Heart failure is a major public health issue, with its prevalence estimated to be 6.5 million adults in the USA. Of the hospitalized heart failure (HF) cases, 50% are characterized by preserved ejection function (HFpEF). In HFpEF, the heart pumps a normal proportion of blood that enters it. However, thickening of the ventricular walls inhibits the chamber filling to normal volume. The direct basis of HFpEF is a slowed elongation of the cardiac muscle during the diastolic phase of the cardiac cycle. Elucidation of mechanisms that mediate relaxation of cardiac muscle could help understand the pathogenic mechanisms in HFpEF. Myocardial contraction and relaxation are tightly controlled processes that involve thick and thin filament regulatory proteins. β-Adrenergic signaling pathway is a major regulator of myocardial contraction and relaxation via the activation of protein kinase A (PKA). Two key myofilament proteins, troponin I (TnI) and myosin binding protein-C (MyBPC), are phosphorylated by PKA following β-adrenergic stimulation. The purpose of this thesis is to develop a liquid chromatography-mass spectrometry (LC-MS) method for the quantification of phosphorylation in TnI and MyBPC and measure the changes in the degree of phosphorylation in transverse-aortic constriction (TAC) mouse hearts, a model representing HFpEF, and sham (control) mouse hearts. The initial approach of the project was to develop a method for quantification of phosphopeptides using synthesized stable isotope labeled (SIL) peptides, both with and without phosphate modification. To accomplish this goal, a multiple reactions monitoring (MRM)-LC-MS method for the quantification of the synthesized SIL peptides was first developed. This method, using low picomole amounts, is applicable to researchers in the field using SIL peptides for quantification. However, when the SIL peptides were actually applied, we determined that there was a selective absorption of some phosphate peptides in the LC column, limiting the use of the SIL peptides for quantification. This result is also of general interest to others trying to identify phosphopeptides, not realizing that some peptides will go unmeasured. Thus, we returned to expanding an earlier method developed in our research group to quantify the degree of phosphorylation. Key to this work was the development of a quantification method directly from heart myofibrillar protein preparations without requiring isolation of individual proteins by gel electrophoresis. Using the LC-MS method developed, we quantified phosphorylation sites of TnI and MyBPC in the TAC and control mouse hearts. The phosphorylation measurements showed no significant difference in phosphorylation between the TAC and control mice, except for one site, S302 in MyBPC that had a 13% decrease in phosphorylation with TAC. We conclude that in our TAC model, PKA dysfunction may not play a role in the initial development of HFpEF.

Millions of square feet of mechanically stabilized earth retaining wall are constructed annually in the United States. When used in highway fill applications in conjunction with bridges, these MSE walls are typically constructed with a roadside barrier system supported on the edge of the wall. This barrier system generally consists of a traffic barrier or bridge rail placed on a continuous footing or structural slab. The footing is intended to reduce the influence of barrier impact loads on the retaining wall system by distributing the load over a wide area and to provide stability for the barrier against sliding or overturning. The proper design of the roadside barrier, the structural slab, and the MSE wall system requires a good understanding of relevant failure modes, how barrier impact loads are transferred into the wall system, and the magnitude and distribution of these loads. In this study, a procedure is developed that provides guidance for designing: 1. the barrier-moment slab, 2. the wall reinforcement, and 3. the wall panels. These design guidelines are developed in terms of AASHTO LRFD procedures. The research approach consisted of engineering analyses, finite element analyses, static load tests, full-scale dynamic impact tests, and a full-scale vehicle crash test. It was concluded that a 44.5 kN (10 kips) equivalent static load is appropriate for the stability design of the barrier-moment slab system. This will result in much more economical design than systems developed using the 240 kN (54 kips) load that some user agencies are using. Design loads for the wall reinforcement and wall panels are also presented.

Mechanically Stabilized Earth (MSE) wall is a civil structure that has been used for various purposes e.g., supporting bridges, residential or commercial buildings, roadways, railroads etc. In general, MSE wall uses either metal strip, bar or geosynthetics materials as reinforcement. Roger et al. (2010) mentioned that an approximately 57% of the MSE wall constructed in U.S. utilize steel strips as the resources of reinforcement. The usage of metal steel strips is followed by usage of steel bar mats (24%) and geosynthetics grids (18%). Even though MSE walls are designed for a service life of 75 to 100 years, early complication has often been reported. Corrosion of the reinforced steel has been the major cause that afflicts the long-term performance of these walls. The deicing salts used on pavements to melt down snow is one of the major cause of corrosion of these reinforced steels. The aggressiveness of deicers in terms of corrosion of these reinforced steel is studied through the potentiodynamic polarization technique at various concentrations. This study aims to determine the corrosion behavior on galvanized steel and bare steel in presence of individual deicing salt or deicers e.g., sodium chloride, calcium chloride, magnesium chloride and potassium acetate at various (i.e., 0.25, 0.50 and 1.0 M) concentration. Subsequently, the surface morphology was analyzed by using Scanning Electron Microscopy (SEM) and the mineralogical composition was observed through X-Ray Diffraction (XRD). In addition, the corrosivity of two backfill aggregates, natural aggregate and recycled concrete aggregate, was compared. The result shows that the corrosion effect of deicers on reinforced steel depends on its chemical composition and concentration. The SEM imaging showed the presence of micro cracks on the surface of galvanized steel, resulting in pitting corrosion rather than general surficial corrosion. Comparing the corrosion rate of these deicers, the aggressiveness of these deicers on galvanized steel can be arranged in the following order: sodium chloride > calcium chloride > magnesium chloride > potassium acetate. Although sodium chloride was most aggressive for both the steel, the aggressiveness of these deicers on bare steel was different from that of galvanized steel and can be arranged in following order: sodium chloride > magnesium chloride > calcium chloride > potassium acetate. The pH and electrical resistivity of the natural and recycled aggregates were compared with standard provided by American Association of State Highway and Transportation Officials (AASHTO) and found to be non-corrosive. The corrosion rate of both the aggregates on galvanized and bare steel were inappreciable. While analyzing the corrosiveness of these two aggregates, recycled concrete aggregate was observed to be more aggressive than the natural aggregate.

Let (X, Y) be bivariate normal random vectors which represent the responses as a result of Treatment 1 and Treatment 2. The statistical inference about the bivariate normal distribution parameters involving missing data with both treatment samples is considered. Assuming the correlation coefficient ρ of the bivariate population is known, the MLE of population means and variance (ξ, η, and σ2) are obtained. Inferences about these parameters are presented. Procedures of constructing confidence interval for the difference of population means ξ – η and testing hypothesis about ξ – η are established. The performances of the new estimators and testing procedure are compared numerically with the method proposed in Looney and Jones (2003) on the basis of extensive Monte Carlo simulation. Simulation studies indicate that the testing power of the method proposed in this thesis study is higher.

Group testing has long been considered as a safe and sensible relative to one-at-a-time testing in applications where the prevalence rate p is small. In this thesis, we applied Bayes approach to estimate p using Beta-type prior distribution. First, we showed two Bayes estimators of p from prior on p derived from two different loss functions. Second, we presented two more Bayes estimators of p from prior on π according to two loss functions. We also displayed credible and HPD interval for p. In addition, we did intensive numerical studies. All results showed that the Bayes estimator was preferred over the usual maximum likelihood estimator (MLE) for small p. We also presented the optimal β for different p, m, and k.

Lightweight cellular concrete (LCC) is an aerated or foamed concrete where 25-80% of the concrete matrix consists of air voids. The high volume of air voids reduces the strength but significantly decreases the weight of the material, which has made it an attractive alternative to soil for retaining structure backfills. Though the use of LCC has increased, little research has been performed on the large-scale behavior of retaining structures containing LCC as backfill. This research test attempts to fill knowledge gaps found with regard to the use of LCC in a mechanically stabilized earth (MSE) wall with a trapezoidal or sliver fill by examining the nature of LCC strength criteria from large-scale failure, failure mechanisms, and failure criteria. A large-scale test box (10 ft. wide x 12 ft. long x 10 ft. high), surrounded by a steel resisting frame, was constructed and filled with a silty sand backfill soil in a 1:1 stair-stepped slope and an LCC sliver fill. The west-facing wall was a two-paneled MSE wall with 16 ribbed steel strip reinforcements running through the LCC backfill. The LCC was poured over three days in equal height lifts to ensure stability. A total of 64 sample cylinder molds and four split mold shear boxes were filled with LCC during placement to help identify LCC material properties, which included density, unconfined compressive strength (UCS), and shear strength. A surcharge test was performed on the large-scale test box six days after initial placement of the LCC due to the unanticipated high strength gain and density found within the placed LCC. Instrumentation collected data on displacement, shear plane, lateral wall pressure, and reinforcement strain throughout testing. Initially, four hydraulic jacks were used during surcharge testing to induce a uniform surcharge load to fail the sliver-fill MSE wall. The strength limit of the steel resisting frame was reached before failure, at which point the number of hydraulic jacks was switched to three for a more critical loading condition. The test was again terminated before complete failure when the steel resisting frame strength limit was met. Though failure was not completed, the sliver-fill MSE wall failure had initiated before testing was terminated at a surcharge load of 70 psi. Results identify the initiation of shear failure within the LCC at about 65 psi, with maximum lateral and axial displacements of about 0.5 in. and 1.2 in., respectively. The shear failure occurs at about 52% of the average UCS of 123 psi. An arcuate shear plane, contrary to the traditional bilinear MSE wall failure surface with inextensible reinforcements, was identified within the LCC backfill, which initiated from the toe of the MSE wall and ended about 8 ft. back from the top of the MSE wall, using lateral displacements from Sondex tube profilometers in the backfill.

20 000 Européens meurent chaque année du mélanome et le taux de mortalité ne cesse de s’accroître. Les cellules de mélanome se caractérisent principalement par la mutation des kinases RAS, B-RAF et RHO-B. Ces mutations leur confèrent une résistance aux agents chimiothérapeutiques. Un grand nombre de travaux a établi que les pigments d’algues présentent un intérêt majeur pour prévenir, diagnostiquer et traiter les cancers. L’objectif de ce travail de thèse est de réaliser un travail de recherche intégré pour identifier des pigments de microalgues pouvant présenter un intérêt pour le diagnostic ou le traitement des mélanomes et de caractériser leur activité pharmacologique. Notre choix s’est porté sur Porphyridium purpureum, une espèce qui contient des phycobiliprotéines, des caroténoïdes dont la zéaxanthine. Nous avons développé des procédés innovants pour l’extraction et l’identification des pigments de microalgues. Ce travail a permis de réaliser la première extraction de phycobiliprotéines assistée sous champ microondes ainsi que l’identification des pigments de microalgue par UPLC-MSE au sein d’un mélange complexe. De plus, nous avons montré l’activité pro-apoptotique de la zéaxanthine et la caractérisation de son mode d’action sur les cellules de mélanome humain A2058. L’IC50 obtenue pour ce pigment est inférieure à celle du cisplatine (agent chimiothérapeutique). Ces résultats montrent le fort potentiel de ce pigment pour le traitement du mélanome résistant à la chimiothérapie. / 20 000 Europeans die from melanoma each year and this number is constantly increasing. Melanoma cells are mainly characterized by the mutation of the RAS, B-RAF and RHO-B kinases. Because of these mutations, the cells are resistant to chemotherapeutic agents. A lot of studies have established that the algae pigments are of major interest to prevent diagnose and treat cancers. The objective of this thesis is to undertake an integrated research work to identify microalgae pigments that may be relevant for the diagnosis or treatment of melanomas and to characterize their pharmacological activity. We selected Porphyridium purpureum, a species which contains phycobiliproteins, carotenoids including zeaxanthin. We developed innovative processes for the extraction and identification of microalgae pigments. This work resulted in the first extraction of phycobiliproteins under microwave-assisted irradiations, and the identification of microalgae pigments by UPLC-MSE within a complex mixture. Moreover, we demonstrated the proapoptotic activity of zeaxanthin and the characterization of its mode of action on A2058 human melanoma cells. The CI50 obtained for this pigment is lower than that of cisplatin (chemotherapeutic drug). These results show the great potential of this pigment for the treatment of melanoma which are resistant to chemotherapy.

Submitted by Erika Demachki (erikademachki@gmail.com) on 2017-03-07T13:37:49Z No. of bitstreams: 4 Dissertação - Aparecido Ferreira de Souza - 2017 - Parte 01.pdf: 17508857 bytes, checksum: 1d04cb16c6e33e54fe0304cecb5e491b (MD5) Dissertação - Aparecido Ferreira de Souza - 2017 - Parte 02.pdf: 14162361 bytes, checksum: b19921eb48893ef7a1aa4ddc2a2e1553 (MD5) Dissertação - Aparecido Ferreira de Souza - 2017 - Parte 03.pdf: 17178000 bytes, checksum: aaf5cfd215078190a7900eafd1e47790 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2017-03-07T15:14:15Z (GMT) No. of bitstreams: 4 Dissertação - Aparecido Ferreira de Souza - 2017 - Parte 01.pdf: 17508857 bytes, checksum: 1d04cb16c6e33e54fe0304cecb5e491b (MD5) Dissertação - Aparecido Ferreira de Souza - 2017 - Parte 02.pdf: 14162361 bytes, checksum: b19921eb48893ef7a1aa4ddc2a2e1553 (MD5) Dissertação - Aparecido Ferreira de Souza - 2017 - Parte 03.pdf: 17178000 bytes, checksum: aaf5cfd215078190a7900eafd1e47790 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2017-03-07T15:14:15Z (GMT). No. of bitstreams: 4 Dissertação - Aparecido Ferreira de Souza - 2017 - Parte 01.pdf: 17508857 bytes, checksum: 1d04cb16c6e33e54fe0304cecb5e491b (MD5) Dissertação - Aparecido Ferreira de Souza - 2017 - Parte 02.pdf: 14162361 bytes, checksum: b19921eb48893ef7a1aa4ddc2a2e1553 (MD5) Dissertação - Aparecido Ferreira de Souza - 2017 - Parte 03.pdf: 17178000 bytes, checksum: aaf5cfd215078190a7900eafd1e47790 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2017-02-21 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq / Fundação de Amparo à Pesquisa do Estado de Goiás - FAPEG / Iron (Fe) is an indispensable metal for most biological systems and is a target of competition in host-pathogen interactions. In humans, most Fe is complexed to the cofactor heme, present in hemoglobin, a molecule that is exploited by pathogens as an iron source. Paracoccidioides spp., a complex of thermodymorphic pathogenic fungi, are the etiological agents of paracoccidioidomycosis (PCM), a systemic mycosis endemic in Latin America. Paracoccidioides spp. are able to use hemoglobin in a receptor(PbRbt5)-mediated process. However experimental evidence points to the existence of a complex system with the presence of other proteins. In the present work, we demonstrated the similarity between PAAG_02225 (PbPga7), from Paracoccidioides lutzii, and the sequence of the heme/hemoglobin receptor Pga7 from Candida albicans, and expressed PbPga7 in Escherichia coli. Due to the presence of rare codons in P. lutzii sequence, compared to the codons preferably used by Escherichia coli, chemical synthesis of the gene was employed. The expression of PbPga7 protein opens perspectives for PbPga7 characterization. In addition, nanoUPLC-MSE was employed to analyze P. lutzii cell wall proteome. We observed that the treatment of fungus with hemoglobin promotes induction of potential adhesins and defense-related enzymes against reactive oxygen species. These data indicate that these proteins may be important for the pathogen to access hemoglobin by adhering and lysing erythrocytes, besides counteracting the toxicity generated by heme/hemoglobin released from erythrocytes, allowing the uptake and use of these molecules. The results obtained in the present work reinforce the complexity of the interaction event between pathogen and host and, in addition, contribute to broaden the understanding of the biology of Paracoccidioides spp. / O Ferro (Fe) é um metal indispensável para a maioria dos sistemas biológicos e é alvo de competição em interações patógeno-hospedeiro. Em humanos, a maioria do Fe encontra-se complexada ao cofator heme, presente na hemoglobina, uma molécula que é explorada por patógenos como uma fonte de Fe. Paracoccidioides spp., um complexo de fungos patogênicos termodimórifocos, são agentes etiológicos da paracoccidioidomicose (PCM), uma micose sistêmica endêmica na América Latina. Paracoccidioides spp. é hábil em utilizar hemoglobina por um processo mediado por receptor (PbRbt5). Contudo, evidências experimentais apontam para a existência de um sistema complexo com a presença de outras proteínas. No presente trabalho, foi demonstrada a similaridade de PAAG_02225 (PbPga7), de Paracoccidioides lutzii, com a sequência do receptor de heme/hemoglobina Pga7 de Candida albicans. A expressão heteróloga de PbPga7 foi realizada em Escherichia coli. Devido a presença de códons raros na sequência de P. lutzii, comparados aos códons utilizados preferencialmente por E. coli, a síntese química do gene foi empregada. A expressão da proteína PbPga7 abre perspectivas para estudos de caracterização da mesma. Adicionalmente, nanoUPLC-MSE foi utilizada para analisar o proteoma de parede celular de P. lutzii. Observou-se que o tratamento do fungo com hemoglobina promove a regulação positiva de potenciais adesinas e enzimas relacionadas com a defesa contra espécies reativas de oxigênio. Estes dados indicam que estas proteínas podem ser importantes para que o patógeno possa acessar a hemoglobina, aderindo e lisando eritrócitos, além de contrapor a toxicidade gerada pelo heme/hemoglobina liberados, permitindo a captação e utilização dessas moléculas. Os resultados obtidos no presente trabalho reiteram a complexidade do evento de interação entre patógeno e hospedeiro e, adicionalmente, contribuem para a ampliação do entendimento da biologia de Paracoccidioides spp.

Submitted by Renata Lopes (renatasil82@gmail.com) on 2017-04-10T13:40:20Z No. of bitstreams: 1 fabianotouzdjianpinheirotavora.pdf: 2717332 bytes, checksum: ef7258702d1bc7c43c78dae666bfb284 (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2017-04-11T11:35:09Z (GMT) No. of bitstreams: 1 fabianotouzdjianpinheirotavora.pdf: 2717332 bytes, checksum: ef7258702d1bc7c43c78dae666bfb284 (MD5) / Made available in DSpace on 2017-04-11T11:35:09Z (GMT). No. of bitstreams: 1 fabianotouzdjianpinheirotavora.pdf: 2717332 bytes, checksum: ef7258702d1bc7c43c78dae666bfb284 (MD5) Previous issue date: 2017-03-03 / A bactéria fitopatogênica Xanthomonas campestris pv. campestris (Xcc) consiste no agente causal da podridão negra que acomete todas as variedades comerciais do gênero Brassica, sendo responsável por perdas significativas na brassicultura nacional e mundial. O objetivo deste trabalho consistiu em traçar o perfil proteômico de dois isolados de Xcc, distintos quanto à virulência, utilizando um sistema in vitro para a identificação de proteínas diferencialmente abundantes relacionadas aos mecanismos de virulência. Inicialmente, curvas de crescimento bacteriano foram desenvolvidas afim de se determinar o momento apropriado para a coleta e extração de proteínas. Os isolados Xcc51 e XccY21 foram cultivados em dois meios de cultura distintos, sendo um nutricionalmente rico (NYG) e outro capaz de induzir a transcrição de genes relacionados à virulência (meio mínimo – XVM1), até atingirem a fase exponencial máxima de crescimento bacteriano (OD600nm = 0,8 em meio NYG e OD600nm = 0,58 em meio XVM1). As proteínas totais dos isolados foram extraídas usando fenol, precipitadas com acetato de amônio em metanol, digeridas com tripsina e analisadas pela técnica 2DnanoUPLC/MSE, utilizando a plataforma de identificação e quantificação de proteínas Protein Lynx Global Server (PLGS). Os dados obtidos foram comparados com sequências depositadas no banco de dados XGB (The Xanthomonas Genome Browser). Foram identificadas mais de 600 proteínas no proteoma total de ambos os isolados de Xcc, revelando a expressão de proteínas exclusivas, bem como um perfil diverso de proteínas aumentadas e diminuídas entre os isolados durante o cultivo nos dois meios. Com o auxílio do software BLAST2GO, foi realizada uma análise baseada na ontologia dos produtos gênicos. Os resultados obtidos evidenciam que durante a condição de indução de genes de patogenicidade, o isolado mais virulento Xcc51 se destacou pela abundância de importantes proteínas relacionadas à infecção bacteriana, como bfeA, TonB, ompP6, clpB, tig, acvB, quando comparado à quantidade exibida no isolado XccY21. Os dados proteômicos gerados pelo presente estudo apresentaram um interessante rol de proteínas diferencialmente aumentadas e supostamente relacionadas à patogenicidade e virulência de Xcc, o qual poderá nortear futuras investigações quanto aos mecanismos moleculares envolvidos na patogênese dessa fitobactéria. / The phytopathogenic bacterium Xanthomonas campestris pv. campestris (Xcc) consist in the black rot disease causal agent, which affects all Brassica genus commercial varieties. This disease results in significant losses for brassicultures worldwide. The present study aimed to analyze the proteomic profile of two distinct Xcc isolates, employing an in vitro system for the identification of differentially abundant proteins, related to pathogenicity and virulence mechanisms. Initially, bacterial growth curves were assessed to determine the appropriate stage for protein extraction. Xanthomonas isolates Xcc51 and XccY21 were cultured in two distinct mediums, a nutritionally rich medium (NYG) and a minimal medium - XVM1, capable of inducing the transcription of pathogenicity genes, until they reached maximum exponential growth phase (OD600nm = 0.8 A. and OD600nm = 0.52 A., respectively). Total proteins were extracted using phenol/ammonium acetate, trypsin digested and analyzed by 2DnanoUPLC/MSE, coupled with Protein Lynx Global Server (PLGS). Xanthomonas Genome Browser database was used, leading to the identification of more than 600 proteins and revealing the expression of unique proteins as well as diverse profiles of increased and decreased proteins. Blast2GO software was applied to analyze gene ontology. Results suggest that during pathogenicity inducing condition, the isolate Xcc51 increases the abundance of crucial infection-related proteins such as bfeA, TonB, ompP6, clpB, acvB, when compared to XccY21 which could explain its higher virulence. The proteomic data showed by the present study delivered a list of interesting proteins presumably related with pathogenicity and virulence of Xcc, which could guide future investigations on molecular mechanisms involved in this phytobacterium pathogenesis.

[pt] Uma abordagem promissora para reduzir o consumo de energia é considerar a quantização grosseira no receptor. Neste estudo, investigamos novas técnicas de pré-codificação no espaço e no tempo para canais de downlink MIMO multiusuário limitados em banda com quantização de 1 bit e sobre amostragem no receptor, considerando a modulação de cruzamento zero. A modulação de instância de tempo de zero cruzamento proposta transmite a informação nas instâncias de tempo de cruzamento zero. Dois critérios de projeto para a instância de tempo de cruzamento zero são investigados, a saber, a distância mínima até o limiar de decisão e o erro quadrático médio entre o sinal recebido e o desejado. A maximização da distância mínima para o limiar de decisão pode ser formulada como um programa quadrático restrito quadraticamente. Como alternativa, um problema equivalente pode ser formulado com base na minimização de potência, o que reduz a complexidade computacional. Além disso, outro método é implementado onde a informação é transmitida nas instâncias de tempo de cruzamento zero em segmentos de forma de onda. Partindo da técnica convencional baseada no erro quadrático médio, um algoritmo mais sofisticado é desenvolvido, o que implica a extensão ativa da constelação para melhorar o desempenho em altaSNR. O problema estendido é resolvido com duas abordagens: formulando o problema como um programa de cone de segunda ordem e considerando um algoritmo de otimização alternada. Outro método baseado no algoritmo de descida de gradiente é implementado com a técnica do erro quadrático médio para reduzir ainda mais a complexidade computacional. Além disso, um limite inferior para a eficiência espectral é obtido. Os resultados numéricos mostram que os métodos de pré-codificação de cruzamento zero de instância de tempo propostos melhoram significativamente a taxa de erro de bit em comparação com os métodos de última geração. Finalmente, a maximização da distância mínima ao limiar de decisão e as técnicas de pré-codificação baseadas no erro quadrático médio são avaliadas considerando um canal de onda milimétrica seletivo em frequência. Os resultados numéricos mostram que ambas as técnicas de pré-codificação respondem bem à seletividade de frequência do canal. / [en] A promising approach to reduce energy consumption is to consider coarse quantization at the receiver. In this study, we investigate novel precoding techniques in space and time for bandlimited multiuser MIMO downlink channels with 1-bit quantization and oversampling at the receiver, considering zero-crossing modulation. The proposed time-instance zero-crossing modulation conveys the information into the time-instances of zero-crossings. Two design criteria for time-instance zero-crossing modulation are investigated, namely, the minimum distance to the decision threshold and the mean-square error between the received and the desired signal. The maximization of the minimum distance to the decision threshold can be formulated as a quadratically constraint quadratic program. As an alternative, an equivalent problem is formulated based on power minimization, which reduces computational complexity. Moreover, another method is implemented where the information is conveyed into the time-instances of zero-crossings using waveform segments. Departing from the conventional mean-square error based technique, a more sophisticated algorithm is developed, which implies active constellation extension to improve the performance at high SNR. The extended problem is solved with two approaches: by formulating the problem as a second-order cone program and by considering an alternating optimization algorithm. Another method based on the gradient descent algorithm is implemented with the mean-square error technique to reduce computational complexity further. Besides, a lower bound on the spectral efficiency is obtained. Numerical results show that the proposed time-instance zero-crossing precoding methods significantly improve the bit error rate compared to the state-of-the-art methods. Finally, the maximization of the minimum distance to the decision threshold and the mean-square error based precoding techniques are evaluated considering a frequency-selective millimeter wave channel. Numerical results show that both precoding techniques respond well to the frequency selectivity of the channel.