508 research outputs found

    Banke kao mjesta počinjenja kaznenih djela razbojništva

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    Banka je financijska institucija koja je od Hrvatske narodne banke dobila odobrenje za rad i koja je osnovana kao dioničko društvo sa sjedištem u Republici Hrvatskoj.1 Dakle, sukladno Zakonu o trgovačkim društvima, banke su organizirane kao dionička društva, te imaju svoje podružnice, poslovnice i ispostave. Sjedišta banaka (centrale) uglavnom se nalaze u velikim gradovima, dok se podružnice nalaze u manjim centrima (županijskim ili općinskim). Poslovnice su razmještene u gradovima i selima, prema tržišnoj orijentaciji banaka; dok se ispostave nalaze na graničnim prijelazima, u trgovačkim centrima, zračnim lukama i si. te u pravilu predstavljaju manje prostore s ograničenim poslovanjem. Banke su poslovne sredine u kojima osnovni vid poslovanja pretpostavlja skup ra¬zličitih transakcija s gotovim novcem i vrijednostima, dragocjenostima te vrijednosnim papirima. Prema tome, kako je u bankama novac primarno manipulativno sredstvo u procesu novčarskih transakcija (uplata/isplata, konverzija, mjenjački poslovi, krediti i si.), postale su zanimljive različitim kriminalnim krugovima koji žele na lak način doći do koristi. S obzirom na te činjenice, banke su postale mjesta kaznenih djela razbojništava, kao najčešćeg oblika kaznenog djela u novčarskim institucijama

    Mechanism of mucosal permeability enhancement of CriticalSorb® (Solutol® HS15) investigated In Vitro in cell cultures.

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    Purpose CriticalSorb™, with the principal component Solutol® HS15, is a novel mucosal drug delivery system demonstrated to improve the bioavailability of selected biotherapeutics. The intention of this study is to elucidate mechanism(s) responsible for the enhancement of trans-mucosal absorption of biological drugs by Solutol® HS15. Methods Micelle size and CMC of Solutol® HS15 were determined in biologically relevant media. Polarised airway Calu-3 cell layers were used to measure the permeability of a panel of biological drugs, and to assess changes in TEER, tight junction and F-actin morphology. The rate of cell endocytosis was measured in vitro in the presence of Solutol® HS15 using a membrane probe, FM 2–10. Results This work initially confirms surfactant-like behaviour of Solutol® HS15 in aqueous media, while subsequent experiments demonstrate that the effect of Solutol® HS15 on epithelial tight junctions is different from a ‘classical’ tight junction opening agent and illustrate the effect of Solutol® HS15 on the cell membrane (endocytosis rate) and F-actin cytoskeleton. Conclusion Solutol® HS15 is the principle component of CriticalSorb™ that has shown an enhancement in permeability of medium sized biological drugs across epithelia. This study suggests that its mechanism of action arises primarily from effects on the cell membrane and consequent impacts on the cell cytoskeleton in terms of actin organisation and tight junction opening

    Poly(triazolyl methacrylate) glycopolymers as potential targeted unimolecular nanocarriers

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    © The Royal Society of Chemistry 2019.Synthetic glycopolymers are increasingly investigated as multivalent ligands for a range of biological and biomedical applications. This study indicates that glycopolymers with a fine-tuned balance between hydrophilic sugar pendant units and relatively hydrophobic polymer backbones can act as single-chain targeted nanocarriers for low molecular weight hydrophobic molecules. Non-covalent complexes formed from poly(triazolyl methacrylate) glycopolymers and low molecular weight hydrophobic guest molecules were characterised through a range of analytical techniques-DLS, SLS, TDA, fluorescence spectroscopy, surface tension analysis-and molecular dynamics (MD) modelling simulations provided further information on the macromolecular characteristics of these single chain complexes. Finally, we show that these nanocarriers can be utilised to deliver a hydrophobic guest molecule, Nile red, to both soluble and surface-immobilised concanavalin A (Con A) and peanut agglutinin (PNA) model lectins with high specificity, showing the potential of non-covalent complexation with specific glycopolymers in targeted guest-molecule delivery.Peer reviewedFinal Published versio

    Effect of polymer topology on non-covalent polymer-protein complexation: miktoarm versus linear mPEG-poly(glutamic acid) copolymers

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    Non-covalent polymer-protein conjugation is emerging as a potential route to improve pharmacokinetics and pharmacodynamics of protein therapeutics. In this study, a family of structurally related block copolymers of mPEG2k - poly(glutamic acid) with linear A-B (mPEG2k-lin-polyGA) and miktoarm A-B3 ((mPEG2k-mik-(polyGA)3) structure was synthesised by N-carboxyanhydride (NCA) ring-opening polymerisation to assess the effect of macromolecular topology of the copolymers on polymer-protein complexation. The data illustrate that the synthesised copolymers are capable of complexing a model protein, lysozyme, at optimal pH conditions through non-covalent interactions, with complexation efficiencies depending on the copolymers composition and molecular architecture. In native gel electrophoresis experiments, linear mPEG2k-lin-GA10 copolymer, possessing a short polyanionic polyGA block, shows a low level of complexation, which does not change when the number of polyGA branches of the same size is increased, using a miktoarm mPEG2k-mik-(GA10)3 copolymer. However, enhanced complexation is observed when the same number of ionisable GA units (30) are displayed on a linear macromolecular scaffold; mPEG2k-mik-(GA10)3 vs. mPEG2k-lin-GA30. Again complexation efficiency did not increase when the number of complexing polyGA branches were increased; mPEG2k-lin-GA30 vs. mPEG2k-mik-(GA30)3. Nanoparticle tracking analysis (NTA) showed that the copolymer-protein complexes possessed hydrodynamic diameters in the 50-200 nm range, suggesting a degree of control in the assembly process. Sequestration of lysozyme within polymer complexes resulted in a decrease in its apparent enzymatic activity, which was re-established on the complexes dissociation upon a treatment with competitive complexant. Intrinsic fluorescence and circular dichroism (CD) studies suggested structural conformation of the protein was not altered following complexation with mPEG2k-polyGA copolymers. Taken together, these results provide an initial structure-function relationship for protein-complexing mPEG2k-polyGA copolymers with variable macromolecular topology, opening the way for their future application in biological and biomedical studies

    Nanoparticle transport in epithelial cells: pathway switching through bioconjugation

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    The understanding and control of nanoparticle transport into and through cellular compartments is central to biomedical applications of nanotechnology. Here, it is shown that the transport pathway of 50 nm polystyrene nanoparticles decorated with vitamin B12 in epithelial cells is different compared to both soluble B12 ligand and unmodified nanoparticles, and this is not attributable to B12 recognition alone. Importantly, the study indicates that vitamin B12-conjugated nanoparticles circumnavigate the lysosomal compartment, the destination of soluble vitamin B12 ligand. Whereas cellular trafficking of soluble B12 is confirmed to occur via the clathrin-mediated pathway, transport of B12-conjugated nanoparticles appears to predominantly take place by a route that is perturbed by caveolae-specific inhibitors. This data suggests that, following its conjugation to nanoparticles, in addition to dramatically increasing the cellular uptake of nanoparticles, the normal cell trafficking of B12 is switched to an alternative pathway, omitting the lysosomal stage: a result with important implications for oral delivery of nanoparticulate diagnostics and therapeutics

    Structural basis of Lewis(b) antigen binding by the Helicobacter pylori adhesin BabA

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    Helicobacter pylori is a leading cause of peptic ulceration and gastric cancer worldwide. To achieve colonization of the stomach, this Gram-negative bacterium adheres to Lewis(b) (Le(b)) antigens in the gastric mucosa using its outer membrane protein BabA. Structural information for BabA has been elusive, and thus, its molecular mechanism for recognizing Le(b) antigens remains unknown. We present the crystal structure of the extracellular domain of BabA, from H. pylori strain J99, in the absence and presence of Le(b) at 2.0- and 2.1-Å resolutions, respectively. BabA is a predominantly α-helical molecule with a markedly kinked tertiary structure containing a single, shallow Le(b) binding site at its tip within a β-strand motif. No conformational change occurs in BabA upon binding of Le(b), which is characterized by low affinity under acidic [K D (dissociation constant) of ~227 μM] and neutral (K D of ~252 μM) conditions. Binding is mediated by a network of hydrogen bonds between Le(b) Fuc1, GlcNAc3, Fuc4, and Gal5 residues and a total of eight BabA amino acids (C189, G191, N194, N206, D233, S234, S244, and T246) through both carbonyl backbone and side-chain interactions. The structural model was validated through the generation of two BabA variants containing N206A and combined D233A/S244A substitutions, which result in a reduction and complete loss of binding affinity to Le(b), respectively. Knowledge of the molecular basis of Le(b) recognition by BabA provides a platform for the development of therapeutics targeted at inhibiting H. pylori adherence to the gastric mucosa

    Presentation/presenting

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    U današnje vrijeme sve više ljudi pripremanje prezentacije počinje u znaku dileme; može li prezentacija biti uspješna? Jesam li ja pravi govornik za temu prezentacije? Sigurno ima mnogo boljih govornika od mene! Mogu li uspješno održati prezentaciju? Problem je u tome što ljudi danas imaju sve manje fizičkog kontakta te nemaju dovoljno samopouzdanja. U trenutku kada trebaju održati prezentaciju uhvati ih trema jer nisu naučeni prezentirati temu ili prenijeti informacije većem broju ljudi. U ovom završnom radu će se prikazati kako postati uspješniji prezenter, odnosno s kojim se to zaprekama susreću ljudi prilikom odabira teme za prezentaciju, kao i korake kako to izbjeći te kako na najbolji način misao svoje prezentacije uspješno prenijeti auditoriju. Razmotrit će se faze u izradi prezentacije te popratni sadržaji koji su potrebni da bi prezentacija bila uspješna. U početnom poglavlju će se prikazati zlatna pravila koja pridonose uspješnijoj prezentaciji, dok će se u sljedećim poglavljima prikazati razne vrste prezentacija, struktura iste, procesi kod pripreme same prezentacije s posebnim naglaskom na neverbalni aspekt prezentiranja, a završno poglavlje će prikazati primjer prezentacije na njemačkom jeziku koja je nastala u svrhu polaganja njemačke DSD diplome

    The importance of the employees emotional labour in the retirement home Ljutomer

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    V svojem diplomskem delu sem v teoretičnem delu najprej predstavila pomen institucionalnega varstva, nato njegovo delovanje ter opredelila skupino, ki ji je to namenjeno. Zanimalo me je, kako sprememba življenjskega okolja ob vselitvi v dom za starejše vpliva na starostnike, nato pa sem se dotaknila čustev starostnikov. Pri tem me je zanimalo, na kakšen način čustvujejo ter kako na njih gledajo manjše populacije. Raziskala sem odnose med zaposlenimi in stanovalci in kako le ti vplivajo na kakovost življenja starostnika v domu. Veliko pozornosti sem namenila predvsem raziskovanju pojma emocionalno delo. Raziskala sem tudi, v kolikšni meri je emocionalno delo prisotno v domovih za starejše ter kakšna je tam sploh potreba po samem izvajanju emocionalnega dela. V raziskovalnem delu sem ugotavljala, v kolikšni meri je emocionalno delo prisotno v DSO Ljutomer, kakšna so pričakovanja stanovalcev in organizacije glede pravil prikazovanja čustev, kako se zaposleni soočajo s stresnimi situacijami in kako jim pri tem pomaga sama organizacija. Ugotovila sem, da je emocionalno delo v DSO Ljutomer prisotno na različnih področjih dela. Za zaposlene je pri njihovem delu najpomembnejše zadovoljstvo stanovalcev doma, zavedajo se pomembnosti pristnih odnosov kot tudi pomembnosti postavljanja meja. Večina stanovalcev nima nobenih posebnih pričakovanj glede prikazovanja čustev zaposlenih, drugače pa je s strani organizacije. Ta pričakuje prijaznost zaposlenih ter pozitivno atmosfero. Organizacija pri soočanju s stresom zaposlenim ne nudi nobene pomoči, zato se zaposleni v stresnih situacijah s pogovorom obrnejo na ožje sodelavce.In the theoretical part of my graduation thesis, I highlighted the importance and meaning of the institutional care and its impact on the recipients. I focused mainly on the emotions and thoughts of elderly when they leave their home and what kind of an impact the change of scenery has on them. My focus were still the emotions of the elderly and their contact with the outside world, workers at the retirement home and with other residents. Through it, I was able to uncover what kind of lifestyle they receive and if the retirement home, provides them good quality of life. Because of the work I had done, I had to analyse the meaning of emotional labour and how different authors perceive the meaning of it. Through experience, I researched to what extent is the emotional labour present in the Retirement Home Ljutomer and when executed, what does it mean to the recipients, how is it executed, what are the rules that apply and how do the employees cope with stress. I concluded that emotional labour applies to different kinds of work and is present in all work that is done with the residents. Employees strive to accomplish the satisfaction of the resident, because they are aware of the importance of authentic and real relations as well as the boundaries that need to be set. The majority of the residents does not expect special display of emotions from the employees, although the retirement homes expects exactly that. They expect the kindness of all the employees, which creates a positive atmosphere. The retirement home does not provide the support to the employees to cope with the stress, so they turn to their co-workers

    Implementation of a cloud application for monitoring the implementation of student internships

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    U svim visokoškolskim ustanovama provodi se određeni oblik stručne studentske prakse. Sam proces provođenja stručne prakse, svakim danom je sve zahtjevniji, a posebno se to odnosi na popratnu dokumentaciju i obvezno praćenje kvalitete u provođenju prakse. U cilju digitalizacije cijeloga procesa, razvijena je oblak aplikacija koja spaja sve dionike ovoga procesa. Studentima se pruža prijava stručne prakse, preuzimanje potrebnih dokumenata te predaja svih dokumenata nakon obavljene stručne prakse. Voditeljima stručne prakse, aplikacija omogućava nadzor i upravljanje cijelim nastavnim procesom te mogućnost generiranja raznih izviješća po obavljenoj stručnoj prakse na razini akademske godine. Treći dionik je sama visokoškolska ustanova, koja ima uvid u cijeli proces te raznim funkcionalnostima u aplikaciji dobiva informacije koje se koriste u procjeni kvalitete ovoga nastavnoga procesa. Aplikacija je izrađena pomoću Spring Boot i AngularJS tehnologije korištenjem integriranoga razvojnoga okruženja Eclipse IDE (engl. Integrated Development Enviroment). Sigurnost aplikacije osigurava implementirana Spring Security okvir koji pruža autentikaciju i autorizaciju korisnika. Aplikacija u svom radu koristi MySQL bazu podataka razvijenu upravo za potrebe ovoga projekta.: In all higher education institutions, a certain form of student internship is conducted. The process of conducting student internship is becoming more and more demanding every day, especially the accompanying documentation and mandatory monitoring of quality in the implementation of practice. In order to digitize the entire process, a cloud application has been developed that connects all stakeholders in this process. Students are given the opportunity to apply for a student internship, download the necessary documents and submit all documents after the internship. For the leaders of student internships, the application enables the supervision and management of the entire teaching process and the possibility of generating various reports on the completed student internship at the level of the academic year. The third stakeholder in student practice is the higher education institution itself. The application institution provides insight into the entire process and obtaining the information needed to assess the quality of this teaching process. The application was created using Spring Boot and AngularJS technology using the Eclipse IDE (Integrated Development Environment). Application security is ensured by the implemented Spring Security framework that provides user authentication and authorization. In its work, the application uses a MySQL database developed specifically for the needs of this project

    Exposure to a Nonionic Surfactant Induces a Response Akin to Heat-Shock Apoptosis in Intestinal Epithelial Cells: Implications for Excipients Safety

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    © 2019 American Chemical Society. Amphipathic, nonionic, surfactants are widely used in pharmaceutical, food, and agricultural industry to enhance product features; as pharmaceutical excipients, they are also aimed at increasing cell membrane permeability and consequently improving oral drugs absorption. Here, we report on the concentration- and time-dependent succession of events occurring throughout and subsequent exposure of Caco-2 epithelium to a "typical" nonionic surfactant (Kolliphor HS15) to provide a molecular explanation for nonionic surfactant cytotoxicity. The study shows that the conditions of surfactant exposure, which increase plasma membrane fluidity and permeability, produced rapid (within 5 min) redox and mitochondrial effects. Apoptosis was triggered early during exposure (within 10 min) and relied upon an initial mitochondrial membrane hyperpolarization (5-10 min) as a crucial step, leading to its subsequent depolarization and caspase-3/7 activation (60 min). The apoptotic pathway appears to be triggered prior to substantial surfactant-induced membrane damage (observed ≥60 min). We hence propose that the cellular response to the model nonionic surfactant is triggered via surfactant-induced increase in plasma membrane fluidity, a phenomenon akin to the stress response to membrane fluidization induced by heat shock, and consequent apoptosis. Therefore, the fluidization effect that confers surfactants the ability to enhance drug permeability may also be intrinsically linked to the propagation of their cytotoxicity. The reported observations have important implications for the safety of a multitude of nonionic surfactants used in drug delivery formulations and to other permeability enhancing compounds with similar plasma membrane fluidizing mechanisms
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