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Convolutional neural networks
No full textOvaj se diplomski rad bavi razradom neuronskih mreža, te specifično konvolucijskih neuronskih mreža. U prvom je dijelu objašnjeno zašto baš neuronske mreže, sama struktura mreže te bitne značajke poput aktivacijske funkcije, funkcije gubitka, metrike te optimizatora. Ukratko su navedeni glavni tipovi mreža. U drugom dijelu su obrađene konvolucijske neuronske mreže koje se koriste u svrhu učenja na slikama. Objašnjeni su tipovi skrivenih slojeva koji se najčešće javljaju u konvolucijskim neuronskim mrežama te njihove značajnosti. U trećem su dijelu navedeni primjeri problema klasifikacije i regresije koristeći KNN. Koristi se skup podataka MNIST koji se sastoji od ručno napisanih brojeva. Taj se skup podataka često koristi dok je u pitanju učenje na slikama jer slike imaju oznake što nije česta okolnost. Kod klasifikacije je cilj napraviti mrežu koja će na dobar način klasificirati nove podatke na kojima nije trenirala te na sličan način kod regresije dobro predvidjeti numeričku vrijednost prikazanu na slikama.This thesis deals with the development of neural networks, and specifically convolutional neural networks. In the first part, it was explained why exactly neural networks, the very structure of the network and essential features such as activation function, loss function, metrics and optimizer. The main types of networks are briefly listed. The second part deals with convolutional neural networks used for learning from images. The types of hidden layers that most often occur in convolutional neural networks and their importance are explained. The third part provides examples of classification and regression problems using KNN. The dataset MNIST is used, which consists of handwritten numbers. This dataset is often used when learning from images because images have labels, which is not a common circumstance. In classification, the goal is to create a network that will properly classify new data on which it has not been trained, and similarly in regression, it will predict the numerical value shown in the images well
In silico and in vitro analysis of the role of LTB gene in head and neck squamous cell carcinoma
No full textRak pločastih stanica glave i vrata (engl. head and neck squamous cell carcinoma, HNSCC)
predstavlja veliki izazov u onkologiji koji otežava liječenje zbog svoje: heterogenosti, otpornosti na
terapije i složenog tumorskog mikrookruženja. Limfotoksin beta (LT-β) je protein za koji kodira gen
LTB i koji sudjeluje u regulaciji upalnih i imunoloških procesa, dok njegova prekomjerna ekspresija u
HNSCC dovodi do aberantne aktivacije puta NF-κB i otpornosti na kemoterapiju. Uloga LT-β u
razvoju i progresiji HNSCC-a nije u potpunsti razjašnjena. Hipoteza ovog istraživanja je da pojačana
ekspresija gena LTB može imati važnu ulogu u razvoju HNSCC-a, te da bi gen LTB mogao poslužiti
kao biomarker i terapijski cilj za poboljšanje ishoda liječenja. Kombinacijom metode in silico i in vitro
istražena je ekspresija gena LTB u zdravom tkivu, primarnim tumorima i tumorskim staničnim
linijama. Analizirani su genetski i epigenetski faktori koji doprinose promjenama u ekspresiji ovog
gena, dok su funkcionalni testovi omogućili procjenu utjecaja utišavanja gena LTB na ključne stanične
procese poput migracije i formiranja kolonija. Rezultati pokazuju da povišena ekspresija gena LTB
korelira s lošom prognozom, modulacijom imunosnog sustava i agresivnošću tumora. Smanjenjem
ekspresije gena LTB smanjuje se proliferacija i pokretljivost tumorskih stanica, potvrđujući njegovu
onkogenu ulogu. Interakcija s imunosnim kontrolnim točkama i onkogenim putevima dodatno
naglašava njegov potencijal kao biomarkera. Ciljanje gena LTB putem siRNA ili imunomodulacijskih
terapija predstavlja obećavajuću strategiju za liječenje HNSCC-a, što zahtijeva daljnja istraživanja.Head and neck squamous cell carcinoma (HNSCC) presents a significant challenge in oncology due to
its heterogeneity, resistance to therapies and complex tumor microenvironment, which complicate
patient treatments. Lymphotoxin beta (LT-β) is a protein, encoded by the LTB gene, that normally
participates in regulation of inflammatory and immune processes. However, its overexpression in
HNSCC leads to aberrant activation of the NF-κB pathway and chemotherapy resistance. The role of
LT-β in the development and progression of HNSCC remains understudied. The hypothesis of this
research is that increased expression of the LTB gene may play a significat role in HNSCC
development and that it could serve as a biomarker and therapeutic target for improving treatment
outcomes. Through a combination of in silico and in vitro methods, the expression of the LTB gene
was examined in healthy tissue, primary tumors and tumor cell lines. Genetic and epigenetic factors
contributing to changes in the gene's expression were analyzed, while functional assays allowed for
the assessment of the impact of LTB gene silencing on key cellular processes, such as migration and
colony formation. The results show that elevated LTB gene expression correlates with poor prognosis,
immune modulation and tumor aggressiveness. LTB knockdown reduces tumor proliferation and
motility, confirming its oncogenic role. Its interaction with immune checkpoints and oncogenic
pathways highlights its potential as a biomarker. Targeting LTB via siRNA or immune-modulating
therapies offers a promising strategy for HNSCC treatment, warranting further investigation
SIRTUIN 3 PROTEIN IN SEX-SPECIFIC MAINTENANCE OF ENERGY HOMEOSTASIS DURING AGING
No full textStarenje je složen biološki proces, a promjene do kojih pritom dolazi počinju na staničnoj razini tedovode do narušene energetske homeostaze. Važnu ulogu u očuvanju energetske homeostaze ima mitohondrijska deacetilaza Sirtuin 3 (Sirt3), čija je funkcija deacetilacija proteina uključenih u metaboličke puteve za proizvodnju energije. Cilj istraživanja bio je ispitati ulogu Sirt3 u promjenama u energetskoj homeostazi ovisnima o spolu tijekom starenja u modelu miševa in vivo i modelu mišjih embrionalnih fibroblasta (MEF) in vitro. U istraživanju na modelu in vitro, korišten je etopozid za umjetno izazivanje promjena povezanih sa starenjem. U uvjetima homeostaze vidljiv je utjecaj nedostatka Sirt3, dok spolne razlike postaju vidljive nakon tretmana etopozidom: ženska knock-out (KO) stanična linija posebno je osjetljiva na stres izazvan tretmanom, potencijalno zbog nemogućnosti nadoknade gubitka Sirt3. U modelu in vivo primijećene su samo spolne razlike: ženke imaju viši energetski status i usmjeravaju metabolizam prema oksidaciji masnih kiselina za dobivanje energije.Aging is a complex biological process that begins at the cellular level, disrupting energy
homeostasis. The mitochondrial deacetylase Sirtuin 3 (Sirt3) plays a crucial role in maintaining
this balance by deacetylating proteins involved in metabolic pathways for energy production.
This research aimed to examine the role of Sirt3 in sex-dependent changes in energy
homeostasis during aging, using an in vivo mouse model and an in vitro mouse embryonic
fibroblasts (MEF) model. In the in vitro model, etoposide was used to induce age-related
changes. Under control conditions, Sirt3 deficiency effects were evident, while etoposide
treatment revealed sex-specific differences: female knock-out (KO) MEFs showed particular
sensitivity, likely due to an inability to compensate for Sirt3 loss. In the in vivo model, only
sex-specific differences were observed, with females generally displaying a higher energy
status and a metabolic shift towards fatty acid oxidation for energy production
Mechanism of interaction of transcription factors SloRfrom Streptococcus mutans and ScaR from Streptococcus gordonii with manganese (II) ions and DNA
No full textOdržavanje homeostaze iona prijelaznih metala neophodno je za preživljavanje i virulenciju bakterija. U bakterijama Streptococcus gordonii i Streptococcus mutans, primarnim kolonizatorima površine zuba, koncentracija dvostruko nabijenih kationa mangana (Mn(II)) regulirana je homodimernim transkripcijskim faktorima osjetljivim na Mn(II), ScaR i SloR, koji kontroliraju ekspresiju proteina uključenih u unos mangana. Kako bi se razjasnio mehanizam kojim vezanje Mn(II) utječe na vezanje proteina ScaR i SloR za DNA, primijenjene su različite računalne (QM i MD) i eksperimentalne (ITC, DSC, EMSA, FA, EPR i CD) metode. Računalni rezultati pokazali su da vezanje Mn(II) inducira konformacijsku promjenu proteina SloR i ScaR koja prvenstveno utječe na položaj i fleksibilnost DNA veznih domena te, posljedično, na afinitet vezanja proteina za DNA. Eksperimentalni rezultati otkrili su da proteini po monomeru vežu dva do tri iona Mn(II), koji stabiliziraju strukturu proteina. Računalna analiza kompleksa protein-DNA pokazala je da oblik DNA, definiran palindromskim nukleotidnim slijedom, igra ključnu ulogu u pravilnom pozicioniranju proteina na DNA.Maintaining transitional metal ion homeostasis is crucial for bacterial survival and virulence. In Streptococcus gordonii and Streptococcus mutans, manganese ion (Mn(II)) concentration is regulated by homodimeric transcription factors ScaR and SloR, which control the expression of proteins involved in manganese uptake. Various computational (QM and MD) and experimental (ITC, DSC, EMSA, FA, EPR, and CD) methods were used to elucidate how Mn(II) binding affects ScaR and SloR binding to DNA. Computational results showed that Mn(II) binding induces a conformational change in SloR and ScaR, affecting the position and flexibility of the DNA binding domains, and thus DNA binding affinity. Experimental results revealed that the proteins bind per monomer two to three Mn(II) ions, which stabilize the protein structure. Computational analysis of the protein-DNA complex indicated that the DNA shape, defined by a palindromic nucleotide sequence, is crucial for proper protein positioning on DNA
Genomic characterization of monkeypox virus isolates (Orthopoxvirus monkeypox)
No full textVirus majmunskih boginja (Orthopoxvirus monkeypox, Orthopoxvirus, Poxviridae MPXV) se smatrao endemskom vrstom zapadne i središnje Afrike sve do globalne epidemije mpox-a 2022. godine kada se proširio u neendemske regije Europe i SAD-a. Tijekom epidemije 2022. godine pojavljuje se linija B.1. Navedenoj liniji je svojstven velik broj mutacija i ubrzana evolucija u odnosu na evolucijsku stopu roda Orthopoxvirus. Filogenetskim analizama utvrđeno je da linije povezane s ovom epidemijom pripadaju filogrupi IIb. Ona se evolucijski odvojila od filogupe I koja je karakteristična za endemska područja. Prvi slučajevi bolesti mpox u Republici Hrvatskoj zabilježeni su u lipnju 2022. godine. U ovom diplomskom radu napravljena je prva genomska karakterizacija sekvenci prikupljenih u Republici Hrvatskoj tijekom 2022. godine te je uspješno uspostavljena metoda metagenomskog sekvenciranja visoke protočnosti. Uspješnim sekvenciranjem i sastavljenjem sekvenci cijelih genoma MPXV potvrdila sam kako su u Hrvatskoj u trenutku epidemije kružile linije ranije zabilježene u Europi, točnije linije B.1, B.1.7 i B.1.3. Rezultati diplomskog rada doprinose dubljem razumijevanju genomske raznolikosti i evolucije MPXV-a, osobito u neendemskim područjima. Ovo istraživanje pruža važan uvid u cirkulirajuće sojeve virusa tijekom epidemije 2022. godine u Hrvatskoj te time i u Europi. Uspostava metagenomske metode pruža mogućnost za buduće praćenje i nadzor širenja virusa.The monkeypox virus (Orthopoxvirus monkeypox, Orthopoxvirus, Poxviridae MPXV) was considered endemic to western and central Africa until the global mpox outbreak in 2022, when it spread to non-endemic regions, including Europe and the United States. During the 2022 outbreak, the B.1 lineage emerged. This lineage is characterized by a large number of mutations and accelerated evolution compared to the evolutionary rate of the Orthopoxvirus genus. Phylogenetic analyses revealed that the lineages associated with this outbreak belong to clade IIb, which evolutionarily diverged from clade I, characteristic of endemic regions. The first cases of mpox in the Republic of Croatia were recorded in June 2022. This thesis presented the first genomic characterization of sequences gathered in the Croatia in 2022, alongside the successful implementation of a metagenomic methodology. Due to successful sequencing and assembly of whole MPXV genomes, I have confirmed that, during the outbreak, some of the lineages already identified for Europe were circulating in Croatia specifically, lineages B.1, B.1.7, and B.1.3. The findings from this thesis contribute to a deeper understanding of the genomic diversity and evolution of MPXV, particularly in non-endemic regions. This research provides important insights into the circulating viral strains during the 2022 epidemic in Croatia, and by extension, in Europe. The implementation of a metagenomic method offers the potential for future surveillance and monitoring of viral spread
UTJECAJ ARBUSKULARNIH MIKORIZNIH GLJIVA NA VINOVU LOZU (Vitis vinifera L.) ZARAŽENU VIRUSIMA
No full textGrapevine hosts many pathogenic viruses, but arbuscular mycorrhizal fungi (AMF) can
modify a plant’s defence response. Experimental treatments with one or multiple AMF
species and viruses were designed to investigate the ability of AMF to modify
grapevine defence response to virus infection, through the analysis of the different
aspects of grapevine physiology and relative quantification of GRSPaV, GLRaV-3 and
GPGV. The main findings point to more detrimental effect of multiple virus infections,
but also more beneficial effect when grapevine is inoculated with multiple AMF species.
The beneficial effect of AMF on grapevine health was seen through increased growth,
photosynthesis rate and phosphorus content. Further, AMF inoculation modified plants
defence response through changes in ROS homeostasis and hormonal profile.
Simultaneously, AMF changed virus titre in the roots and leaves, depending on the
virus, plant tissue and phenological phase. In conclusion, AMF are able to modify
grapevine defence response and potentially make grapevine more tolerant to virus-induced biotic stress.Vinova loza je domaćin mnogim patogenim virusima, ali arbuskularne mikorizne gljive
(AMF) mogu modificirati obrambeni odgovor biljaka. Eksperimentalni tretmani s
jednom ili više vrsta AMF i virusa osmišljeni su kako bi se istražila sposobnost AMF-a
da modificira obrambeni odgovor vinove loze na virusne infekcije, kroz analizu različitih
aspekata fiziologije vinove loze i relativnu kvantifikaciju GRSPaV, GLRaV-3 i GPGV.
Glavni rezultati ukazuju na štetniji učinak koinfekcija virusima, ali i povoljniji učinak
kada je vinova loza inokulirana s više vrsta AMF-a. Koristan učinak AMF-a na zdravlje
vinove loze vidljiv je kroz poticanje rasta, stope fotosinteze i sadržaja fosfora. Nadalje,
inokulacija AMF je modificirala obrambeni odgovor biljaka promjenama u homeostazi
ROS-a te profilu fitohoromona. Istovremeno, AMF je promijenila titar virusa u korijenu
i listovima, ovisno o virusu, biljnom tkivu i fenološkoj fazi. U zaključku, AMF mogu
modificirati obrambeni odgovor vinove loze i potencijalno povećati tolerantnost na
biotički stres uzrokovan virusima
Spin density wave induced by magnetic field in quasi-onedimensional systems
No full textU ovom diplomskom radu proučavao sam valove gustoće spina i njihovo ponašanje pod utjecajem vanjskog magnetskog polja. Započevši od opisa stanja vala gustoće spina i njegovog teorijskog modela, proučavao sam susceptibilnost vala gustoće spina i gniježđenje Fermijeve površine u kvazi-jednodimenzionalnim sustavima. Proučen je zatim utjecaj vanjskog magnetskog polja na svojstva elektronskog plina kojim se val gustoće spina širi i kaskada faza koja je rezultat promjena svojstva sustava.In this thesis, I studied spin density waves and their behavior under the influence of an external magnetic field. Starting from the description of the spin density wave state and its theoretical model, I studied the susceptibility of the spin density wave and the nesting of the Fermi surface in quasi-one-dimensional systems. The influence of an external magnetic field on the properties of the electron gas through which the spin density wave propagates and the phase cascade resulting from the change in the properties of the systems were then studied
Paleoenvironmental reconstruction of the Krka River estuary in Holocene using benthic foraminiferans
No full textKrednjaci su jednostanični heterotrofni organizmi koji su važni paleoindikatori kroz geološku prošlost. U
ovom radu ispituje se važnost recentnih krednjaka kao bioindikatora okoliša i događaja tijekom holocena
na području Jadranskoga mora. Istraživanje je provedeno na Prokljanskom jezeru, dijelu estuarija rijeke
Krke. Analizirana jezgra sedimenata dugačka je 5.3 m i stara više od 9600 godina, odnosno obuhvaća period
od ranog holocena do danas. Napravljene su mikropaleontološke i granulometrijske analize, analize
radioaktivnog izotopa ugljika te organskog dušika i ugljika. Rezultati su omogućili podjelu jezgre na tri
zone i pokazali tijek transgresije mora u estuariju rijeke Krke. Prva zona obuhvaća bazalni dio jezgre u
kojem vrste krednjaka (najviše Ammonia tepida) upućuju na bočati okoliš s ograničenim utjecajem morske
vode. Druga zona je tranzicijski interval sa značajnijim utjecajem mora što se odražava i u prisutnim
zajednicama krednjaka, smanjenjem brojnosti vrste A. tepida. Konačno, treća zona sadrži isključivo vrste
tipične za morski okoliš uz dominaciju vrste Haynesina sp. Istraživanjem je dokazano da se analizom
zajednice krednjaka mogu dobiti važni podaci o nekadašnjem okolišu. Detaljne rekonstrukcije paleookoliša
duž istočne obale Jadrana još uvijek su malobrojne. Stoga će ovaj rad značajno doprinijeti boljem
razumjevanju promjena koje su se tijekom holocena dogodile na istraživanom prostoru.Foraminifera are unicellular heterotrophic protists that are valuable palaeoindicators in geology. This paper
evaluates the importance of the recent foraminifera as proxies of the Holocene paleoenvironmental changes
in the Adriatic Sea. The study was conducted in the Prokljan Lake (Krka River estuary). The analyzed
sediment core is 5.3 m long and over 9.600 years old. The foraminifera assemblages were used for
paleoenvironmental assessment and the obtained data were supplemented with radiocarbon isotope dating,
organic C/N, and grain size analyses. According to the results, the core can be divided into 3 zones. The
first zone, in the basal part of the core, is dominated by Ammonia tepida and it suggests the existence of a
brackish environment with limited marine influence. The second zone is a transitional zone, with a decrease
in the abundance of Ammonia tepida and stronger marine influence. Finally, the third zone has typical
marine species with the dominance of Haynesina sp. This research demonstrated that foraminifera are
important proxies of paleoenvironmental changes. Detailed reconstructions of paleoenvironments along the
eastern coast of the Adriatic are still scarce. Therefore, this work will significantly contribute to a better
understanding of the changes that occurred during the Holocene in the investigated area
NOTCH2 in different meningeoma grades: protein expression and methylation status analysis
No full textMeningeomi su najčešći primarni tumori središnjeg živčanog sustava klasificirani u tri
histološka gradusa; benigni, atipični i anaplastični. Većinom su benignog karaktera,
dok manji dio pripada višim gradusima s lošijom kliničkom slikom, povećanom stopom
recidiva i smrtnosti. Signalni put Notch je neophodan u embriogenezi, ali dokazana je
njegova uloga i u tumorigenezi. Protein NOTCH2 ovisno o vrsti tumora i tkiva može biti
onkogen ili tumor supresor, a njegova uloga u tumorigenezi meningeoma još nije
istražena. Cilj ovog diplomskog rada bio je istražiti metilaciju promotora gena i
ekspresiju proteina NOTCH2 u različitim gradusima intrakranijalnih meningeoma. U
ovom istraživanju, metilacija promotora gena NOTCH2 bila je značajno povezana s
atipičnim oblikom meningeoma. Metilacijski status gena NOTCH2 nije utjecao na
razinu ekspresije proteina. Analiza ekspresije proteina NOTCH2 pokazala je umjerenu
do jaku ekspresiju na razini citoplazme i stanične membrane u većini uzoraka
meningeoma te u kori velikog mozga zdrave osobe. Međutim, ekspresija na razini
jezgre je detektirana samo u tumorskom tkivu te je pozitivno korelirala s intenzitetom
ekspresije u citoplazmi. Rezultati ovog istraživanja upućuju na aktivnost signalnog puta
Notch i uključenost proteina NOTCH2 u tumorigenezi meningeoma.Meningiomas are the most common primary tumors of the central nervous system
classified into three different histological grades; benign, atypical, and anaplastic. They
are usually benign, while smaller part belongs to higher grades with worse clinical
outcomes, higher recurrence, and mortality rates. The Notch signaling pathway is
crucial for embryogenesis and its part in carcinogenesis has also been proven.
Depending on tissue and tumor type, protein NOTCH2 can act as an oncogene or
tumor suppressor, but its role in meningioma tumorigenesis still remains unknown. The
aim of this master thesis was to examine gene promoter methylation and NOTCH2
protein expression in different grades of intracranial meningioma. In this study, gene
promoter methylation was significantly correlated with atypical meningioma and didn't
affect protein expression. Immunohistochemical analysis showed moderate to strong
cytoplasmatic and cell membrane protein expression in all meningioma samples,
including the cerebral cortex of a healthy person. However, expression in the nucleus
was only detected in tumor tissue and it positively correlated with the intensity of
cytoplasmatic expression. The results of this study indicate the activity of the Notch
signalling pathway and involvement of NOTCH2 in meningioma tumorigenesis
The impact of alfa-cypermethrin administration in the gestational period on DNA methylation patterns in neonatal and pubertal rat ovary
No full textMetilacija DNA prva je otkivena te najviše istraživana epigenetička oznaka. Ova oznaka
nalazi se unutar same molekule DNA, a posebnu ulogu ima tijekom uspostavljanja
metilacijskog statusa utisnutih gena čime se postiže spolno-specifična ekspresija gena.
Pravilna uspostava metilacije utisnutih gena preduvjet je za normalan razvoj te reproduktivnu
sposobnost potomaka. Sintetski piretroidni insekticid α-cipermetrin djeluje kao endokrini
disruptor uzrokujući promjene u epigenetičkim mehanizmima čime dolazi do promjena u
regulaciji ekspresije gena. U ovom radu istražen je utjecaj prenatalne izloženosti α-
cipermetrinu na promjene u obrascu metilacije DNA u neonatalnom i u pubertetnom jajniku
štakora. Metodom pirosekvenciranja analizirani su retrotranspozonski sljedovi LINE-1 koji
služe za procjenu globalne metilacije, te diferencijalno metilirane regije utisnutih gena Igf2r i
Mest. Dobiveni rezultati nisu rezultirali statistički značajnim razlikama između kontrolnih i
eksperimentalnih skupina. Ovaj rad prvo je istraživanje kojim se analizirao utjecaj prenatalne
izloženosti α-cipermetrinu na obrasce metilacije DNA u neonatalnom i pubertetnom jajniku
štakora.DNA methylation is the first identified and most researched epigenetic mark. This mark is
located inside the DNA molecule itself, and it plays a special role during the establishment of
the methylation status of imprinted genes, which achieve sex-specific gene expression. Proper
establishment of methylation of imprinted genes is a prerequisite for normal development and
reproductive capacity of offspring. The synthetic pyrethroid insecticide α-cypermethrin acts
as an endocrine disruptor, causing changes in epigenetic mechanisms, which lead to changes
in the regulation of gene expression. In this paper, the impact of α-cypermethrin
administration in the gestational period on the DNA methylation patterns in the neonatal and
pubertal rat ovary was investigated. Using the pyrosequencing method, LINE-1
retrotransposon sequences were analyzed, which were used to assess global methylation, as
well as differentially methylated regions of the imprinted genes Igf2r and Mest. There were
no statistically significant differences between the control and experimental groups. This
work is the first study that analyzed the influence of prenatal exposure to α-cypermethrin on
DNA methylation patterns in neonatal and pubertal rat ovaries