Página 1 dos resultados de 2694 itens digitais encontrados em 0.017 segundos

Semigrupos de operadores lineares aplicados às equações diferenciais parciais

Rosa, Rosemeire Aparecida
Fonte: Universidade Estadual Paulista (UNESP) Publicador: Universidade Estadual Paulista (UNESP)
Tipo: Dissertação de Mestrado Formato: 80 f. : il.
POR
Relevância na Pesquisa
45.91%
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP); Pós-graduação em Matemática - IBILCE; Neste trabalho vamos estudar a existência e unicidade de solução para equações da forma { u + Au = f(t,u) u(t0)= u0 ∈ X, (I) onde X é um espaço de Banach, A : D(A) ⊂ X → X é um operador linear, f é uma função não linear conhecida, u0 ∈ X é um dado inical conhecido e u : I ⊂ R → X é uma função desconhecida e t0 ∈ I. Faremos este estudo usando a Teoria dos Semigrupos de Operadores Lineares. Para melhor entendimento do estudo das equações (I), faremos duas aplicações. A primeira tratando de um modelo (linear) de divisão celular e a segunda, do modelo (não linear) de condução do calor.; In this work we will study the existence and uniqueness of the solutions for the following equation { u + Au = f(t,u) u(t0)= u0 ∈ X, (I) where X is a Banach space, A : D(A) ⊂ X → X is a linear operator, f is a nonlinear function, u : I ⊂ R → X is unknown function. In this study we will use the theory of semigroup of linear operators. For a best understanding of the study of equations (I), we will do two applications. The first one, is a (linear) model of cellular division and the second one, is about the (nonlinear) model od conduction of the heat.

Avaliação de desempenho do enlace reverso de redes celulares que utilizam a técnica CDMA com multiportadoras (MC-CDMA) em um canal rayleigh seletivo em frequência; Performance evaluation of the uplink of cellular networks that employ multicarrier CDMA technique (MC-CDMA) in a frequency selective rayleigh fading channel

Henry Ramiro Carvajal Mora
Fonte: Biblioteca Digital da Unicamp Publicador: Biblioteca Digital da Unicamp
Tipo: Dissertação de Mestrado Formato: application/pdf
Publicado em 16/12/2014 PT
Relevância na Pesquisa
36.12%
Neste trabalho, é avaliado o desempenho do enlace reverso de redes celulares que utilizam a técnica de múltiplo acesso por divisão de código com multiportadoras (MC-CDMA) em termos da probabilidade de erro de bit média (BER) e da eficiência espectral média. O sistema de comunicações analisado utiliza a técnica MC-CDMA, um arranjo linear de antenas na estação rádio base, entrelaçamento em frequência, combinação de máxima razão (MRC), modulação adaptativa, controle de potência e um prefixo cíclico grande o suficiente para eliminar os efeitos da interferência intersimbólica (ISI) e da interferência entre portadoras (ICI). O cenário estudado considera a presença de interferência de múltiplo acesso (MAI) e interferência de co-canal (CCI). A caracterização do canal considera a presença de ruído aditivo gaussiano branco (AWGN), perda de propagação exponencial e desvanecimento lento e seletivo em frequência que segue a distribuição de Rayleigh. Neste contexto, expressões analíticas exatas e fechadas para a BER média tanto para a modulação BPSK, quanto para a modulação M-QAM são obtidas. A exatidão das expressões é validada através de simulações de Monte Carlo. Ademais, uma expressão para a eficiência espectral celular média é determinada...

Isolation and Characterization of Mutants of Escherichia coli with Cellular Division Selectively Affected by Growth on Fatty Acids

Samuel, D.; Paris, S.; Ailhaud, G.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /10/1972 EN
Relevância na Pesquisa
45.91%
Isolation and characterization of mutants of Escherichia coli that beta-oxidize fatty acids at normal rates, but which divide very slowly when grown on fatty acids, are described. These mutants grow normally on other carbon sources. By growth on oleate, experiments with radioactive precursors showed that the rates of incorporation into ribonucleic acid, protein, and cell wall were comparable to those observed with the parent, whereas the rate of incorporation into phospholipids was slightly decreased. Under these conditions the rate of incorporation of 32P-orthophosphate into deoxyribonucleic acid was low. On the other hand, by growth on oleate, neither gross mass increase in the different macromolecules nor loss of viability was observed, whereas in the presence of inducer the derepression of the lac operon enzymes occurred. Therefore, extensive turnover of the macromolecules is involved when these mutants are grown on fatty acids. Studies of the crypticity and of the binding of 1-anilino-8-naphthalene sulfonate show differences in membrane structure between the mutants and the constitutive parent. Properties of these mutants, which are affected in the process of cellular division, are discussed.

ELECTRON MICROSCOPY OF CELLULAR DIVISION IN ESCHERICHIA COLI

Conti, S. F.; Gettner, M. E.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /03/1962 EN
Relevância na Pesquisa
46.04%
Conti, S. F. (Brookhaven National Laboratory, Upton, N. Y.) and M. E. Gettner. Electron microscopy of cellular division in Escherichia coli. J. Bacteriol. 83:544–550. 1962.—Exponentially growing cells of Escherichia coli were fixed in formalin, exposed to uranyl nitrate, dehydrated at low temperatures with ethanol, and embedded in methacrylate. Polymerization was carried out at −70 C, by exposure of specimens to radiation from a cobalt60 source. Electron micrographs revealed that cellular division occurs by the centripetal growth of the cell wall. The fine structure of the cytoplasm, nuclear apparatus, cell wall, and cytoplasmic membrane was also studied.

Rous sarcoma virus infection of synchronized cells establishes provirus integration during S-phase DNA synthesis prior to cellular division.

Humphries, E H; Glover, C; Reichmann, M E
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /04/1981 EN
Relevância na Pesquisa
46.11%
Synchronized chicken embryo fibroblasts, prepared by addition of serum to stationary cells arrested in Go, were exposed to the Prague strain of Rous sarcoma virus. At different times during the cell cycle, high molecular weight DNA was prepared from infected cells and examined for the presence of newly integrated viral DNA sequences. The results demonstrate that newly integrated viral sequences were first detected during S-phase DNA synthesis 9 hr after infection. The presence of colchicine prevented cellular division and delayed the appearance of progeny virus but it did not affect the appearance of viral specific DNA in the high molecular weight fraction of cellular DNA. Our results indicate that provirus integration, occurring during S-phase DNA synthesis, does not require cell division. Previous experiments have demonstrated that Rous sarcoma virus infection of chicken embryo fibroblasts requires cell division to initiate viral RNA synthesis and the production of progeny virus. The findings presented in this report support the hypothesis that division of the infected cells is required for an event that controls viral expression at the level of the integrated provirus.

Ribosomal Slowdown Mediates Translational Arrest during Cellular Division▿

Sivan, Gilad; Kedersha, Nancy; Elroy-Stein, Orna
Fonte: American Society for Microbiology (ASM) Publicador: American Society for Microbiology (ASM)
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
45.91%
Global mRNA translation is transiently inhibited during cellular division. We demonstrate that mitotic cells contain heavy polysomes, but these are significantly less translationally active than polysomes in cycling cells. Several observations indicate that mitotic translational attenuation occurs during the elongation stage: (i) in cycling nonsynchronized cultures, only mitotic cells fail to assemble stress granules when treated with agents that inhibit translational initiation; (ii) mitotic cells contain fewer free 80S complexes, which are less sensitive to high salt disassembly; (iii) mitotic polysomes are more resistant to enforced disassembly using puromycin; and (iv) ribosome transit time increases during mitosis. Elongation slowdown guarantees that polysomes are retained even if initiation is inhibited at the same time. Stalling translating ribosomes during mitosis may protect mRNAs and allow rapid resumption of translation immediately upon entry into the G1 phase.

AN ENZYMATIC LOCUS PARTICIPATING IN CELLULAR DIVISION OF A YEAST

Nickerson, Walter J.
Fonte: The Rockefeller University Press Publicador: The Rockefeller University Press
Tipo: Artigo de Revista Científica
Publicado em 20/03/1954 EN
Relevância na Pesquisa
46.2%
Growing cells of a filamentous mutant of a yeast, Candida albicans, were found to accumulate and reduce tetrazolium dyes whereas cells of the parent strain, growing as a normally budding yeast, accumulated the dye but did not reduce it. In older cultures, in which rapidly metabolizable carbohydrate has been depleted, the parent strain characteristically produces filaments. These cells, growing in the absence of cellular division, also exhibit tetrazolium reduction. The filamentous mutant synthesizes cell mass at a rate almost equal to that of the parent strain and is not distinguished therefrom in fermentation ability, nutritional requirements for growth, rate of endogenous respiration, or polysaccharide composition. These facts, in conjunction with the striking differences in tetrazolium reduction, lead to the conclusion that the morphological mutant has an impairment to a cellular oxidation mechanism at a flavoprotein locus. This locus is, then, the site at which a reaction essential for cellular division, is coupled via an oxidation-reduction to cellular metabolism. Preliminary evidence is presented providing good indication that uncoupling of cellular division (by genetic block) in the mutant or in the parent (by substrate exhaustion) results from impairment to a dissociable metal chelate mechanism which normally couples a reaction essential to cellular division to flavoprotein oxidation.

Effects of cellular and tissue pharmacokinetics on control released growth factors

Wu, David, 1973-
Fonte: Massachusetts Institute of Technology Publicador: Massachusetts Institute of Technology
Tipo: Tese de Doutorado Formato: 150 leaves; 6487625 bytes; 6487430 bytes; application/pdf; application/pdf
ENG
Relevância na Pesquisa
46.07%
Aim: To examine the effects of cellular and tissue pharmacokinetics on control released growth factors. Motivation: The resurgence of interest in controlled drug delivery reflects the increasing appreciation of the importance of local pharmacokinetics in defining the efficacy and potency of bioactive compounds. Despite promising data in vitro, growth factor use in vivo has generally failed to live up to its full potential. Without a theoretical framework to consider local pharmacology, there remains no consensus approach for improving the clinical outcomes of control released growth factors. As a result, a series of experiments incorporating cellular pharmacokinetics, computational modeling, and tissue pharmacokinetics were conducted. CellularPharmacokinetics: The effect of ligand-receptor trafficking was examined on the potency of sustained release versus bolus administration of two growth factors that differed by intracellular trafficking kinetics. Sustained delivery potency was demonstrated to be dependent on both ligand and receptor trafficking and could be predicted based on trafficking considerations.; (cont.) Computational Models: Computational models were conceptualized to describe the relationship between controlled-delivery...

Quantitative analysis and characterization of intracellular gene delivery mechanisms; Quantitative analysis and characterization of cellular gene delivery mechanics

Varga, Csanad M. (Csanad Mathias), 1976-
Fonte: Massachusetts Institute of Technology Publicador: Massachusetts Institute of Technology
Tipo: Tese de Doutorado Formato: 117 leaves; 5577256 bytes; 5577065 bytes; application/pdf; application/pdf
ENG
Relevância na Pesquisa
46.04%
A goal for gene delivery research is to design vectors capable of (a) delivering transgenes to target cells, (b) yielding efficient gene expression, and (c) minimizing any immune, inflammatory, or cytotoxic response. Current research has focused on developing such vehicles using end gene expression as the benchmark. While transgene protein production is the overall objective of successful gene delivery, such qualitative treatment of gene delivery, especially for non-viral vectors, may result in unoptimized vectors and potential rate limiting steps unidentified. Quantitative analysis of the gene delivery pathway is essential for the characterization, comparison, and design of vectors. The complex nature of the mechanisms for gene delivery, particularly at the cellular level, contains multiple potentially rate limiting steps to successful gene expression. Through quantitative methodologies, vector efficacy can be related to molecular characteristics and specific processes within the gene delivery pathway. These potentially rate limiting steps include, but are not limited to, cell surface association, subcellular trafficking, endosomal escape, nuclear translocation, vector unpackaging, and gene expression. Design of synthetic gene delivery vectors seeks to develop molecular systems mimicking virus-like infection behavior...

Cellular responses to mechanical stresses applied via magnetic manipulators

Huang, Hayden.
Fonte: Massachusetts Institute of Technology Publicador: Massachusetts Institute of Technology
Tipo: Tese de Doutorado Formato: 166 p.; 17152852 bytes; 17152609 bytes; application/pdf; application/pdf
ENG
Relevância na Pesquisa
46.09%
A mechanotransduction model aims to explain how a cell senses mechanical forces and translates them into molecular events, such as changes in intracellular ion concentrations, gene expression, post-translational protein modification, or cytoskeletal redistribution. Many studies of mechanotransduction explore the responses of cell populations to large and, occasionally, poorly characterized deformation. More recent techniques provide the means for characterizing the physical properties of the cell, with the potential for uniting the molecular responses with the material properties and deformation characteristics of the cell. These recent techniques have an additional advantage - they can be used to probe cells at the single cell level. Single cell studies have the potential to elucidate more precisely the specific mechanisms by which a cell senses and transmits signals, because the information gathered from each cell is not averaged over thousands or millions of cells. Over the past decade, several approaches to studying mechanical properties at the single cell level were developed. Atomic force microscopy, optical and magnetic tweezers, micropipette aspiration and other techniques have been used to explore and develop physical models of the cell. By using these techniques...

Nanoscale and microscale approaches for engineering the in vitro cellular microenvironment

Khademhosseini, Ali
Fonte: Massachusetts Institute of Technology Publicador: Massachusetts Institute of Technology
Tipo: Tese de Doutorado Formato: 182 leaves; 12976881 bytes; 12985321 bytes; application/pdf; application/pdf
ENG
Relevância na Pesquisa
45.87%
Micro- and nanofabrication approaches have dramatically changed our society through their use in microelectronics and telecommunication industries. These engineering tools are also useful for many biological applications ranging from drug delivery to DNA sequencing, since they can be used to fabricate small features at a low cost and in a reproducible manner. The goal of this thesis was to develop techniques based on the merger of novel materials and nano and microfabrication approaches to manipulate cell microenvironment in culture. To control cell migration and to restrict cell or colony size, cells and proteins were patterned by using molding or printing methods. Poly(ethylene glycol)-based molecules and polysaccharides were used to control cell-substrate interactions and to prevent cell adhesion on specific regions of a substrate. To control cell-cell contact, layer-by-layer deposition of ionic biopolymers (i.e. negatively charged hyaluronic acid and positively charged poly-L-lysine) was used to generate patterned co-cultures. In addition, to control cell-soluble factor interactions, microfluidic-based approaches were developed. To pattern cells and proteins within microchannels, a soft lithographic method was developed to pattern microchannel substrates using printing and molding approaches.; (cont.) To easily immobilize cells within channels...

Towards a microfluidic disease detection deviced based on cellular adhesion differences

Naegle, Kristen M
Fonte: Massachusetts Institute of Technology Publicador: Massachusetts Institute of Technology
Tipo: Tese de Doutorado Formato: 50 leaves
ENG
Relevância na Pesquisa
45.87%
There is a great need in the fields of biology, medicine, and pharmaceuticals to create high-throughput devices for the detection of specific cell states in a heterogeneous mixture of cells. The desire is to differentiate among diseased and healthy cells, cell age, and cell type with the minimum amount of sample pretreatment. This project addresses this need by developing microfluidic devices that exploit the adhesion differences between cell states and cell types to rapidly count cells of different types without the need for labels. There are two avenues in which to explore cell adhesion differences with these devices, the first is a net electrostatic change at the surface of the cell wall and the second is the presence of specific cell-membrane adhesion proteins. It is hypothesized that the forced interaction of the cell wall with the microfabricated microcapillary walls would result in a differential velocity based on cell type that could be detected simply using a microscope and video camera or an interferometer. The eventual integration of cell velocity detection would result in a portable all-inclusive lab-on-a-chip system that could be used in the field for detecting the presence of diseases, such as malaria and cancer as well as in a lab setting for drug discovery.; by Kristen M. Naegle.; Thesis (S.M.)--Massachusetts Institute of Technology...

The role of mismatch repair in mediating cellular sensitivity to cisplatin : the Escherichia coli methyl-directed repair paradigm

Robbins, Jennifer L
Fonte: Massachusetts Institute of Technology Publicador: Massachusetts Institute of Technology
Tipo: Tese de Doutorado Formato: 2 v. (258 leaves)
ENG
Relevância na Pesquisa
45.87%
The anticancer drug cisplatin is in widespread use but its mechanism of action is only poorly understood. Moreover, human cancers acquire resistance to the drug, which limits its clinical utility. A paradox in the field is how loss of mismatch DNA repair leads to clinical resistance to this widely used drug. The phenomenon of cisplatin tolerance in mismatch repair deficient cells was initially discovered in E. coli, where methylation deficient dam mutants show high sensitivity to cisplatin and dam mutants with an additional mutation in either of the mismatch repair genes mutS or mutL show near wildtype levels of resistance. A prevalent explanation for this observation is the abortive repair model, which proposes that in dam mutants, where the strand discrimination signal is lost, mismatch repair attempts futile cycles of repair opposite cisplatin-DNA adducts. Previous findings have supported this model to the extent that MutS, the E. coli mismatch recognition protein, specifically recognizes DNA modified with cisplatin. However it has recently been shown that MutS binding to cisplatin adducts may contribute to toxicity by instead preventing the recombinational repair of a cisplatin-modified substrate, and we have previously shown that recombination is an essential mechanism for tolerating cisplatin damage.; (cont.) In the present study...

Cellular and molecular immunotherapeutics derived from the bone marrow stroma; Cellular and molecular immuno therapeutics derived from the bone marrow stroma

Parekkadan, Biju
Fonte: Massachusetts Institute of Technology Publicador: Massachusetts Institute of Technology
Tipo: Tese de Doutorado Formato: 174 p.
ENG
Relevância na Pesquisa
45.98%
The bone marrow contains a multipotent stromal cell, commonly referred to as a mesenchymal stem cell (MSC). There has been recent interest in the clinical use of MSCs for cell-based therapy because: (1) bone marrow aspiration is a routine method used in medicine thereby allowing for easy accessibility to human MSCs; (2) MSCs are easily isolated and can expand to clinical scales in a relatively short period of time; (3) MSCs can be biopreserved without loss of potency and stored for point-of-care delivery; and (4) human trials of MSCs thus far have shown no adverse reactions to allogeneic versus autologous MSC transplants suggesting that therapy can cross histocompatibility barriers. This thesis describes the development of new modalities and indications for MSC-based treatments by leveraging the endogenous functions of these cells for therapeutic purposes. First, it is known that marrow stromal cells support hematopoiesis by secreting bioactive molecules that aid in the growth, differentiation, function and migration of hematopoietic cells within the marrow cavity. We show that these same secreted molecules derived from MSCs ex vivo can be formulated as an intravenous drug. In a D-galactosamine model of acute liver failure, a bolus injection of a concentrated form of MSC conditioned medium (MSC-CM) led to a significant survival benefit with a one week study endpoint. We employed in vitro and in vivo assays to demonstrate the effect of MSC-CM on leukocytes and resident liver cells. Traditional biochemical approaches were performed to identify active fractions within MSC-CM that were responsible for its therapeutic efficacy. As a corollary to an injectable drug...

Engineering the interface between cellular chassis and synthetic biological systems

Canton, Bartholomew (Bartholomew John)
Fonte: Massachusetts Institute of Technology Publicador: Massachusetts Institute of Technology
Tipo: Tese de Doutorado Formato: 176 p.
ENG
Relevância na Pesquisa
46.07%
The aim of my thesis is to help enable the engineering of biological systems that behave in a predictable manner. Well-established techniques exist to engineer systems that behave as expected. Here, I apply such techniques to two aspects of the engineering of biological systems. First, I address the design and construction of standard biological devices in a manner that facilitates reuse in higher-order systems. I describe the design and construction of an exemplar device, an engineered cell-cell communication receiver using standard biological parts (refined genetic objects designed to support physical and functional composition). I adopt a conventional framework for describing the behavior of engineered devices and use the adopted framework to design and interpret experiments that describe the behavior of the receiver. The output of the device is the activity of a promoter reported in units of Polymerases Per Second (PoPS), a common signal carrier. Second, I begin to address the coupling that exists between engineered biological systems and the host cell, or chassis. I propose that the coupling between engineered biological systems and the cellular chassis might be reduced if fewer resources were shared between the system and the chassis. I describe the construction of cellular chassis expressing both T7 RNA polymerases (RNAP) and orthogonal ribosomes that are unused by the chassis but are available for use by an engineered system. I implement a network in which the orthogonal ribosomal RNA and the gene encoding T7 RNAP are transcribed by T7 RNAP. In turn...

La voie de régulation de la traduction de l’ARNm ASH1 : une concertation entre Khd1, Puf6 et Loc1

Forget, Amélie
Fonte: Université de Montréal Publicador: Université de Montréal
Tipo: Thèse ou Mémoire numérique / Electronic Thesis or Dissertation
FR
Relevância na Pesquisa
46.08%
La localisation des ARNm par transport dirigé joue un rôle dans le développement, la motilité cellulaire, la plasticité synaptique et la division cellulaire asymétrique. Chez la levure Saccharomyces cerevisiæ, la localisation d’ARNm est un phénomène dont les mécanismes de régulation sont conservés auprès de nombreux autres organismes. Lors de la division de la levure, plus d’une trentaine de transcrits sont localisés par transport actif à l’extrémité du bourgeon de la cellule-fille. Parmi ceux-ci, l’ARNm ASH1 est le mieux caractérisé et constitue le modèle utilisé dans cette étude. Pour exercer sa fonction, la protéine Ash1 doit être produite uniquement après la localisation de l’ARNm ASH1. Pour ce faire, les mécanismes de régulation de la traduction de l’ARNm ASH1 empêchent son expression durant le transport. Ce projet de recherche vise à étudier les mécanismes de régulation de la traduction de l’ARNm ASH1 par les répresseurs traductionnels connus, soit Khd1, Puf6 et Loc1. Les études antérieures se sont penchées sur ces facteurs de manière individuelle. Cependant, dans cette étude, nous avons exploré la présence d’une collaboration entre ceux-ci. Ainsi, nous avons voulu déterminer si les répresseurs traductionnels peuvent être intégrés en une seule voie de régulation de la traduction de l’ARNm ASH1. De plus...

Increased antigen specific T cell numbers in the absence of altered migration or division rates as a result of mucosal cholera toxin administration

Kaparakis-Liaskos, Maria; Tate, Michelle D.; Price, Jason D.; Pearse, Martin; Wijburg, Odilia L. C.
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica Formato: 11 pages
Relevância na Pesquisa
46.03%
Cholera toxin (CT) is a mucosal adjuvant capable of inducing strong immune responses to co-administered antigens following oral or intranasal immunization of mice. To date, the direct effect of CT on antigen-specific CD4(+) T cell migration and proliferation profiles in vivo is not well characterized. In this study, the effect of CT on the migration pattern and proliferative responses of adoptively transferred, CD4(+) TCR transgenic T cells in orally or intranasally vaccinated mice, was analyzed by flow cytometry. GFP-expressing or CFSE-labeled OT-II lymphocytes were adoptively transferred to naïve C57BL/6 mice, and mice were subsequently vaccinated with OVA with or without CT via the oral or intranasal route. CT did not alter the migration pattern of antigen-specific T cells, regardless of the route of immunization, but increased the number of transgenic CD4(+) T cells in draining lymphoid tissue. This increase in the number of transgenic CD4(+) T cells was not due to cells undergoing more rounds of cellular division in vivo, suggesting that CT may exert an indirect adjuvant effect on CD4(+) T cells. The findings reported here suggest that CT functions as a mucosal adjuvant by increasing the number of antigen specific CD4(+) T cells independent of their migration pattern or kinetics of cellular division.; Grant support was received from the National Health and Medical Research Council of Australia (NHMRC). OLW is a recipient of an R.D. Wright Career Development Award.

Nitric oxide : cellular effects in vitro and in vivo

Wright, Teresa Leah, 1970-
Fonte: Massachusetts Institute of Technology Publicador: Massachusetts Institute of Technology
Tipo: Tese de Doutorado Formato: 170 leaves; 9263085 bytes; 9262842 bytes; application/pdf; application/pdf
ENG
Relevância na Pesquisa
46.04%
The overall aim of this project was to investigate various cellular responses and toxic effects of nitric oxide, NO' and in vitro and in vivo. Nitric oxide gives rise to a complex spectrum of reactive species in oxygenated solution. The complexity of nitric oxide's chemistry is recapitulated in its effects on cells. Exposure to nitric oxide can result in changes on many different levels in cells ranging from protein and DNA damage, to damage to organelles and changes in gene expression, and even in cell death. Many models to study nitric oxide have been developed and will be used to study various responses to nitric oxide and related species. Nitric oxide and peroxynitrite-induced cellular damage has been and continues to be studied extensively using in vitro systems. Two systems have been used in this project, a delivery system for NO' as well as a cell line, which produces NO'. A Silasticʾ membrane delivery system can be used to treat bacteria or cells to mimic in vivo exposure to nitric oxide. Mutations induced by nitric oxide in a set of Salmonella tester strains can be studied utilizing this delivery system. Activated RAW264.7 macrophage cells have been used as an in vitro model of nitric oxide production and cytotoxicity SJL/J mice bearing the transplantable lymphoma RcsX have been established as an in vivo model of nitric oxide production and toxicity.; (cont.) This in vivo mouse model can be used to test results found in vitro. Specifically...

Scalable computational architecture for integrating biological pathway models; IFN response to virus infection

Shiva, V. A
Fonte: Massachusetts Institute of Technology Publicador: Massachusetts Institute of Technology
Tipo: Tese de Doutorado Formato: 2 v. (xvii, 303 leaves)
ENG
Relevância na Pesquisa
36.14%
A grand challenge of systems biology is to model the cell. The cell is an integrated network of cellular functions. Each cellular function, such as immune response, cell division, metabolism or apoptosis, is defined by an interconnected ensemble of biological pathways. Modeling the cell or even one cellular function requires a computational architecture that integrates multiple biological pathway models in a scalable manner while ensuring minimal effort to maintain the resulting integrated model. Scalable is defined as the ease in which more and more biological pathway models can be integrated. Current architectures for integrating biological pathway models are primarily monolithic and involve combining each biological pathway model's software source code to build one large monolithic model that executes on a single computer. Such architectures are not scalable for modeling complex cellular functions or the whole cell. We present Cytosolve, a new computational architecture that integrates a distributed ensemble of biological pathway models and computes solutions in a parallel manner while offering ease of maintenance of the integrated model. The individual biological pathway models can be represented in SBML, CellML or in any number of formats. The EGFR model of Kholodenko with known solutions is used to compare the Cytosolve solution and computational times with a known monolithic approach. A new integrative model of the interferon (IFN) response to virus infection is developed using Cytosolve. Each model within the integrated model...

Analyzing Spatial Localization of Proteins of the Endoplasmic Reticulum in Budding Yeast, S. Cerevisiae, During Cell Division

Schmiedel, Lindsay
Fonte: University of Delaware Publicador: University of Delaware
Tipo: Tese de Doutorado
EN_US
Relevância na Pesquisa
46.12%
Anne Skaja Robinson; The first organelle of the secretory pathway, the endoplasmic reticulum (ER), is an essential organelle responsible for multiple critical processes of the cell. BiP, the molecular chaperone residing in the ER lumen of yeast, is involved in many of these intracellular processes including karyogamy (nuclear fusion during the mating of diploid cells), ER translocation of nascent protein, protein folding and maturation, and ERAD (ER associated degradation) of misfolded proteins. Due to BiP???s involvement in karyogamy and ER biogenesis, we have examined BiP???s role in the division of budding yeast, S. cerevisiae. The ER is a complex structure consisting of three subdomains including: (i) the peripheral ER found directly beneath the plasma membrane of the cell; (ii) the perinuclear ER, a structure that is continuous with the nuclear envelope; and (iii) a network of ER tubules connecting the former two domains. Using a combination of confocal light microscopy techniques and fluorescent protein variants, we have monitored dividing yeast cells expressing ER luminal proteins BiP and GFP retained in the ER (KGFP), ER membrane protein Sec61, and nuclear pore complex (NPC) protein Nup49, which spans both the perinuclear ER and nuclear membranes. Observation of ER inheritance during cellular division was classified as a three-step process identified by the segregation of ER subdomains. Phase 1 included the spatial localization of proteins to distinct areas of the peripheral ER as a bud emerges and continues to grow. The timescale of Phase 1 was approximately 55 minutes. Phase 2 consisted of nuclear division and was identified as the segregation of the perinuclear ER between the mother and daughter cell...