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The molecular mechanism responsible for degenerative process in the nigrostriatal dopaminergic system in Parkinson’s disease (PD) remains unknown. One major advance in this field has been the discovery of several genes associated to familial PD, including alpha synuclein, parkin, LRRK2, etc., thereby providing important insight toward basic research approaches. There is an consensus in neurodegenerative research that mitochondria dysfunction, protein degradation dysfunction, aggregation of alpha synuclein to neurotoxic oligomers, oxidative and endoplasmic reticulum stress, and neuroinflammation are involved in degeneration of the neuromelanin-containing dopaminergic neurons that are lost in the disease. An update of the mechanisms relating to neurotoxins that are used to produce preclinical models of Parkinson´s disease is presented. 6-Hydroxydopamine, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, and rotenone have been the most wisely used neurotoxins to delve into mechanisms involved in the loss of dopaminergic neurons containing neuromelanin. Neurotoxins generated from dopamine oxidation during neuromelanin formation are likewise reviewed, as this pathway replicates neurotoxin-induced cellular oxidative stress, inactivation of key proteins related to mitochondria and protein degradation dysfunction, and formation of neurotoxic aggregates of alpha synuclein. This survey of neurotoxin modeling—highlighting newer technologies and implicating a variety of processes and pathways related to mechanisms attending PD—is focused on research studies from 2012 to 2014.

This thesis introduces a novel parametric beam model for describing the kinematics and elastic properties of ortho-planar compliant Micro-Electro-Mechanical Systems (MEMS) with straight beams subject to specific buckling loads. Ortho-planar MEMS have the ability to achieve motion out the plane on which they were fabricated, characteristic that can be used to integrate optical devices such as variable optical attenuators and micro-mirrors. In addition, ortho-planar MEMS with large output forces and long strokes could be used to develop new applications such as tactile displays, active Braille, and actuation of micro-mirrors. In order to analyze the kinematics and elasticity of a curved beam contained in a Micro Helico-Kinematic Platform (MHKP) device, this thesis offers an improved model of straight and curved flexures under compressive loads. This model uses an approach similar to the one applied to develop a regular Pseudo-Rigid -Body Model but it differs in the definition of a key parameter, the characteristic radius factor, γ, which is not a constant, but a function of the moment, γ*=γ(M) . This approach allows for the Pseudo-Rigid-Body Model (PRBM) to describe the motion taken by the deflected beam precisely over a large range of motion. In developing the model, this thesis describes kinematic and elastic parameters such as the angle coefficient, C9, the characteristic radius, γl, and the torque coefficient, Tθ. Furthermore, the torque coefficient is divided into two component functions, Tf, and, Tm, which can be used to find the working loads (force and moment) on the beam. The input displacement is the only needed state variable, object variables, which describe the beam, include the material modulus of elasticity, E, the moment of inertia, I, and its length, l.

No description available.

No description available.

A method for representing the design space of ortho-planar mechanisms has been developed. The method is based on the Theorem of Equality of Orientation Set Measures (TEOSM) which allows mechanisms to be represented by points in an abstract space. The method is first developed for single loop planar folded mechanisms with revolute joints, and later extended to mechanisms with prismatic joints and to spherical folded mechanisms. Functions which assign a value to each point in design space can be used to describe classes of mechanisms and evaluate their utility for MEMS design. Additionally, this work introduces the use of spherical mechanisms in MEMS design. Spherical mechanisms have characteristics that may be useful in MEMS, including the capability of spatial positioning of a link and the ability to convert rotation about an axis perpendicular to the substrate to rotation about an axis parallel to the substrate. Spherical kinematics has been used to develop three novel mechanisms, the Micro Helico-Kinematic Platform (MHKP), the Spherical Bistable Mechanism (SBM), and the Three-degree-of-freedom Platform (3DOFP). Mathematical models of these devices have been developed and MEMS prototypes have been designed and fabricated.

No description available.

Orthophosphates and polyphosphates are rarely present at significant levels in raw water source but are purposefully added to the water in various forms to inhibit corrosion, iron oxidation (red water), or calcium carbonate precipitation (scale formation). Orthophosphates serve as building blocks for polyphosphates, which includes structures in linear chain, branched chains (metaphosphate) and "glassy" polyphosphate polymers. The advantage of polyphosphates over ortho phosphates lies in the fact that they slowly revert to orthophosphates and thus provide corrosion inhibition action over longer period of time in distribution systems. A study was completed for Tampa Bay Water on water distribution systems in a changing water quality environment. Blended orthophosphates was used as one of the corrosion inhibitors to study its effects on metal release and thus justify its application in comparison to other corrosion inhibitors like orthophosphates, zinc orthophosphates and silicates. This work focuses on the study of reversion of polyphosphates to ortho phosphates. A first-order model was developed that quantifies reversion as a function of the hydraulic residence time and initial poly phosphate concentration. The same model was used in two different forms - one for the hybrid lines and the other for single material lines. The results from single material lines (estimated by a non linear least square regression using ANOVA) showed that the reversion rate was highest for galvanized pipe followed by unlined cast iron, lined cast iron and the lowest rate in PVC. The first-order reversion rate constant in PVC was almost two log orders less than galvanized line. A high first-order rate constant for the galvanized pipe could be attributed to a rougher surface, large surface area, reaction with the wall surface, pipe material or a combination of these effects. The results from the hybrid PDSs (estimated by an algebraic manipulation of the first-order reaction) substantially agree with the results obtained from the single material lines, with the exception of the PVC material. The data from the hybrid lines confirms that the reversion rate constant is greatest for exposure to galvanized pipe materials, but the hybrid data indicate that the rate constant associated with PVC is somewhat larger than the constants determined for either LCI or UCI. Once an overall first-order rate expression was established, efforts were made to find a relation between polyphosphate reversions with bulk water quality. None of the major water quality parameters were found to significantly affect the reversion. This observation may be attributable to a similar water quality over the study duration. A positive correlation was found between first-order reversion rate constant and temperature. An empirical equation (modified Arrhenius equation) that relates the first-order reversion rate constant with temperature was developed that showed a strong sensitivity to temperature. The results from this study could be used to predict the stability of polyphosphates in distribution systems with varying pipe materials and temperature.

Endosome is a major barrier to efficient gene transfection by synthetic vectors because if the vectors are trapped in the endosome, they will traffic to the lysosome where the DNA is enzymatically degraded. Our hypothesis which serves as the rationale for the design of ortho ester-based lipids and lipoplexes is that cationic lipids which can quickly hydrolyze into membrane-destabilizing fragments in response to a small drop of pH should improve the gene transfection efficiency by facilitating the endosome escape. We designed and synthesized five ortho ester-based acid-labile cationic lipids ( 1-5 ) and developed nine lipoplexes comprising the five lipids. HPLC and LC/MS studies revealed that the ortho ester linkage in lipids ( 1-5 ) hydrolyzed at mildly acidic endosomal pH 5.5. Dioleyl glycerol was identified to be the major hydrolysis product of lipids 1, 2, and 3 . Oleoyl alcohol and 1-oleyloxy-2-trimethylamionium-3-propanol were identified to be the major hydrolysis products of lipids 4 and 5 . Photon Correlation Spectrometry (PCS) studies revealed that acidic endosomal pHs triggered the aggregation of lipoplexes comprising 1, 2, and 3 . Lipoplexes comprising 4 and 5 retained their size over 50 hours at acidic pHs. The fluorescence assay indicated that the ortho ester-based lipoplexes comprising lipids 1, 2, and 3 quickly destabilized a model biomembrane in response to the acidic pH. Acidic pH did not cause the membrane destabilization by lipoplexes comprising 4 and 5 . These results demonstrate that ortho ester-based lipoplexes comprising lipids 1, 2, and 3 hydrolyze into membrane-destabilizing fragments in response to acidic pH. Luciferase gene transfection was conducted on CV-1cultured cells. The lipoplexes comprising ortho ester-based cationic lipids 1, 2, and 3 significantly enhanced the luciferase gene expression. Two lipoplexes 2 /DOPE/DNA and 3 /DOPE/DNA mediated 45-fold and 116-fold, respectively, higher luciferase expression in CV-1 cells compared to the pH-insensitive lipoplex DOTAP/DOPE/DNA. The gene transfection efficiency correlates well with the pH-triggered membrane-destabilization by the ortho ester-based lipoplexes.

Atmospheric deposition is a marginally understood source of nutrient loadings to waterbodies. Atmospheric deposition occurs via wet (rain, snow) and dry (gaseous and particulate transport) pathways. Bulk atmospheric deposition is defined as the total deposition from both wet and dry pathways. Utah Lake is a shallow eutrophic freshwater lake located in central Utah, USA. Recent studies have shown atmospheric deposition to be a significant contributor to the nutrient budget of Utah Lake. This study presents the analysis using three different methods of six years' worth of wet atmospheric deposition samples from nine locations around the lake, though these samples do include some contribution from dry deposition. We present and compare nutrient loads and nutrient loading rates for total phosphorus, total in-organic nitrogen, and ortho-phosphorus. We conclude that wet atmospheric deposition contributed between 309 to 529 tons of total phosphorus, 1,166 to 2,078 tons of total nitrogen, and 106 to 201 tons of ortho-phosphorus to the lake during the study period. We extracted loading rates for the calendar year (in tons per year) and winter/summer month (in tons per month) from the data from each of the three methods of analysis. We show that wet atmospheric deposition is a significant pathway in which nutrients are transported to Utah Lake.