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Astrocytes support the brain through numerous functional interactions in health and disease. The recent advances in our knowledge of astrocyte involvement in various neurological disorders raised up several questions about their role and functioning in the central nervous system. From the evidence discussed in this review, we show that histamine importantly influences the main astrocytic activities such as ion homeostasis, energy metabolism, neurotransmitter clearance, neurotrophic activity and immune response. These processes are mediated through at least three histamine receptor subtypes, H1, H2 and H3, expressed on the astrocyte surface. Thus, we recognize histamine as an important player in the modulation of astrocytic functions that deserves further considerations in exploring involvement of astrocytes in neurological disorders.

Innovative hybrid structural components composed of cross-laminated timber frame and laminated glass infill were tested to examine their response on the reverse-cyclic loading. Ductile timber-frame joints with glued-in steel rods and especially designed glass-to-timber contacts with no adhesive proved to provide high ductility and energy dissipation of structural components. In total, 20 tests of full-scale specimens were carried out; three bare frames, six frames with single glazing and eleven frames with double glazing. Deformation capacity, lateral strength, stiffness and strength deterioration and energy dissipation capacity were analysed in order to provide data for the future development of computational models and design guidance for the new codes.

We used a combination of density functional theory (DFT) calculations and the implicit quantization of the acidic N&ndash, H and O&ndash, H bonds to assess the effect of deuteration on the binding of agonists (2-methylhistamine and 4-methylhistamine) and antagonists (cimetidine and famotidine) to the histamine H2 receptor. The results show that deuteration significantly increases the affinity for 4-methylhistamine and reduces it for 2-methylhistamine, while leaving it unchanged for both antagonists, which is found in excellent agreement with experiments. The revealed trends are interpreted in the light of the altered strength of the hydrogen bonding upon deuteration, known as the Ubbelohde effect, which affects ligand interactions with both active sites residues and solvent molecules preceding the binding, thus providing strong evidence for the relevance of hydrogen bonding for this process. In addition, computations further underline an important role of the Tyr250 residue for the binding. The obtained insight is relevant for the therapy in the context of (per)deuterated drugs that are expected to enter therapeutic practice in the near future, while this approach may contribute towards understanding receptor activation and its discrimination between agonists and antagonists.

Diplomsko delo predstavlja zasnovo in izdelavo hidravličnega amortizerja motocikla. Pri zasnovi smo upoštevali določene slabosti konkurenčnih amortizerjev in jih poskušali odpraviti oz. izboljšati. Izdelan amortizer smo preizkusili s pomočjo razvite in izdelane testne naprave. Preučili smo vpliv posameznih nastavitev amortizerja na dušenje pri povratnem gibu. Nov amortizer omogoča daljši čas dušenja. V primerjavi s tovarniško izdelanim amortizerjem se čas dušenja podaljša od 0,3 do 1,3 s, odvisno od nastavitve. Ugotovili smo, da nastavitev pozicije igle bistveno vpliva na čas dušenja pri povratnem gibu The diploma thesis is a presentation of a design and production of a hydraulic motorcycle shock absorber. When designing the shock absorber, the most common downsides of competitive products were considered and therefore improved or eliminated. The manufactured shock absorber was tested using a highly developed testing device. We studied the effect different settings have on the rebound movement. The newly developed shock absorber provides longer damped period. Compared to a factory produced shock absorber, the damped time may be extended from 0.3 to 1.3 seconds, depending on the settings. Our main finding was that the position of the needle has a significant effect on the damped time of the rebound movement.

The degradation of the advanced polymeric materials: blends of polylactide with poly[(R,S)-3-hydroxybutyrate] was studied in paraffin (an ingredient used in cosmetics) and compared with the degradation of pure poly[(R,S)-3-hydroxybutyrate]. The interaction between the polymeric materials studied and the paraffin was monitored during the degradation experiments, and the effects of this interaction were reported. Gel permeation chromatography, atomic force microscopy, electrospray mass spectrometry, nuclear magnetic resonance, differential scanning calorimetry and thermal gravimetric analysis revealed that degradation of the investigated materials occurs in the presence of paraffin. In the blends, poly[(R,S)-3-hydroxybutyrate] content was found to extend the disintegration time, and for the blends with good miscibility, reduced the degradation rate in the first step of degradation.

Aim The purpose of this study is to review the Slovenian experience with the diagnostics, treatment and outcome in pediatric multiple sclerosis (MS) patients. Methods Children and adolescent diagnosed with MS and followed by Department of Child, Adolescent and Developmental Neurology, University Childrens' Hospital Ljubljana, between 1 January 2000 and 31 December 2012 were included. Data from patients' documentation were analyzed retrospectively to record demographic data, clinical presentation, paraclinical findings, disability progression, relapse rate and treatment strategies. Results The study includes 38 patients up to 18 years with MS diagnosis, with female: male ratio 2.8:1 and the incidence of 0.81 per 100.000 children of 0–18 years. The mean age at the time of diagnosis was 15 years 4 months. Most frequent presenting symptoms were sensory, motor, brain-stem, visual and ataxia and 65% of patients had a relapse in the first year. The value of paraclinical findings was asessed. 74% of patients with definite MS and 36% of those with clinically isolated syndrome received disease modifyng therapy and 68% of them was not affected at the follow-up. Interpretation The characteristics of pediatric MS patients in Slovenia disclose higher annual relapse rates than in adults but also favorable impact of disease modifying treatment on a clinical course. Our data suggest a good treatment tolerance but also the influence of the formulation on a decision to start or switch the treatment.

Diplomsko delo se nanaša na posamezna pravila Uredbe št. 1215/2012 o pristojnosti in priznavanju ter izvrševanju sodnih odločb v civilnih in gospodarskih zadevah, ki so pomembna za razumevanje sodne odločbe v zadevi Pula Parking. Sodišče Evropske unije je v tej zadevi povzelo najpomembnejša pravila razlage pojma »civilna in gospodarska zadeva« ter se prvič ukvarjalo s pojmom »sodišče«, v zvezi s katerim je postavilo pomembne smernice pri odločanju ali se organ šteje za »sodišče« v smislu Uredbe št. 1215/2012. Eno izmed pomembnejših načel razlage Uredbe št. 1215/2012 je načelo avtonomnosti, kar pomeni, da so za opredelitev pojmov odločilna splošna pravna načela in cilji, ki jih je mogoče izpeljati iz pravil prava EU, hkrati pa je potrebno te pojme razlagati s sklicevanjem na cilje in ureditev uredbe. V skladu s tem je Sodišče Evropske unije v zadevi Pula Parking odločilo, da je potrebno za ugotovitev ali gre za civilno in gospodarsko zadevo, preučiti pravno razmerje med strankama spora ter podlago in pravila za uveljavljanje vloženega pravnega sredstva. Glede pojma »sodišče« je Sodišče Evropske unije odločilo, da se v skladu s ciljem uredbe, ki je olajševanje dostopa do sodnega varstva, za sodišče v smislu uredbe štejejo organi, ki so v nacionalnih predpisih držav članic opredeljeni kot sodišče in pa organa, ki jih uredba natančno določa. My thesis deals with individual rules of the Regulation no. 1215/2012 of the European parliament and the council on jurisdiction and the recognition and enforcement of judgements in civil and commercial matters. These rules are decisive for understanding the decision of the Court of Justice of the European Union in the case Pula Parking. In this case the Court of Justice of the European Union summarized the most important rules concerning interpretation of “civil and commercial matters” and for the first time dealt with meaning of the “court”. The Court of Justice of the European Union provided important guidance in deciding whether the body is considered a court within the meaning of the Regulation no. 1215/2012. One of the most important principles of interpretation of Regulation no. 1215/2012 is the necessity of autonomous interpretation, which means that the concepts used in Regulation no. 1215/2012 must be interpreted by reference, first, to the general principles and objectives of European law and, second, to the objectives and scheme of the Regulation no. 1215/2012. Accordingly, in the case Pula Parking the Court of Justice of the European Union decided that it is necessary to identify the legal relationship between the parties to the dispute and to examine the basis and the rules governing the bringing of the action to determine whether the matter is civil and commercial. The Court of Justice of the European Union decided that one of the main objectives of Regulation is facilitating access to justice. In accordance with this objective, bodies which are defined as courts by national rules and bodies that are determined as courts by the regulation, are considered as courts within the meaning of the Regulation no. 1215/2012.

Current data regarding the effects of microplastic (MP) on terrestrial organisms are very scarce. Isopods play an important role in plant litter decomposition processes and are commonly used test species in terrestrial ecotoxicity studies. Their altered feeding behaviour and energy reserves are established biomarkers of adverse effects upon stressor exposure. For this study we assessed the effects of MP derived from plastic bag film (mean size 183 ± 93 μm) and particles from a facial cleanser (mean size 137 ± 51 μm) on the terrestrial isopod, Porcellio scaber. Isopods were exposed to MP via feeding on food pellets (4 mg g− 1 dry weight; 0.4% w w− 1) for 14 days under laboratory conditions. A control group was exposed to food pellets with no MP added. In line with previously suggested modes of MP action on animal ingestion, we assessed the food ingestion rate, defecation rate, food assimilation rate and efficiency, body mass change, mortality and energy reserves (proteins, carbohydrates, and triglycerides) in the digestive glands (hepatopancreas) of individual isopods. Contrary to our expectations, no effects on either end-point were observed under the given exposure conditions. Further work should be carried out to investigate the potential longer-term effects of such exposure. We conclude that 14 days exposure to plastic bag and facial cleanser MP is not severely hazardous to isopods.

Microplastics is widespread in the marine environment where it can cause numerous negative effects. It can provide space for the growth of organisms and serves as a vector for the long distance transfer of marine microorganisms. In this study, we examined the sea surface concentrations of microplastics in the North Adriatic and characterized bacterial communities living on the microplastics. DNA from microplastics particles was isolated by three different methods, followed by PCR amplification of 16S rDNA, clone libraries preparation and phylogenetic analysis. 28 bacterial species were identified on the microplastics particles including Aeromonas spp. and hydrocarbon-degrading bacterial species. Based on the 16S rDNA sequences the pathogenic fish bacteria Aeromonas salmonicida was identified for the first time on microplastics. Because A. salmonicida is responsible for illnesses in fish, it is crucial to get answers if and how microplastics pollution is responsible for spreading of diseases.

The paper presents the application of the seismic assessment procedure developed in the PERPETUATE project on a single monument, the Neoclassical School in the Medieval City of Rhodes. The PERPETUATE methodology for the estimation of seismic risk of cultural heritage assets is based on the principles of performance-based assessment (PBA), using nonlinear static procedures. The outcome of the PBA methodology is the maximum seismic intensity measure compatible to different performance levels. The focus of the paper is on the application of the methodology, considering the effects of both soil–foundation–structure interaction (SFSI) and masonry foundation flexibility on the building response, before and after rehabilitation design measures. It is found that SFSI and foundation flexibility produce larger displacements and reduce the maximum ground acceleration that the building can sustain by over 50 %. However, despite the detrimental effects of SFSI on the acceleration capacity, SFSI and foundation flexibility may have a favorable effect on the structure safety, as they modify the collapse mechanism. The results of seismic analyses showed that the building, in its current state, does not sustain the demands for the Life Safety and Collapse Prevention performance levels. Stiffening the roof of the structure and providing sufficient anchorage to the structure, along with systematic grouting of the masonry walls, are the principal rehabilitation decisions considered herein. Mitigation measures were evaluated, considering SFSI and the analyses revealed the adequacy of the proposed retrofitting measure, which combines vertical (wall) and horizontal (roof) stiffening.

In the paper, possibilities of correlation of structural damage and damage of attached artistic assets on multi-leaf stone masonry walls by means of destructive and non-destructive testing (NDT) methods are investigated. Results from two testing campaigns carried out at the University of Genoa and University of Ljubljana are briefly presented. In particular, diagonal tests with different levels of pre-compression and shear tests under different boundary conditions were carried out in Genoa and Ljubljana, respectively. During the tests, different damage limit states (DL) of both masonry walls (SE) and attached plasters (AA) were investigated by means of NDT’s. Two different types of rubble stone masonry were considered (uncoursed random rubble vs. coursed squared rubble). For AA the results are presented in relative form in dependence from the DL of SE. Obtained results are influenced both by the type of test and tested masonry. Results of NDT revealed strong potential and a need for data fusing of both investigated methods for the evaluation of the state of the degradation behind the plaster.

Within the framework of PERPETUATE project for the case study in Slovenia, the 150 year old Kolizej Palace in Ljubljana was set. The building was for a long time neglected and severely deteriorated due to ageing and moisture problems. Despite the overall opinion among conservators upon its preservation, it was set to be demolished. Prior it’s demolishing in 2011 extensive on-site investigation was carried out, which provided valuable data regarding the influence of deteriorated masonry on the seismic response of the building. Experimental tests proved almost completely saturated moisture conditions in the ground level of the building, while all the stories above were in almost dry condition. The results of tests on masonry revealed that moisture content and state of deterioration affected both strength and stiffness properties of built masonry in large extend. Regardless adopted modelling strategies the vulnerability assessment of the Kolizej Palace has proved that the building in its latest condition was far behind the current code requirements in respect to both static and seismic actions.

The influence of neurotransmitter histamine and cytokine interleukin-6 (IL-6) on nerve growth factor (NGF) release was studied in rat neonatal cortical astrocytes in primary culture. Exposure of astrocytes to either histamine or IL-6 resulted in the stimulation of NGF release. Maximal stimulation of NGF release was obtained using histamine at concentration 100 nM after 24 h of treatment (2.3 fold increase over the basal secretion from the control cells). IL-6 (30 ng/ml) induced NGF secretion was 1.66 fold over the basal level. Time course of NGF release, after histamine or IL-6 treatment, showed elevation of NGF level in the culture medium after 8 h or 24 h, respectively. IL-6 antibody effectively blocked the IL-6 stimulatory effect on NGF release, but did not influence NGF release, evoked by histamine. IL-6 antibody alone did not show any influence on NGF release. Our results suggest that IL-6 and histamine stimulate release of NGF by two different and independent molecular pathways.

Interactions involved in the regulation of nerve growth factor (NGF) release by inflammatory cytokines: interleukin-1β (IL-1β), interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α) and transforming growth factor-β1 (TGF-β1) were examined in rat neonatal cortical astrocytes in primary culture. Abstract Exposure of cultured astrocytes to IL-1β, IL-6, and TGF-β1 resulted in the stimulation of NGF secretion. Treatment of cells for 24 h with IL-1β (10 U/ml), IL-6 (5 ng/ml) and TGF-β1 (5 ng/ml) caused 3-, 1.8-, and 2.8-fold increase in NGF secretion as compared to the control cells. In contrast, TNF-α (30 ng/ml) by itself had no stimulatory action on NGF release whereas co-stimulation of astrocytes with IL-1β and TNF-α showed a synergistic interaction. Co-treatment of astrocytes with IL-1β and TGF-β1 increased NGF secretion in an additive way, whereas simultaneous application of IL-1β and IL-6 resulted in the inhibitory effect on NGF secretion. Our results suggest that interactions between cytokines used cause the stimulation of NGF secretion through different regulatory mechanisms.

Microplastic pollution in the marine environment is a scientific topic that has received increasing attention over the last decade. The majority of scientific publications address microplastic pollution of the sea surface. The protocol below describes the methodology for sampling, sample preparation, separation and chemical identification of microplastic particles. A manta net fixed on an »A frame« attached to the side of the vessel was used for sampling. Microplastic particles caught in the cod end of the net were separated from samples by visual identification and use of stereomicroscopes. Particles were analyzed for their size using an image analysis program and for their chemical structure using ATR-FTIR and micro FTIR spectroscopy. The described protocol is in line with recommendations for microplastics monitoring published by the Marine Strategy Framework Directive (MSFD) Technical Subgroup on Marine Litter. This written protocol with video guide will support the work of researchers that deal with microplastics monitoring all over the world.

Terestrično lasersko skeniranje je metoda zajema podatkov, kjer v krajšem časovnem obdobju zajemamo milijone točk. Rezultat skeniranja je oblak točk, katerega nato obdelujemo do želenega rezultata s programsko opremo, ki to omogoča. V diplomski nalogi smo skenirali dva glasbena instrumenta in uporabili dva skenerja: Riegl VZ–400 in Leica Nova MultiStation MS50. Pri obdelavi podatkov smo uporabljali AutoCAD in RiSCAN PRO. Končni oblak točk smo nato posredovali podjetju, ki se ukvarja s 3D graviranjem stekla. Rezultat diplomske naloge je steklena kocka, v katero je vgraviran oblak točk, ki predstavljajo saksofon. Terrestrial laser scanning is a method of data collection, which in a short period of time captures millions of points . The result of the scan is a point cloud, which is then processed to the desired result with the software that makes this possible. In this thesis, we scanned two musical instruments and used two scanner: Riegl VZ - 400 and Leica Nova MS50 MultiStation. When processing the data we have used AutoCAD and PRO Rîşcani. The final point cloud was then forwarded to the company that deals with 3D engraving of glass . The result of the thesis is a glass cube, which is engraved with a cloud of points representing the saxophone.

Plastics are the most common material of marine litter and have become a global pollution concern. They are persistent in the environment where they gradually degrade into increasingly smaller particles–microplastics (MP). Our study presents results of sea-surface monitoring for MP in the Slovenian part of the Trieste Bay in the Northern Adriatic Sea. In 17 trawls conducted over a 20-month period we found a high average concentration of 406 × 10 3 MP particles/km 2 . Over 80% of the particles were identified as polyethylene. The significant variability of MP concentrations obtained on different sampling dates is explained by use of surface current maps and a recently developed Markov chain marine litter distribution model for the Adriatic Sea.

Zavarovanje obveznosti iz obligacijskih razmerij s stvarnopravnimi instituti izvira že iz rimskega prava. Namen uporabe je utrditev obveznosti, ki se izkaže še posebej pomembna, če dolžnik postane insolventen. Takrat je upnik, zaradi vnaprej zavarovane terjatve, v bolj varnem položaju, napram upnikom, ki svojih terjatev do istega dolžnika niso zavarovali. Upnik je varovan, če upošteva načela in pravila nepremičninskega in stečajnega prava. Z začetkom stečajnega postopka naj upnik pravočasno prijavi svojo terjatev, ki je ni mogoče izpodbiti ter s tem pridobi ločitveno ali izločitveno pravico. Obveznost je mogoče zavarovati z različnimi instituti, v različnih točkah razmerja med strankama. Za najbolj učinkovito sredstvo zavarovanja se je izkazal stvarnopravni institut hipoteke. V največjem možnem obsegu učinkuje, če je ustanovljena s pravnim poslom. Posledice začetka stečajnega postopka vplivajo na pravice, ki so ustanovljene na nepremičnini. Izhajajo iz načela akcesornosti in prednostnega načela. Vse pravice, ustanovljene za hipoteko, ki se realizira, se izbrišejo iz zemljiške knjige. Lastninska pravica na nepremičnini je prosta omejitev, vkolikor ni obremenjena s pravicami, ki so izvzete iz tega pravila Obligations from contractual obligation insured by the institutes of property originates from Roman law. Intended use is to consolidate the commitments that it appears as a highly important if the debtor becomes insolvent. Then the creditor who has insured his claim is in a more secure position against creditors that has their claims against the same debtor unsecured. The creditor is protected if he considers the principles and rules of the real estate and bankruptcy law. With the initiation of bankruptcy proceedings the creditor timely lodge his claim that he can not be called into question and thus obtain a separation or exclusion right. The obligation is to be insured with several institutes in the various stages of the relationship between the parties. For the most effective means of protection has proven Institute of Property mortgages. If established by legal transaction, has the extent possible effect. Consequences of bankruptcy proceedings are affecting the rights established on the property. Their effect arises from the principle of the ancillary nature and principles of priority. All rights created later than the first mortage, will be deleted from the land register. Ownership of the property is free from restrictions implications if it is not encumbered with the rights, which are exempt from this rule.

Poly(l-glutamate) (PGlu) was modified with a second-generation dendron to obtain the dendronized polyglutamate, P(Glu-D). Synthesized P(Glu-D) exhibited a degree of polymerization (DPn) of 46 and a 43% degree of dendronization. Perfect agreement was found between the P(Glu-D) expected structure and the results of nuclear magnetic resonance spectroscopy (NMR) and size-exclusion chromatography coupled to a multi-angle light-scattering detector (SEC-MALS) analysis. The PGlu precursor was modified by coupling with a bifunctional building block (N3-Pr-NH2) in the presence of 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMTMM) coupling reagent. The second-generation polyamide dendron was prepared by a stepwise procedure involving the coupling of propargylamine to the l-lysine carboxyl group, followed by attaching the protected 2,2-bis(methylol)propionic acid (bis-MPA) building block to the l-lysine amino groups. The hydroxyl groups of the resulting second-generation dendron were quantitatively deprotected under mild acidic conditions. The deprotected dendron with an acetylene focal group was coupled to the pendant azide groups of the modified linear copolypeptide, P(Glu-N3), in a Cu(I) catalyzed azide-alkyne cycloaddition reaction to form a 1,4-disubstituted triazole. The dendronization reaction proceeded quantitatively in 48 hours in aqueous medium as confirmed by 1H NMR and Fourier transform infrared spectroscopy (FT-IR) spectroscopy.

V sklopu naloge je bilo študirano obnašanje troslojnih kamnitih zidov, in sicer obnašanje pri tlačnih obremenitvah in pri strižnih obremenitvah v ravnini zidov. Izvedene so bile obsežne eksperimentalne preiskave tlačni in strižni testi skupaj 18 zidov ter spremljajoče preiskave konstituentov (malte in kamna). Preskušani kamniti zidovi so značilni predvsem za reprezentativne starejše objekte, ki pogosto predstavljajo pomemben del naše kulturne dediščine. Za testiran tip zidov je bil sistematično analiziran vpliv morfologije zidov (sestave po prerezu), različnih nivojev pred-obremenitev ter robnih pogojev vpetja na različne karakteristike obnašanja zidov. Poleg nosilnosti je bil poudarek na analizi pomikov ter poškodovanosti zidov v karakterističnih stanjih obnašanja. V odvisnosti od robnih pogojev je pri strižnih testih prišlo do različnih porušnih mehanizmov zidov upogibnega, mešanega in diagonalnega strižnega, pri čemer v nasprotju s pričakovanji izven-ravninski mehanizem ni bil merodajen. Do slednjega je prišlo bolj opazno pri višjih pred-obremenitvah zidov v fazi mehčanja zidov. Za testirani tip zidov povezovalni kamni preko prereza zidu niso prispevali ne k večji nosilnosti ne k večjim mejnim pomikom. Eksperimentalni rezultati nosilnosti in mejnih zasukov so bili primerjani z analitičnimi modeli. Strižno nosilnost se zadovoljivo oceni z obstoječimi modeli za porušitve, do katerih je pri testih dejansko prišlo. Doseženi mejni pomiki zidov so bili pri testih veliko večji, kot so dovoljeni mejni pomiki v standardih (EN 1998-3 in FEMA 306). Ker je pri objektih kulturne dediščine poleg same konstrukcije pogosto v interesu ščititi tudi različne poslikave, je bil na zidove nanesen apneni omet, ki je služil študiju obnašanja umetnostih elementov zidov. Določene so bile vrednosti mejnih zasukov zidov za 4 stanja poškodb ometov, ki so uporabne za oceno potresne odpornosti objektov s stališča poškodovanosti ometov. Drugi del naloge obravnava utrjevanje poškodovanih troslojnih kamnitih zidov. Ker je navadno pri utrjevanju historične zidove zahtevana uporaba kompatibilnih materialov, reverzibilnost ukrepov, itd., je bil v sklopu naloge razvit nov sistem utrjevanja. Poškodovani zidovi so bili injektirani s cementno-apneno injekcijsko mešanico in dodatno utrjeni s stekleno vrvico, s podaljšano apneno malto vgrajeno v horizontalne maltne spojnice, ter z vrvico tudi prečno povezani. Skupaj je bilo z različnimi kombinacijami ukrepov utrjenih in dodatno testiranih 10 zidov. Injektiranje se je izkazalo kot primeren sanacijski ukrep, vrvice v spojnicah pa so povečale duktilnost zidov ter v določenem primeru tudi nosilnost. Rezultati testov neutrjenih zidov so bili aplicirani na dejanski objekt. Na primeru Vile Vipolže je bil numerično analiziran vpliv predpostavke mejnih pomikov zidov na potresno obnašanje objekta, računano z nelinearno statično analizo konstrukcije na modelu z ekvivalentnimi okvirji. Glede na rezultate (nezanemarljivo povečanje odpornosti v primeru povečanja pomikov) bi bilo za bolj duktilno zidovino, kot je navadno zgodovinska, smiselno dodatno preučiti smotrnost povečanja mejnih vrednosti zasukov v predpisih. In the thesis, the behaviour of three-leaf stone masonry walls under compression loading and in-plane shear loading is studied. An extensive experimental campaign was conducted on 18 walls, accompanied by tests on masonry constituents (mortar and stone). The type of the tested masonry is typical for older representative buildings, which often present important cultural heritage assets. Influence of morphology, level of pre-compression and boundary conditions on various characteristics of the walls behaviour was systematically studied. Besides the strength, the greatest emphasis was on the analysis of the displacement capacity and damage of the walls at characteristic stages of their response. Due to various boundary conditions, different failure mechanisms developed rocking, mixed and diagonal shear. Leaf separation and the out-of-plane mechanism of the wall was not critical as expected. It developed more evidently in the post-peak phase of the tests for specimens with higher pre-compression. The presence of connecting stones had no influence neither on the obtained shear strength nor on the displacement capacity of the walls. The experimental results were compared to results of analytical models for prediction of shear resistance. For the tested type of masonry, shear strength can be adequately estimated with existing models for the failure mechanisms that developed in the tests. Drift capacity of the walls was however significantly higher than drift capacity allowed in the code provisions (EN 1998-3 in FEMA 306). In heritage buildings also various artistic assets in the form of painted walls are often present. Lime plaster was applied to the walls in order to study its performance during cyclic shear loading. Reference drift values for walls at 4 different characteristic plaster damage states were determined. They can be used for performance based seismic assessment of historic buildings. The second part of the thesis deals with strengthening of the damaged three-leaf stone masonry walls. For monumental buildings there are usually strict demands upon the use of materials compatible to existing materials, reversibility, etc., therefore a new strengthening system was developed. Walls were retrofitted along the cracks with lime-cement grout, additionally strengthened with near surface mounted (NSM) glass cords and transversally connected 10 walls were strengthened with various combinations of measures and re-tested. Grouting successfully retrofitted the walls, while NSM glass cords increased the displacement capacity and, in one case, also shear resistance substantially. Finally, the results of tests of the un-strengthened walls (drifts) were adopted for the numerical analysis of the seismic performance of an actual building (mansion Vipolže). Nonlinear static analyses using equivalent frame model were conducted. The influence of the assumed drift limits on the seismic resistance was analysed. The increase of seismic performance with increasing drift limits of walls is evident and it would be reasonable to further study the prospect of increasing the drift limits in the code provisions for types of masonry, which are more ductile (historical masonry).

Regardless of the fact, whether the debtor is under insolvency proceeding or the proceeding of preventive restructuring, usually merely financial measures are not an adequate intervention regarding the company's business operation in order to dismiss the grounds for insolvency. Consequently, the Slovenian Financial Operations, Insolvency Proceedings and Compulsory Dissolution Act (ZFPPIPP) itself includes other measures to dismiss the grounds for insolvency. The issue is introduced with a summary of some basic definitions of insolvency and restructuring as derived from the ZFPPIPP. A focus on a complete preparation of financial and business restructuring plan as defined by international practice and used when planning a turn in the companies' businesses is given. The author emphasizes that the described measures are not only urgent only when the company is faced with the elements of insolvency, but should rather be executed by all those who face any financial difficulties. Ne glede na to, ali se nad dolžnikom vodi postopek zaradi insolventnosti ali postopek preventivnega prestrukturiranja, običajno samo ukrepi finančne narave niso dovolj koreniti poseg v poslovanje podjetja, da bi odpravili vzroke za nastanek insolventnosti. Zato so tudi v Zakonu o finančnem poslovanju, postopkih zaradi insolventnosti in prisilnem prenehanju (ZFPPIPP) predvideni drugi ukrepi za odpravo vzrokov insolventnosti. Avtorica v uvodu povzema nekaj osnovnih opredelitev insolventnosti in prestrukturiranja, kot izhajajo iz ZFPPIPP. V nadaljevanju se osredotoči na celovito pripravo načrta finančnega in poslovnega prestrukturiranja, kot ga opredeljuje mednarodna praksa in je v veljavi pri načrtovanjih preobratov poslovanja v podjetjih. Avtorica poudarja, da postopkov, ki jih opisuje, ni nujno opravljati zgolj v fazi, ko je podjetje že ugotovilo znamenja insolventnosti, temveč bi jih morali izvajati vsi, ki so zaznali finančne težave.

V prispevku so opisane preiskave troslojnih kamnitih zidov, namenjene študiju njihovega obnašanja pri potresnih obremenitvah. Preiskave so obsegale tlačne in strižne teste skupaj 18 zidov ter spremljajoče raziskave konstituentov (malte in kamna). Analizirani so rezultati maksimalnih nosilnosti kot tudi pomikov ter poškodovanosti zidov za karakteristična stanja obnašanja pri tlačnih in strižnih obremenitvah. Pri strižnih preiskavah je analiziran tudi vpliv morfologije zidov (sestave po prerezu), različnih nivojev predkompresije in robnih pogojev vpetja. Preizkušani tip kamnitih zidov najdemo v Sloveniji v starejših reprezentativnih objektih (na Primorskem ali tam, kjer je bil pri gradnji prisoten italijanski oziroma beneški vpliv), ti pa predstavljajo pomemben del naše kulturne dediščine. Pri takšnih objektih je poleg konstrukcije pogosto v interesu ščititi različne poslikave, mozaike itd., zato je bil na zidove nanesen tudi apneni omet, ki je služil za analizo obnašanja umetnostnih elementov zidov in določitev vrednosti mejnih zasukov zidov za nadaljnjo uporabo pri oceni potresne odpornosti obstoječih objektov tudi s stališča poškodovanosti ometov.

In this article we report a combined experimental and computational study concerning the effects of deuteration on the binding of histamine and two other histaminergic agonists to 3H-tiotidine-labeled histamine H2 receptor in neonatal rat astrocytes. Binding affinities were measured by displacing radiolabeled tiotidine from H2 receptor binding sites present on cultured neonatal rat astrocytes. Quantum-chemical calculations were performed by employing the empirical quantization of nuclear motion within a cluster model of the receptor binding site extracted from the homology model of the entire H2 receptor. Structure of H2 receptor built by homology modelling is attached in the supporting information (S1 Table) Experiments clearly demonstrate that deuteration affects the binding by increasing the affinity for histamine and reducing it for 2-methylhistamine, while basically leaving it unchanged for 4-methylhistamine. Ab initio quantum-chemical calculations on the cluster system extracted from the homology H2 model along with the implicit quantization of the acidic N–H and O–H bonds demonstrate that these changes in the binding can be rationalized by the altered strength of the hydrogen bonding upon deuteration known as the Ubbelohde effect. Our computational analysis also reveals a new mechanism of histamine binding, which underlines an important role of Tyr250 residue. The present work is, to our best knowledge, the first study of nuclear quantum effects on ligand receptor binding. The ligand H/D substitution is relevant for therapy in the context of perdeuterated and thus more stable drugs that are expected to enter therapeutic practice in the near future. Moreover, presented approach may contribute towards understanding receptor activation, while a distant goal remains in silico discrimination between agonists and antagonists based on the receptor structure.

We used quantum-chemical methods to study seven possible mechanisms of monoamine oxidase (MAO) inhibition by acetylenic inhibitors, considering neutral, cationic, anionic and radical mechanisms. MAO is a flavoenzyme responsible for the metabolism of the important neurotransmitters noradrenaline, serotonin and dopamine. It exists in two isoforms: MAO A and MAO B. Selective MAO A inhibitors are used in the treatment of depression, whereas selective MAO B inhibitors such as rasagiline and selegiline are used to relieve symptoms of Parkinson disease. Rasagiline and selegiline are irreversible MAO B inhibitors, each forming a covalent bond with the enzyme's flavin adenine dinucleotide (FAD) cofactor upon inhibition. Although widely used, they both exhibit numerous adverse effects. Our calculations, performed at the B3LYP/6-311++G(2d, 2p)//B3LYP/6-31+G(d) level of theory, with application of the CPCM solvent reaction field with ϵ = 4 to mimic the polar environment, found that a polar anionic mechanism, involving deprotonation of the inhibitor molecule at the terminal acetylene carbon atom, is the most plausible. The calculated free energies of activation for rasagiline and selegiline by this mechanistic pathway are 19.9 and 23.7 kcal mol–1, respectively, in very good agreement withexperimentally determined values of 20.8 and 21.3 kcal mol–1, respectively. Together with additional experimental and theoretical work, the results presented here could lead to better understanding of the nature of MAO inhibition and possible design of new antiparkinsonians as improved MAO B inhibitors. Some ideas on the strategy to achieve that and perspectives for future work are also given.

Astrocytes participate in the clearance of neurotransmitters by their uptake and subsequent enzymatic degradation. Histamine as a polar and/or protonated molecule must use a carrier to be transported across the cell membrane, although a specific histamine transporter has not been elucidated, yet. In this work we upgraded the kinetic studies of histamine uptake into neonatal rat cultured type 1 astrocytes with quantum chemical calculations of histamine pKa values in conjunction with Langevin dipoles solvation model as the first step toward microscopic simulation of transport. Our results indicate that astrocytes transport histamine by at least two carrier mediated processes, a concentration gradient dependent passive and a sodium-dependent and ATP-driven active transport. We also demonstrated that histamine protonation states depend on the polarity of the environment. In conclusion we suggest that histamine, a polar molecule at physiological pH uses at least two different mechanisms for its uptake into astrocytes -an electrodiffusion and Na(+)-dependent and ouabain sensitive active process. We emphasize relevance of knowledge of histamines protonation states at the rate limiting step of its transport for microscopic simulation that will be possible when structure of histamine transporter is known.