrolyte, the voltage range of the electrochemical tests and cycling time. In particular, the SMM method was applied to MIB technologies for the first time in this work. References I. R. P. United Nations Environment Programme, (available at https://wedocs.unep.org/20.500.11822/8702); J. Niu, Z. Zhang, D. Aurbach, Adv. Energy Mater., 2020, 10, 2000697; Z. Zhao-Karger, M. E. Gil Bardaji, O. Fuhr, M. Fichtner, J. Mater. Chem. A, 2017, 5, 10815–10820; D. Aurbach, Z. Lu, A. Schechter, Y. Gofer, H. Gizbar, R. Turgeman, Y. Cohen, M. Moshkovich, E. Levi, Nature, 2000, 407, 724; R. Dominko, J. Bitenc, R. Berthelot, M. Gauthier, G. Pagot, V. Di Noto, J. Power Sources, 2020, 478, 229027; A. Buchter, J. Hoffmann, A. Delvallée, E. Brinciotti, D. Hapiuk, C. Licitra, K. Louarn, A. Arnoult, G. Almuneau, F. Piquemal, M. Zeier, F. Kienberger, Rev. Sci. Instrum., 2018, 89, 23704; J. Hoffmann, M. Wollensack, M. Zeier, J. Niegemann, H. Huber, F. Kienberger, in 2012 12th IEEE International Conference on Nanotechnology (IEEE-NANO), pp. 1–4.
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Segara, Nuansa Bayu, Enok Maryani, Nana Supriatna, and Mamat Ruhimat. "INVESTIGATED THE IMPLEMENTATION OF MAP LITERACY LEARNING MODEL." Geosfera Indonesia 3, no. 2 (August 28, 2018): 146. http://dx.doi.org/10.19184/geosi.v3i2.7808.
Full textAbstract:
This article presents the results of the first implementation of map literacy learning model in middle school classes - this is the preliminary test. The implementation of this learning model will gain optimal results when it is conducted by following all the component of the model such as the syntax, theoretical framework, social system, teachers' roles, and support system. After the model implementation has been completed, the results showed that there was significantly different in students' spatial thinking skills before and after the treatment. However, the implementation also revealed that the model has some technical issues and thus to be improved. In a social system revision, the teacher has to be flexibly provide scaffolding every time he/she sees that the students need it. Teacher's book is significantly important to help a teacher lead the learning process. After improvement of the model has been completed, then it is ready to be implemented in the main field testing stage.
Keywords: map literacy, social studies learning, spatial thinking
References
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Karsznia, Izabela. "How does the enumeration unit size influence spatial pattern recognition in choropleth maps? User study." Abstracts of the ICA 1 (July 15, 2019): 1–2. http://dx.doi.org/10.5194/ica-abs-1-161-2019.
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<p><strong>Abstract.</strong> The recognition and preservation of the characteristic elements of visualization are one of the fundamental principles of map design, especially in map generalization. As underlined by numerous authors, the importance of preserving or even highlighting the context of the visualization constitutes one of the more significant challenges in cartographic generalization (Mackaness W. A., Ruas A., and Sarjakoski L. T., 2007; Burghardt D., Duchêne C., and Mackaness W. A., 2014). Cartographic generalization, which tailors a map and other graphics to the map’s purpose, detail level, as well as the intended audience’s requirements; is a difficult but necessary task for the map designer. Without careful and meaningful generalization, maps will not convey the essential patterns contained in the data (Maceachren and Ganter, 1990; Mackaness and Edwards, 2002; Zhang and Guilbert, 2016; Yu 2018).</p><p>The research on cartographic generalization and pattern recognition concerning topographic maps is very rich. Since the 1960s, when the period of automated generalization began, the issues connected with pattern recognition and preservation were also being tackled from many aspects. These concerned point pattern preservation, including building typification (Regnauld 2001; Sester 2001; Ai and Liu 2002; Burghardt and Cecconi 2003; Yan and Weibel 2008; Yan and Li 2013; Bereuter and Weibel 2017; Yu 2018), line pattern recognition (Heinzle and Anders 2007; Yang B., Luan X., Li Q.,2010; Touya 2010; Wang 2012; Brewer et al. 2013; Shoman W., and Gülgen F., 2017), and polygon pattern analysis (Steiniger S., et al 2006; Atwood Williams and Wentz 2008; Sayidov and Weibel 2016).</p><p>On the other hand, in thematic mapping, especially in choropleth map design, cartographic generalization and pattern recognition also play an important role as they help to preserve and convey spatial information (Maceachren 1982). The effectiveness with which thematic maps communicate spatial information is reflected in previous research (Maceachren 1982). It is often associated with map complexity, which is influenced by many factors, including the number of classes, the degree of autocorrelation present in the data, the choice of class intervals, and the shape and size of the enumeration units (Mersy 1990). Map complexity is related to spatial pattern recognition and is often ‘regarded as the visual intricacy of the spatial patterns formed by the map symbols’ (Mersy 1990: 15) which form specific patterns that are important to preserve in the thematic map generalization process.</p><p>In thematic maps, generalization takes place when either the number of classes is decreased or the enumeration unit size is increased. While aspects related to optimal data classification methods and the number of classes have been extensively examined (Chang 1976; Chang 1977; Cox 1976; Dent 1999; Slocum et al. 2008; Cabello et al. 2010), the size of the enumeration unit as well as its influence on pattern recognition has not, so far, been the subject of in-depth empirical studies. Robinson (1984) notes that an enumeration unit which is too small in size in thematic map, results in a dispersed image and difficulty in perceiving characteristic elements in the data. A generalization level which is too small causes the image to be blurred and diffuse. As a result the user loses the picture of the whole, the context, and the characteristic elements of the structure – he or she is no longer able to see the relevant spatial patterns. At the same time, a generalization level which is too large, as expressed by the size of the enumeration unit in choropleth maps, also causes the characteristic elements in the data to be lost, as the visualization is too general. In both cases, a too strong simplification of the map pattern might result in the loss of valuable information for the map reader (Bregt and Wopereis 1990). Thus the enumeration unit size for thematic maps should be designed in such a way as to preserve specific global and local spatial patterns.</p><p>The challenge, therefore, is to find the optimal generalization level whereby the spatial patterns present in the data are adequately transformed and can be distinguished by the user. Thus the research goal is an attempt to answer the question as to whether specific presentation methods, namely choropleth maps with particular enumeration unit sizes, result in a more effective recognition of the characteristic patterns or trends in data. We also want to answer the question: do users prefer methods which have specific enumeration unit sizes? The presented research aims to answer where the approximate limit may lie, expressed by the enumeration unit size after which the user loses the possibility of correctly and effectively exploring the spatial patterns presented on thematic maps.</p><p>To answer this research question an empirical user study is being designed. In this study, we would like to investigate the effectiveness of conveying spatial patterns on choropleth maps using different enumeration unit sizes. Within the study, choropleth map variants will be compared to a symbol map presenting the phenomena in a discreet way. The symbol map being used as a reference for the choropleth maps can be treated as a presentation of the raw data. We will consider choropleth maps that have several hexagonal enumeration unit shape. Four enumeration unit sizes will be assessed. The users will be asked to evaluate the similarity of the choropleth map variants to the reference symbol map, and nominate their preferred map. An example of the stimuli to be presented to users is shown in Figure 1.</p><p>The empirical study will be conducted with over 100 high school students. The main assumptions, as well as the preliminary results of the user study, will be discussed. Within the user study, among other tasks, two task types concerning map reading at both a general and a detailed reading level are being planned. One task type concerns map reading, especially the possibilities for conveying spatial patterns at a general reading level. The second task type will concern map comprehension at a detailed reading level. We believe it will allow us to verify which size of enumeration unit works better at a particular map reading level. We also want to explore which enumeration unit size works better for a particular task type. The assumptions will be verified based on the usability performance metrics: the correctness, the speed of the users’ responses as well as the users’ preferences.</p>
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"First person – Yiwei Zhang and Hui Tu." Journal of Cell Science 135, no. 7 (April 1, 2022). http://dx.doi.org/10.1242/jcs.260036.
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ABSTRACT First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping early-career researchers promote themselves alongside their papers. Yiwei Zhang and Hui Tu are co-first authors on ‘ Oligopeptide transporter Slc15A modulates macropinocytosis in Dictyostelium by maintaining intracellular nutrient status’, published in JCS. Yiwei is a PhD student in the lab of Huaqing Cai at Institute of Biophysics, Chinese Academy of Sciences, Beijing, China, where she is interested in understanding the interrelationship between cellular nutrient status and macropinocytic activity, and lipid transport. Hui is a PhD student in the same lab, investigating the mechanisms of macropinocytosis, cell migration and lipid transport.
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Uhde, Jan. "In Front and Behind the Camera." Kinema: A Journal for Film and Audiovisual Media, January 18, 2006. http://dx.doi.org/10.15353/kinema.vi.1137.
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KINEMA SPEAKS WITH CHINESE DIRECTOR XU JINGLEI Xu Jinglei (b. 1974) is one of the most versatile young film talents in Mainland China. She first achieved popularity in her home country for her television roles but soon won acclaim for her film appearances, having starred in ten features since 2002. She received the Chinese Film Society Performance Award for her first major film role in Zhang Yang's Spicy Love Soup (1997), the Baihua Best Actress Award in I Love You (Zhang Yuan, 2003) and the Golden Rooster Award for Best Supporting Actress in Far from Home (Yu Zhong, 2002). More recently, the Beijing-born actress and graduate of the Beijing Film Academy has taken on the role of director. Her first feature Wo he ba ba (My Father and I, 2003) was rewarded at home with a Golden Rooster for Best Directing Debut and invited to a number of international...
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Qu, Rui. "A brief analysis of Bing Xin, Ding Ling and Zhang Ailing's views on women's love in their literary works." International journal of health sciences, May 14, 2022, 6032–49. http://dx.doi.org/10.53730/ijhs.v6ns3.7324.
Full textAbstract:
Bing Xin, Ding Ling and Zhang Ailing are indispensable in the history of modern and contemporary Chinese literature, and they have also opened up a new world in the history of Chinese women's literature. Bing Xin's first short story "Two Families" vividly expresses the necessary factors for Bing Xin for an excellent family in the new era - the necessity of knowledge and the necessity of women to learn knowledge. But in this short story, when Bing Xin shows the current situation of the Kochi family, she incorporates her longing and desire for her future love and family environment. The concept has not yet been fully understood. In Ding Ling's literary creation, through a more in-depth analysis of the female images she created in her literary work "Ms. Sophie's Diary", it can be seen that these women broke through the barriers of feudal tradition and used Her actions interpret what is female liberation, and thus express Ding Ling's "life-oriented" and faith-like view of love. Zhang Ailing's concept of love is more clearly reflected in the more important work of her life - "Love in a Fallen City".