No description available.

No description available.

Molecular chaperones and proteases help maintain protein homeostasis in the cell. While chaperones assist in the folding of polypeptide chains to their native state, proteases degrade misfolded or unfolded proteins and also help regulate protein levels. While mapping chaperone interaction networks, we found that tig (trigger factor chaperone gene), clpP and clpX genes co-localize next to each other on the genome of most examined bacteria. This led us to hypothesize that trigger factor (TF) chaperone and ClpXP protease might interact functionally. TF is a ribosome-associated chaperone that co-translationally folds polypeptide chains. ClpXP is a proteolytic complex that degrades a wide range of substrate proteins. We observed that TF enhanced the rate of the ClpXP degradation of the λO phage protein in vitro and in vivo. TF was also found to enhance the degradation of ribosome-stalled λO thus suggesting the existence of co-translational protein degradation in E. coli.

Thesis advisor: Peter Clote / RNA molecules play important roles in living organisms, such as protein translation, gene regulation, and RNA processing. It is known that RNA secondary structure is a scaffold for tertiary structure leading to extensive amount of interest in RNA secondary structure. This thesis is primarily focused on the development of novel algorithms for the analysis of RNA secondary structure evolution and folding kinetics. We describe a software RNAsampleCDS to generate mRNA sequences coding user-specified peptides overlapping in up to six open reading frames. Sampled mRNAs are then analyzed with other tools to provide an estimate of their secondary structure properties. We investigate homology of RNAs with respect to both sequence and secondary structure information as well. RNAmountAlign an efficient software package for multiple global, local, and semiglobal alignment of RNAs using a weighted combination of sequence and structural similarity with statistical support is presented. Furthermore, we approach RNA folding kinetics from a novel network perspective, presenting algorithms for the shortest path and expected degree of nodes in the network of all secondary structures of an RNA. In these algorithms we consider move set MS2 , allowing addition, removal and shift of base pairs used by several widely-used RNA secondary structure folding kinetics software that implement Gillespie’s algorithm. We describe MS2distance software to compute the shortest MS2 folding trajectory between any two given RNA secondary structures. Moreover, RNAdegree software implements the first algorithm to efficiently compute the expected degree of an RNA MS2 network of secondary structures. The source code for all the software and webservers for RNAmountAlign, MS2distance, and RNAdegree are publicly available at http://bioinformatics.bc.edu/clotelab/. / Thesis (PhD) — Boston College, 2018. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Biology.

In the deformation of layered materials such as geological strata, or stacks of paper, mechanical properties compete with the geometry of layering. Smooth, rounded corners lead to voids between layers, while close packing leads to geometrically induced curvature singularities. When creation of voids is penalized by external pressure, the system trades off these competing effects, leading to various accommodating formations. Three two dimensional energy based nonlinear models are presented to describe the formation of voids at areas of intense geological folding. For each model the layers are assumed to be flexible elastic beams under hard unilateral contact constraint; which are solved as quasi-static obstacle problems with a free boundary. In each case an application of Kuhn-Tucker theory leads to representation as a nonlinear fourth order differential equation. Firstly a single layered model for voiding is presented. An elastic layer is forced into a V-shaped singularity by a uniform overburden pressure, where the fourth order free boundary problem is shown to have a unique, convex, symmetric solution. Drawing parallels with the Kuhn-Tucker theory, virtual work and ideas of duality, the physical significance of this differential equation is emphasised. Finally, appropriate scaling of either the potential energy or the differential equation shows the solutions scale to a single parametric group, for which the size of the void scales inversely with the ratio of overburden pressure to bending stiffness of the layer. Common to structural geology, one or several especially thick layers can dominate the deformation process. As a result, the remaining weak layers must accommodate into the geometry imposed by these competent layers. The second model, extends the first by introducing a plastic hinge to replicate the geometry imposed by the competent layer, and also axial springs to resist the slip over the limbs. The equilibrium equations for the system are investigated using the mathematical techniques developed for the first model. Under rigid loading the system may snap from an initially flat state to a convex voiding solution, as seen in the first model. However, if resistance to slip is high, the slightest imperfection causes the system to jump to a convoluted up-buckled solution, following a de-stiffened path to a point of self contact. These solutions have similarities with the delamination of carbon fibre composites. Finally, we extend the two single layered models to a simple multilayered model, which describes the periodic formation of voids in a chevron fold. The model shows that in the limit of high overburden pressures solutions form voids every layer, producing straight limbs punctured by sharp corners. This analysis shows good agreement when compared with recent experiments. This work provides the basis for future work on the buckling of thin multilayer assemblies in which voids may develop, and emphasizes the importance of the intricate nonlinear constraints of layers fitting together in multilayered folds.

Made available in DSpace on 2014-06-11T19:30:54Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-08-01Bitstream added on 2014-06-13T20:01:01Z : No. of bitstreams: 1 oliveira_rj_dr_sjrp.pdf: 3645510 bytes, checksum: 181949bcc7d9fbd2c0929fdd73a9cf0a (MD5) / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / A difusão desempenha um papel importante na cinética de eno-velamento de proteínas. Nessa tese, desenvolvemos métodos analíticos e computacionais para o estudo do coeficiente de difusão dependente da posi-ção e do tempo. Para estes estudos, utilizou-se sobretudo o modelo baseado na estrutura (modelo G¯o) via simulação computacional da representação em carbonos alfa. Investigou-se o efeito da difusão no enovelamento da proteína cold-shock (TmCSP). Encontrou-se que o efeito temporal da difusão leva a cinéticas não-exponenciais e a estatística não-poissônica da distribuição de tempos de enovelamento. Com relação a dependência com a posição, o coeficiente de difusão revelou ter um comportamento não-monotônico que foi compreendido pela análise dos valores- e da entropia residual no estado nativo. Para uma versão frustrada do modelo, encontrou-se que um baixo nível de frustração energética aumenta a difusão no estado nativo e torna o estado de transição mais homogêneo. Esses resultados corroboram com experimentos recentes de fluorescência de uma única molécula. Esse trabalho também propõe um método para a determinação da superfície de energia de enovelamento de proteína. A partir da caracterização da superfície de energia, definimos a quantidade (LD – Landscape Descriptor) que mostrou uma forte correlação entre a cinética e a termodinâmica de uma dezena de proteínas globulares, tornando-se um método útil para classificar proteínas / Diffusion plays an important role in protein folding kinetics. In this thesis we developed analytical and computational methods in order to study the diffusion coefficient dependent on position and time. For these studies we used mainly the structure-based model (G¯o model) via computer simulation of the alpha-carbon representation. We investigated the effect of diffusion in the folding of the cold-shock protein (TmCSP). We found that the time dependence on diffusion leads to non-exponential kinetics and non-Poisson statistics of folding time distribution. With respect to the position dependence, the diffusion coefficient reveled a non-monotonic behavior that was understood by analyzing the -values and the residual entropy in the native state. For a frustrated version of the model, we found that a low level of frustration energy stabilizes and increases the diffusion in the native state and the transition state becomes more homogeneous. These results are supported by recent single-molecule fluorescence experiments. This work also proposes a method to determine the protein folding energy landscape. With the energy landscape characterized, we defined the quantity (LD – Landscape Descriptor) which showed a strong correlation between kinetics and thermodynamics of a dozen globular proteins making it a useful method to classify proteins

This work investigates how curved-crease origami and the developable surfaces which compose it can be transitioned to engineering design. Methods for creating flexible, tailorable-property surfaces that function as thick panels in place of paper are presented. Concepts from curved-crease origami and developable surfaces that can describe and extend engineering applications are discussed and demonstrated. These concepts are particularly beneficial to applications where curved surfaces are integral to the function, deployability is desired, and planar manufacturing could be beneficial.The first part of this work uses arrays of compliant elements to create flexible-tailorable property surfaces. The key feature to these arrays is the alignment of the most flexible bending axis of the individual elements to the ruling line arrangement of a developable surface. This alignment can enable bending of thick panels while maintaining lower stresses, a quality necessary for the transitioning of curved-crease origami into thick materials. The stiffness and stress of these arrays is modeled and physical prototypes are demonstrated. Additionally, shape factors are developed for these compliant arrays (CAs) to facilitate material selection for the panels and understand how the geometry of the array changes the effective properties of the panel. The second part of this work describes and demonstrates several concepts of curved-crease origami and developable surfaces that can benefit mechanism and structure design, particularly in the context of rolling-contact mechanisms. The design of a rolling-contact joint connected by flexible bands similar to a Jacob's Ladder toy is extended through incorporating curved creases into the design. The resulting design is deployable from a compact state to a functional state and can be manufactured from a single plane and folded into shape. Mathematical formulations are presented to describe the classes of developable surfaces in terms of properties which are frequently important in mechanism design. These natural equations for a single class of developable surface are conducive to modeling the folding motion of rigid-ruling developables, developables whose ruling lines do change location in a surface during folding. These formulations are used to generalize the design of rolling-contact joints to a family of joints capable of single degree of freedom spatial motions, being manufactured from a plane, and exhibiting a tailorable force response. Finally practical design suggestions for the implementation of rolling-contact joints is given. These include methodology to create sunken flexures which serve to increase the normal force between rolling bodies to prevent slip.

No description available.

Thesis (Ph. D.)--University of Washington, 2006. / Vita. Includes bibliographical references (leaves 140-148).

Thesis (M.S.)--University of Delaware, 2006. / Principal faculty advisor: Neal Zondlo, Dept. of Chemistry & Biochemistry. Includes bibliographical references.