Croatian Digital Dissertations Repository
Not a member yet
10487 research outputs found
Sort by
Characterisation of the phenotype, transcriptional markers and T cell receptor repertoire of circulating MAIT and γδ T lymphocytes in psoriasis vulgaris
No full textPsoriasis vulgaris is a chronic T-cell driven autoinflammatory dermatosis in which unconventional mucosal-associated invariant T (MAIT) and γδ T cells play poorly understood roles. Through a comprehensive characterisation of circulating MAIT and γδ T cells, this study revealed alterations in their frequencies, transcriptional profiles, TCR repertoires, and phenotypic and functional properties, influenced by disease duration, severity, age and sex, elucidating their contribution to disease pathogenesis.psoriasis vulgaris, γδ T cells, MAIT cell
An automated stock market trading system based on deep reinforcement learning
No full textOvaj rad predstavlja inovativni sustav za automatsko trgovanje dionicama na tržištu kapitala, koji integrira duboko podržano učenje i naprednu obradu prirodnog jezika. Istraživanje adresira izazove u automatiziranom trgovanju, uključujući volatilnost tržišta, kompleksnost financijskih podataka i potrebu za kontinuiranom adaptacijom trgovačkih strategija. Rad počinje sveobuhvatnim pregledom financijskih tržišta i hipoteze efikasnog tržišta, postavljajući teorijski okvir za razumijevanje tržišne dinamike. Zatim se fokusira na evoluciju tehnika obrade prirodnog jezika, s posebnim naglaskom na Transformer arhitekturu i njenu primjenu u analizi financijskih tekstova. Detaljno je istraženo duboko podržano učenje i njegova primjena u kontekstu financijskog trgovanja. Metodologija istraživanja obuhvaća razvoj dva modela: PrimoGPT, specijalizirani model za generiranje NLP značajki iz financijskih tekstova, i PrimoRL, model dubokog podržanog učenja za donošenje trgovačkih odluka. PrimoGPT, temeljen na naprednoj Transformer arhitekturi, demonstrira sposobnost interpretacije kompleksnih financijskih informacija, dok PrimoRL pokazuje izvanrednu adaptabilnost u dinamičnim tržišnim uvjetima. Eksperimentalna evaluacija provedena je na dionicama vodećih tehnoloških kompanija u periodu od sedam mjeseci. Rezultati konzistentno pokazuju superiornost predloženog sustava nad tradicionalnim trgovačkim strategijama i drugim modelima strojnog učenja. Posebno su impresivne performanse na NFLX dionici s povratom od 41.19%, AAPL s povratom od 24.24% i AMZN dionici s 26.72% povrata, uz održavanje visokih Sharpe omjera. Zaključno, rad unapređuje razumijevanje primjene umjetne inteligencije u financijskom trgovanju i otvara perspektive za razvoj sofisticiranijih automatiziranih trgovačkih sustava.This paper presents an innovative system for automated stock trading in the stock market, integrating deep reinforcement learning and advanced natural language processing. The research addresses challenges in automated trading, including market volatility, the complexity of financial data, and the need to adapt trading strategies continuously. The work begins with a comprehensive review of financial markets and the efficient market hypothesis, establishing a theoretical framework for understanding market dynamics. It then focuses on the evolution of natural language processing techniques, emphasizing the Transformer architecture and its application in financial text analysis. Deep reinforcement learning and its application in the context of financial trading are explored in detail. The research methodology encompasses the development of two models: PrimoGPT, a specialized model for generating NLP features from financial texts, and PrimoRL, a deep reinforcement learning model for making trading decisions. PrimoGPT, based on advanced Transformer architecture, demonstrates the ability to interpret complex financial information, while PrimoRL exhibits exceptional adaptability in dynamic market conditions. Experimental evaluation was conducted on stocks of leading technology companies over seven months. Results consistently show the proposed system's superiority over traditional trading strategies and other machine learning models. Particularly impressive performances were observed on NFLX stock, with a return of 41.19%, AAPL stock, with a return of 24.24%, and AMZN stock, with a 26.72% return, while maintaining high Sharpe ratios. In conclusion, this work advances the understanding of artificial intelligence applications in financial trading and opens perspectives for developing more sophisticated automated trading systems
The transition from the Bronze to the Iron Age at Kapiteljska njiva in Novo Mesto
No full textPrapovijesno groblje iz 1. tisućljeća pr. Krista, Kapiteljska njiva u Novom Mestu smještena je na brijegu Marof, sjeverozapadno od stare gradske jezgre, uz prapovijesnu gradinu. Na temelju analize grobnih priloga kasnobrončanodobnih paljevinskih ravnih grobova, ovaj rad bavi se moćnom kasnobrončanodobnom zajednicom u vrijeme transformacije ili tranzicije čiji je rezultat nastanak jedne od najznačajnijih željeznodobnih zajednica, ne samo u okvirima Dolenjske nego i daleko šire. Riječ je o pojavi prvih željeznih predmeta u kasnobrončanodobnoj tradiciji pokopavanja ljubljanske kulturne skupine koja se naziva i „željezni horizont“. Osim detaljne analize grobnih priloga, oblika grobnih jama i načina ukopa rad se bavi i novim znanstvenim metodama korištenim tijekom suvremenih istraživanja. Na Kapiteljskoj njivi ukupno su do 2018. godine istražena 343 paljevinska groba.
Kronološko-tipološka analiza priloga temelji se na građi 197 grobova, što iznosi 57,43 %, restauriranih grobova. Zbog devastacije prostora u vrijeme Drugog svjetskog rata, a u novije vrijeme još i više zbog mehaničke obrade, statistička je analiza upitna i zapravo ne odražava realno stanje iz vremena nastanka grobova. Percepcija i razumijevanje tipologije grobova ograničeni su na neraspadljive i u vrijeme istraživanja vidljive materijale. Uz analizu tipologije paljevinskih grobova i tipološko-kronološkog pregleda priloga, u radu su predstavljeni i rezultati antropološke analize kremacija. Dosad analizirani kremirani ostaci ukazuju na prevladavanje ukopa jedne osobe, dok je ukop dviju osoba potvrđen u šest slučaja, ukop triju osoba u jednom slučaju te ukop četiriju osoba u dva slučaja. Na temelju svih predstavljenih analiza grobove opredjeljujemo u 4 horizonta kronološke sheme ljubljanske skupine. Najstariji grobovi pripadaju stupnju Ljubljana Ib, najveći dio grobova datira u Ljubljana IIa i IIb stupanj gdje ponekad nije moguće preciznije odrediti podstupanj, dok najmlađi paljevinski grobovi pripadaju Ljubljana IIIa stupnju. Na kraju možemo zaključiti da isto stanovništvo koje već stoljećima živi na Marofu prolazi kroz proces kulturne transformacije što se odražava u promjeni materijalne kulture i načina pokopavanja na Kapiteljskoj njivi. Ujedno potvrđuje i kronološki paralelizam paljevinskog i skeletnog načina pokopavanja uz pojedine elemente materijalne kulture koji se pojavljuju i u jednoj i u drugoj vrsti grobova.Kapiteljska Njiva is located on the Marof hill, northwest of the old city centre, next to a prehistoric hillfort. The cemetery was in use for the entire 1st millennium BC, from the Late Bronze Age, through the Early Iron Age, and into the Late Iron Age. Archaeological excavations have so far been confined to the southern part of the area, while graves continue to the west, north, and east, even in areas where the terrain naturally slopes.
Flat cremation graves of the Late Bronze Age
So far, 343 flat cremation graves belonging to the Late Bronze Age phase of the Urnfield culture have been excavated. Cremation burial is characteristic for all graves, most often with an urn. In three cases (graves 34 a and b, 266 a and b, 335 a and b), we can speak of a double burial in a single grave pit. In 46 instances out of a total of 343 graves (representing 13.41% of the graves), the cremated remains of the deceased and the cremation were placed directly into the grave pit, without an urn. In 42 instances (representing 21.3% of the graves), the cremated remains of the deceased and the cremation were placed in an urn without any additional offerings. It should be noted that not all grave findings have been restored. This work includes 197 restored graves out of the total 343 excavated, which amounts to 57.43% of the entire burial material. Our perception and understanding of the typology of graves are limited to non-decomposable and visible materials at the time of excavation. There is a possibility of much more complex and richer grave content with materials that have decayed (textile, leather, wood, bone). The cremation graves have been classified into three main categories based on their contents, covering all researched and documented graves. The determined categories are:
1. Graves with cremated remains
2. Graves with urns
3. Graves with urns and grave goods.
Graves with cremated remains
Out of a total of 343 graves, cremated remains and bone fragments were placed directly in the grave pit in 46 instances, which amounts to 14%. Graves with cremated remains and bones do not contain an urn but are found in combinations with stone slabs, some with grave goods and some without.
Graves with urns
Out of a total of 343 graves, 106 instances document a grave pit with an urn, which accounts for 31%. The analysis is based on field documentation and restored material. Of the 197 restored graves, 42 graves belong to this category. Graves with urns were documented in combinations with stone slabs.
Graves with urns and grave goods
Out of a total of 343 graves, 189 instances document urns with grave goods, which accounts for 55%. The proportion of graves with urns and grave goods could be even higher after the restoration of all graves, although the composition of most graves is already visible in the field, especially after documenting and floatation of cremated remains in the field and washing ceramic urn fragments also in the field. It is particularly important to note the damage to the upper parts of graves and urns. As many as 11 variations were documented in the category of grave pits with urns and grave goods.
Regardless of the category, in 68 graves (which amounts to 19.83%), a lid was documented. It should be considered that the necropolis area was under agricultural use, indicating damage to the upper parts of graves and the possible destruction of lids. The grave lids were documented in three categories: ceramic lid, stone lid, and a combination of both. All graves are flat cremation graves except for cremation graves 274, 282, 284, 292, and 343, which, due to their location within Early Iron Age inhumation graves, suggest the possibility of burial under a tumulus. The typology of flat cremation graves is very similar in Metlika – Hrib and Borštek in Bela Krajina, as well as their chronological similarity with the graves of Kapiteljska Njiva and Mestne Njive. Very good comparisons are also found in the flat cremation graves of Budinjak, types 1 and 2. The sites of Dolenjska, Gorenjska, and Bela Krajina, along with the Ljubljana area, represent the Ljubljana group of the Urnfield culture. The large flat cremation cemetery at Kapiteljska Njiva with 343 excavated graves is an extremely important site within the Ljubljana group. The graves have been heavily damaged due to the long-term use of the area and deep ploughing. Flat cremation burials were still in use during the Early Iron Age when burials in large tumuli with inhumation had already begun. We can say that one form of burial had not yet ceased, while a new one was already developing and in use. The largest proportion consists of graves with urns and grave goods, in combination with ceramic and stone lids. Undoubtedly, the percentage of preserved stone lids and even entire graves would be higher if it weren't for the repeatedly mentioned mechanical damage.
Chronological and Typological Analysis of Grave Goods
The chronological and typological analysis of grave goods is based on the material from restored graves. This overview includes 197 graves out of a total of 343 excavated, representing 57.43% of the entire burial material. Although the urn is not terminologically a grave good, it is typologically addressed here. The proportion of graves with urns without any additional grave goods is 42, and these will be analysed in the category of urn types. The typology of grave goods is based on the categories of material used for their creation. Therefore, the entire analysis of burial material is based on 175 cremation graves from Kapiteljska Njiva. The large proportion of graves without any grave goods may also be due to the previously mentioned mechanical and natural erosional damage to the graves. Such a structure of graves may also indicate a choice of burial type, which does not necessarily reflect the status of the deceased.
A ceramic vessel serving as an urn appears in the category of graves with urns (42 graves) and in the category of graves with urns and grave goods (115 graves). Out of a total of 157 graves with urns, only one grave contains a ceramic amphora serving as an urn (grave 154), while in the remaining 156 graves, various types of pots are used as urns. The typology of pots used as urns in the cremation graves of Kapiteljska Njiva is based on the typology of pots from Metlika – Hrib and Ljubljana SAZU. In only 4 out of 175 graves (graves with burial material), the grave goods were placed outside the urn. These include grave 274, while in graves 154, 282, and 284, the grave goods were placed both outside the urn and inside it. The typological analysis of grave goods includes 115 graves in the category of graves with urns and grave goods. Ceramic grave goods are represented in the form of vessels, spindle whorls, or parts of vessels, while metal and glass items are most commonly found as parts of attire, with very few being utilitarian objects. Grave goods made from stone and bone are very rare. The category of graves (13 graves) without urns is divided into 3 subcategories: graves without urns with a stone lid (168, 170), graves without urns (27, 131, 134, 173, 196, 197, 203, 219, 292, 305), and a grave without an urn with a stone structure (84). In all 13 graves, grave goods were documented, although they are quite destroyed and poorly preserved, which may indicate grave devastation during mechanical fieldwork.
Based on the analysis of ceramic vessels, and especially metal grave goods, the graves are classified into 4 horizons of the chronological scheme of the Ljubljana group. The oldest graves belong to the Ljubljana Ib phase, while most of the graves date to the Ljubljana IIa and IIb phases, where it is sometimes not possible to determine the sub-phase more precisely. The youngest cremation graves belong to the Ljubljana IIIa phase. While the Ljubljana Ib phase is still entirely from the Late Bronze Age, significant changes and a new era are introduced by the graves of the Ljubljana II phase, which marks the so-called iron horizon and the beginning of the new Iron Age. By the time of the Ljubljana IIIa phase at Kapiteljska Njiva, the first Iron Age tumuli were already present.
Analysis of Cremated Remains of the Deceased from Kapiteljska Njiva
The cremated remains analysed so far from 70 graves indicate that a single individual was most commonly buried. Two individuals were buried in six cases (graves 28, 58, 82, 282, 284, 342), three individuals in one case (grave 322), and four individuals in two cases (graves 288, 291). Most of the combinations include one or two adults with one or two children. The double burials in the case of graves 34a and b, 266a and b, and 335a and b are also interesting. Two urns were placed in one grave pit. Although the cremated remains of the deceased from Kapiteljska Njiva are poorly preserved and very fragmented, their analysis is essential for better understanding not only the burial ritual but also the broader picture of the community during the first centuries of the last millennium BC.
To conclude
In conclusion, we can say that the same population, which had lived on Marof for centuries, went through a process of cultural transformation, which is reflected in the change in material culture and burial practices at Kapiteljska Njiva. This confirms the chronological parallelism between cremation and skeletal burial practices, along with certain elements of material culture that appear in both types of graves
Napredno vođenje procesa šaržne kristalizacije
No full textA method for real-time monitoring of particle size distribution in the batch crystallization process was developed based on an experimental study for the fosamprenavir calcium – methanol system. The aim was to improve the pharmaceutical production process while taking product quality into account. In addition, such a method is a prerequisite for the advanced process control strategy to achieve the desired particle size distribution at the end of batch crystallization. The first part of the research involved the development of an automated laboratory setup for experiments and tests of the developed methods. The next step was the collection of experimental data from the batch crystallization, which was needed for the development of calibration models. The final step of the research was the development and application of methods for real-time monitoring of the particle size distribution of crystallized fosamprenavir calcium. The chord length distribution of the crystallized sample was recorded in real time using focused beam reflectance measurement. Since this type of data is not a reliable representation of the particle size distribution, a calibration model describing the functional relationship between the chord length distribution and the particle size distribution of the crystalline sample is required. The calibration models for real-time monitoring of the particle size distribution were developed separately using partial least squares regression and artificial neural networks. The results of these two mathematical approaches were analyzed. Principal component analysis was used for the preliminary interpretation of the experimental data and for the detection of outliers. Both methods proved to be suitable for this application. Regression models using the partial least squares method proved to be better for this application, although neural networks should not be excluded. For nonlinear systems and a larger amount of available experimental data, artificial neural networks will probably prove to be more suitable than partial least squares regression models. The scientific contribution will be made through the development and application of an original, advanced real-time monitoring strategy for batch crystallization processes. The application of the developed monitoring strategy will, as expected, improve the batch crystallization process and achieve the desired particle size distribution.Na temelju eksperimentalnih istraživanja za sustav fosamprenavir kalcij – metanol razvijena je metoda za praćenje volumne raspodjele veličina čestica u stvarnom vremenu u procesu šaržne kristalizacije. Cilj je poboljšati proces farmaceutske proizvodnje kako bi se ostvarila odgovarajuća kvaliteta proizvoda. Razvijena metoda osnova je za naprednu strategiju vođenja za postizanje željene volumne raspodjele veličina čestica na kraju procesa šaržne kristalizacije. Prvi dio istraživanja uključivao je razvoj automatiziranog i integriranog laboratorijskog sustava za pokuse i ispitivanja razvijenih metoda. Sljedeći korak bilo je prikupljanje eksperimentalnih podataka iz procesa šaržne kristalizacije potrebnih za razvoj kalibracijskih modela. Završni korak istraživanja obuhvatio je razvoj i primjenu metoda za praćenje volumne raspodjele veličina čestica kristaliziranog fosamprenavir kalcija u stvarnom vremenu. Raspodjela veličina čestica izražena duljinom kristaliziranog uzorka snimljena je u stvarnom vremenu pomoću reflektometra s fokusiranim snopom. Budući da ova vrsta podataka ne prikazuje pouzdano raspodjelu veličina čestica, potreban je kalibracijski model koji daje funkcionalni odnos između raspodjele veličina čestica izražene duljinom i volumne raspodjele veličina čestica kristaliziranog uzorka. Kalibracijski modeli za praćenje volumne raspodjele veličina čestica u stvarnom vremenu razvijeni su zasebno primjenom parcijalne regresije najmanjih kvadrata i umjetnih neuronskih mreža. Analizirani su i uspoređeni rezultati ova dva pristupa. Analiza glavnih komponenti primijenjena je za preliminarno tumačenje eksperimentalnih podataka i otkrivanje odstupajućih vrijednosti. Obje metode pokazale su se prikladnima za primjenu. Regresijski modeli dobiveni metodom parcijalnih najmanjih kvadrata pokazali su se boljim. Neuronske mreže, očekivano, bi se trebale pokazati prikladnim rješenjem za nelinearne sustave i veće skupove dostupnih eksperimentalnih podataka. Znanstveni doprinos ostvaren je razvojem i primjenom originalne napredne automatizirane metode praćenja procesa šaržne kristalizacije u stvarnom vremenu. Primjena razvijene metode praćenja u proizvodnji će, očekivano, unaprijediti proces šaržne kristalizacije postizanjem definirane volumne raspodjele veličina čestica
Inductance Standard of 10 µh in Printed Circuit Board Technology
No full textDoktorski rad se bavi razvojem etalona induktiviteta 10 µH u tehnici tiskanih veza. Razvoj preciznih izmjeničnih mjernih otpornika stvorio je potrebu za njihovom karakterizacijom u pogledu određivanja njihovog prijenosnog omjera i faznog kuta, za što su potrebni etaloni induktiviteta, a budući da se radi o vrlo malim faznim kutovima potrebni su etaloni induktiviteta 10 µH kao i manjih induktiviteta. Etaloni induktiviteta bifilarnog tipa u tehnici tiskanih veza prikazani su zajedno s otporničkim djelilima napona, koji omogućavaju skaliranje induktiviteta u omjeru 100:1, kao i njihova primjena u umjeravanju LCR metara . Da bi se osigurala potrebna stabilnost etalona, izrađen je poseban termostat. U radu je određen postupak za umjeravanje etalona, te određivanje temperaturnog koeficijenta njegovog induktiviteta i električnog otpora, kao i karakterizacija termostata. U razvoju etalona primijenit će se numerički alati za proračun elektromagnetskog polja, odnosno metoda konačnih elemenata. U prvom poglavlju (1. Uvod) prikazana je motivacija i ciljevi doktorskog rada koji su proizašli iz javnog razgovora. U ovom poglavlju je razrađen i sadržaj rada. U drugom poglavlju (2. Etaloni induktiviteta) predstavljene glavne značajke mjernih svitaka i kako ih se koristi u elektrotehnici. Pregled mjernih svitaka i utjecaj frekvencije na samu zavojnicu. U ovom poglavlju predstavljeni su i prikazani primarni etaloni induktiviteta. U trećem poglavlju (3. Induktivna djelila napona i transformatori) omogućen je prikaz korištenja induktivnih djelila napona, koja se koriste sa umjeravanje etalona induktiviteta. U četvrtom poglavlju (4. Mjerenje temperature) prikazana su svojstva temperature, temperaturnih mjernih koeficijenata i etalona u području temperature. U petom poglavlju (5. Mjerna nesigurnost) sažeto su iznesene značajke mjernih nesigurnosti. U šestom poglavlju (5. Primjena induktivnih djelila u umjeravanju svitaka) prikazana je načelna upotreba induktivnih djelila napona u mjernim mostovima za umjeravanje mjernih svitaka. U sedmom poglavlju (7. LCR Metri) prikazan je opis LCR metra i njegove glavne značajke. U osmom poglavlju (8. Planarni etalon induktiviteta s dupleks sustavom zavojnica) težište je ovog doktorskog rada, a to je razvoj, simulacijsko modeliranje, izrada i ispitivanje etalona induktiviteta. Poglavlje započinje simulacijskim izvedbama, koje su napravljene metodom konačnih elemenata. Prikazani su načela rada predloženog koncepta etalona induktiviteta, te predloženi dupleks sustav planarnih zavojnica. Izrađeni etalon induktiviteta je ispitan u laboratoriju u klimatskoj komori, na utjecaj i promjenu okolišne temperature. Nakon toga je ispitan na utjecaj vanjskih elektromagnetskih polja i provedeno je mjerenje rezonatne frekvencije. U ovom dijelu su prikazani mjerni postavi, oprema i sami rezultati ispitivanja. Ujedno, ovdje je izvedena i rasprava na same razultate. U devetom (9. Zaključak) poglavlju opisan je zaključak doktorskog rada.Despite several decades of research and many successful software mitigations, modern monolithic operating systems kernel remain intrinsically flawed from a security perspective.
The biggest issue is the lack of kernel address space separation. This issue has been the main point of critique throughout the years as it exacerbates and sometimes even enables the exploitation of various memory corruption vulnerabilities present in the kernel. A single stray memory write in a faulty device driver or system call may crash the system or be used to maliciously manipulate kernel code, enabling an attacker to take control of the most privileged part of the whole machine. To make matters worse, these issues are often hard to reproduce, making debugging and fixing these vulnerabilities a very hard task. Operating system kernels suffer from the same common memory corruption vulnerabilities as userspace software. However, the damage done by a successfully exploited memory corruption vulnerability in an operating system kernel is amplified many times due to the kernel code’s increased privilege level and lack of any form of fault containment. This thesis analyses flaws in existing monolithic operating system kernels and uses it to design a novel, security-oriented monolithic kernel architecture that supports runtime isolation of kernel subsystems
Determination of human ß-defensin 2 in saliva and serum of patients with angioedema in relation to coagulation and clinical-laboratory indicators of the disease
No full textAngioedem je ograničeni, asimetrični, bezbolni otok supkutanog/submukoznog, rahlog intersticijskog tkiva i potencijalno životno ugrožavajuće stanje kod oticanja sluznica. Ovo je istraživanje ispitivalo vrijednosti humanog β-defenzina 2 (HBD2) u slini i serumu bolesnika s angioedemom te usporedilo njihove vrijednosti s koagulacijskim čimbenicima (D-dimeri, fibrinogen, faktor VII) i drugim pokazateljima bolesti. Ovo je presječno istraživanje obuhvatilo ukupno 102 ispitanika, uključujući tri skupine: 33 bolesnika s izoliranim kroničnim angioedemom (prema smjernicama iz 2022.); 33 bolesnika s angioedemom pridruženom kroničnoj urtikariji (KU) (tj. CU+AE) i 35 zdravih ispitanika. Bolesnicima je evaluirana težina angioedema validiranim upitnikom AECT (engl. Angioedema Control Test) i uzet uzorak krvi za analizu vrijednosti serumskih parametara (KKS, SE, CRP, D-dimeri, fibrinogen, faktor VII), i određivanje vrijednosti serumskog i salivarnog HBD2. Od koagulacijskih čimbenika su se samo vrijednosti D-dimera značajno razlikovale te su bile više u bolesnika s angioedemom uz urtikariju (CU+AE) nego u kontrolnoj skupini (p = 0,012), a i znatno češće povišene u obje skupine bolesnika s angioedemom nego u kontrolnoj skupini (p = 0,013; V = 0,293). Također, skupine su se značajno razlikovale po razini salivarnog HBD2 (p = 0,019; ε2 = 0,079) pa je salivarni HBD2 je bio značajno viši kod onih s CU+AE nego u kontrolnoj skupini (p = 0,019), dok se vrijednosti serumskog HBD2 nisu razlikovale između skupina. Pritom nije bilo korelacije između razine HBD2 u slini i serumu (nisu linearno korelirale). Također, koagulacijski faktori pozitivno su korelirali s dobi, a vrijednosti fibrinogena najviše su ovisile o dobi. Kontrola bolesti nije se razlikovala između dviju skupina bolesnika, iako je lošije kontrolirani angioedem nešto češće utvrđen u onih s CU+AE. Postojeći dokazi sugeriraju da je HBD2 potencijalni marker angioedema i također molekula s mogućim terapeutskim učincima te da je jedna od karakteristika angioedema i povećani potencijal zgrušavanja krvi, što može pridonijeti u stvaranju fibrina i biti važno u kontroli napadaja angioedema.Introduction: Angioedema is a limited, asymmetric, gravity-independent and painless swelling of the subcutaneous or submucous loose interstitial tissue, as well as a potentially life-threatening condition when mucosal swelling occurs. This study examined the values of human β-defensin 2 (HBD2) in the saliva and serum of patients with angioedema and compared these values with coagulation factors (d-dimers, fibrinogen and factor VII) and other indicators of the disease.
Methodology: This cross-sectional study included a total of 102 subjects, including three groups: 33 patients with isolated chronic angioedema (according to the 2022 guidelines), 33 patients with angioedema associated with chronic urticaria (CU), i.e., CU+AE, and 35 healthy subjects. Patients were evaluated for the severity of angioedema using a validated questionnaire (Angioedema Control Test) and a blood sample was taken for the analysis of serum parameters (KKS, SE, CRP, d-dimers, fibrinogen and factor VII) as well as determination of serum and salivary HBD2 values.
Results: Of the coagulation factors, only D-dimer values differed significantly and were higher in patients with angioedema with urticaria (CU+AE) than in the control group (p = 0.012), and significantly more frequently elevated in both groups of patients with angioedema than in the control group. (p = 0.013, V = 0.293). The values of fibrinogen and factor VII were not
significantly different between the three groups. Also, the groups differed significantly in the level of salivary HBD2 (p = .019, ε2 = 0.079), with salivary HBD2 being significantly higher in those with CU+AE than in the control group (p = 0.019), while the values of serum HBD2 did not differ between groups. There was no correlation between HBD2 levels in saliva and
serum (they were not linearly correlated). CRP values were significantly more frequently elevated in both angioedema groups than in the control group (85% versus 57%) (p = 0.008, V = 0.308) and were significantly higher in those with isolated angioedema (p = 0.007) and those with CU+AE than in the control group (p = 0.006). Statistically, erythrocyte levels were significantly higher in those with CU+AE than in the control group (p = 0.004) and those with isolated angioedema (p = 0.021). Mainly, decreased basophil levels (93%) were observed, as well as a significant difference in the prevalence of elevated leukocyte levels (p = 0.020, V = 0.277) which were more frequently elevated in those with CU+AE (15%) than those with isolated angioedema (3% ) and the control group (0%). Also, coagulation factors positively correlated with age, and fibrinogen values depended on age the most. With increasing age, the values of factor VII (r = 0.268, p = 0.007), D-dimer (r = 0.309, p = 0.002) and fibrinogen (r = 0.334, p = 0.001) also increased. The values of salivary HBD2 (r = 0.228, p = 0.021) and CRP (r = 0.392, p < 0.001) were linearly positively correlated with age, and platelets (r = −0.313, p = 0.001) were negatively correlated. Disease control did not differ between the two groups of patients, although poorly controlled angioedema was slightly more common in those with CU+AE.
Conclusion: The existing evidence suggests that HBD2 is a potential marker of angioedema and also a molecule with possible therapeutic effects, and that one of the characteristics of angioedema is an increased blood clotting potential, which may contribute to fibrin formation and be important in the control of angioedema attacks
Application and effects of gene modifications mediated by a lentviral vector in the mouse brain
No full textUnos genetskog materijala i genskih preinaka važan je pristup za proučavanje i liječenje genetskih i drugih bolesti. Lentivirusni vektori ističu se kao dominatan sustav dostave u ciljane stanične linije središnjeg živčanog sustava. Glavni cilj ovog istraživanja bio je utvrditi transdukciju neurona i astrocita za njih specifično dizajniranim lentivirusnim vektorom, procjeniti uzrokuje li dostavljen sustav shRNA utišavanje gena Spry2 te utvrditi učinak utišavanja gena Spry2 nakon izazivanja ishemijskog moždanog udara u mišjem modelu. Potvrđena je uspješna transdukcija stanica lentivirusnim vektorom te je analizom kolokalizacije pokazano da lentivirusni vektori s ovojnicom VSV-G transduciraju neurone dok Tet regulirani lentivirusni vektori sa specifičnim promotorom za astrocite i ovojnicom Mokola transduciraju astrocite. Procjenom aktivacije mikroglije i receptora TLR2 pokazano je da unos lentivirusnog vektora uzrokuje kratkotrajnu aktivaciju upalnog odgovora koja je ograničena na područje unosa. Analizom genske ekspresije potvrđeno je utišavanje gena Spry2 u injektiranim regijama mišjeg mozga. Međutim, njegova smanjena ekspresija nije pridonijela značajnom smanjenju volumena ishemijske lezije i funkcionalnom oporavku nakon ishemijskog moždanog udara. Ovo istraživanje potvrdilo je da su primjenjene strategije dizajna lentivirusnih vektora učinkovit sustav dostave koji omogućava ograničenu transdukciju stanica od interesa i uspješno utišavanje gena Spry2.The delivery of genetic material or gene modification is an important approach for the study and treatment of genetic and other diseases. Lentiviral vectors are a dominant delivery system to target cell lines of the central nervous system. The aim of this study was to determine the transduction of target cells with a specifically designed lentiviral vector for the neuron and astrocyte transduction, to assess whether the delivered shRNA system causes silencing of Spry2, and to examine the effect of Spry2 silencing after ischemic stroke induction in a mouse model. Successful cell transduction with the lentiviral vector was confirmed, and colocalization analysis confirmed that VSV-G pseudotyped lentiviral vectors transduce neurons, while Tet-regulated Mokola pseudotyped lentiviral vector with astrocyte-specific promoter transduce astrocytes. Furthermore, lentiviral vector causes a short-term activation of the inflammatory response, which was restricted near the area of injection site. Silencing of the Spry2 was confirmed in the injected regions of the mouse brain. However, downregulation of Spry2 did not reduced the volume of ischemic lesion and contribute to the functional recovery after ischemia. This study confirmed that the applied design strategies of lentiviral vector are an efficient delivery system that allows restricted transduction of cells of interest and successful Spry2 silencing
Phytochemical composition and iological effects of selected Salvia species from the Croatian flora
No full textU okviru ovog doktorskog rada po prvi put su usporedno istraženi fitokemijski sastav i biološki učinci sedam
odabranih biljnih vrsta roda Salvia L. koje samoniklo rastu na području Republike Hrvatske: S. fruticosa
Mill., S. glutinosa L., S. nemorosa L., S. officinalis L., S. pratensis L., S. sclarea L. i S. verticillata L.
Ekstrakcija biološki aktivnih sastavnica iz listova odabranih biljnih vrsta roda Salvia provedena je različitim
organskim otapalima s i bez primjene ultrazvuka, niskotemperaturnim eutektičkim otapalima, ugljikovim(IV)
oksidom u superkritičnom obliku te destilacijom pomoću vodene pare. Kvalitativna i kvantitativna analiza
terpenskih i polifenolnih sastavnica provedena je primjenom spektrofotometrijskih metoda te različitih
kromatografskih tehnika kao što su HPTLC, HPLC-DAD i GC-MS. Ružmarinska kiselina bila je
najzastupljenija fenolna kiselina u svim ispitanim vrstama, dok su glikozidni derivati luteolina i apigenina
otkriveni kao najzastupljeniji flavonoidi. Vrste S. fruticosa i S. officinalis istaknule su se kao vrste izrazito
bogate eteričnim uljem, dok je sadržaj eteričnog ulja u ostalih ispitanih vrsta bio značajno manji. U sastavu
eteričnog ulja vrste S. fruticosa najzastupljenija terpenska sastavnica bio je 1,8-cineol, dok je kariofilen-oksid
prevladavao u eteričnom ulju vrste S. sclarea. Značajni udjeli α- i β-tujona određeni su u eteričnom ulju vrste
S. officinalis, a germakren D bio je glavna sastavnica eteričnih ulja vrsta S. glutinosa i S. verticillata.
Antioksidacijski učinci etanolnih ekstrakata, eteričnih ulja i odabranih terpenskih i polifenolnih sastavnica te
njihova sposobnost inhibicije odabranih enzima koji se smatraju važnim terapijskim metama ispitani su
spektrofotometrijskim metodama u prikladnim eksperimentalnim sustavima. Etanolni ekstrakti ispitanih
biljnih vrsta pokazali su snažna antioksidacijska svojstva na temelju sposobnosti hvatanja slobodnih radikala,
keliranja i redukcije iona željeza te inhibicije lipidne peroksidacije. Ispitani ekstrakti su također imali
sposobnost inhibicije enzima elastaze i tirozinaze, a neki su ekstrakti inhibirali aktivnost enzima
acetilkolinesteraze i α-glukozidaze. Rezultati provedenih fitokemijskih i bioloških ispitivanja odabranih vrsta
roda Salvia L. iz hrvatske flore ukazali su na njihov biomedicinski potencijal i mogućnosti primjene u
sprječavanju i liječenju kroničnih bolesti vezanih uz starenje.
Rad je pohranjen u Središnjoj knjižnici Sveučilišta u Zagrebu Farmaceutsko-biokFor the first time, a comprehensive comparative study of the phytochemical composition and biological
effects of seven insufficiently investigated Salvia species growing wild in Croatia (S. fruticosa Mill., S.
glutinosa L., S. nemorosa L., S. officinalis L., S. pratensis L., S. sclarea L., S. verticillata L.) was conducted
in this thesis. Bioactive natural compounds from the leaves of selected Salvia species were extracted using
various organic solvents, with and without sonication, as well as deep eutectic solvents, supercritical carbon
(IV) oxide and hydrodistillation. The contents of terpenoid and polyphenolic compounds were determined
using spectrophotometric and chromatographic techniques such as HPTLC, HPLC-DAD and GC-MS.
Rosmarinic acid was the predominant phenolic acid, while glycosidic derivatives of apigenin and luteolin
were the most abundant flavonoids. S. fruticosa and S. officinalis were highlighted as species rich in essential
oil, while other tested Salvia species contained significantly smaller amounts of essential oil. The most
abundant terpenoid compound in the essential oil of S. fruticosa was 1,8-cineole and caryophyllene oxide was
the predominant compound in the essential oil of S. sclarea. Furthermore, significant contents of α- and βthujone were present in the essential oil of S. officinalis, whereas germacrene D was the most abundant in the
essential oils of S. glutinosa and S. verticillata. The antioxidant activities of ethanolic extracts, essential oils
and selected terpenoid and polyphenolic compounds, as well as their abilities to inhibit enzymes representing
important therapeutic targets, were determined spectrophotometrically. The ethanolic extracts of selected
Salvia species demonstrated strong antiradical properties, reducing power and metal chelating ability, as well
as lipid peroxidation inhibitory activity. All ethanolic extracts showed anti-elastase and anti-tyrosinase
activity. Moreover, some of them possessed inhibitory activity against acetylcholinesterase and αglucosidase. The results of conducted phytochemical and biological assays point out the biomedical potential
of selected Salvia species from the Croatian flora and the possibilities of their application in the prevention
and treatment of age-related chronic diseases
Utjecaj stupnja konvolucije na rezultate konvolucijskih neuronskih mreža u problemima daljinskih istraživanja
No full textIn recent years, space technologies have become increasingly integral to various industrial and scientific domains, emphasizing the critical role of remote sensing and Earth observation in guiding decision-making processes. This doctoral thesis aims to enhance the understanding of remote sensing applications by leveraging Convolutional Neural Networks (CNNs) across different convolution degrees (1D, 2D, 3D, and 4D). The primary research question explores how the selection of convolution dimensionality influences CNN performance across diverse tasks. 1D, 2D, 3D, and 4D convolutions are selected for recognizing
spectral, spatial, and temporal features of data. A comprehensive systematic literature review was conducted, analyzing publications related to 1D, 2D, 3D, and 4D-CNNs, addressing their domains of application, machine learning techniques used, and corresponding datasets. Findings are synthesized in the form of ontology for CNN architecture selection providing a structured framework, which is further evaluated in four case studies. The 1DCNN proved to be an appropriate method for extracting spectral information sufficient for predicting point parameters such as Secchi disk depth. The 2D-CNN demonstrated success in extracting spatial features from Sentinel-2 images for road detection. The 3D-CNN with its ability to extract spectral-spatial features was successfully applied to the problem of fire propagation potential detection. The 4D-CNN combined temporal with spectral and spatial features, which proved extremely useful in detecting burned areas. Finally, a comparison of all four convolutional neural networks for the task of semantic segmentation of land cover was performed, where the 3D-CNN stood out as the best. Results of all case studies are aligned with the central hypothesis that selecting appropriate convolution degree significantly enhances deep learning performance in environmental monitoring applications. These findings contribute to understanding of convolution strategies in remote sensing, offering insights for researchers and practitioners seeking to optimize neural network architectures for Earth observation technologies.Posljednjih godina svemirske tehnologije postaju sve više sastavni dio različitih industrijskih i znanstvenih domena, naglašavajući ključnu ulogu daljinskog istraživanja i promatranja Zemlje u procesu donošenja odluka. Ova doktorska disertacija ima za cilj unaprijediti razumijevanje primjene daljinskog istraživanja korištenjem konvolucijskih neuronskih mreža (CNN) kroz različite stupnjeve konvolucije (1D, 2D, 3D i 4D). Primarno istraživačko pitanje istražuje kako odabir dimenzionalnosti konvolucije utječe na performanse CNN-a u različitim zadacima. 1D, 2D, 3D i 4D konvolucije odabrane su za prepoznavanje spektralnih, prostornih i vremenskih značajki podataka. Provedena je sveobuhvatna sistematska analiza literature, analizirajući publikacije vezane uz 1D, 2D, 3D i 4D-CNN, njihove domene primjene, korištene tehnike strojnog učenja i odgovarajuće skupove podataka. Nalazi su sintetizirani u obliku ontologije za odabir CNN arhitekture pružajući strukturirani okvir i dodatno su evaluirani u četiri studije slučaja. 1D-CNN pokazao se kao prikladna metoda za izdvajanje spektralnih informacija dovoljnih za predviđnje točkastih parametara poput Secchi dubine diska. 2D-CNN pokazao je uspjeh u izdvajanju prostornih značajki iz Sentinel-2 snimaka za detekciju cesta. 3D-CNN sa svojom sposobnošću izdvajanja spektralno-prostornih značajki uspješno je primijenjen na problem detekcije potencijala širenja požara. 4D-CNN kombinirao je vremenske sa spektralnim i prostornim značajkama, što se pokazalo izuzetno korisnim u otkrivanju izgorjelih područja. Konačno, provedena je usporedba sve četiri konvolucijske neuronske mreže za zadatak semantičke segmentacije zemljišnog pokrova, gdje se 3D-CNN istaknuo kao najbolji. Rezultati svih studija slučaja u skladu su s centralnom hipotezom da odabir odgovarajućeg stupnja konvolucije značajno poboljšava performanse dubokog učenja u aplikacijama za praćenje okoliša. Ovi nalazi doprinose razumijevanju konvolucijskih strategija u daljinskom istraživanju, pružajući uvide istraživačima i stručnjacima koji žele optimizirati arhitekture neuronskih mreža za tehnologije promatranja Zemlje
Impact of sauerkraut intake on the gut microbiota composition of active athletes
No full textCrijevna mikrobiota je od velike važnosti za sportsku izvedbu i zdravlje športaša. Fermentirane namirnice pokazale su se iznimno učinkovitim u personalizaciji crijevne mikrobiote. Cilj ove disertacije bio je ispitati učinak kiseloga kupusa na sastav i funkcionalnost crijevne mikrobiote aktivnih športaša kako bi se ispitao potencijal njegove primjene u personalizaciji njihove crijevne mikrobiote. Nadalje, ispitana je mikrobna zajednica kiseloga kupusa te su praćeni i laboratorijski parametri i rad probave u sklopu intervencije. Provedena su sveukupno tri istraživanja na aktivnim športašima: studija dokazivanja koncepta na profesionalnim športašima, potvrdna studija na rekreativnim športašima te jedna longitudinalna studija na jednom ispitaniku. Pokazali smo kako kod profesionalnih športaša uslijed 10 dana unosa 250g kiseloga kupusa može doći do značajnih promjena u sastavu i funkcionalnosti crijevne mikrobiote, ali ne i po pitanju α-raznolikosti. Kod rekreativnih športaša nakon 10 dana unosa 250g kiseloga kupusa nisu dokazani isti kratkoročni učinci. Time smo pokazali smo kako promjene izazvane intervencijom ovise o početnom sastavu crijevne mikrobiote. Pokazali smo kako unos 250g kiseloga kupusa tokom 10 dana može dugoročno promijeniti sastav i funkcionalnost crijevne mikrobiote. Longitudinalnom studijom te praćenjem probave i nuspojava pokazali smo kako je 250g kiseloga kupusa potrebno unositi minimalno tjedan dana. Utvrđeno je kako 10 dana unosa 250g kiseloga kupusa rezultira značajnim promjenama u diferencijalnoj krvnoj slici i smanjenjem koncentracije vitamina B12. Zaključno možemo ustvrditi kako kiseli kupus ima potencijal u personalizaciji crijevne mikrobiote športaša.The gut microbiota plays a crucial role in athletic performance and the health of athletes. Fermented foods have proven to be effective in personalizing the gut microbiota. This dissertation aimed to investigate the effect of sauerkraut intake on the composition and functionality of the gut microbiota in active athletes to assess its potential application in personalizing their gut microbiota. Additionally, the microbial community of sauerkraut was examined, and laboratory parameters and digestive function were monitored during the intervention. Three studies were conducted on active athletes: a proof-of-concept study on professional athletes, a follow-up study on recreational athletes, and a longitudinal study on a single participant. We demonstrated that a 10-day intake of 250g of sauerkraut can lead to significant changes in the composition and functionality of the gut microbiota in professional athletes, though not in terms of α-diversity. In recreational athletes the same short-term effects were not not observed. We found that the changes induced by the intervention depend on the initial composition of the gut microbiota. We have found that a 10-day intake of 250g of sauerkraut can induce significant long-term changes in the composition and functionality of the gut microbiota Through the longitudinal study and monitoring of digestion and side effects, we determined that a minimum of one week of 250g daily sauerkraut intake is necessary. It was established that a 10-day intake of 250g of sauerkraut results in significant changes in differential blood counts and a decrease in vitamin B12 concentration. In conclusion, sauerkraut has the potential to personalize the gut microbiota of athletes