http://hdl.handle.net/1813/35 Cornell University Graduate School On-line Theses and Dissertations http://dspace.library.cornell.edu/retrieve/49 http://hdl.handle.net/1813/35 Search the Channel search http://dspace.library.cornell.edu/simple-search http://hdl.handle.net/1813/11464 Title: Listeria monocytogenes pathogenesis: Part I: The role of flagella mediated motility Part II: The function of the metalloprotease propeptide <br/> <br/>Authors: O'Neil, Heather <br/> <br/>Abstract: Listeria monocytogenes is a food borne, intracellular bacterial pathogen. Successful infection requires completion of two steps: penetration of the intestinal epithelium and escape from the phagocytic vacuole. This dissertation examines the role of flagella mediated motility in host cell invasion, and the function of the metalloprotease (Mpl) propeptide in mediating the maturation of a bacterial phospholipase required for efficient escape from the phagocytic vacuole. We examined the contribution of flagella to L. monocytogenes pathogenesis. We observed that flagella mediated motility enhance the bacterial rate of invasion. To determine if flagella are adhesins, we performed adhesion and invasion assays with flagellated motile and non-motile bacteria, and non-flagellated bacteria. Flagellated but non-motile bacteria did not adhere to or invade human epithelial cells more efficiently than non-flagellated bacteria. These results indicate that flagella do not function as adhesins to host cells. Instead, motility is important for host cell invasion. Moreover, in vivo motile bacteria out competed non-motile bacteria in the colonization of the mouse intestines and liver at early time points after oral infection, suggesting that flagella-mediated motility enhances L. monocytogenes infectivity soon after bacterial ingestion. Mpl regulates the activity and compartmentalization of a bacterial phospholipase C (PC-PLC). Mpl is secreted as an inactive proprotein. In related proteases, the propeptide can serve as a folding catalyst (either in cis or in trans), influence protein compartmentalization, participate in intracellular trafficking, or decrease folding kinetics. We investigated the role of the Mpl propeptide by monitoring the behavior of Mpl synthesized in absence of its propeptide (Mpl?pro) and of two Mpl mutants with unstable propeptides. All three mutants mediated PC-PLC activation in vitro but were not functional in infected cells. This defect was not rescued by providing the propeptide in trans to the mpl?pro mutant. We also determined that PC-PLC co-purified with wild-type Mpl, Mpl?pro, and the Mpl propeptide indicating that the propeptide is not required for Mpl / PC-PLC interaction. However, the mutant Mpl species were aberrantly secreted in the cytosol of infected cells. These data indicate that the propeptide of Mpl maintains Mpl bacteria-associated, and that localization is essential to Mpl function during infection. http://hdl.handle.net/1813/11463 Title: NUMERICAL SOLUTIONS FOR FINITE STRAIN CRACK TIP FIELDS IN SOFT INCOMPRESSIBLE SOLIDS <br/> <br/>Authors: Krishnan, VenkatRamanan <br/> <br/>Abstract: This dissertation concerns itself with problems involving cracks under finite deformation in incompressible hyperelastic materials with special application to soft materials. The main focus is on using numerical methods, in particular the finite element method (FEM), to find the solution of crack tip fields under applied far field loads, in materials undergoing axisymmetric, plane stress and plane strain deformations. In the first chapter a large strain finite element analysis is used to study the deformation of an incompressible Neo-hookean half space in contact with a flat rigid cylindrical punch. Adhesion is assumed between the elastic solid and punch and the deformation is studied as the punch is retracted. Two interface conditions, frictionless and no slip, are considered. Numerical results are compared with prediction of small strain linear elastic (SSLE) theory. The results show that many aspects of the deformation are not captured by the SSLE theory. For example, the interfacial normal stress at the punch edge is much higher for the case with frictionless boundary condition. The deformation profiles are also very different. The results give important insights on how soft adhesives deform when they detach from a hard surface. The second chapter makes use of a finite element model to study the behavior of the large deformation field near the tip of a crack in a soft incompressible plane stress fracture specimen loaded in Mode I. Results are obtained for the case of a Neohookean solid (ideal rubber) and a hyperelastic solid with exponentially hardening behavior. In contrast to the predictions of linear elastic fracture mechanics (LEFM), the near tip stress fields are dominated by the opening stress which shows a 1/R singularity for the Neohookean material and a -1/RlnR singularity for the exponential hardening solid. The results show very similar qualitative behavior in the near tip stress fields despite the very large difference in strain hardening behavior of the two material models. Further, the results show that the near tip opening stress is controlled by the far field energy release rate for large applied loads. The third chaper presents a numerical study of finite strain deformation fields near the tip of an interface crack between a rigid substrate and an incompressible hyperelastic solid using the finite element method (FEM). The FEM simulations make use of a remeshing scheme to overcome mesh distortion. Analyses are carried out by assuming that the crack tip is either ?pinned?, i.e., the elastic material is perfectly bonded (full friction) to the rigid substrate, or frictionless. The focus is on a material which hardens exponentially. For both the frictionless interface and the pinned crack under plane stress deformation, it is found that the true stress field directly ahead of the crack tip is dominated by the normal stress (T22) and the crack face opens up smoothly. This is also true for an interface crack along a frictionless boundary in plane strain deformation. However, for a pinned interface crack under plane strain deformation, the true opening normal stress (T22) is found to be lower than the shear stress (T12) and the transverse normal stress (T11). Also, the crack opening profile for a pinned crack under plane strain deformation is completely different from those seen in plane stress and in plane strain (frictionless boundary condition). The crack face flips over and the tip angle is almost tangent to the interface. The results suggest that interface friction can play a very important role in interfacial fracture of soft materials on hard substrates. http://hdl.handle.net/1813/11458 Title: TALKING ABOUT THE AESTHETIC OF THE HUMANE: EXPLORING COMMUNICATION IN THE CONTENT AND STRUCTURE OF HEINRICH B?LL?S EARLY NOVELS <br/> <br/>Authors: Low, David <br/> <br/>Abstract: In his Frankfurter Vorlesungen Heinrich B?ll attempts to formulate an aesthetic program that explains how the moral content of writing might be inscribed in its structure. This ?aesthetic of the humane? would involve the subject-matter and orientation of a work?s content toward the representation of the historically real and the truth content of that reality. The ?real? as it is in the historical world and that ?reality? that contains the truth content of the experienced world are to be unified in the aesthetic of the humane, and it is the author who is burdened with the task of mediating the two for her reader. In many of his essays B?ll privileges communication as an inherently moral act, and emphasizes the responsibility of the author to use his vocation humanely. In order to understand how B?ll realized the concept of the aesthetic of the humane in his own writing we may look to how he uses communication within his texts to demonstrate moral action. Communication between characters at the level of plot corresponds to the author?s obligation to depict the ?real? historical component, and communicative structures in the matrix of his novels relate to the ?reality? of mediated experience provided as commentary by the author to the reader. This thesis examines how B?ll delivers these dual messages using the depiction of communication in three of his early novels. B?ll?s early novels were chosen for analysis because they correspond to a period in his career before his writing entered into a direct dialogue with his detractors and political opponents. His later writing may be seen as responses to ?real? historical developments in his life, and as such do not exhibit the balance of the ?real? and ?reality? that are the goal of the engaged writer according to his own essays. Through a discussion of Und sagte kein einziges Wort, Billard um halb zehn, and Ansichten eines Clowns this thesis concludes that as of the moment that he articulates his aesthetic program in 1964 B?ll harbored doubts about its effectiveness to reach his audience and affect any meaningful change in society. http://hdl.handle.net/1813/11454 Title: HEALTHCARE STRATEGIC SUSTAINABILITY: KEY FACTORS AFFECTING THE TRIPLE BOTTOM LINE IN CONVERTING INPATIENT TO OUTPATIENT FACILITIES <br/> <br/>Authors: Zajac, David <br/> <br/>Abstract: Healthcare strategic sustainability seeks to integrate in a cost effective manner sustainable development and design practices with health care facilities that are holistic places of healing for patients; and a safe, efficient, and effective environment for staff. This study focused on six United States Army military healthcare facilities involving conversion from inpatient to outpatient facilities. Data was collected in an intensive interview process from twenty-nine participants representing three stakeholder categories: planners (design and construction), operators (facility management and information technology), and users (clinical staff). The specific research questions addressed what design/building changes were made to accommodate the change from an in-patient to an outpatient care business model; and which existing design/building elements generated significant constraints or benefits when implementing the desired new design concept? The research also explored whether any desired design/building changes were not made, and why; and the extent to which social (quality of care and/or quality of life), economic (cost), or environmental (adaptable and sustainable) factors were considered? The findings confirm the impact of certain design elements on the conversion and adaptability of hospitals; and suggest the need to educate organizations on which design elements to invest in that not only meet cost and environmental quality goals, but also contribute positively to staff quality of life.