Fran Galovic's dramatic opus

Fran Galović posebna je pojava razdoblja književne moderne u Hrvatskoj. To je razdoblje intenzivnih političkih i društvenih previranja na prostorima koji su tada bili u sastavu Austro-Ugarske Monarhije. Novo razdoblje donosi i novu književnu poetiku koja baca novi pogled na klasičnu strukturu književnih djela. Naglasak se stavlja na psihička proživljavanja glavnih junaka. U djelima hrvatske moderne mogu se pronaći i elementi naturalizma,književnog učenja koji se temelji na pretpostavci da je proučavanje književnosti jednako proučavanju ljudskog tijela,a sve ono što je skriveno se ponovno otkriva. Fran Galović je dijalektni pjesnik i prozaik, ali glavni naglasak u ovom radu bit će stavljen na njegov dramski opus. Galovićeve drame stavljaju novo svjetlo na međuljudske odnose, uz smrt koja je neizbježna. Galovićeve drame o kojima će biti riječ u ovom radu su jednočinke Pred smrt i Tamara koje su izvedene nakon Galovićeve smrti 1914. godine. U drami Pred smrt prati se sukob između društva i pojedinca, koji ne želi da mu se nametaju norme. Suočen s prevelikom boli glavni junak bira smrt a , Tamara, zavodnica istoimene drame, u smrt baca svoju novu žrtvu, Putnika koji ju je odbio. Galovićeva smrt u 27. godini života spriječila ga je u potpunom ostvarenju svog književnog talenta, iza njega je ostalo književno blago koje se i danas proučava

N-SULFONYLPURINES AND PEPTIDE PHENANTHRIDINE DERIVATIVES SYNTHESIS, INTERACTIONS WITH POLYNUCLEOTIDES AND BIOLOGICAL TESTING

U ovom radu istra.ene su metode priprave i svojstva dvije vrste biolo.ki aktivnih heterocikla iz grupe malih molekula: 1) N-sulfonilpurina (potencijalnih antitumorskih lijekova i inhibitora enzima purin nukleozid fosforilaze) i 2) peptidnih derivata fenantridina (potencijalnih antitumorskih lijekova i fluorescentnih senzora). Pripravljena je serija C6, N9 supstituiranih purina sa sulfonamidnim farmakoforima. Najprije je sintetizirana serija 6-klorpurinskih derivata uvo.enjem sulfonilnog supstituenta u polo.aj N9 purinske baze. Potom su, supstitucijom klora u C6 polo.aju, sintetizirani 6-morfolino- i 6-bis(2- hidroksietil)amino-derivati N-9-sulfonilpurina. Biolo.ka aktivnost 6-morfolino- i 6-bis(2-hidroksietil)amino-derivata purina ispitana je MTT testom na stani.nim linijama leukemije i limfoma (Raji, HuT 78, K-562), karcinoma (CaCo-2, HeLa) i na normalnoj stani.noj liniji (MDCK I). Najja.i citotoksi.ni u.inak pokazao je 6- morfolino-derivat 17 s trans-Ŕ-stirensulfonilnim supstituentom u N9 polo.aju purina na svim ispitanim stani.nim linijama. 6-morfolinski derivati s tosilnim, naftilsulfonilnim i bifenilsulfonilnim supstituentom u N9 polo.aju purina (8, 9 i 10) pokazali su srednje jako antiproliferativno djelovanje na Raji i HuT 78 stani.ne linije, a spojevi 9 i 10 pokazali su i srednje jako djelovanje na stanice K-562. Ispitana je i sposobnost inhibicije PNP enzima izoliranog iz dva soja bakterije Helicobacter pylori te PNP enzima iz bakterije Escherichia coli. Najbolji rezultati dobiveni su s 6-morfolinoderivatima 8 i 18. Peptidni derivati fenantridina pripravljeni su klasi.nim metodama peptidne kemije (sinteza u otopini). Negishijevom reakcijom pripravljen je alaninski derivat fenantridina 22 koji je funkcionaliziran peptidnom okosnicom nadogra.enom preko N-terminalnog kraja. Pripravljeni su di-, tri- i tetrapeptidni derivati s fenantridinom u bo.nom lancu, koji sadr.e gvanidinopirolnu, gvanidinsku (arginin), pirensku ili fluorensku strukturnu jedinicu. Gvanidinopirolni i argininski derivati prevedeni su u hidrokloridne soli. Ispitane su interakcije odabranih spojeva (gvanidinopirolni derivati 28b i 29b) s polinukleotidima pomo.u spektrofotometrijskih (UV/Vis, CD, fluorimetrija) metoda. Spojevi su, ovisno o konformaciji u kojoj se nalaze, pokazali razli.iti tip interakcija. Spoj 28b, .iji vii kromofori nisu u intramolekulskoj interakciji u blago kiselom mediju, najvjerojatnije se ve.e u mali utor DNA i veliki utor RNA. Spoj 29b, .iji kromofori su u intramolekulskoj .-. interakciji, ve.e se uz okosnicu polinukleotida. U neutralnom mediju oba spoja aglomeriraju uz fosfatnu okosnicu.The thesis presents preparation and characteristics of two types of biologically active heterocyclic small molecules: 1) N-sulfonylpurines (potential antitumor agents and inhibitors of the purine nucleoside phosphorylase enzyme, and 2) peptide phenanthridine derivatives (potential antitumor agents and fluorescent probes). Series of C6, N9 substituted purines bearing sulfonamide pharmacophore has been prepared. Series of 6-chloropurine derivatives has been prepared by introduction of sulfonyl substituent at the N9 position of the purine base. Substitution of chlorine at the C6 position yielded 6- morpholino- and 6-bis(2-hydroxyethyl)amino-derivatives of N-9-sulfonylpurine. Biological activities 6-morpholino- and 6-bis(2-hydroxyethyl)aminopurine derivatives have been tested by MTT test on the leukemia and lymphoma (Raji, HuT 78, K-562), carcinoma (CaCo-2, HeLa) and normal (MDCK 1) cell line. Compound 17, bearing trans--styrenesulfonyl substituent at N9 position of the purine base produced the strongest cyctotoxic effect on all of the tested cell lines. 6-morpholino-derivatives with tosyl, naphtylsulfonyl and biphenylsulphonyl substituent at the N9 position of the purine (8, 9 and 10) exhibited moderate antiproliferative effect on the Raji and HuT 78 cell lines, while 9 and 10 exhibted moderate antiproliferative effect on the K-562 cell line too. The inhibition of the PNP enzyme isolated from two strains of Helicobacter pylori and PNP from Escherichia coli was also tested. Best results are obtained with 6-morpholino-derivatives 8 and 18. Peptide phenanthridine derivatives were prepared by classic peptide chemistry methods (synthesis in solution). Alanine derivative of phenanthridine 22 was prepared by Negishi reaction, and subsequently functionalized by peptide backbone constructed starting from the Nterminus of 22. Di-, tri- and tetrapeptide phenanthridine derivatives with guanidinopyrrole, guanidine (arginine), pyrene or fluorene moiety have been prepared as well. Finally, guanidinopyrrole and arginine derivatives have been converted into hydrochloride salts. ix Interactions of chosen compounds (guanidinopyrrole derivatives 28b and 29b) with polynucleotides have been studied via several spectrophotometric methods, namely UV/visible, circular dichroism and fluorescence spectroscopies. The compounds have shown different types of interactions, depending on their conformation. Compound 28b, whose chromophores are not interacting mutually in mildly acidic media, most likely binds to minor groove of DNA and major groove of RNA. Compound 29b, whose chromophores are involved in intramolecular - interaction, binds on the phosphate backbone of the polynucleotide. In neutral media both compounds agglomerate along the phosphate backbone

Fran Galovic's dramatic opus

Fran Galović posebna je pojava razdoblja književne moderne u Hrvatskoj. To je razdoblje intenzivnih političkih i društvenih previranja na prostorima koji su tada bili u sastavu Austro-Ugarske Monarhije. Novo razdoblje donosi i novu književnu poetiku koja baca novi pogled na klasičnu strukturu književnih djela. Naglasak se stavlja na psihička proživljavanja glavnih junaka. U djelima hrvatske moderne mogu se pronaći i elementi naturalizma,književnog učenja koji se temelji na pretpostavci da je proučavanje književnosti jednako proučavanju ljudskog tijela,a sve ono što je skriveno se ponovno otkriva. Fran Galović je dijalektni pjesnik i prozaik, ali glavni naglasak u ovom radu bit će stavljen na njegov dramski opus. Galovićeve drame stavljaju novo svjetlo na međuljudske odnose, uz smrt koja je neizbježna. Galovićeve drame o kojima će biti riječ u ovom radu su jednočinke Pred smrt i Tamara koje su izvedene nakon Galovićeve smrti 1914. godine. U drami Pred smrt prati se sukob između društva i pojedinca, koji ne želi da mu se nametaju norme. Suočen s prevelikom boli glavni junak bira smrt a , Tamara, zavodnica istoimene drame, u smrt baca svoju novu žrtvu, Putnika koji ju je odbio. Galovićeva smrt u 27. godini života spriječila ga je u potpunom ostvarenju svog književnog talenta, iza njega je ostalo književno blago koje se i danas proučava

N-SULFONYLPURINES AND PEPTIDE PHENANTHRIDINE DERIVATIVES SYNTHESIS, INTERACTIONS WITH POLYNUCLEOTIDES AND BIOLOGICAL TESTING

U ovom radu istra.ene su metode priprave i svojstva dvije vrste biolo.ki aktivnih heterocikla iz grupe malih molekula: 1) N-sulfonilpurina (potencijalnih antitumorskih lijekova i inhibitora enzima purin nukleozid fosforilaze) i 2) peptidnih derivata fenantridina (potencijalnih antitumorskih lijekova i fluorescentnih senzora). Pripravljena je serija C6, N9 supstituiranih purina sa sulfonamidnim farmakoforima. Najprije je sintetizirana serija 6-klorpurinskih derivata uvo.enjem sulfonilnog supstituenta u polo.aj N9 purinske baze. Potom su, supstitucijom klora u C6 polo.aju, sintetizirani 6-morfolino- i 6-bis(2- hidroksietil)amino-derivati N-9-sulfonilpurina. Biolo.ka aktivnost 6-morfolino- i 6-bis(2-hidroksietil)amino-derivata purina ispitana je MTT testom na stani.nim linijama leukemije i limfoma (Raji, HuT 78, K-562), karcinoma (CaCo-2, HeLa) i na normalnoj stani.noj liniji (MDCK I). Najja.i citotoksi.ni u.inak pokazao je 6- morfolino-derivat 17 s trans-Ŕ-stirensulfonilnim supstituentom u N9 polo.aju purina na svim ispitanim stani.nim linijama. 6-morfolinski derivati s tosilnim, naftilsulfonilnim i bifenilsulfonilnim supstituentom u N9 polo.aju purina (8, 9 i 10) pokazali su srednje jako antiproliferativno djelovanje na Raji i HuT 78 stani.ne linije, a spojevi 9 i 10 pokazali su i srednje jako djelovanje na stanice K-562. Ispitana je i sposobnost inhibicije PNP enzima izoliranog iz dva soja bakterije Helicobacter pylori te PNP enzima iz bakterije Escherichia coli. Najbolji rezultati dobiveni su s 6-morfolinoderivatima 8 i 18. Peptidni derivati fenantridina pripravljeni su klasi.nim metodama peptidne kemije (sinteza u otopini). Negishijevom reakcijom pripravljen je alaninski derivat fenantridina 22 koji je funkcionaliziran peptidnom okosnicom nadogra.enom preko N-terminalnog kraja. Pripravljeni su di-, tri- i tetrapeptidni derivati s fenantridinom u bo.nom lancu, koji sadr.e gvanidinopirolnu, gvanidinsku (arginin), pirensku ili fluorensku strukturnu jedinicu. Gvanidinopirolni i argininski derivati prevedeni su u hidrokloridne soli. Ispitane su interakcije odabranih spojeva (gvanidinopirolni derivati 28b i 29b) s polinukleotidima pomo.u spektrofotometrijskih (UV/Vis, CD, fluorimetrija) metoda. Spojevi su, ovisno o konformaciji u kojoj se nalaze, pokazali razli.iti tip interakcija. Spoj 28b, .iji vii kromofori nisu u intramolekulskoj interakciji u blago kiselom mediju, najvjerojatnije se ve.e u mali utor DNA i veliki utor RNA. Spoj 29b, .iji kromofori su u intramolekulskoj .-. interakciji, ve.e se uz okosnicu polinukleotida. U neutralnom mediju oba spoja aglomeriraju uz fosfatnu okosnicu.The thesis presents preparation and characteristics of two types of biologically active heterocyclic small molecules: 1) N-sulfonylpurines (potential antitumor agents and inhibitors of the purine nucleoside phosphorylase enzyme, and 2) peptide phenanthridine derivatives (potential antitumor agents and fluorescent probes). Series of C6, N9 substituted purines bearing sulfonamide pharmacophore has been prepared. Series of 6-chloropurine derivatives has been prepared by introduction of sulfonyl substituent at the N9 position of the purine base. Substitution of chlorine at the C6 position yielded 6- morpholino- and 6-bis(2-hydroxyethyl)amino-derivatives of N-9-sulfonylpurine. Biological activities 6-morpholino- and 6-bis(2-hydroxyethyl)aminopurine derivatives have been tested by MTT test on the leukemia and lymphoma (Raji, HuT 78, K-562), carcinoma (CaCo-2, HeLa) and normal (MDCK 1) cell line. Compound 17, bearing trans--styrenesulfonyl substituent at N9 position of the purine base produced the strongest cyctotoxic effect on all of the tested cell lines. 6-morpholino-derivatives with tosyl, naphtylsulfonyl and biphenylsulphonyl substituent at the N9 position of the purine (8, 9 and 10) exhibited moderate antiproliferative effect on the Raji and HuT 78 cell lines, while 9 and 10 exhibted moderate antiproliferative effect on the K-562 cell line too. The inhibition of the PNP enzyme isolated from two strains of Helicobacter pylori and PNP from Escherichia coli was also tested. Best results are obtained with 6-morpholino-derivatives 8 and 18. Peptide phenanthridine derivatives were prepared by classic peptide chemistry methods (synthesis in solution). Alanine derivative of phenanthridine 22 was prepared by Negishi reaction, and subsequently functionalized by peptide backbone constructed starting from the Nterminus of 22. Di-, tri- and tetrapeptide phenanthridine derivatives with guanidinopyrrole, guanidine (arginine), pyrene or fluorene moiety have been prepared as well. Finally, guanidinopyrrole and arginine derivatives have been converted into hydrochloride salts. ix Interactions of chosen compounds (guanidinopyrrole derivatives 28b and 29b) with polynucleotides have been studied via several spectrophotometric methods, namely UV/visible, circular dichroism and fluorescence spectroscopies. The compounds have shown different types of interactions, depending on their conformation. Compound 28b, whose chromophores are not interacting mutually in mildly acidic media, most likely binds to minor groove of DNA and major groove of RNA. Compound 29b, whose chromophores are involved in intramolecular - interaction, binds on the phosphate backbone of the polynucleotide. In neutral media both compounds agglomerate along the phosphate backbone

SEC2MWD: A MATLAB toolbox for derivation of molecular weight distributions from size exclusion chromatography

Size exclusion chromatography (SEC) is a type of liquid chromatography used for separating molecules based on their size. The pipeline for converting a raw chromatogram to a molecular weight distribution involves multiple steps and require various parameters to be defined for each step. Commercial software lack transparency in terms of methods and algorithms, and it may be cumbersome to explore effects of different parameter settings. We have therefore developed a MATLAB toolbox that reproduces the main functionality of commercial software in a transparent and flexible manner. The toolbox consists of seven main functions, each representing a step in the calculation pipeline. The modular architecture makes it easy to modify or replace individual steps of the pipeline if necessary.publishedVersio

The Phenanthridine-modified Tyrosine Dipeptide: Synthesis and Non-covalent Binding to DNA and RNA

Dipeptide 4 containing two unnatural amino acids, a modified tyrosine and a phenanthridine derivative, was synthesized. Binding of the dipeptide to a series of polynucleotides including ct-DNA, poly A - poly U, poly (dAdT)2, poly dG - poly dC and poly (dGdC)2 was investigated by thermal denaturation experiments, fluorescence spectroscopy and circular dichroism. Thermal denaturation experiments indicated that dipeptide 4 at pH 5.0, when phenanthridine is protonated, stabilizes ds-DNA, whereas it destabilizes ds-RNA. At pH 7.0, when the phenanthridine is not protonated, effects of 4 to the polynucleotide melting temperatures are negligible. At pH 5.0, dipeptide 4 stabilized DNA double helices, and the changes in the CD spectra suggest different modes of binding to ds-DNA, most likely the intercalation to poly dG- poly dC and non-specific binding in grooves of other DNA polynucleotides. At variance to ds-DNA, addition of 4 destabilized ds-RNA against thermal denaturation and CD results suggest that addition of 4 probably induced dissociation of ds-RNA into ss-RNA strands due to preferred binding to ss-RNA. Thus, 4 is among very rare small molecules that stabilize ds-DNA but destabilize ds-RNA. However, fluorescence titrations with all polynucleotides at both pH values gave similar binding affinity (log Ka ≈ 5), indicating nonselective binding. Preliminary photochemical experiments suggest that dipeptide 4 reacts in the photochemical reaction, which affects polynucleotides chirality, presumably via quinone methide intermediates that alkylate DNA. This work is licensed under a Creative Commons Attribution 4.0 International License

USA–China Trade War: Causes, Effects and Ethical Aspects

Rad donosi pregled nedavnih protekcionističkih mjera Sjedinjenih Američkih Država (SAD) prema Kini te daje uvid u dvogodišnji trgovinski rat između te dvije države. Analiziraju se postupci i posljedice na svjetsko gospodarstvo. Osim direktnih posljedica na Kinu i SAD, promatra se i neizravan utjecaj na druge zemlje. Promatra se svjetski trend nametanja trgovinskih mjera, njihove prednosti i nedostatci te etičke nedoumice povezane s međunarodnom trgovinskom razmjenom.At the beginning of 2018, the USA imposed a variety of tariffs and import duties. Since China was most affected by these taxes, the trade war began. The total value of US customs tariffs imposed on Chinese goods is worth US$550bn, while the total value of Chinese customs tariffs imposed on US goods amounts to US$ 185bn. Late in 2019, the end was looming — China committed to importing US$ 200bn worth of US goods over the next two years, while the US agreed to “halve” the tariffs on Chinese goods. One of the reasons behind the war is the fact that China exports much more to the US than it imports, while the reverse is true for the US. The US claims that China’s inadequate position in the WTO and manipulations of the RMB/USD exchange rate are to blame for its vast trade deficit. Another reason is the realization that through acquisitions and takeovers, China is acquiring advanced technology for which it has not been paying a fair corresponding price. However, higher import prices helped some USA corporations which compete with foreign exports, but at the same time increased domestic production costs and reduced the purchasing power of American households, thus negatively affecting consumption, investment and employment. This in turn amplified economic uncertainty and reduced potential economic growth in the long run. The ethics of the US decision to protect certain domestic companies from international competition, while at the same time inflicting greater costs on other economic entities (notably consumers) in the USA and around the globe are difficult to defend