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Title: A COMPRHENSIVE MECHANISTIC STUDY OF PEPTIDOMIMETICS ON MODEL MEMBRANE SYSTEMS
Creator: Bianchi, Christopher P.
Date: 2014, 2014-12
Description: Peptidomimetics are a broad class of structural variant synthetic mimics of antimicrobial peptides (AMPs). AMPs are natural antibiotics found...
Show morePeptidomimetics are a broad class of structural variant synthetic mimics of antimicrobial peptides (AMPs). AMPs are natural antibiotics found in almost entirety throughout all living organisms. Although, AMPs were once thought of as promising therapeutics to combat infectious bacteria, key shortcomings such as low bioavailability, as well as high manufacturing costs have prevented them from reaching a clinical market. Peptidomimetics capitalize on the characteristics of AMPs thought to be responsible for their antibacterial activity, such as net cationic charge and amphiphilicity, while introducing key structural differences. The principal mode of antibacterial activity of AMPs is causing disruption to the bacteria cell membrane of both Gram-positive and Gram-negative bacteria types. The complexities of cell membranes with their various lipid molecule species and proteins makes it difficult to determine mechanistic details of AMPs. It is for this reason model membrane systems such as Langmuir monolayers and supported bilayers composed of the lipid species found in that of actual cell membrane are used. In the present work we have investigated the mechanism of action of different types of peptidomimetics such as N-substituted glycines (peptoids) and oligomers of acylated-lysines (OAKs) on model bacteria and cancer cell membrane systems using various experimental techniques, such as epifluorescence microscopy (EFM), atomic force microscopy (AFM), X-ray reflectivity, and grazing incidence X-ray diffraction (GIXD). From these studies structure function relationships can be obtained, which help aid in the design of new and more effective peptidomimetics. Through these investigations it was found that the substitution of hydrogen atoms for fluorine atoms in the phenyl side chains of cyclic peptoids increases antibacterial on both Gram-positive and Gram-negative model membrane systems, guanidino containing side chains compared to amino containing side chains in α-peptide-β-peptoid chimeras show greater activity on model membrane systems mimicking the cytoplasmic membrane of both Gram-positive and Gram negative bacteria. In addition, insights were gained on the anticancer mechanisms of the naturally occurring AMP magainin-2 and OAK C12K-7α8. The significance of the model membrane system being used cannot be overstated, when the overall arching goal is to bring these peptidomimetics to a clinical market. Thus, the biological relevance of the model membrane system is of great importance. It is this motivation that has lead our research group to develop a floating planar lipid bilayer that is bound to a lipid monolayer functionalized with polyethylene glycol, which to our knowledge has not been previously done. This system and the planar Langmuir monolayer that were used in this work are ideal systems for the use of high energy X-rays that are produced from synchrotron radiation facilities. From such measurements as X-ray reflectivity (XR) and grazing incidence X-ray diffraction (GIXD) molecular scale resolution of the peptidomimetic interactions with the model membrane systems can be achieved.
Ph.D. in Physics, December 2014
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Title: LIVE LOAD FACTORS FOR CONTINUOUS GIRDER BRIDGES
Creator: Wang, Qing
Date: 2016, 2016-07
Description: Live load factors of Strength I limit state for continuous girder highway bridges are calibrated based on reliability concept adopted by...
Show moreLive load factors of Strength I limit state for continuous girder highway bridges are calibrated based on reliability concept adopted by AASHTO LRFD and LRFR specifications. A uniform reliability is maintained for multi-girder highway bridges with various span lengths. WIM data, gathered by California, Michigan, New York, Oregon, and Illinois State Department of Transportation are analyzed. Live load effects produced by WIM data are calculated using influence lines. Expected maximum live load effects in given periods are modeled and extrapolated by Gumbel distribution. A relativecalibration formula is developed in order to derive live load correction factors for designing/evaluating continuous highway bridges at a reliability level that is in consistent with simply supported highway bridges. Computer programming is conducted for data sorting and traffic statistical analysis.
Ph.D. in Civil Engineering, July 2016
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Title: ADULTS WITH SICKLE CELL DISEASE: THE DISEASE'S IMPACT ON PAIN NEUROPSYCHOLOGICAL DYSFUNCTION AND QUALITY OF LIFE
Creator: Vernale Iii, Michael A.
Date: 2013, 2013-07
Description: The primary aim of this study is to address the neuropsychological functioning of adults with Sickle Cell Disease (SCD) by examining the...
Show moreThe primary aim of this study is to address the neuropsychological functioning of adults with Sickle Cell Disease (SCD) by examining the association of illness-related and psychosocial factors with cognition. The neuropsychological functioning of adults with SCD will be compared to that of controls matched on gender, race, and age. There is considerable evidence for neuropsychological complications associated with SCD (Anie, 2005; Schatz, 2004). Much of the cognitive deficits are thought to be the result of cerebrovascular accidents commonly suffered by this population. Studies of cognition in children with SCD suggest that cognitive complications tend to increase with age. Particularly implicated are deficits in attention, concentration, and executive functioning. Although the specific neuropsychological morbidity is not as clearly understood for adults with SCD as it is for children, global cognitive impairment within this population has been documented. In addition, pain negatively affects cognitive functioning in both children and adults (Libon et al., 2010). The pattern of impairment was suggested to be the result of additional demands on attentional capacity. However, the relationship between pain and cognitive performance in adults with sickle cell disease is less clear. As a result of frequent pain, individuals with SCD often report a low evaluation of quality of life particularly as a result of health complaints (Anie, 2005). Thus, the inter-dynamic of health -related quality of life, pain , and cognitive dysfunction is not entirely clear within the sickle cell population and therefore warrants examination.
PH.D in Psychology, July 2013
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Title: ANTIBODY AND PEPTIDE CONJUGATES OF BIFUNCTIONAL CHELATORS FOR TARGETED CANCER THERAPY AND IMAGING
Creator: Kang, Chi Soo
Date: 2014, 2014-07
Description: A bifunctional ligand that can rapidly form a stable complex with a metal while conjugated to a tumor-targeting moiety is essential for...
Show moreA bifunctional ligand that can rapidly form a stable complex with a metal while conjugated to a tumor-targeting moiety is essential for targeted therapy and imaging of cancer. New bifunctional chelators in the NETA and DEPA series were developed for targeted radiation cancer therapy. The chelators showed rapid complexation kinetics with 90Y and 177Lu, and the corresponding radiolabeled complexes were stable in vitro and in vivo. Trastuzumab, Panitumumab, and c(RGDyK) conjugates (targeting HER-2, HER-1, and integrin αvβ3, respectively) of the novel bifunctional ligands were prepared. The conjugates displayed fast complexation kinetics with 90Y, 177Lu, and 205/6Bi, and the antibody and peptide conjugates labeled with 90Y, 177Lu, or 205/6Bi exhibited excellent stability and tumor targeting in mice bearing human colorectal cancer (LS-174T). Transferrin (Tf) and bile acid (BA) conjugates of novel chelators in the NE3TA series were prepared for targeted iron chelation therapy (ICT) and positron emission tomography (PET) imaging applications of cancer. Tf and BA conjugates of NE3TA had high cytotoxicity on HeLa, HT29, and PC3 cancer cells. The Tf-N-NE3TA and BA-N-NE3TA also displayed rapid complexation kinetics with 64Cu, and the Tf and BA conjugates of N-NE3TA labeled with 64Cu were stable and had high cellular uptake in HeLa and PC3 cancer cells. Tf-N-NE3TA was further conjugated with a fluorescence dye (Cy5.5) to develop targeted theranostic agent of cancer. Tf-N-NE3TA-Cy5.5 showed great radiolabeling efficiency with 64Cu, and the Tf-N-NE3TA-Cy5.5 labeled with 64Cu exhibited high cellular uptake in HeLa, HT29, and PC3 cancer cells. In summary, we have developed new bifunctional ligands having excellent chelation chemistry of 90Y, 177Lu, 205/6Bi, and 64Cu, and the tumor-specific antibody and peptide conjugates of the novel bifunctional chelators have a great potential for targeted cancer therapy and imaging as well as theranostic applications of cancer.
Ph.D. in Biology, July 2014
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Title: RELIABILITY AND ENERGY ANALYSIS FOR EXTREME SCALE SYSTEMS
Creator: Yu, Li
Date: 2015, 2015-12
Description: Reliability and energy are two of the top major concerns in the development of today's supercomputers. To build a powerful machine while at...
Show moreReliability and energy are two of the top major concerns in the development of today's supercomputers. To build a powerful machine while at the same time satisfying reliability requirement and energy constraint, HPC scientists continue to seek a better understanding of system and component behaviors. Toward this end, modern systems are deployed with various monitoring and logging tools to track reliability and energy data during system operations. Since these data contain important information about system reliability and energy, they are valuable resources for understanding system behaviors. However, as system scale and complexity continue to grow, the process of collecting system data to extracting meaningful knowledge out of overwhelming reliability and energy data faces a number of key challenges. To address these challenges, my work consists of three parts, including data preprocessing, data analysis and advanced modeling.
Ph.D. in Computer Science, December 2015
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Title: MULTIPLE SIGNAL TRANSDUCTION EVENTS AND MODULATION OF OLFACTORY RESPONSES IN MOUSE OLFACTORY SENSORY NEURONS
Creator: Yu, Yiqun
Date: 2012-04-30, 2012-07
Description: In the mammalian olfactory system, one olfactory sensory neuron (OSN) expresses a single olfactory receptor (OR) gene. I studied two subsets...
Show moreIn the mammalian olfactory system, one olfactory sensory neuron (OSN) expresses a single olfactory receptor (OR) gene. I studied two subsets of mouse OSNs, hereafter refered to as Ho-OSNs and AB-OSNs, in intact mouse olfactory turbinates using calcium imaging. Both of Ho-OSNs and AB-OSNs were located in the most ventral olfactory receptor zone. Ho-OSNs were specifically responsive to 2-heptanone (Ho), heptaldehyde (H) and cis-4-heptenal (cH). Dose-dependent analysis indicated that their responses to individual odorant was saturated within one logarithm unit of concentrations, a typical characteristic of isolated OSNs. Binary mixture and crossadpatation studies showed that these three odorants bound to the same binding sites in Ho-OSNs. However, these three structurally similar odorants activated distinct signaling pathways in Ho-OSNs. In detail, 2-heptanone-evoked intracellular calcium elevation was mediated by AC-cAMP signaling, while heptaldehyde triggered the PLC-DAG pathway. The cis-4-heptenal-evoked [Ca2+]i increases resulted from a combination of cAMP mediated activation and suppression involving PLC signaling. Furthermore, the PLCmediated intracellular calcium alteration was independent of IP3 signaling. A further complexity is that these olfactory receptors were able to interact with other types of Gprotein coupled receptors (GPCRs), such as purinergic receptors. I determined that both the P2X3 and P2Y2 receptor subtypes were expressed in Ho-OSNs. Application of purinergic agonists elevated [Ca2+]i increases in Ho-OSNs. It was discovered that the ATP-induced calcium response required either intracellular or extracellular calcium, while depletion of intracellular calcium stores blocked the UTP-evoked [Ca2+]i increases. Purinergic agonists were able to modulate the odor response in Ho-OSNs, and purinergic antagonist experiments showed that modulation of heptaldehyde-induced calcium responses was due to activation of P2X3 receptor subtypes while heptanone-induced calcium responses was not. Although AB-OSNs were found adjacent to Ho-OSNs, they had complete separate response profiles. AB-OSNs were sensitive to acetophenone (Ace) and benzaldehyde (Ben). In AB-OSNs, both acetophenone and benzaldehyde activated the PLC signaling pathway. Pharmacological characterization indicated that in AB-OSNs, P2X1 and P2Y2 receptors were present, which is different from that in Ho-OSNs. P2X and P2Y agonists modulated odorant responses in AB-OSNs. Purinergic signaling differentially regulated the various odorant responses in AB-OSNs. The acetophenoneevoked [Ca2+]i increases were negativly modulated through activation of the P2Y2 receptor, while the calcium response induced by benzaldehyde was modulated by P2X1 receptor activation. Collectively, these studies suggest that a complex signaling mechanism exists in OSNs, which has important implications for understanding the mechanism of information process in the olfactory system.
Ph.D. in Biology, July 2012
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Title: PAST- AND FUTURE- ORIENTED COGNITIONS IN PTSD: THE RELATIONSHIP BETWEEN RUMINATION AND WORRY IN DEPRESSION AND ANXIETY SYMPTOMS
Creator: Stickney, Laurie
Date: 2016, 2016-07
Description: Post-Traumatic Stress Disorder (PTSD) is a complex disorder characterized by symptoms of both anxiety and depression. Likewise, individuals...
Show morePost-Traumatic Stress Disorder (PTSD) is a complex disorder characterized by symptoms of both anxiety and depression. Likewise, individuals with PTSD experience Repetitive Negative Cognitions in the form of rumination and worry that may be focused on the past, present, or future. Although cognitions in individuals with PTSD have been studied, there is some question as to what types of cognitions individuals with PTSD generally experience and to what extent different types of cognitions contribute to different PTSD symptomatology. Further, although worry and rumination in PTSD have been studied, the question of the importance of the time-focus of cognitions in PTSD has not been adequately addressed. Time-focused cognitions and the relationships among depression, anxiety, rumination and worry were examined in this study using experience sampling method. Participants were asked to fill out a short survey measuring depression, anxiety, rumination, worry and time-focus five times per day for seven days. Results indicated that the presence of Current-focused cognitions strengthened the relationship between worry and anxiety compared to Future-focused cognitions. These findings suggest that in terms of the relationship between anxiety and worry, it is current-focus that is important not future-focus. Additionally, worry partially mediated the relationship between rumination and anxiety, and rumination partially mediated the relationship between worry and depression. Overall, the results suggest that time-focus may be important in some areas of PTSD, and the study highlights the complex relationships among depression, anxiety, rumination, worry and time-focused cognitions.
Ph.D. in Psychology, July 2016
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Title: INTERNET-BASED CONTACT PROGRAMS TO FIGHT THE STIGMA OF SCHIZOPHRENIA
Creator: Wassel, Abigail K.
Date: 2014, 2014-07
Description: Stigma is an insidious problem that has resulted in loss of opportunities for people with mental illness. Research suggests that contact...
Show moreStigma is an insidious problem that has resulted in loss of opportunities for people with mental illness. Research suggests that contact provided through a structured talk by a person with mental illness could serve as an effective tool in combating stigma and promoting attitude change. Additionally, research on imagined contact suggests this approach can also decrease negative stereotypes toward people with schizophrenia. The current study examined the effectiveness of these two approaches in changing attitudes toward people with mental illness when delivered via the Internet. It was hypothesized that both a videotaped contact and an imagined contact approach would increase positive attitudes and decrease negative attitudes toward people with mental illness when presented alone, and that efficacy would increase when combined. Findings showed no significant changes for any experimental condition from baseline attitudes or relative to a control condition, which suggests that interventions used in this study are not successful in creating sustainable attitude change over the Internet.
Ph.D. in Psychology, July 2014
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Title: A C-OMPARISON OF TWO ALGORITHMS FOR ADAPTING INTERVIEWS TO PERSONALITY SCORES
Creator: Van Overberghe, Courtney T.
Date: 2012-04-18, 2012-05
Description: Two adaptive interviews – adding questions based on low or high scores from a personality assessment – were compared to a structured interview...
Show moreTwo adaptive interviews – adding questions based on low or high scores from a personality assessment – were compared to a structured interview. In a mock selection process, it was found that the adaptive and structured interviews had similar correlations with performance on a role play task. However, due to the added length of the adaptive interview, it had slightly less utility than a structured interview. A cognitive measure and the interview conditions were better predictors of performance than the personality questionnaire, which had no relationship with performance. A post-hoc analysis found that the social desirable scale from the personality instrument correlated negatively with the structured interview, the role play and the IQ test, and positively correlated with the personality composite score.
Ph.D. in Psychology, May 2012
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Title: OPTIMAL DESIGN OF PERMANENT MAGNET SYNCHRONOUS MACHINES BASED ON MAGNETIC FIELD DISTRIBUTION ASSESSMENT AND PERFORMANCE ANALYSIS
Creator: Jiang, Yong
Date: 2015, 2015-05
Description: The detailed magnetic field distribution of a permanent magnet electric motor is very important for the accurate prediction of performance...
Show moreThe detailed magnetic field distribution of a permanent magnet electric motor is very important for the accurate prediction of performance parameters such as back electromotive force (back-EMF), rotor and stator losses, winding inductances, noise and vibration, torque profiles, etc. Although finite element analysis is a good option for accurately calculating magnetic field distribution in electrical machines, it is typically timeconsuming and does not provide closed form solutions. Alternatively, analytical calculation of magnetic field distribution can be conducted in Fourier series, which is more suitable for a design tool to predict the motor performance. This dissertation presents a novel numerical technique for calculating exact magnetic field distribution in the air gap of a surface mounted permanent magnet machine. This solution can be obtained via a two-dimension analytical solution with Laplacian and quasi-Poisonian equations, assuming that the iron is infinitely permeable and the air gap is slotless. Slot effects can be added in the model by using relative air gap permeance calculated by the conformal transformation of slot geometry. This technique is constructed by multiplying the relative permeance function expressed in an infinite Fourier series with the distribution of magnetic field in the slotless air gap. This method shows a very good alignment with finite element method for a surface mounted permanent magnet machine with radial magnetization. It can also be extended to calculating magnetic field distribution of interior permanent magnet motors including consideration of magnetic saturation, crosssaturation between d-axis and q-axes, affecting both inductances and flux linkages, as well as localized effects due to rotor bridges. Furthermore, this approach can be used to create a closed-form solution, which is the first step towards inverse modeling of electric machines. This is a complete paradigm shift in the design process for electric machines, which can reduce the time taken to design an electric machine, while reducing the active material content to make them power dense with significant reduction in cost. Furthermore, availability of analytical description of the field components will aid in the designer’s ability to distinguish between the control and magnetic design aspects.
Ph.D. in Electrical and Computer Engineering, May 2015
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Title: DEVELOPMENT OF NANOPARTICLE APPLICATIONS IN CELL IMAGING, BIOASSAY AND REACTIVE OXYGEN SPECIES DETECTION BASED ON SURFACE-ENHANCED RAMAN SPECTROSCOPY
Creator: Yiming, Huang
Date: 2011-08, 2011-07
Description: After mid-1970, the exploration of surface-enhanced Raman scattering (SERS) has been studied by many research groups. Compared to traditional...
Show moreAfter mid-1970, the exploration of surface-enhanced Raman scattering (SERS) has been studied by many research groups. Compared to traditional Raman spectroscopy, enormous cross section of molecules can be obtained in SERS by placing the molecules within the electromagnetic field present in metal surfaces. This enhancement is due to resonance between the optical field and surface plasmon of the metal substrate. Nanoshells which are composed of a silica core and a thin gold shell can greatly enhance Raman scattering without the need to pre-aggregate the particles, due to their tunable optical property. In our study, we synthesized nanoshells as our SERS substrates for Raman tags. The stability of nanoshells coated with three different self-assembled monolayers containing poly(ethylene glycol) (PEG) molecules has been studied. Probes with Raman active PEG molecules have been delivered and imaged in macrophage cells and MCF7 cells, based on SERS technique. The benefits of this imaging technique we developed here are: 1) it is faster; 2) it requires less preparation; 3) it can provide the information of nanoshells in a semi-quantitative way in vitro. We also developed a rapid and easy-to-execute half-sandwich bioassay for the detection of low volumes (< 2 μL) of antigens on nitrocellulose membrane, based on SERS. Multiple antibodies with MW from 18.2 kDa to 170 kDa were bioconjugated to polymers and grafted to nanoshell surface to detect antigens on the membrane. SERS-based biosensors were tagged with Raman active PEGs for recognition and quantification. Here, the bioassay showed great sensitivity to very low concentration x viii of antigens and multiplexed testing have been successfully conducted on different antigens simultaneously. Moreover, SERS-based novel reactive oxygen species (ROS) sensors were designed by establishing mixed-monolayer consisting of poly(ethylene) glycol thiol (PEGSH) and either 4-nitrobenzenethiol (4-NBT) or 4-mercaptophenol (4-MP) on the surface of nanoshells. By analyzing the changes in the molecular Raman spectrum, we were able to track the production of hydroxyl radicals in low concentrations (~ 10 μM). The sensors have been delivered into the cells and did not show significant oxidative stress to the cells. Therefore, these designed sensors are very promising for tracking ROS produced by cells when they are under oxidative stress.
Ph.D. in Chemistry, July 2011
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Title: THE MOLECULAR MECHANISM OF BAXΔ2-MEDIATED CELL DEATH AND ITS TISSUE DISTRIBUTION IN COLON CANCER
Creator: Zhang, Honghong
Date: 2014, 2014-07
Description: Bax is a pro-death tumor suppressor in the Bcl-2 family, and is frequently mutated in microsatellite instable tumors, especially Hereditary...
Show moreBax is a pro-death tumor suppressor in the Bcl-2 family, and is frequently mutated in microsatellite instable tumors, especially Hereditary Non-Polyposis Colorectal Cancer (HNPCC). The loss of apoptotic Bax contributes to tumor development and chemoresistance. We recently uncovered that the combination of a Bax microsatellite mutation with a specific alternative splicing generated a unique Bax isoform (BaxΔ2) in Bax-negative cells. Similar to the prototype Baxα, BaxΔ2 is a potent pro-apoptotic molecule. However, the pro-apoptotic mechanism, therapeutic implication, and tumor tissue distribution of BaxΔ2 protein remain elusive. In this thesis research, we isolated and analyzed isogenic sub-cell lines that represent different Bax microsatellite statuses from colorectal cancer cells. We found that the colon cancer cells harboring Bax microsatellite G7/G7 alleles produced low levels of endogenous BaxΔ2 transcripts and proteins. BaxΔ2-positive cells were selectively sensitive to a subgroup of chemotherapeutics in comparison with BaxΔ2-negative cells. Different from other Bax isoforms, which mostly act through targeting mitochondria, BaxΔ2 recruited caspase-8 into the aggregates for activation, and consequently induced cell death independent of the mitochondrial pathway. Furthermore, the distribution of BaxΔ2 protein was mostly found in well-differentiated epithelial cells in primary colon tumor tissues or in primary squamous buccal cells, which contain Bax G7 mutation. However, not all cells harboring the Bax G7 mutation had a detectable level of BaxΔ2 proteins. These data suggest that, similar to Baxα, BaxΔ2 protein is pro-apoptotic, but not toxic to normal cells; expression of BaxΔ2 protein restores apoptotic program in Bax negative cells via a non-classical signaling pathway. Importantly, BaxΔ2 may provide a selective chemotherapeutic advantage for certain Bax-negative colon tumors.
Ph.D. in Biology, July 2014
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Title: DEVELOPMENT OF COMPUTER-AIDED DIAGNOSIS METHODS IN MAMMOGRAPHY
Creator: Wang, Juan
Date: 2015, 2015-12
Description: Computer-aided diagnosis (CAD) is developed as a diagnostic aid to provide a “second opinion” in diagnosis of breast cancer in early stage....
Show moreComputer-aided diagnosis (CAD) is developed as a diagnostic aid to provide a “second opinion” in diagnosis of breast cancer in early stage. Clustered microcalcifications (MCs) can be an important early sign of breast cancer. The goal of this work is to develop automatic CAD methods in mammography for breast cancer. Its contribution consists of both development of machine learning algorithms and study of related issues in detection and diagnosis of breast cancer with clustered MCs. First, a bi-thresholding scheme is proposed for reduction of false-positives (FPs) associated with linear structures in MC detection. An unified classifier with dummy variable modeling is further developed to reduce the FPs caused by both linear structures and MC-like noise patterns. It is demonstrated that both of the proposed algorithms can reduce FPs in MC detection, and thus, improve the detection accuracy significantly. Second, a spatial density modeling approach is investigated to quantify the spatial distribution of the MCs in a cluster when the MC detection is inaccurate. A spatial density function (SDF) is defined such that the extracted features are more robust to the presence of FPs and false-negatives (FNs) in MC detection. The results show that the features extracted from the SDF can achieve better class separation while being robust to the variations in MC detection when compared with those extracted from a traditional region-based method. Third, a retrieval-boosted approach is studied to discriminate between the benign and malignant MC lesions. A retrieval strategy is proposed to boost the classification performance by taking into account the similarity both in image features and in pathology. An adaptive Adaboost classifier, which can be adapted to the retrieved cases at a low computational cost, is applied to demonstrate the benefit of the retrieval strategy. The results show that the retrieval-boosted approach can signifishow that the features extracted from the SDF can achieve better class separation while being robust to the variations in MC detection when compared with those extracted from a traditional region-based method. Third, a retrieval-boosted approach is studied to discriminate between the benign and malignant MC lesions. A retrieval strategy is proposed to boost the classification performance by taking into account the similarity both in image features and in pathology. An adaptive Adaboost classifier, which can be adapted to the retrieved cases at a low computational cost, is applied to demonstrate the benefit of the retrieval strategy. The results show that the retrieval-boosted approach can significantly outperform its baseline classifier and that inclusion of pathology information in the retrieval can further improve the classification accuracy. Fourth, the perceptual similarity of MC lesions by radiologists is studied. The issues investigated include the degree of variability in the similarity ratings, the impact of this variability on agreement between readers in retrieval of similar lesions, and the factors contributing to the readers’ similarity ratings. The results indicate that perceptually similar lesions could be of diagnostic value in diagnosis for clustered MCs. Fifth, the feasibility of modeling the perceptual similarity of MC lesions is investigated. A support vector regression (SVR) is applied to model the perceptual similarity of clustered MCs, and a feature saliency analysis derived from SVR is used to determine the most relevant image features among a large set of candidate features. The results demonstrate that the relevant features are consistent in radiologists’ similarity ratings among different MC lesions, indicating that the perceptual similarity of MC lesions by radiologists can be effectively modeled. Finally, whether retrieval of similar images can effectively assist radiologists in diagnosis of clustered MCs is investigated. A retrieval system for relevant images is designed by considering both perceptually similar image features and the likelihood of malignancy of the lesion under consideration. An observer study is conducted to evaluate the diagnostic value of the proposed retrieval system. The results indicate that the proposed retrieval system has the potential to improve the reader’s ability in diagnosis of breast cancer with clustered MCs.
Ph.D. in Electrical Engineering, December 2015
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Title: Quantitative Tools for Stochastic Dynamical Systems: Invariant Structures and Escape Probabilities
Creator: Kan, Xingye
Date: 2012-07-16, 2012-07
Description: Three types of quantitative structures, stochastic inertial manifolds, random invariant foliations, and escape probabilities, are investigated...
Show moreThree types of quantitative structures, stochastic inertial manifolds, random invariant foliations, and escape probabilities, are investigated to study stochastic dynamical systems. Invariant structures for stochastic dynamical systems are reviewed and detailed techniques for their simulation, approximation and construction are presented with several illustrative examples. First, a numerical approach for the simulation of inertial manifolds of stochastic evolutionary equations with multiplicative noise is presented and illustrated. After splitting the stochastic evolutionary equations into a backward and a forward part, a numerical scheme is devised for solving this backward-forward stochastic system, and an ensemble of graphs representing the inertial manifold is consequently obtained. This numerical approach is tested in two illustrative examples: one is for a stochastic differential equation and the other is for a stochastic partial differential equation. Second, invariant foliations for dynamical systems with small white noisy perturbation are approximated via asymptotic analysis. In other words, random invariant foliations are represented as a perturbation of the corresponding deterministic invariant foliations, with deviation errors estimated. The escape probability is a deterministic concept making methods of partial differential equations theory attainable to stochastic dynamics. Finally, the escape probability p(x) for dynamical systems driven by non-Gaussian L´evy motions, especially symmetric α-stable L´evy motions, is considered and characterized. More precisely, it is represented as the solution of the Balayage-Dirichlet problem of a certain partial differential-integral equation. This issue has been investigated previously for dynamical systems driven by Wiener process. Differences between escape probabilities for dynamical systems driven by Gaussian and non-Gaussian noises are highlighted.
Ph.D. in Applied Mathematics, July 2012
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Title: POWER PROFILING, ANALYSIS, LEARNING, AND MANAGEMENT FOR HIGH-PERFORMANCE COMPUTING
Creator: Wallace, Sean
Date: 2017, 2017-05
Description: As the field of supercomputing continues its relentless push towards greater speeds and higher levels of parallelism the power consumption of...
Show moreAs the field of supercomputing continues its relentless push towards greater speeds and higher levels of parallelism the power consumption of these large scale systems is steadily transitioning from a burden to a serious problem. While the machines are highly scaleable, the buildings, power supplies, etc. are not. Even the most power efficient systems today consume one to two megawatts per peata op/s. Multiplying that by 1,000 to reach the next generation of supercomputer (i.e., exascale) and the power necessary just to turn the machine on is simply impractical. Thus, power has become a primary design constraint for future supercomputing system designs. As such, it has become a matter of paramount importance to understand exactly how current generation systems utilize power and what implications this has on future systems. As the saying goes, you can't manage what you don't measure. This work addresses several large hurdles in fully understanding the power consumption of current systems and making actionable decisions based on this understanding. First, by leveraging environmental data collected from runs of real leadership class applications we analyze power consumption and temperature as it pertains to scale on a production IBM Blue Gene/Q supercomputer. Then, through development of a new power monitoring library, MonEQ, we quantitatively studied how power is consumed in major portions of the system (e.g., CPU, memory, etc.) through profiling of microbenchmarks. Expanding on this, we then studied how scale and network topology affect power consumption for several well-known benchmarks. Wanting to increase the effectiveness of our power monitoring library, we extended it to work with many of the most common classes of hardware available in today's HPC landscape. In doing so, we provided an in-depth analysis of what data is obtainable, what the process of obtaining it is like, and how data from different systems compares. Next, utilizing the knowledge gained from these experiences, we developed a new scheduling approach which utilizing power data can effectively keep a production system's power consumption under a user-specified power cap without modification to the applications running on the system. Finally, we extend this scheduling approach to be applicable to more than just one objective. In doing so, the scheduler can now optimize on multiple criteria instead of simply considering system utilization.
Ph.D. in Computer Science, May 2017
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Title: SEISMIC DESIGN STUDY OF STEEL PLATE SHEAR WALL
Creator: Moshiri, Ali
Date: 2012-04-20, 2012-05
Description: plate shear walls are an innovative lateral load-resisting system capable of effectively and economically bracing a building against both wind...
Show moreplate shear walls are an innovative lateral load-resisting system capable of effectively and economically bracing a building against both wind and earthquake forces. The system consists of infill steel plates connected to boundary beams and columns over the full height of the framed bay. Beam-to-column connections can be rigid or shear connections and the infill plates can be either stiffened or unstiffened, depending on the design philosophy of the infill plates. The view of some structural designers is to use heavy stiffeners to reinforce and increase the buckling capacity of shear walls, whereas, if the walls are left unstiffened and allowed to buckle, their energy absorption will increase significantly due to the post-buckling capacity. Performance of 9-story SPSW with moment resisting beam to column connections was studied under quasi-static loading condition and 10 earthquake records recorded in Los Angeles by developing a nonlinear dynamic explicit finite element models in ABAQUS. All the models were validated with experimental results. Effect of stiffness of boundary elements (VBE and HBE) and plate thickness on general behavior of the structure were also investigated. In design of SPSWs, vertical boundary elements play a major role in increasing the capacity of the system. In high seismic zones there is always a chance of plastic hinge formation in the boundary elements specially columns in any intermediate floor. It is recommended that SPSWs not be used for medium to high rise buildings in high seismic regions until the lack of capacity design requirements for this type of SPSW is rectified.
Ph.D. in Structural Engineering, May 2012
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Title: POLARIZATION INDUCED BY A TERAHERTZ ELECTRIC FIELD ON A CONDUCTIVE PARTICLE
Creator: Shen, Tao
Date: 2013, 2013-05
Description: Interactions of an electromagnetic wave with an object of dimensions small compared to the wavelength can often be accounted for by...
Show moreInteractions of an electromagnetic wave with an object of dimensions small compared to the wavelength can often be accounted for by considering the dipole moments, which are effective in explaining the scattering characteristics in the frequency range referred to as the Rayleigh region. Dielectric functions derived from polarization processes due to molecular orientation or bound charge displacements have been employed over the years to account for the scattering properties of particles. In the presence of mobile charges, bulk conductivity may be incorporated with a complex dielectric function to explain the peak in absorption near the plasma frequency exhibited by metallic particles in the optical region. With the current interest in nanostructures, an investigation of the electromagnetic properties of a conductive particle with attention given to space-charge effects would appear timely. This can be accomplished by coupling the transport equations of the charge carriers to the Maxwell’s equations. Results of computations performed for elementary structures such as plates and particles revealed the screening of the internal field while dispersion and absorptions effects are shown by the complex dipole moments. To gain insight into the nature of charge-wave interactions, results based on quasi-static formulation for the electric field will be compared with those based on full-wave analysis, with special attention given to the charge and current distributions within the structure. By consideration of the physical process of charge carrier motion and lattice polarization, the equivalent circuit model for a conductive nanoparticle in the terahertz frequency range is developed. All circuit elements are of electrical nature and can be directly expressed in terms of material parameters. The equivalent circuit can serve as the basis of analysis for composite structures and aggregates of which the conductive nanoparticle is a constituent.
PH.D in Electrical Engineering, May 2013
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Title: COMPUTATIONAL MODELS OF TRANSPARENT WATER STORAGE ENVELOPES FOR ENERGY EFFICIENT COMMERCIAL BUILDINGS
Creator: Liu, Xiangfeng
Date: 2012-04-25, 2012-05
Description: Transparent Water Storage Envelopes (TWSEs) are climatic adaptive fenestration systems. The major part of the system is an array of modular...
Show moreTransparent Water Storage Envelopes (TWSEs) are climatic adaptive fenestration systems. The major part of the system is an array of modular transparent water containers which are integrated into frames of curtain walls, and serve as both façade and auxiliary water tanks for a commercial building. The concept originates from the idea of combing transparency with dynamic benefits of thermal mass in summer, as well as passive solar heating in winter. Optical and thermal characteristics of TWSEs, including their energy performance, have been studied systematically via numerical approaches. Two numerical procedures covered in the thesis: one is based on the simplified synchronized onedimensional nodal thermal model, and the other is based on the more complex and accurate synchronized CFD model. In each numerical procedure, a triple-step simulation methodology and the correlated computational models of TWSEs are employed. Based on the calculation and simulation results, it can be definitely concluded that TWSEs are energy efficient fenestration systems. They can outperform conventional glazing as long as being designed elaborately with the consideration of the unique physical characteristics, applied under suitable climatic conditions, and operated with appropriate energy efficiency measures. Furthermore, the innovative technical paradigm of TWSEs and the numerical approach developed for energy simulation of TWSEs demonstrate great potential to be implemented in engineering practice for energy efficient commercial buildings.
Ph.D. in Architecture, May 2012
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Title: VERIFICATION OF LARGE-SCALE ON-CHIP POWER GRIDS
Creator: Xiong, Xuanxing
Date: 2013, 2013-05
Description: As technology scaling continues, the performance and reliability of integrated circuits become increasingly susceptible to power supply noises...
Show moreAs technology scaling continues, the performance and reliability of integrated circuits become increasingly susceptible to power supply noises, such as IR drops and Ldi/dt noises in the on-chip power grids. Reduced supply voltage levels in the grid can increase the gate delay, leading to timing violations and logic failures. In order to ensure a reliable chip design, it is critical to verify that the power grid is robust, i.e., the power supply noises are acceptable for all possible runtime situations. Hence, power grid verification has become an indispensable step in modern design flow of integrated circuits. Nowadays, it is common practice to verify power grids by simulation. Typically, an equivalent RC/RLC circuit model of the grid is extracted from the layout, and designers perform simulations to evaluate the power supply noises based on the current waveforms drawn by the circuit. As power grid simulation can only be performed after the circuit design is done, vectorless power grid verification has been introduced to enable early power grid verification with incomplete current specifications, so that the power grid design can be better tuned and optimized at early design stages, thus reducing the design time. Due to the increasing complexity of modern chips, power grid verification has become very challenging. The broad goal of this dissertation is to explore efficient algorithms for verifying large-scale on-chip power grids. Specifically, we study parallel power grid transient simulation, vectorless steady-state verification and vectorless transient verification. Parallel forward and back substitution algorithms are designed for efficient transient simulation; a set of novel algorithms are developed to incrementally improve the runtime efficiency of vectorless steady-state verification; and an efficient approach is proposed for vectorless transient verification with novel constraint setting.
PH.D in Electrical Engineering, May 2013
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Title: EXPLORING THE SHEAR-AND-TIME DEPENDENT DEGRADATION OF VON WILLEBRAND FACTOR UNDER VENTRICULAR ASSIST DEVICE-RELATED FLOW CONDITIONS
Creator: Yang, Shuo
Date: 2015, 2015-12
Description: Abnormalities in VWF can cause impaired blood coagulation which results in higher bleeding tendency in patients with this disorder. Alteration...
Show moreAbnormalities in VWF can cause impaired blood coagulation which results in higher bleeding tendency in patients with this disorder. Alteration in VWF is characteristic in ventricular assist devices (VADs) implanted subjects with failing hearts. The nature of the abnormalities produced and the conditions which produce such abnormalities are not fully understood. The studies in this thesis investigate quantitatively the effects of VADs and VAD-related flow conditions on VWF degradation. This thesis consists of three studies: 1) an in vitro VAD loop study in which was investigated the degradation effects of three VADs either under preclinical development (VAD I) or being commercially available (VAD II & III); 2) a viscometer shear study in which was investigated a variety of factors under the controlled condition of a modified Couette viscometer, namely, shear stress, exposure time, pulsatile frequency and protease function, with respect to VWF degradation 3) a tubular shear study in which was investigated the relative degradation effects of shear stress versus exposure time under more VAD-related shear stresses (10 - 100 times higher than physiological levels) and exposure times of miliseconds. In the VAD flow loop, significant VWF degradation induced by VADs wee observed with an approximately 95% loss of high molecular weight VWF by 60 minutes. In the viscometer and the tubular studies, the factors studied enhanced VWF degradation in the following manner: increased shear stress above physiological levels, prolonged exposure time and higher pulsatile shear frequency were associated with greater degradation; shear stress was a more dominant factor than exposure time with respect to the degradation; and a various shear stress regions demonstrated maximal degradation effects. In addition, calcium-dependent protease function was a necessity for VWF degradation at all shear stress levels investigated. The studies also revealed that the unfolding of VWF to expose the cleavage sites appeared to take more time under shear than the refolding to re-cover those sites under static conditions. Critical shear regions may be important for unfolding and degrading VWF multimers of various sizes.
Ph.D. in Biomedical Engineering, December 2015
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