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Development of the system for robot instalation on the steam generator's tube sheet
No full textU ovom radu prikazan je razvoj sustava za instalaciju robota na cijevnu stijenu generatora pare. Prvi korak razvojnog procesa opisanog u radu je istraživanje tržišta u sklopu kojeg su prikazani relevantni sustavi dostupni na tržištu kao i nekoliko patenata. Na temelju analize tržišta i pregleda patenata generirana je funkcijska dekompozicija prema kojoj je generirana morfološka matrica unutar koje su opisani neki od mogućih načina rješavanja parcijalnih problema definiranih funkcijskom dekompozicijom. Kombiniranjem rješenja iz morfološke matrice generirana su tri koncepta koja su zatim uspoređena i vrednovana i odabran je koncept za daljnju razradu. Odabrani koncept je razrađen, odabrane su i proračunate komponente, izrađen 3D model i na kraju je izrađena tehnička dokumentacija.This thesis presents the development of the system for robot installation on the steam generator’s tube sheet. The first step of the development process described in this paper is market research in which the relevant systems and patents are presented. Based on the market analysis and patent review, a functional decomposition was generated according to which a morphological matrix was generated within which some of the possible ways of solving partial problems defined by functional decomposition were described. By combining the solutions from the morphological matrix, three concepts were generated which were then compared and evaluated and a concept was selected for further elaboration. The selected concept was elaborated, components were selected and calculated, a 3D model was created and finally the technical documentation was prepared
Determination of non-essential elements in encapsulated dietary supplements for the treatment of inflammatory bowel diseases
No full textUpalne bolesti crijeva pogađaju sve veći broj pacijenata diljem svijeta. U današnje vrijeme brojni
pacijentu se okreću samoliječenju i posežu za brojnim dodacima prehrani. Provode se brojna
istraživanja kojima se dokazuje njihova korisnost. Međutim, jako je važno zaštiti pacijente i osigurati
kvalitetu dodataka prehrani propisanu smjernicama. Jedan od zahtjeva smjernica je i količina
elementarnih onečišćenja koja mogu imati toksične učinke na ljudsko zdravlje. Stoga je cilj ovoga
diplomskog rada bio odrediti sadržaj srebra, kositra i barija u dodacima prehrani za liječenje upalnih
bolesti crijeva. Sadržaj navedenih neesencijalnih elemenata određen je metodom grafitne atomske
apsorpcijske spektrometrije. Srednja vrijednost koncentracije srebra i kositra niža je u mekim
kapsulama, dok se sadržaj barija u tvrdim i mekim kapsulama nije statistički značajno razlikovao.
Količine elementarnih onečišćenja srebra, kositra i barija odgovaraju zahtjevima aktualnih smjernica
ICH Q3 o najvećem dopuštenom dnevnom unosu elementarnog onečišćenja.Inflammatory bowel diseases are affecting an increasing number of patients worldwide. Today, many
patients turn to self-medication and use various dietary supplements. Numerous studies are being
conducted to demonstrate their effectiveness. However, it is crucial to protect patients and ensure
the quality of dietary supplements as prescribed by the guidelines. One of the requirements of these
guidelines is the limitation of elemental impurities, which can have toxic effects on human health.
Therefore, this thesis aimed to determine the content of silver, tin and barium in dietary supplements
for the treatment of inflammatory bowel diseases. The content of the mentioned non-essential
elements was determined using the graphite furnace atomic absorption spectrometry method. The
average concentration of silver and tin is lower in soft capsules, while the barium content in hard
and soft capsules did not differ statistically significantly. The levels of silver, tin and barium
elemental impurities comply with the requirements of the current ICH Q3 guidelines regarding the
maximum permissible daily intake of elemental impurities
Macroelements in formulated dietary supplements for the treatment of inflammatory bowel diseases
No full textDodaci prehrani sadrže brojne minerale koji su vrlo važni za očuvanje fizioloških funkcija ljudskog organizma, a samim time i za očuvanje zdravlja. Kod bolesnika s upalnim bolestima crijeva dodatan unos minerala ublažava simptome uzrokovane deficitom minerala. Zbog toga je cilj ovog rada bio odrediti sadržaj makroelemenata (Na, K, Ca, Mg) u tržišno dostupnim dodacima prehrani za liječenje upalnih bolesti crijeva. Ispitivanje je provedeno plamenom tehnikom - atomskom apsorpcijskom spektrometrijom nakon postupka vlažnog spaljivanja mikrovalnom digestijom. Dobiveni rezultati su pokazali da je sadržaj analiziranih makroelemenata izrazito varijabilan. Kalij je bio najzastupljeniji mineral u ispitivanim uzorcima i imao je puno veću varijabilnost od kalcija, natrija i magnezija. Tvrde kapsule su sadržavale više koncentracije makroelemenata nego meke kapsule. I na kraju je važno za naglasiti kako se analiziranim dodacima prehrani primjenim u preporučenim i maksimalnim dozama unose manje količine od preporučenih za pojedini element, te tako nema opasnosti od njihove potencijalne toksičnosti.Dietary supplements contain numerous minerals that are very important for preserving the physiological functions of the human body and, thus for preserving health. In patients with inflammatory bowel diseases, additional intake of minerals alleviates symptoms caused by mineral deficiency. Therefore, this work aimed to determine the content of macroelements (Na, K, Ca, Mg) in commercially available dietary supplements for the treatment of inflammatory bowel diseases. The test was carried out using the flame technique - atomic absorption spectrometry after the process of wet burning with microwave digestion. The obtained results showed that the content of analyzed macroelements is highly variable. Potassium was the most abundant mineral in the tested samples and they have a much higher variability than calcium, sodium and magnesium. Hard capsules contain more concentration of macronutrients than soft capsules. Finally, it is important to emphasize that when used in recommended and maximum doses, the analyzed dietary supplements are taken in smaller amounts than recommended for each element, so there is no danger of their potential toxicity
Neuroprotective activity of cholinesterase reactivators in organophosphate poisoning
No full textKationski piridinijevi oksimi koriste se kao reaktivatori inhibiranih enzima acetilkolinesteraze (AChE) i butirilkolinesteraze (BChE) pri liječenju trovanja organofosfornim (OP) živčanim bojnim otrovima i pesticidima. Međutim, neučinkoviti su za reaktivaciju sinaptičke AChE u mozgu zbog otežanog prolaska kationa kroz krvno-moždanu barijeru, što može potaknuti neuroupalu i trajno oštetiti moždane funkcije. Cilj ovog istraživanja bio je ispitivanje neuroprotektivnog potencijala triju novosintetiziranih skupina oksima s obzirom na poboljšane fizikalno-kemijske karakteristike u odnosu na piridinijeve oksime. Od osam oksima kationske imidazolijeve skupine, 1,3-dibenzil-2-((hidroksiimino)metil)imidazolijev bromid pokazao se učinkovitim reaktivatorom fosfilirane BChE s kojom je kao pseudokatalitički par u ex vivo uvjetima unutar 5 minuta vratio 60 % enzimske aktivnosti, što ga čini izvrsnim kandidatom za razgradnju OP spojeva u cirkulaciji prije nego dođu do ciljnih tkiva. Također, tri zwitterionska acetamidna bis-oksima na modelu miša pokazala su bolji zaštitni indeks i manju akutnu toksičnost od standardnih oksima. Terapija jednim od bis-oksima vratila je oko 70 % aktivnosti inhibirane AChE u mozgu i značajno je smanjila ekspresiju neuroupalnih biljega astroglioze i mikroglioze. Analizirani bis-oksimi imaju kapacitet sprječavanja aktivacije neuroupalnih procesa i pokazuju perspektivna fizikalno-kemijska svojstva za razvoj poboljšane terapije u slučaju trovanja OP spojevima.Cationic pyridinium oximes are used as reactivators of inhibited acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in the treatment of poisoning with organophosphorus (OP) nerve agents and pesticides. However, they are ineffective in reactivating synaptic AChE in the brain due to the difficulty of cation passage through the blood-brain barrier, which can induce neuroinflammation and permanently damage brain functions. The goal of this research was determining the neuroprotective potential of three newly synthesized oxime groups with regard to improved physicochemical characteristics compared to pyridinium oximes. Out of the eight cationic imidazolium oximes,
1,3-dibenzyl-2-((hydroxyimino)methyl)imidazolium bromide proved to be an effective ex vivo reactivator of phosphorylated BChE and as a pseudocatalytic pair it restored 60 % of the enzyme activity with a 10-fold excess cyclosarin, which makes it an excellent candidate for the degradation of OP compounds in the circulation before they reach the target tissues. Three zwitterionic acetamide bis-oximes showed a better protective index and less acute toxicity than standard oximes in a mouse model. Therapy with one of the bis- oximes restored about 70 % of the inhibited AChE in the brain and significantly reduced the expression of neuroinflammatory markers of astrogliosis and microgliosis. The analyzed bis- oximes have the capacity to prevent the activation of neuroinflammation and show promising physicochemical properties for the improvement of therapy in case of OP poisoning
Synthesis of new ferrocene-pyridine ligands and their metal complexes
No full textCilj ovog rada bila je sinteza novih ferocen-piridinskih liganada (6–9) i njihovih
Re(I)-(6-Re–8-Re) i Ru(II)-kompleksa (6-Ru-cim–9-Ru-cim, 8-Ru–fenil). Ligandi su sintetizirani regioselektivnom 1,3-dipolarnom cikloadicijom iz prethodno sintetiziranih terminalnih ferocenskih alkina (3–5) i kloriranog piridin-2-aldoksima (2). Terminalni ferocenski alkini (3–5) sintetizirani su O-propargiliranjem ferocen alkohola, ferocen aldoksima i ferocen karboksilne kiseline s propargil-bromidom uz prisutstvo baze. Klorirani aldoksimski
prekursor (2) sintetiziran je iz piridin-2-aldehida u dva stupnja. U prvom je stupnju
piridin-karbaldehid preveden u piridin-aldoksim (1), koji je u drugom stupnju kloriran s N-klorsukcinimidom. Sintetizirani piridin-izoksazoli (6–9) korišteni su kao ligandi za metalne komplekse s renij(I) pentakarbonil-kloridom (6-Re–8-Re), diklor(benzen)rutenij(II) dimerom (8-Ru–fenil) i diklor(p-cimen)rutenij(II) dimerom (6-Ru-cim–9-Ru-cim). Strukture spojeva potvrđene su spektroskopijom 1H i 13C NMR.The aim of this work was the synthesis of new ferrocene-pyridine ligands (6–9) and their Re(I)-(6-Re–8-Re) and Ru(II)-complexes (6-Ru-cym–9-Ru-cym, 8-Ru-phenyl). Ligands were synthesized by regioselective 1,3-dipolar cycloaddition from previously synthesized terminal ferrocene alkynes (3–5) and chlorinated pyridine-2-aldoxime (2). Terminal ferrocene alkynes (3–5) were synthesized by O-propargylation of ferrocene alcohol, ferrocene aldoxime and ferrocene carboxylic acid with propargyl bromide in the presence of a base. The chlorinated aldoxime precursor (2) was synthesized from pyridine-2-carbaldehyde in two steps. In the first step, pyridine carbaldehyde was converted into pyridine aldoxime (1), which was chlorinated with N-chlorosuccinimide in the second step. Synthesized pyridine isoxazoles (6–9) were used as ligands for metal complexes with rhenium(I) pentacarbonyl chloride, dichloro(benzene)ruthenium(II) dimer and dichloro(p-cymene)ruthenium(II) dimer.
The structures of the compounds were confirmed by 1H and 13C NMR spectroscopy
Synthesis of novel coumarin-isoxazole hybrids with potential antitumor activity
No full textCilj ovog rada bio je sintetizirati i spektroskopski okarakterizirati nove hibride kumarina i izoksazola s potencijalnim antitumorskim djelovanjem. Spojevi (6a−h) su sintetizirani bazno kataliziranom reakcijom 1,3-dipolarne cikloadicije O-alkiliranog derivata kumarina (2) i kloriranih oksima (5a−h). Spoj 2 pripravljen je propargiliranjem 4-hidroksikumarina (1). Klorirani oksimi (5a−h) sintetizirani su kloriranjem benzaldehidoksima (4a−h) s N-klorsukcinimidom. Strukture spojeva potvrđene su spektroskopijom 1H i 13C NMR. U tijeku je ispitivanje antitumorske aktivnosti novosintetiziranih spojeva.The aim of this work was to synthesize and spectroscopically characterize new coumarine-isoxazole hybrids with potential anticancer activity. Compounds (6a−h) were synthesized by the base-catalyzed 1,3-dipolar cycloaddition from O-alkylated coumarine derivative (2) and chlorinated oximes (5a−h). Compound 2 was prepared by propargylation of 4-hydroxycoumarine (1). Chlorinated oximes (5a−h) were synthesized from benzaldehyde oximes (4a−h) with N-chlorosuccinimide. The structures of compounds were confirmed by
1H and 13C NMR spectroscopy. Anticancer evaluations of the newly synthesized compounds are in progress
Synthesis of novel aryl-substituted coumarin and quinoline derivatives with potential cytostatic activity
No full textCilj ovog rada je sinteza novih aril-supstituiranih derivata kumarina i kinolina (5c−e, 6a−e, 7e, 8, 9) te njihovih Re(I)- (5d-Re, 8-Re, 10-Re) i Ru(II)-kompleksa (5d-Ru-fenil, 10-Ru-fenil, 5d-Ru-cim, 10-Ru-cim). Izoksazolni derivati kumarina i kinolina (5c−e, 6a−e, 7e) dobiveni su regioselektivnom 1,3-dipolarnom cikloadicijom propargiliranog kumarinskog (1) ili kinolinskog (2) derivata i odgovarajućeg kloriranog aldoksima (4a−e) uz trietilamin. Cijano-supstituirani izoksazolni derivati kinolina i kumarina (5e, 6e) prevedni su u fenilamidoksimske analoge (8, 9). Spojevi 5d i 10 korišteni su kao ligandi za metalne komplekse s renij(I) pentakarbonil-kloridom (5d-Re, 10-Re), diklor(benzen)rutenij(II) dimerom (5d-Ru-fenil, 10-Ru-fenil) i diklor(p-cimen)rutenij(II) dimerom (5d-Ru-cim, 10-Ru-cim). Strukture spojeva potvrđene su spektroskopijom 1H i 13C NMR, strukture cijano (6e) i fenilamidoksimskog (9) derivata kinolina potvrđene su spektroskopijom IR, a određivanje rendgenske strukture na monokristalu kompleksa te biološka ispitivanja novosintetiziranih spojeva (5−10, 5d-Re, 5d-Ru-fenil, 5d-Ru-cim, 10-Re, 10-Ru-fenil, 10-Ru-cim) su u tijeku.The aim of this work was the synthesis of new aryl-substituted coumarin and quinoline derivatives (5c−e, 6a−e, 7e, 8, 9) and their Re(I)- (5d-Re, 8-Re, 10-Re) and Ru(II)-complexes (5d-Ru-phenyl, 10-Ru-phenyl, 5d-Ru-cym, 10-Ru-cym). Isoxazole derivatives (5c−e, 6a−e, 7e) were obtained by regioselective 1,3-dipolar cycloaddition of propargylated coumarin (1) or quinoline (2) derivative and corresponding chlorinated aldoximes (4a−e) with triethylamine. Cyano-substituted isoxazole derivatives (5e, 6e) were converted to their phenylamidoxime analogues (8, 9). Compounds 5d and 10 were used as ligands for metal complexes with rhenium(I) pentacarbonyl chloride (5d-Re, 10-Re), dichloro(benzene)ruthenium(II) dimer (5d-Ru-phenyl, 10-Ru-phenyl) and
dichloro(p-cymene)ruthenium(II) dimer (5d-Ru-cym, 10-Ru-cym). The structures of all compounds have been confirmed by 1H and 13C NMR spectroscopy, the structures of cyano (6e) and phenylamidoxime (9) quinoline derivatives are characterized by IR spectroscopy, while structure determination by X-ray diffraction on single crystals of complexes and biological evaluations of newly synthesized compounds (5-10, 5d-Re, 5d-Ru-phenyl, 5d-Ru-cym, 10-Re, 10-Ru-phenyl, 10-Ru-cym) are in progress
Targeting the fusion protein RIOX1-dSpCas9 to the promoter region of B4GALT1 for removal of the histone mark H3K4me3
No full textŠest epigenetičkih mehanizama simultanim djelovanjem regulira gensku ekspresiju, a njihove su interakcije, zastupljenosti i efekti na transkripcijski status određenog gena specifični u odnosu na kromatinski „okoliš“. Cilj istraživanja bio je ukloniti histonsku oznaku H3K4me3 u promotorskoj regiji gena B4GALT1 pomoću fuzijskog proteina RIOX1-dSpCas9 navođenog na specifičnu regiju sa šest različitih molekula sgRNA (od engl. single guide RNA). Također, cilj je bio dizajnirati testove za analizu stupnja metilacije pirosekvenciranjem ove regije. Metodom kromatinske precipitacije CUT&RUN, nakon koje slijedi qPCR, utvrđeno je da nije došlo do statistički značajnog smanjenja u količini histonske oznake H3K4me3 kao ni do povećanja stupnja metilacije DNA u analiziranoj regiji. Metodom kvantitativnog PCR je utvrđeno da nije došlo do promjene u genskoj ekspresiji. Gen B4GALT1 ima složenu genetičku i epigenetičku regulaciju, a efekt fuzijskog proteina RIOX1-dSpCas9 mogao je ostati nezapažen zbog uskog područja koje je analizirano, ali i zbog već prisutnih epigenetičkih modifikacija i strukture kromatina koji su mogli onemogućiti njegovo vezanje ili katalitičku aktivnost.Gene expression is regulated by six epigenetic mechanisms that work simultaneously. Their interactions as well as their effects on the transcriptional status of a certain gene are specific and depend on chromatin context. The goal of this research was to remove the histone mark H3K4me3 from the promoter region of the B4GALT1 gene using the fusion protein RIOX1-dSpCas9, which was guided to a specific region by six different sgRNA molecules. Also, the goal was to design assays for pyrosequencing in order to analyze DNA methylation level in this region. The CUT&RUN chromatin precipitation method followed with qPCR revealed no statistically significant change in the amount of histone mark H3K4me3 nor in DNA methylation level of the analyzed region. Quantitative PCR showed no change in the the B4GALT1 gene transcriptional activity. The B4GALT1 gene has complex genetic and epigenetic regulation, and the effect of the RIOX1-dSpCas9 fusion protein could have gone unnoticed due to the narrow region in the gene promoter that was analyzed. Also, the already present epigenetic modifications and chromatin structure in the targeted region could have prevent the binding or catalytic activity of RIOX1-dSpCas9
Parameterization of 3D CAD models of pipe systems for prefabricated construction
No full textU ovom radu opisan je proces izrade parametarskog modela cijevnih sustava prefabricirane gradnje koji služi za brzu i jednostavnu prilagodbu elemenata sustava prema zahtjevima projekta. Rad započinje kratkim osvrtom na prisutnost parametrizacije u gradnji te se prikazuju prednosti parametrizacije računalnih modela. Nakon toga provedena je analiza cijevnih sustava i njihovih elemenata koji se koriste u prefabriciranoj gradnji. Ova analiza je poslužila za bolje razumijevanje cjevovodnih sustava te je pružila jasniju sliku o tome kako bi različite vrste cijevnih sustava trebale izgledati u obliku parametarskog modela. U sljedećem koraku prikazana je važnost korištenja računalnih alata za izradu 3D modela proizvoda te je objašnjeno zašto se 2D alati ne bi mogli koristiti u ovakvo kompleksnim primjenama parametrizacije. Objašnjeni su pojedini alati koji su korišteni za izradu rada te su istaknute ostale bitne stavke korištenog 3D CAD sustava. Potom su formulirani parametri za raspored i dimenzije elemenata cijevnih sustava te je prikazana raspodjela i parametrizacija za različite vrste cijevnih sustava. Nakon prikupljanja dovoljno informacija o parametrizaciji i cijevnim sustavima općenito, u nastavku je prikazana razrada završnog parametarskog modela, a kojom je moguće postići brzu i jednostavnu prilagodbu rasporeda cijevnih sustava za različite izvedbe prefabriciranih kupaonica.This thesis describes the process of creating parametric models for prefabricated construction which are used for quick and easy adjustment of the system elements according to specific project requirements. The thesis begins with a brief overview of the presence of parametrization in construction and highlights the advantages of parametric models. After that, pipe systems and their components used in prefabricated construction were studied. This analysis serves to enhance understanding of pipeline systems and provides a clearer picture of how different types of pipe systems should appear in parametric model. In the next step, the importance of using 3D tools in model creation is presented and it is explained why 2D tools may not be suitable for such complex applications of parametrization. Some of the tools used in thesis are explained and other important items of the 3D CAD system which were used are highlighted. Parameters for the layout and dimensions of pipe system elements are then formulated, followed by the demonstration of distribution and parametrization for different pipeline systems. After gathering sufficient information on parametrization and pipe systems in general, the subsequent sections present the development of the final parametric model. This model allows a quick and easy adaptation of the layout of pipe systems for various configurations of prefabricated bathrooms
Synthesis of fulleretic composite materials by liquid-directed mechanochemical templation
No full textPredmet istraživanja je usmjeravajući učinak tekućine i fulerena u kontroliranoj mehanokemijskoj sintezi polimorfnih i kompozitnih faza cinkova imidazolata. Osim dosad poznatih faza cinkova imidazolata čije su strukture „preguste“ za apsorpciju fulerena, pripravljene su tri nove topologije kompozita cinkova imidazolata s fulerenom: C 70 @CHA- ZnIm 2 i C 60 @CHA-ZnIm 2 , C60 @X-ZnIm 2 i C 60 @T-ZnIm 2 . X i T faze su zasad nove i nepoznate topologije. Dobiveni spojevi su izučavani difrakcijom rentgenskih zraka na praškastim uzorcima, termogravimetrijom, infracrvenom spektroskopijom i elektronskom spinskom rezonancijom. Dok se CHA-ZnIm 2 i X-ZnIm 2 faza mogu pripraviti samo uz prisustvo fulerena, T-ZnIm 2 faza se može pripraviti i bez fulerena, ali manje količine enkapsuliranog fulerena dodatno stabiliziraju ovu nestabilnu fazu. Količina apsorbiranog fulerena ovisi o vrsti i količini dodanog fulerena (C 60 ili C70 ) i o tipu faze kompozita.The subject of research is the directing effect of liquid and fullerene in the controlled mechanochemical synthesis of polymorphic and composite phases of zinc imidazolate. In addition to the previously known zinc imidazolate phases whose structures are “too dense” for fullerene absorption, the inclusion of fullerene in the structure stabilized three new topologies of zinc imidazolate composites: C70 @CHA-ZnIm 2 and C 60 @CHA-ZnIm 2 , C 60 @X-ZnIm 2 and C 60 @T-ZnIm 2 . X and T phases have a new unreported topology. The obtained compounds were studied by X-ray diffraction on powder samples, thermogravimetry, infrared spectroscopy and electronic paramagnetic resonance. While the CHA-ZnIm 2 and X-ZnIm 2 phases can only be prepared with the addition of fullerene, T-ZnIm 2 phase can be prepared without the presence of fullerenes, but small amounts of encapsulated fullerene additionally stabilize the otherwise unstable phase. The amount of fullerene absorbed depends on the type of fullerene (C 60 or C 70 ), the amount of added fullerene and the type of composite phase