Kinetic and thermodynamic analysis of proteinlike heteropolymers: Monte Carlo histogram technique

Using Monte Carlo dynamics and the Monte Carlo Histogram Method, the simple three-dimensional 27 monomer lattice copolymer is examined in depth. The thermodynamic properties of various sequences are examined contrasting the behavior of good and poor folding sequences. The good (fast folding) sequences have sharp well-defined thermodynamic transitions while the slow folding sequences have broad ones. We find two independent transitions: a collapse transition to compact states and a folding transition from compact states to the native state. The collapse transition is second order-like, while folding is first order. The system is also studied as a function of the energy parameters. In particular, as the average energetic drive toward compactness is reduced, the two transitions approach each other. At zero average drive, collapse and folding occur almost simultaneously; i.e., the chain collapses directly into the native state. At a specific value of this energy drive the folding temperature falls below the glass point, indicating that the chain is now trapped in local minimum. By varying one parameter in this simple model, we obtain a diverse array of behaviors which may be useful in understanding the different folding properties of various proteins.Comment: LaTeX, 16 pages, figures in separate uufile. Requires psfig.sty Minor revision, fixed typo in preprint number (no other changes

Folding Kinetics of Protein Like Heteropolymers

Using a simple three-dimensional lattice copolymer model and Monte Carlo dynamics, we study the collapse and folding of protein-like heteropolymers. The polymers are 27 monomers long and consist of two monomer types. Although these chains are too long for exhaustive enumeration of all conformations, it is possible to enumerate all the maximally compact conformations, which are 3x3x3 cubes. This allows us to select sequences that have a unique global minimum. We then explore the kinetics of collapse and folding and examine what features determine the various rates. The folding time has a plateau over a broad range of temperatures and diverges at both high and low temperatures. The folding time depends on sequence and is related to the amount of energetic frustration in the native state. The collapse times of the chains are sequence independent and are a few orders of magnitude faster than the folding times, indicating a two-phase folding process. Below a certain temperature the chains exhibit glass-like behavior, characterized by a slowing down of time scales and loss of self-averaging behavior. We explicitly define the glass transition temperature (Tg), and by comparing it to the folding temperature (Tf), we find two classes of sequences: good folders with Tf > Tg and non-folders with Tf < Tg.Comment: 23 pages (plus 10 figures included in a seperate file) LaTeX, no local report nu

Catalytic upgrading of phenolic compounds using ceria-based materials

This dissertation describes the catalytic upgrading of phenolic compounds over ceria-based materials. The work was motivated by the need to find alternative industrial uses for the light rare earth elements (e.g. cerium) as part of the Critical Materials Institute. Cerium is typically encountered in the +3 or +4 oxidation state and its dioxide is the most technologically advanced cerium compound. Cerium dioxide (ceria) is best known for its ability to release and store oxygen, thereby acting as an oxygen buffer in many catalytic systems. The oxygen storage and release capability has been exploited in three-way catalysis and is one of the most industrialized uses of cerium. Traditionally, ceria has been explored for small molecule (e.g. CO) oxidation catalysis, while its utility as a catalyst for organic oxidations has been gaining attention. The unique oxygen-activating property of ceria has delayed its study as a catalyst component for reductive transformations. Phenolics represent an interesting class of oxygenates for transformation over ceria-based materials. The chemistry of hydroxyl-containing compounds over ceria is well-studied and is often preceded by reactive adsorption to form activated intermediates. The economic importance of phenolics as precursors for nylon production and the oxygenate-activating ability of ceria-based materials provide a good starting point for determining alternative industrial uses for cerium. Furthermore, phenolics can be derived from renewable resources, an industrial sector that is expected to see large growth during the current century. Identifying active, selective, and environmentally friendly catalytic systems that convert biorenewable compounds into commodity chemicals is thus critical for ushering in the biorefinery era. The catalytic systems described here demonstrate ceria-based materials are active for the reductive transformation of phenolics using molecular hydrogen and aliphatic alcohols. Palladium supported on high-surface-area ceria was found to effectively catalyze the hydrogenation of phenol to cyclohexanone at atmospheric pressure and room temperature under batch conditions. The activity was highly dependent on the catalyst prereduction temperature which led to optimization of Pd dispersion and metal-support interactions. Analogous to alkyl alcohols, phenol underwent dissociative adsorption on ceria to yield cerium-bound phenoxy and water. The phenoxy species were activated toward dearomatization by molecular hydrogen. Palladium supported on high-surface-area ceria (Pd/CeO2) and sodium-modified ceria (Pd/Ce-Na) were used as catalysts for the aqueous-phase transfer hydrogenation of phenol using 2-propanol under flow conditions. Both catalysts were active and showed constant activity for 7 days on-stream. Pd/Ce-Na showed a marked increase (6x) in transfer hydrogenation activity over Pd/CeO2. Modification of ceria by sodium provided more 2-propanol adsorption sites and redox active sites (i.e. defects) for 2-propanol dehydrogenation which resulted in higher phenol transfer hydrogenation activity. For primary alcohols, reduction of the ceria support to from cerium hydroxy carbonate occurred and led to irreversible deactivation of the catalyst. A deactivation mechanism involving C-C scission of acyl and carboxylate intermediates to form CO was proposed. Deposition of trimethylphosphate onto ceria followed by thermal treatment resulted in formation of surface phosphates with retention of redox activity. The introduction of phosphates generated Brønsted acidic sites and decreased the number of Lewis acidic sites on the surface. Upon deposition of Pd, the multifunctional material showed enhanced activity for phenolic hydrogenolysis compared to Pd on the unmodified ceria support. This was attributed to the cooperativity between the Lewis acid sites, which activate phenolics for dearomatization, and the redox/acid property, which catalyzes hydrogenolysis

An Evaluation of Oracle\u27s StillImage Plugin as a Platform for Dynamic Image Search

In this project, we look at some different off­-the­-shelf solutions for creating an image search engine that, given an unknown cover for a comic book, would return relevant information about a matching comic book in the database. The project first examines some alternative tools available to developers to do image search and comparison, and then looks at Oracle\u27s solution for image comparison, Still Image. A prototype search is built to test Oracle\u27s capabilities and is evaluated on speed and quality of results. In the end, Oracle is determined to be a useful tool for storing and comparing images, but is still not capable of searching for an image in a reasonable amount of time

Templated synthesis of nickel nanoparticles: Toward heterostructured nanocomposites for efficient hydrogen storage

The world is currently facing an energy and environmental crisis for which new technologies are needed. Development of cost-competitive materials for catalysis and hydrogen storage on-board motor vehicles is crucial to lead subsequent generations into a more sustainable and energy independent future. This thesis presents work toward the scalable synthesis of bimetallic heterostructures that can enable hydrogen to compete with carbonaceous fuels by meeting the necessary gravimetric and volumetric energy densities and by enhancing hydrogen sorption/desorption kinetics near ambient temperatures and pressures. Utilizing the well-known phenomenon of hydrogen spillover, these bimetallic heterostructures could work by lowering the activation energy for hydrogenation and dehydrogenation of metals. Herein, we report a novel method for the scalable synthesis of silica templated zero-valent nickel particles (Ni⊂SiO2) that hold promise for the synthesis of nickel nanorods for use in bimetallic heterostructures for hydrogen storage. Our synthesis proceeds by chemical reduction of a nickel-hydrazine complex with sodium borohydride followed by calcination under hydrogen gas to yield silica encapsulated nickel particles. Transmission electron microscopy and powder X-ray diffraction were used to characterize the general morphology of the resultant nanocapsules as well as the crystalline phases of the incorporated Ni0 nanocrystals. The structures display strong magnetic behavior at room temperature and preliminary data suggests nickel particle size can be controlled by varying the amount of nickel precursor used in the synthesis. Calcination under different environments and TEM analysis provides evidence for an atomic migration mechanism of particle formation. Ni⊂SiO2 nanocapsules were used as seeds to induce heterogeneous nucleation and subsequent growth within the nanocapsule via electroless nickel plating. Nickel nanoparticle growth occurs under high temperature alkaline conditions, however silica nanocapsule integrity is not maintained due to the incompatibility of silica with the growth conditions. Silica nanocapsule integrity is maintained under low temperature neutral conditions, but nickel particle growth is not observed. Through FTIR and UV/Vis analysis, we show the degree of crosslinking and condensation increases in calcined silica compared to as-synthesized silica. We propose the increased density of the silica nanocapsule hinders mass transfer of the bulky nickel precursor complex from solution and onto the surface of the catalytic zero-valent nickel seed within the nanocapsule cavity. Decreasing the density of the silica nanocapsule can be achieved through co-condensation of tetraethylorthosilicate with an alkyl functionalized silane followed by calcination to remove the organic component or by chemical etching in alkaline solution, but will not be addressed in this thesis

MODULAR CABLE - DRIVEN SURGICAL ROBOTS

A surgical robot can be configured for minimally invasive surgery ( MIS ) and other types of surgery with modular link geometry and disposable components. In some examples, the surgical robot includes a cable driver comprising at least one drive motor configured for tensioning a cable. The surgical robot includes an articulated surgical tool coupled to the drive motor by the cable. The articulated surgical tool comprises at least first and second articulated links and a joint coupling the first and second articulated links. The cable passes through the joint, and the joint comprises an elastic antagonist biased in opposition to tension from the cable to allow bidirectional actuation of the joint. The surgical robot includes a safety lock configured to lock the joint from allowing articulation of the first and second articulated links in response to a loss of tension in the cable

The Ras effector NORE1A forms a tumor suppressor complex with BRCA1.

Ras proteins function as molecular signaling switches that can stimulate multiple mitogenic pathways in response to extracellular signaling. Oncogenic activation of Ras by structural mutation is a highly transforming event in ~1/3 of human cancers. However, aberrant Ras activation can also promote oncogene-induced senescence. This Ras-induced irreversible growth arrest is a physiological process that acts as a barrier to malignancy. The mechanisms by which Ras drives senescence and how this process is bypassed during Ras-driven transformation remains poorly understood. Although mutations in the RAS gene are extremely rare in human breast cancer, the Ras signaling pathway is constitutively activated in roughly half of all primary breast tumors. This is largely due to aberrant activation of upstream regulators of Ras, like the EGFR family member Her2 and inactivation of negative Ras regulators, such as NF1. NORE1A (RASSF5) is a direct Ras effector that acts as a tumor suppressor by promoting apoptosis and senescence. Expression of NORE1A is frequently lost in primary breast tumors and breast cancer cell lines, though its mechanism of action in breast cancer pathogenesis remains unclear. BRCA1 is a tumor suppressor that plays a key role in DNA DSB repair. Loss of BRCA1 is associated with hereditary breast and ovarian cancer, and is also thought to play a role in sporadic breast cancer. Recently, BRCA1 was shown to play a role in both Her2 and Ras senescence, but the mechanism underlying the communication between Her2/Ras and BRCA1 was not identified. I have discovered that NORE1A forms an endogenous, Her2/Ras-regulated complex with BRCA1. I show that dual suppression of NORE1A and BRCA1 has a synergistic effect on transformation. Furthermore, I show that NORE1A loss suppresses the BRCA1-mediated senescence effect. Finally, I show that NORE1A and BRCA1 synergize to modulate DNA repair. Thus, I identify a novel tumor suppressor complex that connects Her2/Ras senescence signaling to BRCA1 in breast cancer