49 research outputs found
Josef Fulka
No full textZkoumá vztah mezi francouzskou teorií a psychoanalýzou (viz jeho Psychoanalýza a francouzské myšlení, 2008). Je známý svými překlady prací francouzských filozofů 20. století (Derrida, Foucault, Barthes, Balibar). Jeho poslední kniha pojednává o myšlení R. Barthese (Roland Barthes: od ideologie k fantasmatu, 2010). Učí filozofii na Fakultě humanitních studií Univerzity Karlovy v Praze a je též výzkumníkem na Akademii věd. Zabývá se filozofií 18. a 20. století, literární teorií, psychoanalýzou,..
Development of imidazotetrazines for the treatment of glioblastoma & as synthetic precursors to diazo species
No full textGlioblastoma multiforme (GBM), a grade IV astrocytoma, is the most prevalent, aggressive, and deadly form of malignant brain tumor with only 10% of patients surviving five years. The current standard treatment for GBM patients is bulk surgical resection and radiotherapy with concomitant and adjuvant temozolomide (TMZ), a small molecule DNA alkylating agent. The antitumor effect of TMZ is ultimately mediated through methylation of the O6-position of guanine and subsequent mismatch repair (MMR)-dependent cell death. Although TMZ was first synthesized in 1984 and has been FDA approved for two decades, certain key derivatives have been inaccessible due to synthetic challenges, precluding a broad exploration of the link between imidazotetrazine structure and biological activity. Novel synthetic strategies provided access to several new classes of C8-substituted imidazotetrazines and an evaluation of their aqueous stabilities enabled the derivation of a predictive model for imidazotetrazine hydrolytic stability based on the Hammett constant of the C8 substituent. Promising compounds modified at the C8 position were identified and found to have appropriate hydrolytic stability, enhanced blood-brain barrier permeability, lower hematological toxicity profiles, and superior activity relative to TMZ in a mouse model of GBM.
Despite its widespread use, certain GBM patient populations do not respond to TMZ therapy. Expression of O6-methylguanine DNA methyltransferase (MGMT) and loss of MMR function are the primary clinical modes of resistance to TMZ. Imidazotetrazine analogs modified at the N3 position were designed to deliver alternative DNA adducts that were irremovable by MGMT. An analog bearing a propargyl group at N3 demonstrated MGMT-independent activity in GBM cells in culture. Tuning the stability with an electron-donating chloro substituent at the C8 position produced novel dual-substituted imidazotetrazine CPZ, which displayed anticancer activity irrespective of MGMT expression and MMR status.
Imidazotetrazines such as TMZ are precursors to alkyl diazoniums, used therapeutically to alkylate DNA and elicit an anticancer effect. Given their stability as prodrugs and the reactivity of the species released, imidazotetrazines were repurposed into synthetic surrogates for diazomethane and other diazoalkanes. TMZ was employed to conduct esterifications and metal-catalyzed cyclopropanations, with methyl ester formation from a wide variety of substrates proving efficient and operationally simple. As a commercially available solid that is non-explosive and non-toxic, TMZ should find broad utility as a synthetic replacement for diazomethane.Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2022-05-01The student, Riley Svec, accepted the attached license on 2020-04-14 at 17:59.The student, Riley Svec, submitted this Dissertation for approval on 2020-04-14 at 18:07.This Dissertation was approved for publication on 2020-04-16 at 13:46.DSpace SAF Submission Ingestion Package generated from Vireo submission #14980 on 2020-08-25 at 17:40:15Made available in DSpace on 2020-08-27T00:49:56Z (GMT). No. of bitstreams: 3
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Agora
No full textVeletržní palác – Korzo Svoboda a etika života. Okolo Jana Sokola Připravili: Jan Vašíček (Arcibiskupské gymnázium, Praha) a Matěj Král (Gymnázium na Vítězné pláni, Praha) Kdy: 19:00-20:00 Jazyk: česky Násilí a občanství. Okolo Étienna Balibara Připravili: Richard Cisler (Praxis, FF UK) a Josef Matoušek (FHS UK) Kdy: 23:15-00:15 Jazyk: anglicky Bios and Politikos. Okolo Judith Revel Připravili: Nicolas Garrera (FHS UK), Jan Lockenbauer (FHS UK) a Philippe Charlebois (FHS UK) Kdy: 0:15-1:15 Ja..
Agoras
No full textRegister for the agora of your choice by 15 June at [email protected]! The Trade Fair Palace – Korzo Freedom and Ethics of Life Around Jan Sokol Prepared by: Jan Vašíček (Arcibiskupské Gymnázium, Prague) and Matěj Král (Gymnázium na Vítězné pláni, Praha) When: 7-8 PM Language: Czech Violence and Civility. Around Étienne Balibar Prepared by: Richard Cisler (Praxis, FF UK) and Josef Matoušek (FHS UK) When: 11:15-0:15 AM Language: English Bios and Politikos. Around Judith Revel Prepared by: Nicolas G..
Human Enhancement
No full textFaculty of Arts – room 200 Language Otherwise: Deafness as a Philosophical Problem Who: Josef Fulka What: Short Lecture When: 9:15 PM Language: Czech Humanism, Post-Humanism, Trans-Humanism Who: Emil Višňovský What: Short Lecture When: 9:45 PM Language: Slovak The Improved Body Who: Claire Marin What: Short Lecture When: 10:15 PM Language: French with simultaneous Czech translation Human Enhancement: A Deadly Ambition Who: Jean-Michel Besnier What: Short Lecture When: 10:45 PM Language: Fre..
Agora
No full textVeletržní palác – Korzo Svoboda a etika života. Okolo Jana Sokola Připravili: Jan Vašíček (Arcibiskupské gymnázium, Praha) a Matěj Král (Gymnázium na Vítězné pláni, Praha) Kdy: 19:00-20:00 Jazyk: česky Násilí a občanství. Okolo Étienna Balibara Připravili: Richard Cisler (Praxis, FF UK) a Josef Matoušek (FHS UK) Kdy: 23:15-00:15 Jazyk: anglicky Bios and Politikos. Okolo Judith Revel Připravili: Nicolas Garrera (FHS UK), Jan Lockenbauer (FHS UK) a Philippe Charlebois (FHS UK) Kdy: 0:15-1:15 Ja..
Formal Specification in “Z” Language by Software Z/EVES
No full textThe paper shows a short overview of representation formalisms, which can be used for specification of technical system functional requirements. Some basic model schemas of function called User Identification of ITS are presented by formal specification “Z” language and software Z/EVES
Petr Urban
No full textPetr Urban is a philosopher and translator based at the Czech Academy of Sciences where he leads the Department of Contemporary Continental Philosophy (Institute of Philosophy). His expertise lies in the areas of phenomenological philosophy and care ethics. He is author or editor of The Birth of Phenomenology (2010 in German), Phenomenology of the Body (2011 in Czech) and The Early Husserl and the Philosophy of Language (2013 in Czech). Apart from questioning the human-animal line, the conund..
'Annotata quaedam ex praelectionibus'
No full textFull title: 'Annotata quaedam ex praelectionibus | Dom: Doct: et Adjunct: Acrell in Phar|macop Svec die xxiii Oct: MDCCLXXVII | inceptis'. Notes from a lecture on pharmacology given by Johan Gustaf Acrel on 23 October 1777, probably when he was teaching at Uppsala University.
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