The current generation of sequencing technologies has led to significant advances in identifying novel disease-associated mutations and generated large amounts of data in a highthroughput manner. Such data in conjunction with clinical routine data are proven to be highly useful in deriving population-level and patient-level predictions, especially in the field of cancer precision medicine. However, data harmonization across multiple national and international clinical sites is an essential step for the assessment of events and outcomes associated with patients, which is currently not adequately addressed. The Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM) is an internationally established research data repository introduced by the Observational Health Data Science and Informatics (OHDSI) community to overcome this issue. To address the needs of cancer research, the genomic vocabulary extension was introduced in 2020 to support the standardization of subsequent data analysis. In this review, we evaluate the current potential of the OMOP CDM to be applicable in cancer prediction and how comprehensively the genomic vocabulary extension of the OMOP can serve current needs of AI-based predictions. For this, we systematically screened the literature for articles that use the OMOP CDM in predictive analyses in cancer and investigated the underlying predictive models/tools. Interestingly, we found 248 articles, of which most use the OMOP for harmonizing their data, but only 5 make use of predictive algorithms on OMOP-based data and fulfill our criteria. The studies present multicentric investigations, in which the OMOP played an essential role in discovering and optimizing machine learning (ML)-based models. Ultimately, the use of the OMOP CDM leads to standardized data-driven studies for multiple clinical sites and enables a more solid basis utilizing, e.g., ML models that can be reused and combined in early prediction, diagnosis, and improvement of personalized cancer care and biomarker discovery.

Diaminopropionate ammonia lyase (DAPAL) which belongs to the  class of PLP enzymes is reported only from prokaryotes. It is involved in the removal of two amino groups from its substrate, diaminopropionate, to form ammonia and pyruvate. DAPAL from Escherichia coli (eDAPAL) and Salmonella typhimurium (sDAPAL) was cloned, over expressed and purified using either affinity chromatography or conventional procedures. It was observed that eDAPAL (90 units / mg) was comparatively less active than sDAPAL (200 units / mg). Also the enzymes with the N-terminal His tag were found to be many fold less active than the enzymes without tag. DAPAL had a characteristic absorption maximum at 414nm due to the Schiff`s linkage between PLP and the € - amino group of the active site lysine residue. The apoenzyme was prepared by reaction with L-cysteine, and the resulting thiazolidine complex was easily dialyzed. On reconstitution with PLP, complete regain of absorption spectrum and 60% activity was seen. All the three enzymes (apo-, holo and reconstituted), when subjected to gel filtration chromatography were found to be homodimers of 88 kDa. The active site lysine 78 was mutated to glutamine, and the enzyme was purified to homogeneity. In the mutant enzyme PLP continued to be bound at the active site, but in a different orientation with an absorbance maximum at 406nm. The K78Q enzyme had negligible activity as compared to the wild type enzyme confirming the role of K78 in catalysis. Only a few of the enzymes of the  class have been investigated for their unfolding pathways. Urea induced unfolding studies on sDAPAL revealed that at lower concentrations of urea there was a loss in activity due to the disruption of Schiff's linkage. No gross conformational changes were observed at these concentrations of urea as seen from fluorescence and gel filtration experiments. Increase in concentration of urea led to unfolding of the protein thereby causing a shift in fluorescence maximum from 340nm to 357 nm due to the exposure of the buried tryptophans to the less hydrophobic environment. A considerable amount of aggregation was seen at intermediate urea concentrations, which was possibly the reason for the inability of the protein to refold completely. Based on the results, a concerted mechanism for dissociation and unfolding was proposed for sDAPAL. Aminooxy compounds, which are mechanism-based inhibitors for PLP enzymes have been used as drugs against various disorders for the last few decades. In order to probe the mechanism and efficiency with which these compounds inhibit sDAPAL, cycloserine (D and L), methoxyamine (MA) and aminooxyacetic acid (AAA) were chosen for the inhibition studies. The inhibition rates were measured by monitoring decrease in absorbance at 414nm, increase in the range of 320-330nm due to the product formation and loss of activity upon incubation with the inhibitor. It was seen that both the enantiomers of cycloserine were equally effective in disrupting the Schiff’s linkage with the second order rate constants of 15.8 and 36 M -1 sec –1 respectively. Spectral measurements showed two isosbestic points in the case of DCS and one in the case of LCS. Product of this inhibition reaction was identified to be a heat and acid stable compound namely a hydroxyisooxazole derivative of PMP. It was similar in nature to that reported from GABA aminotransferase. These results showed that unlike in the case of alanine racemase, sDAPAL could be inhibited equally well by both the enantiomers. The inhibition studies with the other two inhibitors namely AAA and MA, showed AAA to be more efficient at disrupting the Schiff’s linkage and causing inactivation of the enzyme. The visible absorbance spectrum showed a single isosbestic point in both the cases, indicative of a single step involved in the formation of the final product. The elution profile of the product of the enzymatic as well as non-enzymatic reactions on a C-18 HPLC column was similar and the product was identified to be an oxime. These inhibitors reacted with sDAPAL many fold better than the other PLP dependent enzymes and therefore these compounds can serve as potential drugs for sDAPAL.

Submitted by Victor de Abreu Campos null (victorde.ac@gmail.com) on 2017-09-27T02:41:28Z No. of bitstreams: 1 dissertacao.pdf: 5473435 bytes, checksum: 1e76ecc15a4499dc141983740cc79e5a (MD5) / Approved for entry into archive by Monique Sasaki (sayumi_sasaki@hotmail.com) on 2017-09-28T13:43:21Z (GMT) No. of bitstreams: 1 campos_va_me_sjrp.pdf: 5473435 bytes, checksum: 1e76ecc15a4499dc141983740cc79e5a (MD5) / Made available in DSpace on 2017-09-28T13:43:21Z (GMT). No. of bitstreams: 1 campos_va_me_sjrp.pdf: 5473435 bytes, checksum: 1e76ecc15a4499dc141983740cc79e5a (MD5) Previous issue date: 2017-08-31 / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / A quantidade vertiginosa de conteúdo multimídia acumulada diariamente tem demandado o desenvolvimento de abordagens eficazes de recuperação. Nesse contexto, ferramentas de reconhecimento de locutor capazes de identificar automaticamente um indivíduo pela sua voz são de grande relevância. Este trabalho apresenta uma nova abordagem de reconhecimento de locutor modelado como um cenário de recuperação e usando algoritmos de aprendizado não supervisionado recentes. A abordagem proposta considera Coeficientes Cepstrais de Frequência Mel (MFCCs) e Coeficientes de Predição Linear Perceptual (PLPs) como características de locutor, em combinação com múltiplas abordagens de modelagem probabilística, especificamente Quantização Vetorial, Modelos por Mistura de Gaussianas e i-vectors, para calcular distâncias entre gravações de áudio. Em seguida, métodos de aprendizado não supervisionado baseados em ranqueamento são utilizados para aperfeiçoar a eficácia dos resultados de recuperação e, com a aplicação de um classificador de K-Vizinhos Mais Próximos, toma-se uma decisão quanto a identidade do locutor. Experimentos foram conduzidos considerando três conjuntos de dados públicos de diferentes cenários e carregando ruídos de diversas origens. Resultados da avaliação experimental demonstram que a abordagem proposta pode atingir resultados de eficácia altos. Adicionalmente, ganhos de eficácia relativos de até +318% foram obtidos pelo procedimento de aprendizado não supervisionado na tarefa de recuperação de locutor e ganhos de acurácia relativos de até +7,05% na tarefa de identificação entre gravações de domínios diferentes. / The huge amount of multimedia content accumulated daily has demanded the development of effective retrieval approaches. In this context, speaker recognition tools capable of automatically identifying a person through their voice are of great relevance. This work presents a novel speaker recognition approach modelled as a retrieval scenario and using recent unsupervised learning methods. The proposed approach considers Mel-Frequency Cepstral Coefficients (MFCCs) and Perceptual Linear Prediction Coefficients (PLPs) as features along with multiple modelling approaches, namely Vector Quantization, Gaussian Mixture Models and i-vector to compute distances among audio objects. Next, rank-based unsupervised learning methods are used for improving the effectiveness of retrieval results and, based on a K-Nearest Neighbors classifier, an identity decision is taken. Several experiments were conducted considering three public datasets from different scenarios, carrying noise from various sources. Experimental results demonstrate that the proposed approach can achieve very high effectiveness results. In addition, effectiveness gains up to +318% were obtained by the unsupervised learning procedure in a speaker retrieval task. Also, accuracy gains up to +7,05% were obtained by the unsupervised learning procedure in a speaker identification task considering recordings from different domains. / FAPESP: 2015/07934-4

Die Dissertation befasst sich mit der Untersuchung der Ko-Expression des GFAP- und des PLP-Promotors in Müllerzellen der Netzhaut transgener Mäuse. Die verwendete Mauslinie ist tripel-transgen für den GFAP- und den PLP-Promotor sowie für einen ROSA26-Reporter. Durch die Quantifizierung der EYFP-Expression in Müllerzellen konnte gezeigt werden, dass es nach akuter ischämischer Schädigung sowie einer angeborenen retinalen Degeneration in Müllerzellen zu einer Aktivierung des oligodendrozytären PLP-Promotors kommt. Weiterhin wurde festgestellt, dass die Aktivierung des Transkriptionsfaktors Sox-9, der sowohl für die Entwicklung der Müllerzellen als auch für die Oligodendrogenese von entscheidender Rolle ist, mit dieser Promotoraktivierung korreliert. Diese Ergebnisse implizieren, dass Müllerzellen im Rahmen ihrer Stammzelleigenschaften in der Lage sind, auf embryonale Entwicklungsprozesse, die auch die oligodendrozytäre Zellreihe beinhalten, zurückgreifen zu können.

Die Dissertation befasst sich mit der Untersuchung der Ko-Expression des GFAP- und des PLP-Promotors in Müllerzellen der Netzhaut transgener Mäuse. Die verwendete Mauslinie ist tripel-transgen für den GFAP- und den PLP-Promotor sowie für einen ROSA26-Reporter. Durch die Quantifizierung der EYFP-Expression in Müllerzellen konnte gezeigt werden, dass es nach akuter ischämischer Schädigung sowie einer angeborenen retinalen Degeneration in Müllerzellen zu einer Aktivierung des oligodendrozytären PLP-Promotors kommt. Weiterhin wurde festgestellt, dass die Aktivierung des Transkriptionsfaktors Sox-9, der sowohl für die Entwicklung der Müllerzellen als auch für die Oligodendrogenese von entscheidender Rolle ist, mit dieser Promotoraktivierung korreliert. Diese Ergebnisse implizieren, dass Müllerzellen im Rahmen ihrer Stammzelleigenschaften in der Lage sind, auf embryonale Entwicklungsprozesse, die auch die oligodendrozytäre Zellreihe beinhalten, zurückgreifen zu können.:Inhaltsverzeichnis ....................................................................................................................... 3 Bibliographische Darstellung ..................................................................................................... 5 Abkürzungsverzeichnis und Erläuterungen ................................................................................ 6 1 Einleitung ............................................................................................................................ 8 1.1 Die Retina als Teil des Auges ................................................................................................. 8 1.1.1 Aufbau .............................................................................................................................. 8 1.2 Die gliale Müllerzelle ............................................................................................................ 12 1.2.1 Definition und Morphologie der Müllerzellen ............................................................... 12 1.2.2 Funktion .......................................................................................................................... 13 1.2.3 Ursprung und Ontogenese der Müllerzelle ..................................................................... 14 1.3 Erkrankungen der Netzhaut .................................................................................................. 15 1.3.1 Akute Läsionen ............................................................................................................... 15 1.3.2 Chronische Erkrankungen der Netzhaut ......................................................................... 15 1.3.3 Die Rolle der Müllerzelle in der erkrankten Retina ....................................................... 16 1.4 Mausgenetik .......................................................................................................................... 18 1.4.1 Das Cre-loxP-System ..................................................................................................... 18 1.5 Pax-6 und Sox-9: Transkriptionsfaktoren spezifizieren das Zellschicksal ........................... 24 1.5.1 Die PAX-Familie ............................................................................................................ 24 1.5.2 SOX-9-Gene ................................................................................................................... 25 2 Ziele .................................................................................................................................. 26 3 Material und Methoden ..................................................................................................... 27 3.1 Material ................................................................................................................................. 27 3.1.1 Chemikalien .................................................................................................................... 27 3.1.2 Antikörper ....................................................................................................................... 27 3.1.3 Größenstandards ............................................................................................................. 28 3.1.4 Mauslinien ...................................................................................................................... 29 3.1.5 Geräte ............................................................................................................................. 31 3.2 Methoden .............................................................................................................................. 31 3.2.1 Genotypisierung transgener Mäuse ................................................................................ 31 3.2.2 Akute retinale Läsion durch Anlegen eines erhöhten Augeninnendrucks („high intraocular pressure“, HIOP) .......................................................................................... 37 3.2.3 Herstellung und Fixierung der retinalen Gewebsproben ................................................ 37 3.2.4 Immunhistochemische Färbungen .................................................................................. 38 3.2.5 Mikroskopische Auswertung .......................................................................................... 39 3.2.6 Datenverarbeitung und Statistik ..................................................................................... 41 4 Ergebnisse ......................................................................................................................... 42 4.1 Technische Aspekte: Vergleich der Quantifizierung in Ganzpräparate und Querschnitte ... 42 4.1.1 Vergleich der Abbildungen ............................................................................................ 42 4.1.2 Auszählung Retina-Ganzpräparate ................................................................................. 43 4.1.3 Auszählung der Zellen in Querschnitten der Netzhaut ................................................... 45 4.1.4 Vergleich der Quantifizierung von Ganzpräparaten und Querschnitten ........................ 46 4.1.5 Quantifizierung ............................................................................................................... 48 4.2 Analyse der Reporterexpression in der Retina tripel-transgener Mäuse ............................... 49 4.2.1 Quantitative Auswertung GS-positiver Müllerzellen ..................................................... 49 4.2.2 Quantitative Auswertung EYFP-positiver Müllerzellen ................................................ 51 4.2.3 Auswertung des prozentualen Anteils der EYFP-positiven Müllerzellen ...................... 53 4.3 Auswertung der Transkriptionsfaktorexpression von Pax-6 und Sox-9 ............................... 56 4.3.1 Auswertung der Pax-6-positiven Müllerzellen ............................................................... 57 4.3.2 Auswertung der Sox-9-positiven Müllerzellen .............................................................. 60 5 Diskussion ......................................................................................................................... 63 5.1 Die GFAP-Expression in der Müllerzellgliose ..................................................................... 63 5.2 Auswertung und Vergleich der retinalen Ganzpräparate und Querschnitte ......................... 64 5.3 Die Untersuchung der Promotoraktivität nach retinaler Ischämie ........................................ 65 5.4 Die Untersuchung der Promotoraktivität bei angeborener retinaler Degeneration ............... 66 5.5 Die Rolle der Transkriptionsfaktoren Pax-6 und Sox-9 ........................................................ 68 5.5.1 Pax-6 ............................................................................................................................... 68 5.5.2 Sox-9 ............................................................................................................................... 69 5.6 Einordnung der Ergebnisse in die Zellbiologie der Müllerzelle ........................................... 72 6 Zusammenfassung ............................................................................................................. 74 7 Literaturverzeichnis .......................................................................................................... 77 8 Lebenslauf ......................................................................................................................... 83 9 Danksagung ....................................................................................................................... 84 10 Eigenständigkeitserklärung ............................................................................................... 85

No description available.

Master's thesis compares the standard for digital terrestrial television broadcasting of the first generation DVB-T/H and the second generation DVB-T2 with particular emphasis on the modulator, a security channel interference, the signal from the transmitting environment itself and the modulation signal. The following description of specific models of transmission channels for fixed, portable and mobile reception of digital terrestrial signal. Comparison with the particular relates of the transmission parameters for different types of reception of digital terrestrial television with achieving efficiency and effectiveness of transmission at the level of laboratory measurements and computer simulation.

Vehicular communication networks are essential to the development of intelligent navigation systems and improvement of road safety. Unlike most terrestrial networks of today, vehicular networks are characterized by stringent reliability and latency requirements. In order to design efficient networks to meet these requirements, it is important to understand the system-level performance of vehicular networks. Stochastic geometry has recently emerged as a powerful tool for the modeling and analysis of wireless communication networks. However, the canonical spatial models such as the 2D Poisson point process (PPP) does not capture the peculiar spatial layout of vehicular networks, where the locations of vehicular nodes are restricted to roadways. Motivated by this, we consider a doubly stochastic spatial model that captures the spatial coupling between the vehicular nodes and the roads and analyze the performance of vehicular communication networks. We model the spatial layout of roads by a Poisson line process (PLP) and the locations of nodes on each line (road) by a 1D PPP, thereby forming a Cox process driven by a PLP or Poisson line Cox process (PLCP). In this dissertation, we develop the theory of the PLCP and apply it to study key performance metrics such as coverage probability and rate coverage for vehicular networks under different scenarios. First, we compute the signal-to-interference plus noise ratio (SINR)-based success probability of the typical communication link in a vehicular ad hoc network (VANET). Using this result, we also compute the area spectral efficiency (ASE) of the network. Our results show that the optimum transmission probability that maximizes the ASE of the network obtained for the Cox process differs significantly from that of the conventional 1D and 2D PPP models. Second, we calculate the signal-to-interference ratio (SIR)-based downlink coverage probability of the typical receiver in a vehicular network for the cellular network model in which each receiver node connects to its closest transmitting node in the network. The conditioning on the serving node imposes constraints on the spatial configuration of interfering nodes and also the underlying distribution of lines. We carefully handle these constraints using various fundamental distance properties of the PLCP and derive the exact expression for the coverage probability. Third, building further on the above mentioned works, we consider a more complex cellular vehicle-to-everything (C-V2X) communication network in which the vehicular nodes are served by roadside units (RSUs) as well as cellular macro base stations (MBSs). For this setup, we present the downlink coverage analysis of the typical receiver in the presence of shadowing effects. We address the technical challenges induced by the inclusion of shadowing effects by leveraging the asymptotic behavior of the Cox process. These results help us gain useful insights into the behavior of the networks as a function of key network parameters, such as the densities of the nodes and selection bias. Fourth, we characterize the load on the MBSs due to vehicular users, which is defined as the number of vehicular nodes that are served by the MBS. Since the limited network resources are shared by multiple users in the network, the load distribution is a key indicator of the demand of network resources. We first compute the distribution of the load on MBSs due to vehicular users in a single-tier vehicular network. Building on this, we characterize the load on both MBSs and RSUs in a heterogeneous C-V2X network. Using these results, we also compute the rate coverage of the typical receiver in the network. Fifth and last, we explore the applications of the PLCP that extend beyond vehicular communications. We derive the exact distribution of the shortest path distance between the typical point and its nearest neighbor in the sense of path distance in a Manhattan Poisson line Cox process (MPLCP), which is a special variant of the PLCP. The analytical framework developed in this work allows us to answer several important questions pertaining to transportation networks, urban planning, and personnel deployment. / Doctor of Philosophy / Vehicular communication networks are essential to the development of intelligent transportation systems (ITS) and improving road safety. As the in-vehicle sensors can assess only their immediate environment, vehicular nodes exchange information about critical events, such as accidents and sudden braking, with other vehicles, pedestrians, roadside infrastructure, and cellular base stations in order to make critical decisions in a timely manner. Considering the time-sensitive nature of this information, it is of paramount importance to design efficient communication networks that can support the exchange of this information with reliable and high-speed wireless links. Typically, prior to actual deployment, any design of a wireless network is subject to extensive analysis under various operational scenarios using computer simulations. However, it is not viable to rely entirely on simulations for the system design of highly complex systems, such as the vehicular networks. Hence, it is necessary to develop analytical methods that can complement simulators and also serve as a benchmark. One of the approaches that has gained popularity in the recent years for the modeling and analysis of large-scale wireless networks is the use of tools from stochastic geometry. In this approach, we endow the locations of wireless nodes with some distribution and analyze various aspects of the network by leveraging the properties of the distribution. Traditionally, wireless networks have been studied using simple spatial models in which the wireless nodes can lie anywhere on the domain of interest (often a 1D or a 2D plane). However, vehicular networks have a unique spatial geometry because the locations of vehicular nodes are restricted to roadways. Therefore, in order to model the locations of vehicular nodes in the network, we have to first model the underlying road systems. Further, we should also consider the randomness in the locations of vehicles on each road. So, we consider a doubly stochastic model called Poisson line Cox process (PLCP), in which the spatial layout of roads are modeled by random lines and the locations of vehicles on the roads are modeled by random set of points on these lines. As is usually the case in wireless networks, multiple vehicular nodes and roadside units (RSUs) operate at the same frequency due to the limited availability of radio frequency spectrum, which causes interference. Therefore, any receiver in the network obtains a signal that is a mixture of the desired signal from the intended transmitter and the interfering signals from the other transmitters. The ratio of the power of desired signal to the aggregate power of the interfering signals, which is called as the signal-to-interference ratio (SIR), depends on the locations of the transmitters with respect to the receiver. A receiver in the network is said to be in coverage if the SIR measured at the location of the receiver exceeds the required threshold to successfully decode the message. The probability of occurrence of this event is referred to as the coverage probability and it is one of the fundamental metrics that is used to characterize the performance of a wireless network. In our work, we have analytically characterized the coverage probability of the typical vehicular node in the network. This was the first work to present the coverage analysis of a vehicular network using the aforementioned doubly stochastic model. In addition to coverage probability, we have also explored other performance metrics such as data rate, which is the number of bits that can be successfully communicated per unit time, and spectral efficiency. Our analysis has revealed interesting trends in the coverage probability as a function of key system parameters such as the density of roads in a region (total length of roads per unit area), and the density of vehicles on the roads. We have shown that the vehicular nodes in areas with high density of roads have lower coverage than those in areas with sparsely distributed roads. On the other hand, the coverage probability of a vehicular node improves as the density of vehicles on the roads increases. Such insights are quite useful in the design and deployment of network infrastructure. While our research was primarily focused on communication networks, the utility of the spatial models considered in these works extends to other areas of engineering. For a special variant of the PLCP, we have derived the distribution of the shortest path distance between an arbitrary point and its nearest neighbor in the sense of path distance. The analytical framework developed in this work allows us to answer several important questions pertaining to infrastructure planning and personnel deployment.

No description available.

No description available.