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Imunosno posredovane patologije u mišjem modelu s insuficijencijom optineurina
No full textAmyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are adult-onset
neurodegenerative diseases characterized by neuronal loss, neuroinflammation and TAR DNA
binding protein 43 (TDP-43) protein aggregation in distinct regions of the central nervous system
(CNS). Both diseases may be caused by mutations in the same genes, one of which is OPTN,
encoding for optineurin. Optineurin is a ubiquitin-binding adaptor protein that regulates various
cellular functions, including inflammatory signaling, autophagy, vesicular and mitochondrial
trafficking. To study its role in disease, a truncation mouse model of optineurin insufficiency that
lacks the ubiquitin-binding region (Optn470T) was generated by our group. Aging is the major risk
factor for neurodegenerative diseases, which strongly affects the immune system and results in a
chronic low-grade inflammation (inflammaging). Since optineurin plays a role in inflammatory
signaling, which was shown to be impaired in ALS/FTD patients, we have performed detailed
analyses of Optn470T mice during aging, which include evaluations of motor and cognitive abilities,
neuropathology (neuronal loss, TDP-43 aggregation and lipofuscin accumulation) and
neuroinflammation. We observed that aging of Optn470T mice did not exaggerate the decrease in
motor and cognitive abilities found in wild-type (WT) mice. This was corroborated by the absence
of neuropathology and exaggerated neuroinflammation in aged Optn470T mice. Given that
peripheral immune cells are also affected in ALS patients and during aging, we analyzed T cell
polarization. We found a decreased percentage of tumor necrosis factor (TNF)- and interleukin
(IL)-17A-producing CD4+ helper T cells and an increased percentage of TNF-producing CD8+ T
cells in Optn470T mice in comparison to WT mice. One of the new potential ALS hallmarks is
decreased phagocytosis of microglia and macrophages, reported during aging and in ALS patients.
Here, we reported a decreased percentage of phagocytic bone-marrow derived macrophages
(BMDMs) from aging mice, which was unaffected by optineurin insufficiency. To test if additional
genetic hits will precipitate the disease phenotype, we crossed Optn470T mice with TDP-43G348C
mice, where the latter have been reported to develop ALS/FTD-like symptoms. We successfully
confirmed the generation of Optn470T/TDP-43G348C, which showed lower expression levels of TDP
43G348C transgene compared to TDP-43G348C mice, suggesting a potential protective mechanism of
Optn470T truncation. TDP-43 was previously reported to directly regulate inflammatory nuclear
factor (NF)-B-mediated signaling, which we did not observe in our experiments in BMDMs. In contrast, lipopolysaccharide (LPS)-stimulated BMDMs from Optn470T/TDP-43G348C mice have
shown unaffected NF-B and decreased TANK-binding kinase (TBK1) signaling when compared
to BMDMs from TDP-43G348C mice. Aged Optn470T/TDP-43G348C mice have shown decreased
body weight and improved motor and cognitive abilities compared to TDP-43G348C mice of the
same age. We also analyzed these mice in inflammatory conditions, which were reported to
aggravate ALS/FTD phenotype. A three-day LPS administration resulted in a significant body
weight loss and higher mortality of TDP-43G348C mice, which was rescued in Optn470T/TDP
43G348C mice. LPS-administered Optn470T/TDP-43G348C mice have shown decreased numbers of
splenocytes, B cells, classical dendritic (cDC) and natural killer cells. Lastly, we observed an
increase in chemokine (C-C motif) ligand 2 (CCL2) and IL-10 serum levels in TDP-43G348C and
Optn470T/TDP-43G348C mice, respectively. Altogether, the presence of Optn470T truncation was
insufficient to cause ALS/FTD-like neuropathology during aging. In contrast, Optn470T truncation
has shown a protective effect in the presence of TDP-43G348C transgene in the basal state and during
inflammation in aged mice, which could have been caused by decreased TDP-43G348C transgene
levels in Optn470T/TDP-43G348C mice. Analysis of neuropathology and neuroinflammation in the
hippocampus (region responsible for memory) and denervation of neuromuscular junctions will
be performed to confirm this.Amiotrofična lateralna skleroza (ALS) i frontotemporalna demencija (FTD) su
neurodegenerativne bolesti odraslih ljudi koje su karakterizirane gubitkom neurona,
neuroinflamacijom i agregacijom TAR DNA-vezujućeg proteina 43 (TDP-43) u različitim
dijelovima središnjeg živčanog sustava (SŽS). Obje bolesti mogu biti uzrokovane mutacijama istih
gena, jedan od kojih je OPTN, koji kodira protein optineurin. Optineurin je ubikvitin-vezujući
adaptorski protein koji regulira razne stanične funkcije, uključujući upalnu signalizaciju,
autofagiju, vezikularno i mitohondrijalno prometovanje. Kako bismo izučili ulogu optineurina u
bolesti, naša istraživačka skupina generirala je mišji model insuficijencije optineurina (Optn470T)
kojem nedostaje ubikvitin-vezujuća regija. Starenje je glavni faktor rizika neurodegenerativnih
bolesti koji znatno utječe na imunosni sustav te rezultira kroničnom upalom slabog intenziteta,
odnosno „upalnim starenjem“. S obzirom na ulogu optineurina u upalnoj signalizaciji, koja je
poremećena u ALS/FTD pacijenata, proveli smo detaljnu analizu Optn470T miševa tijekom starenja.
Evaluirali smo simptome ALS/FTD-a analizirajući motoričke i kognitivne sposobnosti,
neuropatologiju (gubitak neurona, TDP-43 agregacija i akumulacija lipofuscina) i
neuroinflamaciju. Zamijetili smo da starenje Optn470T miševa nije pogoršalo gubitak motoričkih i
kognitivnih sposobnosti pronađenih u miševima divljeg tipa (WT). Ove nalaze potvrdili smo
nedostatkom neuropatologije i pojačane neuroinflamacije u starim Optn470T miševima. S obzirom
da ALS i starenje također utječu na periferne imunosne stanice, analizirali smo polarizaciju T
stanica. Pronašli smo smanjeni postotak CD4+ pomoćničkih T stanica koje proizvode faktor
nekroze tumora (TNF) i interleukin (IL)-17A te povećan postotak CD8+ T stanica u Optn470T
miševima u odnosu na WT miševe. Jedan od novih potencijalnih obilježja ALS-a je smanjena
fagocitoza mikroglije i makrofaga koja je pronađena tijekom starenja i u ALS pacijenata. Ovdje
smo pronašli smanjeni postotak fagocitirajućih makrofaga deriviranih iz koštane srži (BMDM
ovi) starih miševa, koja nije bila poremećena u prisustvu insuficijencije optineurina. Kako bismo
testirali ukoliko će dodatne genetske mutacije doprinijeti razvoju bolesti, proveli smo križanje
Optn470T i TDP-43G348C miševa, gdje je za potonjeg pokazano da razvija ALS/FTD simptome.
Uspješno smo potvrdili generaciju Optn470T/TDP-43G348C miševa, koji su pokazali nižu razinu
ekspresije TDP-43G348C transgena u usporedbi s TDP-43G348C miševima, što je potencijalni
protektivni mehanizam Optn470T trunkacije. Pronađeno je kako TDP-43 direktno regulira upalnu signalizaciju posredovanu nuklearnim faktorom (NF)-B, što mi nismo zamijetili u našim
eksperimentima s BMDM-ovima. Suprotno tome, BMDM-ovi iz Optn470T/TDP-43G348C miševa
stimulirani lipopolisaharidom (LPS-om) su pokazali normalnu NF-B te smanjenu aktivaciju
TANK-vezujuće kinaze 1 (TBK1) signalizacije u usporedbi s BMDM-ovima iz TDP-43G348C
miševa. Ostarjeli Optn470T/TDP-43G348C miševi pokazali su nižu tjelesnu masu te unaprijeđene
motoričke i kognitivne sposobnosti u usporedbi s TDP-43G348C miševima iste dobi. Ove miševe
smo također analizirali u upalnim uvjetima za koje je pokazano da pogoršavaju ALS/FTD fenotip.
Trodnevna administracija LPS-a rezultirala je značajnim gubitkom tjelesne mase i visokom
smrtnošću TDP-43G348C miševa, koje su bile značajno ublažene u Optn470T/TDP-43G348C miševima.
U Optn470T/TDP-43G348C miševa administriranih LPS-om pronađen je niži broj splenocita, B
stanica, klasičnih dendritičkih stanica (cDC) i prirodnih stanica ubojica. Na kraju smo pronašli
povećanje kemokinog C-C liganda 2 (CCL2) i interleukina-10 u TDP-43G348C i Optn470T/TDP
43G348C miševima. Sveukupno, prisustvo Optn470T trunkacije je nedovoljno za izazivanje ALS/FTD
neuropatologije tijekom starenja. Međutim, Optn470T trunkacija je pokazala protektivni učinak u
prisustvu TDP-43G348C transgena u bazalnom stanju i tijekom upale u starih miševa, što bi moglo
biti uzorkovano smanjenim razinama TDP-43G348C transgena u Optn470T/TDP-43G348C miševima.
Analiza neuropatologije i neuroinflamacije u hipokampusu (regiji odgovornoj za memoriju) te
denervacije neuromišićnih spojnica će biti provedene kako bismo to potvrdili
Generički radni okvir za ugradnju naprednih analitičkih komponenti u SCADA-sustave vođene događajima
No full textThe research sets out to show the following contributions:
• Generic framework architecture with component templates for advanced analytics, with the goal of integration into event-driven SCADA systems.
• Metamodel for the aggregated data from the SCADA system and external sources, with the goal of the description of the generic framework interfaces.
• Prototype of the system applicable in the field of electric power systems.
First, an overview of the different ways advanced analytics like machine learning or soft com-
puting are used to enhance the functionality of SCADA systems is given. A data metamodel is
constructed, connecting SCADA system data models with datasets used by advanced analytics.
This serves as a basis for designing a generic framework that can be used for fast prototyping
of advanced analytical SCADA components. An overview of the framework implementation
and use is given, followed by realistic examples of the framework use like measurement fore-
casting or state estimation. The thesis concludes by comparing the research with the anticipated
contributions, confirming them.Istraživanje se fokusira na sljedeće doprinose:
• Arhitektura generičkog radnog okvira s predlošcima komponenti za napredne analitičke alate s ciljem ugradnje u SCADA-sustave vođene događajima
• Metamodel za definiranje agregiranih podataka iz SCADA sustava i vanjskih izvora s ciljem opisa sučelja generičkog okvira
• Prototip sustava implementiranog generičkim radnim okvirom s primjenom u području energetike
Prvo, dan je pregled najboljih metoda ugradnje naprednih analitičkih modela u SCADA-sustave vođene događajima. Dan je pregled raznih načina kako se napredne analitičke metode poput strojnog učenja ili mekog računarstva koriste za proširivanje funkcionalnosti SCADA-sustava. Dizajniran je podatkovni metamodel koji spaja podatkovni model SCADA-sustava sa skupovima podataka koje koriste napredni analitički modeli. Ovo je temelj za dizajn generičkog radnog okvira za brzu izgradnju prototipova naprednih analitičkih komponenti SCADA-sustava. Dan je opis implementacije i načina korištenja generičkog okvira, a nakon toga i stvarni primjeri uporabe radnog okvira za probleme predviđanja vrijednosti mjerenja ili procjene stanja električne mreže
Structural and functional changes in the retina and optic nerve of patients with dysthyroid orbitopathy and elevated intraocular pressure
No full textDistiroidna orbitopatija (DO) je autoimuni poremećaj koji se javlja uslijed Gravesove bolesti, a manifestira se retrakcijom vjeđa, proptozom, zadebljanjem ekstraokularnih mišića, kemozom i periorbitalnim edemom. Neka od navedenih stanja mogu dovesti do povišenog intraokularnog tlaka (IOT-a) i posljedičnog glaukomatoznog oštećenja oka. Stoga je cilj ovoga istraživanja bio utvrditi može li sekundarno povišeni IOT koji nastaje kao posljedica DO-a dovesti do specifičnih strukturnih promjena u oku, napose u sloju živčanih stanica mrežnice, vidnom živcu i kompleksu ganglijskih stanica makule te, posljedično tome, i do funkcionalnih promjena.
Istraživanje je provedeno na 90 ispitanika podijeljenih u tri skupine: bolesnici bez DO-a s primarnim glaukomom otvorenog kuta (POAG) (kontrola), bolesnici s DO-om bez povišenog IOT-a (skupina 1) i bolesnici s DO-om i povišenim IOT-om (skupina 2). Podaci su prikupljani tijekom dvije godine korištenjem alata vidnoga polja Octopus 900 i optičke koherentne tomografije. Utvrđene su i uspoređene vrijednosti pokazatelja strukturnih i funkcionalnih promjena oka te IOT-a između skupina. Izračunate su korelacije između tih parametara te su analizirani najvažniji prediktori tih oštećenja.
U istraživanje je bilo uključeno trostruko više ispitanika ženskog nego muškog spola. Bolesnici u kontrolnoj skupini bili su 16 godina stariji od ispitanika u skupinama 1 i 2. Retrakcija vjeđa, proptoza i zadebljanje ekstraokularnih mišića bili su najučestaliji u skupini 2, potom u skupini 1, a najmanja učestalost je bila u kontrolnoj skupini. Među nalazima standarnog oftalmološkog pregleda ističu se statistički značajne razlike u vrijednostima IOT-a (p < 0,001) koji je bio najviši u skupini 2, a slijede kontrolna skupina i skupina 1. Među strukturnim promjenama najvažniji nalazi bili su statisitčki značajno tanji sloj retinalnih živčanih vlakana (RNFL) (p < 0,001), veće vrijednosti parametara promjena papile vidnog živca te tanji sloj ganglijskih stanica makule (GCC) u ispitanika kontrolne skupine u odnosu na preostale dvije ispitivane skupine. IOT je tijekom cijelog razdoblja istraživanja bio najviši u skupini 2, nešto niži u kontrolnoj, a najniži u skupini 1. Sekundarno povišeni IOT u bolesnika s DO-om bio je statistički značajno pozitivno povezan s MD-om i LV-om, a statistički značajno negativno povezan s prosječnom debljinom RNFL-a i prosječnom debljinom GCC-a makule.
Statistički značajna pozitivna povezanost utvrđena je između debljine medijalnog ravnog mišića, egzoftalmometrije, retrakcije vjeđa i intraokularnog tlaka na početku istraživanja. Debljina lateralnog ravnog mišića bila je statistički značajno pozitivno povezana samo s retrakcijom vjeđa. Glavni prediktori funkcionalnog i strukturnog oštećenja oka su bili mlađa dob, ženski spol, veća debljina medijalnog ravnog mišića, veće vrijednosti egzoftalmometrije, prisutna retrakcija vjeđa, te povišeni IOT na početku istraživanja i tijekom prve godine praćenja.
Ovim istraživanjem utvrđeno je da su strukturne i funkcionalne promjene oka veće u bolesnika s POAG-om, nego u bolesnika s DO-om, no sekundarno povišeni intraokularni tlak u bolesnika s DO-om, ukoliko se ne tretira, dovodi do promjena u perimetrijskom nalazu i nalazu optičke koherentne tomografije.Dysthyroid orbitopathy (DO) is an autoimmune disorder that occurs as a result of Graves' disease, and is manifested by eyelid retraction, proptosis, extraocular muscle thickening, chemosis, and periorbital edema. Some of the mentioned conditions can lead to increased intraocular pressure (IOP) and consequent glaucomatous damage to the eye. Therefore, the aim of this research was to determine whether the secondary elevated IOT that occurs as a result of DO can lead to specific structural changes in the eye, especially in the nerve cell layer of the retina, the optic nerve and the macular ganglion cell complex, and, consequently, to functional changes.
The research was conducted on 90 subjects divided into three groups: patients without DO with primary open-angle glaucoma (POAG) (control), patients with DO without elevated IOT (group 1) and patients with DO and elevated IOT (group 2 ). Data was collected over two years using the Octopus 900 visual field and optical coherence tomography. The values of indicators of structural and functional eye changes and IOT between groups were determined and compared, correlations between these parameters were calculated and the most important predictors of these damages were analyzed.
The study included three times more female than male participants. Patients in the control group were, on average, 16 years older than participants in Groups 1 and 2. Eyelid retraction, proptosis, and thickening of extraocular muscles were most prevalent in Group 2, followed by Group 1, with the lowest prevalence observed in the control group. Among the findings from the standard ophthalmologic examination, statistically significant differences were noted in intraocular pressure (IOP) values (p < 0.001), which were highest in Group 2, followed by the control group, and lowest in Group 1.
Among the structural changes, the most important findings were a statistically significantly thinner retinal nerve fiber layer (RNFL) (p < 0.001), greater values in optic nerve head parameter changes, and a thinner ganglion cell complex (GCC) in the control group compared to the other two groups. IOP remained highest in Group 2 throughout the entire study period, slightly lower in the control group, and lowest in Group 1. Secondary elevated IOP in patients with dysthyroid orbitopathy (DO) was statistically significantly positively correlated with mean defect (MD) and loss variance (LV) and statistically significantly negatively correlated with the average thickness of the RNFL and GCC. A statistically significant positive correlation was found between the thickness of the medial rectus muscle, exophthalmometry values, eyelid retraction, and IOP at the beginning of the study. The thickness of the lateral rectus muscle was statistically significantly positively correlated only with eyelid retraction.
The main predictors of functional and structural eye damage were younger age, female sex, greater thickness of the medial rectus muscle, higher exophthalmometry values, the presence of eyelid retraction, and elevated IOP at the beginning of the study and during the first year of follow-up.
This study determined that structural and functional changes in the eye are more pronounced in patients with primary open-angle glaucoma (POAG) than in patients with DO. However, if secondary elevated intraocular pressure in patients with DO is not treated, it can lead to changes in perimetric findings and optical coherence tomography results
Development of a System for Assessing the Condition of School Buildings and Models for Assessing Energy, Energy Sources and Water Consumption
No full textZgrade čine više od 40 % potrošnje energije u mnogim zemljama svijeta, a među njima je i Republika Hrvatska. Zgrade za obrazovanje imaju velik udio u potrošnji energije te nakon plaća djelatnika, troškovi energije predstavljaju drugi najveći izdatak školske zgrade. Pregledom literature uočen je nedostatak istraživanja na temu procjene potrošnje energije školskih zgrada u Republici Hrvatskoj dok je nedostatak istraživanja na temu procjene potrošnje vode školskih zgrada utvrđen diljem svijeta. Osim toga, istraživanja koja su se bavila razlikom između proračunske i stvarne potrošnje energije školskih zgrada odnosno energetskim jazom također su nedostajuća u Hrvatskoj. Nadalje, uočeno je da velik broj zgrada brzo propada radi starenja i preopterećenja, unatoč tome što imaju kulturni i povijesni značaj, a među njima su i školske zgrade. Preopterećenje u ovom kontekstu odnosi se na stanje kada zgrada, zbog povećanog broja korisnika, nepravilne upotrebe ili nedostatka održavanja, doživljava veće opterećenje od onog na koje je bila projektirana. Pregledom literature uočeno je da je velik broj istraživanja proveden s ciljem pronalaženja odgovarajućih kriterija za ocjenjivanje, no također je primijećen nedostatak takvih istraživanja u Hrvatskoj. U doktorskom radu razvijeni su modeli procjene potrošnje električne energije, toplinske energije te mjesečne i godišnje potrošnje vode školskih zgrada koristeći uzorak zgrada osnovnih i srednjih škola na području Osječko-baranjske županije. Nadalje, utvrđena je i razlika između stvarne i proračunske potrošnje energije školskih zgrada u Osječko-baranjskoj županiji i uzroci te razlike. Osim toga, uspostavljen je i sustav procjene stanja, također koristeći uzorak školskih zgrada iz Osječko-baranjske županije koji omogućuje ocjenu stanja zgrade na razini elementa te ukupnu ocjenu na razini cijele zgrade koji se zasniva na preostalim uporabnim vjekovima materijala od kojih su izrađeni elementi školske zgrade. Podaci korišteni za analize, za razvoj modela i za uspostavljanje sustava preuzeti su iz Informacijskog sustava za gospodarenje energijom (ISGE) te iz energetskih certifikata predmetnih zgrada. Za razvoj modela i sustava korištene su tradicionalne metode kao što je višestruka linearna regresija i napredne metode kao što su umjetne neuronske mreže te algoritam nasumične šume. Prednost svih razvijenih modela i sustava je što se temelji na malom broju neovisnih varijabli koje su jednostavno mjerljive i relativno lako dostupne korisnicima. Provedena je i validacija razvijenih modela procjene potrošnje i sustava procjene stanja na posebnom uzorku za validaciju za koju je korišten uzorak školskih zgrada izvan Osječko-baranjske županije. Korišteno je ukupno 40 školskih zgrada pri čemu je 20 iz kontinentalne Hrvatske, a 20 iz primorske kako bi se utvrdilo jesu li razvijeni modeli i sustav primjenjivi i izvan granica županije. Na temelju prikazanih rezultata i analize predložene su smjernice za daljnja istraživanja te praktične smjernice za upravljanje imovinom u smislu energetske učinkovitosti i održivosti školskih zgrada.Buildings account for more than 40% of energy consumption in many countries worldwide, including the Republic of Croatia. Educational buildings represent a significant share of energy consumption, and after employee salaries, energy costs are the second-largest expense for schools. A review of the literature revealed a lack of research on the topic of energy consumption prediction in school buildings in the Republic of Croatia, while the lack of research on water consumption prediction in school buildings has been identified globally. Furthermore, studies addressing the discrepancy between projected and actual energy consumption in school buildings, also known as the energy performance gap, are similarly scarce in Croatia. Additionally, it has been observed that a large number of buildings, including school buildings, deteriorate rapidly due to aging and overuse, despite their cultural and historical significance. Overuse in this context refers to the condition when a building, due to an increased number of users, improper use or lack of maintenance, experiences a higher load than that for which it was designed. A review of the literature found that numerous studies have been conducted to establish appropriate standards for evaluation, but a lack of such research has also been noted in Croatia. In the doctoral dissertation, models were developed to predict electricity consumption, thermal energy consumption, and monthly and annual water consumption in school buildings using a sample of primary and secondary school buildings from Osijek-Baranja County. Furthermore, the difference between actual and calculated energy consumption in school buildings in Osijek-Baranja County, along with the causes of these differences, was identified. In addition, a school building condition assessment system was established using the same sample of school buildings from Osijek-Baranja County, enabling the evaluation of the building's condition at the element level and providing an overall assessment at the level of the entire building. The data used for the analyses, model development, and system establishment were sourced from the Energy Management Information System (EMIS) and the energy certificates of the respective buildings. Traditional methods, such as multiple linear regression, and advanced methods, such as artificial neural networks and the random forest algorithm, were used to develop the models and system. The advantage of all the developed models and systems is that they are based on a small number of independent variables that are easy to measure and relatively accessible. Validation of the developed consumption estimation models and condition assessment systems was also conducted using a separate validation sample, consisting of school buildings outside Osijek-Baranja County. A total of 40 school buildings were used, with 20 from continental Croatia and 20 from the coastal region, to determine whether the developed models and systems are applicable beyond the boundaries of the county. Based on the presented results and analysis, guidelines for further research and practical recommendations for asset management in terms of energy efficiency and sustainability of school buildings were proposed
Determination of genomic pathogenicity determinants of QX strain of infectious bronchitis virus
No full textU okviru ovog doktorskog rada provedena je atenuacija divljeg virusa zaraznog bronhitisa, soja QX. Usporedbom sekvence cijelog genoma atenuiranog virusa i ishodnog soja ispitano je koje su determinante patogenosti ovog soja IBV-a. Nadalje, ispitana je prikladnost atenuiranog soja virusa kao cjepnog soja u proizvodnji živog atenuiranog cjepiva za perad, kroz opsežna ispitivanja sigurnosti i učinkovitosti. Atenuirani soj je dodano pročišćen plakiranjem te uspoređen s ishodnim nepročišćenim sojem u pogledu sigurnosti, učinkovitosti te kinetike rasta. Rezultati su pokazali da je virus uspješno atenuiran, da je procesom pasažiranja došlo do mutacija koje su rezultirale promjenama 13 aminokiselina na proteinskom nivou te da je pročišćeni virus bio značajno manje imunogen nego ishodni atenuirani virus. Kao determinante patogenosti osim S gena potvrđeni su i replikazni gen te geni E, M i 5b. Nije identificirana niti jedna promjena sekvence nukleotida u genomu virusa IBV QX dobivenog u ovom istraživanju koja bi bila zajednička svim dostupnim sekvencama atenuiranih virusa IBV soja QX.As part of this doctoral dissertation, attenuation of the wild-type infectious bronchitis virus (IBV), QX strain, was carried out. By comparing the whole genome sequence of the attenuated virus with the original strain, the determinants of pathogenicity of this IBV strain were investigated. Furthermore, the suitability of the attenuated virus strain as a vaccine strain for the production of a live attenuated poultry vaccine was examined through extensive safety and efficacy testing. The attenuated strain was further purified by plaque selection and compared with the original unpurified strain in terms of safety, efficacy, and growth kinetics. The results showed that the virus was successfully attenuated, that the passaging process led to mutations resulting in 13 amino acid changes at the protein level, and that the purified virus was significantly less immunogenic than the original attenuated virus. In addition to the S gene, the replicase gene and genes E, M, and 5b were confirmed as determinants of pathogenicity. There was no changes in the nucleotide sequence identified in the genome of the IBV QX virus obtained in this study that was common to all available sequences of attenuated IBV QX strains
Impact of environmental factors on genomic structural variation
No full textStrukturne varijante (SV) su oblik genetičke varijacije koja utječe na fenotip, pridonoseći biološkoj raznolikosti i bolestima. Ova disertacija istražuje utjecaj okoliša na strukturne varijante unutar jedne generacije na mišjem modelu u pokusu prehrane bogate mastima i na mikroevolucijskoj razini kod prirodnih populacija meksičke tetre (Astyanax mexicanus) uslijed prilagodbe na život u podzemlju. Genomske analize podataka optičkog mapiranja genoma i sekvenciranja sljedeće generacije otkrile su da okolišni čimbenici pojačavaju postojeću strukturnu varijaciju u genomu, dok selekcija oblikuje funkcionalne prilagodbe, pretežito kroz povećanje broja kopija.Structural variants (SVs) are a form of genetic variation that affects phenotype, contributing to biological diversity and disease. This dissertation explores environmental impacts on SVs within a single generation in mice fed high-fat diet and, on a microevolutionary scale, in natural populations of the Mexican tetra (Astyanax mexicanus) upon adaptation to subterranean environment. Genomic analyses of genome optical mapping and next generation sequencing data revealed that environmental factors amplify variation at sites of existing SVs, and that selection shapes functional adaptations, mainly through copy-number increase
Formativ assesment in science and social studies teaching
No full textCilj ovog rada je sagledavanje prirode formativnog vrednovanja i njegove implementacije u nastavni proces. Teorijski dio rada daje uvid u proces vrednovanja te nakon analize jezičnih i strukturalnih karakteristika, ispituje se njegova povezanost s pojmom vrijednosti, pozicijom unutar obrazovne politike i pitanjem ocjenjivanja kao sastavnice vrednovanja u odgojno obrazovnom sustavu. Daljnji teorijski pregled se fokusira na odnos sumativnog i formativnog vrednovanja te interakcije formativnog vrednovanja s elementima koje istražujemo u empirijskom dijelu rada, unutar okvira nastave prirode i društva. Naglašavamo podržavajuće sadržajno okruženje nastavnog predmeta Prirode i društva za pimjenu metoda i tehnika formativnog vrednovanja. Cilj empirijskog djela rada je bio putem kvazi-eksperimentalnog postupka utvrditi povezanost uvođenja nezavisne varijable, primjene postupka formativnog vrednovanja u nastavi prirode i društva sa stupnjem znanja sadržaja nastavnog predmeta Prirode i društva, motivacijom za učenje sadržaja nastavnog predmeta Prirode i društva i zadovoljstva nastavom prirode i društva kod učenika četrvrtih razreda zagrebačkih osnovnih škola. U istraživanju tijekom drugog obrazovnog razdoblja u šk.god 2020./2021. sudjelovalo je 14 razrednih odjela iz 7 zagrebačkih osnovnih škola podijeljenih u tretmanske i kontrolne skupine. Ukupan uzorak iznosio je 178 učenika. Podaci su prikupljani u trima točkama testiranja (inicijalnom, transfernom i finalnom) te obrađivani putem mješovite analize varijance uz dodatne statističke metode. Iz dobivenih rezultata vidljiva je povećana učenička motivacija za učenje i zadovoljstvo nastavom prirode i društva učenika u tretmanskoj skupini nakon implementacije formativnog vrednovanja u nastavni proces prirode i društva, u odnosu s kontrolnom skupinom. No, s obzirom da su učenici tretmanske skupine bili već i prije uvođenja formativnog vrednovanja motiviraniji i zadovoljniji nastavom prirode i društva, hipoteze se djelomično potvrđuju. Nadalje, rezultati istraživanja podržavaju postavljenu hipotezu o razlikama u rezultatima na provjerama znanja nastavnog sadržaja Prirode i društva, potvrđujući da je formativno vrednovanje rezultiralo boljim rezultatima na provjerama znanja učenika iz tretmanske skupina u usporedbi s kontrolnom skupinom u prvom i drugom mjerenju nakon intervencije, iako su učenici iz kontrolne i tretmanske skupine ostvarivali podjednake rezultate prije intervencije. Stoga zaključujemo da je potvrđena povezanost primjene formativnog vrednovanja sa stupnjem znanja nastavnog sadržaja prirode i društva te se formativno vrednovanje u tom području pokazalo učinkovitije od tradicionalnog vrednovanja.Assessment is a procedure in education that can provide significant information, useful for improving education at different levels. Targeted planning of the teaching process, constructive selection and harmonization of teaching and learning methods with assessment methods and educational outcomes by the teacher opens up the potential for improving teacher teaching and student learning. Each component of assessment has the potential for quality implementation, which successively contributes to the ultimate purposes of assessment, such as motivation for learning, learning guidance, correction of learning errors, etc. The concept of this paper is based on the theoretical analysis of the notion of assessment and formative assessment at the level of the entire educational process and within the field of the subject of Science and Social Studies. This theoretical content is considered through eight chapters, from the conceptual definition of assessment, formative assessment in relation to other categories to ways of its application in the teaching of the subject Science and Social Studies. At the beginning of the paper, the notion of assessment is etymologically analyzed along with a review of literature in Croatian and English. Inconsistency in the terminology of assessment is observed, where the term for assessment (hrv. vrednovanje) in the Croatian language is used as a synonym for the terms evaluacija and valorizacija. In professional literature in English there is a certain overlap or complete distinction between the terms assessment and evaluation. The components as integrated parts of assessment and the principles of assessment as didactic foundations provide a framework for the development of the evaluation process in teaching. We correlate the axiological aspect of pedagogical science with the concept of assessment, because for assessment to be effective, productive and purposeful, it must have value in itself and the evaluator's internalized values are reflected in the assessment process itself. Educational policies determine the development of assessment, while each actor within educational policies (government bodies, the scientific community and teachers) bears responsibility for the implementation and execution of well-argued pedagogical and didactic evaluation methods. Assessment is a complex procedure whose form is determined by a number of different division criteria. This paper examines assessment theoretically in detail according to the criterion of the nature of evaluation, considering the relationship between summative and formativ assessment. It highlights their characteristics and the possibilities of their complementation and integration in teaching in order to more effectively achieve the purpose of assessment. Various research related to the field of formative assessment is listed in the theoretical part. The focus is on the approaches of formative assessment, assessment for learning and assessment as learning, and their connection with feedback, motivation, knowledge and satisfaction in school. The subject Science and Social Studies is presented in a contemporary context through a constructivist paradigm and a holistic approach. The contents of the Science and Social Studies course, which is characterized by completeness and comprehensiveness and the prevalence of phenomenologically oriented integration, enables the application of various formative evaluation techniques during all stages and types of lessons. This paper presents the techniques of formative assessment used in a quasi-experiment as the empirical research on which this paper is based. Their applications and connection with the development of cognitive, psychomotor and affective dimensions of the students’ personality are described. The empirical part of the research is based on a quasi-experiment, rarely used in educational research due to the necessary respect for high ethical principles as well as complex and demanding preparatory and logistical actions. The research was conducted in the 2020./2021. school year in seven primary schools in Zagreb, on a sample of 178 students. 14 fourth-grade classes participated, two classes from each elementary school. The research was conducted during the second educational period when formative assessment was introduced in the treatment groups, while in the classes that represented the control group, traditional evaluation continued with the control and equalization of all other available factors. The goal of the research was to determine the contribution of formative assessment in the teaching of the subject Science and Social Studies, in learning, motivation and satisfaction with teaching in relation to the traditional assessment model. The tasks of the research from which further hypotheses were derived were as follows: determining the connection between the application of formative assessment in the teaching of the subject Science and Social Studies and the level of knowledge of the content of the subject among students of the 4th grade of elementary school, determining the connection between the application of formative assessment in the teaching of Science and Social Studies and the motivation for learning the subject matter of 4th grade elementary school students and determining the connection between the application of formative assessment in the teaching of Science and Social Studies and satisfaction with teaching among 4th grade elementary school students. In conclusion, the described additional analyses confirmed the conclusions of the analysis of variance and support the hypothesized difference in the results of the Science and Social Studies knowledge tests - formative assessment led to better results of students from the treatment group in the first and second measurements after the intervention, although students from the control group and treatment groups achieved equal results before the intervention. As for motivation and satisfaction with the class, the results partially confirm the set hypothesis: although students from the treatment group achieved higher results on the measure of motivation and satisfaction with teaching than students from the control group after the introduction of formative assessment, it seems that these students were more motivated and satisfied even before the introduction of formative assessment teaching. Therefore, based on these results, the increase in motivation to learn the content of the subject of Science and Social Studies and satisfaction with teaching cannot be attributed to the introduction of formative assessment
Association of symptoms of anxiety and depression with work ability in women with breast cancer
No full textCilj istraživanja provedenog u Kliničkom bolničkom centru Zagreb bio je ispitati povezanost simptoma anksioznosti i depresije s radnom sposobnošću žena oboljelih od raka dojke. Istraživanje je uključilo 83 zaposlene žene s dijagnozom raka dojke stadija I–III, koje su u prva tri mjeseca nakon dijagnoze (M1) i godinu dana nakon M1 (M2) ispunile sociodemografski upitnik, Upitnik za procjenu indeksa radne sposobnosti (WAI), Beckov inventar depresije-II, Upitnik anksioznosti kao stanja i osobine ličnosti te EORTC upitnik za kvalitetu života sa specifičnim modulom za rak dojke. Klinički podaci preuzeti su iz medicinske dokumentacije.
Otprilike polovica ispitanica imala je klinički izražene simptome anksioznosti, a četvrtina simptome depresije, uz dobar rezultat WAI. Ispitanice su pokazale poboljšanje u općem zdravstvenom stanju/kvaliteti života, emocionalnom funkcioniranju, apetitu i perspektivi zdravlja, ali pogoršanje simptoma ruku. Pronađena je značajna negativna povezanost između simptoma anksioznosti kao osobine ličnosti i depresije u M1 te rezultata WAI u M2. Simptomi anksioznosti kao osobine ličnosti i depresije te obrazovanje značajni su prediktori radne sposobnosti. Ispitanice s manje izraženim simptomima i višim stupnjem obrazovanja u M1 imale su viši rezultat WAI u M2. Simptomi anksioznosti kao osobine ličnosti i depresije te rezultat WAI značajni su prediktori kvalitete života. Ispitanice s manje izraženim simptomima i višim rezultatom WAI u M1 imale su bolju kvalitetu života u M2. Rezultati ukazuju na potrebu da se u standardnu onkološku skrb uključe rane intervencije usmjerene na poboljšanje radne sposobnosti i upravljanje simptomima anksioznosti i depresije, što može doprinijeti boljem mentalnom zdravlju, radnoj sposobnosti i kvaliteti života oboljelih žena.The aim of the study conducted at the Clinical Hospital Centre Zagreb was to examine the association between symptoms of anxiety and depression and work ability in women with breast cancer (BC). This study enrolled 83 employed women with BC stages I–III who completed a sociodemographic questionnaire, the Work Ability Index (WAI), Beck Depression Inventory-
II, State-Trait Anxiety Inventory, and EORTC Quality of Life Questionnaire with a breast cancer-specific module in the first three months following a BC diagnosis (baseline) and one year after baseline (follow-up). Clinical data were obtained from medical records. Approximately half of the participants had clinically significant symptoms of anxiety, and a quarter had symptoms of depression, along with good WAI scores. Participants showed improvements in general health status/quality of life, emotional functioning, appetite, and future health perspectives but experienced worsening of arm-related symptoms. A significant negative correlation was found between the symptoms of trait anxiety and depression at baseline and the WAI scores at follow-up. Symptoms of trait anxiety and depression, along with education level, are significant predictors of work ability. Participants with lower symptoms and a higher educational level at baseline had higher WAI scores at follow-up. Symptoms of trait anxiety and depression, along with WAI scores, are predictors of quality of life. Participants with lower symptoms and a higher WAI score at baseline had a better quality of life at follow-up. The results highlight the need for early interventions focused on improving work ability and managing symptoms of anxiety and depression to be included in standard oncology care, which can contribute to better mental health, work ability, and quality of life for women with breast
cancer
Zdravstveni inspektorat kao alat za poboljšanje kvalitete zdravstvene zaštite u javnim ustanovama primarne zdravstvene zaštite na Kosovu
No full textKosovo applies a healthcare organization quality model based on an internal mechanism - Quality Coordinators (QC), and the external mechanism - Health Inspectorate of the Ministry of Health. The hypothesis of this research was that the Health Inspectorate is an efficient regulatory tool for quality improvement in public institutions of primary healthcare (PHC) in Kosovo.
Purposefully selected 14 PHC organisations were subjected to initial, follow-up, and final inspections to monitor adherence to 32 basic standards of healthcare quality (BSHQ). QC from the same institutions were tested for healthcare quality knowledge. The lowest scores of both provided selection for seven QC who were subjected to training, and focus group discussion on motivation to serve, experiences, factors that impact quality and suggestions for improvement.
Results showed that over the years, adherence to 32 BSHQ and QC knowledge improved. QC believed that the Health Inspectorate positively influences healthcare quality. Suggestions for improvement included QC role, Health Inspectorate and healthcare in general.
In conclusion, the research hypothesis was confirmed. The Health Inspectorate can use its formal power to foster a culture of healthcare quality in everyday practices by requesting authorities to provide resources as a prerequisite for quality enhancement.Kosovo primjenjuje model kvalitete zdravstvene organizacije koji se temelji na internom mehanizmu - Koordinatorima kvalitete (QC) i vanjskom mehanizmu - Zdravstvenoj inspekciji Ministarstva zdravlja. Hipoteza ovog istraživanja bila je da je zdravstvena inspekcija učinkovit regulatorni alat za poboljšanje kvalitete javnih ustanova primarne zdravstvene zaštite (PZZ) na Kosovu.
Svrhovito odabranih 14 organizacija PZZ-a podvrgnuto je početnim, naknadnim i završnim inspekcijama kako bi se pratilo pridržavanje 32 temeljna standarda zdravstvene kvalitete (BSHQ). QC iz istih ustanova testirani su na poznavanju kvalitete zdravstvene zaštite. Najniže ocjene obje dale su odabir za sedam QC-a koji su bili podvrgnuti obuci i diskusiji u fokusnoj grupi o motivaciji za služenje, iskustvima, čimbenicima koji utječu na kvalitetu i prijedlozima za poboljšanje.
Rezultati su pokazali da se tijekom godina poštivanje 32 BSHQ i QC znanja poboljšalo. QC smatra da zdravstvena inspekcija pozitivno utječe na kvalitetu zdravstvene zaštite. Prijedlozi za poboljšanje uključivali su ulogu QC-a, zdravstvene inspekcije i
zdravstva općenito.
Zaključno, hipoteza istraživanja je potvrđena. Zdravstvena inspekcija može koristiti svoje formalne ovlasti za njegovanje kulture kvalitete zdravstvene skrbi u svakodnevnoj praksi tražeći od vlasti da osiguraju resurse kao preduvjet za poboljšanje kvalitete
Bora wind turbulence above complex coastal terrain
No full textTema ovog rada su mikro- i submezoskalna svojstva bure u zavjetrini sjevernog dijela Dinarida. Rad je podijeljen u tri cjeline, pri čemu se dvije cjeline odnose na turbulenciju bure u prizemnom sloju atmosfere, specifično, njene statističke značajke i numeričku simulaciju. Treća se cjelina odnosi na horizontalne rotacijske značajke pulsacija bure – njihov opis i numeričko modeliranje.
U prvoj cjelini proučavam razlike u statističkim značajkama turbulencije bure u prizemnom sloju atmosfere, i to na dvjema bliskim postajama, Senju i Vratniku (jedna u podnožju, a druga na grebenu planine), za skup podataka u trajanju od približno 6 mjeseci. Slična analiza značajki turbulencije bure do sada nije provedena za ovako dug vremenski period. Analiza potvrđuje neka saznanja prijašnjih radova temeljenih na usporedbi ove dvije postaje za jedan izdvojen događaj bure, npr. da je kinetička energija turbulencije (TKE) u Senju dvostruko veća u odnosu na Vratnik. Raspodjela viskozne disipacije TKE () na dvjema postajama približno je jednaka, što je u suprotnosti s prethodnim zaključcima utemeljenim na jednom događaju bure. Dvije vremenske skale koriste se za odvajanje turbulencije od mezoskale – konstantna (15 min) i varijabilna; potonja je korištena s ciljem odvajanja submezoskalnih gibanja od lokalne turbulencije. Zaključci su u pravilu nepromijenjeni s obzirom na odabir vremenske skale. Podaci na postajama uspoređeni su s obzirom na teoriju sličnosti neutralnog prizemnog sloja (NPS). Odstupanja od NPS-a na Vratniku su manja od onih u Senju, što znači da je ravnoteža TKE na Vratniku bliža NPS-u (tj. smično-disipacijskoj ravnoteži). Određena odstupanja karakteristična su za utjecaj sloja hrapavosti (SH), s obzirom da je visina mjernih uređaja na objema postajama usporediva s visinom elemenata hrapavosti u njihovoj blizini. Ovo je posebice zamjetno u pomacima spektralnih maksimuma prema nižim frekvencijama. Utjecaj SH također pomaže objasniti neočekivanu jednakost na dvjema postajama. Naime, jedna od značajki SH nelokalni su ponori TKE koji smanjuju , a koja uobičajeno samostalno uravnotežuje izvore TKE. Utjecaj SH je prisutan i kod ovisnosti statističkih momenata o azimutu prizemnog vjetra, što se može objasniti anizitropijom površinske hrapavosti. Izračunate su integralne duljinske skale turbulencije i intenzitet turbulencije. Postignute vrijednosti intenziteta u skladu su s preporučenim vrijednostima, ali odstupaju od vrijednosti izmjerenih na srednjem Jadranu.
Druga cjelina usredotočena je na izračun mikroskalnih svojstava bure (preciznije, TKE) numeričkim modelom. Za validaciju simulacije korišten je skup podataka prikupljen u zaleđu grada Rijeke na 100-m tornju s anemometrima na 5 visina. Ovo predstavlja dosad najviša neprekidna toranjska mjerenja brzine vjetra i turbulencije bure u prizemnom sloju atmosfere. Osim 10-min usrednjenih vrijednosti horizontalne brzine i smjera vjetra, anemometri su mjerili i standardne devijacije, što omogućava procjenu TKE i usporedbu sa simulacijom. Ovo je značajno jer je usporedba dosad provedenih simulacija, izuzev avionskih ili indirektnih mjerenja, u pravilu provedena s mjerenjima na relativno niskoj razini iznad tla. Simulacija koraka mreže 0,3 km je provedena za slučaj ekstremno dugotrajnog niza jakih do orkanskih bura iz siječnja i veljače 2012. godine, a kojeg su mjerni uređaji na tornju zabilježili u cijelosti. Točnost simulacije usrednjene vrijednosti brzine i TKE je u rasponu od razumne do izvrsne, ovisno o brzini vjetra i dubini bure. Periodi s izvrsnim podudaranjem su zabilježeni pri brzini vjetra većoj od 20 m s-1 i tijekom plitke bure, dok je podudaranje tijekom duboke bure te pri početku i kraju događaja lošije. Podudaranje je usporedivo sa simulacijama bure na južnom Jadranu, također relativno kratkog koraka mreže, dok odstupanja zabilježena kod većeg koraka mreže naglašavaju važnost reprezentacije reljefa u brdovitom terenu.
U trećoj cjelini proučavam rotacijske značajke pulsacija bure u horizontalnoj ravnini – njihovu strukturu, orijentaciju i smjer rotacije – koristeći rotacijsku spektralnu analizu. Metoda je primijenjena na događaje bure iz istog skupa podataka u Senju kao u prvoj cjelini. Struktura pulsacija je kvazilinearna, tj. česti zraka osciliraju duž izduženih elipsa, a os oscilacije nije jednaka smjeru prizemnog vjetra, već je bliža smjeru vektora smicanja. Doprinos predstavlja rotacija pulsacija u horizontalnoj ravnini, a koja je gotovo isključivo pozitivna, tj. u smjeru suprotnom od kazaljke na satu. Ove značajke ukazuju da su na promatranom skupu događaja bure najvjerojatniji uzroci nastanka pulsacija Kelvin-Helmholtzova nestabilnost ili horizontalno propagirajući zavjetrinski valovi, iako ne nude objašnjenje prevladavajućeg smjera rotacije. Numerička simulacija ljetnog događaja bure je provedena s ciljem proučavanja ovog zapažanja. Simulacija je uspješna s obzirom na period, prevladavajući smjer rotacije i kut između smjera prizemnog vjetra i osi oscilacije pulsacija. Amplituda pulsacija osjetljiva je na vertikalni i horizontalni korak mreže, ali rotacijske značajke nisu. Uzrok pulsacija u simulaciji je Kelvin-Helmholtzova nestabilnost. Ohrabren podudaranjem simulacije i mjerenja, proučio sam prostornu raspodjelu rotacijskih značajki u Velebitskom kanalu. Pozitivna rotacijska komponenta nadjačava negativnu na gotovo čitavom području kanala, iako je njihova relativna jakost vremenski promjenjiva. Iznad Senja i u blizini planinskih vrhova, prevladavajući smjer rotacije pulsacija koreliran je s poljem vremenski usrednjene vertikalne komponente vrtložnosti, a iznad otvorenog mora sa smicanjem smjera vjetra na vrhu niske mlazne struje. Predlažem da je rotacija na frekvenciji pulsacija uzrokovana naginjanjem vrtložnih linija lateralne komponente vrtložnosti unutar ili ispod vrhova Kelvin-Helmholtzovih valova. U prisustvu smicanja smjera vjetra, naginjanje može imati prevladavajući smjer. Budući rad trebao bi se usredotočiti na analizu polja vertikalne komponente vrtložnosti u simulacijama sa stvarnim i idealiziranim reljefom.EXTENDED ABSTRACT
1 Introduction
Bora is a strong, gusty wind that occurs along the eastern coast of the Adriatic. It belongs to the category of downslope windstorms (e.g., Ólafsson and Ágústsson 2007), and it develops due to synoptic disturbances which pull or push air over the Dinarides. Interest in the study of bora is driven mainly by its gustiness (over 60 m s-1; e.g., Grisogono and Belušić 2009) and spatial heterogeneity, which causes a myriad of problems in tourism, architecture and traffic (e.g., Keresturi 2014).
Bora research started at the end of the 19th century (Mohorovičić 1889). It initially focused on the spatial and temporal variability of the mean wind speed and duration (e.g., Poje 1992). The analysis of synoptic charts and radiosoundings yielded two classifications of bora events, one with respect to the synoptic disturbance causing the cross-mountain flow, and the second with respect to the flow depth. As a result, bora event can be cyclonic, anticyclonic or frontal (e.g., Yoshino 1976; Jurčec 1988; Heimann 2001), and shallow or deep. Several subjective and objective weather-type classifications have been developed as a prognostic aid (e.g., Poje 1965; Vozila et al. 2021), newest of which claim that the winter cyclonic bora events (associated with the highest wind speed) will become less frequent in the future warming scenarios (Vozila et al. 2021). When it comes to the understanding of the physical causes of severe bora, the most important development occured as a result of ALPEX (Kuettner and O’Neill 1981) and MAP (Bougeault et al. 2001) projects. Works by Smith (1987) and Klemp and Durran (1987) did away with the notion of bora as a katabatic wind, showing instead that the flow speedup can be caused by two mechanisms, hydraulic transition from sub- to supercritical flow (can be described by two-layer shallow water models), and nonlinear amplification and breaking of mountain waves (the stratified fluid case). Both mechanisms can be present at the same time, and their relative importance depends on the stratification profile, presence and height of the critical level (level where the cross-mountain flow component is zero) and other effects (e.g., Smith and Skyllingstad 2011). In both cases, the resulting lee flow structure is similar – a strong low-level jet (LLJ) develops, topped by a layer of low wind speed and near neutral static stability (the stagnation zone).
The breaking mountain wave and the LLJ present a „stage“ of sorts for this thesis. It is split into three chapters; two deal with the turbulence developed at the lower boundary of the LLJ, and the third aims to describe the horizontal rotational characteristics of bora pulsations (submesocale motion originating from the wave breaking region or the boundary between the LLJ and the stagnation zone; Figure 3) using point measurements and a numerical model simulation. The next three subsections summarize the relevant literature and motivation for each chapter, while the fourth presents the goals and structure of the rest of the text.
1.1 Bora turbulence measurements
As a result of strong shear at the LLJ top and bottom, strong turbulence is developed in the lee of the mountain. Turbulence strength in the lower layer is characterized by a handful of statistical properties like the turbulence kinetic energy (TKE), its dissipation rate () and turbulent fluxes of heat, momentum, moisture, etc. Specialized fields like wind engineering use different but related statistical properties like the turbulence intensity, gust speed and integral turbulence length scales. How these properties relate to each other and vary with height is published in engineering compendia as benchmarks in calculating wind loads on structures.
The first high-frequency measurements of bora-related turbulence were undertaken within ALPEX and MAP projects (aircraft-mounted instruments sampled alongshore and cross-shore profiles of TKE; Smith 1987; Večenaj 2012). First mast-mounted instrument was installed in 2001 at the town of Senj (cup anemometer; 1 Hz sampling rate); Belušić et al. (2006) used these measurements to distinguish local turbulence and low-frequency pulsations. From 2004 to 2006, a pair of 3D anemometers (4 Hz sampling rate) was mounted at Senj and at the Vratnik pass (~10 km to the east of Senj). Using this data, Belušić and Klaić (2006) show that TKE at Senj can reach values as high as 40 m2 s-2. Večenaj (2012) compared a single bora event that occured simultaneously at the two stations, and concluded that both TKE and are twice as large at Senj; therefore, turbulence strength grew along the downslope (Senj is located at the foothill, and Vratnik at the mountain ridge). The importance of turbulence averaging interval selection was emphasized; overly large averaging interval can include motions such as pulsations into turbulence, inflating TKE and related statistics by as much as ~30%. Belušić et al. (2013) also used this dataset to identify simultaneous flow regimes between the two stations via clustering.
Sustained interest in bora turbulence lead to further experiments. Within the frame of the WINDEX project (Horvath et al. 2010a, b), a tower with ultrasonic anemometers at several heights was installed in the hinterland of the city of Split. This dataset was used to point out the error in applying established engineering codes (mostly developed from data measured over flat, homogeneous terrain) to areas under the influence of bora (Lepri et al. 2015; 2017), to test the applicability of the Monin-Obukhov (MOST) similarity theory (Babić 2013; Babić et al. 2016b; Lisac 2014), to evaluate higher statistical moments (Večenaj et al. 2021) and the TKE balance, etc. Further instruments were installed at the Maslenica bridge (Večenaj et al. 2015), and used to show that the distributions of the turbulence statistical properties do not depend on the bora synoptic type (Šoljan et al. 2018) and to study jugo wind turbulence (Zajec 2022). The most recent measurement campaign – project SESAR – focused on the effect of the bora turbulence on the air traffic at the Dubrovnik airport (e.g., Jurković et al. 2018).
Within the context of the bora turbulence properties, these studies fall into one of the two categories. In the first, a large dataset at a particular station is analyzed (e.g., Lepri et al. 2017; Lepri 2023). In the second, two measurement locations are compared for a single simultaneous bora event (Večenaj 2012). A long-term comparison of bora turbulence statistics for two or more stations was not undertaken thus far. This represents the main motivation for this chapter. Best candidates for this comparison are the stations in Senj and at the Vratnik pass; the first is located at the foothill of the coastal mountain range, and the second one is located atop the ridgeline, ~10 km to the east of Senj. Both stations have recorded a large amount of simultaneous bora events spanning the 9-month interval from September 2004 to June 2005.
1.2 Numerical modeling of bora turbulence
Measurement campaigns outlined in the previous section were followed by numerical experiments with steadily decreasing numerical grid spacing. Along-coast jet and wake distribution was successfully reproduced even with ~3 km grid spacing (Enger and Grisogono 1998; Grubišić 2004; Belušić and Klaić 2006). Decreasing the spacing to ~1 km enabled study of submesoscale structures such as pulsations, rotors and lee waves (Belušić et al. 2007; Stiperski et al. 2012; Horvath et al. 2013). This decrease was especially important for the reproduction of near-ground wind in the immediate lee of coastal mountains. A good recent example is the well-reproduced wind speed at the Dubrovnik airport (ZLD) in Večenaj et al. (2019); they used a 0.5 km grid spacing and achieved substantial improvements with respect to coarse 8- and 4 km simulations (Simić 2019). A good example of errors caused by coarse grid spacing in the study of downslope windstorms is provided in e.g., Águstsson and Ólafsson (2014).
Micrometeorological measurements described in the previous section also sparked interest in studying the ability of numerical models and planetary boundary layer (PBL) schemes to reproduce bora turbulence statistics. Here as well, the errors tend to decrease with grid spacing, although it depends on the vicinity of complex terrain. Offshore, even coarse grid spacing may yield good agreement with the measurements of TKE and its dissipation rate (Večenaj et al. 2012). This is not true in the immediate lee of the mountains, e.g., Belušić and Klaić (2006) and Simić (2019) compared surface TKE measurements at, respectively, Senj and Vratnik and at the ZLD (~10 m instrument mounting height) with simulations with 3 and 4 km grid spacing. TKE is in both cases underestimated by a factor of 3–4. Večenaj et al. (2019) simulated a bora event at the ZLD, but they instead used a 0.5 km grid spacing and obtained very good agreement with the TKE measurements. Even finer simulations (in the so-called large-eddy mode) were used to study TKE balance in the hinterland of Split (Horvath et al. 2013); the model output was verified using measurements at 10 m, 22 m and 40 m above the ground.
One of the main issues regarding the simulation of turbulence in downslope windstorms, except the terrain representation which in principle can be solved by using more computational resources, concerns the parametrization schemes of the momentum, heat and moisture exchanges in the surface layer and the PBL. Most of these schemes were developed using data above flat and homogeneous terrain, often underestimating turbulence length scales (Grisogono and Belušić 2009; Večenaj et al. 2010; Večenaj 2015). Consequently, surface wind speed can be overestimated and position of the lee rotor can be misjudged (e.g., Muñoz-Esparza et al. 2016). These discrepancies are, in part, due to a lack of measurements, especially at heights above a few dozen meters above the ground level (a.g.l.). From the measurement campaigns outlined in the previous section, only the WINDEX campaign delivered high-frequency measurements above 20 m a.g.l., although this was partially supplemented by airplane (MAP project; Bougeault et al. 2001), sodar (Stiperski et al. 2012; Horvath et al. 2013) and lidar measurements (Jurković et al. 2018). Therefore, additional measurements of the mean wind speed and turbulence are needed, especially above ~20 m a.g.l. Using such measurements, the ability of the numerical model to reproduce vertical wind and turbulence profiles can be evaluated. In January 2012, a 100-m tower with anemometers at five heights was installed in the hinterland of the city of Rijeka. Besides the mean wind speed and direction, the instruments also recorded their standard deviations, thus enabling the estimation of the TKE and its comparison to numerical model results. In January and February of 2012, the instruments recorded a three-week series of strong to severe bora events. Presenting this dataset and comparing it to the model output presents the main motivation of this chapter.
1.3 Bora pulsations
Pulsations, i.e., quasi-periodic motions with periods of 1–20 min represent a type of secondary instability caused by the strong shear in the wave breaking region and at the LLJ-stagnation zone interface (e.g., Figure 1). They were first studied in the famous Boulder windstorm (e.g., Zipser and Bedard 1982), where structures with decoherence length of ~10 km could be observed (via lidar) moving with the mean wind (Neiman et al. 1988). In numerical experiments, three pulsation generation mechanisms were identified, Kelvin-Helmholtz instability (KHI; Scinocca and Peltier 1989; Peltier and Scinocca 1990), tilting of the base-state vorticity associated with the breaking mountain wave (Clark and Farley 1984), and the trapped, travelling lee waves (Clark and Hall 1994). A schematic view of all three mechanisms is shown in Figure 3. Pulsations exist in bora as well. First measurements and theoretical considerations originate in the late 1980s (Rakovec 1987; Petkovšek 1987). Further development occured at the start of 2000s due to the installation of a high-frequency (1 Hz) anemometer at the town of Senj. In a series of papers, Belušić et al. (2004; 2006; 2007) reveal the underlying phenomena regarding the cessation of pulsations and the appearance of a high-level jet. They simulate the pulsations using COAMPS model, identifying KHI as the generating mechanism for that particular bora event. Furthermore, Orlić et al. (2005) use 3D anemometer data (mounted at Senj in 2004) to point out the difference in pulsations and turbulence. Pulsations were studied at other locations at the Adriatic cost as well, e.g., Horvath et al. (2013) observed pulsations with periods of 3–15 min. They found that the latter are connected to the upstream variation in profiles of wind speed and static stability.
The research focus in the past was the period, wavelength and phase speed of the pulsations, as well as their numerical simulation. The aim of this chapter is to study the characteristic structure of pulsations in the horizontal plane using the rotational spectral analysis method – RSA (Gonella 1972; O’Brien and Pillsbury 1974). RSA (described in the Section 4.3.3) decomposes the 2D vector time series (at a certain frequency) into a positively and negatively rotating component, and can give insight into properties such as the preferred sense of rotation, coherence and the type of motion (rectilinear, circular or elliptical). RSA was previously used at the Adriatic coast in the study of diurnal rotation of sea breeze (Prtenjak et al. 2008) and the rotational characteristics of bora in the vertical plane (Orlić et al. 2005). Latter example is notable since RSA showed that pulsations and local turbulence exhibit different structures, and thus have different generating mechanisms. The choice of the subject and the method was motivated by observing a large set of bora events recorded by a 3D anemometer at the town of Senj. After the rotation of the data into the mean-wind system, I noticed large variability in the ratio of the pulsation energy in the along-wind and cross-wind directions, even within a single bora event. This variability implies change in either the orientation of the structure, or its type (i.e., from rectilinear to circular). Since different pulsation generation mechanisms produce different structures in the horizontal plane (Section 3.2), RSA can be used to deduce the dominant one. Finally, a numerical model (WRF-ARW) can be used to reproduce these characteristics and (if successful) study their spatial and temporal variability.
1.4 Objectives and structure
The aim of the first chapter is to compare the statistical properties of the bora turbulence at two nearby stations, one at the foot of the mountain and the other at a ridgeline, for a large number of bora events. The combination of length of the analyzed dataset and the comparison of turbulence statistical properties at two stations represents the original contribution of this chapter. After the selection of an appropriate turbulence averaging interval (constant or variable), I will calculate the TKE, , momentum flux and other relevant parameters. Because of the differences in the surface cover and instrument mounting height (Section 4.1.2), the data is compared in the context of the statically neutral surface layer similarity (Section 3.1). The deviation of the nondimensional statistical properties from theoretical values can point towards possible differences in the TKE balance between the two stations.
In the second chapter, I intend to verify the ability of the WRF-