Comparsion of dentin bond strength using conventional adhesive application and co-curing technique

Istovremena svjetlosna polimerizacija caklinsko-dentinskog adhezijskog sustava i prvog sloja kompozitnog materijala, tj. co-curing metoda, jedna je od predloženih tehnika za smanjenje polimerizacijskog skupljanja i povećanje rubnog brtvljenja nadomjestaka. Svrha ovog in vitro istraživanja bila je ispitati utječu li različite metode polimerizacije caklinsko-dentinskih adhezijskih sustava i kompozitnog materijala, različiti caklinsko-dentinski adhezijski sustavi, različite dubine presjeka zuba, vrsta zuba i starenje uzoraka na veznu čvrstoću dentina. Ispitana su tri komercijalno dostupna caklinsko-dentinska adhezijska sustava: G-Premio Bond, Clearfil SE Bond 2 i Adper Single Bond 2 koja su bila stvrdnjavana polimerizacijskom svjetlošću odvojeno ili istovremeno s kompozitnim uzorkom. Napravljeno je ukupno 480 dentinskih uzoraka koji su nasumično raspoređeni u 24 eksperimentalne skupine (2 načina polimerizacije x 3 caklinsko-dentinska adhezijska sustava x 4 vremenske točke mjerenja) po 20 uzoraka po skupini. Nakon uranjanja uzoraka u destiliranoj vodi i skladištenja u inkubatoru, smična vezna čvrstoća testirana je nakon mjesec dana, 3 mjeseca, 6 mjeseci i 1 godine. Nakon testiranja vezne čvrstoće, slomljeni uzorci su bili pregledani s lupama povećanja 3,6 x kako bi se karakterizirala vrsta frakture. Za statističku analizu koristila se analiza varijance i Weibullova analiza. Skupine kod kojih su caklinsko-dentinski adhezijski sustav, ne ovisno koji, i kompozitni materijal bili polimerizirani odvojeno pokazali su statistički značajno veće vrijednosti u odnosu na uzorke polimerizirane „co-curing“ metodom. Usporedba vezne čvrstoće između različitih caklinskodentinskih adhezijskih sustava koji su polimerizirani istom metodom pokazala je statistički značajnu razlika između svih skupina (p < 0,001), pri čemu je Clearfil SE Bond 2 pokazivao najveće vrijednosti. Starenjem uzoraka došlo je do pada u veznoj čvrstoći, pri čemu su prve promjene zabilježene nakon 6 mjeseci. Veću veznu čvrstoću pokazali su okluzalni tj. površinski dijelovi dentina u odnosu na radikularne dijelove. Nije opažena statistički značajna razlika između maksilarnih i mandibularnih trećih molara u veznoj čvstoći. Adhezijske frakture bile su opažene u najvećem postotku. Eksperimentalne skupine s najvišom prosječnom veznom čvrstoćom nakon 1 i 3 mjeseca starenja nisu pokazivale najveću pouzdanost materijala.Adhesion serves as the basis for modern restorative dentistry. As an intermediary material, a dental adhesive system binds restorative materials to hard dental tissues and improves the retention, marginal sealing, and resistance of the tooth-restoration interface. Polymerization stress, however, is the biggest restriction in the field of resin composite and one of the primary causes of the clinical failure of today's adhesion systems. Polymerization shrinkage, which happens when monomers are transformed into polymers during the curing process of composite resins, causes a reduction in total volume. As a result, internal contraction stresses and stresses at the restoration's edges may emerge. If the bond strength is compromised by contraction pressures, pulp injury, postoperative sensitivity, marginal microleakage, marginal staining, and secondary caries will result. Numerous variables, such as the configuration factor, cavity shape, application procedure and elastic modulus of the restorative material, all affect the creation of stress. To decrease polymerization shrinkage and improve the marginal sealing of restorations, several clinical treatments and approaches have been proposed. One of the suggested techniques is the co-curing process, which involves light curing both the resin adhesive and the initial layer of the composite resin at the same time. The aim of this in vitro study was to evaluate the effects of different methods of polymerization of adhesion systems and composite resin, different adhesion systems, different depths of dentin sections, types of teeth and aging of samples on dentin shear bond strength. Materials and Methods: A mid-coronal section of 222 intact third human molars with completed root formation was made to create flat bonding substrates. Specimens were prepared using a low-speed saw, embedded in an acrylic resin and wet grounded to create a flat bonding area. Three bonding agents; G-Premio Bond (GC), Clearfil SE Bond 2 (Kuraray) and Adper Single Bond 2 (3M ESPE) were applied to the dentin. The application of each adhesion system was performed in two different ways. In half of the specimens, bonding agents were light cured immediately after their application (conventional application). The other half were not light cured until resin composite application (co-curing technique). Composite cylinders (diameter = 2.38 mm, height = 2 mm) were prepared using a bulk-fill composite SDR Plus Bulk Fill Flowable (Dentsply Sirona). A total of 480 specimens were prepared (3 adhesives × 2 method of application × 4 aging times x 20 specimens per experimental group). Shear bond strength was evaluated after 1 month, 3 months, 6 months and 1 year of water storage in incubator at 37 °C by loading the specimens in bond strength testing machine UltraTester. Bond strength was tested by loading specimens in a testing machine at a constant crosshead speed of 1 mm/min until fracture. Shear dentin bond strength was measured according to a ISO 29022: 2013 protocol. The fractured fragments were examined with a optical loupes to characterize the failure mode. Bond strength data (MPa) were analyzed using analysis of variance (ANOVA) and Weibull statistics (reliability analysis). In brittle materials (such as adhesion systems or dental composites) there are defects that affect the strength of the material. The source of these errors are inhomogeneities in the material, such as air bubbles, microcracks and pores. The stress at which the material cracks depends on the distribution of these errors, so the variability of the measured bond strength values cannot be attributed to experimental / measurement errors, but is at least partly due to the natural properties of the material. Conventional statistics (ANOVA) do not take this into account, but attribute it all to experimental error or measurement error. Results: The highest mean bond strength was obtained for Clearfil SE Bond 2 conventional one month after storage (38.48 MPa), whilst the lowest bond strength was observed when co-curing was used after one year (particularly, Adper Single Bond 2 7.83 MPa). The results showed a statistically significant difference between conventional and co-curing methods in all materials (p < 0.001). Within each bonding system, bond strength values attained by co-curing were significantly lower than the corresponding values attained by conventional curing. Between all the different experimental groups in which the adhesion systems were applied and polymerized by the same method (conventional or “co-curing”), with the exception of Adper Single Bond 2 and G-Premio Bond conventionally, a statistically significant difference was observed. Although G-Premio Bond showed a higher mean bond strength compared to Adper Single Bond 2, the difference was not demonstrated in the group comparison. Over time a decrease in mean bond strength values was observed in all experimental groups. After 6 months, there was a decrease in bond strength compared to 1 month and an additional decrease in bond strength occurs after 12 months. After one year bond strength was significantly lower compared to 1, 3 and 6 months. In the occlusal parts of the teeth, on average, a statistically significantly higher bonding strength was recorded compared to the radicular parts of the teeth. Between maxillary and mandibular teeth, no difference in bond strength was recorded. The frequency of adhesion fractures was 86 %, while cohesion fractures were not observed. In descriptive statistics, the experimental group Clearfil SE Bond 2 conventional had the highest mean value at all time points. The same applies to the characteristic strength in the reliability analysis. The lowest variability (the highest Weibull modulus) after one month of aging was recorded with G-Premio Bond conventional, after 3 months with Clearfil SE Bond 2 co-curing, and after 6 and 12 months with Clearfil SE Bond 2 conventional. Conclusion: Under the limitations of this study, it can be concluded that bond strength is influenced by differences in polymerization of adhesive systems and composite resin, types of adhesive systems, depth of dentin section, and aging time. In the experimental model adopted for this study, specimens prepared with the conventional application technique produced higher shear bond strength according to conventional statistics and reliability analysis. The materials with the highest mean bond strength are not always materials with the highest reliability

Popravak križnih veza između DNA i topoizomeraza 1 i 2

DNA-protein crosslinks (DPCs) are frequent and damaging DNA lesions that affect all DNA transactions, which can lead to the formation of DSBs (double-strand DNA breaks), genomic instability and cell death. At the organismal level, impaired DPC repair (DPCR) is associated with cancer, aging, and neurodegeneration. Repair of the two most abundant enzymatic DPCs, involving topoisomerase 1 and 2 was studied in cell models, but data from organisms are still limited. Here, using a zebrafish model and human cells, we show that endogenous TOP1-DPCs are repaired by TDP1 and SPRTN through independent pathways. Notably, chemically induced TOP1-DPCs, using camptothecin or formaldehyde, require an epistatic action of both enzymes, and effectively prevent the accumulation of TOP1-DPC-related damage. Furthermore, we identified the zebrafish Tdp2 orthologue, Tdp2b, as the enzyme responsible for the removal of Top2-DPC residues. Reduced Tdp2 function, observed in both, living organisms and cellular models, causes significant phenotypic changes. This study provides the first insights into the repair of TOP1- and TOP2-DPCs in vivo.Križne veze proteina i DNA (eng. DPCs) su česte i štetne lezije DNA koje ometaju sve procese na DNA, što može dovesti do pojave dvostrukih lomova, genomske nestabilnosti i stanične smrti. Na razini organizma, neefikasan popravak križnih veza proteina i DNA povezan je s nastankom tumora, starenjem i neurodegeneracijom. Dok je popravak najčešćih enzimskih DPC-a, Topoizomeraze 1 i 2, pručavan u staničnim modelima, podaci o ovom popravku u organizmima još uvijek su nedostatni. U ovom istraživanju, koristeći model ribe zebrice i ljudske stanične kulture , pokazali smo in vivo da se endogeni popravak TOP1-DPC odvija putem enzima TDP1 i SPRTN, pri čemu ti enzimi djeluju neovisno jedan o drugome. Nadalje, DPC-evi s TOP1 inducirani kemijski, korištenjem kamptotecina ili formaldehida, zahtijevaju međusobno ovisno djelovanje oba enzima kako bi se učinkovito spriječilo nakupljanje oštećenja povezanih s TOP1-DPC-ovima. U ovom radu, pokazali smo kako je zebričin Tdp2 ortolog, Tdp2b, enzim odgovoran za uklanjanje ostataka Top2-DPC-a s DNA. Smanjenje aktivnosti Tdp2, kako u živim organizmima tako i u staničnim modelima, rezultira značajnim fenotipskim promjenama. Ovo istraživanje pruža prve uvide u mehanizme popravka TOP1- i TOP2-DPC-eva in vivo

Stavovi i znanja o psihodelicima i psihoterapiji potpomognutoj psihodelicima

Objectives: The studies described in this dissertation aimed to create and validate a standardized questionnaire for the assessment of attitudes about psychedelics, to apply this questionnaire by assessing a group of European psychiatrists about their attitudes, and to complement these findings by conducting selected interviews with European psychiatrists on the same topic. Methods: The first and second studies were cross-sectional and used an online survey. The third study was a qualitative study, based on a reflective thematic analysis of semi-structured interviews. Results: The first research showed the validity of the new instrument and provided preliminary data on the attitudes of the Croatian general population about psychedelics, where it was shown that many people do not even have basic knowledge about psychedelics. The second study showed that European psychiatrists are open to psychedelics, but are concerned about the possible side effects and abuse of these substances. More positive attitudes in that group were associated with previous personal use of psychedelics, greater knowledge about psychedelics, younger age, male gender, and spirituality. Variables related to professional training and practice did not show a significant influence on attitudes on psychedelics. The third study showed the complexity of attitudes on psychedelics and their deep connection to the social, political and historical context. Attitudes on psychedelics in psychiatry are mixed and a large number of psychiatrists believe that the evidence for their therapeutic effectiveness is still not sufficiently convincing. Conclusions: The new instrument we validated has a many potential uses for future research. General knowledge about psychedelics is poor, and psychiatrists state that this topic is underrepresented in their education. This should be improved in order to hold high-quality informed discussions about the future of psychedelic therapy. Our findings suggest that psychedelics are a topic where it is difficult to remain impartial, especially as an education or treatment provider.Ciljevi: Istraživanja opisana u ovoj disertaciji imala su za cilj stvoriti i validirati standardizirani upitnik za procjenu stavova o psihodelicima, taj upitnik primijeniti u ispitivanju skupine europskih psihijatara o njihovim stavovima te nadopuniti te nalaze provođenjem ciljanih intervjua s europskim psihijatrima o istoj temi. Metode: Prvo i drugo istraživanje bili su presječnog nacrta te su koristili online anketu. Treće je istraživanje bilo kvalitativno, temeljeno na refleksivnoj tematskoj analizi polustrukturiranih intervjua. Rezultati: Prvo istraživanje je pokazalo validnost novog standardiziranog i dalo preliminarne podatke o stavovima hrvatske opće populacije o psihodelicima, gdje se pokazalo da mnogo osoba nema niti osnovno znanje o psihodelicima. Drugo istraživanje je pokazalo da su europski psihijatri otvoreni prema psihodelicima, ali da su najviše nesigurni oko mogućih nuspojava i zloporabe tih supstanci. Pozitivniji stavovi kod te skupine bili su vezani uz prethodno osobno korištenje psihodelika, veće znanje o psihodelicima, mlađu dob, muški spol i duhovnost. Varijable vezane uz stručnu izobrazbu i rad nisu pokazale značajan utjecaj na stavove o psihodelicima. Treće istraživanje prikazalo je kompleksnost stavova o psihodelicima i njihovu duboku vezanost uz društveni, politički i povijesni kontekst. Stavovi u psihijatriji o psihodelicima su miješani, a veliki broj psihijatara smatra da dokazi o njihovoj terapeutskoj učinkovitosti još uvijek nisu dovoljno uvjerljivi. Zaključci: Novi instrument koji smo validirali ima široki potencijal primjene u budućim istraživanjima. Opće znanje o psihodelicima je loše, a psihijatri navode da je ta tema premalo zastupljena u njihovom obrazovanju. To bi trebalo promijeniti kako bi se moglo imati kvalitetne i informirane rasprave o budućnosti terapije psihodelicima. Naši nalazi upućuju na to da su psihodelici tema gdje je teško ostati nepristran, posebno kao osoba koja prenosi znanje o njima ili provodi terapiju

Rekonstrukcija zajedničkoga pretka eukariota kladističkim i filogenetičkim pristupom

Organisation and diversity of the eukaryotic cells are well documented phenomena today, so it is already known scientific theory that LECA (the Last Eukaryotic Common Ancestor) harboured mitochondrion, nucleus, endoplasmic reticulum made of bacterial lipids, sex, meiosis, and eukaryotic life cycle. None of the aforementioned traits has been found in prokaryotes. The origin of those eukaryotes traits has, on the other side, been an unresolved issue for many years. It is questionable whether the mitochondrion (bacterial endosymbiont) entered the archaeal host cell prior to the formation of the nucleus or later; it has never been systematically studied if LECA had a single or many nuclei; it has not been quantified how many gene duplications there were in LECA, and what is their origin. Furthermore, cladistic terminology is often misapplied in molecular evolution and studies are rarely based on taxon-rich sampling, meaning that eukaryotic diversity is not well covered. This dissertation, hence, aims to discuss cladistics and its interpretation in theory, with emphasis on the definition of eukaryotes; and practically, by analyses, to shed some light on the genome organization, morphology, and physiology of LECA. Eukaryotes/Eukarya are defined as a monophyletic, holophyletic group with polyphyletic, reticulated origin. Because of the reticulated origin of eukaryotes and because mitochondria and the nucleus are not regarded as prokaryotes anymore, both Bacteria and Archaea are paraphyletic, i.e., monophyletic groups. Many duplications were present in LECA and the Bacteria-derived ones were found to be prevalent what suggests that mitochondria-early hypothesis might be correct. Except for the genes that originated from plastid acquisition (Cyanobacteria), no specific genes were found within eukaryotic supergroups, suggesting that differential loss and genome duplications are the major forces of the eukaryotic evolution. Ubiquity of the multinucleate state across the eukaryotic domain is presented. Traits annotated on the eukaryotic tree were multinucleate state presence and absence, open vs. closed nuclear division, as well as 'control traits' for which it is known to be ancestral to LECA (presence of sex, mitochondria) or for which it is known not to be ancestral to LECA (plastid, polyploidy). Ancestral state reconstruction did not reject the hypothesis that LECA was multinucleated, similar to modern aseptate fungi or myxomycetes, and exhibited closed nuclear division. It is confirmed (i.e., not rejected) that LECA was sexual, had mitochondria, did not have plastid and was not polyploid. The results of ancestral state investigations presented in this work indicate that, contrary to popular beliefs, LECA was likely not a uninucleate cell, from which it follows that uninuclear eukaryotes possibly represent highly specialized forms, of which some, such as Excavata might even have originated long time ago from LECA's gametes.Raznolikost eukariota i organizacija njihovih stanica danas su već dobro poznati pa se može smatrati znanstvenom teorijom da je LECA (engl. Last Eukaryotic Common Ancestor, Posljednji zajednički predak eukariota) imao je mitohondrij, jezgru, unutarstaničnu mrežu membrana građenu od bakterijskih lipida, spol, mejozu i eukariotski životni ciklus. U prokariota, usporedbe radi, ne postoji ni jedno od ovih obilježja. Usprkos dobrom poznavanju njihove građe, postanak eukariota i dalje je jedan od neriješenih problema moderne znanosti. Ne zna se je li mitohondrij (bakterijski endosimbiont) ušao u arheju prije ili nakon formacije jezgre; nikad nije utvrđeno je li LECA imao samo jednu ili je imao više jezgara; do sada nije određeno koliko je LECA imao dupliciranih gena i koje im je porijeklo. Uza sve to, u molekularnoj evoluciji često se pogrešno koristi terminologija sistematike, a radovi najčešće ne uključuju veliku raznolikost, tj. nije pokriveno mnogo svojti. Ciljevi ove disertacije jesu teoretski raspraviti terminologiju sistematike i njezinu interpretaciju, s naglaskom na definiciju eukariota; kao i istražiti organizaciju genoma, morfologiju i fiziologiju LECA-e praktičnim analizama. Eukarioti (Eukaryota/Eukarya) su definirani kao monofiletska; holofiletska skupina polifiletskog postanka. Zbog hibridnog postanka eukariota i budući da se mitohondrij i jezgra više ne smatraju prokariotima, i bakterije (Bacteria) i arheje (Archaea) su parafiletske tj. monofiletske skupine. Otkriveno je da je LECA imala mnogo duplikacija i da je najviše onih koje potječu od bakterija što ide u prilog hipotezi da je mitohondrij bio prisutan tijekom same eukariogeneze. Osim plastidnih gena koji su porijeklom iz cijanobakterija (Cyanobacteria), nisu pronađeni jedinstveni geni niti u jednoj supergrupi što znači da su veliki gubitci dijelova genoma i duplikacije gena glavne sile evolucije eukariotskog genoma. Višejezgrene stanice su učestale među eukariotima i u disertaciji je prikazana njihova raznolikost. Na stablu eukariota označene su prisutnost i odsutnost višejezgrenih stanica te otvorena i zatvorena dioba jezgre, kao i „kontrolna svojstva“, tj. ona za koja se zna da li su predačka LECA-i (spol, mitohondrij) i ona za koja se zna da nisu (plastid, poliploidija). Rekonstrukcija predačkih svojstava nije odbacila pretpostavke da je LECA bila višejezgrena, vjerojatno slična današnjim aseptičnim gljivama i sluznjačama (Myxomycetes), kao ni da je imala zatvorenu diobu jezgri. Potvrđeno je također, tj. nije odbačeno, da je LECA bila spolni organizam, da je imala mitohondrije, da nije imala plastide i da nije bila poliploidna. Suprotno uvriježenom mišljenju, LECA najvjerojatnije nije bila jednojezgreni organizam i prema tome jednojezgreni jednostanični eukarioti vjerojatno predstavljaju visokospecijalizirane organizme, od kojih neki poput supergrupe Excavata—smisleno nagađanje—možda čak potječu od LECA-inih gameta

Model kompleksnosti zračnog prometa temeljen na radnim zadaćama kontrolora zračnoga prometa

Existing models for determining air traffic complexity that are based on air traffic controllers' subjective assessment are not consistent due to possible deviations in complexity assessment. The aim of this research is to create a mathematical model for air traffic complexity which is based on the air traffic controller tasks. The model will use the data on area radar air traffic controller tasks that are defined according to the traffic situation. Certain air traffic controller tasks, such as a conflict resolution, are perceived as one task, but they actually represent a set of multidimensional tasks that need to be defined precisely in order to be used later in mathematical model. Moreover, the existing models for determining air traffic complexity which use the subjective air traffic controller assessments also include the problem of subjectivity resulting from the learned mode of operation in a given airspace. For the purpose of this research new generic airspace will be created. This research introduces a new approach to design a model for determining air traffic complexity which is based on defining area radar air traffic controller tasks for the given traffic situations. Area radar air traffic controllers will be asked to decide which of the two traffic situations is more complex by using the comparison method. In this way, any inconsistency in subjective assessments will be avoided, since air traffic controllers tend to give the same complexity score for different levels of air traffic complexity. Using machine learning, inputs such as defined air traffic controller tasks and data gained through comparison method, will be used to develop a new mathematical model for determining air traffic complexity. The validation of the model will be carried out by the same comparison method using the traffic situation data on a different airspace.Rast potražnje u prometu pokretač je razvoja zračnog prometa. Ipak, to bi moglo dovesti i do negativnih posljedica poput zagušenja zračnog prostora, kašnjenja letova, velike gustoće prometa, neučinkovitost leta zbog pretjerano dugih ruta, povećane potrošnje goriva, a samim time i povećanih troškova leta i utjecaja na okoliš. Ti će problemi postati još izraženiji u narednim godinama, zbog povećane potražnje u prometu. Trend rasta zračnog prometa u zoni EUROCONTROL od 2013. godine nastavljen je do 2018. godine, nakon nekoliko godina stagnacije uzrokovane globalnom gospodarskom krizom. Broj letova temeljen na pravilima instrumentalnog leta (IFR) u prosjeku je porastao za 3,8% u odnosu na promet u 2017. Rast zračnog prometa veći je u pogledu broja putnika nego u odnosu na letove (6,1% u odnosu na 2017.), što je također slučaj u prethodnim godinama [1]. Taj se rast nastavio u prvoj polovici 2019. godine, a broj kontroliranih letova u zoni EUROCONTROL u prosjeku je porastao za 1,6% u odnosu na 2018. godinu [2]. Prema srednjoročnoj prognozi EUROCONTROL-a, procjenjuje se da će rast prometa IFR-a nastaviti u sljedećim godinama do 2025. godine, s prosječnim godišnjim rastom od 2,0% [3]. U takvim se uvjetima događaju kompleksnije situacije u zračnom prometu, koje mogu otežati pružanje usluge kontrole zračnog prometa, a posebno za specifične zadatke kontrolora zračnog prometa. To može rezultirati povećanim radnim opterećenjem kontrolora zračnog prometa koje predstavlja potencijalni sigurnosni rizik. Kako bi udovoljili prometnoj potražnji, pružatelji usluga u zračnoj plovidbi moraju osigurati odgovarajući sektorski kapacitet koji će omogućiti siguran i učinkovit zračni promet. Budući da kapacitet sektora ovisi o radnom opterećenju kontrolora zračnog prometa, kompleksnost zračnog prometa postaje jedan od ključnih čimbenika koji se razmatra pri istraživanju ovih pokazatelja i sustavu upravljanja zračnim prometom. Kompleksnost zračnog prometa definira se kao poteškoća u praćenju i upravljanju određenom situacijom u zračnom prometu [4]. Jedinstveno europsko nebo (SES), projekt modernizacije i poboljšanja europskog upravljanja zračnim prometom, ima za cilj povećanje sigurnosti prometa, kapaciteta i učinkovitosti, kao i smanjenje negativnih posljedica povećane potražnje zračnog prometa. Nekoliko novih tehnologija (rješenja) razvijeno je putem SESAR-ovog programa upravljanja zračnim prometom (SESAR) kako bi se zadovoljile velike prometne potražnje i osigurala sigurnost u prometu. Kompleksnost zračnog prometa istražuje se i unutar SESAR-a, što je rezultiralo SESAR-ovim rješenjem br. 19 Automatizirana podrška za otkrivanje i rješavanje kompleksnosti (iz SESAR-a 1). Jedna od potfunkcionalnosti koja će se razviti u okviru SESAR2020 je automatizirana podrška za procjenu kompleksnosti prometa koja je propisana Provedbenom uredbom Komisije (EU) br. 716/2014 od 27. lipnja 2014. o uspostavljanju zajedničkog pilot projekta koji podržava provedbu europskog glavnog plana (Master plan) upravljanja zračnim prometom. Ovaj rad daje istraživački pregled modela i metoda za utvrđivanje i ocjenu kompleksnosti zračnog prometa. Na temelju prethodnih istraživanja identificirani su nedostatci postojećih modela, predstavljena je nova metoda za određivanje kompleksnosti zračnog prometa i predložen je novi model koji bi trebao nadmašiti nedostatke koji su i dalje prisutni u ovom polju istraživanja. Cilj istraživanja: Izraditi model kompleksnosti zračnog prometa temeljen na radnim zadaćama kontrolora zračnog prometa. Hipoteza: Kompleksnost zračnog prometa moguće je odrediti na temelju radnih zadaća kontrolora zračnog prometa. Argumenti koji potkrepljuju hipotezu: • Subjektivne procjene kontrolora zračnog prometa u postojećim modelima određivanja kompleksnosti zračnog prometa nisu konzistentne. • Modeli za određivanje kompleksnosti zračnog prometa temeljeni na subjektivnim procjenama kontrolora zračnog prometa definirani su u ovisnosti o karakteristikama određenog zračnog prostora te ne daju valjane rezultate u primjeni na druge zračne prostore. • Radne zadaće aktiviraju se na temelju karakteristika prometnih situacija te su neovisne o kontroloru zračnog prometa koji ih provodi. • Povećanje kompleksnosti zračnog prometa za posljedicu ima povećanje radnog opterećenja kontrolora zračnog prometa, a radno opterećenje se može izraziti kao skup radnih zadaća kontrolora zračnog prometa. S ciljem potvrđivanja postavljene znanstvene hipoteze, istraživanje će biti provedeno kroz šest temeljnih faza. U prvoj fazi istraživanja definirat će se radne zadaće oblasnog radarskog kontrolora zračnog prometa koristeći metodu intervjuiranja kontrolora, analizom postojeće literature te priručnika koji objašnjavaju radne zadaće kontrolora te metodom promatranja rada kontrolora na radnom mjestu. Kontrolori zračnog prometa izvršavaju radne zadaće ovisno o prometnoj situaciji stoga je iznimno važno pravilno definirati sve radne zadaće koje se provode te kreirati veliki broj različitih prometnih situacija. S obzirom na to da se određene radne zadaće, poput razrješavanja konflikta, broje kao jedan problem, a u stvarnosti su višedimenzionalni problem, potrebno je definirati takve, višedimenzionalne radne zadaće koje će se moći koristiti u matematičkom modelu. U drugoj fazi istraživanja potrebno je kreirati prometne situacije iz kojih se mogu iščitati sve potrebne informacije koje će omogućiti oblasnom radarskom kontroloru zračnog prometa da procijeni kompleksnost prometne situacije. Prometne situacije kreirat će se kao statične slike koje će sadržavati sve potrebne informacije za procjenu kompleksnosti situacije, poput brzine zrakoplova, smjera letenja zrakoplova, destinacije zrakoplova, ulazne i izlazne točke u sektoru, namjere pilota, definirane granice zračnog prostora, trenutne visine zrakoplova, izlazne visine itd. Prometne situacije bit će definirane za generički zračni prostor da se izbjegne subjektivnost ocjenjivanja na poznatim zračnim prostorima i prometnim situacijama. Također, razlog korištenja generičkog zračnog prostora je mogućnost kasnije primjene modela na različite zračne prostore. Prometne situacije imat će varijabilan broj zrakoplova, različite međusobne interakcije ovisno o poziciji, visini, smjeru i brzini kretanja, različit položaj u prostoru, udaljenost od granice prostora, itd. Također u ovoj fazi istraživanja kreirat će se prometne situacije za drugi zračni prostor koji će se kasnije koristiti u zadnjoj fazi istraživanja za validaciju modela na različite zračne prostore. U trećoj fazi istraživanja bit će potrebno odrediti radne zadaće na temelju prometnih situacija. Definirane radne zadaće iz prve faze istraživanja dodjeljivat će se prometnim situacijama iz druge faze uz pomoć automatiziranog sustava. Radne zadaće definirane su ovisno o prometnim situacijama gdje za svaku radnu zadaću postoje jasno definirana pravila kada se aktiviraju i kada se trebaju provesti. Primjeri radnih zadaća koje se provode su: monitoriranje zračnog prometa, izvršavanje zahtijeva pilota, koordinacija sa susjednim zračnim prostorom, razrješavanje konflikta, itd. Na taj način postojat će jasno definirane radne zadaće za svaku prometnu situaciju. U četvrtoj fazi istraživanja testirat će se oblasni radarski kontrolori zračnog prometa. Primijenit će se metoda komparacije kojom će oblasni radarski kontrolori zračnog prometa između dvije ponuđene prometne situacije morati odrediti koja je kompleksnija. Primijenit će se 120 prometnih situacija koje će omogućiti aktivaciju svih mogućih radnih zadaća. Po završetku usporedbi prometnih situacija, kontrolori će imati jasan poredak od najmanje do najviše kompleksne prometne situacije koju su sami prethodno poredali metodom komparacije te ih grupirati u ocijene kompleksnosti prometa od 1 do 5. Na osnovu tih ocjena, te prethodnih usporedbi prometnih situacija dodijelit će se linearno interpolirane ocijene ostalim prometnim situacijama. Istom metodom prikupit će se podaci za drugi zračni prostor za potrebe validacije modela. U petoj fazi istraživanja uz pomoć strojnog učenja trenirat će se linearni model koristeći Bayesian Ridge regresije da se radnim zadaćama (istraživačkim varijablama) dodjele težinske vrijednosti na osnovu linearno interpoliranih ocjena iz prethodne faze (ciljane varijable). Na taj način izraditi će se model za određivanje kompleksnosti zračnog prometa na temelju radnih zadaća kontrolora zračnog prometa. U šestoj fazi istraživanja radit će se validacija matematičkog modela temeljem subjektivnih procjene kontrolora zračnog prometa dobivenim na drugom zračnom prostoru, te će se vidjeti je li moguća primjena modela na različite zračne prostore

The effect of polymers on the radiolytic synthesis of magnetic iron oxide nanoparticles

U ovom doktorskom radu istražen je utjecaj različitih polimera i drugih eksperimentalnih čimbenika na γ-radiolitičku sintezu magnetskih nanočestica željezovih oksida. Redukcija Fe3+ do koje dolazi γ-ozračivanjem prekursorske suspenzije praćena je spektrofotometrijski metodom s 1,10-fenantrolinom. Uz dekstran, dietilaminoetil-dekstran i dekstran sulfat moguće je postići 100 %-tnu redukciju te nastaju stabilne suspenzije magnetskih nanočestica. Uz dietilaminoetil-dekstran pri dozama 10 – 36 kGy nastaju superparamagnetske nanočestice magnetita, dok pri dozama 50 – 130 kGy nastaju magnetski nanodiskovi feroksihita. Uz dekstran sulfat nastaju getit i željezov(III) sulfat hidroksid. Uz poli(etilen-oksid) (PEO) i poli(vinil-pirolidon) nastaju magnetski polimerni gelovi ili magnetske suspenzije, a znatno slabija redukcija (~55 %) rezultira nastankom magnetita i getita, čak i pri visokim dozama (300 kGy). Stupanj umreženja i čvrstoća PEO gela rastu s dozom i koncentracijom prekursora, a do umrežavanja dolazi i preko nanočestica. Osim polimera i doze zračenja, važan utjecaj na stupanj redukcije i fazni sastav produkta imaju i koncentracija 2-propanola i Fe3+ prekursora, pH te koncentracija i molekulska masa polimera.In this thesis, the effect of different polymers and other experimental factors on the γ-radiolytic synthesis of magnetic iron oxides nanoparticles (NPs) was investigated. γ-irradiation-induced Fe3+ reduction was monitored spectrophotometrically with the 1,10-phenanthroline method. With dextran, diethylaminoethyl-dextran, and dextran sulfate colloids, it is possible to achieve a 100 % reduction and formation of stable suspensions of magnetic NPs. With DEAE-dextran, superparamagnetic magnetite NPs form in the dose range of 10 – 36 kGy, while magnetic feroxyhyte nanodiscs form in the 50 – 130 kGy dose range. With dextran sulfate, goethite and iron(III) sulfate hydroxide form. Synthesis with poly(ethylene oxide) (PEO) and poly(vinylpyrrolidone) resulted in the formation of magnetic polymer hydrogels or magnetic suspensions. Significantly lower reduction (~55 %) results in the formation of magnetite and goethite, even at high doses (300 kGy). Degree of crosslinking and strength of PEO gels improve with dose and precursor concentration, while NPs act as additional crosslinkers. Besides the polymer and dose absorbed, 2-propanol and precursor concentrations, pH, polymer concentration and molar mass also affect the reduction and phase composition of the products

Ferrocene as a chiroptical sensor for determining the chirality of amino acids and peptides

U radu je provedena konformacijska analiza i karakterizacija obrazaca vodikovih veza na odabranim skupovima monosupstituiranih ferocenskih peptidomimetika hijerarhijskim pristupom odnosno kombinacijom molekulsko- i kvantno-mehaničkih metoda. Računalno dobiveni rezultati uspoređeni su s eksperimentalnim podacima. Računalnom kemijom utvrđeno je da središnja kiralnost aminokiseline i/ili helična kiralnost kratkog peptidnog lanca izravno ili preko kratke akiralne poveznice vezanih na ferocensku skupinu utječu na predznak apsorpcijskog maksimuma ferocenskog kromofora (oko 470 nm) u spektru cirkularnog dikroizma. Predznak i veličina Cottonovog efekta u korelaciji su s predznakom i veličinom diedarskog kuta χ kojim je opisana rotacija amidne skupine izravno vezane na ferocenski ciklopentadienilni prsten. Uvođenje akiralnih aminokiselina, poput 2-amino-2-metilpropanske kiseline (Aib) i 1-aminocikloheksankarboksilne kiseline (Ac6c), stvaranjem β-okreta i 310 uzvojnica vodi k većoj zastupljenosti jednog od konformera u Boltzmannovoj raspodjeli pri 298 K. Navedeno bi se moglo iskoristiti u dizajnu nove skupine selektivnih kirooptičkih senzora temeljenih na ferocenskom kromoforu za određivanje središnje kiralnosti aminokiselina i helične kiralnosti kratkih peptidnih lanaca.n this thesis conformational analysis and characterization of hydrogen bond patterns were performed using a hierarchical approach combining molecular and quantum mechanics methods on selected groups of monosubstituted ferrocene peptidomimetics. The computational results were compared with experimental data. Computational chemistry confirmed the central chirality of the amino acid and/or the helical chirality of the short peptide chain, directly or via a short achiral linker attached to the ferrocene group, affect the sign of the absorption maximum of the ferrocene chromophore (at 470 nm) in the circular dichroism spectrum. The sign and magnitude of the Cotton effect correlates with the sign and magnitude of the dihedral angle χ describing the rotation of the amide group directly attached to the cyclopentadienyl ring of ferrocene. The introduction of achiral amino acids, such as 2-amino-2-methylpropanoic acid and 1-aminocyclohexanecarboxylic acid, through the formation of β-turns and 310 helices, results in a greater prevalence of a single conformer in the Boltzmann distribution at 298 K. This information could be used in the development of a new group of selective chiroptical sensors based on ferrocene chromophores to determine the central chirality of amino acids and the helical chirality of short peptide chains

Activities on small Solar System bodies and modern methods of determining their physical characteristics

U Sunčevom sustavu, osim Sunca i planeta, do danas je otkriveno gotovo milijun malih tijela Sunčevog sustava. Zbog njihovih malih dimenzija, oni spadaju u objekte čije istraživanje često zahtijeva teleskope velikih promjera ili primjenu suvremenih opažačkih metoda. Jedna od suvremenih opažačkih metoda određivanja fizikalnih karakteristika malih tijela Sunčevog sustava, koja dozvoljava razlučivosti veće od bilo koje druge zemaljske metode, jest metoda zvjezdanih okultacija. Mala tijela po sastavu i orbitalnim parametrima možemo klasificirati u asteroide i komete. Međutim, među asteroidima se pojavljuje malobrojna skupina objekata koji pokazuju aktivnosti slične kometskim. U doktorskom radu istražena je mikroaktivnost malog tijela 95P/(2060) Chiron. Zbog nedavne indikacije da bi Chiron mogao posjedovati prstenove, njegov mehanizam gubitka mase može biti objašnjen udarima krhotina iz Chironove orbite koje padaju na njegovu površinu. Opažanja su prikupljana na Španjolskoj zvjezdarnici Calar Alto, a za analizu su uglavnom korištene fotometrijske metode. Određivanjem Chironove rotacijske krivulje sjaja i njegove apsolutne zvjezdane veličine, potvrđena je pretpostavka da Chiron posjeduje prstenove. Kao primjer primjene metode zvjezdanih okultacija u svrhu istraživanja fizičkih karakteristika malih tijela Sunčevog sustava, opisano je određivanje veličine, oblika, albeda i gustoće patuljastog planeta Haumea, gornje granice Haumeine atmosfere, te otkriće i karakterizacija prstenova oko glavnog tijela Haumee. U svrhu poboljšanja vremenske razlučivosti opažanja zvjezdanih okultacija s malim tijelima, istražena je i opisana mogućnost primjene atmosferskih Čerenkovljevih teleskopa MAGIC. Njihovi veliki promjeri i osjetljivi fotomultiplikatorski detektori s visokim frekvencijama uzorkovanja, osim za unapređenje razlučivosti u određivanju fizičkih karakteristika malih tijela Sunčevog sustava, mogu biti korišteni za izravna mjerenja promjera zvijezda. U doktorskom radu opisana je metoda određivanja zvjezdanih promjera pomoću detekcije Fresnelovih difrakcijskih uzoraka, koji se mogu opaziti tijekom zvjezdanih okultacija. Detaljno je modeliran signal kakav bi bio opažen teleskopima MAGIC, uzevši u obzir karakteristike teleskopa i osjetljivost detektora. Kroz opažačke prijedloge ostvareno je teleskopsko vrijeme za opažanje zvjezdanih okultacija s MAGIC teleskopima.Extended abstract - Besides the Sun and the planets, our Solar System contains nearly 1 million discovered small Solar System bodies. Due to their small size, they belong to objects whose research often requires large-sized telescopes or the application of modern observation methods. One of today’s modern observational methods used for determining the physical characteristics of the small Solar System bodies, allowing several orders of magnitude better resolutions than any other Earth-based method, is the stellar occultations method. By composition and orbital parameters, small Solar System bodies can be classified into asteroids and comets. Nevertheless, there is a group of asteroid-like objects that show cometlike activities. This doctoral thesis consists of 3 parts. In part one, the observed micro activity of the small Solar System body 95P/(2060) Chiron was investigated. In part two, as an extensive example of the application of the stellar occultation method to investigate the physical characteristics of small Solar System bodies, the determination of the dwarf planet’s Haumea size, shape, albedo, and density was described. In part three, in order to improve the temporal resolution of observations of stellar occultations with small bodies, the potential of using the atmospheric Cherenkov telescopes MAGIC for observing stellar occultations was investigated. Activity of 95P/(2060) Chiron The minor planet 95P/(2060) Chiron belongs to the asteroid group of centaurs, which according to dynamic parameters belongs to asteroids. Chiron has an orbit far away from the Sun, in which sublimation of water ice is not considered as a possible cause for triggering mass loss mechanisms. The expected rate of collisions among small bodies in the region of centaurs is not expected to be high. Regardless of that, since its discovery, Chiron has repeatedly shown indications of cometary activity (Kowal et al. 1979; Tholen et al. 1988; Meech Belton 1990). In 2015, Ortiz et al. (2015) found indications that (2060) Chiron possesses rings. Motivated by these findings, additional observations and interpretations of the cause of its activity were made and described in this doctoral thesis (and published in Cikota et al., 2018). Observations were carried out in three different observation campaigns between 2014 and 2016, using three different instruments located at the Calar Alto Observatory (CAHA) in Almeria, Spain - 3.5 m MOSCA, 1.23 m DLR-MKIII and 2.2 m CAFOS. From the collected observations, amplitudes of Chiron’s rotational light curves and measurements of Chiron’s absolute magnitudes were determined. The measured amplitudes are consistent with the model proposed by Ortiz et al. (2015) which is taking into account both, Chiron’s triangular ellipsoid-like shape and the light contribution of rings around Chiron. Although the frequency of collisions among small bodies in the centaur region is very low, iv due to the recent indication that Chiron possesses rings, and assuming that there is debris orbiting around Chiron, it is well possible that some of this debris may be continually falling and impacting on its surface, producing outbursts and forming a bound or quasi-bound coma. Consequently, a dust release mechanism triggered by impacts should not be excluded as a possible cause for its activity. To study this hypothesis, the scatter in Chiron’s photometric data was compared to the scatter of comparison stars of similar brightness as Chiron. The scatter of Chiron’s photometric measurements for the observations carried out on July 23 and 24, 2014, with the DLR-MKIII 1.23 m CAHA telescope was found to be 0.027 mag, while the comparison star’s scatter is 0.014 mag. During the photometric campaign in 2015, containing data collected with CAFOS 2.2 m CAHA telescope on September 11 and September 13, the scatter of Chiron’s photometric measurements was determined to be 0.029 mag, while the comparison star’s scatter values were 0.018 mag. The noticeable difference between the comparison star’s and Chiron’s photometric scatter supports our hypothesis of continuous micro activity on Chiron. That mechanism could also be a plausible explanation for impulsive brightening on a timescale of hours that have been observed by Luu Jewitt (1990). We hypothesize that some activity outbursts on regular comets could also be triggered by collisions, either with debris orbiting them or with meteoroids. Additionally, the data collected with the CAFOS 2.2 m CAHA telescope over 3 nights between September 11 and September 14, 2015, was used to search for comet-like activity signs like coma or tail. The data was combined to a false-color image of Chiron that contains 95 integrations of 300 s each, resulting in a total integration time of 28500 s (475 min). The combined image of Chiron shows that the coma itself is not detectable, but a very faint asymmetric shape with a measured position angle of ∼ 87◦ was observed. The feature can be explained by a ∼5 arcsec long comet-like tail, of a determined surface brightness of 25.3 mag(R)/arcsec2. Determination of the dwarf planet Haumea’s physical characteristics - Five dwarf planets are currently known in our Solar system. (1) Ceres is the closest dwarf planet to us, and the only dwarf planet orbiting in the inner part of the Solar system, within the main belt of asteroids. Four dwarf planets - (134340) Pluto, (136199) Eris, (136108) Haumea, and (136472) Makemake, are members of the Kuiper belt, located in the outer part of the Solar system beyond Neptune’s orbit. Due to the large distances of dwarf planets in the outer Solar system, indirect observation methods are necessary to accurately determine their physical characteristics. Among trans-Neptunian objects, the dwarf planet Haumea stands out in its elongated shape and extremely short rotation period (Brown et al. 2005; Rabinowitz et al. 2006; Brown et al. 2007). Unlike other dwarf planets (Sicardy et al. 2011; Ortiz et al. 2012; Stern et al. v 2015), Haumea’s physical characteristics were not precisely determined. In this doctoral thesis, the determination of Haumea’s size, shape, albedo, and density was described, as well as the discovery and characterization of its rings (published in Ortiz et al. 2017). On January 21, 2017, a stellar occultation of the dwarf planet Haumea was observed. The occulted star URAT1 533-182543 with its apparent brightness of = 17.6 mag made it observable already for small- and mid-sized telescopes. Therefore, the occultation event was observed from many locations and resulted in 12 positive detections from 10 different sites across Europe. From the collected sequences of CCD images, photometric measurements of the synthetic aperture were performed. In the case of data collected from the Črni Vrh Observatory by the drift method, a special procedure of photometric analysis was applied to the stellar trail. By fitting a square well model to the collected photometric measurements, the times of the star’s disappearance and reappearance were determined, and occultation chords were generated for each observation location. To the chords in the projected plane, an elliptical limb was fitted by minimizing a 2 function. By that, the apparent edge of the shape of the ellipse, which represents the outline of Haumea’s shadow, was determined. The determined parameters of the major and minor axis of the ellipse are 1 704 ± 4 km and 1 138 ± 26 km respectively. The position angle of the minor axis is -76.3◦ ± 1.2◦. A search for an atmosphere was performed and the upper value of Haumea’s atmospheric pressure was determined by using the best available data set collected by the Asiago Observatory. From Haumea’s mass, and assuming that the body is in hydrostatic equilibrium, an average surface gravity of 0.39 ms−2 was determined. By comparing a modelled occultation light curve with the observed light curve, the upper value of Haumea’s pure isothermal global atmosphere of 2 in thermal equilibrium can be determined. Assuming a surface temperature of 40 K, we find a 1 upper limit for surface(2) = 3 nbar, and a 3 upper limit for surface(2) = 15 nbar. In addition to the main occultation, there are brief dimmings prior to and after the main event. These dips are consistently explained by a narrow and dense ring around Haumea that absorbed about 50% of the incoming stellar flux. A distinct cross-sectional profile of the rings collected in an observation with the 1 m telescope of the Konkoly Observatory reveals a radial ring width of ring ≈ 74 km at the occultation ingress and ring ≈ 44 km at the occultation egress, with corresponding apparent transparency of p’ = 0.55 and p’ = 0.56. The locations of twelve detected secondary events, projected in the sky plane, allow the retrieval of the full ring orbit, assuming an apparent elliptical shape, and using the same approach as used for fitting Haumea’s limb. The parameters of the elliptical fit to the rings are 0 ring = 2287+75 −45 km for the apparent semimajor axis, and 0 ring = 541 ± 23 km for a semiminor axis. The position angle of the minor vi axis is ring = -74.3◦ ± 1.3◦. Assuming the rings are circular, it implies a radius of the ring of ring = 2287+75 −45 km and an inclination angle of ring = 13,8◦ ± 0.5◦. The circular ring assumption is supported by the fact that the center of the ring ellipse coincides with the order of uncertainty with the center of the limb of Haumea’s main body. The position angle of the ring minor axis ring = -74.3◦ ±1.3◦ coincides with that of the limb minor axis limb = -76.3◦ ± 1.2◦, which is another strong argument that we are observing a ring that settled into Haumea’s equatorial plane. Furthermore, it was found that the radius of the rings coincides with the area where 3:1 spin-orbit resonances are expected. From the determined parameters of Haumea’s limb, a three-dimensional shape and density of Haumea were determined. The obtained parameters of the triaxial ellipsoid a × b × c are (1 161 ± 30) km × (852 ± 2) km × (513 ± 16) km. The mean value of the Haumea density, determined through the parameters of the triangular ellipsoid, and the mass determined by the orbital period of the Hi’iake satellite, is 1 885 ± 80 kg m−3. The geometric albedo of Haumea determined by our observations is 0.51, which is significantly smaller than the value of 0.804, as available in the most recent literature (Fornasier et al. 2013). Application of the atmospheric Cherenkov telescopes MAGIC for observing stellar occultations - In order to accurately determine the physical characteristics of small bodies by using the occultation method, a high temporal resolution of the detector is required. In order to improve the observational methods of stellar occultations, the use of the MAGIC (Major Atmospheric Gamma Imaging Cherenkov) telescopes was considered. With its sensitive central pixel, the MAGIC-II telescope has shown to be an excellent instrument for detecting millisecond flashes in the visible spectra. Compared to any other optical telescope used for observing stellar occultations, its central pixel with a temporal resolution of 10 kHz, combined with a large 17 m aperture, the MAGIC-II telescope enables reaching two orders higher resolutions. However, some of its limiting characteristics are the inability to control the sampling frequency, sensitivity only in the visible spectrum between 300 and 400 nm, and a low angular resolution (due to physically large pixels) responsible for a limitation in the apparent brightness of m = 13.5 ± 0.6 mag. In addition to determining the physical characteristics of small bodies, using the stellar occultation method enables us to determine the angular sizes of the occulted stars. Since stars are not point sources (they have a finite angular diameter), during the occultation of a stellar disk, its light curve does not show a sharp brightness drop but describes a Fresnel interference pattern whose details depend on the angular diameter of the occulted star. High sampling rates make it possible to record these interference patterns. Therefore, the high temporal resolution vii of the detector is the key for direct measurements of stellar radii. In this doctoral thesis, the method of determining stellar radii by observing Fresnel diffraction patterns that can be detected during stellar occultations is described. Models of the expected signal were performed, taking into account the characteristics of the MAGIC telescopes and the sensitivity of its detectors. Through observational proposals, telescope time was granted and first observations of stellar occultations with the MAGIC telescopes were acquired. Additionally, the effects of limb darkening of stellar disks were investigated. It was found that diffraction patterns formed by occultations of large disks with angular diameters of 0.7 mas and high limb darkening factors of u = 1.0 deviate in intensity up to approximately 5% from diffraction patterns of homogeneously illuminated stellar disks (u = 0.0). For stellar disks of smaller diameters or smaller limb darkening factors, the intensity deviations are smaller. These deviations in the intensity of diffraction patterns are reflected in the determination of the angular diameters of stellar disks. It was found that the angular radius of a homogeneously illuminated stellar disk, compared to a disk with a limb darkening factor of u = 1.0 taken into account, deviates by approximately 12.4%. Taking the limb darkening factors into account contributes to the accuracy of measurements of the angular diameters of stellar disks, but to achieve this accuracy, photometric measurements with uncertainties below 5% are required. Historically, almost all measurements of the stellar radii smaller than ∼1 arc millisecond have been performed by interferometric measurements. Measurements of stellar radii by observing occultations with asteroids allow reaching angular resolutions up to 0.1 milliarcseconds, which is at least a factor of two larger than the one available through interferometric measurements, and a factor of 10 larger than what can be achieved by observing lunar occultations. Therefore, the asteroid occultation method is extremely useful for measuring the angular diameters of stars below 1 milliarcsecond. In the period from December 2017 to February 2020, a total of 6 occultation observations with the MAGIC-II telescope were scheduled. Four observations were not successfully acquired due to bad weather or technical reasons. Two occultation events, those by the small bodies (83) Beatrix and (28) Bellona, were successfully acquired but resulted in a negative detection. Although the occultation events of (83) Beatrix and (28) Bellona occurred over sufficiently bright sources, and their probability of observation was estimated at 99%, the negative detections can be explained by a too small brightness drops, ∼1.5 mag for the (83) Beatrix event (2.5 ), and ∼0.9 mag for the (28) Bellona event (1.5 ). Based on the analysis presented in this thesis, we expect that any event with a brightness drop larger than 1.8-3.0 mag (3-5 above background noise) should be detected. Therefore, the observation campaign of occultations on MAGIC telescopes will be continued in the future

Influence of TLR5 (rs2072493) and TLR7 (rs5935436) polymorphisms on transcriptome and metabolome of in vitro model of metastatic non-small cell lung carcinoma

Karcinom pluća je jedna od najčešćih i najsmrtonosnijih malignih bolesti u svijetu. Uz izloženost duhanskom dimu, važan čimbenik u nastanku i razvoju navedene bolesti je i genetska podloga. Aktivacijom receptora Toll-like (TLR) pokreće se složeni signalni put koji u konačnici kulminira oslobađanjem različitih transkripcijskih čimbenika. Istraživanja koja su prethodila doktorskoj disertaciji pokazala su povezanost polimorfizma u genima TLR5 (rs2072493) i TLR7 (rs5935436) s nastankom karcinoma pluća. Cilj ovog istraživanja bio je ispitati utjecaj ovih polimorfizama na transkriptom i metabolom u uvjetima in vitro. Rezultati analize transkriptoma pokazuju da polimorfizam rs2072493 utječe na promjene u aktivnosti signalnog puta receptora spregnutim s proteinima G (GPCR). Rezultati analize metaboloma pokazuju da prisutnosti polimorfizma rs2072493 mijenja aktivnosti metabolizma triptofana. Nadalje, povećanjem ekspresije gena TLR7, metastatske stanice karcinoma pluća, H1299, postaju osjetljivije na kotretman imikvimodom i paklitakselom. Također, promjena u ekspresiji TLR7 utječe na promjene u aktivnosti staničnog puta glikolize, signalnog puta HIF-1, i signalnog puta AMPK.Lung cancer is one of the leading causes of cancer-related deaths worldwide. Exposure to smoke is the main cause of developing lung cancer, genetic background also has a significant role. Activation of Toll-like receptors (TLR) starts a complex signaling pathway, which in the end releases transcriptional factors. Previous associations studies linked polymorphisms in TLR5 (rs2072493) and TLR7 (rs5935436) with higher susceptibility of developing lung cancer. The aim of this research was to examine the effect of these polymorphisms on the transcriptome and metabolome in vitro. The results of the transcriptome analysis show that the rs2072493 polymorphism affects changes in the activity of the G protein-coupled receptor (GPCR) signaling pathway. The results of the metabolome analysis show that the presence of the rs2072493 polymorphism changes the activity of tryptophan metabolism. Furthermore, metastatic lung cancer cells, H1299, overexpressing TLR7 are more sensitive to co-treatment with imiquimod and paclitaxel. Also, the change in TLR7 expression affects the activity of glycolysis metabolism, the HIF-1 signaling pathway, and the AMPK signaling pathway

The impact of iodine intake on functional parameters of the thyroid in pregnant women

Istraživanje je proučavalo utjecaj unosa joda na funkciju i volumen štitnjače (Tvol) u trudnica na području Zagreba. Unos joda je određen mjerenjem koncentracije joda u urinu (UIC). Cilj istraživanja bio je utvrditi unos joda i utjecaj dodatnog unosa joda putem dodataka prehrani u trudnica u svim trimestrima trudnoće na funkciju i Tvol, vrijednost tireoglobulina (Tg) kao biljega unosa joda u trudnoći i utjecaj morfoloških promjena štitnjače na njegovu vrijednost. Hipoteza istraživanja je da trudnice koje ne uzimaju dodatke prehrani s jodom imaju niže vrijednosti UIC, niže koncentracije slobodnog tiroksina (FT4), više koncentracije tireotropina (TSH) i Tg-a u serumu i veći Tvol. Istraživanje je obuhvatilo 91 trudnicu koje su uzimale i 100 trudnica koje nisu uzimale dodatke prehrani s jodom. Medijan UIC u trudnica koje nisu uzimale dodatke prehrani s jodom iznosio je 158 μg/L, a koje su uzimale 169 μg/L, što je dostatan unos joda u obje skupine i cjelokupnom uzorku. Trudnice koje nisu uzimale dodatke prehrani s jodom imale su statistički značajno niže vrijednosti FT4, a više vrijednosti Tg-a i Tvol (p˂0.05). Tireoglobulin je koristan biljeg unosa joda u trudnoći. Difuzne promjene štitnjače značajno povećavaju razinu Tg-a u serumu. Nije utvrđena korelacija Tg-a i ostalih ispitivanih prametara štitnjače.The study investigated the impact of iodine intake on thyroid function (TF) and thyroid volume (Tvol) in pregnant women from Zagreb. Iodine status was determined by measurement of urinary iodine concentration (UIC). The aim of the study was to asess iodine intake and the impact of iodine supplementation (IS) in pregnant women in all trimesters of pregnancy on TF and Tvol, the value of Thyroglobulin (Tg) as potential biomarker of iodine intake in pregnancy as well as the influence of morphological changes on Tg measurement. It is hypothesized that pregnant women without IS have lower UIC values, lower free thyroxine (FT4), higher thyrotropin (TSH) and higher serum Tg concentrations, as well as higher Tvol. We enrolled 91 pregnant women with IS and 100 pregnant women without IS. Median UIC was 158 μg/L in pregnant women without IS, and 169 μg/L in pregnant women with IS, indicating sufficient iodine intake in both groups as well as in overall sample. Pregnant women without IS had significantly lower FT4, and higher Tg and Tvol values (p˂0.05). Thyroglobulin is a valuable biomarker of iodine intake in pregnancy. Diffuse thyroid pattern increases Tg values. There was no correlation between Tg and other thyroid parameters