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Programming using frameworks
No full textRazvoj Interneta započinje u SAD-u šezdesetih godina prošlog stoljeća kao produkt vojnih potreba. Glavni je zadatak bio razvoj slanja paketa podataka preko mreže. Veliki korak koji je doveo do ubrzanog širenja Interneta dogodio se 1990. godine uspostavljanjem jedne od najatraktivnijih mrežnih usluga, World Wide Weba. Daljnjim razvojem Interneta, došlo je do razvoja aplikacija (kojih je svakim danom sve više) i programskih jezika prilagođenih potrebama Interneta.
Programski jezik JavaScript u to se vrijeme postavio kao idealno rješenje jer je zadovoljio potrebe komunikacije klijenta i servera. Daljnjim napretkom tehnologije i potrebom korisnika za modernijim sučeljima, JavaScript se dodatno razvija. Nastaju razne biblioteke koje se po potrebi uključuju (dodaju) prilikom programiranja te se ovisno o kombinaciji dodanih biblioteka mijenjaju funkcionalnosti aplikacije, a samim time pružaju i širok spektar novih mogućnosti.
Biblioteke su na svom početku bile idealno rješenje, no kasnije su se neke biblioteke u sličnim ili čak istim kombinacijama uključivale u program pa su zbog toga nastali okviri (engl. framework) koji već u sebi imaju uključene najčešće korištene biblioteke. Na taj način je programeru smanjena potreba za odabirom pojedinih biblioteka, ali je za programera osigurano da na početku ima sve što je potrebno, ovisno o području tj. potrebi aplikacije koju razvija. Okviri su danas jako popularni te se velika većina web aplikacija izrađuje pomoću njih, no ipak imaju i neke mane kao što su uporaba drugačije sintakse od čistog JavaScript jezika.
Obzirom da svi programeri ne poznaju JavaScript ili neku od njegovih inačica u dovoljnoj mjeri, razvili su se tzv. wrapperi. To su programska okruženja koja omogućuju programeru pisanje koda u već poznatom programskom jeziku, a wrapper, tzv. omotač, doslovno omota sloj oko napisanog koda te ga prevede u JavaScript kod ili neki drugi programski jezik, naravno ovisno o wrapperu. Prednost im je kodiranje u već poznatom jeziku, ali često postoje i mane kao što su ograničenje wrappera koji ima onoliko mogućnosti koliko ih wrapper podržava.
Kako bi i studenti bili u tijeku s novim tehnologijama, na fakultetima se osmišljavaju novi kolegiji koji o njima poučavaju. Ipak, satnice na fakultetu su premale da bi se mogla dobiti konkretna znanja o svemu potrebnom za rad u realnim situacijama, ali ipak daju širu sliku što studenta čeka u budućnosti.The history of the Internet began in the USA in the 1960s as a product of military needs. The main task was to develop sending data packages using network. The big step that led to the rapid expansion of the Internet occurred in 1990 by establishing one of the most demanding network services, the World Wide Web. With the further development of the Internet, there has been an increase in the number of applications (more and more each day) and Internetbased programming languages. At that time, the programming language JavaScript was set up as an ideal solution because it met the needs of client and server communication. By further technology developing and user needs for more modern interfaces, JavaScript is evolving. Various libraries are appearing, which are optionally included when programming, and depending on the combination of the added libraries, they change the application's functionality and thus provide a wide range of features. In the beginning, libraries were the ideal solution, but later some libraries were included in the program in similar or even same combinations, which resulted developing frameworks that already include those libraries. With that option, the programmer has fewer choices but in the start has everything that is needed for the application develeoping. Frameworks are very popular today and the majority of web applications use them, but they still have some flaws like different syntax from pure JavaScript language. Since there are developers that don't know or use JavaScript language or some of versions, wrappers have been developed. They are program environments that offer writing code in a known programming language, and that wrapper, literally wrap a layer around the written
code and translate it into a JavaScript code or other programming language, of course depending on the wrapper. Theirs great advantage for the programmer is coding in a language they already know, but there are often shortcomings such as wrapper limitations and having as many features as the wrapper has. In order for the students to be in the process of using new technologies, new courses are being set up at the colleges that teach them. However, number of hours are too small to be able to get specific knowledge of everything needed to work in realistic situations but still give a wider picture of what the student is looking forward to in the future
Misconceptions and different teaching approaches in introductory programming at the K-12 level
No full textProgramiranje je poseban način razmišljanja kojim se od postavljenog problema dolazi do rješenja izvedivog na računalu. Upravo je zbog toga učenje programiranja danas tako važno. Istovremeno, ono je i zahtjevno, pa je prirodno tražiti načine kako ga olakšati primjenom različitih obrazovnih alata. Poučavanje programiranja bit će uspješnije ukoliko učitelji steknu uvid u ono što učenici znaju, ali također i u ono što ne znaju, pa je poznavanje najčešćih pogrešnih shvaćanja učenika nužno. Dodatnu prepreku uspješnom poučavanju mogu predstavljati i apstrakcije, koje su temeljni koncept programiranja. To se posebno odnosi na učenike petih i šestih razreda osnovne škole jer se oni nalaze u konkretnoj fazi kognitivnog razvoja i imaju poteškoće već u ranim fazama učenja apstraktnih programerskih koncepata, koji nisu prikladni njihovu uzrastu. Problemi su još izraženiji ukoliko se u poučavanju koriste tradicionalni oblici nastave te isključivo tekstualni programski jezici, kod kojih je naglasak na sintaksi umjesto na semantici. U cilju prevladavanja navedenih poteškoća, a budući da postoji nedostatak sličnih istraživanja kod učenika koji još uvijek nisu dosegli formalnu fazu kognitivnog razvoja, osmišljeno je istraživanje u četiri faze. Rezultati istraživanja ukazali su na najčešće miskoncepcije učenika te dobi o kojima treba voditi računa prilikom planiranja uvodnog poučavanja programiranja. Rezultati su također potvrdili da na uspjeh učenika ne utječe vrsta odabranog tekstualnog programskog jezika za poučavanje. Osim toga, dobiveni rezultati pokazali su da vizualizacija nema utjecaj ne rezultate učenja, dok vizualno programiranje ima pozitivan učinak na usvajanje svih ispitivanih osnovnih programerskih koncepata kod programera početnika osnovnoškolske (K-12) razine, čime opravdava svoju primjenu u poučavanju.Programming is a unique way of thinking that leads from a given problem to a solution achievable on a computer. This is precisely why learning programming holds such importance today. Simultaneously, it is also challenging, prompting a natural search for ways to facilitate it through the use of various educational tools. Teaching programming will be more successful if educators gain insight into what students know, but also into what they don't, thus understanding the most common misconceptions students hold is essential. Additional hurdles to effective teaching can arise from abstractions, which constitute fundamental programming concepts. This concern is particularly relevant to fifth and sixth-grade elementary school students, as they find themselves in a concrete phase of cognitive development and face difficulties in the early stages of learning abstract programming concepts that are not suitable for their developmental age. These challenges are exacerbated when traditional teaching methods are employed, coupled with exclusively textual programming languages that emphasize syntax over semantics. In order to overcome the aforementioned difficulties, and due to the lack of similar research involving students who have not yet reached the formal stage of cognitive development, a four-phase study was devised. Research results highlighted the most common misconceptions held by students of this age group, which need to be taken into account when planning introductory programming education. The findings also confirmed that the choice of textual programming language for teaching does not influence student success. Furthermore, the obtained results demonstrated that visualization does not impact learning outcomes, while visual programming, in contrast, has a positive effect on the acquisition of all examined fundamental programming concepts among beginner K-12 level programmers. This effect justifies its application in teaching
Bacterial resistance to antibiotics in Acinetobacter isolates from wastewater treatment plants in Croatia
No full textCilj ovog istraživanja bio je ispitati fenotipsku osjetljivost izolata roda Acinetobacter na različite antibiotike. Uzorci vode su prikupljeni u uređajima za pročišćavanje otpadnih voda (UPOV) Katalinića brig i Stupe u Splitu, te na pripadajućim podmorskim ispustima. Ukupno je identificiran 91 izolat, među kojima su najzastupljeniji bili A. baumannii i A. pittii, dok su ostale vrste bile manje prisutne. Rezultati su pokazali značajnu razinu rezistencije na karbapeneme (meropenem, imipenem) i peniciline s inhibitorima β-laktamaze (piperacilin/tazobaktam, tikarcilin/klavulanska kiselina). A. baumannii je pokazao najveću učestalost rezistencije, dok je A. sichuaensis bio najosjetljiviji na testirane antibiotike. Najviša stopa rezistencije zabilježena je kod izolata iz influenta UPOV-a Katalinića brig, što može biti posljedica ulijevanja bolničkih otpadnih voda u ovaj UPOV. Naime, prethodne studije su pokazale da značajan selekcijski pritisak u takvim uvjetima povećava udio višestruko rezistentnih sojeva. Ovo istraživanje naglašava ulogu otpadnih voda kao rezervoara rezistentnih oportunističkih patogena, uključujući patogena kritičnog prioriteta, karbapenem-rezistentnog A. baumannii, kao i potrebu njihovog rigoroznog praćenja u cilju smanjenja javnozdravstvene prijetnje.The aim of this study was to examine the phenotypic sensitivity of isolates of the genus Acinetobacter to different antibiotics. Samples were collected from wastewater treatment plants (WWTP) of Katalinić brig and Stupe in Split, including their submarine outfalls. A total of 91 isolates were identified, among which A. baumannii and A. pittii were the most abundant, while other species were less present. Results showed a significant level of resistance to carbapenems (meropenem, imipenem) and penicillins with β-lactamase inhibitors (piperacillin/tazobactam, ticarcillin/clavulanic acid). A. baumannii showed the highest resistance rate whereas A. sichuaensis was the most sensitive to the antibiotics used. The highest resistance rate was recorded for isolates from the influent of UPOV Katalinić brig, which could be attributed to the presence of hospital wastewater. It was previously found that the selection pressure under such conditions increases the proportion of multiple resistant strains. The study highlights the role of wastewater as a reservoir of antibiotic-resistant opportunistic pathogens, including the WHO critical-priority pathogens, the carbapenem-resistant A. baumannii, as well as the need for their rigorous monitoring to reduce the public health threat
Strukturalna karakterizacija, antimikrobna aktivnost i toksičnost antimikrobnih peptida identificiranih u trakavice (Taenia solium Linnaeus, 1758)
No full textAll living organisms are constantly threatened by large number and great diversity of pathogens which is why all of them synthesize antimicrobial peptides (AMPs) as a first line of defense as a part of their innate immunity. These molecules show direct antimicrobial and/or immunomodulatory properties which make them a potential source of new therapeutics during global antimicrobial resistance crisis. As one of the most successful animal groups in nature, parasitic helminths (worms) found different ways to overcome and avoid expulsion by their host’s immune system. One of them is by secreting different immunomodulatory molecules one of which are also AMPs. Helminth’s coevolution with the host gut microbiome and reciprocal adaptation which favors development of compounds minimally invasive to the host make helminthic AMPs especially interesting for further investigation. The aim of this thesis was to characterize three potential AMPs from tapeworm (Taenia solium). That included bioinformatical analysis, structural characterization by CD spectroscopy, determination of antimicrobial activity and subsequent mode of action by propidium iodide (PI) uptake assay using flow cytometry. Cytotoxic activity was tested with MTT assay and late confirmed with PI uptake assay using flow cytometry. Two out of three peptides showed potent antibacterial activity with borderline levels of toxicity which should be addressed if the peptides undergo further studies for potential therapeutical applications.Svi živi organizmi konstantno su ugroženi velikim brojem i velikom raznolikošću patogena, zbog čega sintetiziraju antimikrobne peptide (AMP) kao prvu liniju obrane i dio svog urođenog imunološkog odgovora. Ove molekule pokazuju izravno antimikrobno i/ili imunomodulacijsko djelovanje što ih čini potencijalnim izvorom novih lijekova tijekom globalne krize razvoja rezistencije na antibiotike. Kao jedna od najuspješnijih životinjskih skupina u prirodi, parazitski crvi su pronašli različite načine da nadvladaju i izbjegnu imunološki sustav svog domaćina. Jedan od njih je izlučivanje različitih imunomodulacijskih molekula kao što su npr. antimikrobni peptidi. Koevolucija parazitskih crva s crijevnim mikrobiomom domaćina i recipročna prilagodba koja pogoduje sekreciji minimalno invazivnih spojeva čini ove antimikrobne peptide posebno zanimljivima za daljnje istraživanje. Cilj ovog rada bio je istražiti biološku aktivnost tri potencijalna AMP-a iz trakavice, Taenia solium. To je uključivalo bioinformatičku analizu, strukturnu karakterizaciju CD spektroskopijom, određivanje antimikrobne aktivnosti i mehanizma djelovanja koristeći propidij jodid i protočnu citometriju. Citotoksična aktivnost ispitana je MTT testovima i kasnije potvrđena koristeći propidij jodid (PI) i protočnu citometriju . Dva od tri peptida pokazala su potencijalno antibakterijsko djelovanje s graničnim razinama toksičnosti koju bi trebalo poboljšati ukoliko se peptidi budu dalje istraživali u svrhu potencijalne terapijske primjene
Optimization of protein extraction methods for LC-MS/MS analysis: Preliminary analysis of the proteome of the Croatian oak plant (Quercus virgiliana (Ten.) Ten. )
No full textU ovome radu proveli smo analizu metoda ekstrakcije proteina za opisivanje proteoma lista i tkiva modificiranog hrastovom osicom biljke hrvatskog hrasta (drmun, Quercus virgiliana (Ten.) Ten.) pomoću LC-MS spektrometrije masa. Testirana su četiri različita protokola kako bi se odredila najučinkovitija metoda za ekstrakciju i izolaciju proteoma: SDC-FASP, ekstrakcija fenolom u kombinaciji sa SDC-FASP, taloženje TCA/acetonom praćeno ekstrakcijom fenolom i SDC-FASP, te taloženje TCA/acetonom u kombinaciji sa SDC-FASP. Cilj je bio utvrditi najučinkovitiju metodu za izolaciju i pročišćavanje proteina za pripremu uzoraka uz pomoć filtera (engl. filter-assisted sample preparation, FASP). Identifikacija proteina i posttranslacijske modifikacije (PTM) analizirane su korištenjem softvera ProteinPilot™ prema bazi podataka referentnog proteoma Quercus lobata. Iako su izmjereni niski prinosi proteina za sve protokole, taloženje TCA/acetonom praćeno ekstrakcijom fenolom i SDC-FASP dalo je najveći broj identificiranih proteina. Ukupni ionski kromatogrami (engl. total ion chromatograms, TIC) također su potvrdili niske signale peptidnih iona koji ukazuju na niske koncentracije proteina. Usporedna analiza uzoraka lista i tkiva modificiranog hrastovom osicom (engl. gall-wasp) pokazala je različite proteomske profile. Tkiva lista bila su bogata proteinima povezanim s fotosintezom, energetskim metabolizmom i odgovorima na stres, dok tkiva modificiranog hrastovom osicom sadrže proteine povezane s prikupljanjem hranjivih tvari, regulacijom razvoja i imunološkom modulacijom, odražavajući fiziološke učinke modificiranog tkiva na domaćina.In this study, we performed an analysis of protein extraction methods suitable for proteomic experiments of oak leaves and oak gall wasp-modified tissue from Quercus virgiliana using LC-MS-based mass spectrometry. Four extraction protocols were tested for optimal protein isolation: SDC-FASP, phenol extraction combined with SDC-FASP, TCA/acetone precipitation with phenol extraction and SDC-FASP, and a combination of TCA/acetone precipitation and SDC-FASP. The aim was to determine the most effective method for protein isolation and purification for filter-assisted sample preparation (FASP). Protein identification and post-translational modifications (PTMs) were analyzed using ProteinPilot™ with reference to the Quercus lobata proteome. While low protein yields were observed for all protocols, TCA/acetone precipitation followed by phenol extraction and SDC-FASP yielded the highest number of identified proteins. The total ion chromatograms (TIC) also confirmed the low peptide ion signals indicating low protein concentrations. Comparative analysis of leaf and gall wasp-modified tissues revealed different proteomic profiles. The leaf tissues were rich in proteins related to photosynthesis, energy metabolism and stress responses, while gall wasp-modified tissues had proteins related to nutrient acquisition, developmental regulation and immune modulation, reflecting the physiological effects of gall production on the host
Bacterial resistance to antibiotics in Klebsiella and Enterobacter isolates from wastewater treatment plants in Croatia
No full textCilj ovog diplomskog rada je izolirati karbapenem-rezistentne Klebsiella i Enterobacter izolate iz uzoraka otpadne vode iz uređaja za otpadne vode (UPOV-i) grada Splita i morske vode u blizini pripadajućih podmorskih ispusta u srednjem Jadranu, te testirati njihovu fenotipsku osjetljivost na antibiotike. Određena je razina fekalnog onečišćenja u uzorcima te je 108 izolata identificirano do vrste i ispitana njihova fenotipska osjetljivost na 16 antibiotika metodom disk-difuzije na Mueller-Hinton agaru. Najveći broj izolata pokazao je rezistenciju na cefoksitin (97,22%), piperacilin (90,74%), aztreonam (84,26%) i meropenem (79,63%), dok je najmanja učestalost rezistencije zabilježena na trimetoprim-sulfametoksazol (17,59%). Rezultati pokazuju visok postotak rezistencije na različite klase antibiotika, odnosno višestruko rezistentni fenotip izolata i moguću prisutnost karbapenemaza. Također, obzirom da UPOV Katalinića Brig obrađuje i otpadne vode iz KBC-a Split, mogući su rizici širenja bolničkih rezistentnih sojeva u morski okoliš, što potvrđuje potrebu za daljnjim praćenjem njihove učestalosti te nastavkom istraživanja u smjeru određivanja genotipa rezistencije ovih oportunističkih patogena kritičnog prioriteta.The aim of this thesis was to isolate carbapenem-resistant Klebsiella and Enterobacter isolates from wastewater samples from wastewater treatment plants (WWTPs) of the city of Split and seawater from the adjacent submarine outlets in the central Adriatic, and to test their phenotypic sensitivity to antibiotics. The level of fecal contamination in the samples was determined, and 108 isolates were identified to species and their phenotypic sensitivity to 16 antibiotics was tested using the disk-diffusion method on Mueller-Hinton agar. The largest number of isolates showed resistance to cefoxitin (97.22%), piperacillin (90.74%), aztreonam (84.26%) and meropenem (79.63%), while the lowest frequency of resistance was recorded against trimethoprim-sulfamethoxazole (17.59%). The results show a high percentage of resistance to different classes of antibiotics, i.e. the multiple resistant phenotype of the isolates and the possible presence of carbapenemases. Also, considering that UPOV Katalinića Brig also processes wastewater from University Hospital Split, there are possible risks of the spread of hospital resistant strains into the marine environment, which confirms the need for further monitoring of their frequency and the continuation of research in the direction of determining the resistance genotype of these WHO critical-priority opportunistic pathogens
Plan upravljanja istraživačkim podacima-CROVes-PhyBA
No full textPlan upravljanja istraživačkim podacima za završno razdoblje projekta "Hrvatske vrste roda Veronica: identifikacija i biološka aktivnost
Adaptations of marine mammals to diving conditions
No full textMorski sisavci imaju posebne prilagodbe koje im omogućuju ronjenje. Pohranjuju zalihe kisika u plućima, krvi i mišićima pomoću većih koncentracija hemoglobina i mioglobina. Za vrijeme duljih zarona mišići im prelaze na anaerobni metabolizam te mogu tolerirati visoke razine mliječne kiseline. Tijekom ronjenja usporavaju otkucaje srca, a krv usmjeravaju prema vitalnim organima poput mozga i srca. Pluća im imaju mogućnost kolabiranja radi smanjenja apsorpcije dušika i rizika od dekompresijske bolesti. Kitovi rone s punim plućima, a tuljani izdišu prije zarona. Najdublje zarone izvode kitovi zubani, dok sirene rone na najpliće dubine.Marine mammals have special adaptations that enable them to dive. They store oxygen in their lungs, blood, and muscles through higher concentrations of hemoglobin and myoglobin. During longer dives, their muscles switch to anaerobic metabolism and can tolerate high levels of lactic acid. During diving, they slow their heart rate and direct blood to vital organs such as the brain and heart. Their lungs can collapse to reduce nitrogen absorption and the risk of decompression sickness. Whales dive with full lungs, while seals exhale before diving. Toothed whales dive the deepest, while sirenians dive to the shallowest depths
Learning styles in teaching programming using the STEMI hexapod robot
No full textKorištenjem robota, učenici se mogu aktivno uključiti u proces učenja, a programiranje postaje interaktivno i zabavno. U ovom radu izrađena je mobilna aplikacija na edukacijskoj platformi MIT App Inventor korištenjem programskog jezika Scratch koja služi za upravljanje robotom STEMI hexapod. Kao glavni dio rada provodi se istraživanje interakcije različitih stilova učenja u poučavanju programiranja korištenjem robota STEMI hexapod. U obradi podataka koristi se factorial ANOVA kao metoda višefaktorske analize varijance za četiri dimenzije stilova učenja prema Felder-Silvermanovom modelu. Na uzorku od 97 ispitanika, utvrđeno je da učenici koji su verbalni po vizualno/verbalnoj dimenziji i ujedno racionalni po racionalno/intuitivnoj dimenziji postižu statistički značajno bolje rezultate u programiranju robota od učenika koji imaju druge kombinacije stilova učenja prema Felder-Silvermanovom modelu.By using robots, students can actively engage in the learning process, and programming becomes interactive and fun. In this study, a mobile application was developed on the educational platform MIT App Inventor using the Scratch programming language, which is used to control the STEMI hexapod robot. The main part of the project involves researching the interaction of different learning styles on programming learning using the STEMI hexapod robot. Factorial ANOVA is used as a method of multivariate analysis of variance for four dimensions of learning styles according to the Felder-Silverman model. Based on a sample of 97 participants, it was found that students who are verbal on the visual/verbal dimension and rational on the rational/intuitive dimension achieve statistically significantly better results in robot programming than students with other combinations for all four dimensions of learning styles according to the Fedler-Silverman model
Activity of antimicrobal peptides from tapeworm (Taenia solium Linnaeus, 1758) against gram-negative bacteria and cancer cell lines
No full textGlobalno širenje antimikrobne rezistencije jedna je od vodećih prijetnji suvremenog doba. Sposobnost brze prilagode bakterija na okolišne čimbenike sve češće rezultira pojavom rezistentih bakterija dovodeći tako u pitanje učinkovitost postojećih antibiotika. Izazov današnjice je pronalazak bioaktivnih tvari efektivnih u suzbijanju bakterijskih infekcija, a potencijalni obećavajući kandidati su antimikrobni peptidi (AMP) - multifunkcionalne efektorske molekule s direktnom antimikrobnom aktivnosti i/ili imunomodulatornim djelovanjem. Pozornost diplomskog rada usmjerena je na karakterizaciju i proučavanje širokog spektra djelovanja peptida identificiranog u trakavici Taenia solium (Linnaeus, 1758), nazvanog TSO8, kao i njegovih fragmenata. U tom kontekstu, spektroskopijom cirkularnog dikroizma opažene su strukturne promjene TSO8 peptida u izotropnom i anizotropnim otapalu, te u prisutnosti liposoma. Ispitana je antimikrobna aktivnost svih peptida na panelu gram-negativnih bakterija, te se nastojalo djelomično definirati mehanizam djelovanja TSO8 peptida promatrajući kinetiku rasta bakterija u ovisnosti o različitim koncentracijama peptida. S druge strane, makromolekule ovog tipa često imaju i antitumorsko djelovanje koje je ispitano MTT testom na karcinomskoj staničnoj liniji mokraćnog mjehura i karcinomskoj liniji raka dojke.The rapid spread of antimicrobial resistance is one of the leading threats of modern times. The ability of bacteria to quickly adapt to environmental factors is rapidly resulting in the emergence of resistant bacterial strains, thus calling into question the effectiveness of existing antibiotics. Today's challenge is to find bioactive substances effective in suppressing bacterial infections, and potential lead compounds in this sense are antimicrobial peptides (AMPs) - multifunctional effector molecules with direct antimicrobial activity and/or immunomodulatory properties. The focus of the thesis is on the characterization and study of the broad spectrum of action of the peptide identified in the tapeworm Taenia solium (Linnaeus, 1758), and therefore named TSO8, as well as its fragments. In this context, structural changes of TSO8 peptides in isotropic and anisotropic solvent and in the presence of liposomes were observed by circular dichroism spectroscopy. The antimicrobial activity of all peptides was tested against a panel of Gram-negative bacteria, and an attempt was made to partially define the mechanism of action of the these AMPs by observing the kinetics of bacterial growth depending on different peptide concentrations. On the other hand, macromolecules of this type often also have anticancer properties, which was tested by the MTT test on a bladder cancer and a breast cancer cell line