Submitted by PPG Biotecnologia Farmac?utica (mpbf@pucrs.br) on 2017-12-20T19:17:22Z No. of bitstreams: 1 ANA_SOFIA_OLIVEIRA-DIS.pdf: 959707 bytes, checksum: 29ee77d841ca692f44c6db51a03d5a23 (MD5) / Approved for entry into archive by Caroline Xavier (caroline.xavier@pucrs.br) on 2017-12-26T17:46:20Z (GMT) No. of bitstreams: 1 ANA_SOFIA_OLIVEIRA-DIS.pdf: 959707 bytes, checksum: 29ee77d841ca692f44c6db51a03d5a23 (MD5) / Made available in DSpace on 2017-12-26T17:48:46Z (GMT). No. of bitstreams: 1 ANA_SOFIA_OLIVEIRA-DIS.pdf: 959707 bytes, checksum: 29ee77d841ca692f44c6db51a03d5a23 (MD5) Previous issue date: 2017-06-20 / Dengue fever is an arboviral infection highly common in Brazil, and it corresponds to a major public health problem. Annually, its incidence overcomes 50,000,000, from which about 25,000 are associated to death cases. Due to this high incidence and number of death, it is of great urgency to identify this disease while in an early state. That way, would be possible to avoid any progression of the disease to more severe cases. A major problem related to dengue is that the virus is represented by four subtypes, which are phylogenetically distinct (DENV1, DENV2, DENV3 and DENV4). This means that, although the manifestations and the forms of dissemination are the same, an infection caused by one of the serotypes will not protect against the others. In fact, an infection caused by one of the four serotypes may intensify even more the disease caused by a secondary infection by the three others. One hypothesis that could explain this relationship between heterotypic infections and severe cases of the disease is the ADE hypothesis (antibody-dependent enhancement), which suggests that a secondary infection would cause a cross-reaction between antigen and antibody, preventing the virus of being inactivated. As a consequence, it would result in an increase of the production of inflammatory mediators and vascular permeability that would intensify the disease. Therefore, it?s very important to identify the disease while it is still in an initial stage. However, this early identification is hard and its diagnosis is still limited. Thus, a serological marker would be highly valuable. Recently, serological biomarkers for early diagnosis have become a topic of great interest. These biomarkers have advantages of not being invasive to the patient and inexpensive to produce and analyze. Thus, in this project, we introduce a new technology for the search of such markers, the peptoids. Peptoids are synthetic oligomers, composed of N-substituted glycine units, and can be used for several biological utilities that provide an alternative technology for the investigation and the elucidation of the immune response. Moreover, they have been used and reported as a potential candidate for the search of serological biomarkers due to their chemical stability in fluids where degradative enzymes can be found. In addition to that, the fact that there is no need for a prior knowledge about the target only make them even more attractive for such ?job?. In this project, a combinatorial library of about one million of peptoids was screened in sera from dengue positive patients, as well as negative patients. Hereby we report the potential of this synthetic molecules for the identification of antibodies with clinical relevance present in the patients' serum. The results here reported were generated by 3 consecutive screening steps, where 33 reactive peptoids were identified as potential biomarkers. Because of the impartiality of this technique, we believe that at least one of these 33 peptoids are extremely specific for the studied disease. Currently, they have been sent for the sequencing and re-synthesis step, so that new experiments can be done and the study can continue. We are very excited and we don?t expect nothing less than promising results in the field of diagnosis and dengue. / A dengue ? uma arbovirose de alta incid?ncia no Brasil, e corresponde a um grande problema de sa?de p?blica. Ela possui uma incid?ncia anual de mais de 50.000.000 e resulta num elevado n?mero de casos de ?bito, cerca de 25.000. Devido a isso, ? de grande urg?ncia que possamos identificar esta doen?a enquanto ela ainda se encontra em um estado inicial, para que, deste modo, possamos evitar a progress?o da doen?a para casos mais severos. Um grande problema relacionado a dengue ? que o v?rus ? representado por quatro subtipos, os quais s?o filogen?ticamente distintos (DENV1, DENV2, DENV3 e DENV4). Isso quer dizer que, por mais que as manifesta??es e formas de dissemina??o sejam iguais, a contamina??o por um dos sorotipos n?o ir? proteger contra as demais. Ao contr?rio do que muitos acreditam, a infec??o por um sorotipo pode at? assentuar uma infec??o secund?ria pelos demais. Uma hip?tese para explicar casos mais severos da doen?a devido a infec??es heterot?picas ? a hip?tese de ADE (antibody-dependent enhancement), a qual sugere que a rea??o cruzada resulta na falta da inativa??o viral, aumentando assim a produ??o de mediadores inflamat?rios e permeabilidade vascular devido a uma estimula??o da replica??o do v?rus. Devido a isso, ? de grande necessidade a identifica??o da doen?a antes das manifesta??es severas, e, porque essa identifica??o cl?nica, principalmente no est?gio inicial da doen?a, ? dif?cil, um marcardor sorol?gico seria muito valioso. Marcadores sorol?gicos para diagn?stico de doen?as v?m se tornando um t?pico de recente interesse. Esses biomarcadores t?m a vantagem de n?o serem invasivos para o paciente e baratos de produzir e analizar. Sendo assim, aqui, apresentamos uma nova tecnologia para a busca desses marcadores, os pept?ids. Pept?ids s?o olig?meros sint?ticos, compostos por unidades de glicina N-substitu?da e possuem uma variada utilidade biol?gica que proporcionam uma tecnologia alternativa para a investiga??o e elucida??o da resposta imune. O mesmo, v?m se destacando para busca de biomarcadores sorol?gicos devido a sua estabilidade qu?mica em flu?dos onde enzimas degradativas podem estar presentes e devido a resultados promissores sem a necessidade de um conhecimento pr?vio sobre o ant?geno natural e o seu anticorpo correspondente. Neste projeto, foi realizado a triagem de uma biblioteca combinatorial com cerca de um milh?o de pept?ids, os quais passaram por etapas de triagens em soros de pacientes positivos para dengue, bem como para pacientes negativos. Aqui provamos o potencial dessas mol?culas sint?ticas na identifica??o de anticorpos com relev?ncia cl?nica presente no soro dos pacientes. Os resultados obtidos foram gerados atrav?s de 3 etapas de triagem consecutivas, onde 33 pept?ids reativos foram identificados. Devido a imparcialidade desta t?cnica, acreditamos que pelo menos um desses 33 pept?ids seja extremamente espec?fico para a doen?a estudada. Os mesmos foram enviados para sequenciamento e re-s?ntese para que novos experimentos sejam feitos e para que os estudos continuem. Espera-se resultados muito promissores na ?rea de diagn?stico para dengue.

Ponencia que aborda la experiencia de la Universidad Peruana de Ciencias Aplicadas en la aplicación del ORCID ID, en especial a las tesis.

Three related sedimentary successions located in Arizona, Utah, and California were deposited in basins on proto-North America during the early rifting of Rodinia (~780 Mya). Previous detrital zircon U-Pb maximum ages for the units are inexact, making it difficult to piece together what happened at this point in Earth history. We report better maximum age constraints on these units obtained by subjecting detrital zircons to high-precision CA-ID-TIMS analysis, which provide more exact 206 Pb/238U ages. These new data significantly improve the precision for the base of the ChUMP units, with an average age of 775. 63 ± 0.27 Ma acquired for the bottom of the Chuar Group, where earlier work put the age at 782 Ma. An average age of 775.44 ± 0.73 Ma for the bottom of the Pahrump Group is also younger than the previously reported 787 ± 11 Ma. Zircons of the Uinta Mountain Group provided ages of about 766.88 ± 2.31 Ma, which is on par with an earlier age of 766.4 ± 4.8 Ma. These high precision ages for the young detrital zircons in the ChUMP units improve links between the units and provide better context for geochemical, isotopic, and biological events that occurred during the initial rifting of Rodinia.

<p>ID projects are characterized by a complex network of stakeholders that often lead to the tangledrelationships among various parties. Different stakeholders therefore can exert the influence overan ID project in different ways resulting in both constructive and counter-productive impacts tothe projects. The implementation stage, in many ways, is considered the most significantlyimportant phase in the project life cycle where all the project activities are materialized. Thus,understanding the intricacy of the stakeholders’ impacts to the project implementation is criticalto facilitate the project results.</p><p>A multiple-case study of the two ID projects executed in Vietnam is undertaken with the aim toinvestigate the impacts of the key stakeholders on ID projects beyond the early phases of IDproject life cycle, focusing in particular on the implementation phase. In order to have the wholepicture of the key stakeholders’ impacts to the project implementation, this research alsoexplores the contributing factors of the identified impacts as well as examines how powerful thekey stakeholders are in controlling the decisions making and/or facilitating the projecti mplementation represented through their different degrees of influence.</p><p>Results of the findings suggest both similarities and differences in which the reported impacts ofthe key stakeholders tend to be more counter-productive than constructive to the projectimplementation. The similarities of the findings indicate that the two distinctive projects facecommon issues in the implementation phase whilst the differences can be explained by thespecific circumstances that surround the projects. The representation of the counter-productiveaspects in the findings signify the risks associated with the key stakeholders which is worth while considering in terms of the risk mitigation in the implementation phase of an ID project.</p>

The pancreas is an endodermally derived organ consisting of three major cell lineages. The endocrine cells, organised into the Islets of Langerhans, regulate blood glucose homeostasis by producing and secreting hormones such as glucagon and insulin into the bloodstream. The major part of the pancreas consists however of acinar cells that produce digestive enzymes that are transported via a highly branched ductal system to the duodenum where they function in breakdown of food. Early in pancreas development a dorsal and ventral evagination of the foregut epithelium appear, resulting in the formation of the dorsal and ventral pancreatic bud. These pancreatic buds subsequently grow, branch and differentiate to form the mature pancreas via a process controlled by intrinsic factors, such as transcription factors, and extracellular signals. Insulin promoter factor 1 (Ipf1), also known as Pdx1 (for Pancreatic duodenal homeobox gene 1), is required for pancreas development. Although the evagination of pancreatic buds still occurs in Ipf1/Pdx1 mutant mice, the subsequent proliferation, branching and differentiation is impaired, resulting in complete pancreatic agenesis. Gene array profiling identified several candidate Ipf1/Pdx1 target genes, including FgfR2IIIb, ErbB3, Ptf1a/p48, Pax6 and Nkx6.1, in pancreatic progenitor cells. Together these genes provide a mechanistic explanation for the pancreatic growth arrest observed in Ipf1/Pdx1 deficient mice. In addition, Spondin1, which has not previously been described in the pancreas, was identified to be regulated by Ipf1/Pdx1. The spatial and temporal expression pattern of Spondin1 defines Spondin1 as a marker for early pancreatic progenitor cells. The Notch signalling pathway controls cell type specification and differentiation during pancreas development. The Fringe family of proteins have previously been shown to regulate Notch signalling by altering the interaction between Notch receptors and their ligands, hence affecting the cellular response. Manic Fringe (MFng) is transiently expressed in pancreatic pro-endocrine cells between E9.5 and E14.5. The expression of MFng is regulated by Ngn3, which may suggest a role for MFng in pro-endocrine cell maturation. The lack of a pancreatic phenotype in transgenic mice overexpressing MFng in the pancreatic epithelium and in MFng null mutant mice, however, provide evidence that MFng is dispensable for the specification, differentiation and function of the adult pancreas. Inhibitors of DNA binding (Id) proteins are generally known as inhibitors of differentiation, a feature they mainly perform by forming non-functional heterodimers with bHLH proteins, thereby inhibiting downstream targets of the bHLH proteins. Id proteins also promote cell proliferation by interacting with the cell cycle machinery. In the developing pancreas Id2 and Id3 are co-expressed in an overlapping manner during the period of massive proliferation and expansion of the pancreatic epithelium, suggestive of a role for the Id proteins during these processes. In addition, Id4 expression is also detected in the embryonic pancreas, albeit at lower levels. Gain- and loss- of- function analyses suggest however that specification, differentiation and function of the adult pancreas are largely independent of Id function.

Bit-interleaved coded modulation with iterative decoding (BICM-ID)is a spectral efficient coded modulation technique to improve the performance of digital communication systems. It has been widely known that for fixed signal constellation, interleaver and error control code, signal mapping plays an important role in determining the error performance of a BICM-ID system. This thesis concentrates on signal mapping designs for BICM-ID systems. To this end, the distance criteria to find the best mapping in terms of the asymptotic performance are first analytically derived for different channel models. Such criteria are then used to find good mappings for various two-dimensional 8-ary constellations. The usefulness of the proposed mappings of 8-ary constellations is verified by both the error floor bound and simulation results. Moreover, new mappings are also proposed for BICM-ID systems employing the quadrature phase shift keying (QPSK) constellation. The new mappings are obtained by considering many QPSK symbols over a multiple symbol interval, which essentially creates hypercube constellations. Analytical and simulation results show that the use of the proposed mappings together with very simple convolutional codes can offer significant coding gains over the conventional BICM-ID systems for all the channel models considered. Such coding gains are achieved without any bandwidth nor power expansion and with a very small increase in the system complexity.

Bit-interleaved coded modulation with iterative decoding (BICM-ID)is a spectral efficient coded modulation technique to improve the performance of digital communication systems. It has been widely known that for fixed signal constellation, interleaver and error control code, signal mapping plays an important role in determining the error performance of a BICM-ID system. This thesis concentrates on signal mapping designs for BICM-ID systems. To this end, the distance criteria to find the best mapping in terms of the asymptotic performance are first analytically derived for different channel models. Such criteria are then used to find good mappings for various two-dimensional 8-ary constellations. The usefulness of the proposed mappings of 8-ary constellations is verified by both the error floor bound and simulation results. Moreover, new mappings are also proposed for BICM-ID systems employing the quadrature phase shift keying (QPSK) constellation. The new mappings are obtained by considering many QPSK symbols over a multiple symbol interval, which essentially creates hypercube constellations. Analytical and simulation results show that the use of the proposed mappings together with very simple convolutional codes can offer significant coding gains over the conventional BICM-ID systems for all the channel models considered. Such coding gains are achieved without any bandwidth nor power expansion and with a very small increase in the system complexity.

ID projects are characterized by a complex network of stakeholders that often lead to the tangledrelationships among various parties. Different stakeholders therefore can exert the influence overan ID project in different ways resulting in both constructive and counter-productive impacts tothe projects. The implementation stage, in many ways, is considered the most significantlyimportant phase in the project life cycle where all the project activities are materialized. Thus,understanding the intricacy of the stakeholders’ impacts to the project implementation is criticalto facilitate the project results. A multiple-case study of the two ID projects executed in Vietnam is undertaken with the aim toinvestigate the impacts of the key stakeholders on ID projects beyond the early phases of IDproject life cycle, focusing in particular on the implementation phase. In order to have the wholepicture of the key stakeholders’ impacts to the project implementation, this research alsoexplores the contributing factors of the identified impacts as well as examines how powerful thekey stakeholders are in controlling the decisions making and/or facilitating the projecti mplementation represented through their different degrees of influence. Results of the findings suggest both similarities and differences in which the reported impacts ofthe key stakeholders tend to be more counter-productive than constructive to the projectimplementation. The similarities of the findings indicate that the two distinctive projects facecommon issues in the implementation phase whilst the differences can be explained by thespecific circumstances that surround the projects. The representation of the counter-productiveaspects in the findings signify the risks associated with the key stakeholders which is worth while considering in terms of the risk mitigation in the implementation phase of an ID project.

Vehicular ad-hoc network (VANETs) has been a hot research topic in recent years. In this environment, each vehicle can broadcast messages to other vehicles and inform drivers to change their route right away in order to enhance the efficiency of driving and to avoid accidents. Since vehicles communicate through wireless tunnel, many malicious attacks may occur during the transmission of messages. Consequently, ensuring the correctness of receiving messages and verifying the authenticity of the sender is necessary. Besides, we also need to protect the real identities of vehicles from revealing to guarantee the privacy. To satisfy these security properties, many related researches have been proposed. However, they all have some drawbacks. For example: 1. The cost of the certificate management and the exposure problem of the certificate. 2. Waiting for RSU to verify the messages: Once more vehicles need RSU, RSU will have much more overhead and it can¡¦t achieve real-time authentication. In this thesis, we come up with an anonymous authentication and key agreement scheme based on chameleon hashing and ID-based cryptography in the vehicular communication environment. In our scheme, every vehicle can generate many different chameleon hash values to represent itself, and others can prove the ownership of chameleon hash value. Furthermore, unlike other pseudonymous authentication schemes, we also achieve one-to-one private communication via ID-based cryptography. Finally, we not only overcome some problems in previous works but also fulfill some necessary security requirements in vehicular communication environment.

(骨・関節系理学療法研究部会)(専門領域研究部)