University of Maryland, Baltimore County
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BIOCHEMICAL AND STRUCTURAL CHARACTERIZATION OF CATALYTIC AND REGULATORY CONSTRUCTS OF SOLUBLE GUANYLATE CYCLASE
No full textSoluble guanylate cyclase (sGC) is a key enzyme in the NO-sGC-cGMP signaling cascade and is crucial to cardiovascular regulation. NO binding to sGC regulatory domain enhances its basal catalytic activity to convert GTP to cGMP. The second messenger cGMP modulates downstream targets leading to vasodilation. Low output of this system results in hypertension and acute heart failure, two leading causes of death globally. sGC is a heterodimer of two homologous subunits: α and β. Each subunit contains an N-terminal regulatory domain (HNOX: Heme Nitric oxide OXygen), central dimerization HNOX associated (HNOXA) and coiled coil (CC) domains, and a C-terminal catalytic domain (GC). The enzyme is basally active in the absence of NO, but NO binding to the heme group of the β subunit HNOX domain enhances catalytic output several hundred fold. This domain acts as a brake on catalytic activity, but the mechanism by which the HNOX domain inhibits activity in the basal state and relays the NO activation signal to the catalytic domain remains elusive. By studying truncated sGC catalytic constructs, abGC and abCC-GC, we determined structural features necessary for enzymatic activity. Here, we report the first 1.9 � crystal structure of wild type human heterodimeric αβGC and specific catalytic activity normalized per molecule of αβGC heterodimer using native mass spectrometry. cGMP activity measurements show that the isolated catalytic domain only exhibits 0.01% of the basal activity of full-length sGC despite its ability to heterodimerize. We propose that additional domains are needed to achieve sGC full catalytic output. We further provide preliminary data suggesting that 29 C-terminal residues in αGC regulate enzymatic activity by modulating the heterodimeric interface of sGC catalytic domains. Preliminary small-angle X-ray scattering and computational modeling data provide first evidence for spatial domain orientations of the HNOX and HNOXA domains in heme-free homodimeric MBP-βHNOX-HNOXA-CCtruncated construct. This study provides a knowledge base for individual domain contributions to sGC activation and suggests which conformational changes may occur during activation. As such, the herein reported results could serve as a starting point for the rational structure-aided design of novel sGC activators for the treatment of cardiovascular diseases
Development of a Geared Infinitely Variable Transmission
No full textIn this work, a Geared Infinitely Variable Transmission (GIVT) which uses gears to transfer torque rather than frictional components is detailed. A comparison is made to existing continuously variable and infinitely variable transmission technology and a description of function in past and present GIVT designs is presented. The new GIVT features non-circular gearing and a scotch yoke mechanism to achieve zero speed fluctuation and avoid losses due to torque recirculation. A functioning prototype was designed and manufactured to test the performance of the scotch yoke mechanism. The theoretical efficiency was calculated and reported. New equations were derived to analyze the frictional power loss of a rack and pinion gear mesh, something which has been missing in gear design literature to date. The prototype efficiency was measured and compared to the theoretical efficiency. Using the theoretical and experimental results, several changes are proposed which will improve the performance and efficiency of the GIVT
Multigrid solution of distributed optimal control problems constrained by semilinear elliptic PDEs
No full textOptimization constrained by partial differential equations (PDEs) is a research area in which the scientific and engineering communities have seen a growing interest over the last decade. The recent rise in interest was fostered by the tremendous increase in computing power over the last twenty years. This can be attributed both to the tremendous advances in high-performance computing technologies and to its wide range of applicability. However, just growth in computing power is insufficient for tackling PDE-constrained optimization problems and there is always a need for ever-increasing efficient algorithms. The objective of this dissertation is to develop, analyze and implement multigrid preconditioners for the linear systems arising in the Newton-Krylov solution process for the nonlinear PDE constraints. Our main focus is on semilinear elliptic constraints with no additional control or state constraints. We analyze the preconditioners both theoretically and numerically. In this work we show that the multigrid preconditioners are of optimal order (p = 2) for piecewise linear finite element approximations. We also study control-constrained optimal control problems constrained by linear-elliptic equations. This problem is non-trivial from the optimization point of view as the KKT system is now a complementarity system. We employ semismooth Newton methods (SSNMs) to solve this problem efficiently. The multigrid preconditioners discussed here are extensions of preconditioners developed previously for the unconstrained case. We present some new results and techniques that yield optimal order multigrid preconditioners, at least for the case when the control is discretized using piecewise-constant finite elements
Acculturation, construction of gender and social identity in a sample of Afghan immigrants in the U.S.
No full textThis qualitative study, informed by the phenomenological approach, was an effort to examine the post-migration experiences of Afghan immigrants in the United States. Sarbin's social role theory framed the exploration of three processes: acculturation, construction of social identity and gender. Findings reveal that the three processes were not entirely distinct but influenced each other in important ways. Additionally, the pre-migration and post-migration factors shaped how they adapted within each of the four ecologies defined by Sarbin (1970). Furthermore, the sociopolitical context of relations between the United States and Afghanistan shaped the processes of acculturation, construction of gender and social identity of the participants. The implications of these findings for future research and programs are discussed
Modelling and Estimation of Characteristics of the Rainfall Distribution
No full textRainfall varies in space and time in a highly irregular manner and is described naturally in terms of a stochastic process. A characteristic of rainfall statistics is that they depend strongly on the space-time scales over which rain data are averaged. A spectral model of precipitation has been developed based on a stochastic differential equation of fractional order, which allows concise description of the second moment statistics over any space-time averaging scale. The model is thus capable of providing a unified description of both radar and rain gauge data. We test the model with radar and gauge data collected contemporaneously at the NASA TRMM ground validation sites located near Melbourne, Florida. Understanding precipitation is an essential component of climate modeling. Part of the calibration process for the recently launched GPM satellite involves comparison with radar observations. Ensuring that the radars are well calibrated is an import part of this process. We have used the developed stochastic model to explore sampling error for gauge and radar derived estimates of rain rates. This allows us to detect the presence and estimate the magnitude of any retrieval errors for the radar or gauge. We also formulated a standard linear regression analysis approach to the intercomparison of radar and gauge rain rate estimates in terms of the appropriate observed and model-derived quantities
Anomaly Detection in Data Streams with A-Distance: Effects of Multiple Anomalous Operators on Accuracy
No full textRecent research has shown positive outcomes in using the A-Distance metric to evaluate the current state of a planning domain to find anomalies with a low false positive rate. In order to use the A-Distance metric, which compares two arbitrary probability distributions, previous research converted the planning domains from a symbolic representation to a vector representation. Each column of the vector represents a predicate in the domain, which means there are as many data streams as there are predicates. When creating an anomaly, previous work removed a single operator from the planning domain, which causes a shift in the types of problems that can be solved. However, anomalies can affect many operators. In this thesis, an investigation on the effects of multiple anomalous operators on accuracy was conducted. These anomalous operators included adding multiple new operators to the domain under the closed world assumption, deleting multiple existing operators from the domain, and implementing failure rates to the original set of operators in the domain. Additionally, an exploration of three ways to structure the data streams in the interest of further minimizing the false positive rates was carried out. These methods include taking the sum of all values in a vector, taking the sum of the absolute values of their discrete derivatives, and running a Principle Component Analysis (PCA) on the data streams
Development Of Advanced Sandwich Core Topologies Using Fused Deposition Modeling And Electroforming Processes
No full textNew weight efficient materials are needed to enhance the performance of vehicle systems allowing increased speed, maneuverability and fuel economy. This work leveraged a multi-length-scale composite approach combined with hybrid material methodology to create new state-of-the-art additive manufactured sandwich core material. The goal of the research was to generate a new material to expands material space for strength versus density. Fused-Deposition-Modeling (FDM) was used to remove geometric manufacturing constraints, and electrodepositing was used to generate a high specific-strength, bio-inspired hybrid material. Microtension samples (3mm x 1mm with 250�m x 250�m gage) were used to investigate the electrodeposited coatings in the transverse (TD) and growth (GD) directions. Three bath chemistries were tested: copper, traditional nickel sulfamate (TNS) nickel, and nickel deposited with a platinum anode (NDPA). NDPA shows tensile strength exceeding 1600 MPa, significantly beyond the literature reported values of 60MPa. This strengthening was linked to grain size refinement into the sub-30nm range, in addition to grain texture refinement resulting in only 17% of the slip systems for nickel being active. Anisotropy was observed in nickel deposits, which was linked to texture evolution inside of the coating. Microsample testing guided the selection of 15�m layer of copper deposition followed by a 250 �m NDPA layer. Classical formulas for structural collapse were used to guide an experimental parametric study to establish a weight/volume efficient strut topology. Length, diameter and thickness were all investigated to determine the optimal column topology. The most optimal topology exists when Eulerian buckling, shell micro buckling and yielding failure modes all exist in a single geometric topology. Three macro-scale sandwich topologies (pyramidal, tetrahedral, and strut-reinforced-tetrahedral (SRT) were investigated with respect to strength-per-unit-weight. The topologies were optimized across length scales using texture on the nano-scale microsamples on the micro-scale, and the parametric column study on the meso-scale. The results showed that additive manufacturing as a viable method for removing geometric constraints observed by other manufacturing methods. The SRT was the most optimized topology showing the highest strength-per-unit-weight. The final topology sits in a best-of-both areas of material space exceeding the commercially available honeycombs strength per relative density by 1670%
Contextual Information Fusion for the Detection of Cyber-Attacks
No full textResearch in cyber-security has demonstrated that dealing with cyber-attacks is by no means an easy task. One particular limitation of existing research comes from the uncertainty of information gathered and used to discover attacks. Part of this uncertainty is related to lack of attack prediction models that take advantage of contextual information to analyze activities that target computer networks. A major challenge of the existing attack detection approaches is the identification of relevant information to a particular situation, and the use of such information to perform multi-evidence intrusion detection. Addressing such limitations require combining several aspects of context to better predict, avoid and respond to attacks so that several consistent evidence contribute to the decisions about the relevancy of attacks that target the network. A promising path along this direction is to elevate contextual information as a first class object in collecting and analyzing cyber security data. Yet again, the quality and adequacy of contextual information is important to decrease uncertainty in correctly identifying potential cyber-attacks. This dissertation introduces a novel framework that extracts and uses contextual information to discover cyber-attacks. A systematic methodology has been used to identify contextual dimensions that need to be considered to consequently improve the effectiveness of cyber-attack detection process. A methodology which combines graph, probability, and information theories along with domain knowledge is utilized to create several context-based attack prediction models that analyze data at a high- and low-level. This context-based framework identifies not only known, but also unknown attacks which an Intrusion Detection System (IDS) is not aware-of. The outlined framework can be mainly applied in conjunction with existing intrusion detection techniques to improve attack detection rate. In addition to showing the theoretical properties of the generated prediction models, several types of experiments have been conducted to evaluate the prediction models of known and unknown attacks. A comparison with other methodologies shows that a multi-layer fusion of contextual information in the process of attack discovery leads to superior results in terms of better attack detection and fewer false positive rates
Recoloring Web Pages For Color Vision Deficiency Users
No full textColor vision begins with the activation cone cells. When one of the cone cells dys- function, color vision deficiency (CVD) ensues. Due to CVD, users become unable to differentiate as many colors a normal person can. Lack of this ability results in less rich web experience, incomprehension of basic information and thus frustration. Solutions such as carefully choosing colors while designing or recolor web pages for CVD users exist. We first present the improvement in the time complexity of an existing tool SPRWeb[6] to re- color web pages. After that we present our tool, FBRecolor, which explores the foreground- background relationship between colors in a web page. Using this relationship we propose FBRecolor, which preserves naturalness, pair-differentiability and subjectivity. In the last part, we add an additional step in to FBRecolor to ensure that the contrast in the parsed color pairs meets the required W3C guidelines[5]. In evaluation, we found that FBRecolor does significantly better in preserving pair-differentiability and produces lower total cost solutions than SPRWeb. Quantitative experimentation of extension to FBRecolor shows that contrast ratio in each replacement pair is more than 4.5 as required for readability
Gum (2014)
No full textPromotional materials produced for Gum, performed by the UMBC Theatre Department in March 2014. Includes playbill, program, and ten publicity photographs.March 27-March 30, 201