Search results for: Maja S. Todorovic
Commenced in January 2007
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Edition: International
Paper Count: 43

Search results for: Maja S. Todorovic

13 Anti-Inflammatory Effect of Carvedilol 1% Ointment in Topical Application to the Animal Model

Authors: Berina Pilipović, Saša Pilipović, Maja Pašić-Kulenović

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Inflammation is the body's response to impaired homeostasis caused by infection, injury or trauma resulting in systemic and local effects. Inflammation causes the body's response to injury and is characterized by a series of events including inflammatory response, response to pain receptors and the recovery process. Inflammation can be acute and chronic. The inflammatory response is described in three different phases. Free radical is an atom or molecule that has the unpaired electron and is therefore generally very reactive chemical species. Biologically important example of reaction with free radicals is called Lipid peroxidation (LP). Lipid peroxidation reactions occur in biological membranes, and if at the outset is not stopped with the action of antioxidants, it will bring damage to the membrane, which results in partial or complete loss of their physiological functions. Calcium antagonists and beta-adrenergic receptor antagonists are known drugs, and for many years and widely used in the treatment of cardiovascular diseases. Some of these compounds also show antioxidant activity. The mechanism of antioxidant activities of calcium antagonists and beta-blockers is unknown, since their structure varies widely. This research investigated the possible local anti-inflammatory activity of ointments containing 1% carvedilol in the white petrolatum USP. Ear inflammation was induced by 3% croton oil acetone solution, in quantity of 10 µl on both mouse ears. Albino Swiss mouse (n = 8) are treated with 2.5 mg/ear ointment, and control group was treated on the same way as previous with hydrocortisone 1% ointment (2.5 mg/ear). The other ear of the same animal was used as control one. Ointments were administered once per day, on the left ear. After treatment, ears were observed for three days. After three days, we measured mass (mg) of 6 mm ear punch of treated and controlled ears. The results of testing anti-inflammatory effects of ointments with carvedilol in the mouse ear model show stronger observed effect than ointment with 1% hydrocortisone in the same basis. Identical results were confirmed by the difference between the mass of 6 mm ears punch. The results were also confirmed by histological examination. Ointments with carvedilol showed significant reduction of the inflammation process caused by croton oil on the mouse inflammation model.

Keywords: antioxidant, carvedilol, inflammation, mouse ear

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12 Preliminary WRF SFIRE Simulations over Croatia during the Split Wildfire in July 2017

Authors: Ivana Čavlina Tomašević, Višnjica Vučetić, Maja Telišman Prtenjak, Barbara Malečić

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The Split wildfire on the mid-Adriatic Coast in July 2017 is one of the most severe wildfires in Croatian history, given the size and unexpected fire behavior, and it is used in this research as a case study to run the Weather Research and Forecasting Spread Fire (WRF SFIRE) model. This coupled fire-atmosphere model was successfully run for the first time ever for one Croatian wildfire case. Verification of coupled simulations was possible by using the detailed reconstruction of the Split wildfire. Specifically, precise information on ignition time and location, together with mapped fire progressions and spotting within the first 30 hours of the wildfire, was used for both – to initialize simulations and to evaluate the model’s ability to simulate fire’s propagation and final fire scar. The preliminary simulations were obtained using high-resolution vegetation and topography data for the fire area, additionally interpolated to fire grid spacing at 33.3 m. The results demonstrated that the WRF SFIRE model has the ability to work with real data from Croatia and produce adequate results for forecasting fire spread. As the model in its setup has the ability to include and exclude the energy fluxes between the fire and the atmosphere, this was used to investigate possible fire-atmosphere interactions during the Split wildfire. Finally, successfully coupled simulations provided the first numerical evidence that a wildfire from the Adriatic coast region can modify the dynamical structure of the surrounding atmosphere, which agrees with observations from fire grounds. This study has demonstrated that the WRF SFIRE model has the potential for operational application in Croatia with more accurate fire predictions in the future, which could be accomplished by inserting the higher-resolution input data into the model without interpolation. Possible uses for fire management in Croatia include prediction of fire spread and intensity that may vary under changing weather conditions, available fuels and topography, planning effective and safe deployment of ground and aerial firefighting forces, preventing wildland-urban interface fires, effective planning of evacuation routes etc. In addition, the WRF SFIRE model results from this research demonstrated that the model is important for fire weather research and education purposes in order to better understand this hazardous phenomenon that occurs in Croatia.

Keywords: meteorology, agrometeorology, fire weather, wildfires, couple fire-atmosphere model

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11 Governance Models of Higher Education Institutions

Authors: Zoran Barac, Maja Martinovic

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Higher Education Institutions (HEIs) are a special kind of organization, with its unique purpose and combination of actors. From the societal point of view, they are central institutions in the society that are involved in the activities of education, research, and innovation. At the same time, their societal function derives complex relationships between involved actors, ranging from students, faculty and administration, business community and corporate partners, government agencies, to the general public. HEIs are also particularly interesting as objects of governance research because of their unique public purpose and combination of stakeholders. Furthermore, they are the special type of institutions from an organizational viewpoint. HEIs are often described as “loosely coupled systems” or “organized anarchies“ that implies the challenging nature of their governance models. Governance models of HEIs describe roles, constellations, and modes of interaction of the involved actors in the process of strategic direction and holistic control of institutions, taking into account each particular context. Many governance models of the HEIs are primarily based on the balance of power among the involved actors. Besides the actors’ power and influence, leadership style and environmental contingency could impact the governance model of an HEI. Analyzing them through the frameworks of institutional and contingency theories, HEI governance models originate as outcomes of their institutional and contingency adaptation. HEIs tend to fit to institutional context comprised of formal and informal institutional rules. By fitting to institutional context, HEIs are converging to each other in terms of their structures, policies, and practices. On the other hand, contingency framework implies that there is no governance model that is suitable for all situations. Consequently, the contingency approach begins with identifying contingency variables that might impact a particular governance model. In order to be effective, the governance model should fit to contingency variables. While the institutional context creates converging forces on HEI governance actors and approaches, contingency variables are the causes of divergence of actors’ behavior and governance models. Finally, an HEI governance model is a balanced adaptation of the HEIs to the institutional context and contingency variables. It also encompasses roles, constellations, and modes of interaction of involved actors influenced by institutional and contingency pressures. Actors’ adaptation to the institutional context brings benefits of legitimacy and resources. On the other hand, the adaptation of the actors’ to the contingency variables brings high performance and effectiveness. HEI governance models outlined and analyzed in this paper are collegial, bureaucratic, entrepreneurial, network, professional, political, anarchical, cybernetic, trustee, stakeholder, and amalgam models.

Keywords: governance, governance models, higher education institutions, institutional context, situational context

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10 Measuring the Visibility of the European Open Access Journals with Bibliometric Indicators

Authors: Maja Jokić, Andrea Mervar, Stjepan Mateljan

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Peer review journals, as the main communication channel among researchers, fully achieve their objective if they are available to the global research community, which is accomplished through open access. In the EU countries, the idea of open access has spread over the years through various projects, initiatives, and strategic documents. Consequently, in this paper we want to analyze, using various bibliometric indicators, visibility, and significance of open access peer review journals compared to the conventional (non-open access) ones. We examine the sample of open access (OA) journals in 28 EU countries in addition to open access journals in three EU candidate countries (Bosnia and Herzegovina, FYR Macedonia and Serbia), all indexed by Scopus (N=1,522). These journals comprise 42% of the total number of OA journals indexed by Scopus. The distribution of OA journals in our sample according to the subject fields indicates that the largest share has OA journals in Health Sciences, 29% followed by Social Sciences and Physical Sciences with 25%, and 21% in Life Sciences. At the same time, the distribution according to countries (N=31) shows the dominance of EU15 countries with the share of 68.3% (N=1041) while post-socialist European countries (EU11 plus three candidate EU countries) have the share of 31.6% (N=481). Bibliometric indicators are derived from the SCImago Journal Ranking database. The analysis of OA journals according to their quartile scores (that reflect the relation between number of articles and their citations) shows that the largest number of OA journals from our sample was in the third quartile in 2015. For comparison, the majority of all academic journals indexed in Scopus from the countries in our sample were in the same year in the first quartile. The median of SJR indicator (SCImago Journal Rankings) for 2015 that measures the journal's prestige, amounted 0.297 for OA journals from the sample, while it was modestly lower for all OA journals, 0.284. The value of the same indicator for all journals indexed by Scopus (N=11,086) from our group of countries was 0.358, which is significantly different from the one for OA journals. Apart from the number of OA journals we also confirm significant differences between EU15 and post-socialist countries in bibliometric status of OA journals. The median SJR indicator for 2015 for EU15 countries was 0.394, while for post-socialist countries it amounted to 0.226. The changes in bibliometric indicators: quartile score, SJR (SCImago Journal Rankings), SNIP (Sources Normalised Impact by Paper) and IPP (Impact per Publication) of OA journals during 2012-2015 period, as well as H-index for the main four subject fields (Life Sciences, Physical Sciences, Social Sciences and Health Sciences) in the whole sample as well as in two main groups of European countries, show increasing trend of acceptance and visibility of OA journals within the academic community. More comprehensive insights into the visibility of OA journals could be reached by using additional qualitative research methods such as for example, interviews with researchers.

Keywords: bibliometric analysis, European countries, journal evaluation, open access journals

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9 High Purity Germanium Detector Characterization by Means of Monte Carlo Simulation through Application of Geant4 Toolkit

Authors: Milos Travar, Jovana Nikolov, Andrej Vranicar, Natasa Todorovic

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Over the years, High Purity Germanium (HPGe) detectors proved to be an excellent practical tool and, as such, have established their today's wide use in low background γ-spectrometry. One of the advantages of gamma-ray spectrometry is its easy sample preparation as chemical processing and separation of the studied subject are not required. Thus, with a single measurement, one can simultaneously perform both qualitative and quantitative analysis. One of the most prominent features of HPGe detectors, besides their excellent efficiency, is their superior resolution. This feature virtually allows a researcher to perform a thorough analysis by discriminating photons of similar energies in the studied spectra where otherwise they would superimpose within a single-energy peak and, as such, could potentially scathe analysis and produce wrongly assessed results. Naturally, this feature is of great importance when the identification of radionuclides, as well as their activity concentrations, is being practiced where high precision comes as a necessity. In measurements of this nature, in order to be able to reproduce good and trustworthy results, one has to have initially performed an adequate full-energy peak (FEP) efficiency calibration of the used equipment. However, experimental determination of the response, i.e., efficiency curves for a given detector-sample configuration and its geometry, is not always easy and requires a certain set of reference calibration sources in order to account for and cover broader energy ranges of interest. With the goal of overcoming these difficulties, a lot of researches turned towards the application of different software toolkits that implement the Monte Carlo method (e.g., MCNP, FLUKA, PENELOPE, Geant4, etc.), as it has proven time and time again to be a very powerful tool. In the process of creating a reliable model, one has to have well-established and described specifications of the detector. Unfortunately, the documentation that manufacturers provide alongside the equipment is rarely sufficient enough for this purpose. Furthermore, certain parameters tend to evolve and change over time, especially with older equipment. Deterioration of these parameters consequently decreases the active volume of the crystal and can thus affect the efficiencies by a large margin if they are not properly taken into account. In this study, the optimisation method of two HPGe detectors through the implementation of the Geant4 toolkit developed by CERN is described, with the goal of further improving simulation accuracy in calculations of FEP efficiencies by investigating the influence of certain detector variables (e.g., crystal-to-window distance, dead layer thicknesses, inner crystal’s void dimensions, etc.). Detectors on which the optimisation procedures were carried out were a standard traditional co-axial extended range detector (XtRa HPGe, CANBERRA) and a broad energy range planar detector (BEGe, CANBERRA). Optimised models were verified through comparison with experimentally obtained data from measurements of a set of point-like radioactive sources. Acquired results of both detectors displayed good agreement with experimental data that falls under an average statistical uncertainty of ∼ 4.6% for XtRa and ∼ 1.8% for BEGe detector within the energy range of 59.4−1836.1 [keV] and 59.4−1212.9 [keV], respectively.

Keywords: HPGe detector, γ spectrometry, efficiency, Geant4 simulation, Monte Carlo method

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8 Preparation and Chemical Characterization of Eco-Friendly Activated Carbon Produced from Apricot Stones

Authors: Sabolč Pap, Srđana Kolaković, Jelena Radonić, Ivana Mihajlović, Dragan Adamović, Mirjana Vojinović Miloradov, Maja Turk Sekulić

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Activated carbon is one of the most used and tested adsorbents in the removal of industrial organic compounds, heavy metals, pharmaceuticals and dyes. Different types of lignocellulosic materials were used as potential precursors in the production of low cost activated carbon. There are, two different processes for the preparation and production of activated carbon: physical and chemical. Chemical activation includes impregnating the lignocellulosic raw materials with chemical agents (H3PO4, HNO3, H2SO4 and NaOH). After impregnation, the materials are carbonized and washed to eliminate the residues. The chemical activation, which was used in this study, has two important advantages when compared to the physical activation. The first advantage is the lower temperature at which the process is conducted, and the second is that the yield (mass efficiency of activation) of the chemical activation tends to be greater. Preparation of activated carbon included the following steps: apricot stones were crushed in a mill and washed with distilled water. Later, the fruit stones were impregnated with a solution of 50% H3PO4. After impregnation, the solution was filtered to remove the residual acid. Subsequently impregnated samples were air dried at room temperature. The samples were placed in a furnace and heated (10 °C/min) to the final carbonization temperature of 500 °C for 2 h without the use of nitrogen. After cooling, the adsorbent was washed with distilled water to achieve acid free conditions and its pH was monitored until the filtrate pH value exceeded 4. Chemical characterizations of the prepared activated carbon were analyzed by FTIR spectroscopy. FTIR spectra were recorded with a (Thermo Nicolet Nexus 670 FTIR) spectrometer, from 400 to 4000 cm-1 wavenumbers, identifying the functional groups on the surface of the activated carbon. The FTIR spectra of adsorbent showed a broad band at 3405.91 cm-1 due to O–H stretching vibration and a peak at 489.00 cm-1 due to O–H bending vibration. Peaks between the range of 3700 and 3200 cm−1 represent the overlapping peaks of stretching vibrations of O–H and N–H groups. The distinct absorption peaks at 2919.86 cm−1 and 2848.24 cm−1 could be assigned to -CH stretching vibrations of –CH2 and –CH3 functional groups. The adsorption peak at 1566.38 cm−1 could be characterized by primary and secondary amide bands. The sharp bond within 1164.76 – 987.86 cm−1 is attributed to the C–O groups, which confirms the lignin structure of the activated carbon. The present study has shown that the activated carbons prepared from apricot stone have a functional group on their surface, which can positively affect the adsorption characteristics with this material.

Keywords: activated carbon, FTIR, H3PO4, lignocellulosic raw materials

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7 Potential of Croatia as an Attractive Tourist Destination for the Russian Market

Authors: Maja Martinovic, Valentina Zarkovic, Hrvoje Maljak

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Europe is one of the most popular tourist destinations in the world, in which tourism occupies a significant place among the most relevant economic activities, and this applies to the Republic of Croatia as well. Based on this study, the authors intended to encourage and support the creation of an effective tourism policy in Croatia that would be based on the profiling of certain target groups. Another objective was to compare the results obtained from the customer analysis with the market analysis of the tourism industry in Croatia. The objective is to adapt the current tourist offer according to the identified needs and expectations of a particular tourist group in order to increase the attractiveness of Croatia as a tourist destination and motivate greater attendance of the targeted tourist groups. The current research was oriented towards the Russian market as the target group. Therefore, the authors wanted to encourage a discussion on how to attract more Russian guests. Consequently, the intention of the research was a detailed analysis of Russian tourists, in order to gain a better understanding of their travelling motives and tendencies. Furthermore, attention was paid to the expectations of Russian customers and to compare them with the Croatian tourist offer, and to determine whether there is a possibility for an overlap. The method used to obtain the information required was a survey conducted among Russian citizens about their travelling habits. The research was carried out on the basis of 166 participants of different age, gender, profession and income group. The sampling and distribution of the survey took place between May and July 2016. The results provided from the research indicate that Croatian tourism has certain unrealized potential considering the popularization of Croatia as a tourist destination, and there is a capacity for increasing the revenues within the group of Russian tourists. Such a conclusion is based on the fact that the Croatian tourist offer and the preferences of the Russian guests are compatible, i.e. they overlap in many aspects. The results demonstrate that beautiful nature, cultural and historical heritage as well as the sun and sea, play a leading role in attracting more Russian tourists. It is precisely these elements that form the three pillars of the Croatian tourist offer. On the other hand, the profiling revealed that the most desirable destinations for the Russian guests are Italy and Spain, both of which provide the same main tourist attractions as Croatia. Therefore, the focus of the strategic ideas given in the paper shifted to other tourism segments, such as type of accommodation, sales channels, travel motives, additional offer and seasonality etc., in order to gain advantage in the Russian market, the Mediterranean region and tourism in general. The purpose of the research is to serve as a foundation for analysing the attractiveness of the other tourist destinations in the Russian market, as well as to be a general basis for a more detailed profiling of the various specific target groups of the Russian and other tourist groups.

Keywords: Croatia, Russian market, target groups, tourism, tourist destination

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6 Electron Bernstein Wave Heating in the Toroidally Magnetized System

Authors: Johan Buermans, Kristel Crombé, Niek Desmet, Laura Dittrich, Andrei Goriaev, Yurii Kovtun, Daniel López-Rodriguez, Sören Möller, Per Petersson, Maja Verstraeten

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The International Thermonuclear Experimental Reactor (ITER) will rely on three sources of external heating to produce and sustain a plasma; Neutral Beam Injection (NBI), Ion Cyclotron Resonance Heating (ICRH), and Electron Cyclotron Resonance Heating (ECRH). ECRH is a way to heat the electrons in a plasma by resonant absorption of electromagnetic waves. The energy of the electrons is transferred indirectly to the ions by collisions. The electron cyclotron heating system can be directed to deposit heat in particular regions in the plasma (https://www.iter.org/mach/Heating). Electron Cyclotron Resonance Heating (ECRH) at the fundamental resonance in X-mode is limited by a low cut-off density. Electromagnetic waves cannot propagate in the region between this cut-off and the Upper Hybrid Resonance (UHR) and cannot reach the Electron Cyclotron Resonance (ECR) position. Higher harmonic heating is hence preferred in heating scenarios nowadays to overcome this problem. Additional power deposition mechanisms can occur above this threshold to increase the plasma density. This includes collisional losses in the evanescent region, resonant power coupling at the UHR, tunneling of the X-wave with resonant coupling at the ECR, and conversion to the Electron Bernstein Wave (EBW) with resonant coupling at the ECR. A more profound knowledge of these deposition mechanisms can help determine the optimal plasma production scenarios. Several ECRH experiments are performed on the TOroidally MAgnetized System (TOMAS) to identify the conditions for Electron Bernstein Wave (EBW) heating. Density and temperature profiles are measured with movable Triple Langmuir Probes in the horizontal and vertical directions. Measurements of the forwarded and reflected power allow evaluation of the coupling efficiency. Optical emission spectroscopy and camera images also contribute to plasma characterization. The influence of the injected power, magnetic field, gas pressure, and wave polarization on the different deposition mechanisms is studied, and the contribution of the Electron Bernstein Wave is evaluated. The TOMATOR 1D hydrogen-helium plasma simulator numerically describes the evolution of current less magnetized Radio Frequency plasmas in a tokamak based on Braginskii’s legal continuity and heat balance equations. This code was initially benchmarked with experimental data from TCV to determine the transport coefficients. The code is used to model the plasma parameters and the power deposition profiles. The modeling is compared with the data from the experiments.

Keywords: electron Bernstein wave, Langmuir probe, plasma characterization, TOMAS

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5 Analyzing the Participation of Young People in Politics: An Exploratory Study Applied on Motivation in Croatia

Authors: Valentina Piric, Maja Martinovic, Zoran Barac

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The application of marketing to the domain of politics has become relevant in recent times. With this article the authors wanted to explore the issue of the current political engagement among young people in Croatia. The question is what makes young people (age 18-30) politically active in young democracies such as that of the Republic of Croatia. Therefore, the objective of this study was to discover the real or hidden motivations behind the decision to actively participate in politics among young members of the two largest political parties in the country – the Croatian Democratic Union and the Social Democratic Party of Croatia. The study expected to find that the motivation for political engagement of young people is often connected with a possible achievement of individual goals and egoistic needs such as: self-acceptance, social success, financial success, prestige, reputation, status, recognition from the others etc. It was also expected that, due to the poor economic and social situation in the country, young people feel an increasing disconnection from politics. Additionally, the authors expected to find that there is a huge potential to engage young people in the political life of the country through a proper and more interactive use of marketing communication campaigns and social media platforms, with an emphasis on highly ethical motives of political activity and their benefits to society. All respondents included in the quantitative survey (sample size [N=100]) are active in one of the two largest political parties in Croatia. The sampling and distribution of the survey occurred in the field in September 2016. The results of the survey demonstrate that in Croatia, the way young people feel about politics and act accordingly, are in fact similar to what the theory describes. The research findings reveal that young people are politically active; however, the challenge is to find a way to motivate even more young people in Croatia to actively participate in the political and democratic processes in the country and to encourage them to see additional benefits out of this practice, not only related to their individual motives, but related more to the well-being of Croatia as a country and of every member of society. The research also discovered a huge potential for political marketing communication possibilities, especially related to interactive social media. It is possible that the social media channels have a stronger influence on the decision-making process among young people when compared to groups of reference. The level of interest in politics among young Croatians varies; some of them are almost indifferent, whilst others express a serious interest in different ways to actively contribute to the political life of the country, defining a participation in the political life of their country almost as their moral obligation. However, additional observations and further research need to be conducted to get a clearer and more precise picture about the interest in politics among young people in Croatia and their social potential.

Keywords: Croatia, marketing communication, motivation, politics, young people

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4 Drivers of Satisfaction and Dissatisfaction in Camping Tourism: A Case Study from Croatia

Authors: Darko Prebežac, Josip Mikulić, Maja Šerić, Damir Krešić

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Camping tourism is recognized as a growing segment of the broader tourism industry, currently evolving from an inexpensive, temporary sojourn in a rural environment into a highly fragmented niche tourism sector. The trends among public-managed campgrounds seem to be moving away from rustic campgrounds that provide only a tent pad and a fire ring to more developed facilities that offer a range of different amenities, where campers still search for unique experiences that go above the opportunity to experience nature and social interaction. In addition, while camping styles and options changed significantly over the last years, coastal camping in particular became valorized as is it regarded with a heightened sense of nostalgia. Alongside this growing interest in the camping tourism, a demand for quality servicing infrastructure emerged in order to satisfy the wide variety of needs, wants, and expectations of an increasingly demanding traveling public. However, camping activity in general and quality of camping experience and campers’ satisfaction in particular remain an under-researched area of the tourism and consumption behavior literature. In this line, very few studies addressed the issue of quality product/service provision in satisfying nature based tourists and in driving their future behavior with respect to potential re-visitation and recommendation intention. The present study thus aims to investigate the drivers of positive and negative campsite experience using the case of Croatia. Due to the well-preserved nature and indented coastline, camping tourism has a long tradition in Croatia and represents one of the most important and most developed tourism products. During the last decade the number of tourist overnights in Croatian camps has increased by 26% amounting to 16.5 million in 2014. Moreover, according to Eurostat the market share of campsites in the EU is around 14%, indicating that the market share of Croatian campsites is almost double large compared to the EU average. Currently, there are a total of 250 camps in Croatia with approximately 75.8 thousands accommodation units. It is further noteworthy that Croatian camps have higher average occupancy rates and a higher average length of stay as compared to the national average of all types of accommodation. In order to explore the main drivers of positive and negative campsite experiences, this study uses principal components analysis (PCA) and an impact-asymmetry analysis (IAA). Using the PCA, first the main dimensions of the campsite experience are extracted in an exploratory manner. Using the IAA, the extracted factors are investigated for their potentials to create customer delight and/or frustration. The results provide valuable insight to both researchers and practitioners regarding the understanding of campsite satisfaction.

Keywords: Camping tourism, campsite, impact-asymmetry analysis, satisfaction

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3 Influence of Cryo-Grinding on Particle Size Distribution of Proso Millet Bran Fraction

Authors: Maja Benkovic, Dubravka Novotni, Bojana Voucko, Duska Curic, Damir Jezek, Nikolina Cukelj

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Cryo-grinding is an ultra-fine grinding method used in the pharmaceutical industry, production of herbs and spices and in the production and handling of cereals, due to its ability to produce powders with small particle sizes which maintain their favorable bioactive profile. The aim of this study was to determine the particle size distributions of the proso millet (Panicum miliaceum) bran fraction grinded at cryogenic temperature (using liquid nitrogen (LN₂) cooling, T = - 196 °C), in comparison to non-cooled grinding. Proso millet bran is primarily used as an animal feed, but has a potential in food applications, either as a substrate for extraction of bioactive compounds or raw material in the bakery industry. For both applications finer particle sizes of the bran could be beneficial. Thus, millet bran was ground for 2, 4, 8 and 12 minutes using the ball mill (CryoMill, Retsch GmbH, Haan, Germany) at three grinding modes: (I) without cooling, (II) at cryo-temperature, and (III) at cryo-temperature with included 1 minute of intermediate cryo-cooling step after every 2 minutes of grinding, which is usually applied when samples require longer grinding times. The sample was placed in a 50 mL stainless steel jar containing one grinding ball (Ø 25 mm). The oscillation frequency in all three modes was 30 Hz. Particle size distributions of the bran were determined by a laser diffraction particle sizing method (Mastersizer 2000) using the Scirocco 2000 dry dispersion unit (Malvern Instruments, Malvern, UK). Three main effects of the grinding set-up were visible from the results. Firstly, grinding time at all three modes had a significant effect on all particle size parameters: d(0.1), d(0.5), d(0.9), D[3,2], D[4,3], span and specific surface area. Longer grinding times resulted in lower values of the above-listed parameters, e.g. the averaged d(0.5) of the sample (229.57±1.46 µm) dropped to 51.29±1.28 µm after 2 minutes grinding without LN₂, and additionally to 43.00±1.33 µm after 4 minutes of grinding without LN₂. The only exception was the sample ground for 12 minutes without cooling, where an increase in particle diameters occurred (d(0.5)=62.85±2.20 µm), probably due to particles adhering to one another and forming larger particle clusters. Secondly, samples with LN₂ cooling exhibited lower diameters in comparison to non-cooled. For example, after 8 minutes of non-cooled grinding d(0.5)=46.97±1.05 µm was achieved, while the LN₂ cooling enabled collection of particles with average sizes of d(0.5)=18.57±0.18 µm. Thirdly, the application of intermediate cryo-cooling step resulted in similar particle diameters (d(0.5)=15.83±0.36 µm, 12 min of grinding) as cryo-milling without this step (d(0.5)=16.33±2.09 µm, 12 min of grinding). This indicates that intermediate cooling is not necessary for the current application, which consequently reduces the consumption of LN₂. These results point out the potential beneficial effects of millet bran grinding at cryo-temperatures. Further research will show if the lower particle size achieved in comparison to non-cooled grinding could result in increased bioavailability of bioactive compounds, as well as protein digestibility and solubility of dietary fibers of the proso millet bran fraction.

Keywords: ball mill, cryo-milling, particle size distribution, proso millet (Panicum miliaceum) bran

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2 Genome-Wide Analysis Identifies Locus Associated with Parathyroid Hormone Levels

Authors: Antonela Matana, Dubravka Brdar, Vesela Torlak, Marijana Popovic, Ivana Gunjaca, Ozren Polasek, Vesna Boraska Perica, Maja Barbalic, Ante Punda, Caroline Hayward, Tatijana Zemunik

Abstract:

Parathyroid hormone (PTH) plays a critical role in the regulation of bone mineral metabolism and calcium homeostasis. Higher PTH levels are associated with heart failure, hypertension, coronary artery disease, cardiovascular mortality and poorer bone health. A twin study estimated that 60% of the variation in PTH concentrations is genetically determined. Only one GWAS of PTH concentration has been reported to date. Identified loci explained 4.5% of the variance in circulating PTH, suggesting that additional genetic variants remain undiscovered. Therefore, the aim of this study was to identify novel genetic variants associated with PTH levels in a general population. We have performed a GWAS meta-analysis on 2596 individuals originating from three Croatian cohorts: City of Split and the Islands of Korčula and Vis, within a large-scale project of “10,001 Dalmatians”. A total of 7 411 206 variants, imputed using the 1000 Genomes reference panel, with minor allele frequency ≥ 1% and Rsq ≥ 0.5 were analyzed for the association. GWAS within each data set was performed under an additive model, controlling for age, gender and relatedness. Meta-analysis was conducted using the inverse-variance fixed-effects method. Furthermore, to identify sex-specific effects, we have conducted GWAS meta-analyses analyzing males and females separately. In addition, we have performed biological pathway analysis. Four SNPs, representing one locus, reached genome-wide significance. The most significant SNP was rs11099476 on chromosome 4 (P=1.15x10-8), which explained 1.14 % of the variance in PTH. The SNP is located near the protein-coding gene RASGEF1B. Additionally, we detected suggestive association with SNPs, rs77178854 located on chromosome 2 in the DPP10 gene (P=2.46x10-7) and rs481121 located on chromosome 1 (P=3.58x10-7) near the GRIK1 gene. One of the top hits detected in the main meta-analysis, intron variant rs77178854 located within DPP10 gene, reached genome-wide significance in females (P=2.21x10-9). No single locus was identified in the meta-analysis in males. Fifteen biological pathways were functionally enriched at a P<0.01, including muscle contraction, ion homeostasis and cardiac conduction as the most significant pathways. RASGEF1B is the guanine nucleotide exchange factor, known to be associated with height, bone density, and hip. DPP10 encodes a membrane protein that is a member of the serine proteases family, which binds specific voltage-gated potassium channels and alters their expression and biophysical properties. In conclusion, we identified 2 novel loci associated with PTH levels in a general population, providing us with further insights into the genetics of this complex trait.

Keywords: general population, genome-wide association analysis, parathyroid hormone, single nucleotide polymorphisms.

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1 Investigation of the Controversial Immunomodulatory Potential of Trichinella spiralis Excretory-Secretory Products versus Extracellular Vesicles Derived from These Products in vitro

Authors: Natasa Ilic, Alisa Gruden-Movsesijan, Maja Kosanovic, Sofija Glamoclija, Marina Bekic, Ljiljana Sofronic-Milosavljevic, Sergej Tomic

Abstract:

As a very promising candidate for modulation of immune response in the sense of biasing the inflammatory towards an anti-inflammatory type of response, Trichinella spiralis infection was shown to successfully alleviate the severity of experimental autoimmune encephalomyelitis, the animal model of human disease multiple sclerosis. This effect is achieved via its excretory-secretory muscle larvae (ES L1) products which affect the maturation status and function of dendritic cells (DCs) by inducing the tolerogenic status of DCs, which leads to the mitigation of the Th1 type of response and the activation of a regulatory type of immune response both in vitro and in vivo. ES L1 alone or via treated DCs successfully mitigated EAE in the same manner as the infection itself. On the other hand, it has been shown that T. spiralis infection slows down the tumour growth and significantly reduces the tumour size in the model of mouse melanoma, while ES L1 possesses a pro-apoptotic and anti-survival effect on melanoma cells in vitro. Hence, although the mechanisms still need to be revealed, T. spiralis infection and its ES L1 products have a bit of controversial potential to modulate both inflammatory diseases and malignancies. The recent discovery of T. spiralis extracellular vesicles (TsEVs) suggested that the induction of complex regulation of the immune response requires simultaneous delivery of different signals in nano-sized packages. This study aimed to explore whether TsEVs bare the similar potential as ES L1 to influence the status of DCs in initiation, progression and regulation of immune response, but also to investigate the effect of both ES L1 and TsEVs on myeloid derived suppressor cells (MDSC) which present the regular tumour tissue environment. TsEVs were enriched from the conditioned medium of T. spiralis muscle larvae by differential centrifugation and used for the treatment of human monocyte-derived DCs and MDSC. On DCs, TsEVs induced low expression of HLA DR and CD40, moderate CD83 and CD86, and increased expression of ILT3 and CCR7 on treated DCs, i.e., they induced tolerogenic DCs. Such DCs possess the capacity to polarize T cell immune response towards regulatory type, with an increased proportion of IL-10 and TGF-β producing cells, similarly to ES L1. These findings indicated that the ability of TsEVs to induce tolerogenic DCs favoring anti-inflammatory responses may be helpful in coping with diseases that involve Th1/Th17-, but also Th2-mediated inflammation. In MDSC in vitro model, although both ES L1 and TsEVs had the same impact on MDSC phenotype i.e., they acted suppressive, ES L1 treated MDSC, unlike TsEVs treated ones, induced T cell response characterized by the increased RoRγT and IFN-γ, while the proportion of regulatory cells was decreased followed by the decrease in IL-10 and TGF-β positive cells proportion within this population. These findings indicate the interesting ability of ES L1 to modulate T cells response via MDSC towards pro-inflamatory type, suggesting that, unlike TsEVs which consistently demonstrate the suppresive effect on inflammatory response, it could be used also for the development of new approaches aimed for the treatment of malignant diseases. Acknowledgment: This work was funded by the Promis project – Nano-MDCS-Thera, Science Fund, Republic of Serbia.

Keywords: dendritic cells, myeloid derived suppressor cells, immunomodulation, Trichinella spiralis

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