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Silli, Stefani. "Utjecaj japanske likovne i kulturne tradicije na umjetnički izričaj Takashija Murakamija." Tabula, no. 16 (November 29, 2019): 161–74. http://dx.doi.org/10.32728/tab.16.2019.11.
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Suvremeni umjetnik Takashi Murakami devedesetih godina prošloga stoljeća se dokazao kao jedan od najprovokativnijih i najutjecajnijih japanskih umjetnika svojega vremena. Kult njegove osobnosti je već odavno prerastao granice domovine. U umjetničkome svijetu poznat kao inovator suvremene japanske umjetnosti, uspjelo mu je promijeniti način poimanja umjetnosti unutar granica vlastite države i pozicionirati estetiku i senzibilitet japanske umjetnosti na svjetski umjetnički trg kao odgovor na postojeće uvjete i težnje postmodernoga doba. To novo je umjetničko načelo nazvao superflat. Murakami je predstavio superflat kao spoj visoke umjetnosti i pop-kulture, no istovremeno i kao istraživanje kulturno i društveno definiranih interpretacija umjetnosti u Japanu koje je potrebno nanovo vrednovati i definirati. Njegova su djela bogati amalgam simbola i značenja, koja nam daju duboki uvid u šarolikost tradicionalne i moderne japanske povijesti umjetnosti i kulture. Kratko ću predstaviti život i ključna djela Takashija Murakamija i njegov umjetnički pravac superflat. Cilj je ovoga rada pokazati i utvrditi opseg i značaj utjecaja Murakamijevih likovnih predaka na razvoj njegova umjetničkoga identiteta i izraza. Predstavit ću stilske karakteristike pojedinih likovnih škola i umjetnika iz različitih razdoblja japanske povijesti. Te iste oblikovne karakteristike ću usporedbom pojedinih djela potražiti u Murakamijevu opusu i umjetnosti superflata.
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Anan, Nobuko. "Two-Dimensional Imagination in Contemporary Japanese Women's Performance." TDR/The Drama Review 55, no. 4 (December 2011): 96–112. http://dx.doi.org/10.1162/dram_a_00125.
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Contemporary Japanese visual artist Murakami Takashi's theory of “superflat” Japanese arts and culture is nationalist and masculinist. However, women artists—including Yanagi Miwa and the performers of the Takarazuka Revue and Kegawa-zoku—use two-dimensional aesthetics to challenge the nationalist and masculinist construction of Japanese womanhood.
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STEINBERG, MARC. "Otaku consumption, superflat art and the return to Edo." Japan Forum 16, no. 3 (October 2004): 449–71. http://dx.doi.org/10.1080/0955580042000257927.
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Yunizal, Dwi. "KAJIAN BUDAYA JEPANG PADA PROSES DAN TEKNIK SENI LUKIS TAKASHI MURAKAMI." Gorga : Jurnal Seni Rupa 11, no. 2 (December 25, 2022): 513. http://dx.doi.org/10.24114/gr.v11i2.39802.
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Contemporary artist Takashi Murakami from Japan works in painting, sculpture, and commercial media including fashion, merchandise and animation with the superflat theory. The creative process combines traditional culture with contemporary culture, this study aims to understand Murakami's background in managing the dynamics of traditional culture with critical and genius visual discourse. The superflat theory was finally able to lead Murakami to become a well-known artist, due to the meeting of the dynamics of traditional and capitalist culture in the global market. The use of kawaii elements which mean cute and sweet, both as a style and a way of life can be found in Murakami's art. Symbolism plays an important role in attracting people's attention and working to elevate otaku culture's status as a representation of Japan. Murakami's mythical sensibility presents traditional Japanese, Chinese, and Buddhist myths giving mythopoeic achievements. This study uses library research with a semi-systematic approach that originates from journals, dissertations, theses, and internet media, based on the results of data and information processing, the works of artist Murakami are influenced by Japanese cultural structures such as Soga Shohaku, kawaii, and otaku. Murakami's awareness in understanding art discourse by incorporating a kawaii style, so that it is easily accepted in the global art market. Understanding how Murakami's formula manages traditional culture to become today's art, can be analyzed in a work entitled “Dragon in Clouds – Indigo Blue”. The conclusion of Murakami's work is the symbolism influenced by his personal experience.Keywords: soga shohaku, kawaii, otaku, superflat. AbstrakSeniman kontemporer Takashi Murakami dari Jepang mengerjakan karya lukisan, patung, dan media komersial termasuk fashion, barang dagang, dan animasi dengan teori superflat. Proses kreatif memadukan budaya tradisional dengan budaya kontemporer. Penelitian ini bertujuan memahami latar belakang Murakami mengelola dinamika budaya tradisional dengan wacana visual yang kritis dan jenius. Teori superflat akhirnya mampu mengantarkan Murakami menjadi seniman ternama, karena pertemuan dinamika budaya tradisional dan kapitalis di pasar global. Penggunaan unsur kawaii yang berarti imut dan manis, baik sebagai gaya maupun gaya hidup dapat ditemukan dalam karya seni Murakami. Simbolisme memainkan peran penting untuk menarik perhatian orang, dan berupaya mengangkat status budaya otaku sebagai representasi Jepang. Kepekaan mitis Murakami menghadirkan mitos tradisional Jepang, Cina, dan Buddha memberikan pencapaian mythopoeic. Penelitian ini menggunakan penelitian kepustakaan dengan pendekatan semi-sistematik yang bersumber dari jurnal, disertasi, tesis, dan media internet. Berdasarkan hasil pengolahan data dan informasi, karya seniman Murakami dipengaruhi oleh struktur budaya Jepang seperti soga shohaku, kawaii, dan otaku. Kesadaran Murakami dalam memahami wacana seni dengan memasukkan gaya kawaii, sehingga mudah diterima di pasar seni global. Memahami bagaimana formula Murakami mengelola budaya tradisional menjadi seni masa kini, dapat dianalisis dalam karya berjudul “Dragon in Clouds – Indigo Blue”. Kesimpulan dari karya Murakami adalah simbolisme yang dipengaruhi pengalaman pribadinya.Kata Kunci: soga shohaku, kawaii, otaku, superflat. Author:Dwi Yunizal : Institut Seni Indonesia Yogyakarta References:Birlea, O. M. (2021). “Cute Studies”. Kawaii (“Cuteness”) – A New Research Field. Philobiblon, 26(1), 83–100. https://doi.org/10.26424/philobib.2021.26.1.05.Borggreen, G. (2011). Cute and Cool in Contemporary Japanese Visual Arts. The Copenhagen Journal of Asian Studies, 29(01), 39–60. https://doi.org/10.22439/cjas.v29i1.4020.Hashimoto, M. (2007). Visual Kei Otaku Identity - An Intercultural Analysis. Intercultural Communication Studies, XVI(1), 87–99. https://www.researchgate.net/publication/239576790_Visual_Kei_Otaku_Identity-An_Intercultural_Analysis.Hu, X. (2021). Is Takashi Murakami’s Art an Exploration of Symbolism ?. Proceedings of the 2021 6th International Conference on Modern Management and Education Technology, 582, 560–564. https://doi.org/10.2991/assehr.k.211011.101.Khairi, I. A ., & Hafiz, H. (2022). Kajian Estetika Lukisan Realis Kontemporer Drs. Irwan, M.Sn. yang Berjudul di Ujung Tanduk. Gorga: Jurnal Seni Rupa, 11(01), 138-146. https://doi.org/10.24114/gr.v11i1.34129. Mamat, R., Rashid, R. A., Paee, R., & Ahmad, N. (2022). VTubers and anime culture: A case study of Japanese learners in two public universities in Malaysia. International Journal of Health Sciences, 6(S2), 11958–11974. https://doi.org/10.53730/ijhs.v6nS2.8231.Pellitteri, M. (2018). Kawaii Aesthetics from Japan to Europe: Theory of the Japanese “Cute” and Transcultural Adoption of Its Styles in Italian and French Comics Production and Commodified Culture Goods. Arts, 7(3), 24. https://doi.org/10.3390/arts7030024.Raman, K., Othman, A. N., Idris, M. Z., & Muniady, V. (2021). Kawaii-Style Pedagogical Agents Designs in Virtual Learning Environment: A Research Conceptual Framework. International Journal of Academic Research in Progressive Education and Development, 10(01), 154-170. https://doi.org/10.6007/IJARPED/v10-i1/8489.Raubenheimer, L. (2006). Blandness and the digital sublime in Takashi Murakami’s designs for Louis Vuitton. South African Journal of Art History, 21(2), 74–88. http://hdl.handle.net/2263/10629.Rupadha, I. K. (2016). Memahami Metode Analisis Pasangan Bibliografi (Bibliographic Coupling) dan Ko-Sitasi (Co-Citation) Serta Manfaatnya untuk Penelitian Kepustakaan. Lentera Pustaka, 2(1), 58–69. https://doi.org/10.14710/lenpust.v2i1.12358. Sanjaya, B. & Citra, P. A. C. (2022). Fenomena Aku Setelah Pandemi Covid-19 sebagai Ide Penciptaan Karya Seni Lukis. Gorga: Jurnal Seni Rupa, 11(01), 107-113. https://doi.org/10.24114/gr.v11i1.33867.Sari, M. (2020). Penelitian Kepustakaan (Library Research) dalam Penelitian Pendidikan IPA. NATURAL SCIENCE: Jurnal Penelitian Bidang IPA dan Pendidikan IPA. 6(1). 41-53. https://ejournal.uinib.ac.id/jurnal/index.php/naturalscience/article/view/1555.Sharp, K. (2007). Superflatlands : The global cultures of Takashi Murakami and superflat art. ACCESS: Critical Perspectives on Communication, Cultural & Policy Studies, 26(1), 32–42. https://search.informit.org/doi/10.3316/informit.665904534038717. Uzelac. G. (2022). Harnessing The Myths of Now :Restoring Social Harmony Through Mythic Art. The University of Sydney, 1-69. https://hdl.handle.net/2123/27724.Yazovskaya, O., (2018). Artistic Language of Mass Culture As Illustrated By Takashi Murakami (On Materials From “Under The Radiation Falls” Exhibit, 2017-2018, Moscow). IJASOS-International E-Journal of Advances in Social Sciences, IV(11), 516-520. https://doi.org/10.18769/ijasos.455682.
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Beynon, Davi. "From Techno-cute to Superflat: Robots and Asian Architectural Futures." Mechademia 7, no. 1 (2012): 129–48. http://dx.doi.org/10.1353/mec.2012.0004.
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Choi, Jaehyuk. "Murakami Takashi’s Changing “Superflat” After the 2011 Great East Japan Earthquake." Japanese Cultural Studies 67 (July 31, 2018): 345–66. http://dx.doi.org/10.18075/jcs..67.201807.345.
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Looser, Thomas. "Superflat and the Layers of Image and History in 1990s Japan." Mechademia 1, no. 1 (2006): 92–109. http://dx.doi.org/10.1353/mec.0.0043.
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Mujika, Iñigo. "From Superfit to Superfat." International Journal of Sports Physiology and Performance 6, no. 3 (September 2011): 293–94. http://dx.doi.org/10.1123/ijspp.6.3.293.
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Loh, Waiyee. "Superflat and the Postmodern Gothic: Images of Western Modernity in Kuroshitsuji." Mechademia 7, no. 1 (2012): 111–27. http://dx.doi.org/10.1353/mec.2012.0007.
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Cheng, Guangming, Banghong Guo, Yunfei Zhou, Shi Chen, and Zhenhua Li. "Wavelength selective switch with superflat passbands based on a microelectromechanical system micromirror array." Optical Engineering 53, no. 12 (December 9, 2014): 127102. http://dx.doi.org/10.1117/1.oe.53.12.127102.
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Li, Jinying. "From Superflat Windows to Facebook Walls: Mobility and Multiplicity of an Animated Shopping Gaze." Mechademia 7, no. 1 (2012): 203–21. http://dx.doi.org/10.1353/mec.2012.0010.
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Kamrowska, Agnieszka. "Summer Wars: międzypokoleniowe anime." Media - Kultura - Komunikacja Społeczna 3, no. 15 (February 19, 2020): 45–53. http://dx.doi.org/10.31648/mkks.5148.
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Celem autorki artykułu jest analiza konfliktu pokoleń wpisującego się w szerszą opozycję japońskiej tradycji i nowoczesności w animowanym filmie autorstwa Mamoru Hosody. Reżyser przedstawia w nim tradycyjną, wielopokoleniową japońską rodzinę, której nestorka będzie obchodzić 90. urodziny. Przygotowania do uroczystości zostają zakłócone przez atak na wirtualną platformę społecznościową Oz, którego skutki są odczuwalne w świecie realnym. W obliczu zagrożenia rodzina jednoczy się i wspólnymi siłami pokonuje wirtualnego wroga. Reżyser skonfrontował ze sobą dwa światy: japońskiej tradycji, która powoli odchodzi w zapomnienie, oraz współczesności, która rozgrywa się głównie w cyberprzestrzeni. Do zobrazowania wirtualnego świata wykorzystał stylistykę japońskiego ruchu artystycznego Superflat. Z niebywałym pietyzmem przedstawił w filmie strukturę japońskiego rodu, składającego się z linii głównej i liniibocznych, uwikłanych we wzajemne zależności. W sytuacji zagrożenia rodzina jednoczy się ponad familijnymi waśniami i pokoleniowymi konfliktami, aby działając razem w przestrzeni wirtualnej i fizycznej, pokonać wroga. Film Hosody ukazuje, że nawet w zdigitalizowanym współczesnym świecie wciąż jest miejsce na tradycyjne wartości i międzypokoleniową solidarność.
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Longo, Angela. "Da animação para o anime: configurações estéticas de composição e intervalo." Diálogo com a Economia Criativa 4, no. 11 (August 20, 2019): 71. http://dx.doi.org/10.22398/2525-2828.41171-88.
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Esse artigo propõe uma análise sobre como determinadas configurações estéticas dentro da animação japonesa vieram a determinar as características distintas do que convencionamos a chamar de Anime. Nós iremos olhar para a história estética do anime, desde os primeiros experimentos com animação de recorte, celofane e celuloide para compreender a formalização do modelo de produção da animação limitada. Posteriormente, iremos analisar como as configurações das técnicas full limited, hyper-limited e superflat propuseram espaços compositivos inovadores e um uso diferenciado do intervalo entre e através das imagens. O campo digital também criou um espaço aberto para o intercâmbio de técnicas aparentemente distintas que trouxeram inovações compositivas para o Anime. Por essa razão, iremos analisar como a habilidade de composição de camadas da animação veio a ser importante na inserção e combinação de elementos móveis e imóveis dentro do espaço digital. Por fim, concluímos sobre como esse cenário trouxe uma composição intercambiável no espaço diegético e como isso afetou a composição e o intervalo dentro do Anime.
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Chatenet, Ludovic, and Anne Beyaert-Geslin. "From communication to art: McDonald’s and flat design." Comunicação e Sociedade 31 (June 29, 2017): 391–402. http://dx.doi.org/10.17231/comsoc.31(2017).2625.
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The status of communication objects or images always changes. This paper proposes to observe this phenomenon from a semiotics point of view in order to analyse how a brand reinvents its visuals and how this reinvention is related to a new marketing strategy. In fact, this paper tries to show how meaning of posters reveals the importance of brands in contemporary everyday life. We will show that the ads created by TBWA for McDonald’s 2015 campaign are rather considered as an aestheticisation project than an artisticisation. While inspired by the brand’s “mythologic” history and pushing properties of the product into the background, flat design exemplifies the latest forms of life to date. Therefore, brands seem more involved and rooted in social life as their communication strategy is rather based on gathering a community than advertising their products. Visual ads are hence absorbed by an aestheticisation practice, specific to connected life, from which they adopt the norms. As it remains distinctive, art also maintains its criticizing position and Murakami’s superflat thus discloses a certain disenchantment concealed in standardised designs.
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Gottesman, Zachary Samuel. "The Rotoscopic Uncanny: Aku no Hana and the Aesthetic of Japanese Postmodernity." Animation 13, no. 3 (November 2018): 192–206. http://dx.doi.org/10.1177/1746847718799416.
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CGI has led to a theoretical revolution in media studies. What is cinema when reality can be created on a computer? What is animation when superflat 2D aesthetics are becoming haunted by 3D digital graphics? This article adds a third term to the debate: rotoscoping. The author analyzes the first exclusively rotoscoped Japanese anime, Aku no Hana (The Flowers of Evil), a contemporary reinterpretation of Charles Baudelaire’s Les Fleurs du Mal that reflects on postmodern malaise, rural decay and depopulation, and otaku escapism, in order to examine the aesthetic of the rotoscope in relation to cinema and anime. He argues that rotoscoping is an uncannying of the cinematism and animitism, or a polemical response to both the ideologies of Disney immersive realism and anime flat animation. The article investigates the narrative’s ‘writer of postmodern life’ Sawa Nakamura in relation to Baudelaire’s modernism and the conditions of postmodernity themselves: the structure of Japanese imperialism today and its effect on Gunma prefecture, the setting of the show. Finally, the author analyzes the hostile response to the show among otaku to explore how the hauntology of the rotoscopic machine channels the ghosts of neoliberalism, the super-exploited laborers of the third world.
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Shinohara, Keisuke, Satoshi Shimomura, and Satoshi Hiyamizu. "Sharp Transmission Coefficient in GaAs/AlAs Resonant Tunneling Diodes with (411)A Superflat Interfaces Grown by Molecular Beam Epitaxy." Japanese Journal of Applied Physics 38, Part 1, No. 9A (September 15, 1999): 5037–39. http://dx.doi.org/10.1143/jjap.38.5037.
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Kitada, Takahiro, Keisuke Nii, Tetsuya Hiraoka, Satoshi Shimomura, and Satoshi Hiyamizu. "Improved interface abruptness in pseudomorphic InGaAs/AlGaAs quantum wells with (411)A superflat interfaces grown by molecular beam epitaxy." Journal of Vacuum Science & Technology B: Microelectronics and Nanometer Structures 19, no. 4 (2001): 1546. http://dx.doi.org/10.1116/1.1388602.
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Chatenet, Ludovic, and Anne Beyaert-Geslin. "Da comunicação à arte: a McDonald’s e o flat design." Comunicação e Sociedade 31 (June 29, 2017): 377–90. http://dx.doi.org/10.17231/comsoc.31(2017).2624.
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O estado dos objetos ou imagens de comunicação está sempre a mudar. Este artigo propõe-se observar este fenómeno de um ponto de vista da semiótica, a fim de analisar de que forma uma marca reinventa a sua imagem e de que forma esta reinvenção está relacionada com uma nova estratégia de marketing. De facto, este artigo tenta demonstrar de que forma o significado dos pósteres revela a importância das marcas na vida quotidiana contemporânea. Iremos demonstrar que os anúncios criados pela TBWA para a campanha de 2015 da McDonald’s são mais considerados um projeto de estetização do que uma artistização. Apesar de inspirado na história “mitológica” da marca e empurrando as propriedades do produto para segundo plano, o flat design exemplifica as últimas formas de vida até à data. Por conseguinte, as marcas parecem estar mais envolvidas e enraizadas na vida social, uma vez que a sua estratégia de comunicação se baseia mais em reunir uma comunidade do que em publicitar os seus produtos. Os anúncios visuais são, consequentemente, absorvidos por uma prática de estetização, específica de um estilo de vida conectado, do qual adotam as normas. Como continua a ser distintiva, a arte também mantém a sua posição de crítica, e o superflat de Murakami revela, assim, um certo desencanto que se esconde por trás de designs normalizados.
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Shinohara, Keisuke, Yasuyuki Shimizu, Satoshi Shimomura, and andSatoshi Hiyamizu. "Recovery of (411)A Superflat Interfaces in GaAs/Al0.3Ga0.7As Quantum Wells Grown on (411)A GaAs Substrate by Molecular Beam Epitaxy." Japanese Journal of Applied Physics 38, Part 1, No. 8 (August 15, 1999): 4715–17. http://dx.doi.org/10.1143/jjap.38.4715.
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Gazi, Jeeshan. "Soiveillance: Self-Consciousness and the Social Network in Hideaki Anno’s Love & Pop." Surveillance & Society 16, no. 1 (April 1, 2018): 84–111. http://dx.doi.org/10.24908/ss.v16i1.6434.
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This article analyses the surveillance aesthetic of Hideaki Anno’s 1998 film Love & Pop. It is proposed that the film communicates the concept of “soiveillance”—a watching (veillance) that is of one’s self (soi). What underpins soiveillance is the paranoia associated with social surveillance (Marwick 2012), specifically the self-consciousness involved in the image sharing that constructs the virtual self of the social media user (Willett 2009). With its theme of enjo kosai—or “paid-dates” between adult males and female teenagers—Love & Pop’s communication of soiveillance further illuminates the impact of one’s gender status within the social network, and the manner in which real-world patriarchy and misogyny pass into the virtual construction of selves. The methodology used to argue these points rests on a reconfigured take on the term “scopophilia” within the study of visual media. Scopophilia, rethought as a love of vision itself, aligns with Murakami’s (2000) theory of the superflat on three key points: the acknowledgment that emerging technologies have created new image-functions and image-structures that require a broadening of our theoretical vocabulary; an atemporal approach to the reading of images, such that a late-nineties film like Anno’s can provide important insights into 21st century concerns; and a recognition of intermedial convergence, which allows us to read the activity of online video sharing as a form of narrative equivalent to the sequencing of shots within a cinematic montage.
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Ardern, Jon, and Anab Jain. "Superflux." Ubiquity: The Journal of Pervasive Media 4, no. 1 (June 1, 2015): 69–74. http://dx.doi.org/10.1386/ubiq.4.1-2.69_7.
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Bhat, Vikas, Andrew J. Gale, John H. Griffin, Laurent O. Mosnier, and Annette von Drygalski. "Reversal of Novel Oral Anticoagulant (NOAC)-Induced Bleeding in Mice By Engineered superfactor Va." Blood 124, no. 21 (December 6, 2014): 695. http://dx.doi.org/10.1182/blood.v124.21.695.695.
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Abstract Introduction and Objectives: Novel oral anticoagulants (NOACs), such as Factor (F) Xa inhibitors (Rivaroxaban and Apixaban) or the direct thrombin inhibitor (Dabigatran), are used for prevention of venous thromboembolism and ischemic strokes. However, conventional hemostatic reversal strategies in case of bleeding or surgery are ineffective, posing a major unmet clinical need. We recently demonstrated that superFVa, a novel FVa variant engineered with mutations of 3 activated protein C (APC) cleavage sites and a disulfide bond between the A2 and A3 domains, has enhanced biological activity and APC resistance. SuperFVa provided efficient normalization of hemostasis in hemophilia A mice and in animal models of APC-induced bleeding. Moreover, superFVa synergistically reduced bleeding in combination with recombinant human (rh) FVIIa in hemophilia mice. Thus, superFVa fits the criteria for a prohemostatic biologic. Therefore, the in vitro and in vivo effects of superFVa alone and in combination with other prohemostatic agents such as rhFVIIa or 4-Factor prothrombin complex concentrates (4F-PCC) as a novel hemostatic reversal strategy for NOAC-induced bleeding were determined. Materials and Methods: In vitro procoagulant properties of superFVa alone and in combination with rhFVIIa or 4F-PCC were studied using thrombin generation assays in normal human plasma (NHP) in the presence of FXa inhibitors (Rivaroxaban, Apixaban) or the direct thrombin inhibitor (Dabigatran, active form). In vivo prevention of blood loss by superFVa after intravenous injection of Rivaroxaban, Apixaban, or Dabigatran was studied using the tail clip model in BalbC mice. Results: Rivaroxaban and Apixaban each dose-dependently reduced thrombin generation in NHP and reduced the Endogenous Thrombin Potential (ETP) by ~60% at therapeutic concentrations (200 nM). Addition of either superFVa (50 nM) or rhFVIIa (40 nM, equivalent to a 90 µg/kg therapeutic dose in hemophilia patients), increased thrombin generation to some extent. However, ETP and thrombin peak height increased dose-dependently when increasing concentrations of superFVa (6.25 to 400 nM) were added with rhFVIIa (40 nM). superFVa effects appeared synergistic, with a plateau reached at 25-50 nM superFVa and ETP restored to ~93% of normal. Synergistic effects of superFVa were also present and even more pronounced in combination with 4F-PCC (1.35 U/ml; therapeutic plasma concentration). In the presence of Dabigatran (1 µM), superFVa (0.1 nM-100 nM) in combination with rhFVIIa (40 nM) or 4F-PCC (1.35 U/ml) showed a concentration dependent reduction of the lag time of thrombin generation. However, in contrast to the FXa inhibitors, in the presence of Dabigatran, no effects on ETP and thrombin peak height were observed for the addition of superFVa or combinations of superFVa and rhFVIIa or 4F-PCC. The in vivo efficacy of superFVa to reduce NOAC-induced bleeding was determined by blood loss after tail transection in BalbC mice injected i.v. with Rivaroxaban (40 mg/kg), Apixaban (20 mg/kg), or Dabigatran (0.4 mg/kg). Mean blood loss in mice injected with Rivaroxaban (16 µL/g), Apixaban (16.5 µL/g) or Dabigatran (14.5 µL/g) was significantly higher than baseline bleeding (4 µL/g, p<0.001). superFVa reduced blood loss after Rivaroxaban or Apixaban administration significantly in a dose dependent manner, e.g., superFVa at 40 U/kg significantly reduced bleeding to the baseline control level (5 µL/g). RhFVIIa (1 mg/kg) was able to reduce bleeding caused by Rivaroxaban but not by Apixaban. Neither superFVa nor rhFVIIa was able to reduce bleeding caused by Dabigatran. Conclusion: superFVa alone or in combination with rhFVIIa significantly improved in vitro thrombin generation in the presence of FXa inhibitors and to some extent in the presence of a direct thrombin inhibitor. SuperFVa alone consistently reduced bleeding in mice treated with FXa inhibitors, whereas a mixed response dependent on the type of FXa inhibitor was obtained with rhFVIIa. None of the agents was able to decrease bleeding in mice induced by Dabigatran. Because superFVa exerts a potent class effect as a hemostatic reversal strategy for FXa inhibitor-induced bleeding, it deserves further consideration for potential development as a hemostatic agent. Disclosures Gale: University of California, San Diego: University of California, San Diego Patents & Royalties. Griffin:The Scripps Research Institute: The Scripps Research Institute Patents & Royalties. Mosnier:The Scripps Research Institute: The Scripps Research Institute Patents & Royalties. von Drygalski:University of California, San Diego: University of California, San Diego Patents & Royalties.
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Bhat, Vikas, Annette von Drygalski, Andrew J. Gale, John H. Griffin, and Laurent O. Mosnier. "Synergistic Effect in Bleed Reduction By superfva and Recombinant Human FVIIa in Vivo Suggests a Novel Bypassing Strategy for Hemophilia Patients with Inhibitors." Blood 124, no. 21 (December 6, 2014): 692. http://dx.doi.org/10.1182/blood.v124.21.692.692.
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Abstract Introduction: In Hemophilia patients with inhibitors, recombinant human (rh)FVIIa-based bypassing strategy does not always achieve hemostasis indicating a clinical need for improved treatment strategies. We engineered an activated FVa variant (superFVa) with mutations at 3 activated protein C cleavage sites (R506, R306 and R679) and an engineered interdomain disulfide bond (H609C-E1691C) connecting the A2 and A3 domains. SuperFVa resisted inactivation and showed superior hemostatic properties in FVIII-deficient plasma and in mouse models of Hemophilia A compared to wild type rhFVa. Therefore, the hemostatic effects of superFVa alone and in combination with rhFVIIa in hemophilia with inhibitors were determined in more detail. Materials and Methods: Procoagulant and clot stabilizing properties of superFVa, rhFVIIa, and combinations thereof were studied in thrombin generation (endogenous thrombin potential (ETP) and peak height) and clot lysis assays in hemophilia A and normal plasma with or without high titer inhibitors. In vivo efficacy of superFVa alone and in combination with rhFVIIa for bleed reduction in hemophilia was tested in FVIII-deficient mice using a tail clip model. Results: Extensive dose-response titrations of superFVa, rhFVIIa, and combinations thereof in hemophilic or normal plasma with inhibitors indicated synergistic responses for normalization of thrombin generation or clot stabilization. For instance, at 0.4 nM rhFVIIa (1/100 of the therapeutic plasma level), the concentration of superFVa required to normalize thrombin generation was reduced 10-fold. Vice versa, rhFVIIa tested up to 40 nM only marginally improved thrombin generation, however, rhFVIIa in the presence of a low concentration of superFVa (3 nM) normalized thrombin generation at concentrations 50-fold below the therapeutic plasma level. Saturation of the synergistic effect between superFVa and rhFVIIa was evident as thrombin generation reached a plateau at ~110% of normal plasma at higher concentrations of superFVa and rhFVIIa. Similar synergistic normalization of clot lysis time was observed when superFVa and rhFVIIa were used together at low concentration. Beneficial effects of superFVa and rhFVIIa combinations were also observed in 5 individual plasma samples of hemophilia A patients with inhibitors (41-280 BU/ml). ETP and peak height improved ~1.5-3 fold when both superFVa (3 nM) and rhFVIIa (2 nM) were present compared to the individual 10 to 20-fold higher concentrations of superFVa (30 nM) or rhFVIIa (40 nM). Also, a therapeutic dose of rhFVIIa administered to 2 hemophilia patients with inhibitors (32 & 64 BU/ml) provided unremarkable improvements of thrombin generation in plasma taken before and 10 minutes post-infusion, whereas thrombin generation was fully restored upon titration of superFVa ex-vivo. In-vivo tail bleed analysis of FVIII-deficient mice showed a dose dependent reduction of bleeding by superFVa (mean blood loss was 25.9 µL/g at 10 U/kg; 9.7 µL/g at 40 U/kg and 2.5 µL/g at 200 U/kg of superFVa compared to 26.3 µL/g for saline). At the highest dose of superFVa (200 U/kg), bleed reduction was indistinguishable from the bleed reduction by rhFVIII (200 U/kg; 2.9 µL/g). Injection of 1 or 3 mg/kg rhFVIIa, reduced mean blood loss from 25.9 µL/g (saline control) to 16.8 (p=0.1) or 7.2 µL/g (p=0.003), respectively, but rhFVIIa’s effects did not reach the blood loss reduction achieved with rhFVIII (2.9 µL/g, p=0.03). However, combination of rhFVIIa (1 mg/kg) with 10 U/kg superFVa, a concentration that did not reduce bleeding by itself, significantly reduced bleeding from 16.7 to 10.2 µL/g (p=0.05). Combination of rhFVIIa (3 mg/kg) with superFVa (40 U/kg) decreased bleeding even further (1.6 µL/g; p=0.01), similar to what was observed with rhFVIII. Conclusion: The engineered superFVa variant showed synergistic procoagulant effects with rhFVIIa in vitro in hemophilic and normal plasma with inhibitors in thrombin generation and clot lysis assays. Notably, in vivo, superFVa reduced bleeding similar to rhFVIII in FVIII-deficient mice in a dose-dependent fashion, and it was able to enhance further bleed reduction when administered in combination with rhFVIIa. These results warrant further characterization of the potential therapeutic benefits of superFVa as a novel bypassing strategy either alone or in combination with rhFVIIa-based therapy in hemophilia patients with inhibitors. Disclosures von Drygalski: University of California, San Diego: University of California, San Diego Patents & Royalties. Gale:University of California, San Diego: University of California, San Diego Patents & Royalties. Griffin:The Scripps Research Institute: The Scripps Research Institute Patents & Royalties. Mosnier:The Scripps Research Institute: The Scripps Research Institute Patents & Royalties.
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Gale, Andrew J., John H. Griffin, Laurent O. Mosnier, Vikas Bhat, and Annette von Drygalski. "Improved coagulation and haemostasis in haemophilia with inhibitors by combinations of superFactor Va and Factor VIIa." Thrombosis and Haemostasis 115, no. 03 (2016): 551–61. http://dx.doi.org/10.1160/th15-07-0525.
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SummaryBypassing inhibitors in haemophilia patients is limited to activated (a) Factor(F)VII products. We introduced “FVa activity augmentation” as another bypassing strategy and studied effects of an engineered FVa variant designated superFVa. Procoagulant and clot stabilising properties of superFVa and recombinant human (rh)FVIIa, either alone or in combination, were studied in thrombin generation and clot lysis assays in normal human plasma (NHP) with or without anti-FVIII inhibitors, in haemophilia plasma, and in FVIII-deficient mice or in wild-type mice with anti-FVIII inhibitors. SuperFVa was as effective as rhFVIIa to improve thrombin generation or clot lysis. Furthermore, procoagulant effects were significantly enhanced when these compounds were combined. RhFVIIa at 40 nM (a therapeutic concentration) improved thrombin generation mildly, but markedly improved thrombin generation when combined with a low concentration (e. g. 3 nM) of superFVa. In clot lysis studies, the concentration of rhFVIIa to normalise clot lysis times could be reduced by 100-fold (e. g. from 40 nM to 0.4 nM) when combined with a low concentration (0.37 nM) of superFVa. In haemostasis studies of FVIII-deficient mice, blood loss was dose-dependently reduced by either superFVa or rhFVIIa. SuperFVa (200 U/kg) corrected mean blood loss indistinguishably from rhFVIII. Blood loss correction by rhFVIIa was greatly improved when combined with superFVa. Similar blood loss correction results were observed for therapies in wild-type mice after infusion with anti-FVIII inhibitors. Thus, superFVa may be an effective procoagulant agent in the setting of haemophilia with inhibitors and it merits further evaluation for new bypassing strategies.Supplementary Material to this article is available online at www.thrombosis-online.com.
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Rahman, Abdul, Chang-Won Lee, and Heejeong Jeong. "Frequency tunable superflash based on an electromagnetically induced transparency (EIT)." Optics Express 30, no. 15 (July 7, 2022): 26570. http://dx.doi.org/10.1364/oe.463679.
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We present a new controllable superflash, a maximum transient peak at the falling edge of a square pulse, using a three-level electromagnetically induced transparency (EIT). The superflash in a two-level system occurs at a certain value of the detuning of the probe laser (Δ peak ) when the optical depth (OD) of the medium is sufficiently large and constant. Here, we show the external tunability of the Δ peak for obtaining the maximum transient peak by introducing a three-level EIT. Owing to the EIT dispersion properties, we effectively tune the phase of the forward-scattered light (E s ) by externally controlling the EIT coupling light intensities associated with the Rabi frequency (Ω c ). When the incident light is turned off, the total transmitted field (E t ) experiences an out-of-phase shift, producing a peak intensity that is three times higher than the input. We observe that this new class of superflash (Type II) occurs near the EIT window and exhibits inverse-linearity of the OD, which is in contrast with the characteristics of the previously reported two-level superflash (Type I). Furthermore, we find the quadratic nature of tunability in Δ peak (Ω c ).The new tunability of the superflash by the Rabi frequency may facilitate more rapid and effective control of the superflash compared to a passive optical medium.
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Stensmyr, Marcus C. "Superfly." Current Biology 23, no. 8 (April 2013): R298—R300. http://dx.doi.org/10.1016/j.cub.2013.03.018.
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Kube, M. C., O. E. Rossler, and J. L. Hudson. "A “superfat” chaotic attractor." Chaos, Solitons & Fractals 3, no. 2 (March 1993): 141–48. http://dx.doi.org/10.1016/0960-0779(93)90060-e.
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Joseph, Bilgimol Chumappumkal, Byron Y. Miyazawa, Charles T. Esmon, Mitchell J. Cohen, Annette von Drygalski, and Laurent O. Mosnier. "An engineered activated factor V for the prevention and treatment of acute traumatic coagulopathy and bleeding in mice." Blood Advances 6, no. 3 (February 3, 2022): 959–69. http://dx.doi.org/10.1182/bloodadvances.2021005257.
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Abstract Acute traumatic coagulopathy (ATC) occurs in approximately 30% of patients with trauma and is associated with increased mortality. Excessive generation of activated protein C (APC) and hyperfibrinolysis are believed to be driving forces for ATC. Two mouse models were used to investigate whether an engineered activated FV variant (superFVa) that is resistant to inactivation by APC and contains a stabilizing A2-A3 domain disulfide bond can reduce traumatic bleeding and normalize hemostasis parameters in ATC. First, ATC was induced by the combination of trauma and shock. ATC was characterized by activated partial thromboplastin time (APTT) prolongation and reductions of factor V (FV), factor VIII (FVIII), and fibrinogen but not factor II and factor X. Administration of superFVa normalized the APTT, returned FV and FVIII clotting activity levels to their normal range, and reduced APC and thrombin-antithrombin (TAT) levels, indicating improved hemostasis. Next, a liver laceration model was used where ATC develops as a consequence of severe bleeding. superFVa prophylaxis before liver laceration reduced bleeding and prevented APTT prolongation, depletion of FV and FVIII, and excessive generation of APC. Thus, prophylactic administration of superFVa prevented the development of ATC. superFVa intervention started after the development of ATC stabilized bleeding, reversed prolonged APTT, returned FV and FVIII levels to their normal range, and reduced TAT levels that were increased by ATC. In summary, superFVa prevented ATC and traumatic bleeding when administered prophylactically, and superFVa stabilized bleeding and reversed abnormal hemostasis parameters when administered while ATC was in progress. Thus, superFVa may be an attractive strategy to intercept ATC and mitigate traumatic bleeding.
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Von Drygalski, Annette, Thomas J. Cramer, John H. Griffin, Andrew J. Gale, and Laurent O. Mosnier. "Superior in Vivo Hemostatic Properties of an Engineered Factor Va Variant for Hemophilia Mice." Blood 120, no. 21 (November 16, 2012): 17. http://dx.doi.org/10.1182/blood.v120.21.17.17.
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Abstract Abstract 17 Approximately 1/3rd of hemophiliacs with inhibitors fail treatment with FVIIa-based bypassing agents. New intervention strategies are urgently needed. Activated FV (FVa) enhances thrombin formation by the prothrombinase complex, but is rapidly inactivated by activated protein C (APC). Mutation of the APC cleavage site, R506Q (FVLeiden), is prothrombotic and improves hemostasis in humans and mice with hemophilia. We therefore engineered FV-derivatives with additional mutations of the APC cleavage sites (Arg506/306/679Gln) and introduced a disulfide bond (Cys609-Cys1691) connecting the A2 and A3 domains (FV(A2-SS-A3)). Introduction of the disulfide bond prevents the dissociation of the A2 domain as the final irreversible step of inactivation. All FV mutants were activated with thrombin prior to experimentation. Procoagulant properties of FVa mutants were studied in vitro and in hemophilia mouse models. Mutation of all three APC cleavage sites (Arg506/306/679) and addition of the disulfide bond yielded “superFVa” that had 2- to 3-fold higher specific activity compared to recombinant human (rh)FVa, rhFVa(A2-SS-A3), rhFVaLeiden or rhFVaLeiden(A2-SS-A3) in purified prothrombinase assays and in thrombin generation assays in FV- and FVIII-deficient plasma. superFVa corrected the aPTT at 20-fold lower concentrations compared to rhFVa in FV-deficient plasma. superFVa was highly resistant to inactivation by APC in purified prothrombinase assays and in thrombin generation assays in FV-deficient plasma. While superFVa retained 90–100% activity in the presence of APC, FVa(A2-SS-A3) and FVaLeiden(A2-SS-A3) lost ∼90% and ∼40% of their activities, respectively. In FVIII-deficient mice, superFVa reduced bleeding significantly compared to rhFVa in a dose dependent fashion after tail clip (n=10–17 per group). Blood loss was determined separately for the first and second 10 min after tail clip to study the effects of FVa mutants on re-bleeding. FVa mutants were dosed at equal activities determined in prothrombinase assays (expressed in arbitrary units). At low doses of intravenous FVa mutants (40 units), mean blood loss during the first 10 min after clip in FVIII-deficient mice was significantly decreased following injection of superFVa compared to saline (6.5 μL/g vs. 15.5 μL/g; p=0.02), whereas blood loss following injection of rhFVa was not (16.7 μL/g). At high doses of FVa mutants (100 units), superFVa and rhFVa were effective in reducing blood loss in FVIII-deficient mice following intravenous injection. Mean blood loss with superFVa was further improved to 3.9 μl/g, and with rhFVa was 8.2 μl/g. Both results were significant compared to mean blood loss following saline injection (15.5 μL/g; p≤0.05). FVIII-deficient mice were considered protected at 10 min when blood loss was ≤ 9.9 μL/g, which is the mean plus 3 SDs derived from tail bleeding of wild-type BalbC mice. While only ∼45% of FVIII-deficient mice injected with saline or rhFVa (40 units) were protected, protection against bleeding increased to 83% with superFVa (40 units). When 100 units of FVa mutants were given, protection with both mutants (superFVa or FVa) was ≥ 90%. Of note, during the second 10 min and therefore during the combined 20 min of bleeding, only superFVa at high dose (100 units) effectively reduced bleeding. Mean blood loss in FVIII-deficient mice following intravenous superFVa was 11.7 μL/g during the 2nd 10 minutes of bleeding, compared to 20.2 μL/g with saline (p=0.02). Our results indicate that molecular engineering of FV, which combined two alterations for improving thrombin generation (increased specific activity and APC resistance), provided a FVa-mutant, superFVa, with unique procoagulant properties. In vivo, superFVa not only decreased initial bleeding, but also significantly decreased re-bleeding, indicating that superFVa efficiently improved clot formation and also enhanced clot stabilization. These results warrant more in depth characterization of the potential therapeutic benefits of superFVa as a novel bypassing strategy in hemophilia patients with inhibitors. Disclosures: No relevant conflicts of interest to declare.
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Ferreira, Raúl, Arturo de Pablo, Fernando Quirós, and Julio D. Rossi. "Superfast quenching." Journal of Differential Equations 199, no. 1 (May 2004): 189–209. http://dx.doi.org/10.1016/j.jde.2003.11.001.
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Peyricot, Olivier, and Vincent Beaubois. "Superflux ralenti." Multitudes 53, no. 2 (2013): 198. http://dx.doi.org/10.3917/mult.053.0198.
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Tu, Zuo-Lin, Qin Wu, Wenbo Wang, G. Q. Zhang, Zi-Ke Liu, and F. Y. Wang. "Convolutional Neural Networks for Searching Superflares from Pixel-level Data of the Transiting Exoplanet Survey Satellite." Astrophysical Journal 935, no. 2 (August 1, 2022): 90. http://dx.doi.org/10.3847/1538-4357/ac7f2c.
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Abstract In this work, six convolutional neural networks (CNNs) have been trained based on 15,638 superflare candidates on solar-type stars, which are collected from the three years of Transiting Exoplanet Survey Satellite (TESS) observations. These networks are used to replace the manually visual inspection, which was a direct way of searching for superflares, and exclude false-positive events in recent years. Unlike other methods, which only used stellar light curves to search for superflare signals, we try to identify superflares through TESS pixel-level data with lower risk of mixing false-positive events and give more reliable identification results for statistical analysis. The evaluated accuracy of each network is around 95.57%. After applying ensemble learning to these networks, the stacking method promotes accuracy to 97.62% with a 100% classification rate, and the voting method promotes accuracy to 99.42% with a relatively lower classification rate at 92.19%. We find that superflare candidates with short duration and low peak amplitude have lower identification precision, as their superflare features are hard to be identified. The database includes 71,732 solar-type stars and 15,638 superflare candidates from TESS with corresponding feature images and arrays, and the trained CNNs in this work are public available.
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GABARRA-NIECKO, Veronica, Patricia J. KEELY, and Michael D. SCHALLER. "Characterization of an activated mutant of focal adhesion kinase: ‘SuperFAK’." Biochemical Journal 365, no. 3 (August 1, 2002): 591–603. http://dx.doi.org/10.1042/bj20020065.
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Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that plays an important role in normal cellular processes such as adhesion, spreading, migration, proliferation and survival. In addition, FAK is overexpressed in a variety of cancer cells and tumours and may play a role in the development of human cancer. As a prelude to modelling the role of aberrant FAK signalling in the initiation of cancer, the goal of the present study was to engineer point mutations in FAK that would enhance enzymic activity. A number of substitutions that were reported as activating mutations in other tyrosine kinases were introduced into FAK. Glutamic acid substitutions for two lysine residues in the activation loop of FAK, based upon the K650E (Lys650→Glu) mutant of fibroblast-growth-factor receptor 3, were made to create ‘SuperFAK'. Two brain-specific exons were engineered into avian FAK to create FAK6.7. SuperFAK and, to a lesser extent, FAK6.7, exhibited increased catalytic activity in vitro compared with wild-type FAK. The expression of SuperFAK and FAK6.7 in fibroblasts led to hyperphosphorylation of FAK substrates. Although the catalytic activity of SuperFAK and FAK6.7 was largely independent of cell adhesion, tyrosine phosphorylation of downstream substrates was adhesion-dependent. Further, since SuperFAK exhibited the same ability as wild-type FAK to recruit Src family kinases, tyrosine phosphorylation of substrates was likely due to direct phosphorylation by FAK. In addition to enhanced biochemical signalling, SuperFAK also increased the motility of epithelial cells. SuperFAK and FAK6.7 may be valuable molecular tools to investigate the potential role of aberrant FAK signalling in human disease.
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Chumappumkal Joseph, Bilgimol, Laurent O. Mosnier, and Annette von Drygalski. "Superfactor Va, an Engineered Factor V Molecule, Effectively Reduces Bleeding and Acute Coagulopathy in Mouse Models of Trauma and Shock." Blood 134, Supplement_1 (November 13, 2019): 1101. http://dx.doi.org/10.1182/blood-2019-124433.
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Traumatic bleeding is a leading cause of death and disability, without targeted interventions available outside blood component resuscitation and tranexamic acid. Acute traumatic coagulopathy (ATC) in association with bleeding occurs in ~30-50% of patients and carries a high mortality risk. Recent evidence suggests a role of activated protein C (APC) in the development of ATC, whereby excessive generation of APC leads to rapid depletion of Factor(F) V, FVIII and hyperfibrinolysis causing depletion of fibrinogen. Here, we investigated to what extent targeted intervention with an engineered activated FV variant (superFVa), resistant to inactivation by APC, can reduce traumatic bleeding and prevent or normalize hemostasis parameters indicative of ATC, a process thought to be different from disseminated intravascular coagulation (DIC). SuperFVa was engineered to withstand cleavage by APC through mutations of 3 APC cleavage sites (Arg506/306/679Gln), with additional stability provided by introduction of a disulfide bond (Cys609-Cys1691) between the A2 and A3 domains. Materials and Methods First, an established trauma/shock model for ATC (Chesebro et al. 2009) was used. Here, trauma is induced by laparotomy and shock is induced by blood withdrawal (~500ul) to reduce and maintain the mean arterial pressure [MAP] from 75±5 to 35±5 mmHg for 1 hour. SuperFVa (0.4-0.8 mg/kg) was administered by continuous infusion 30 minutes after trauma/shock induction. Second, a liver laceration model was used where ATC develops as the consequence of severe bleeding. SuperFVa was administered either as bolus (0.4-0.8mg/kg) before injury or as continuous infusion (0.8mg/kg) started 30 minutes after injury. Bleeding, APTT clotting times, clotting factor activity levels (FII, FV, FVIII, FX, fibrinogen) and Thrombin-Antithrombin (TAT) complexes were assessed to determine the extent of ATC at various time points. Results In the trauma/shock model, only mice subjected to both trauma and shock developed ATC, evident from a significant APTT prolongation (25.4±0.2 to 36.1±0.2 seconds), associated with a severe reduction of FV (14%) and FVIII( 6%), a partial reduction of fibrinogen (44%), and no effect on FX (89%) and FII (89%). Administration of superFVa normalized the APTT (27.1±0.2 seconds) despite the persistence of shock, returned FV and FVIII levels to their normal range, but had no effect on fibrinogen. TAT levels increased significantly upon trauma/shock (1522 ±125 ng/mL) and were reduced by superFVa administration (511±125 ng/mL), suggesting improved hemostasis. After liver laceration severe bleeding occurred within 60 minutes, causing shock (MAP decreased to 35±5), selective reductions of FV, FVIII, and fibrinogen levels, and prolongation of the APTT clotting time, indicating the development of ATC. SuperFVa prophylaxis prior to liver laceration reduced blood loss significantly (non-treated mice 0.54±0.01 vs. pre-treated mice 0.34±0.01 mL, p<0.0001), prevented APTT prolongation and depletion of FV and FVIII. Thus, prophylactic administration of superFVa prevented the development of ATC. Most bleeding after liver laceration occurred in the first 15-30 minutes (0.44±0.01mL at 30 minutes) and ATC became evident at 30 min (APTT prolongation to 32.63±0.2 seconds; partial depletion (~50%) of FV and FVIII). To determine effects of superFVa on the reversal of ongoing ATC, superFVa intervention was started therefore at the 30-minute time point. superFVa blunted additional blood loss after 30 minutes, normalized prolonged APTT clotting times and reversed FV and FVIII levels to their normal range. Reversal of ATC by superFVa was associated with a reduction of TAT levels (646.5±125 ng/mL) that were increased by ATC (1577.0 ±125 ng/mL). Conclusion SuperFVa restored hemostasis in two mouse models of ATC where coagulopathy was induced by either trauma/shock or by severe bleeding. Improved hemostasis in ATC by superFVa was achieved by correction of APTT clotting times and normalization of depleted FV and FVIII levels and was associated with a reduction of elevated TAT levels. Because superFVa rescued traumatic bleeding to prevent the development of ATC and was also efficacious for the reversal of ongoing ATC, targeted interception of ATC by superFVa therefore may be an attractive strategy to reduce complications associated with ATC. Disclosures Mosnier: The Scripps Research Institute: Membership on an entity's Board of Directors or advisory committees, Patents & Royalties. von Drygalski:University of California San Diego: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties; UniQure, Bayer, Bioverativ/Sanofi, Pfizer, Novo Nordisk, Biomarin, Shire, CSL Behring: Consultancy; Hematherix Inc.: Membership on an entity's Board of Directors or advisory committees, Other: Founder.
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MARLEY, NIGEL J., SANDRA J. MCINNES, and CHESTER J. SANDS. "Phylum Tardigrada: A re-evaluation of the Parachela." Zootaxa 2819, no. 1 (April 14, 2011): 51. http://dx.doi.org/10.11646/zootaxa.2819.1.2.
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We assessed the available morphological evidence to see if this corroborates the paraphyly in the Parachela (Tardigrada) as suggested by recent molecular data. We reconcile molecular phylogenetics with alpha morphology, focusing on claw and apophysis for the insertion of the stylet muscles (AISM). We combine molecular and morphological evidence to define six new taxa within the Parachela Schuster et al 1980. These include two new families of Isohypsibiidae fam. nov. and Ramazzottidae fam. nov. along with four new superfamilies of Eohypsibioidea superfam. nov., Hypsibioidea super- fam. nov., Isohypsibioidea superfam. nov., and Macrobiotoidea superfam. nov.
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von Drygalski, Annette, Vikas Bhat, Andrew J. Gale, Patricia M. Averell, Thomas J. Cramer, Darlene J. Elias, John H. Griffin, and Laurent O. Mosnier. "An engineered factor Va prevents bleeding induced by direct-acting oral anticoagulants by different mechanisms." Blood Advances 4, no. 15 (August 10, 2020): 3716–27. http://dx.doi.org/10.1182/bloodadvances.2020001699.
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Abstract Control of bleeding with direct-acting oral anticoagulants (DOACs) remains an unmet clinical need. Activated superFactor V (superFVa) is an engineered activated protein C (APC)–resistant FVa variant with enhanced procoagulant activity resulting from an A2/A3 domain disulfide bond and was studied here for control of DOAC-induced bleeding. SuperFVa reversed bleeding induced by FXa inhibitors (rivaroxaban, apixaban), and the FIIa inhibitor dabigatran in BalbC mice. The blocking anti-protein C and APC [(A)PC] antibody SPC-54 also reduced FXa inhibitor induced bleeding similar to superFVa, whereas dabigatran-induced bleeding was not affected. This indicated that sufficient APC was generated to contribute to bleeding in the presence of FXa inhibitors, but not in the presence of dabigatran, suggesting that mechanisms contributing to bleeding differed for FXa and FIIa inhibitors. Despite different mechanisms contributing to bleeding, superFVa effectively reduced bleeding for all DOACs, indicating the versatility of superFVa’s properties that contribute to its universal prohemostatic effects for DOAC associated bleeding. Supported by thrombin generation assays on endothelial cells in normal plasma spiked with DOACs and patient plasma anticoagulated with DOACs, 3 complementary mechanisms were identified by which superFVa achieved DOAC class-independent prohemostatic efficiency. These mechanisms are resistance to inactivation by APC, overcoming the FV activation threshold, and maximizing the efficiency of the prothrombinase complex when the available FXa is increased by FVIIa-based prohemostatics. In summary, it is this versatility of superFVa that delineates it from other prohemostatic agents as a promising class-independent rescue agent in bleeding situations associated with DOACs.
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Von Drygalski, Annette, Andrew J. Gale, Laurent Burnier, Thomas J. Cramer, John H. Griffin, and Laurent O. Mosnier. "An Engineered Factor Fva Prevents Bleeding Induced By Anticoagulant Wild Type Activated Protein C." Blood 122, no. 21 (November 15, 2013): 203. http://dx.doi.org/10.1182/blood.v122.21.203.203.
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Abstract Increased risk of bleeding is observed in patients receiving therapy with a variety of anticoagulant drugs, and there is an unmet need for prohemostatic agents that reduce bleeding risk. In some clinical trials, wild type (wt) APC therapy was associated with an increased risk of serious bleeding. In most animal models of inflammatory injury and disease where APC was beneficial, APC’s cytoprotective effects were responsible for the protective effects of APC therapy whereas its anticoagulant effects were neither required nor contributing. Thus, wt APC’s anticoagulant activities and associated risk of bleeding may be a limiting factor for potential novel wt APC therapies. The availability of a wt APC-anticoagulant specific antidote or reversal agent that does not affect wt APC’s cytoprotective activities would be highly desirable. We hypothesized that superFVa, an engineered FVa-variant that potently normalizes hemostasis in hemophilia, fits the criteria for a prohemostatic biologic that could reduce wt APC-anticoagulant-induced bleeding, and here we test this hypothesis. SuperFVa has enhanced specific activity compared to wt FVa due to an engineered disulfide bond (Cys609-Cys1691) between the A2 and A3 domains (FV(A2-SS-A3)) and, its biological activity is augmented by mutations of the APC cleavage sites (Arg506/306/679Gln). As a result of these modifications, superFVa was found to be resistant to wt APC and normalized hemostatic properties and prevented bleeding in a hemophilic mouse model much more efficiently than wt FVa. In aPTT clotting assays both superFVa and wt FVa dose-dependently normalized clotting times when wt-APC was used to prolong clotting (aPTT > 100 sec). However, superFVa normalized the aPTT at 100-fold lower concentrations compared to wt FVa. In thrombin generation assays using either human or murine plasma, superFVa fully restored thrombin generation at concentrations where wt FVa did not show effects. In an ex vivo whole blood aPTT assay, intravenous (iv) injection of murine recombinant wt APC (0.5 mg/kg) in Balb/c mice doubled clotting times from 30 sec to ∼ 60 sec (n=40). Addition of superFVa (1 nM) to whole blood significantly normalized aPTT clotting times whereas wt FVa failed to show a significant effect. In a tail clip-bleeding model in Balb/c mice, injection (iv) of human recombinant or plasma-derived wt APC induced significant bleeding at 1.25 mg/kg and mean blood loss increased from 3.4 µL/g with saline to 27 µL/g with wt APC treatment. SuperFVa injected (iv 3.5 mg/kg) 2 min prior to wt APC administration reduced bleeding significantly to 9.2 µL/g (n∼10 per group). In another bleeding model, liver laceration was used because it provides important information concerning microvessel-mediated bleeding after acute organ injury. After adaptation and technical modifications of the model used in rats and rabbits for mouse anatomy and validation in hemophilia versus control mice, this model provided a reliable assessment of bleeding with a ∼ 4-fold reduced inter-individual range of blood loss compared to the tail clip-bleeding model. Injection (iv) of human wt APC increased blood loss from 29 µL/g to 49 µL/g, and the excessive bleeding was associated with a ∼40% mortality rate. SuperFVa reduced wt APC-induced bleeding after 20 min significantly to 29 µL/g and abolished bleeding-induced mortality. Remarkably, bleeding patterns in the tail clip and liver laceration models were different when blood loss was determined separately for the 1st and 2nd 10 min after injury. In the tail clip-model wt-APC-induced bleeding during both 1st and 2nd 10 min after tail clip and superFVa decreased blood loss during both phases. In the liver laceration model, most blood loss occurred immediately after injury and bleeding during the 2nd 10 min was less pronounced. In this model, however, superFVa corrected blood loss entirely during the 1st 10 min phase and fully prevented bleeding during the 2nd 10 min phase. Our results provide proof of principle that superFVa is effective in the prevention and reversal of wt APC-induced bleeding. Thus, in addition to improving hemostasis in hemophilia, superFVa protects against bleeding in 2 different mouse models where bleeding was induced by wt APC. Hence, superFVa deserves future consideration for development as a prohemostatic agent in situations where bleeding is a serious risk. Disclosures: No relevant conflicts of interest to declare.
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Durrande, José-Laure. "L'homme superflu." Littérature 65, no. 1 (1987): 109–27. http://dx.doi.org/10.3406/litt.1987.1421.
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Betrián-Blasco, Pedro, Gerard Marti-Aguasca, and Gemma Giralt-Garcia. "Sinus Superflex DS© early collapse in systemic arterial duct." Cardiology in the Young 30, no. 3 (February 4, 2020): 436–37. http://dx.doi.org/10.1017/s1047951120000189.
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AbstractWe implanted two sinus Superflex DS© stents in a systemic non-stenotic arterial duct of a newborn with hypoplastic left heart syndrome. Forty-eight hours later an important collapse of the stent was detected and treated with a balloon expandable stent. Sinus Superflex DS© has been specifically designed for systemic ducts. This complication generates doubts about its radial force in this scenario.
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Lee, Jun-Hoe, Kevin M. Lewis, Timothy W. Moural, Bogdan Kirilenko, Barbara Borgonovo, Gisa Prange, Manfred Koessl, Stefan Huggenberger, ChulHee Kang, and Michael Hiller. "Molecular parallelism in fast-twitch muscle proteins in echolocating mammals." Science Advances 4, no. 9 (September 2018): eaat9660. http://dx.doi.org/10.1126/sciadv.aat9660.
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Detecting associations between genomic changes and phenotypic differences is fundamental to understanding how phenotypes evolved. By systematically screening for parallel amino acid substitutions, we detected known as well as novel cases (Strc, Tecta, and Cabp2) of parallelism between echolocating bats and toothed whales in proteins that could contribute to high-frequency hearing adaptations. Our screen also showed that echolocating mammals exhibit an unusually high number of parallel substitutions in fast-twitch muscle fiber proteins. Both echolocating bats and toothed whales produce an extremely rapid call rate when homing in on their prey, which was shown in bats to be powered by specialized superfast muscles. We show that these genes with parallel substitutions (Casq1, Atp2a1, Myh2, and Myl1) are expressed in the superfast sound-producing muscle of bats. Furthermore, we found that the calcium storage protein calsequestrin 1 of the little brown bat and the bottlenose dolphin functionally converged in its ability to form calcium-sequestering polymers at lower calcium concentrations, which may contribute to rapid calcium transients required for superfast muscle physiology. The proteins that our genomic screen detected could be involved in the convergent evolution of vocalization in echolocating mammals by potentially contributing to both rapid Ca2+ transients and increased shortening velocities in superfast muscles.
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Palatinus, Lukas. "SUPERFLIP: unpublished features." Acta Crystallographica Section A Foundations of Crystallography 66, a1 (August 29, 2010): s106. http://dx.doi.org/10.1107/s0108767310097709.
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Hadfield, Robert H. "Superfast photon counting." Nature Photonics 14, no. 4 (March 27, 2020): 201–2. http://dx.doi.org/10.1038/s41566-020-0614-0.
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Fitzgerald, Richard J. "Superfast superconducting vortices." Physics Today 70, no. 10 (October 2017): 30. http://dx.doi.org/10.1063/pt.3.3723.
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Knight, K. "MITES' SUPERFAST MUSCLES." Journal of Experimental Biology 213, no. 15 (July 16, 2010): iii. http://dx.doi.org/10.1242/jeb.048462.
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Davidson, D. "'Superfleas' bounce back?" Veterinary Record 131, no. 10 (September 5, 1992): 223. http://dx.doi.org/10.1136/vr.131.10.223.
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Ucciani, Louis. "La médiation superflue." Philosophique, no. 11 (January 1, 2008): 41–53. http://dx.doi.org/10.4000/philosophique.260.
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Soininen, P. I., and N. B. Kopnin. "Stability of superflow." Physical Review B 49, no. 17 (May 1, 1994): 12087–94. http://dx.doi.org/10.1103/physrevb.49.12087.
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PENG, KUANGDING. "THE SOLITARY WAVE MODEL OF SUPERFLUIDITY." International Journal of Modern Physics B 19, no. 01n03 (January 30, 2005): 99–102. http://dx.doi.org/10.1142/s0217979205028001.
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We propose the solitary wave model of superfluidity. According to harmonic oscillator model of quasi-lattice of liquid, it is proven that superfluid domains (SD) exist in He liquid, in which the resistanceless motion of liquid molecules (LM) can be carry out. At temperature lower than T c, all SD connect with each other and superflow in whole liquid takes place. Applying Toda's potential, under continuous conditions, we obtain the motion equation of LM, and its exact solution. Substituting these results into Schrödinger equation of LM, we can prove the existence of solitary waves of LM and the non-linear Schrödinger equation of LM. The motion of solitons of LM leads to a superflow. On the basis of coherent condition of wave of LM, we derive the formula of transition temperature Tc of superfluidity. From the formula, the relation of the onset temperature Tc of superflow on inert layers is explained.
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Yu, Yongle. "The second law of thermodynamics and entropy-decreasing processes with 4He superflows." Modern Physics Letters B 30, no. 29 (October 28, 2016): 1630008. http://dx.doi.org/10.1142/s0217984916300088.
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We review on a recently proposed quantum exception to the second law of thermodynamics (SLT). We emphasize that 4He superflows, like any other forms of flows, shall carry entropy or heat in a thermal environment. Following that, one can use a heterogeneous 4He superflow loop to realize entropy-decreasing processes. We also mention that the heat content of a superflow has an unusual dependence on flow velocity, which is an important factor contributing to the entropy-decreasing processes.
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Iamonico, Duilio. "Nomenclatural notes on some annual mallows (Malvaceae)." Acta Botanica Croatica 77, no. 1 (April 1, 2018): 28–35. http://dx.doi.org/10.1515/botcro-2017-0018.
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AbstractA nomenclatural study concerning the annual mallows (Lavaterasect.Lavatera) is presented here. The namesLavatera africana,L. biennis,L. grandiflora,L. moschataby Miergues,L. punctata,L. punctatavar.maroccana,L. rosea,L. trimestrisvar.brachypoda,L. trimestrisvar.trimestrisf.colorata,Olbia deflexa, andStegia lavateraare investigated.Lavatera grandiflora,L. rosea,L. moschataby Miergues,Olbia deflexa, andStegia lavateraare illegitimate names according to Arts. 52.1, 52.2 or 53.1 of the ICN. The other names are valid and legitimate and are lecto- or neotypified on specimens preserved in the herbaria BM, LE, MAF, MPU, P, and TO. Three species belonging toLavaterasect.Lavateraare AcceptedL. trimestriss.lat.,L. maroccana, andL. punctata(=Olbia deflexa, nom. superfl. et illeg. =L. biennis). Three varieties are here recognized forL. trimestris: var.trimestris(≡Malva rosea, nom. superfl. et illeg.Lavatera grandiflora, nom. superfl. et illeg.Stegia lavatera, nom. superfl. et illeg. =L. africana=L. trimestrisvar.trimestrisf.colorata), var.brachypoda, and var.moschata(a new combination).