Este trabalho trata de ambientes de software para a realização de teste e caracterização de dispositivos, componentes ou circuitos eletro-eletrônicos, de forma automatizada. Ênfase especial é dada à problemática relacionada ao teste e caracterização automatizados de dispositivos e circuitos integrados. O assunto é tratado sob dois pontos de vista distintos e complementares: i) Sob o ponto de vista do engenheiro de teste e caracterização, que realiza experimentos físicos, que são as medidas e aquisições de dados, processa, visualiza e analisa dados. ii) Sob o ponto de vista do projetista de ferramentas de software, que desenvolve programas de computador para automatizar as tarefas rotineiramente realizadas durante o teste e a caracterização. Após a analise do assunto em questão, um ambiente de software (Framework), chamado SGC, é proposto e implementado. O SGC foi implementado em ambiente MS-WindowsTM através de um paradigma de orientação a objetos, e pretende atender as necessidades inerentes ao teste e caracterização automatizados, quando tratados sob os dois pontos de vista citados. O ambiente SGC é um sistema aberto, a fim de permitir o fácil acoplamento de novas facilidades, bem como mostra-se um sistema prático para suportar rotinas de teste e caracterização em laboratório. / This work deals with software environments for automatic test and characterization of electro-electronical devices, components and circuits. Special attention is paid to the features of testing and characterizing integrated devices and circuits. The subject is treated in two different and complementary views: i) The needs of the test and characterization engineer are addressed. The test engineer carries out physical experiments, which embody measurements and data acquisitions, data processing, visualization and analysis. ii) The needs of the software tools developer, who develops computer programs for the automation of the procedures that are usually carried out during test and characterization, are also addressed. After the analysis of the subject under study, a software framework, called SGC ("Sistema de Gerenciamento e Controle"), is proposed and implemented. The SGC Framework was implemented under MS-WindowsTm using a object oriented approach. The SGC framework aims to fulfill the needs inherent to the automatic test and characterization, when treated using the approaches mentioned above. The SGC Framework is a open system, supporting the easy integration of new software functions to the environment, as well as a practical system for test and characterization laboratory routines.

Canine distemper disease is a severe multisystem disease that affects the respiratory, hemolymphatic, gastrointestinal and neurological systems. The lesions induced by replication of canine distemper virus (CDV) produce an increase in reactive oxygen species (ROS), leading to oxidative stress. The aim of this study was to investigate parameters of oxidative stress by measuring the lipid peroxidation through the thiobarbituric acid reactive substances (TBARS) and the activity of the enzymes catalase (CAT) and superoxide dismutase (SOD) in dogs naturally infected with distemper virus. In this study we used 33 animals positive for CDV, attended at the Veterinary Hospital of the University of Rio Grande do Sul (UFRGS) and 21 clinically healthy animals were used as control. For the confirmation of the diagnosis RT-PCR (Reverse Transcription Polymerase Chain Reaction) was performed in samples of rectal swab and/or serum. This study demonstrated a significant difference in lipid peroxidation, SOD and CAT activities in the analyzed groups, suggesting the involvement of oxidative stress in the pathogenesis of the disease. / A cinomose canina é uma doença multissistêmica grave, que afeta os sistemas respiratório, hemolinfático, gastrointestinal e neurológico. As lesões induzidas pela replicação do vírus da cinomose canina (VCC) produzem um aumento das espécies reativas de oxigênio (EROs), que levam a um quadro de estresse oxidativo. O objetivo deste trabalho foi verificar parâmetros de estresse oxidativo através da mensuração da peroxidação lipídica através das substâncias reativas ao ácido tiobarbitúrico (TBARS) e da atividade das enzimas catalase (CAT), superóxido dismutase (SOD) em cães naturalmente infectados com o vírus da cinomose. Neste estudo, foram utilizados 33 animais positivos para o VCC, provenientes do atendimento da rotina do Hospital de Clínicas Veterinárias da Universidade Federal do Rio Grande do Sul (UFRGS) e 21 animais clinicamente sadios como controle. Para a confirmação do diagnóstico da doença a técnica de RT-PCR (Reação em Cadeia da Polimerase pela Transcriptase Reversa) foi realizada em amostras de swab retal e/ou soro. Este estudo demonstrou que houve diferença significativa na peroxidação lipídica, atividades da SOD e CAT entre grupos analisados, sugerindo o envolvimento do estresse oxidativo na patogênese desta doença.

Submitted by Luciana Ferreira (lucgeral@gmail.com) on 2017-04-05T14:15:45Z No. of bitstreams: 2 Dissertação - Mayara Vieira Santos - 2017.pdf: 4242091 bytes, checksum: e1114c1030f1c4a78d59b8f716e90e79 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2017-04-05T14:16:02Z (GMT) No. of bitstreams: 2 Dissertação - Mayara Vieira Santos - 2017.pdf: 4242091 bytes, checksum: e1114c1030f1c4a78d59b8f716e90e79 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2017-04-05T14:16:02Z (GMT). No. of bitstreams: 2 Dissertação - Mayara Vieira Santos - 2017.pdf: 4242091 bytes, checksum: e1114c1030f1c4a78d59b8f716e90e79 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2017-02-24 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Usually the inoculum used during the beginning of the harvest of ethanol production is constituted by the combination of two or more yeasts strains and in the end the most adapted one will predominate, either inoculated yeast or indigenous wild yeast. The proportion used in these industries are established empirically, of which little is known about the kinetic parameters and the influence that each yeast has on the production of ethanol and on the other metabolites. An experimental design from the blending design with Saccharomyces cerevisiae ATCC7754, S. cerevisiae CAT-1, S. cerevisiae PEDRA-2, S. cerevisiae MONASTRELL strains was proposed to understand how the interaction among the different blends occurs comparing with the ethanol, biomass, acetic acid, glycerol and biomass consumption. This study showed that the inherent characteristics to each yeast can influence the behavior of the kinetics parameters of the culture with two yeasts. It was verified that the combination among three yeasts presented similar metabolic behavior. From the blending design it was possible to elaborate mathematical models that predicts the ethanol, biomass, glycerol, acetic acid and residual sucrose amount in all four yeasts mixtures. It was also possible to identify that the mixture of CAT-1 and PEDRA-2 presented higher ethanol production when cultivated in a 1: 1 ratio, and also in the cultivation with the two yeasts (CAT-1 and PEDRA-2) to CAT-1 was higher in yeast. This research also presents the synthetic cane juice composition and the detail of growth kinetics, substrates consume and production of MONASTRELL yeast products that had not been studied until now. / Normalmente o inóculo utilizado durante o início da safra da produção de etanol é constituído da combinação de duas ou mais linhagem de leveduras e no final prevalece aquela que mais se adaptar, seja as leveduras inoculadas ou leveduras selvagens autóctones. Quanto as proporções utilizadas nas industrias essas são estabelecidas de forma empírica, dos quais sabe-se pouco sobre os parâmetros cinéticos e a influência que cada levedura acarreta sobre a produção do etanol e sobre os outros metabólitos. Um planejamento experimental a partir do delineamento de mistura com as cepas de Saccharomycescerevisiae ATCC7754, S. cerevisiae CAT-1, S. cerevisiae PEDRA-2, S. cerevisiae MONASTRELL foi proposto para entender como ocorre a interação entre as diferentes misturas comparando com os cultivos puros diante das respostas etanol, biomassa, ácido acético, glicerol e consumo de biomassa. Neste estudo mostrou que as características inerentes a cada levedura podem influenciar no comportamento dos parâmetros cinéticos do cultivo com duas leveduras. Verificou-se que a maioria das combinações entre três leveduras apresentam comportamento metabólico semelhante. A partir do delineamento de mistura pôde elaborar modelos matemáticos que predizem a quantidade de etanol, biomassa, glicerol, ácido acético e sacarose residual nas misturas das quatro leveduras. Conseguiu-se também identificar que o ensaio com a mistura de CAT-1 e PEDRA-2 apresentou maior produção de etanol na proporções de 1:1 da concentração de inóculo, e ainda neste cultivo a CAT-1 se sobressaiu em quantidade de leveduras. Esta pesquisa ainda apresenta a composição de caldo de cana-de-açúcar sintético e o detalhamento da cinética de crescimento, consumo de substrato e produção de produtos da levedura MONASTRELL que até então não tinham sido estudada.

The aim of the diploma thesis is to evaluate the motivation and satisfaction of employees in a selected company. The thesis is divided into two parts -- theoretical and practical. First, the thesis defines the theoretical concept of motivation and satisfaction and defines a projective method called Colour Association Technique (CAT) from the concept of Balance Management. The practical part of the thesis presents the company where the research was done. Further methodology of research is presented in this part. In the methodology of research a questionnaire survey was chosen. A questionnaire survey focused on 7 areas of motivation and satisfaction covering 25 study-factors. Further, individual interviews were held with a selected sample of employees, and the projective method mentioned was used. The main body of the practical part consists of an evaluation of the results using all research methods. Individual results are compared and in conclusion recommendations for improving the current situation in the company are suggested. These final recommendations may become a basis for the future development of an optimal motivation program, which the company has not yet implemented.

Submitted by Luis Ricardo Andrade da Silva (lrasilva@uefs.br) on 2016-02-27T01:06:25Z No. of bitstreams: 1 DISSERTACAO_CLAUDIANO_DA_HORA_DE_CRISTO.pdf: 1498427 bytes, checksum: df928264d2581e7f3f3304d6c0704c5e (MD5) / Made available in DSpace on 2016-02-27T01:06:25Z (GMT). No. of bitstreams: 1 DISSERTACAO_CLAUDIANO_DA_HORA_DE_CRISTO.pdf: 1498427 bytes, checksum: df928264d2581e7f3f3304d6c0704c5e (MD5) Previous issue date: 2015-09-03 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / This research problematized the cycle of social policies of Rural Education in the sense of understand the contribution of social agents of the State and civil society in the formulation process and problematization of its effectuation. It has as study objective the performance of Collective of the Project get to know, Analyze and Transform the reality of the field (CAT Project) in the mobilization of the social policy agenda of Rural Education in Bahia municipalities. This research had as guiding question: what is the contribution of the Collective Project "CAT" to the formulation and questioning of effectuation of social policies in the Field Education for a compound set of 26 municipalities in the state of Bahia, in the period of 2003 - 2010. Faced with this question was formulated the following overall goal: to analyze the actions and propositions of the CAT Collective Project in the formulation and problematization process of the implementation of social policies of Rural Education in the basic system of elementary school. The epistemological approach that directs this research is the critical-dialectic whose matrix is the historical-dialetic materialism. This survey was operationalized through data analysis technique, whose main source were the Annual Reports of the CAT Project, the year 2003 to 2010, which record the activities developed by the Collective of this Project. As analysis categories stand out: social policies and popular education. Conducted by theoretical - Methodological references we can analyze the social policies of Rural Education in Brazil and its particular expression, the Project CAT and we found that the CAT Collective Project, despite some contradiction, put on the agenda the Rural Education policy. However, in relation of a local situation, national and international hegemony of neoliberal policy, which resulted in a loss of radical social movements, building consensus among antagonistic social classes and focused on public policies, geared to alleviate poverty and, Therefore, social conflicts, the actions of CAT Collective Project did not succeed. / A presente pesquisa problematizou o ciclo das pol?ticas sociais de Educa??o do Campo, no sentido de compreender a contribui??o de agentes sociais do Estado, e da sociedade civil, no processo de sua implementa??o. Ela tem como objeto de estudo a atua??o do Coletivo do Projeto Conhecer, Analisar e Transformar a realidade do campo (Projeto CAT) na mobiliza??o da agenda da pol?tica social de Educa??o do Campo em munic?pios baianos. Essa pesquisa teve como pergunta norteadora: qual a contribui??o do Coletivo do Projeto CAT para a formula??o e efetiva??o de pol?ticas sociais de Educa??o do Campo, para um conjunto formado por 26 munic?pios do Estado da Bahia, no per?odo de 2003 a 2010? Diante dessa pergunta, foi formulado o seguinte objetivo geral: analisar as a??es e proposi??es do Coletivo do Projeto CAT no processo de formula??o e implementa??o das pol?ticas sociais de Educa??o do Campo nas redes b?sicas de Ensino Fundamental. A abordagem epistemol?gica que orienta esta pesquisa ? a cr?tico-dial?tica, cuja matriz ? o materialismo hist?rico-dial?tico. Essa pesquisa foi operacionalizada por meio da t?cnica de an?lise de dados, cuja principal fonte foram os Relat?rios Anuais do Projeto CAT, do ano de 2003 a 2010, que registraram as atividades desenvolvidas pelo Coletivo desse Projeto. Como categorias de an?lises destacam-se: pol?ticas sociais e educa??o popular. Conduzido pelas refer?ncias te?rico-metodol?gicas podemos analisar as pol?ticas sociais de Educa??o do Campo no Brasil e sua express?o particular, o Projeto CAT, e constatamos que o Coletivo do Projeto CAT, apesar de algumas contradi??es, colocou em pauta a pol?tica de Educa??o do Campo. Contudo, diante de uma conjuntura local, nacional e internacional de hegemonia da pol?tica neoliberal, que resultou numa perda da radicalidade dos movimentos sociais, na constru??o do consenso entre classes sociais antag?nicas e em pol?ticas p?blicas focalizadas, voltadas para amenizar a pobreza, e, por conseguinte, os conflitos sociais, as a??es do Coletivo do Projeto CAT n?o lograram ?xito.

La classe des graphes de groupes libres à groupes d'arêtes cycliques constitue une source importante d'exemples en théorie géométrique des groupes, en particulier dans le cadre des groupes hyperboliques. Un résultat récent de Wilton montre qu'un tel groupe à un bout et hyperbolique contient un sous-groupe de surface, répondant à une question attribuée à Gromov. Cette thèse est consacrée à l'étude de ces groupes lorsqu'ils se présentent comme des groupes fondamentaux de certains complexes carrés à courbure négative ou nulle. Les complexes carrés en question, appelés graphes tubulaires de graphes, sont obtenus en attachant des tubes (un tube est un produit cartésien d'un cercle avec l'intervalle unitaire) à une collection finie de graphes finis. Le but principal de cette thèse est de construire deux décompositions de base pour les groupes fondamentaux de graphes tubulaires de graphes : leur décomposition de Grushko et leur décomposition JSJ. Dans la première partie de la thèse, nous développons un algorithme en temps polynomial, dont l'entrée est un graphe tubulaire de graphes, et qui produit le scindement de Grushko de son groupe fondamental. Comme application, nous obtenons une version alternative d'un algorithme de Stallings, qui prend un ensemble fini de mots W dans un groupe libre F de rang fini, et décide s'il existe ou non un scindement libre de F relatif à W. Dans la deuxième partie de la thèse, nous développons un algorithme en temps doublement exponentiel, dont l'entrée est un graphe tubulaire de graphes avec un groupe fondamental hyperbolique à un bout, et qui produit le scindement JSJ du groupe fondamental. Nous remarquons qu'il s'agit du premier algorithme sur les scindements JSJ de groupes avec une borne effective sur la complexité de temps. La principale raison de l'efficacité de cet algorithme est que certaines propriétés asymptotiques du groupe, qui déterminent si le groupe se scinde au dessus un sous-groupe cyclique, admettent des caractérisations locales en raison de la structure cubique CAT(0). Comme application de ce résultat, nous obtenons un algorithme en temps doublement exponentiel, dont l'entrée est un groupe libre F de rang fini muni d'un ensemble fini de sous-groupes cycliques W tels que F est librement indécomposable relatif à W, et qui produit le scindement JSJ de F relativement à W. Une conséquence des résultats ci-dessus est que le problème d'isomorphisme pour les groupes considérés se réduit à l'algorithme de Whitehead. / The class of graphs of free groups with cyclic edge groups constitutes an important source of examples in geometric group theory, particularly of hyperbolic groups. A recent result of Wilton shows that any such group which is one-ended and hyperbolic contains a surface subgroup, answering a question attributed to Gromov. This thesis is devoted to the study of these groups when they arise as fundamental groups of certain nonpositively curved square complexes. The square complexes in question, called tubular graphs of graphs, are obtained by attaching tubes (a tube is a Cartesian product of a circle with the unit interval) to a finite collection of finite graphs. The main goal of this thesis is to construct two fundamental decompositions, the Grushko decomposition and the JSJ decomposition, of the fundamental groups of tubular graphs of graphs. In the first part of the thesis we develop an algorithm of polynomial time-complexity that takes a tubular graph of graphs as input and returns the Grushko decomposition of its fundamental group. As an application, we obtain an alternative version of an algorithm of Stallings, which takes a finite set of words W in a finite rank free group F as input, and decides whether or not there exists a free splitting of F relative to W. In the second part of the thesis we develop an algorithm of double exponential time-complexity that takes a tubular graph of graphs with one-ended hyperbolic fundamental group as input and returns the JSJ decomposition of the fundamental group. We remark that this is the first algorithm on JSJ decompositions of groups with an effective bound on the time-complexity. The main reason for the efficiency of this algorithm is that certain asymptotic properties of the group, which determine whether the group splits over a cyclic subgroup, admit local characterisations due to the CAT(0) cubical structure of these groups. As an application of this result, we obtain an algorithm of double exponential time-complexity that takes a finite rank free group F and a finite set of maximal cyclic subgroups W such that F is freely indecomposable relative to W as input and returns the relative JSJ decomposition of F relative to W. A consequence of the above results is that the isomorphism problem for the groups under consideration is reduced to the Whitehead algorithm.

The Diploma work deals with the implementation of LTE Cat-M technology in the simulation tool Network Simulator 3 (NS-3). The work describe LPWA technologies and their use cases. In first are described the main parts of the Internet of Things (IoT) and Machine-to-Machine (M2M) communication. Subsequently are described and defined the most used technologies in LPWA networks. Technologies which are used in the LPWA networks are Sigfox, LoRaWAN, Narrowband IoT (NB-IoT) and Long Term Evolution for Machines (LTE Cat-M), where LTE Cat-M technology is described in more details. Simulations are simulated in simulation tool NS-3 and use LENA module. In NS 3 tool are simulated Simulations, which give us informations of Network state according to different Network set up. At the end are done changes of Radio Resource Control (RRC) states in NS-3 tool. These changes are required for correct implementation LTE Cat-M technology in NS-3 tool. Then we are able to simulate simulations, which meet to definition of LTE Cat-M technology.

Bakgrund: Kvaliteten på sjuksköterskans omvårdnadsjournal kan återspegla den vårdkvalitet som tillhandahålls patienter. Patienter med en höftfraktur har ofta ett omfattande vårdbehov där omvårdnadsjournalen har en viktig funktion att strukturera dokumentation av vårdinsatser genom patientens vårdförlopp. Patienter med höftfraktur har ofta en komplex sjukdomsbild, där omvårdnadsdokumentationens kvalitet kan bidra till en säkrare vård för patienten. Kvaliteten på dokumentationen ökar vid en strukturerad journal och framförallt när ett standardiserat språk används. Journalgranskning är ett sätt att göra kvalitetskontroll av dokumentation. Motiv: Att drabbas av en höftfraktur innebär stora hälsorisker för en ofta redan skör person. Omvårdnadsdokumentationens kvalitet vid höftfraktur kan bidra till att patienten får bättre förutsättningar för att undvika komplikationer och till kortare vårdtid. Syfte: Att undersöka kvaliteten av omvårdnadsdokumentation för patienter med höftfraktur.Metod: En retrospektiv, deskriptiv och jämförande design där granskning av omvårdnadsjournaler användes för att besvara studiens syfte. Ett konsekutivt urval har gjorts av omvårdnadsdokumentation från 40 vårdtillfällen med patienter över 60 år som vårdats för en höftfraktur på en akutortopedisk avdelning. För granskningen användes journalgranskningsinstrumentet Cat-ch-ing. Resultat: De granskade omvårdnadsjournalernas kvalitet var varierande; ingen av journalerna hade en komplett dokumentation. Dokumentation av vårdplan och resultat av omvårdnadsåtgärder saknades i en majoritet av journalerna. Dokumentationen var av bättre kvalitet i gruppen yngre äldre patienter vid jämförelse med gruppen äldre äldre patienter. Ingen skillnad av kvalitet i dokumentationen kunde urskiljas utifrån vårdtidens längd då patienter som vårdats mindre än sju dygn eller sju dygn eller mer jämfördes. Konklusion: Kvaliteten av omvårdnadsdokumentationen var inte komplett. Det krävs ytterligare kunskap om förbättringsåtgärder i den kliniskas verksamheten för att säkerställa en omvårdnadsdokumentation av god kvalitet där patienter med höftfraktur vårdas. / Background: The quality of the nursing record can reflect the quality of nursing care provided to patients. Patients with a hip fracture often have an extensive need for care. The nursing record has an important function of describing the nursing process, nursing diagnoses and interventions. Patients with hip fractures often have complex health care needs and the nursing documentation can contribute to patient safety. The quality of the documentation increases with a structured journal. Furthermore, it should be written in a standardized language. Audit of nursing documentation can contribute to quality of care. Motive: Great health risks is a fact when suffering from a hip fracture, especially an already fragile person. The quality of the nursing documentation can contribute to better outcome in patient safety and the length of stay. Aim: To explore the quality of nursing documentation for patients with hip fractures. Methods: A retrospective descriptive and comparative design where audit of nursing records was used to attain the study's aim. A consecutive sample was used, where 40 patients’ health care records of nursing documentation for patients over the age of 60 with a hip fracture in an emergency orthopedic ward were included. The audit instrument Cat-ch-Ing was used. Result: The result showed that the quality was variable; none of the records had a complete documentation. Documentation of care plans were missing in a majority of the records. The documentation was of better quality in the group of younger elderly patients compared to that of older elderly patients. No quality differences were seen based on the length of stay. Conclusion: None of the records had a complete documentation. Further knowledge of how good quality nursing documentation on hip fractur patients can be implement for a sustainable result in clinical activities.

Modern technology affects all aspects of human life, and translation is not an exception. The development of translation technology -computer-assisted translation (CAT) and machine translation (MT)- is causing shifts in professional competencies and significant changes in the work of human translators, who are concerned about the future of their profession. Furthermore, insufficient collaboration between translators and technology developers leads to dissatisfaction with translation tools, contempt for machine translation, and mutual misunderstandings. The aim of this master's thesis is to promote the dialogue between professional translators and translation technology experts. First, a questionnaire survey is conducted among translators; then, its results are consulted with experts in translation technology. It is confirmed that the inevitable changes do not mean that the profession will become obsolete, but rather transformed. In addition, there are various possibilities for collaboration between translators and developers. However, for this collaboration to be as effective as possible, it will be necessary to address the differences between the views of both sides.

<p>Akrilamid&nbsp; je toksična hemijska supst anca koja je već dugi niz godina prisutna u životnoj sredini,&nbsp; jer se kao važan monomer koristi u različite industrijske i laboratorijske svrhe. U poslednjih petnaest godina, akrilamid je postao posebno zanimljiv za &scaron;ire naučne krugove jer&nbsp; se pokazalo da&nbsp; se&nbsp; nalazi&nbsp; i u&nbsp; hrani&nbsp; biljnog porekla, posebno hrani bogatoj skrobom, koja se priprema pečenjem ili prženjem na temperaturama vi&scaron;im od 120&deg;C.&nbsp; Do sada ustanovljeni negativni zdravstveni efekti akrilamida su veoma raznovrsni i mogu biti rezultat delovanja samog&nbsp; akrilamida ili delovanja njegovog metabolita glicidamida koji nastaje&nbsp; in vivo&nbsp; kada se jedan deo molekula akrilamida metaboli&scaron;e oksigenacijom dvostruke veze pomoću enzima citohrom P450 2E1 (CYP2E1). Akrilamid je supstanca koja ima dokazan negativan efekat&nbsp; na organske sisteme kod ljudi i životinja, i koja je svrstana u moguće humane karcinogene. Negativan efekat akrilamida na egzokrini pankreas je poznat, ali o mogućim efektima akrilamida na endokrini pankreas se i dalje veoma malo zna. Ima puno dokaza koji&nbsp; ukazuju na to da akrilamid ima citotoksični efekat koji se&nbsp; manifestuje kroz uticaj na redoks-status ćelija i dovodi do promena u vrednostima biomarkera oksidativnog i nitrozativnog stresa, kao i u aktivnosti antioksidativnih enzima. Pankreas&nbsp; je&nbsp; jedan od ciljnih&nbsp; organa za delovanje akrilamida te je&nbsp; glavni predmet istraživanja&nbsp; doktorske teze&nbsp; bio proučavanje potencijalnog efekta akrilamida na endokrini pankreas pacova.&nbsp; Ispitivanje je vr&scaron;eno na 3&nbsp; eksperimentalne grupe&nbsp; juvenilnih&nbsp; mužjaka pacova soja Wistar,&nbsp; od kojih je&nbsp; jedna grupa bila kontrolna, dok su dve bile tretirane&nbsp; sa akrilamidom u dozama od 25 mg/kg tm i 50 mg/kg tm,&nbsp; 5 dana nedeljno,&nbsp; tokom 3 nedelje. Po isteku tretmana,&nbsp; nakon dekapitacije, kompletno tkivo pankreasa&nbsp; je&nbsp; fiksirano u 10% rastvoru formalina&nbsp; tokom&nbsp; 24&nbsp; h i obrađeno prema&nbsp; standardnoj proceduri za kalupljenje u parafinu.&nbsp; Parafinski kalupi su sečeni na serijske preseke debljine 5 &micro;m, nakon čega su bojeni&nbsp; histohemijskom i imunohistohemijskim metodama.&nbsp; Kod eksperimentalnih grupa posmatrane&nbsp; su&nbsp; histolo&scaron;ke promene na endokrinom pankreasu, sa akcentom na &alpha;-&nbsp; i &beta;-ćelije.&nbsp; Takođe, posmatrana je&nbsp; i&nbsp; ekspresija&nbsp; hormona insulina i glukagona, enzima inducibilne azot -oksi d&nbsp; sintetaze (iNOS) i&nbsp; CYP2E1,&nbsp; kao&nbsp; i ekspresija&nbsp;&nbsp; antioksidativnih enzima&nbsp; katalaza&nbsp; (CAT) i superoksid dismut aza 1 i 2&nbsp; (SOD1 i SOD2)&nbsp; u ćelijama Langerhansovih ostrvaca. Potencijalna promena u funkcionalnosti &beta;-ćelija je ispitana i kroz analizu nivoa glukoze u serumu pacova tretiranih sa akrilamidom.<br />Budući da &beta;-ćelije čine 80% ćelija koje grade Langerhansova ostrvca pankreasa,&nbsp; pored in vivo&nbsp; eksperimenata, ispitana&nbsp; je&nbsp; i toksičnost akrilamida na&nbsp; Rin-5F ćelijsku liniju insulinoma &beta;-ćelija pacova u in vitro uslovima. Glavni cilj in vitro&nbsp; istraživanja je bio&nbsp; da se&nbsp; ispita&nbsp; uticaj&nbsp; rastućih&nbsp; koncentracija akrilamida na preživljavanje tretiranih&nbsp; Rin-5F&nbsp; ćelija, ali i efekat IC₅₀&nbsp; koncentracije ove supstance primenjene&nbsp; tokom&nbsp; različitih vremenskih intervala&nbsp; (0,5, 1, 3, 6, 12 i 24 h)&nbsp; na pojavu oksidativnog i nitrozativnog stresa. Redoks-status Rin-5F ćelija tretiranih&nbsp; sa akrilamidom je ispitan preko analize prisustva biomarkera oksidativnog i nitrozativnog stresa, akrivnosti CAT i ukupne SOD, kao i promene u ekspresiji gena za CAT, SOD1, SOD2&nbsp;&nbsp; i iNOS.&nbsp; Pored toga, analiziran je i efekat istog tretmana na&nbsp; ekspresiju gena za insulin, CYP2E1, Bax i Bcl-2. U okviru teze je pokazano da akrilamid ne dovodi do&nbsp; značajnih promena u histolo&scaron;koj građi, dijametru i broju Langerhansovih ostrvaca&nbsp; kod&nbsp; tretiranih životinja.&nbsp; Primena stereolo&scaron;kih metoda&nbsp; je&nbsp; ukazala&nbsp; na mikrostrukturne promene na&nbsp; endokrinom pankreasu na nivou &alpha;-&nbsp; i &beta;-ćelija. U ovoj tezi je po prvi put pokazano da tretman akrilamidom negativno utiče na broj i povr&scaron;inu &beta;-ćelija pankreasa.&nbsp; U tezi je, takođe,&nbsp; pokazan&nbsp; značajan dozno-zavisni pad u prisustvu insulina u &beta;-ćelijama&nbsp;&nbsp; pankreasa. Uprkos&nbsp; tome, kod&nbsp; akrilamidom tretiranih&nbsp; životinja&nbsp; nije konstatovana&nbsp; promena&nbsp; u&nbsp; koncentraciji serumske glukoze.&nbsp; U&nbsp; ovoj tezi je pokazano da tretman akrilamidom dovodi do&nbsp;&nbsp; statistički značajnog porasta&nbsp; u broju &alpha;-ćelija&nbsp; kod životinja koje su primale nižu dozu tretmana, dok se&nbsp; broj &alpha;-ćelija&nbsp; kod životinja koje su primale vi&scaron;u dozu tretmana&nbsp; ne razlikuje značajno od kontrole.&nbsp; Tretman akrilamidom je doveo do značajnog&nbsp; porasta u količini&nbsp;&nbsp; prisutnog glukagona&nbsp; u &alpha;-ćelijama pankreasa.<br />Tretman akrilamidom nije doveo do značajne promene u ekspresiji CAT, SOD1 i SOD2 u ćelijama Langerhansovih ostrvaca.&nbsp; Kod&nbsp; tretiranih životinja&nbsp; do&scaron;lo do značajnog dozno-zavisnog porasta&nbsp; u ekspresiji&nbsp; enzima iNOS,&nbsp; dok je ekspresija&nbsp; CYP2E1 značajno dozno-zavisno opala&nbsp; nakon tretmana. U&nbsp; tezi je pokazano da tretman akrilamidom negativno utiče na vijabilnost Rin-5F ćelija, i utvrđeno je da IC50&nbsp; koncentracija akrilamida za Rin-5F ćelije iznosi 10 mM.&nbsp; Rezultati teze pokazuju da tretman akrilamidom u IC₅₀&nbsp; koncentraciji u Rin-5F ćelijskoj liniji značajno povećava nivo malondialdehida (MDA) nakon tretmana u trajanju od 1, 12 i 24 h.&nbsp; Isti tretman&nbsp; značajno smanjuje nivo redukovanog GSH nakon tretmana od 1, 3, 6, 12 i<br />24 h, kao i nivo slobodnih&nbsp; &ndash;SH grupa nakon tretmana od 3 i 6 h. Tretman akrilamidom u IC_50&nbsp; koncentraciji signifikantno pojačava aktivnost CAT nakon tretmana od 1 h, dok tretman u trajanju od 12 h značajno smanjuje aktivnost ovog enzima. Ovaj tretman smanjuje aktivnost SOD nakon 1, 12 i 24 h, dok&nbsp; tretman u trajanju od 6 h značajno pojačava aktivnost enzima SOD.&nbsp; U tezi je, takođe, pokazan i veoma značajan porast&nbsp; u nivou prisutnih nitrita,&nbsp; koji&nbsp; je direktno proporcionalan&nbsp; sa nivoom azot-oksida i nivoom akivnosti enzima iNOS.&nbsp; Ovaj&nbsp; nalaz ukazuje na potencijalnu pojavu nitrozati vnog stresa u akrilamidom-tretiranim Rin-5F ćelijama.&nbsp; U&nbsp; tezi je po prvi put pokazano da tretman&nbsp; akrilamidom dovodi do&nbsp; značajnih&nbsp; varijacija&nbsp; u transkripciji gena za iNOS, SOD1, SOD2,&nbsp; CAT,&nbsp; CYP2E1,&nbsp; Bax i Bcl-2 u tretiranim Rin-5F ćelijama, dok isti tretman ne dovodi do&nbsp; promene nivoa&nbsp; transkripcije gena za insulin.&nbsp; Tretman akrilamidom u koncentraciji od 10<br />mM tokom rastućih vremenskih perioda dovodi do porasta u relativnoj količini iRNK<br />gena za iNOS u svim tačkama tretmana, do porasta&nbsp; nivoa&nbsp; iRNK za SOD1 i SOD2 nakon tretmana od 12 i 24 h, kao i do porasta&nbsp; količine&nbsp; iRNK za CAT nakon tretmana od 3 h.&nbsp; U&nbsp; tezi je pokazano&nbsp; i&nbsp; da akrilamid&nbsp; izaziva&nbsp; promene&nbsp; u sintezi&nbsp; iRNK&nbsp; za enzim&nbsp; CYP2E1&nbsp; koji je&nbsp; posebno značajan u kontekstu detoksikacije ove toksične supstance.&nbsp; Porast u transkripciji gena za&nbsp; CYP2E1&nbsp; je uočen&nbsp; nakon tretmana u trajanju od 0,5 i 1 h, dok je&nbsp; do smanjenja transkripcije&nbsp; do&scaron;lo&nbsp; nakon tretmana od 12&nbsp; i 24&nbsp; h.&nbsp; Tretman akrilamidom u koncentraciji od&nbsp; 10 mM tokom rastućih vremenskih perioda dovodi do porasta u relativnoj količini iRNK&nbsp; gena za Bax u svim tačkama tretmana, i do porasta u transkripciji gena za Bcl-2 nakon tretmana od 0,5, 1 i 3 h.<br />Sumirajući&nbsp; sve&nbsp; rezultate&nbsp; ove teze,&nbsp; moze se zaključiti&nbsp; da je endokrini pankreas&nbsp; jedno od&nbsp; ciljnih tkiva, na koje akrilamid ostvaruje vi&scaron;estruki negativni uticaj.</p> / <p>Acrylamide is a toxic chemical used as an important monomer for various industrial and laboratory purposes, which makes it highly present in the environment. In the last fifteen years, acrylamide has become especially interesting for wider scientific circles when it was found in staple foodstuff rich in starch, prepared at temperatures higher than 120&deg;C. The established negative health effects of acrylamide are very diverse and can be the result of the acrylamide action itself or the action of its metabolite glycidamide that occurs in vivo, when acrylamide molecule is metabolized via oxygenation of the double bond by the cytochrome P450 2E1 (CYP2E1). Acrylamide is a substance with a proven adverse effect on humans and animals, and it is classified as a possible human carcinogen. The negative effect of acrylamide on the exocrine pancreas has already been recognized, but the possible effects of acrylamide&nbsp; on endocrine pancreas are still mostly undetermined. There is a significant amount of evidence to suggest that acrylamide exerts a cytotoxic effect which manifests through the changes in level of oxidative and nitrosative stress biomarkers, as well as in the activity of antioxidant enzymes. Since, pancreas is one of the target organs for acrylamide, the main subject of doctoral thesis was to investigate the potential effect of acrylamide on the rat endocrine pancreas. The investigation was conducted on 3 experimental groups of juvenile male Wistar rats, of which one group was the control group, while two groups were treated with acrylamide at doses of 25 mg/kg bw and 50 mg/kg bw, 5 days a week, during 3 weeks. After termination of the treatment, decapitation was performed, and the complete pancreatic tissue was fixed in a 10% formalin solution for 24 h and treated according to the standard paraffin embedding procedure. Paraffin molds were cut into 5 &mu;m thick serial sections, after which they were stained with histochemical and immunohistochemical methods. Histological changes ofthe endocrine pancreas, with the emphasis on &alpha;- and &beta;-cells, were examined in three experimental groups of rats. In addition, the expression of insulin and glucagon hormone, the inducible nitric oxide synthase (iNOS) and CYP2E1 enzymes, and the expression of antioxidative enzymes catalase (CAT) and superoxide dismutases 1 and 2&nbsp; (SOD1 and SOD2) in the islets of Langerhans were also investigated. A potential change in the functionality of &beta;-cells was also examined by analyzing glucose level in the serum of rats treated with acrylamide. In pancreatic islets of Langerhans the majority of cells (&gt;80%) are &beta;-cells. Therefore, in addition to in vivo experiments, the toxicity of acrylamide was examined in vitro on rat insulinoma Rin-5F cell line.The main goal of in vitro research was to investigate the impact of increasing acrylamide concentrations on the viability of treated Rin-5F cells, and also to examine whether IC50 concentration of this substance, applied at different intervals of time (0.5, 1, 3, 6, 12 and 24 h), induce oxidative and nitrosative stress. Redox-status of Rin-5F cells treated with acrylamide was examined by analyzing oxidative and nitrosative stress biomarkers, CAT and total SOD activity, as well as changes in the expression of the CAT, SOD1, SOD2 and iNOS. In addition, the effect of the same treatment on the transcription of the insulin, CYP2E1, Bax and Bcl-2 gene was analyzed.The results of the thesis showed that acrylamide treatment does not lead to significant changes in the histological structure, diameter and number of islets of Langerhans of treated animals. Application of stereological methods indicated microstructural changes of &alpha;- and &beta;-cells ofendocrine pancreas. It has been shown for the first time that treatment with acrylamide negatively affects the number and surface area of pancreatic &beta;-cells. In addition, a significant dose-dependent decline in the amount of insulin in pancreatic &beta;-cells was also demonstrated. However, no change in serum glucose level was observed in treated animals. Acrylamide treatment led to a statistically significant increase in the number of &alpha;-cells in animals receiving a lower dose of treatment, while the number of &alpha;-cells in animals receiving a higher dose of treatment did not differ significantly from the control. Treatment with acrylamide led to a significant increase in the amount of the glucagon in &alpha;-cells. Treatment with acrylamide did not cause a significant change in the expression of CAT, SOD1 and SOD2 in islets of Langerhans. However, there was a significant dosedependent increase in the&nbsp; expression of iNOS enzyme, whereas expression of CYP2E1 significantly decreased in dose-dependent manner in treated animals. Results of the thesis showed that acrylamide exerts a negative effect on the viability of Rin-5F cell line. It has been established that the IC50 concentration of acrylamide for the Rin-5F cell line is 10 mM. The results of the thesis indicate that treatment of Rin-5F cell line with IC50 concentration of acrylamide for 1, 12, and 24 h significantly increased the level of malondialdehyde (MDA). Exposure to acrylamide for 1, 3, 6, 12 and 24 h significantly decreased the level of reduced GSH, while the level of free -SH groups was reduced after 3 and 6 h of acrylamide treatments. Treatment with IC50 concentration of acrylamide significantly enhanced CAT activity after 1 h of acrylamide exposure, while 12 h exposure significantly reduced the activity of this enzyme. Application of acrylamide reduced SOD activity after 1, 12, and 24 h exposure, while 6 h exposure significantly increased the activity of SOD enzymes. Results of the thesis also showed a very significant increase of the nitrite level, which is directly proportional to the level of nitrogen oxide (NO) and the level of the iNOS activity. This finding points to the potential occurrence of nitrosative stress in acrylamide-treated Rin-5F cells. It has been shown for the first time that acrylamide treatment leads to significant variations in transcription of iNOS, SOD1, SOD2, CAT, CYP2E1, Bax and Bcl-2 genes in treated Rin-5F cells, while the same treatment does not affect transcription of the insulin gene. Treatment with acrylamide at a concentration of 10 mM for increasing periods of time leads to an increase in the relative amount of the iNOS gene iRNA at all treatment points. Twelve and and 24 h of acrylamide exposure increased the transcription of the SOD1 and SOD2 genes. Transcription of CAT gene was increased after 3 h&nbsp; ofacrylamide exposure. Furthermore, it has been shown that acrylamide treatment leads to variations in the mRNA synthesis of CYP2E1 gene, which is particularly significant in the context of detoxification of this toxic substance. An increase in the transcription ofthe CYP2E1&nbsp; gene was observed after 0.5 and 1 h of acrylamide exposure, while the reduction of&nbsp; transcription occurred after 12 and 24 h of acrylamide exposure. The treatment with 10 mM acrylamide has led to an increase of the transcription of the Bax gene at all treatment points, and also to an increase of transcription of the Bcl-2 gene after of 0.5, 1, and 3 h of acrylamide exposure. Summarizing all the results of this thesis, it can be concluded that the endocrine pancreas&nbsp; is one of the target tissues of acrylamide, to which this substance exerts a multiple adverse effects.</p>