<p>Kontekst savremenih dru&scaron;tvenih promena u sferi obrazovanja i učenja u Republici Srbiji doseže do problema koji prati i obrazovno/vaspitni proces u bolnicama. U oblasti pedago&scaron;kih nauka istraživanja koja se odnose na obrazovno/vaspitni rad u bolnicama su veoma skromna. Cilj istraživanja u doktorskoj disertaciji je da se na osnovu analize utvrdi konzistentnost ciljeva obrazovno/vaspitnog rada u bolnicama Republike Srbije sa ciljevima obrazovnog sistema osnovnih i srednjih &scaron;kola, istraže adekvatni pedago&scaron;ki pristupi u obrazovanju i učenju hospitalizovanih učenika, ustanove parametri stvaranja povoljne klime za učenje u bolničkim uslovima i ponude odgovori na izazove i potrebe obrazovanja učenika na bolničkom lečenju u 21. veku. U tom kontekstu nametnula se potreba za analizom pristupa pedago&scaron;kog rada u bolnicama u zemljama koje u ovoj oblasti imaju dugu i bogatu tradiciju, to su: Kraljevina &Scaron;vedska, Savezna Republika Nemačka, Republika Slovenija, Republika Hrvatska i Republika Mađarska. Ujedno zanimalo nas je da li postojeće obrazovanje i učenje u bolnicama Republike Srbije ima značajnija odstupanja u odnosu na navedene zemlje.<br />Ovako koncipiran istraživački rad opredelio nas je za primenu sledećih metodolo&scaron;kih pristupa: istorijske i komparativne metode i metode teorijske analize. Na&scaron;e istraživanje je potvrdilo osnovna očekivanja da su ciljevi obrazovanja/vaspitanja u bolnicama Republike Srbije konzistentni sa ciljevima osnovnog i srednjeg obrazovanja koji se odnose na redovne &scaron;kole s obzirom da proističu iz Strategija razvoja obrazovanja u Republici Srbiji do 2020. godine, Zakona o osnovama sistema obrazovanja i vaspitanja u Republici Srbiji i Zakona o osnovnom i srednjem obrazovanju. Zaključak je da se pristupi obrazovno/vaspitnom radu u bolnicama Republike Srbije razlikuju u smislu doslednosti po&scaron;tovanja prava deteta, upravljanju i organizaciji obrazovno/vaspitnog rada, teorijskim pristupima i u parametrima stvaranja povoljne klime za obrazovanje i učenje u bolnicama, odnosno da su potrebne promene u pristupu obrazovno/vaspitnog rada sa učenicima u bolnicama Republike Srbije kako bi se on unapredio. U okviru ovih zaključaka mi&scaron;ljenja smo da je potrebno animirati pedago&scaron;ku i dru&scaron;tvenu javnost za veću podr&scaron;ku i značaj ovom obliku pedago&scaron;kog rada.</p> / <p>The context of modern social changes in the sphere of education and learning in the Republic of Serbia reaches the problems that follow the educational process in hospitals. In the field of pedagogical sciences research related to education / educational work in hospitals are very modest. The purpose of this research was to find, on the basis of analysis and determination of the consistency of the goals of the educational process in hospitals in the Republic of Serbia with the goals of the educational systems of elementary and high schools, adequate pedagogical approaches in the education of hospitalized students, to give an account of parameters for the creation of suitable climate for learning in hospital conditions, and give answer to the challenges and needs of the education of students undergoing hospital treatments in the 21st century.<br />In that context, there was a need for analysis of the approach to the pedagogical work with hospitalized students in the countries which have a long tradition in this field and those are: the Kingdom of Sweden, the Federal Republic of Germany, the Republic of Slovenia, the Republic of Croatia and the Republic of Hungary. We were also interested in discovering if the existing education and learning in hospitals in the Republic of Serbia have significant deviations from those observed in the aforementioned countries.<br />Our research being conceptualized thus, we opted for the application of the following methodological approaches: historical and comparative methods and the method of theoretical analysis. The research confirmed our basic expectations that the goals of education in hospitals in the Republic of Serbia are consistent with the goals of the systems of elementary and high education in regular schools, as they stem from The Education Development Strategy in the Republic of Serbia until 2020, Law on the Basis of Education System in the Republic of Serbia, as well as the Law on Primary and Secondary Education.<br />The conclusion has been reached that the educational work with students undergoing medical treatments in the Republic of Serbia differs in the field of respect of the children&rsquo;s rights, management and organization of educational work, theoretical approaches, and the parameters for the suitable climate for education and learning in hospital conditions, i.e. that the changes in the educational work with hospitalized students in the Republic of Serbia are needed for the enhancement of this kind of pedagogical work. It has also been concluded that this kind of pedagogical work is not given enough importance in the professional pedagogical<br />and social public of the Republic of Serbia. Wit hen the conclusion of these opinions thet we need animate pedagogical and social public foe greater support for the pedagogical work.</p>

The upland (Pseudacris feriarum) and midland (P. triseriata) chorus frogs are closely related cryptic species that are best distinguished genetically. The distribution of these species within the Commonwealth of Kentucky has previously been defined by only a handful of genetic samples, making delineation of range limits for each species difficult. Accurate understanding of species distributions, and the genetic structure within them, are vitally important for conservation management of amphibian species. In this study, I have collected genetic samples from across the putative ranges of P. triseriata and P. feriarum in Kentucky and used next-generation sequencing technology to generate more fine-scale estimates of species ranges. The genetic data generated in this study support the delineation of two species in Kentucky, and the species assignments of all individuals and populations are in general concordance with the previously hypothesized species distributions. However, I have identified two previously unrecognized contact zones for these species and revealed areas of hybridization. By delineating species distributions and identifying potentially important regions of genetic admixture, this study will be informative to future conservation management and conservation genetic research of chorus frogs in Kentucky.

<p>The eukaryotic genome integrity is safeguarded by the DNA damage response, which is composed of a network of signal transduction pathways that upon genotoxic stresses, arrest cell cycle progression, motivate repair processes, or induce apoptosis or senescence when cells incur irreparable DNA damage. During this process, DNA damage-induced post-translational modifications, most notably protein phosphorylation, of a variety of DNA damage-responsive proteins has been shown to mediate the initiation, transduction and reception of the DNA damage signals, resulting in alterations of their stability, activities or subcellular localizations, ultimately leading to activation of various downstream effector pathways. </p><p>While a lot has been elucidated on the downstream events of the DNA damage response, little is known about how DNA damage is detected. Two still ongoing studies of this dissertation attempt to address this question. Our preliminary work on ATM indicates that serine 2546 is critical for its kinase activity. Substitution of this residue with phosphomimetic aspartate, but not nonphosphorylable alanine, abrogates the kinase activity of ATM and fails to rescue the checkpoint-deficient phenotype exhibited by the ATM-deficient cells, suggesting that removal of an inhibitory phospho group at S2546 might be required for the activation of ATM. In another study, we identified a novel DNA-damage responsive threonine residue (T622) in Rad17, which undergoes ATM/ATR-dependent phosphorylation in vitro and in vivo. Ectopic expression of a phosphodeficient mutant (T622A) of Rad17, but not its wild-type control, shows a pronounced defect in sustaining Chk1 phosphorylation and the corresponding G2/M checkpoint upon DNA damage, suggesting that phosphorylation at T622 might complement that on the two previously reported phosphorylation sites, S635 and S645, to mediate G2/M checkpoint activation while the latter is primarily responsible for intra-S phase checkpoint. </p><p>Although a large amount of knowledge has been accumulated about the initiation and activation process of the DNA damage response, how cells recover, the equally important flip side of the response, has remained poorly understood. We have found that in cells recovering from replication stress, RPA32 phosphorylation at ATM/ATR-responsive sites T21 and S33, which reportedly suppresses DNA replication and recruiting other checkpoint and repair proteins to the DNA lesions, is reversed by the serine/threonine protein phosphatase 2A (PP2A). Cells with a RPA32 persistent-phosphorylation mimic (T21D/S33D) exhibit normal checkpoint activation and re-enter the cell cycle normally after recovery, but display a pronounced defect in the repair of DNA breaks. These data indicate that PP2A-mediated RPA32 dephosphorylation may be a required event during the repair process in the DNA damage response. </p><p>In summary, these studies in this dissertation highlight the importance of reversible phosphorylation and dephosphorylation in the modulation of the DNA damage response. What's more, they also extend our knowledge and deepen our understanding of this process by revealing that dephosphorylation may positively regulate the activation of cell cycle checkpoints, which is seemingly dominated by protein phosphorylation upon DNA damage, that phosphorylation of certain checkpoint proteins at different sites may result in distinct consequences, and that dephosphorylation of some activated checkpoint/repair proteins may function as an important mechanism for cells to recover from the DNA damage response.</p> / Dissertation

Zugl.: Paderborn, University, Diss., 2005.

Zugl.: Berlin, Techn. Univ., Diss., 2008

Thèse (Ph. D.) -- Université Laval, 1997. / Bibliogr.: f. [166]-192. Publié aussi en version électronique.

Universiẗat, Diss., 2002--Dortmund.

Next-Generation Sequencing (NGS) technologies have been evolving at an unparalleled pace. The ability to generate millions of base pairs of data in a short time and at lower cost than previously has led to a dramatic expansion of technologies within the field. This dissertation discusses the development and validation of new methods for assessing genomic variation, dynamic changes in gene expression, high-accuracy sequencing, and analysis of recombination events. By reducing the cost of analyzing many samples for genetic divergence by genotyping the same region of the genome in multiple samples, researchers can pursue investigations on a larger scale. Next-RAD (Nextera fragmentation with Restriction-Associated Digestion) allows analysis of a uniform subset of loci between organisms for comparison of populations by genetic differences with reduced burdens of cost and data analysis. This method was applied to the Anopheles darlingi mosquito to identify three distinct species that were thought to be a uniform population. The lowering cost of large-scale sequencing investigations allows for massively parallel analysis of genomic function in a single assay. Regulation of gene expression in response to stress is a complex process which can only be understood by analyzing many pathways in tandem. A novel method is described which quantifies on a genome-wide scale the expression of millions of randomer tags driven by associated transcriptional enhancers. This method provides novel data in the form of high-resolution analysis of gene regulation. Aside from generating novel data types, another force behind development of new technologies is to improve data quality. One limitation of NGS is the inherent error rate. PELE-Seq (Paired End Low Error Sequencing) was developed to address this problem, by employing completely overlapping paired-end reads as well as a dual barcoding strategy to eliminate incorrect sequences resulting from final library amplification. This new tool improves data quality dramatically. Finally, the rapid expansion of tools necessitates the identification of new applications for these technologies. To this end, 10x Genomics Linked-Read sequencing was employed to identify recombination events in multiple species. The haplotype-resolved nature of the data generated from such assays has many promising applications.

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2017-03-09T23:04:25Z No. of bitstreams: 1 VanessaDeAlmeidaDantas_TESE.pdf: 3738312 bytes, checksum: de5a62b1338eeb90aff1798f2d02d2e7 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2017-03-14T00:07:59Z (GMT) No. of bitstreams: 1 VanessaDeAlmeidaDantas_TESE.pdf: 3738312 bytes, checksum: de5a62b1338eeb90aff1798f2d02d2e7 (MD5) / Made available in DSpace on 2017-03-14T00:07:59Z (GMT). No. of bitstreams: 1 VanessaDeAlmeidaDantas_TESE.pdf: 3738312 bytes, checksum: de5a62b1338eeb90aff1798f2d02d2e7 (MD5) Previous issue date: 2016-08-31 / O Rad?nio (Rn-222) ? um g?s nobre-radiativo, incolor, inodoro, ins?pido, denso (9,73 kg/m3) e altamente sol?vel na ?gua (solubilidade de 1,67x10-4 a 25?C e 1Atm) que, com exce??o do Di?xido de Carbono, ? o g?s com maior solubilidade na Atmosfera. Neste estudo foram analisadas a varia??o e correla??o das vari?veis meteorol?gicas com as emana??es de Rad?nio e ?ons atmosf?ricos em um ambiente de floresta equatorial e Caatinga do estado do Rio Grande do Norte, Brasil. Especificamente em biomas do Nordeste do Brasil (NEB) pouco se sabe sobre o comportamento Rn-222, no que diz respeito ? distribui??o nos diferentes n?veis da baixa troposfera, a exemplo da Mata Atl?ntica Dunar e Caatinga. Assim, o objetivo foi de investigar a rela??o entre vari?veis meteorol?gicas, as concentra??es atmosf?ricas de Rn-222 e ?ons atmosf?ricos para o per?odo caracterizado como seco e chuvoso, no munic?pio de Apod?-RN e Parnamirim-RN no per?odo seco, inseridos no bioma de Caatinga e Mata Atl?ntica Dunar Nordestina que abrange cerca de 800.000 Km2 e 19.427 km?, respectivamente. As medidas foram realizadas a 1,5 m do solo. Coletaram-se dados de temperatura do ar, umidade relativa, velocidade e dire??o do vento e press?o atmosf?rica bem como concentra??es de Rn-222 e de ?ons atmosf?ricos. Os resultados mostraram um padr?o bimodal no comportamento di?rio da concentra??o de Rn-222, nas primeiras horas da manh? observado em todos os dias. Comportamento semelhante foi observado para a concentra??o de ?ons entre 04:00 e 05:00 HL (Hor?rio Local) em Parnamirim. Em Apod?, o ciclo di?rio da concentra??o de Rn-222 mostrou um padr?o semelhante ao de Parnamirim, com um m?ximo principal de 29,38 Bq/m3 e 24,00 Bq/m3 durante a esta??o seca e chuvosa, respectivamente, em torno de 17:00 HL e um m?ximo secund?rio ?s 15:00 HL com 27,37 Bq/m3 (esta??o seca) e 19,00 Bq/m3 (esta??o chuvosa). Estes ciclos s?o consistentes com situa??es de uma atmosfera estaticamente neutra devido ? transi??o de per?odos de est?vel para regimes inst?veis (primeiro pico) e inst?veis para est?vel (segundo pico) de acordo com o n?mero de Richardson Bulk tamb?m observado neste estudo. Atrav?s do modelo de regress?o linear m?ltipla via an?lise de componentes principais as vari?veis meteorol?gicas que se mostraram mais correlacionadas com a concentra??o de Rn-222, com explica??o de 88% foram a umidade relativa, velocidade do vento e a radia??o solar global. / The Radon (Rn-222) is a radioactive noble-gas, colorless, odorless, tasteless, dense (9.73 kg / m3) and highly soluble in water (solubility 1,67x10-4 25 ? C and 1 atm) that, except for carbon dioxide is the gas with greater solubility in the atmosphere. This study analyzed the variation and correlation of meteorological variables with the emanations of Radon and atmospheric ions in a rainforest environment and Caatinga in the state of Rio Grande do Norte, Brazil. Specifically, in Northeast biomes of Brazil (NEB) little is known about the Rn-222 behavior in relation to the distribution in the different levels of the lower troposphere, such as the Atlantic Forest Dune and Caatinga. The objective was to investigate the relationship between meteorological variables, atmospheric concentrations of Rn-222 and atmospheric ions to the period characterized as dry and rainy in the municipality of Apodi-RN and Parnamirim-RN in the dry season, entered in the biome Caatinga and Northeast Atlantic Forest Dune which covers about 800,000 km2 and 19,427 square kilometers respectively. The measurements were taken at 1.5 m above the ground. Collected from the air temperature data, relative humidity, wind speed and direction, atmospheric pressure and Rn-222 and atmospheric ion concentrations. The results showed bimodal pattern in the daily behavior of the concentration of Rn-222, in the early morning hours observed in every day. Similar behavior was observed for the concentration of ions between 04:00 and 05:00 HL (Local Time) in Parnamirim. In Apodi, the daily cycle of concentration of Rn-222 showed a pattern similar to Parnamirim, with a maximum principal of 29.38 Bq / m3 and 24.00 Bq / m3 during the dry and rainy seasons, respectively, around 17:00 HL and a secondary maximum at 15:00 HL with 27.37 Bq / m3 (dry season) and 19.00 Bq / m3 (rainy season). These cycles are consistent with conditions of a statically neutral atmosphere due to the periods of transition from stable to unstable regimes (first peak) and unstable stable (second peak) according to the Richardson number Bulk also observed in this study. Through multiple linear regression model via principal component analysis the meteorological variables that were more correlated with the concentration of Rn-222, with 88% explanation were the relative humidity, wind speed and solar radiation.

The small GTP-binding protein Rad (RRAD, Ras associated with diabetes) is the founding member of the RGK (Rad, Rem, Rem2, and Gem/Kir) family that regulates voltage-dependent calcium channel function. Given its expression in both excitable and non-excitable cell types, the control mechanisms for Rad regulation and the potential for novel functions for Rad beyond calcium channel modulation are open questions. Here we report a novel interaction between Rad and Enigma, a scaffolding protein that also binds to the E3 ubiquitin ligase Smad ubiquitin regulatory factor 1 (Smurf1). Overexpression of Smurf1, but not of a catalytically inactive mutant enzyme, results in ubiquitination of Rad and down regulation of Rad protein levels. The Smurf1-mediated decrease in Rad levels is sensitive to proteasome inhibition and requires the ubiquitination site Lys204, suggesting that Smurf1 targets Rad for degradation. Rad protein levels, but notably not mRNA levels, are increased in the hearts of Enigma-/- mice, leading to the hypothesis that Enigma may function as a scaffold to enhance Smurf1 regulation of Rad. In addition to ubiquitination, phosphorylation of RGK proteins represents another potential means of regulation. Indeed, Rem phosphorylation has been shown to abolish calcium channel inhibition. We demonstrate that b-adrenergic signaling promotes Rad phosphorylation at Ser39. Rad Ser39 phosphorylation is correlated with a decrease in the interaction between Rad and the CaVb subunit of the calcium channel and an increase in Rad binding to 14-3-3. Interestingly, Enigma overexpression promotes an increase in Rad Ser39 phosphorylation as well. Despite an interaction between Enigma and the CaV1.2 calcium channel subunit, overexpression of Enigma had no effect on Rad-mediated channel inhibition. Thus, Rad Ser39 phosphorylation alters its association with the calcium channel, but its impact on calcium channel regulation has yet to be determined. Finally, we report a novel function for Rad in the regulation of bone homeostasis. Rad deletion in mice results in a significant decrease in bone mass. Dynamic histomorphometry in vivo and primary calvarial osteoblast assays in vitro demonstrate that bone formation and osteoblast mineralization rates are depressed in the absence of Rad. Microarray analysis revealed that canonical osteogenic gene expression is not altered in Rad-/- osteoblasts; instead robust up-regulation of matrix Gla protein (MGP, +11-fold), an inhibitor of mineralization and a protein secreted during adipocyte differentiation, was observed. Strikingly, Rad deficiency also resulted in significantly higher bone marrow adipose tissue (BMAT) levels in vivo and promoted spontaneous in vitro adipogenesis of primary calvarial osteoblasts. Adipogenic differentiation of WT osteoblasts resulted in the loss of endogenous Rad protein, further supporting a role for Rad in the control of BMAT levels. These findings reveal a novel in vivo function for Rad signaling in the complex physiological control of skeletal homeostasis and bone marrow adiposity. In summary, this dissertation expands our understanding of Rad regulation through identification of a novel binding partner and characterization of post-translational regulatory mechanisms for Rad function. This work also defines a new role for Rad that may not depend upon its calcium channel regulatory properties: regulation of the bone-fat balance. These findings suggest that the regulation of Rad GTPase is likely more complex than guanine nucleotide cycling and that functions of Rad in non-excitable tissues warrant further study.