PREDVIĐANJE PRIHVAĆANJA USLUGA MOBILNOG BANKARSTVA U SJEVERNOJ MAKEDONIJI KOD POTROŠAČA

Smartphones and mobile technologies are becoming increasingly available and affordable in the Republic of North Macedonia. Followed by this trend, many banks are providing banking services to customers via smartphones. They are increasingly investing in mobile channels by providing new mobile banking services. Therefore, the goal of this research is to examine predictors of consumer intention to use mobile banking services in North Macedonia. In order to get insights regarding the user adoption of m-banking services in the country, a survey was conducted among more than 150 mobile users. The research model proposed in this study examines the influence of several basic constructs that explain technology acceptance and innovation diffusion (performance expectancy, effort expectancy, social influence and facilitating conditions). In addition, its originality and practical implications is reflected in determining the significance of additional constructs that are specific for the m-banking domain, such as perceived risk and bank’s reputation. The results of the empirical study indicate that three of the four basic constructs of the UTAUT model (performance expectancy, effort expectancy, and facilitating conditions) determine intention to use mobile banking, while social influence does not significantly influence mobile banking adoption in the sample. Regarding the two new constructs in the model, risk and bank’s reputation, they are both confirmed as important antecedents of consumer intention to use m-banking in our sample. By highlighting the usefulness of integrating constructs from different theories of technology acceptance, this research is a holistic approach representing a solid base for future studies on the adoption of new technologies in the country. From practitioner’s viewpoint, this research offers valuable insights for developing m-banking solutions.Pametni telefoni i mobilne tehnologije postaju sve dostupniji i pristupačniji u Republici Sjevernoj Makedoniji. Prateći ovaj trend, brojne banke klijentima pružaju bankarske usluge putem pametnih telefona. Sve više ulažu u mobilne kanale pružajući nove usluge mobilnog bankarstva. Stoga je cilj ovog istraživanja ispitati prediktore namjere potrošača da koriste usluge mobilnog bankarstva u sjevernoj Makedoniji. Kako bi se stekao uvid u prihvaćanje usluga m-bankarstva u zemlji, provedeno je istraživanje među više od 150 korisnika mobilnih uređaja. Model istraživanja predložen u ovoj studiji ispituje utjecaj nekoliko osnovnih konstrukata koji objašnjavaju prihvaćanje tehnologije i difuziju inovacija (očekivane performanse, očekivani napori, društveni utjecaj i olakšavajući uvjeti). Osim toga, njegova originalnost i praktičnost se ogledaju u određivanju značaja dodatnih konstrukata koji su specifični za m-bankarstvo, poput percipiranog rizika i reputacije banke. Rezultati empirijskog istraživanja pokazuju da tri od četiri osnovna konstrukta UTAUT modela (očekivane performanse, očekivani napori i olakšavajući uvjeti) određuju namjeru uporabe mobilnog bankarstva, dok društveni utjecaj nema značajan utjecaj na prihvaćanje mobilnog bankarstva. Što se tiče dva nova konstrukta u modelu, rizika i ugleda banke, oba su potvrđena kao važni prethodnici namjere potrošača da koriste m-bankarstvo. Ističući korisnost integriranja konstrukata iz različitih teorija prihvaćanja tehnologije, ovo istraživanje svom holističkom pristupu predstavlja solidnu osnovu za buduće studije o usvajanju novih tehnologija u zemlji. Sa stajališta praktičara, ovo istraživanje nudi vrijedne uvide za razvoj mobilnog bankarstva

DETERMINANTS OF MOBILE INTERNET USAGE AND OPPORTUNITIES FOR M-MARKETING AMONG YOUTH IN THE REPUBLIC OF MACEDONIA

The number of mobile Internet users is growing rapidly worldwide and the use of mobile Internet is changing consumer behaviour. Therefore, companies are extending their marketing opportunities and reaching their audience via mobile devices. Mobile marketing is gaining popularity in the last couple of years, due to the possibilities offered by new technologies embedded in smart phones. There have been several theoretical models that explain technology acceptance. Building on the extensions on UTAUT, consumer use and acceptance of technology led to UTAUT2 model. The aim of the research is to connect use of mobile Internet among young people in the Republic of Macedonia and opportunities of mobile marketing. The penetration rate of smart phones is increasing globally and in the last trimester of 2015 more than 72% of the Internet users in the country used smart phones to access the Internet (DSZ, 2015). The survey was conducted in April /May 2016 among more than 300 young people. Original UTAUT2 model is proposed to examine the influence of several constructs that influence use behaviour (performance expectancy, effort expectancy, social influence, facilitating conditions, hedonic motivation, price value, and habit). The factors are explained in the context of the research and attention is paid on habit, hedonic motivation and price value as predictors of the mobile Internet usage. The results of the empirical study are fully supporting the model. Namely, all relationships hypothesized in the model are proved to be significant in our sample. However, the moderators such as age, gender and experience used in the original UTAUT2 model were not included, but are expected to be influential when analysed in larger and more representative sample. The significance of the proposed predictors can help managers formulate their marketing strategies and profound their marketing communication efforts

Development of a T-cell Receptor Mimic Antibody against Wild-Type p53 for Cancer Immunotherapy

The tumor suppressor p53 is widely dysregulated in cancer and represents an attractive target for immunotherapy. Due to its intracellular localization, p53 is inaccessible to classical therapeutic monoclonal antibodies, an increasingly successful class of anti-cancer drugs. However, peptides derived from intracellular antigens are presented on the cell surface in the context of major histocompatibility class I (MHC I), and can be bound by T cell receptors (TCRs). Here, we report the development of a novel antibody, T1-116C, that acts as a TCR mimic to recognize an HLA-A*0201-presented wild-type p53 T cell epitope, p5365-73(RMPEAAPPV). The antibody recognizes a wide range of cancers, does not bind normal peripheral blood mononuclear cells, and can activate immune effector functions to kill cancer cells in vitro. In vivo, the antibody targets p5365-73 peptide-expressing breast cancer xenografts, significantly inhibiting tumor growth. This represents a promising new agent for future cancer immunotherapy

Developing anti-p53/HLA-A*0201 T-cell receptor mimic antibodies for cancer immunotherapy

T-cell receptor mimic (TCRm) antibodies target a dual antigen epitope consisting of a peptide derived from an intracellular protein, and the major histocompatibility complex class I (MHC-I) molecule that presents the peptide at the cell surface. As traditional antibodies typically target cell surface or secreted antigens, TCRm antibodies advantageously expand the range of targetable antigens to include peptides derived from intracellular proteins. This thesis describes the development of TCRm antibodies targeting peptides that are derived from the wild type p53 protein and are presented by human leukocyte antigen (HLA)-A2. We further characterised the specificity and safety of the T1-116C TCRm antibody, which was the most extensively studied TCRm antibody in the laboratory prior to the start of this DPhil project. We showed that T1-116C labels primary AML and myeloma cells. We investigated the specificity of the T1-116C TCRm antibody for the p5365-73 peptide, RMPEAAPPV, by substituting each amino acid within the peptide individually, and showed that T1-116C recognises multiple tumour antigens. Using in silico analysis we identified 271 potentially cross-reactive peptides. We tested a panel of 25 peptides that are conserved in mice in vitro, showing that T1-116C binds peptides derived from a broad range of normal tissues. Despite these findings, in vivo testing of T1-116C cross-reactivity in human HLA-A2 transgenic mice demonstrated that T1-116C does not cause toxicity to normal mouse tissues. We also generated chimeric antigen receptors (CARs) for T-cell therapy using the single chain variable fragment of p53-targeting TCRm antibodies to provide the CAR specificity. We found that the CAR derived from T2-2A, a TCRm antibody that targets the p53187-197 peptide, GLAPPQHLIRV, demonstrated superior specificity for target peptide-HLA-A2 tetramers and cell lines to the T1-116C CAR. Through these studies, the T2-2A TCRm antibody has emerged as a potential therapeutic agent when used in the CAR format. </p

Therapeutic antibodies against intracellular tumor antigens

Monoclonal antibodies are among the most clinically effective drugs used to treat cancer. However their target repertoire is limited as there are relatively few tumor-specific or tumor-associated cell surface or soluble antigens. Intracellular molecules represent nearly half of the human proteome and provide an untapped reservoir of potential therapeutic targets. Antibodies have been developed to target externalized antigens, have also been engineered to enter into cells or may be expressed intracellularly with the aim of binding intracellular antigens. Furthermore, intracellular proteins can be degraded by the proteasome into short, commonly 8-10 amino acid long, peptides that are presented on the cell surface in the context of major histocompatibility complex class I (MHC-I) molecules. These tumor-associated peptide-MHC-I complexes can then be targeted by antibodies known as T-cell receptor mimic (TCRm) or T-cell receptor (TCR)-like antibodies, which recognize epitopes comprising both the peptide and the MHC-I molecule, similarly to the recognition of such complexes by the TCR on T cells. Advances in the production of TCRm antibodies have enabled the generation of multiple TCRm antibodies, which have been tested in vitro and in vivo, expanding our understanding of their mechanisms of action and the importance of target epitope selection and expression. This review will summarize multiple approaches to targeting intracellular antigens with therapeutic antibodies, in particular describing the production and characterization of TCRm antibodies, the factors influencing their target identification, their advantages and disadvantages in the context of TCR therapies, and the potential to advance TCRm-based therapies into the clinic

PRODUCTION AND PRODUCTIVITY OF AGRICULTURE IN MACEDONIA DURING THE XX CENTURY

“In the period of (around) 1855, Europe knows that several years ago the American Joseph Henry invented the first electromotor, but doesn’t know that in some regions of Macedonia, instead of oxen, men were harnessed to plough the land” (Janevski, 1970). Period of XX century in Macedonia was extremely turbulent, besides the fact that it was century of 4 wars on this territory. This historical change has strong impact to the all-economic and social aspects of ordinary life, including agriculture. So the main aim of this paper is to enlightening little bit more situation and condition of agriculture in North Macedonia during the XX century. Methodology was mainly desk research of historical and statistical data relevant for this field and changes, which are following agricultural production and productivity in this period (XX century). In Macedonia, during the XIX century, institutional settings established in the Ottoman Empire have been put into force. The owner of the land was the Turkish aristocrat “spahija”. The people who worked on the spahija’s assets were “raja”. Private agriculture in Macedonia has been established around 1912 when Macedonia was finally freed from the Ottoman occupation. There are four phases in the historical development of agriculture and agricultural relations in Macedonia throughout history, actual within the XX century: the period of the Ottoman Empire; the period between the two World Wars; the period of Socialism (1945-1990); and the period since independence until now. The transition to the modern, as opposed to historic, period in Macedonia started in 1990 and continues to today. Each of these periods has their sociological, economic and cultural characteristics. Of course, each period has different means of production and productivity that depend not only on the technological and technical development, but also, perhaps much more, on the social characteristics

Therapeutic Antibodies against Intracellular Tumor Antigens

Monoclonal antibodies are among the most clinically effective drugs used to treat cancer. However their target repertoire is limited as there are relatively few tumor-specific or tumor-associated cell surface or soluble antigens. Intracellular molecules represent nearly half of the human proteome and provide an untapped reservoir of potential therapeutic targets. Antibodies have been developed to target externalized antigens, have also been engineered to enter into cells or may be expressed intracellularly with the aim of binding intracellular antigens. Furthermore, intracellular proteins can be degraded by the proteasome into short, commonly 8-10 amino acid long, peptides that are presented on the cell surface in the context of major histocompatibility complex class I (MHC-I) molecules. These tumor-associated peptide-MHC-I complexes can then be targeted by antibodies known as T-cell receptor mimic (TCRm) or T-cell receptor (TCR)-like antibodies, which recognize epitopes comprising both the peptide and the MHC-I molecule, similarly to the recognition of such complexes by the TCR on T cells. Advances in the production of TCRm antibodies have enabled the generation of multiple TCRm antibodies, which have been tested in vitro and in vivo, expanding our understanding of their mechanisms of action and the importance of target epitope selection and expression. This review will summarize multiple approaches to targeting intracellular antigens with therapeutic antibodies, in particular describing the production and characterization of TCRm antibodies, the factors influencing their target identification, their advantages and disadvantages in the context of TCR therapies, and the potential to advance TCRm-based therapies into the clinic

Comprehensive mutagenesis identifies the peptide repertoire of a p53 T-cell receptor mimic antibody that displays no toxicity in mice transgenic for human HLA-A*0201

T-cell receptor mimic (TCRm) antibodies have expanded the repertoire of antigens targetable by monoclonal antibodies, to include peptides derived from intracellular proteins that are presented by major histocompatibility complex class I (MHC-I) molecules on the cell surface. We have previously used this approach to target p53, which represents a valuable target for cancer immunotherapy because of the high frequency of its deregulation by mutation or other mechanisms. The T1-116C TCRm antibody targets the wild type p5365-73 peptide (RMPEAAPPV) presented by HLA-A*0201 (HLA-A2) and exhibited in vivo efficacy against triple receptor negative breast cancer xenografts. Here we report a comprehensive mutational analysis of the p53 RMPEAAPPV peptide to assess the T1-116C epitope and its peptide specificity. Antibody binding absolutely required the N-terminal arginine residue, while amino acids in the center of the peptide contributed little to specificity. Data mining the immune epitope database with the T1-116C binding consensus and validation of peptide recognition using the T2 stabilization assay identified additional tumor antigens targeted by T1-116C, including WT1, gp100, Tyrosinase and NY-ESO-1. Most peptides recognized by T1-116C were conserved in mice and human HLA-A2 transgenic mice showed no toxicity when treated with T1-116C in vivo. We conclude that comprehensive validation of TCRm antibody target specificity is critical for assessing their safety profile