Near infrared fluorescent sensors and their use in vivo /

Includes vita.In an effort to design near-infrared (NIR), water soluble glucose sensors, several pH sensitive NIR cyanine derivates were designed and synthesized to provide insight into the viability of the cyanine platform as the fluorophore core for performing minimally invasive long term glucose monitoring in vivo. Many previous efforts to build effective fluorescent sensors for glucose have provided guidance towards the architecture of binding groups and fluorescent response required to achieve this goal, but have not provided appropriate solubility, or excitation and emission characteristics for in vivo sensing. In an effort to address the aqueous solubility of the highly rigid cyanine platform, a tetra sulfonated core was chosen for this work. Though fully water soluble, pH sensitive derivates still showed some aggregation characteristics. Simple sugarbinding boronic acid derivatives showed appropriate fluorescent responses, but poor binding. Efforts to improve binding through synthesis of bis-boronic acid compounds proved elusive.Dr. Timothy E. Glass, Dissertation Supervisor.|Includes vita.Includes bibliographical references (pages 101-118)

Preliminary design of a 100 kW turbine generator

The National Science Foundation and the Lewis Research Center have engaged jointly in a Wind Energy Program which includes the design and erection of a 100 kW wind turbine generator. The machine consists primarily of a rotor turbine, transmission, shaft, alternator, and tower. The rotor, measuring 125 feet in diameter and consisting of two variable pitch blades operates at 40 rpm and generates 100 kW of electrical power at 18 mph wind velocity. The entire assembly is placed on top of a tower 100 feet above ground level

Proceedings of the 3rd Annual Conference on Aerospace Computational Control, volume 1

Conference topics included definition of tool requirements, advanced multibody component representation descriptions, model reduction, parallel computation, real time simulation, control design and analysis software, user interface issues, testing and verification, and applications to spacecraft, robotics, and aircraft

A discontinuous Galerkin method for the solution of compressible flows

This thesis presents a methodology for the numerical solution of one-dimensional (1D) and two-dimensional (2D) compressible flows via a discontinuous Galerkin (DG) formulation. The 1D Euler equations are used to assess the performance and stability of the discretisation. The explicit time restriction is derived and it is established that the optimal polynomial degree, p, in terms of efficiency and accuracy of the simulation is p = 5. Since the method is characterised by minimal diffusion, it is particularly well suited for the simulation of the pressure wave generated by train entering a tunnel. A novel treatment of the area-averaged Euler equations is proposed to eliminate oscillations generated by the projection of a moving area on a fixed mesh and the computational results are validated against experimental data. Attention is then focussed on the development of a 2D DG method implemented using the high-order library Nektar++. An Euler and a laminar Navier–Stokes solvers are presented and benchmark tests are used to assess their accuracy and performance. An artificial diffusion term is implemented to stabilise the solution of the Euler equations in transonic flow with discontinuities. To speed up the convergence of the explicit method, a new automatic polynomial adaptive procedure (p-adaption) and a new zonal solver are proposed. The p-adaptive procedure uses a discontinuity sensor, originally developed as an artificial diffusion sensor, to assign appropriate polynomial degrees to each element of the domain. The zonal solver uses a modification of a method for matching viscous subdomains to set the interface conditions between viscous and inviscid subdomains that ensures stability of the flow computation. Both the p-adaption and the zonal solver maintain the high-order accuracy of the DG method while reducing the computational cost of the simulation

THE ROLE OF CYTOSOLIC CALCIUM IN POTENTIATION OF MOUSE LUMBRICAL MUSCLE

Following contractile activity, fast twitch skeletal muscle exhibits increases in submaximal force known as potentiation. Although there is no consensus on the purpose of potentiation, it is known to enhance power during rapid dynamic contractions and counteract the early stages of peripheral fatigue. Potentiation is primarily attributed to phosphorylation of the myosin regulatory light chain (RLC) through a calcium-mediated process which results in increased calcium-sensitivity of crossbridge formation. However, there is a growing body of evidence showing that potentiation can be achieved in the absence of RLC phosphorylation, albeit to a lesser degree. A secondary characteristic of the potentiated contraction is an acceleration of relaxation properties, which could be teleologically beneficial to enhance the cycling rate of rapid motions (e.g. running). However, accelerated relaxation is inconsistent with elevations in calcium-sensitivity as this would tend to slow the time course and slow relaxation. Therefore there are multiple mechanisms involved in potentiation, some of which enhance crossbridge formation, and some of which enhance crossbridge detachment. A possible explanation for these events involves contraction-induced changes in the intracellular cytosolic calcium signal that triggers muscle contraction. For example, elevations in submaximal force could be achieved by increasing the amplitude of the calcium signal while enhanced relaxation speed could be achieved by a shorter duration of the calcium signal. Thus the main objective of this thesis was to investigate the contribution of changes in cytosolic Ca2+ to force potentiation. To achieve this objective, intact lumbrical muscles were extracted from the hind feet of C57BL/6 mice for use as the experimental model. The first study in this thesis examined cytosolic calcium signals during posttetanic potentiation using high (AM-fura-2 and AM-indo-1) and low (AM-furaptra) affinity calcium-sensitive fluorescent indicators to monitor resting and peak calcium respectively, both before and after a potentiating stimulation protocol of 2.5 s of 20 Hz stimulation at 37oC. This protocol resulted in an immediate 17±3% increase in twitch force (n=10; P2+ was also increased following the potentiating stimulus as indicated by increases of 11.1 ± 1.3% and 8.1 ± 1.3% in the fura-2 and indo-1 fluorescence ratios respectively. Like the force potentiation, these increases were short lived, lasting 20-30 s. No changes were detected in either the amplitude or kinetics of the Ca2+ transients following the potentiating stimulus. Western blotting analysis of the myosin heavy chain isoforms which determine the contractile phenotype of lumbrical muscle revealed predominance of fast type IIX fibres, while immunohistochemical analysis of proteins important for relaxation, namely parvalbumin, sarco-endoplasmic reticulum Ca2+ ATPase (SERCA) 1a and SERCA2a, revealed that the expression of these proteins in lumbrical moderated those found in the soleus (slow) and EDL (fast) archetypes. Surprisingly, despite the fast phenotype of the lumbrical, it exhibited low expression of the skeletal muscle isoform of myosin light chain kinase, the enzyme responsible for phosphorylating the myosin RLC, and high expression of myosin targeting phosphatase subunit 2, the enzyme responsible for dephosphorylating the myosin RLC. These data were corroborated by a complete lack of myosin RLC phosphorylation in either the rested or potentiated states. It was thus concluded that elevations in resting cytosolic calcium concentration, in the absence of changes in the intracellular calcium transient and RLC phosphorylation, can potentiate twitch force. The next objective of this thesis was to determine if there are changes in the cytosolic calcium transient during staircase potentiation, defined as a stepwise increase in twitch force during low frequency stimulation (oC. This stimulation protocol resulted in a 26.8 ± 3.2 % increase in twitch force at 37oC (PoC (PoC than 37oC (PoC. The increases in the duration of the calcium transient were mirrored by increases in the half relaxation time of the twitch contractions at both 30 and 37oC, which had initially been reduced by ~20 and 9 % at 30 and 37oC during the first 2 s of the protocol. Therefore the degree of staircase potentiation depends, in part, on the magnitude of the decline in the amplitude and the degree of slowing of the cytosolic calcium transient. The declines in calcium transient amplitude noted above occurred simultaneously with increased rates of relaxation and abbreviated contraction times. To determine if there was a causal relationship between the reduced amplitude and the faster contractions, AM-furaptra-loaded lumbrical muscles were stimulated at 8 Hz for 2 s in the presence and absence of caffeine, an agonist of the calcium release channel. Caffeine treatment attenuated the decline of the calcium transient amplitude (PoC (PoC (P<0.05). Despite the increases in calcium and force, the relaxation times and rates of relaxation exhibited a greater acceleration following caffeine treatment (P<0.05). Therefore the relaxation-enhancing factor during potentiated twitches cannot be attributed to the calcium transient, and must be localized to changes on the myofilament. The case for inorganic phosphate as the effector is made. Similar to the findings of the posttetanic potentiation study, the resting cytosolic calcium concentration was elevated during staircase potentiation, as revealed by fura-2 ratio signals. The largest increase occurring immediately following the first twitch of the protocol. This coincided with the largest increases in force potentiation at both 30 and 37oC. This finding is in accordance with the initial conclusion that elevations in resting calcium can enhance twitch force and contribute to potentiation, though the mechanism of action is unclear. One possibility is that increases in resting calcium, sub-threshold for force production, can enhance the number of attached but non-force producing crossbridges, thereby accelerating the transition of crossbridges to force-producing states upon calcium-release following stimulation. To test this hypothesis, the resting stiffness, a measure of crossbridge attachment, of lumbrical muscles was examined before and after a potentiating stimulus of 20 Hz 2.5 s. Resting stiffness was assessed using sinusoidal length oscillations, ~0.5 nm per half sarcomere in amplitude and ranging in frequency from 10-200 Hz. Subsequent analysis revealed decreases in the elastic stiffness (P<0.05) that lasted for ~20 s which were greater in magnitude (P<0.05) than increases in viscous stiffness which only lasted for ~5 s. This finding is consistent with the disappearance of short range elastic component (SREC) upon stretch or muscle activation which is commonly attributed to a population of stable, bound crossbridges in resting muscle. Subsequent analysis using imposed length changes to eliminate the SREC prior to contraction had no effect on the amplitude or duration of a subsequent twitch or tetanic contraction, and the changes in elastic and viscous stiffness of resting muscle were identical whether SREC was ablated by a contraction or imposed length change. Therefore it appears that potentiation occurs without an associated increase in bound crossbridges at rest, and may actually occur with fewer bound crossbridges at rest than the unpotentiated state. The lack of effect may be related to the relaxation-enhancing factor discussed above, and be an important feature of skeletal muscle serving to protect against damage via an involuntary eccentric contraction. This thesis describes potentiation as a complex and important biological function which is the sum of factors that serve to enhance and oppose force production

Performance-Based Design in Structural Fire Engineering

The performance-based design of structures in fire is gaining growing interest as a rational alternative to the traditionally adopted prescriptive code approach. This interest has led to its introduction in different codes and standards around the world. Although engineers widely use performance-based methods to design structural components in earthquake engineering, the adoption of such methods in fire engineering is still very limited. This Special Issue addresses this shortcoming by providing engineers with the needed knowledge and recent research activities addressing performance-based design in structural fire engineering, including the use of hotspot analysis to estimate the magnitude of risk to people and property in urban areas; simulations of the evacuation of large crowds; and the identification of fire effects on concrete, steel, and special structures

Aeronautical Engineering: A continuing bibliography with indexes

This bibliography lists 725 reports, articles and other documents introduced into the NASA scientific and technical information system in April 1985