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- Genre: Doctoral Dissertation
Description
Intermittent social defeat stress induces cross-sensitization to psychostimulants and escalation of drug self-administration. These behaviors could result from the stress-induced neuroadaptation in the mesocorticolimbic dopamine circuit. Brain-derived neurotrophic factor (BDNF) in the ventral tegmental area (VTA) is persistently elevated after social defeat stress, and may contribute to the stress-induced neuroadaptation in the mesocorticolimbic dopamine circuit. BDNF modulates synaptic plasticity, and facilitates stress- and drug-induced neuroadaptations in the mesocorticolimbic system. The present research examined the role of mesolimbic BDNF signaling in social defeat stress-induced cross-sensitization to psychostimulants and the escalation of cocaine self-administration in rats. We measured drug taking behavior with the acquisition, progressive ratio, and binge paradigms during self-administration. With BDNF overexpression in the ventral tegmental area (VTA), single social defeat stress-induced cross-sensitization to amphetamine (AMPH) was significantly potentiated. VTA-BDNF overexpression also facilitates acquisition of cocaine self-administration, and a positive correlation between the level of VTA BDNF and drug intake during 12 hour binge was observed. We also found significant increase of DeltaFosB expression in the nucleus accumbens (NAc), the projection area of the VTA, in rats received intra-VTA BDNF overexpression. We therefore examined whether BDNF signaling in the NAc is important for social defeat stress-induced cross-sensitization by knockdown of the receptor of BDNF (neurotrophin tyrosine kinase receptor type 2, TrkB) there. NAc TrkB knockdown prevented social defeat stress-induced cross-sensitization to psychostimulant. Also social defeat stress-induced increase of DeltaFosB in the NAc was prevented by TrkB knockdown. Several other factors up-regulated by stress, such as the GluA1 subunit of Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor and BDNF in the VTA were also prevented. We conclude that BDNF signaling in the VTA increases social defeat stress-induced vulnerability to psychostimulants, manifested as potentiated cross-sensitization/sensitization to AMPH and escalation of cocaine self-administration. Also BDNF signaling in the NAc is necessary for the stress-induced neuroadaptation and behavioral sensitization to psychostimulants. Therefore, TrkB in the NAc could be a therapeutic target to prevent stress-induced vulnerability to drugs of abuse in the future. DeltaFosB in the NAc shell could be a neural substrate underlying persistent cross-sensitization and augmented cocaine self-administration induced by social defeat stress.
ContributorsWang, Junshi (Author) / Hammer, Ronald (Thesis advisor) / Feuerstein, Burt (Committee member) / Nikulina, Ella (Committee member) / Neisewander, Janet (Committee member) / Arizona State University (Publisher)
Created2013
Description
Induced pluripotent stem cells (iPSCs) are an intriguing approach for neurological disease modeling, because neural lineage-specific cell types that retain the donors' complex genetics can be established in vitro. The statistical power of these iPSC-based models, however, is dependent on accurate diagnoses of the somatic cell donors; unfortunately, many neurodegenerative diseases are commonly misdiagnosed in live human subjects. Postmortem histopathological examination of a donor's brain, combined with premortem clinical criteria, is often the most robust approach to correctly classify an individual as a disease-specific case or unaffected control. We describe the establishment of primary dermal fibroblasts cells lines from 28 autopsy donors. These fibroblasts were used to examine the proliferative effects of establishment protocol, tissue amount, biopsy site, and donor age. As proof-of-principle, iPSCs were generated from fibroblasts from a 75-year-old male, whole body donor, defined as an unaffected neurological control by both clinical and histopathological criteria. To our knowledge, this is the first study describing autopsy donor-derived somatic cells being used for iPSC generation and subsequent neural differentiation. This unique approach also enables us to compare iPSC-derived cell cultures to endogenous tissues from the same donor. We utilized RNA sequencing (RNA-Seq) to evaluate the transcriptional progression of in vitro-differentiated neural cells (over a timecourse of 0, 35, 70, 105 and 140 days), and compared this with donor-identical temporal lobe tissue. We observed in vitro progression towards the reference brain tissue, supported by (i) a significant increasing monotonic correlation between the days of our timecourse and the number of actively transcribed protein-coding genes and long intergenic non-coding RNAs (lincRNAs) (P < 0.05), consistent with the transcriptional complexity of the brain, (ii) an increase in CpG methylation after neural differentiation that resembled the epigenomic signature of the endogenous tissue, and (iii) a significant decreasing monotonic correlation between the days of our timecourse and the percent of in vitro to brain-tissue differences (P < 0.05) for tissue-specific protein-coding genes and all putative lincRNAs. These studies support the utility of autopsy donors' somatic cells for iPSC-based neurological disease models, and provide evidence that in vitro neural differentiation can result in physiologically progression.
ContributorsHjelm, Brooke E (Author) / Craig, David W. (Thesis advisor) / Wilson-Rawls, Norma J. (Thesis advisor) / Huentelman, Matthew J. (Committee member) / Mason, Hugh S. (Committee member) / Kusumi, Kenro (Committee member) / Arizona State University (Publisher)
Created2013
Description
It is commonly known that the left hemisphere of the brain is more efficient in the processing of verbal information, compared to the right hemisphere. One proposal suggests that hemispheric asymmetries in verbal processing are due in part to the efficient use of top-down mechanisms by the left hemisphere. Most evidence for this comes from hemispheric semantic priming, though fewer studies have investigated verbal memory in the cerebral hemispheres. The goal of the current investigations is to examine how top-down mechanisms influence hemispheric asymmetries in verbal memory, and determine the specific nature of hypothesized top-down mechanisms. Five experiments were conducted to explore the influence of top-down mechanisms on hemispheric asymmetries in verbal memory. Experiments 1 and 2 used item-method directed forgetting to examine maintenance and inhibition mechanisms. In Experiment 1, participants were cued to remember or forget certain words, and cues were presented simultaneously or after the presentation of target words. In Experiment 2, participants were cued again to remember or forget words, but each word was repeated once or four times. Experiments 3 and 4 examined the influence of cognitive load on hemispheric asymmetries in true and false memory. In Experiment 3, cognitive load was imposed during memory encoding, while in Experiment 4, cognitive load was imposed during memory retrieval. Finally, Experiment 5 investigated the association between controlled processing in hemispheric semantic priming, and top-down mechanisms used for hemispheric verbal memory. Across all experiments, divided visual field presentation was used to probe verbal memory in the cerebral hemispheres. Results from all experiments revealed several important findings. First, top-down mechanisms used by the LH primarily used to facilitate verbal processing, but also operate in a domain general manner in the face of increasing processing demands. Second, evidence indicates that the RH uses top-down mechanisms minimally, and processes verbal information in a more bottom-up manner. These data help clarify the nature of top-down mechanisms used in hemispheric memory and language processing, and build upon current theories that attempt to explain hemispheric asymmetries in language processing.
ContributorsTat, Michael J (Author) / Azuma, Tamiko (Thesis advisor) / Goldinger, Stephen D (Committee member) / Liss, Julie M (Committee member) / Arizona State University (Publisher)
Created2013
Description
Practical communication systems are subject to errors due to imperfect time alignment among the communicating nodes. Timing errors can occur in different forms depending on the underlying communication scenario. This doctoral study considers two different classes of asynchronous systems; point-to-point (P2P) communication systems with synchronization errors, and asynchronous cooperative systems. In particular, the focus is on an information theoretic analysis for P2P systems with synchronization errors and developing new signaling solutions for several asynchronous cooperative communication systems. The first part of the dissertation presents several bounds on the capacity of the P2P systems with synchronization errors. First, binary insertion and deletion channels are considered where lower bounds on the mutual information between the input and output sequences are computed for independent uniformly distributed (i.u.d.) inputs. Then, a channel suffering from both synchronization errors and additive noise is considered as a serial concatenation of a synchronization error-only channel and an additive noise channel. It is proved that the capacity of the original channel is lower bounded in terms of the synchronization error-only channel capacity and the parameters of both channels. On a different front, to better characterize the deletion channel capacity, the capacity of three independent deletion channels with different deletion probabilities are related through an inequality resulting in the tightest upper bound on the deletion channel capacity for deletion probabilities larger than 0.65. Furthermore, the first non-trivial upper bound on the 2K-ary input deletion channel capacity is provided by relating the 2K-ary input deletion channel capacity with the binary deletion channel capacity through an inequality. The second part of the dissertation develops two new relaying schemes to alleviate asynchronism issues in cooperative communications. The first one is a single carrier (SC)-based scheme providing a spectrally efficient Alamouti code structure at the receiver under flat fading channel conditions by reducing the overhead needed to overcome the asynchronism and obtain spatial diversity. The second one is an orthogonal frequency division multiplexing (OFDM)-based approach useful for asynchronous cooperative systems experiencing excessive relative delays among the relays under frequency-selective channel conditions to achieve a delay diversity structure at the receiver and extract spatial diversity.
ContributorsRahmati, Mojtaba (Author) / Duman, Tolga M. (Thesis advisor) / Zhang, Junshan (Committee member) / Tepedelenlioğlu, Cihan (Committee member) / Reisslein, Martin (Committee member) / Arizona State University (Publisher)
Created2013
Description
Digital sound synthesis allows the creation of a great variety of sounds. Focusing on interesting or ecologically valid sounds for music, simulation, aesthetics, or other purposes limits the otherwise vast digital audio palette. Tools for creating such sounds vary from arbitrary methods of altering recordings to precise simulations of vibrating objects. In this work, methods of sound synthesis by re-sonification are considered. Re-sonification, herein, refers to the general process of analyzing, possibly transforming, and resynthesizing or reusing recorded sounds in meaningful ways, to convey information. Applied to soundscapes, re-sonification is presented as a means of conveying activity within an environment. Applied to the sounds of objects, this work examines modeling the perception of objects as well as their physical properties and the ability to simulate interactive events with such objects. To create soundscapes to re-sonify geographic environments, a method of automated soundscape design is presented. Using recorded sounds that are classified based on acoustic, social, semantic, and geographic information, this method produces stochastically generated soundscapes to re-sonify selected geographic areas. Drawing on prior knowledge, local sounds and those deemed similar comprise a locale's soundscape. In the context of re-sonifying events, this work examines processes for modeling and estimating the excitations of sounding objects. These include plucking, striking, rubbing, and any interaction that imparts energy into a system, affecting the resultant sound. A method of estimating a linear system's input, constrained to a signal-subspace, is presented and applied toward improving the estimation of percussive excitations for re-sonification. To work toward robust recording-based modeling and re-sonification of objects, new implementations of banded waveguide (BWG) models are proposed for object modeling and sound synthesis. Previous implementations of BWGs use arbitrary model parameters and may produce a range of simulations that do not match digital waveguide or modal models of the same design. Subject to linear excitations, some models proposed here behave identically to other equivalently designed physical models. Under nonlinear interactions, such as bowing, many of the proposed implementations exhibit improvements in the attack characteristics of synthesized sounds.
ContributorsFink, Alex M (Author) / Spanias, Andreas S (Thesis advisor) / Cook, Perry R. (Committee member) / Turaga, Pavan (Committee member) / Tsakalis, Konstantinos (Committee member) / Arizona State University (Publisher)
Created2013
Description
Continuous monitoring in the adequate temporal and spatial scale is necessary for a better understanding of environmental variations. But field deployments of molecular biological analysis platforms in that scale are currently hindered because of issues with power, throughput and automation. Currently, such analysis is performed by the collection of large sample volumes from over a wide area and transporting them to laboratory testing facilities, which fail to provide any real-time information. This dissertation evaluates the systems currently utilized for in-situ field analyses and the issues hampering the successful deployment of such bioanalytial instruments for environmental applications. The design and development of high throughput, low power, and autonomous Polymerase Chain Reaction (PCR) instruments, amenable for portable field operations capable of providing quantitative results is presented here as part of this dissertation. A number of novel innovations have been reported here as part of this work in microfluidic design, PCR thermocycler design, optical design and systems integration. Emulsion microfluidics in conjunction with fluorinated oils and Teflon tubing have been used for the fluidic module that reduces cross-contamination eliminating the need for disposable components or constant cleaning. A cylindrical heater has been designed with the tubing wrapped around fixed temperature zones enabling continuous operation. Fluorescence excitation and detection have been achieved by using a light emitting diode (LED) as the excitation source and a photomultiplier tube (PMT) as the detector. Real-time quantitative PCR results were obtained by using multi-channel fluorescence excitation and detection using LED, optical fibers and a 64-channel multi-anode PMT for measuring continuous real-time fluorescence. The instrument was evaluated by comparing the results obtained with those obtained from a commercial instrument and found to be comparable. To further improve the design and enhance its field portability, this dissertation also presents a framework for the instrumentation necessary for a portable digital PCR platform to achieve higher throughputs with lower power. Both systems were designed such that it can easily couple with any upstream platform capable of providing nucleic acid for analysis using standard fluidic connections. Consequently, these instruments can be used not only in environmental applications, but portable diagnostics applications as well.
ContributorsRay, Tathagata (Author) / Youngbull, Cody (Thesis advisor) / Goryll, Michael (Thesis advisor) / Blain Christen, Jennifer (Committee member) / Yu, Hongyu (Committee member) / Arizona State University (Publisher)
Created2013
Description
Global Positioning System (GPS) is a navigation system widely used in civilian and military application, but its accuracy is highly impacted with consequential fading, and possible loss of communication due to multipath propagation and high power interferences. This dissertation proposes alternatives to improve the performance of the GPS receivers to obtain a system that can be reliable in critical situations. The basic performance of the GPS receiver consists of receiving the signal with an antenna array, delaying the signal at each antenna element, weighting the delayed replicas, and finally, combining the weighted replicas to estimate the desired signal. Based on these, three modifications are proposed to improve the performance of the system. The first proposed modification is the use of the Least Mean Squares (LMS) algorithm with two variations to decrease the convergence time of the classic LMS while achieving good system stability. The results obtained by the proposed LMS demonstrate that the algorithm can achieve the same stability as the classic LMS using a small step size, and its convergence rate is better than the classic LMS using a large step size. The second proposed modification is to replace the uniform distribution of the time delays (or taps) by an exponential distribution that decreases the bit-error rate (BER) of the system without impacting the computational efficiency of the uniform taps. The results show that, for a BER of 0.001, the system can operate with a 1 to 2 dB lower signal-to-noise ratio (SNR) when an exponential distribution is used rather than a uniform distribution. Finally, the third modification is implemented in the design of the antenna array. In this case, the gain of each microstrip element is enhanced by embedding ferrite rings in the substrate, creating a hybrid substrate. The ferrite rings generates constructive interference between the incident and reflected fields; consequently, the gain of a single microstrip element is enhanced by up to 4 dB. When hybrid substrates are used in microstrip element arrays, a significant enhancement in angle range is achieved for a given reflection coefficient compared to using a conventional substrate.
ContributorsRivera-Albino, Alix (Author) / Balanis, Constantine A (Thesis advisor) / Tepedelenlioğlu, Cihan (Committee member) / Kiaei, Sayfe (Committee member) / Aberle, James T (Committee member) / Arizona State University (Publisher)
Created2013
Description
Distributed estimation uses many inexpensive sensors to compose an accurate estimate of a given parameter. It is frequently implemented using wireless sensor networks. There have been several studies on optimizing power allocation in wireless sensor networks used for distributed estimation, the vast majority of which assume linear radio-frequency amplifiers. Linear amplifiers are inherently inefficient, so in this dissertation nonlinear amplifiers are examined to gain efficiency while operating distributed sensor networks. This research presents a method to boost efficiency by operating the amplifiers in the nonlinear region of operation. Operating amplifiers nonlinearly presents new challenges. First, nonlinear amplifier characteristics change across manufacturing process variation, temperature, operating voltage, and aging. Secondly, the equations conventionally used for estimators and performance expectations in linear amplify-and-forward systems fail. To compensate for the first challenge, predistortion is utilized not to linearize amplifiers but rather to force them to fit a common nonlinear limiting amplifier model close to the inherent amplifier performance. This minimizes the power impact and the training requirements for predistortion. Second, new estimators are required that account for transmitter nonlinearity. This research derives analytically and confirms via simulation new estimators and performance expectation equations for use in nonlinear distributed estimation. An additional complication when operating nonlinear amplifiers in a wireless environment is the influence of varied and potentially unknown channel gains. The impact of these varied gains and both measurement and channel noise sources on estimation performance are analyzed in this paper. Techniques for minimizing the estimate variance are developed. It is shown that optimizing transmitter power allocation to minimize estimate variance for the most-compressed parameter measurement is equivalent to the problem for linear sensors. Finally, a method for operating distributed estimation in a multipath environment is presented that is capable of developing robust estimates for a wide range of Rician K-factors. This dissertation demonstrates that implementing distributed estimation using nonlinear sensors can boost system efficiency and is compatible with existing techniques from the literature for boosting efficiency at the system level via sensor power allocation. Nonlinear transmitters work best when channel gains are known and channel noise and receiver noise levels are low.
ContributorsSantucci, Robert (Author) / Spanias, Andreas (Thesis advisor) / Tepedelenlioðlu, Cihan (Committee member) / Bakkaloglu, Bertan (Committee member) / Tsakalis, Kostas (Committee member) / Arizona State University (Publisher)
Created2013
Description
Specific dendritic morphologies are a hallmark of neuronal identity, circuit assembly, and behaviorally relevant function. Despite the importance of dendrites in brain health and disease, the functional consequences of dendritic shape remain largely unknown. This dissertation addresses two fundamental and interrelated aspects of dendrite neurobiology. First, by utilizing the genetic power of Drosophila melanogaster, these studies assess the developmental mechanisms underlying single neuron morphology, and subsequently investigate the functional and behavioral consequences resulting from developmental irregularity. Significant insights into the molecular mechanisms that contribute to dendrite development come from studies of Down syndrome cell adhesion molecule (Dscam). While these findings have been garnered primarily from sensory neurons whose arbors innervate a two-dimensional plane, it is likely that the principles apply in three-dimensional central neurons that provide the structural substrate for synaptic input and neural circuit formation. As such, this dissertation supports the hypothesis that neuron type impacts the realization of Dscam function. In fact, in Drosophila motoneurons, Dscam serves a previously unknown cell-autonomous function in dendrite growth. Dscam manipulations produced a range of dendritic phenotypes with alteration in branch number and length. Subsequent experiments exploited the dendritic alterations produced by Dscam manipulations in order to correlate dendritic structure with the suggested function of these neurons. These data indicate that basic motoneuron function and behavior are maintained even in the absence of all adult dendrites within the same neuron. By contrast, dendrites are required for adjusting motoneuron responses to specific challenging behavioral requirements. Here, I establish a direct link between dendritic structure and neuronal function at the level of the single cell, thus defining the structural substrates necessary for conferring various aspects of functional motor output. Taken together, information gathered from these studies can inform the quest in deciphering how complex cell morphologies and networks form and are precisely linked to their function.
ContributorsHutchinson, Katie Marie (Author) / Duch, Carsten (Thesis advisor) / Neisewander, Janet (Thesis advisor) / Newfeld, Stuart (Committee member) / Smith, Brian (Committee member) / Orchinik, Miles (Committee member) / Arizona State University (Publisher)
Created2013
Description
Radio frequency (RF) transceivers require a disproportionately high effort in terms of test development time, test equipment cost, and test time. The relatively high test cost stems from two contributing factors. First, RF transceivers require the measurement of a diverse set of specifications, requiring multiple test set-ups and long test times, which complicates load-board design, debug, and diagnosis. Second, high frequency operation necessitates the use of expensive equipment, resulting in higher per second test time cost compared with mixed-signal or digital circuits. Moreover, in terms of the non-recurring engineering cost, the need to measure complex specfications complicates the test development process and necessitates a long learning process for test engineers. Test time is dominated by changing and settling time for each test set-up. Thus, single set-up test solutions are desirable. Loop-back configuration where the transmitter output is connected to the receiver input are used as the desirable test set- up for RF transceivers, since it eliminates the reliance on expensive instrumentation for RF signal analysis and enables measuring multiple parameters at once. In-phase and Quadrature (IQ) imbalance, non-linearity, DC offset and IQ time skews are some of the most detrimental imperfections in transceiver performance. Measurement of these parameters in the loop-back mode is challenging due to the coupling between the receiver (RX) and transmitter (TX) parameters. Loop-back based solutions are proposed in this work to resolve this issue. A calibration algorithm for a subset of the above mentioned impairments is also presented. Error Vector Magnitude (EVM) is a system-level parameter that is specified for most advanced communication standards. EVM measurement often takes extensive test development efforts, tester resources, and long test times. EVM is analytically related to system impairments, which are typically measured in a production test i environment. Thus, EVM test can be eliminated from the test list if the relations between EVM and system impairments are derived independent of the circuit implementation and manufacturing process. In this work, the focus is on the WLAN standard, and deriving the relations between EVM and three of the most detrimental impairments for QAM/OFDM based systems (IQ imbalance, non-linearity, and noise). Having low cost test techniques for measuring the RF transceivers imperfections and being able to analytically compute EVM from the measured parameters is a complete test solution for RF transceivers. These techniques along with the proposed calibration method can be used in improving the yield by widening the pass/fail boundaries for transceivers imperfections. For all of the proposed methods, simulation and hardware measurements prove that the proposed techniques provide accurate characterization of RF transceivers.
ContributorsNassery, Afsaneh (Author) / Ozev, Sule (Thesis advisor) / Bakkaloglu, Bertan (Committee member) / Kiaei, Sayfe (Committee member) / Kitchen, Jennifer (Committee member) / Arizona State University (Publisher)
Created2013