Ekspresija neuralnih adhezionih molekula (NCAM) u zdravom i obolelom bubrežnom tkivu

Introduction: Kidney performs essential physiological roles that include metabolic waste excretion and maintenance of fluid and electrolyte balance. Different factors may lead to renal dysfunction. Kidney diseases are currently a global public health problem. Fortunately, dialysis and transplantation provide life-saving treatments, but these therapies are rife with limitations. Thus, new ways of therapies, such as stem cell treatment are more than required as an alternative and new glimmer of hope to all nephrology patients. Neural cell adhesion molecule (NCAM) is widely expressed during kidney development and it presents potential marker for renal stem/progenitor cells. Aim: Aim of this dissertation was evaluation of NCAM presence in different types of renal tissue (normal fetal or adult, and pathologically changed), and comparison and correlation of NCAM expression with already defined stem cell markers in order to more closely characterize renal fetal progenitor cells. Method: Specifically designed primers were used for reverse transcriptase PCR, after mRNA isolation from fetal, neonatal, adult normal, adult tissues with interstitial fibrosis and tumor tissues, to clarify presence of different NCAM on nucleotide level. Also, Western Blot tests were performed in order to identify expression of different NCAM protein isoforms in healthy and kidney with disease. Further, FACS analysis was done on renal cell lines to correlate NCAM expression with adult renal stem cell markers CD24 and CD133. Co-expression and co-localization of NCAM with other cell surface markers was also examined using immunohistochemistry and double immunofluorescent staining. Results: Our results showed aberrant NCAM expression in renal tumor tissues as well as in tissue with interstitial fibrosis. Interestingly in both types of mentioned tissues NCAM had co-expression with FGFR1, tyrosine kinase receptor, responsible for cell proliferation and aggressive behavior in some epithelial tumors. Considering NCAM expression on fetal samples possible renal progenitor population cell pool of NCAM+CD24+ cells was found, which was not the case with NCAM+CD133+ cell pool. Also, we had detected that NCAM molecules were post-trasnaltionally modified...UVOD: Bubreg ima značajnu fiziološku ulogu u izlučivanju štetnih produkata metabolizma putem urina, kao i ulogu u održanju ravnoteže vode i elektorlita. Različiti faktori mogu dovesti do poremećaja funkcije bubrega. Bolesti bubrega su trenutno globalni problem javnog zdravlja. Dijaliza i transplantacija su trenutno dominantni vidovi terapije koje se primenjuju u lečenju bubrežne isuficijencije, ali uz puno ograničenja. Novi načini terapije, kao što je tretman matičnim ćelijama, su više nego potrebni kao alternativa standardnim metodama lečenja i predstavljaju novi tračak nade za sve pacijente koji imaju neki oblik bubrežne disfunkcije. Neuralni ćelijski adhezioni molekul (NCAM) je široko ispoljen tokom razvoja bubrega i predstavlja potencijalni marker renalnih stem/progenitorskih ćelija. CILJ: Cilj ove disertacije je evaluacija NCAM ekspresije u različitim tipovima bubrežnog tkiva (fetalno, adultno normalno i adultno tkivo sa intersticijskom fibrozom i tumorsko tkivo), kao i njena korelacija sa ekspresijom već definisanih markera renalnih stem ćelija kako bi se preciznije definisale fetalne renalne progenitorske ćelije. METOD: Detekcija različitih NCAM izoformi na nivou nukleotida je vršena primenom RT-PCR metode, nakon izolacije iRNK iz fetalnog i normalnog adultnog tkiva, kao i tumorskog i tkiva sa intersticijskom fibrozom. Prisustvo NCAM isoformi na proteinskom nivou, u pomenutim tkivima detektovano je upotrebom Western blot-a i Imunoprecipitacije. Ko-ekspresija NCAM-a sa CD24 i CD133, markerima adultnih renalnih progenitora ispitivana je upotrebom protočne citomertije (FACS) na renalnim ćelijskim linijama. Imunohistohemijskim i dvostrukim imunofluorescentnim bojenjem ispitivana je koekspresija i kolokalizaciji NCAM-a sa drugim ćelijskim markerima. REZULTATI: RT-PCR rezultati ove doktorske disertacije su pokazale da sve ćelijske linije i ispitivana tkiva, osim tumorskog tkiva eksprimiraju tri glavne NCAM isoforme NCAM-120, NCAM-140 i NCAM-180. Takođe, detektovana je aberentnaprekomerna NCAM ekspresija u tumorskom, kao i u tkivu sa intersticijskom fibrozom. Interesantan nalaz čini pokazana koekspresija NCAM-a sa FGFR1, tirozin kinaznim receptorom, koji ima ulogu u ćelijskoj proliferaciji i agresivnom ponašanju pojedinih 7 epitelnih tumora

Verbal vs. visual coding in modified mental imagery map exploration task

We modified classical mental exploration task introducing verbal modality. Consequently, we could test robust effects from lexical processing in an attempt to understand whether the underlying mental representation is strictly propositional. In our three experiments, in addition to map modality (visual or verbal), lexical frequency, concreteness and visual frequency were also varied. The symbolic distance effect was replicated, regardless of map modality. Exploration of distances was regularly faster on pictorial maps. Effects of lexical frequency and concreteness were not significant for verbal maps. However, when visual frequency was introduced on pictorial maps both type of frequencies generated measurable effects. Our findings directly contradict the assumptions of propositional theories (1) subjects were faster in the visual modality, which would be difficult to explain if the perceptual code had to be transformed into propositional, (2) word frequency and concreteness did not contribute as would be expected if propositional code were a default

A Modification of the Random Curds Model by Markov Chain as a Design Tool in Architecture

The procedure of generating fractal rhythm in architecture with the help of the random curds model proposed by Carl Bovill had its limitations in practice, related to the number of possible states of architectural elements. Namely, the binary relation: "survives" – "does not survive" between the model units was directly transferred to relationships of architectural elements, which, consequently, can be only in one of these two possible conditions: "this one exists - that one exists". Authors of this paper, in their effort to overcome the aforementioned limitation, in addition to the cell that does not exist, suggest the existence of not only one, but of several different "living cells". The suggested procedure is interpreted as a Markov chain with several states, through several scales. This way, the authors created a modification of the random curds model in this paper, within which they achieved an arbitrary predefined, finite or countable infinite set of states

Dynamic modeling of disc brake contact phenomena

Interakcija između diska kočnice i frikcionog materijala disk kočnice motornih vozila se odlikuje velikim brojem kontaktnih fenomena. Nastanak ovih fenomena je vezan za radne uslove kočnice (pritisak aktiviranja, brzina, temperatura u kontaktu) kao i za karakteristike materijala frikcionog para. Dinamičke i izraženo nelinearne promene, koje se dešavaju u kontaktu frikcionog para, izazivaju teško predvidivu promenu momenta kočenja, kao najvažnije izlazne performanse kočnice. Složena situacija u kontaktu frikcionog para se ne može lako modelirati i predvideti korišćenjem klasičnih matematičkih metoda. Zbog toga su istraživane mogućnosti razvoja metode za predviđanje uticaja radnih režima disk kočnice na pojavu tzv. 'stickslip' fenomena tokom ciklusa kočenja. Korišćenjem dinamičkih neuronskih mreža, razvijen je dinamički model uticaja radnih uslova disk kočnice na pojavu kontaktnih fenomena i način promene momenta kočenja.An interaction between a brake disc and friction material of automotive brake is characterized by a number of braking phenomena. These phenomena are influenced by brake operation conditions (applied pressure, speed, and brake interface temperature) and material characteristics of a friction couple. The dynamic and highly non-linear changes occurred in the contact of the friction pair, provokes hard-to-predict change of braking torque as the most important brake's output performance. Complex disc brake contact situation is causing sudden change of braking torque and could not be easily modeled and predicted using classical mathematical methods. That is why, the possibilities for development of the method for prediction of influence of braking regimes on generation of the stick-slip phenomena during a braking cycle has been investigated in this paper. Dynamic neural networks have been employed for development of the model of influences of the disc brake operation conditions on contact phenomena generation and 'nature' of braking torque change

Dynamic modeling of disc brake contact phenomena

Interakcija između diska kočnice i frikcionog materijala disk kočnice motornih vozila se odlikuje velikim brojem kontaktnih fenomena. Nastanak ovih fenomena je vezan za radne uslove kočnice (pritisak aktiviranja, brzina, temperatura u kontaktu) kao i za karakteristike materijala frikcionog para. Dinamičke i izraženo nelinearne promene, koje se dešavaju u kontaktu frikcionog para, izazivaju teško predvidivu promenu momenta kočenja, kao najvažnije izlazne performanse kočnice. Složena situacija u kontaktu frikcionog para se ne može lako modelirati i predvideti korišćenjem klasičnih matematičkih metoda. Zbog toga su istraživane mogućnosti razvoja metode za predviđanje uticaja radnih režima disk kočnice na pojavu tzv. 'stickslip' fenomena tokom ciklusa kočenja. Korišćenjem dinamičkih neuronskih mreža, razvijen je dinamički model uticaja radnih uslova disk kočnice na pojavu kontaktnih fenomena i način promene momenta kočenja.An interaction between a brake disc and friction material of automotive brake is characterized by a number of braking phenomena. These phenomena are influenced by brake operation conditions (applied pressure, speed, and brake interface temperature) and material characteristics of a friction couple. The dynamic and highly non-linear changes occurred in the contact of the friction pair, provokes hard-to-predict change of braking torque as the most important brake's output performance. Complex disc brake contact situation is causing sudden change of braking torque and could not be easily modeled and predicted using classical mathematical methods. That is why, the possibilities for development of the method for prediction of influence of braking regimes on generation of the stick-slip phenomena during a braking cycle has been investigated in this paper. Dynamic neural networks have been employed for development of the model of influences of the disc brake operation conditions on contact phenomena generation and 'nature' of braking torque change

Development of neural network model of disc brake operation

Kvalitet veštačkih neuronskih modela pretežno zavisi od pravilnog izbora arhitekture veštačke neuronske mreže, odnosno algoritma učenja, funkcije prenosa, opsega i raspodele podataka korišćenih za obuku, validaciju i testiranje. Osnovni cilj ovog rada se odnosi na istraživanje kako arhitekture veštačkih neuronskih mreža utiču na uspešnost predviđanja tj. sposobnost generalizacije mreža za isti set podataka za obuku i testiranje. Kompleksni postupak razvoja veštačkog neuronskog modela je demonstriran na primeru disk kočnice. Modeliran je uticaj radnih uslova disk kočnice (pritisak aktiviranja, početna brzina i temperatura) na njene maksimalne performanse kao i performanse opadanja i obnavljanja efikasnosti. Veštački neuronski model je razvijan kroz istraživanje na koji način sinergija različitih parametara mreže, poput algoritma učenja, funkcije prenosa i broja neurona u skrivenim slojevima, utiče na sposobnosti neuronskog modela da predvidi performanse disk kočnice. U ovom radu je pokazano da kompleksne nelinearne zavisnosti između posmatranih ulaznih i izlaznih parametara mogu biti modelirane odgovarajućom analizom i podešavanjem parametara veštačke neuronske mreže.The quality of artificial neural network models mostly depends on a proper setting of neural network architecture i.e. learning algorithm, transfer functions, range and distribution of data used for training, validation, and testing, etc. The goal of this paper is related to the investigation on how artificial neural network architectures influence the network's generalization performance based on the same input/output parameters. The complex procedure of an artificial neural network model development has been demonstrated related to the disc brake performance. The influence of disc brake operation conditions (application pressure, initial speed, and temperature) has been modeled related to the disc brake cold, fade, and recovery performance. The artificial neural network model has been developed through investigation of how the synergy of different network's parameters, such as learning algorithm, transfer functions, the number of neurons in the hidden layers, affect the neural model abilities to predict the disc brake performance. It was shown in this paper that complex non-linear interrelations between the disc brake input/output variables can be modeled by proper analysis and setting of artificial neural network parameters.

Intestinal helminth parasites of the grey wolf (Canis lupus L.) in Serbia

The grey wolf (Canis lupus L.) is the most widespread large carnivore in Europe with large populations in the Eastern part of Europe and the Balkan Peninsula. In this study, a total of 102 wolves were examined for intestinal helminth parasites. The carcasses were collected within the Serbian part of the wolf’s range during the period 2009–2014. Nine helminth species were found: one nematode, Toxocara canis (3.9%), one trematode, Alaria alata (1.0%), and seven cestodes, Taenia pisiformis (1.0%), T. hydatigena (9.8%), T. polyacantha (2.9%), T. taeniaeformis (2.0%), T. (syn. Multiceps) multiceps (3.9%), T. serialis (1.0%) and Mesocestoides litteratus (1.0%). Taenia (syn. Hydatigera) taeniaeformis has been registered for the first time in a wolf from Europe. An overall moderate prevalence (16.7%) of infected wolves was recorded. There was no statistically significant difference in prevalence between sexes. Of the years studied, the highest prevalence was found in 2014 (57.1%). The maximum number of helminth species per host specimen was four

Teachers' perceptions of factors impeding school improvement in Serbia

In the last ten years the education system in Serbia has undergone a series of innovations which have encountered various obstacles. Teachers, as the key actors in the implementation of innovations, have implicit perceptions which may impact on the success of any school improvement. Therefore this study employed a mixed methods research strategy to investigate what teachers see as the obstacles to school improvement. A qualitative study implied four focus groups with teachers, while quantitative data was gathered through a questionnaire completed by 1,441 teachers from 40 primary schools from different regions around Serbia. Factor analysis confirmed that the potential obstacles could be grouped into six factors (Teachers' incompetence, Material and organizational barriers, Lack of systemic support, Student related barriers, Lack of communication within the school, Lack of communication between schools and stakeholders). Teachers see the biggest obstacles to school improvement in student related and material and organizational barriers. Teachers do not see themselves as the most significant source of problems in improving the work of schools, but transfer responsibility onto more general issues and external agents

Risk analysis and management on Public Private Partnership Projects (PPP) in Serbia

nfrastructure projects are going through a lot of difficulties, mostly connected with non standard established financing in South Eastern Europe countries. During and after transition period, undeveloped, insufficient but before all obsolete infrastructure in Serbia became a essential problem for further development of main economic resources (transportation, agriculture, mining, tourism etc.). Infrastructure network is necessity for the development of different sectors (energetic, agriculture, industry, commerce etc.). Domestic regulation is not clear in allowing project financing through Public Private Partnership (PPP) model, which is great opportunity for opening new projects and finishing many projects with on hold status. The main problem in decision making and starting financing projects in that model is too many risks on the market, which endanger projects from very beginning, especially in initiation phase so many investors decide to leave projects in very early phases. The analysis of potential risk elements, throughout the processes from bidding to operational infrastructure projects, is one of the most important elements to maximizing profit and functionality, and properly develop country infrastructure, while minimalizing potential difficulties that may arise. Much of the risk of a PPP project comes from the complexity of financing, taxation, law regulatory, aquired technical documentation and construction process involved in a major infrastructure venture. Main risks, their analyze and management on infrastructure projects are explained in this paper. After risk analyze, risk management tools are presented, together with method of managing risks on PPP projects in Serbia

The surrealist transformation of metaphor and its neo-rhetorical status in the poetry of Jules Supervieille, Jean Cocteau and Jean Tardieu

Metafora, kao pojam koji u okviru čitavog razvoja retorike, od Aristotela pa do savremenih novoretoričkih tumačenja, zauzima značajno mesto kao predmet različitih estetičkih, lingvističkih, filozofskih i psiholoških promišljanja. Iako se tumačenje metafore najčešće vezuje za područje lingvističkih nauka i stilistike, a zatim za kognitivne nauke u kojima se ispituju njena konceptualna svojstva, pažnja ovog istraživanja usmerena je na retoričku praksu svojstvenu poetskom jeziku. Teorijsko definisanje i ispitivanje u ovom radu baziraju se na pristupu ruskog formalizma, strukturalističkim, semiotičkim i poststrukturalističkim principima, dok interpretacija tekstova sledi načela hermeneutike i komparativne metode. Evolucija pojma metafore i njenog statusa u istoriji naučnih, umetničkih i filozofskih upotreba i tumačenja, kao i obnovljen interes za nju počev od prvih decenija 20. veka u vidu teorijskog i estetičkog preispitivanja pojma i njegove upotrebe u umetničkoj praksi, navode nas na ponovno definisanje metafore i njeno drugačije teorijsko predstavljanje. Aktuelno stanje u društveno-humanističkim naukama svedoči o stalno prisutnoj potrebi da se tradicionalni obrasci neprestano preispituju, najpre kroz njihovu dekonteksualizaciju i izvođenje iz teorijsko-praktičnog kontinuiteta (istorije) i kroz promatranje primenljivosti njihovih osnovnih struktura u sadašnjim naučnim preokupacijama i potrebama. Epistemološka vrednost metafore posebno se ističe u savremenom pristupu metafori, posebno u okvirima kognitivnih nauka, gde se ukazuje na njenu moć u procesu spoznaje, ali i produbljivanja značenja. Navedena činjenica ukazuje na dijahronijski kontinuitet stava da je metaforički proces u osnovi generički, te se metafora postavlja u centar interdisciplinarnog interesovanja koje potvrđuje da je ona rezultat, ali i uslov, spoznajne i semiotičke aktivnosti. Predmet ove disertacije postavlja se u kontekst poezije 20. veka, momenat rehabilitacije retoričkog nasleđa i metafore koja, pritom, postaje najznačajniji izraz i simptom literarnosti. Nadrealizam, kao pokret koji je u datom trenutku književne istorije najdoslednije (re)afirmisao metaforu, i to u okviru svoje poetike kao nužan postupak ostvarenja sinteze stvarnog i nadstvarnog, dakle, celovitog iskustva sveta kroz poetsko iskustvo, predstavlja nezaobilazno mesto obnavljanja interesa za pitanje metaforičkog izraza. Polje istraživanja ove disertacije obrazuje se oko poezije trojice pesnika 20. veka, Žila Sipervjela, Žana Koktoa i Žana Tardije čije su se poetike razvijale u dodiru sa nadrealizmom i nadrealističkom estetikom. Njena literarna upotreba se, stoga, može (i mora) predstaviti kao jedan deo širokog interesovanja za metaforičke procese, pa se tumačenje metafore u čisto literarnom kontekstu poezije 20. veka može smatrati doprinosom boljoj teoretizaciji ovog pojma. Analiza metafore u poeziji trojice navedenih pesnika osvetljava pozni momenat njene evolucije, koji je iz ugla teorija 20. veka viđen kao korenita promena i prevrat u tradicionalnoj umetničkoj praksi, a opus koji obuhvata heterogeni književnoistorijski period, kao i komparativno čitanje triju poetika, ukazuje na dinamiku tog procesa, osobine moderne metafore i njen kreativni potencijal, kao i nov pritup tumačenju poezije izabranih pesnika. Stoga se u radu sprovodi uporedba metaforičkih obrazaca i to na dva plana – u odnosu na nadrealističku metaforu, pri čemu se pokazuje kako je ona prevaziđena, nakon što je, manje ili više, inkorporirana u sve tri poetike; a zatim se poređenje fokusira traženje međusobnih veza i razilaženja u formiranju metafora. Poseban doprinos odabranih pesnika u teorijskoj i praktičnoj upotrebi metafore ogleda se u prevazilaženju granica poezije kao diskurzivnog sistema, prenos značenja iz jednog autonomnog sistema u drugi, pri čemu se ne narušava samo logika na kojoj je on zasnovan, već se poništava i granica među njima – bilo da su to dva različita jezika, ili pak dva sistema označavanja koja funkcionišu sa različitim označiteljima, kao što su to poezija i slikarstvo, poezija i nauka, itd. Moderna metafora u analiziranim pesmama, naime, saopštava činjenicu da autonomnih sistema zapravo i nema: ona im ne poriče specifičnost, ali omogućava njihovo spajanje. Cilj istraživanja je, dakle, da se utvrde poetički uticaji nadrealističkog pokreta na metaforičnost u poeziji Žana Koktoa, Žila Sipervjela i Žana Tardijea, kao i da se ukaže na novoretorički status moderne metafore koju odabrani pesnici koriste. Definisani pristup omogućava i sagledavanje filozofske, estetičke i književne implikacije istorijskog momenta u kome je nastajala poezija izabranih autora. To je ciljani horizont ovog istraživanja, a njegov osnovni akademski cilj je teorijski, istorijski i kritički određen.Metaphor, as a concept that within the entire development of rhetoric, from Aristotle to modern neo-rhetorical interpretations, occupies an important place as a subject of various aesthetic, linguistic, philosophical and psychological considerations. Although the interpretation of metaphor is most often related to the field of linguistics and stylistics, and then to cognitive sciences in which its conceptual properties are examined, the attention of this research is focused on rhetorical practice in poetic language. The theoretical definition and examination in this dissertation are based on the approach of Russian formalism, structuralist, semiotic and poststructuralist principles, while the interpretation of the texts follows the principles of hermeneutics and comparative methods. The evolution of the concept of metaphor and its status in the history of scientific, artistic and philosophical uses and interpretations, as well as renewed interest in it since the first decades of the 20th century in the form of theoretical and aesthetic rethinking of the concept and its use in artistic practice, lead us to redefine metaphor and its different theoretical representations. The current situation in the social sciences and humanities testifies to the constant need to constantly re-examine traditional patterns, first through their decontextualization and derivation from theoretical-practical continuity (history) and through observing the applicability of their basic structures in current scientific preoccupations and needs. The epistemological value of metaphor is especially emphasized in the modern approach to metaphor, especially in the framework of cognitive sciences, where its power in the process of cognition is pointed out, but also the deepening of meaning as a phenomenon. This fact indicates the diachronic continuity that determines the metaphorical process as basically generic, and the metaphor is placed in the center of interdisciplinary interest, which confirms that it is the result, but also a condition of cognitive and semiotic activity. The subject of this dissertation is placed in the context of 20th century poetry, a moment of rehabilitation of rhetorical heritage and theory of metaphor, which, at the same time, becomes the most significant expression and symptom of literature and its property. Surrealism, as a movement that, at a given moment in literary history most consistently (re)affirmed metaphor, and within its poetics as a necessary procedure for the synthesis of real and surreal, therefore, the complete experience of the world through poetic experience, is an unavoidable place to renew interest in metaphorical expression. The field of research of this dissertation is formed around the poetry of three poets of the 20th century, Jules Supervieille, Jean Cocteau and Jean Tardieu, whose poetics developed in contact with surrealism and surrealist aesthetics. The literary use of metaphor, therefore, can (and must) be presented as one part of a broad interest in metaphorical processes, so the interpretation of metaphor in the purely literary context of 20th century poetry can be considered a contribution to better theorizing of this concept. The analysis of metaphor in the poetry of the three mentioned poets illuminates the late moment of its evolution, which from the point of view of 20th century theories is seen as a radical change and revolution in traditional artistic practice, and the opus that process the features of modern metaphor and its creative potential, as well as a new approach to the interpretation of the poetry of selected poets. Therefore, the dissertation compares their metaphorical patterns on two levels - in relation to the surrealist metaphor, showing how it has been overcome, after, more or less, been incorporated into all three poetics; and then the comparison focuses on looking for mutual connections and differences in the formation of poetic metaphors. The special contribution of selected poets in the theoretical and practical use of metaphor is reflected in overcoming the boundaries of poetry as a discursive system, transferring meaning from one autonomous system to another, not only violating the logic they are based on, but also nullifying the boundaries between them - whether they are two different languages, or two systems of signification that work with different signifiers, such as poetry and painting, poetry and science, etc. The modern metaphor in the analyzed poems, in fact, communicates the fact that there are no autonomous systems: it does not deny their specificity, but enables their merging. The aim of the research is, therefore, to determine the poetic influences of the Surrealist movement on metaphoricity in the poetry of Jean Cocteau, Jules Supervieille and Jean Tardieu, as well as to point out the neo-rhetorical status of modern metaphor used by selected poets. The defined approach also enables the consideration of the philosophical, aesthetic and literary implications of the historical moment in which the poetry of selected authors was created. This is the target horizon of this research, and its basic academic goal is theoretically, historically and critically determined