Effect of arginine and oscillatory calcium ion (II) on vascular response mediated via nitric oxide signaling in normal and salt sensitive hypertensive rat mesenteric arterioles

Hypertension, a major risk factor in the cardiovascular system, is characterized by an increase in the arterial blood pressure. High dietary sodium is linked to multiple cardiovascular disorders including hypertension. Salt sensitivity, a measure of how the blood pressure responds to salt intake is observed in more than 50% of the hypertension cases. Nitric Oxide (NO), as an endogenous vasodilator serves many important biological roles in the cardiovascular physiology including blood pressure regulation. The physiological concentrations for NO bioactivity are reported to be in 0-500 nM range. Notably, the vascular response to NO is highly regulated within a small concentration spectrum. Hence, much uncertainty surrounds how NO modulates diverse signaling mechanisms to initiate vascular relaxation and alleviate hypertension. Regulating the availability of NO in the vasculature has demonstrated vasoprotective effects. In addition, modulating the NO release by different means has proved to restore endothelial function. In this study we addressed parameters that regulated NO release in the vasculature, in physiology and pathophysiology such as salt sensitive hypertension. We showed that, in the rat mesenteric arterioles, Ca2+ induced rapid relaxation (time constants 20.8 ± 2.2 sec) followed with a much slower constriction after subsequent removal of the stimulus (time constants 104.8 ± 10.0 sec). An interesting observation was that a fourfold increase in the Ca 2+ frequency improved the efficacy of arteriolar relaxation by 61.1%. Our results suggested that, Ca2+ frequency-dependent transient release of NO from the endothelium carried encoded information; which could be translated into different steady state vascular tone. Further, Agmatine, a metabolite of L-arginine, as a ligand, was observed to relax the mesenteric arterioles. These relaxations were NO-dependent and occurred via &agr;-2 receptor activity. The observed potency of agmatine (EC50, 138.7 ± 12.1 ± μM; n=22), was 40 fold higher than L-arginine itself (EC50, 18.3 ± 1.3 mM; n = 5). This suggested us to propose alternative parallel mechanism for L-arginine mediated vascular relaxation via arginine decarboxylase activity. In addition, the biomechanics of rat mesentery is important in regulation of vascular tone. We developed 2D finite element models that described the vascular mechanics of rat mesentery. With an inverse estimation approach, we identified the elasticity parameters characterizing alterations in normotensive and hypertensive Dahl rats. Our efforts were towards guiding current studies that optimized cardiovascular intervention and assisted in the development of new therapeutic strategies. These observations may have significant implications towards alternatives to present methods for NO delivery as a therapeutic target. Our work shall prove to be beneficial in assisting the delivery of NO in the vasculature thus minimizing the cardiovascular risk in handling abnormalities, such as hypertension.

Effect of Arginine and Oscillatory Ca2+ on Vascular Response Mediated Via Nitric Oxide Signaling in Normal and Salt Sensitive Hypertensive Rat Mesenteric Arterioles

Hypertension, a major risk factor in the cardiovascular system, is characterized by an increase in the arterial blood pressure. High dietary sodium is linked to multiple cardiovascular disorders including hypertension. Salt sensitivity, a measure of how the blood pressure responds to salt intake is observed in more than 50% of the hypertension cases. Nitric Oxide (NO), as an endogenous vasodilator serves many important biological roles in the cardiovascular physiology including blood pressure regulation. The physiological concentrations for NO bioactivity are reported to be in 0-500 nM range. Notably, the vascular response to NO is highly regulated within a small concentration spectrum. Hence, much uncertainty surrounds how NO modulates diverse signaling mechanisms to initiate vascular relaxation and alleviate hypertension. Regulating the availability of NO in the vasculature has demonstrated vasoprotective effects. In addition, modulating the NO release by different means has proved to restore endothelial function. In this study we addressed parameters that regulated NO release in the vasculature, in physiology and pathophysiology such as salt sensitive hypertension. We showed that, in the rat mesenteric arterioles, Ca2+ induced rapid relaxation (time constants 20.8 ± 2.2 sec) followed with a much slower constriction after subsequent removal of the stimulus (time constants 104.8 ± 10.0 sec). An interesting observation was that a fourfold increase in the Ca2+ frequency improved the efficacy of arteriolar relaxation by 61.1%. Our results suggested that, Ca2+ frequency-dependent transient release of NO from the endothelium carried encoded information; which could be translated into different steady state vascular tone. Further, Agmatine, a metabolite of L-arginine, as a ligand, was observed to relax the mesenteric arterioles. These relaxations were NO-dependent and occurred via α-2 receptor activity. The observed potency of agmatine (EC50, 138.7 ± 12.1 µM; n=22), was 40 fold higher than L-arginine itself (EC50, 18.3 ± 1.3 mM; n = 5). This suggested us to propose alternative parallel mechanism for L-arginine mediated vascular relaxation via arginine decarboxylase activity. In addition, the biomechanics of rat mesentery is important in regulation of vascular tone. We developed 2D finite element models that described the vascular mechanics of rat mesentery. With an inverse estimation approach, we identified the elasticity parameters characterizing alterations in normotensive and hypertensive Dahl rats. Our efforts were towards guiding current studies that optimized cardiovascular intervention and assisted in the development of new therapeutic strategies. These observations may have significant implications towards alternatives to present methods for NO delivery as a therapeutic target. Our work shall prove to be beneficial in assisting the delivery of NO in the vasculature thus minimizing the cardiovascular risk in handling abnormalities, such as hypertension.

Organizational response to employment under the ADA of workers with psychiatric disabilities: Four case studies

Title 1 of the Americans with Disabilities Act (ADA) requires all employers, public and private, with more than fifteen employees to provide reasonable accommodation to qualified individuals with disabilities if the accommodation would, within limits, allow the individual to perform the essential functions of the job. Seven years after Congress enacted the law and five years after the initial provisions became effective, little information is available about the experience of organizations faced with requests for workplace accommodation.^ The question addressed in this study is: How are organizations responding to the ADA mandate to fit individuals with psychiatric disabilities in the workplace? The data sources are three organizations that allowed access to this sensitive information, and a fourth that had two disability discrimination charges filed against it.^ A brute-force case method approach applied to the four organizations yields the following information: Attorneys are hesitant to allow inquiry into company policy owing to fear of litigation; workers are not disclosing and requesting accommodation; tacit accommodation of long-standing employees appears to be a regular practice; knowledge of the intent of the ADA makes a difference in terms of equality of treatment; and insensitivity to employee privacy results in an adversarial situation.^ Implications are relevant to the need to improve lines of communication between human resource, EEO, supervisory, and legal staff; consequences of failure to address accommodations on an explicit level; need for better understanding of the availability and use of outside resources for achieving accommodation; and improvement of self-advocacy and disclosure by the employees with disabilities. ^

Consumer (dis)satisfaction response to disconfirmation: An examination of the form and the underlying process

The purpose of this dissertation was to examine the form of the consumer satisfaction/dissatisfaction (CS/D) response to disconfirmation. In addition, the cognitive and affective processes underlying the response were also explored. ^ Respondents were provided with information from a prior market research study about a new brand of printer that was being tested. This market research information helped set prior expectations regarding the print quality. Subjects were randomly assigned to an experimental condition that manipulated prior expectations to be either positive or negative. Respondents were then provided with printouts that had performance quality that was either worse (negative disconfirmation) or better (positive disconfirmation) than the prior expectations. In other words, for each level of expectation, respondents were assigned to either positive or negative disconfirmation condition. Subjects were also randomly assigned to a condition of either a high or low level of outcome involvement. ^ Analyses of variance indicated that positive disconfirmation led to a more intense CS/D response than negative disconfirmation, even though there was no significant difference in the intensity for positive and negative disconfirmation. Intensity of CS/D was measured by the distance of the CS/D rating from the midpoint of the scale. The study also found that although outcome involvement did not influence the polarity of the CS/D response, the more direct measures of processing involvement such as the subjects' concentration, attention and care in evaluating the printout did have a significant positive effect on CS/D intensity. ^ Analyses of covariance also indicated that the relationship between the intensity of the CS/D response and the intensity of the disconfirmation was mediated by the intensity of affective responses. Positive disconfirmation led to more intense affective responses than negative disconfirmation. ^

The non-linear acousto-mechanical and thermodynamic response of spherical absorbers to laser pulses of various temporal profiles

This study is to theoretically investigate shockwave and microbubble formation due to laser absorption by microparticles and nanoparticles. The initial motivation for this research was to understand the underlying physical mechanisms responsible for laser damage to the retina, as well as the predict threshold levels for damage for laser pulses with of progressively shorter durations. The strongest absorbers in the retina are micron size melanosomes, and their absorption of laser light causes them to accrue very high energy density. I theoretically investigate how this absorbed energy is transferred to the surrounding medium. For a wide range of conditions I calculate shockwave generation and bubble growth as a function of the three parameters; fluence, pulse duration and pulse shape. In order to develop a rigorous physical treatment, the governing equations for the behavior of an absorber and for the surrounding medium are derived. Shockwave theory is investigated and the conclusion is that a shock pressure explanation is likely to be the underlying physical cause of retinal damage at threshold fluences for sub-nanosecond pulses. The same effects are also expected for non-biological micro and nano absorbers. ^

Characterization of ultra wideband antennas for personal communication devices using finite difference time domain technique

The current mobile networks don't offer sufficient data rates to support multimedia intensive applications in development for multifunctional mobile devices. Ultra wideband (UWB) wireless technology is being considered as the solution to overcome data rate bottlenecks in the current mobile networks. UWB is able to achieve such high data transmission rates because it transmits data over a very large chunk of the frequency spectrum. As currently approved by the U.S. Federal Communication Commission it utilizes 7.5 GHz of spectrum between 3.1 GHz and 10.6 GHz. ^ Successful transmission and reception of information data using UWB wireless technology in mobile devices, requires an antenna that has linear phase, low dispersion and a voltage standing wave ratio (VSWR) ≤ 2 throughout the entire frequency band. Compatibility with an integrated circuit requires an unobtrusive and electrically small design. The previous techniques that have been used to optimize the performance of UWB wireless systems, involve proper design of source pulses for optimal UWB performance. The goal of this work is directed towards the designing of antennas for personal communication devices, with optimal UWB bandwidth performance. Several techniques are proposed for optimal UWB bandwidth performance of the UWB antenna designs in this Ph.D. dissertation. ^ This Ph.D. dissertation presents novel UWB antenna designs for personal communication devices that have been characterized and optimized using the finite difference time domain (FDTD) technique. The antenna designs reported in this research are physically compact, planar for low profile use, with sufficient impedance bandwidth (>20%), antenna input impedance of 50-Ω, and an omni-directional (±1.5 dB) radiation pattern in the operating bandwidth. ^

Design and fabrication of two switched superconductivity microstrip hairpin filters using series micro-electro-mechanical systems (MEMS) switches

Series Micro-Electro-Mechanical System (MEMS) switches based on superconductor are utilized to switch between two bandpass hairpin filters with bandwidths of 365 MHz and nominal center frequencies of 2.1 GHz and 2.6 GHz. This was accomplished with 4 switches actuated in pairs, one pair at a time. When one pair was actuated the first bandpass filter was coupled to the input and output ports. When the other pair was actuated the second bandpass filter was coupled to the input and output ports. The device is made of a YBa2Cu 3O7 thin film deposited on a 20 mm x 20 mm LaAlO3 substrate by pulsed laser deposition. BaTiO3 deposited by RF magnetron sputtering in utilized as the insulation layer at the switching points of contact. These results obtained assured great performance showing a switchable device at 68 V with temperature of 40 K for the 2.1 GHz filter and 75 V with temperature of 30 K for the 2.6 GHz hairpin filter. ^

Algebraic theory of minimal nondeterministic finite automata with applications

Since the 1950s, the theory of deterministic and nondeterministic finite automata (DFAs and NFAs, respectively) has been a cornerstone of theoretical computer science. In this dissertation, our main object of study is minimal NFAs. In contrast with minimal DFAs, minimal NFAs are computationally challenging: first, there can be more than one minimal NFA recognizing a given language; second, the problem of converting an NFA to a minimal equivalent NFA is NP-hard, even for NFAs over a unary alphabet. Our study is based on the development of two main theories, inductive bases and partials, which in combination form the foundation for an incremental algorithm, ibas, to find minimal NFAs. An inductive basis is a collection of languages with the property that it can generate (through union) each of the left quotients of its elements. We prove a fundamental characterization theorem which says that a language can be recognized by an n-state NFA if and only if it can be generated by an n-element inductive basis. A partial is an incompletely-specified language. We say that an NFA recognizes a partial if its language extends the partial, meaning that the NFA’s behavior is unconstrained on unspecified strings; it follows that a minimal NFA for a partial is also minimal for its language. We therefore direct our attention to minimal NFAs recognizing a given partial. Combining inductive bases and partials, we generalize our characterization theorem, showing that a partial can be recognized by an n-state NFA if and only if it can be generated by an n-element partial inductive basis. We apply our theory to develop and implement ibas, an incremental algorithm that finds minimal partial inductive bases generating a given partial. In the case of unary languages, ibas can often find minimal NFAs of up to 10 states in about an hour of computing time; with brute-force search this would require many trillions of years.

Hybrid multi-objective optimization and hybridized self-organizing response surface method

Numerical optimization is a technique where a computer is used to explore design parameter combinations to find extremes in performance factors. In multi-objective optimization several performance factors can be optimized simultaneously. The solution to multi-objective optimization problems is not a single design, but a family of optimized designs referred to as the Pareto frontier. The Pareto frontier is a trade-off curve in the objective function space composed of solutions where performance in one objective function is traded for performance in others. A Multi-Objective Hybridized Optimizer (MOHO) was created for the purpose of solving multi-objective optimization problems by utilizing a set of constituent optimization algorithms. MOHO tracks the progress of the Pareto frontier approximation development and automatically switches amongst those constituent evolutionary optimization algorithms to speed the formation of an accurate Pareto frontier approximation. Aerodynamic shape optimization is one of the oldest applications of numerical optimization. MOHO was used to perform shape optimization on a 0.5-inch ballistic penetrator traveling at Mach number 2.5. Two objectives were simultaneously optimized: minimize aerodynamic drag and maximize penetrator volume. This problem was solved twice. The first time the problem was solved by using Modified Newton Impact Theory (MNIT) to determine the pressure drag on the penetrator. In the second solution, a Parabolized Navier-Stokes (PNS) solver that includes viscosity was used to evaluate the drag on the penetrator. The studies show the difference in the optimized penetrator shapes when viscosity is absent and present in the optimization. In modern optimization problems, objective function evaluations may require many hours on a computer cluster to perform these types of analysis. One solution is to create a response surface that models the behavior of the objective function. Once enough data about the behavior of the objective function has been collected, a response surface can be used to represent the actual objective function in the optimization process. The Hybrid Self-Organizing Response Surface Method (HYBSORSM) algorithm was developed and used to make response surfaces of objective functions. HYBSORSM was evaluated using a suite of 295 non-linear functions. These functions involve from 2 to 100 variables demonstrating robustness and accuracy of HYBSORSM.

Customization of the design of antenna using genetic algorithm and finite-difference time-domain technique

Antenna design is an iterative process in which structures are analyzed and changed to comply with certain performance parameters required. The classic approach starts with analyzing a "known" structure, obtaining the value of its performance parameter and changing this structure until the "target" value is achieved. This process relies on having an initial structure, which follows some known or "intuitive" patterns already familiar to the designer. The purpose of this research was to develop a method of designing UWB antennas. What is new in this proposal is that the design process is reversed: the designer will start with the target performance parameter and obtain a structure as the result of the design process. This method provided a new way to replicate and optimize existing performance parameters. The base of the method was the use of a Genetic Algorithm (GA) adapted to the format of the chromosome that will be evaluated by the Electromagnetic (EM) solver. For the electromagnetic study we used XFDTD™ program, based in the Finite-Difference Time-Domain technique. The programming portion of the method was created under the MatLab environment, which serves as the interface for converting chromosomes, file formats and transferring of data between the XFDTD™ and GA. A high level of customization had to be written into the code to work with the specific files generated by the XFDTD™ program. Two types of cost functions were evaluated; the first one seeking broadband performance within the UWB band, and the second one searching for curve replication of a reference geometry. The performance of the method was evaluated considering the speed provided by the computer resources used. Balance between accuracy, data file size and speed of execution was achieved by defining parameters in the GA code as well as changing the internal parameters of the XFDTD™ projects. The results showed that the GA produced geometries that were analyzed by the XFDTD™ program and changed following the search criteria until reaching the target value of the cost function. Results also showed how the parameters can change the search criteria and influence the running of the code to provide a variety of geometries.

Effective knowledge integration in emergency response organizations

Natural and man-made disasters have gained attention at all levels of policy-making in recent years. Emergency management tasks are inherently complex and unpredictable, and often require coordination among multiple organizations across different levels and locations. Effectively managing various knowledge areas and the organizations involved has become a critical emergency management success factor. However, there is a general lack of understanding about how to describe and assess the complex nature of emergency management tasks and how knowledge integration can help managers improve emergency management task performance. ^ The purpose of this exploratory research was first, to understand how emergency management operations are impacted by tasks that are complex and inter-organizational and second, to investigate how knowledge integration as a particular knowledge management strategy can improve the efficiency and effectiveness of the emergency tasks. Three types of specific knowledge were considered: context-specific, technology-specific, and context-and-technology-specific. ^ The research setting was the Miami-Dade Emergency Operations Center (EOC) and the study was based on the survey responses from the participants in past EOC activations related to their emergency tasks and knowledge areas. The data included task attributes related to complexity, knowledge area, knowledge integration, specificity of knowledge, and task performance. The data was analyzed using multiple linear regressions and path analyses, to (1) examine the relationships between task complexity, knowledge integration, and performance, (2) the moderating effects of each type of specific knowledge on the relationship between task complexity and performance, and (3) the mediating role of knowledge integration. ^ As per theory-based propositions, the results indicated that overall component complexity and interactive complexity tend to have a negative effect on task performance. But surprisingly, procedural rigidity tended to have a positive effect on performance in emergency management tasks. Also as per our expectation, knowledge integration had a positive relationship with task performance. Interestingly, the moderating effects of each type of specific knowledge on the relationship between task complexity and performance were varied and the extent of mediation of knowledge integration depended on the dimension of task complexity. ^

A digital signal processing approach for affective sensing of a computer user through pupil diameter monitoring

Recent research has indicated that the pupil diameter (PD) in humans varies with their affective states. However, this signal has not been fully investigated for affective sensing purposes in human-computer interaction systems. This may be due to the dominant separate effect of the pupillary light reflex (PLR), which shrinks the pupil when light intensity increases. In this dissertation, an adaptive interference canceller (AIC) system using the H∞ time-varying (HITV) adaptive algorithm was developed to minimize the impact of the PLR on the measured pupil diameter signal. The modified pupil diameter (MPD) signal, obtained from the AIC was expected to reflect primarily the pupillary affective responses (PAR) of the subject. Additional manipulations of the AIC output resulted in a processed MPD (PMPD) signal, from which a classification feature, PMPDmean, was extracted. This feature was used to train and test a support vector machine (SVM), for the identification of stress states in the subject from whom the pupil diameter signal was recorded, achieving an accuracy rate of 77.78%. The advantages of affective recognition through the PD signal were verified by comparatively investigating the classification of stress and relaxation states through features derived from the simultaneously recorded galvanic skin response (GSR) and blood volume pulse (BVP) signals, with and without the PD feature. The discriminating potential of each individual feature extracted from GSR, BVP and PD was studied by analysis of its receiver operating characteristic (ROC) curve. The ROC curve found for the PMPDmean feature encompassed the largest area (0.8546) of all the single-feature ROCs investigated. The encouraging results seen in affective sensing based on pupil diameter monitoring were obtained in spite of intermittent illumination increases purposely introduced during the experiments. Therefore, these results confirmed the benefits of using the AIC implementation with the HITV adaptive algorithm to isolate the PAR and the potential of using PD monitoring to sense the evolving affective states of a computer user.