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Cellular heterogeneity is a key factor in various cellular processes as well as in disease development, especially associated with immune response and cancer progression. Cell-to-cell variability is considered to be one of the major obstacles in early detection and successful treatment of cancer. Most present technologies are based on

Cellular heterogeneity is a key factor in various cellular processes as well as in disease development, especially associated with immune response and cancer progression. Cell-to-cell variability is considered to be one of the major obstacles in early detection and successful treatment of cancer. Most present technologies are based on bulk cell analysis, which results in averaging out the results acquired from a group of cells and hence missing important information about individual cells and their behavior. Understanding the cellular behavior at the single-cell level can help in obtaining a complete profile of the cell and to get a more in-depth knowledge of cellular processes. For example, measuring transmembrane fluxes oxygen can provide a direct readout of the cell metabolism.

The goal of this thesis is to design, optimize and implement a device that can measure the oxygen consumption rate (OCR) of live single cells. A microfluidic device has been designed with the ability to rapidly seal and unseal microchambers containing individual cells and an extracellular optical oxygen sensor for measuring the OCR of live single cells. The device consists of two parts, one with the sensor in microwells (top half) and the other with channels and cells trapped in Pachinko-type micro-traps (bottom half). When the two parts of the device are placed together the wells enclose each cell. Oil is flown in through the channels of the device to produce isolated and sealed microchamber around each cell. Different fluids can be flowed in and out of the device, alternating with oil, to rapidly switch between sealed and unsealed microenvironment around each cell. A fluorescent ratiometric dual pH and oxygen sensor is placed in each well. The thesis focuses on measuring changes in the oxygen consumption rate of each cell within a well. Live and dead cells are identified using a fluorescent live/dead cell assay. Finally, the technology is designed to be scalable for high-throughput applications by controlling the flow rate of the system and increasing the cell array density.
ContributorsRodrigues, Meryl (Author) / Meldrum, Deirdre (Thesis advisor) / Kelbauskas, Laimonas (Committee member) / LaBelle, Jeffrey (Committee member) / Arizona State University (Publisher)
Created2014
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Description
Single cell analysis has become increasingly important in understanding disease onset, progression, treatment and prognosis, especially when applied to cancer where cellular responses are highly heterogeneous. Through the advent of single cell computerized tomography (Cell-CT), researchers and clinicians now have the ability to obtain high resolution three-dimensional (3D) reconstructions of

Single cell analysis has become increasingly important in understanding disease onset, progression, treatment and prognosis, especially when applied to cancer where cellular responses are highly heterogeneous. Through the advent of single cell computerized tomography (Cell-CT), researchers and clinicians now have the ability to obtain high resolution three-dimensional (3D) reconstructions of single cells. Yet to date, no live-cell compatible version of the technology exists. In this thesis, a microfluidic chip with the ability to rotate live single cells in hydrodynamic microvortices about an axis parallel to the optical focal plane has been demonstrated. The chip utilizes a novel 3D microchamber design arranged beneath a main channel creating flow detachment into the chamber, producing recirculating flow conditions. Single cells are flowed through the main channel, held in the center of the microvortex by an optical trap, and rotated by the forces induced by the recirculating fluid flow. Computational fluid dynamics (CFD) was employed to optimize the geometry of the microchamber. Two methods for the fabrication of the 3D microchamber were devised: anisotropic etching of silicon and backside diffuser photolithography (BDPL). First, the optimization of the silicon etching conditions was demonstrated through design of experiment (DOE). In addition, a non-conventional method of soft-lithography was demonstrated which incorporates the use of two positive molds, one of the main channel and the other of the microchambers, compressed together during replication to produce a single ultra-thin (<200 µm) negative used for device assembly. Second, methods for using thick negative photoresists such as SU-8 with BDPL have been developed which include a new simple and effective method for promoting the adhesion of SU-8 to glass. An assembly method that bonds two individual ultra-thin (<100 µm) replications of the channel and the microfeatures has also been demonstrated. Finally, a pressure driven pumping system with nanoliter per minute flow rate regulation, sub-second response times, and < 3% flow variability has been designed and characterized. The fabrication and assembly of this device is inexpensive and utilizes simple variants of conventional microfluidic fabrication techniques, making it easily accessible to the single cell analysis community.
ContributorsMyers, Jakrey R (Author) / Meldrum, Deirdre (Thesis advisor) / Johnson, Roger (Committee member) / Frakes, David (Committee member) / Arizona State University (Publisher)
Created2012
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Description
Since the collapse of the Medellin Cartel in Colombia in 1993, the Mexican drug cartels have been increasing in strength and international presence. Along with the organization's political and economic involvement, a deeply rooted culture has been developing. Three distinct time periods define this culture: pre-Medellin Cartel collapse (1970s-1993), post-Medellin

Since the collapse of the Medellin Cartel in Colombia in 1993, the Mexican drug cartels have been increasing in strength and international presence. Along with the organization's political and economic involvement, a deeply rooted culture has been developing. Three distinct time periods define this culture: pre-Medellin Cartel collapse (1970s-1993), post-Medellin Cartel Collapse (1993-2006) and post-President Calderon's Drug War announcement (2006-present day). More specifically, the history and fascination with the cartel is documented in songs, known as narcocorridos, which celebrate and support the drug cartels. The science of political sociology addresses the power relationship that exists between a state, its citizens, and the state's social groups. This study investigates the political sociology of each period, specifically how society viewed the cartel and their roles within the cartel. I argue that the narcocorridos accurately describe the evolution of narcoculture in Mexican society. This study consists of analyses of narcocorrido song lyrics, the political sociology of each time period, and finally, the societal perception of the drug cartel. First, I will evaluate the most popular songs' lyrics of the three defining time periods in the Mexican Drug Cartel history. Next, I will analyze the lyrics and determine whether or not they accurately reflect the political sociological features of the time period. Last, I will discuss what the societal perceptions of being associated with the cartel were during each time period. This study concludes by hypothesizing what the future of narcocorriodos will be. This prediction will demonstrate how the songs will continue to reflect the political sociology of the time period, including the societal attitudes towards the cartel.
ContributorsRichardson, Katherine Ann (Author) / Rothenberg, Daniel (Thesis director) / Canales, Carlos (Committee member) / School of Politics and Global Studies (Contributor) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
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The emerging field of neuroprosthetics is focused on the development of new therapeutic interventions that will be able to restore some lost neural function by selective electrical stimulation or by harnessing activity recorded from populations of neurons. As more and more patients benefit from these approaches, the interest in neural

The emerging field of neuroprosthetics is focused on the development of new therapeutic interventions that will be able to restore some lost neural function by selective electrical stimulation or by harnessing activity recorded from populations of neurons. As more and more patients benefit from these approaches, the interest in neural interfaces has grown significantly and a new generation of penetrating microelectrode arrays are providing unprecedented access to the neurons of the central nervous system (CNS). These microelectrodes have active tip dimensions that are similar in size to neurons and because they penetrate the nervous system, they provide selective access to these cells (within a few microns). However, the very long-term viability of chronically implanted microelectrodes and the capability of recording the same spiking activity over long time periods still remain to be established and confirmed in human studies. Here we review the main responses to acute implantation of microelectrode arrays, and emphasize that it will become essential to control the neural tissue damage induced by these intracortical microelectrodes in order to achieve the high clinical potentials accompanying this technology.

ContributorsFernandez, Eduardo (Author) / Greger, Bradley (Author) / House, Paul A. (Author) / Aranda, Ignacio (Author) / Botella, Carlos (Author) / Albisua, Julio (Author) / Soto-Sanchez, Cristina (Author) / Alfaro, Arantxa (Author) / Normann, Richard A. (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2014-07-21
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Description

In this study, a low-cycle fatigue experiment was conducted on printed wiring boards (PWB). The Weibull regression model and computational Bayesian analysis method were applied to analyze failure time data and to identify important factors that influence the PWB lifetime. The analysis shows that both shape parameter and scale parameter

In this study, a low-cycle fatigue experiment was conducted on printed wiring boards (PWB). The Weibull regression model and computational Bayesian analysis method were applied to analyze failure time data and to identify important factors that influence the PWB lifetime. The analysis shows that both shape parameter and scale parameter of Weibull distribution are affected by the supplier factor and preconditioning methods Based on the energy equivalence approach, a 6-cycle reflow precondition can be replaced by a 5-cycle IST precondition, thus the total testing time can be greatly reduced. This conclusion was validated by the likelihood ratio test of two datasets collected under two different preconditioning methods Therefore, the Weibull regression modeling approach is an effective approach for accounting for the variation of experimental setting in the PWB lifetime prediction.

ContributorsPan, Rong (Author) / Xu, Xinyue (Author) / Juarez, Joseph (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2016-11-12
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Description

Studies about the data quality of National Bridge Inventory (NBI) reveal missing, erroneous, and logically conflicting data. Existing data quality programs lack a focus on detecting the logical inconsistencies within NBI and between NBI and external data sources. For example, within NBI, the structural condition ratings of some bridges improve

Studies about the data quality of National Bridge Inventory (NBI) reveal missing, erroneous, and logically conflicting data. Existing data quality programs lack a focus on detecting the logical inconsistencies within NBI and between NBI and external data sources. For example, within NBI, the structural condition ratings of some bridges improve over a period while having no improvement activity or maintenance funds recorded in relevant attributes documented in NBI. An example of logical inconsistencies between NBI and external data sources is that some bridges are not located within 100 meters of any roads extracted from Google Map. Manual detection of such logical errors is tedious and error-prone. This paper proposes a systematical “hypothesis testing” approach for automatically detecting logical inconsistencies within NBI and between NBI and external data sources. Using this framework, the authors detected logical inconsistencies in the NBI data of two sample states for revealing suspicious data items in NBI. The results showed that about 1% of bridges were not located within 100 meters of any actual roads, and few bridges showed improvements in the structural evaluation without any reported maintenance records.

ContributorsDin, Zia Ud (Author) / Tang, Pingbo (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2016-05-20
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Background: Robotic devices have been utilized in gait rehabilitation but have only produced moderate results when compared to conventional physiotherapy. Because bipedal walking requires neural coupling and dynamic interactions between the legs, a fundamental understanding of the sensorimotor mechanisms of inter-leg coordination during walking, which are not well understood but are

Background: Robotic devices have been utilized in gait rehabilitation but have only produced moderate results when compared to conventional physiotherapy. Because bipedal walking requires neural coupling and dynamic interactions between the legs, a fundamental understanding of the sensorimotor mechanisms of inter-leg coordination during walking, which are not well understood but are systematically explored in this study, is needed to inform robotic interventions in gait therapy.

Methods: In this study we investigate mechanisms of inter-leg coordination by utilizing novel sensory perturbations created by real-time control of floor stiffness on a split-belt treadmill. We systematically alter the unilateral magnitude of the walking surface stiffness and the timing of these perturbations within the stance phase of the gait cycle, along with the level of body-weight support, while recording the kinematic and muscular response of the unperturbed leg. This provides new insight into the role of walking surface stiffness in inter-leg coordination during human walking. Both paired and unpaired unadjusted t-tests at the 95 % confidence level are used in the appropriate scenario to determine statistical significance of the results.

Results: We present results of increased hip, knee, and ankle flexion, as well as increased tibialis anterior and soleus activation, in the unperturbed leg of healthy subjects that is repeatable and scalable with walking surface stiffness. The observed response was not impacted by the level of body-weight support provided, which suggests that walking surface stiffness is a unique stimulus in gait. In addition, we show that the activation of the tibialis anterior and soleus muscles is altered by the timing of the perturbations within the gait cycle.

Conclusions: This paper characterizes the contralateral leg’s response to ipsilateral manipulations of the walking surface and establishes the importance of walking surface stiffness in inter-leg coordination during human walking.

ContributorsSkidmore, Jeffrey (Author) / Artemiadis, Panagiotis (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2016-03-22
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The recently emerging trend of self-driving vehicles and information sharing technologies, made available by private technology vendors, starts creating a revolutionary paradigm shift in the coming years for traveler mobility applications. By considering a deterministic traveler decision making framework at the household level in congested transportation networks, this paper aims

The recently emerging trend of self-driving vehicles and information sharing technologies, made available by private technology vendors, starts creating a revolutionary paradigm shift in the coming years for traveler mobility applications. By considering a deterministic traveler decision making framework at the household level in congested transportation networks, this paper aims to address the challenges of how to optimally schedule individuals’ daily travel patterns under the complex activity constraints and interactions. We reformulate two special cases of household activity pattern problem (HAPP) through a high-dimensional network construct, and offer a systematic comparison with the classical mathematical programming models proposed by Recker (1995). Furthermore, we consider the tight road capacity constraint as another special case of HAPP to model complex interactions between multiple household activity scheduling decisions, and this attempt offers another household-based framework for linking activity-based model (ABM) and dynamic traffic assignment (DTA) tools. Through embedding temporal and spatial relations among household members, vehicles and mandatory/optional activities in an integrated space-time-state network, we develop two 0-1 integer linear programming models that can seamlessly incorporate constraints for a number of key decisions related to vehicle selection, activity performing and ridesharing patterns under congested networks. The well-structured network models can be directly solved by standard optimization solvers, and further converted to a set of time-dependent state-dependent least cost path-finding problems through Lagrangian relaxation, which permit the use of computationally efficient algorithms on large-scale high-fidelity transportation networks.

ContributorsLiu, Jiangtao (Author) / Kang, Jee Eun (Author) / Zhou, Xuesong (Author) / Pendyala, Ram (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2017-06-15
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Description

Despite the fact that seizures are commonly associated with autism spectrum disorder (ASD), the effectiveness of treatments for seizures has not been well studied in individuals with ASD. This manuscript reviews both traditional and novel treatments for seizures associated with ASD. Studies were selected by systematically searching major electronic databases

Despite the fact that seizures are commonly associated with autism spectrum disorder (ASD), the effectiveness of treatments for seizures has not been well studied in individuals with ASD. This manuscript reviews both traditional and novel treatments for seizures associated with ASD. Studies were selected by systematically searching major electronic databases and by a panel of experts that treat ASD individuals. Only a few anti-epileptic drugs (AEDs) have undergone carefully controlled trials in ASD, but these trials examined outcomes other than seizures. Several lines of evidence point to valproate, lamotrigine, and levetiracetam as the most effective and tolerable AEDs for individuals with ASD. Limited evidence supports the use of traditional non-AED treatments, such as the ketogenic and modified Atkins diet, multiple subpial transections, immunomodulation, and neurofeedback treatments. Although specific treatments may be more appropriate for specific genetic and metabolic syndromes associated with ASD and seizures, there are few studies which have documented the effectiveness of treatments for seizures for specific syndromes. Limited evidence supports l-carnitine, multivitamins, and N-acetyl-l-cysteine in mitochondrial disease and dysfunction, folinic acid in cerebral folate abnormalities and early treatment with vigabatrin in tuberous sclerosis complex. Finally, there is limited evidence for a number of novel treatments, particularly magnesium with pyridoxine, omega-3 fatty acids, the gluten-free casein-free diet, and low-frequency repetitive transcranial magnetic simulation. Zinc and l-carnosine are potential novel treatments supported by basic research but not clinical studies. This review demonstrates the wide variety of treatments used to treat seizures in individuals with ASD as well as the striking lack of clinical trials performed to support the use of these treatments. Additional studies concerning these treatments for controlling seizures in individuals with ASD are warranted.

ContributorsFrye, Richard E. (Author) / Rossignol, Daniel (Author) / Casanova, Manuel F. (Author) / Brown, Gregory L. (Author) / Martin, Victoria (Author) / Edelson, Stephen (Author) / Coben, Robert (Author) / Lewine, Jeffrey (Author) / Slattery, John C. (Author) / Lau, Chrystal (Author) / Hardy, Paul (Author) / Fatemi, S. Hossein (Author) / Folsom, Timothy D. (Author) / MacFabe, Derrick (Author) / Adams, James (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2013-09-13
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Description

There is a growing body of scientific evidence that the health of the microbiome (the trillions of microbes that inhabit the human host) plays an important role in maintaining the health of the host and that disruptions in the microbiome may play a role in certain disease processes. An increasing

There is a growing body of scientific evidence that the health of the microbiome (the trillions of microbes that inhabit the human host) plays an important role in maintaining the health of the host and that disruptions in the microbiome may play a role in certain disease processes. An increasing number of research studies have provided evidence that the composition of the gut (enteric) microbiome (GM) in at least a subset of individuals with autism spectrum disorder (ASD) deviates from what is usually observed in typically developing individuals. There are several lines of research that suggest that specific changes in the GM could be causative or highly associated with driving core and associated ASD symptoms, pathology, and comorbidities which include gastrointestinal symptoms, although it is also a possibility that these changes, in whole or in part, could be a consequence of underlying pathophysiological features associated with ASD. However, if the GM truly plays a causative role in ASD, then the manipulation of the GM could potentially be leveraged as a therapeutic approach to improve ASD symptoms and/or comorbidities, including gastrointestinal symptoms.

One approach to investigating this possibility in greater detail includes a highly controlled clinical trial in which the GM is systematically manipulated to determine its significance in individuals with ASD. To outline the important issues that would be required to design such a study, a group of clinicians, research scientists, and parents of children with ASD participated in an interdisciplinary daylong workshop as an extension of the 1st International Symposium on the Microbiome in Health and Disease with a Special Focus on Autism (www.microbiome-autism.com). The group considered several aspects of designing clinical studies, including clinical trial design, treatments that could potentially be used in a clinical trial, appropriate ASD participants for the clinical trial, behavioral and cognitive assessments, important biomarkers, safety concerns, and ethical considerations. Overall, the group not only felt that this was a promising area of research for the ASD population and a promising avenue for potential treatment but also felt that further basic and translational research was needed to clarify the clinical utility of such treatments and to elucidate possible mechanisms responsible for a clinical response, so that new treatments and approaches may be discovered and/or fostered in the future.

ContributorsFrye, Richard E. (Author) / Slattery, John (Author) / MacFabe, Derrick F. (Author) / Allen-Vercoe, Emma (Author) / Parker, William (Author) / Rodakis, John (Author) / Adams, James (Author) / Krajmalnik-Brown, Rosa (Author) / Bolte, Ellen (Author) / Kahler, Stephen (Author) / Jennings, Jana (Author) / James, Jill (Author) / Cerniglia, Carl E. (Author) / Midtvedt, Tore (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2015-05-07