VictorJuiz/thesis huggingface dataset:
Illuminating glycoconjugate interactions and glycosyltransferase substrates using photocrosslinking sugar analogs [electronic resource]
Keywords: Chemistry

The cell surface is composed of a heterogeneous array of proteins and lipids, many of which are modified by carbohydrate structures. Glycoconjugates, which include both glycoproteins and glycolipids, play vital roles in cellular functions, mediating communication with the extracellular environment. A frequent modification to cell surface carbohydrates is the addition of a nine-carbon [alpha]-keto acid, sialic acid. Sialic acid-dependent interactions are often characterized by large equilibrium dissociation constants and rapid dissociation rates, precluding the use of traditional biological techniques for isolating these complexes. To investigate glycan-mediated interactions, I employed the use of metabolic oligosaccharide engineering to introduce a panel of diazirine-modified sialic acids onto the cell surface. I demonstrate that the sialic acid analogs covalently trap both glycoprotein- and glycolipid-mediated interactions, illustrating the utility of the photoactivatable sugars. These results are significant as they yield a new set of tools for studying ephemeral interactions that are otherwise inaccessible.
Illuminating the function of dopaminergic neurons in reward [electronic resource]
Keywords: Neurosciences.

This thesis examines a neural substrate (i.e. dopaminergic signaling) of reward, by integrating techniques designed to manipulate and quantify changes in behavior, neural activity, and neurotransmitter release in freely-moving animals. Dopaminergic signaling is essential to the brain's reward system. The majority of dopaminergic neurons reside in the ventral tegmental area (VTA) and project to diverse brain regions including the nucleus accumbens (NAc), one of the major integrative hubs of reward signals. Dopaminergic neurons are known to fire in two distinct modes (phasic, > 15Hz; tonic, < 10Hz) under different behavioral conditions. Both firing modes are known to be involved in multiple reward-related behaviors in normal and neuropsychiatric conditions. However, the casual role of dopaminergic neuron activity in reward-related behaviors remains unclear, largely due to a lack of technologies to selectively control dopaminergic neuron signaling in freely-moving animals during reward-related behavioral tasks. To solve this problem, we first developed a set of optogenetic technologies to selectively control dopaminergic neuron activity in vivo. By targeting a light-sensitive microbial opsin, channelrhodopsin-2 (ChR2), to the VTA dopaminergic neurons we were able to modulate dopaminergic neuron activity in freely-moving mice during behavioral tasks. We accomplished this using a thin optical fiber to deliver precisely-timed trains of light flashes directly into the VTA. We found that phasic and not tonic firing evoked by light in dopaminergic neurons is sufficient to mediate a strong conditioned place preference in rodents in the absence of other reward. Similarly, phasic dopaminergic neuron firing reinforces the lever-pressing behavior during an operant conditioning task. Phasic firing also induced substantial transient dopamine release in NAcc, as measured by fast scan cyclic Voltammetry (FSCV). Together, our behavioral and electrochemical data demonstrate a causal role of phasic dopaminergic neuron firing in behavioral conditioning. The integration of cell-specific targeting techniques with electrophysiological, behavioral, and biochemical readout methods proves to be a powerful approach to studying the role of dopaminergic signaling in the brain reward system and is likely to prove effective in the study of neuropsychiatric disorders such as depression and addiction.
Image authentication using distributed source coding [electronic resource]
Keywords: Electrical Engineering

Image authentication is important in content delivery via untrusted intermediaries, such as peer-to-peer (P2P) file sharing. Many differently encoded versions of the original image might exist. In addition, intermediaries might tamper with the contents. Distinguishing legitimate diversity from malicious manipulations is the challenge addressed in this dissertation. We propose an approach using distributed source coding for the image authentication problem. The key idea is to provide a Slepian-Wolf encoded quantized image projection as authentication data. This version can be correctly decoded with the help of an authentic image as side information. Distributed source coding provides the desired robustness against legitimate variations while detecting illegitimate modification. The decoder incorporating expectation maximization (EM) algorithms can authenticate images which have undergone contrast, brightness, and affine warping adjustments. Our novel authentication system also offers tampering localization by using inference over a factor graph that represents tampering models. Video quality monitoring is closely related to the image authentication problem. We contribute an approach using distributed source coding. The video receiver sends the Slepian-Wolf coded video projections to the quality monitoring server which has access to the original video. Distributed source coding provides rate-efficient encoding of the projection by exploiting the correlation between the projections of the original and received videos. We show that the projections can be encoded at a low rate of just a few kilobits per second. Compared to the ITU-T J.240 Recommendation for remote PSNR monitoring, our scheme achieves a bit-rate which is lower by at least one order of magnitude.
Imaging Redshift Estimates for BL Lacertae Objects
Keywords: Physics
BL Lacertae objects
BL Lacs
Thesis

We describe an imaging campaign to constrain the redshifts of candidate or known gamma-ray BL Lacertae objects (BL Lacs) for which redshifts remain undetermined despite prior spectroscopy. As it has been argued that BL Lac host galaxies are roughly standard candles, a BL Lac host detection provides a redshift estimate. Similarly, a host flux upper limit yields a redshift lower limit. By obtaining high dynamic range, good natural seeing i′ images of 49 BL Lacs, we detected 25 of their host galaxies (resulting in redshift estimates) and placed flux upper limits on the remaining 24 hosts (resulting in redshift lower bounds). The mean of the fit redshifts (and lower limits) is higher than that of spectroscopic solutions in the radio-loud and gamma-ray-loud parent samples, suggesting corrections may be needed for the luminosity function and evolution of these sources. We describe several follow-up projects and compare our redshift constraints for specific objects with those recently obtained via alternative means, finding good agreement.
Immigrant exclusion and insecurity in Africa [electronic resource]
Keywords: Political Science

Why do some immigrant communities integrate into their host societies in Africa while others face exclusion and violence? My dissertation offers new insights on the determinants of identity and group relations in ethnically diverse societies, through the lens of South-to-South migration. It argues and finds that immigrant exclusion in Africa is a function of both the economic competition that characterizes relations between immigrant and indigenous traders, and the bargains that immigrant community leaders strike with local police to become monopoly providers of immigrant socio-economic security. These dynamics structure the incentives of immigrants and hosts alike; cultural similarities between immigrant and host communities decrease the cost of passing as indigenous and threaten the positions of immigrant leaders and indigenous hosts. As a result, cultural overlap between immigrants and hosts in West Africa tends to exacerbate immigrant exclusion.
Implantable fluorescence sensor for continuous molecular monitoring in live animals [electronic resource]
Keywords: Electrical Engineering

Molecular imaging is an established technique used to visualize and quantify functional information about biological processes in living systems. In vivo fluorescence imaging, in particular, is a molecular imaging technique capable of quantitatively imaging one or more fluorophores at high spatial and temporal resolution with high sensitivity, either at microscopic or macroscopic (whole-body) scales. While current fluorescent imaging technologies have led to key advances in the understanding of biology and biochemistry, there are limitations. Modern in vivo fluorescence imagers are bulky, and typically take snapshots, and only sample discrete points of continuous, dynamic processes. In order to overcome these obstacles and enable long-term, continuous fluorescence imaging in live animals, we have miniaturized the components of the optical imaging system, allowing for direct implantation. Miniature fluorescence sensors have been fabricated to match a particular fluorescent probe utilizing semiconductor processing technology and appropriate materials. We present the design and fabrication of a monolithically integrated semiconductor (GaAs-based) sensor for far-red to near infrared (NIR) in vivo fluorescence sensing. The sensor incorporates three basic components of a fluorescence system, including: a 675nm vertical-cavity surface-emitting laser (VCSEL) excitation source, a GaAs PIN photodiode, and a fluorescence emission filter. We have packaged the sensors in several integrated configurations, and developed readout mechanisms that include a system that can be implanted in small rodents. We have utilized this device to demonstrate that in vivo fluorescence imaging is possible with miniaturized, un-cooled semiconductor devices, including a demonstration of sensing in a freely-moving rodent. Such miniaturized, implantable biomedical devices have the potential to accelerate pre-clinical research and revolutionize clinical care by providing an inexpensive means for diagnosis, monitoring disease progression, and evaluating long-term treatment efficacy. By integrating this implantable sensor with the appropriate read-out electronics and wireless telemetry, un-tethered operation can ultimately be achieved.
An improved hydrogen/oxygen mechanism based on shock tube/laser absorption measurements [electronic resource]
Keywords: Mechanical Engineering

H2/O2 combustion chemistry is the core of all hierarchical hydrocarbon combustion mechanisms. Because of this, H2/O2 combustion chemistry has been the target of extensive research and our understanding has been improved substantially over the years. However, there still remains a critical need for improvements and the development of an even higher fidelity H2/O2 mechanism. These improvements require the researcher to go beyond existing methodologies and to adopt new approaches and better tools. This thesis outlines the work carried out to produce such a high-fidelity mechanism. In particular, a three-part strategy was implemented: 1) new shock tube/laser absorption tools were developed, 2) rates constants of selected HO2/H2O2 reaction were measured, and 3) a new mechanism was developed and validated. 1) Within the scope of this dissertation work, two major tools were developed: a modified shock tube and a sensitive H2O diagnostic. A standard shock tube was modified to eliminate gradual temperature or pressure rises behind reflected shock waves due to non-ideal effects. Long and uniform test times were achieved with the modified shock tube behind reflected shock waves, where kinetics experiments were carried out. H2O time-histories behind reflected shock waves were recorded with an H2O laser absorption diagnostic part of whose development was also included in this study. Accurate knowledge of trace amounts of H2O in combustion systems provides a unique new capability in studies of combustion chemistry. In addition, an OH laser absorption diagnostic for OH that has been well-established in this laboratory was used in combination with the H2O diagnostic for a more thorough understanding of combustion kinetics. 2) The rate constants of four important reactions within the H2/O2 combustion system were experimentally determined. By combining the modified shock tube technique with the laser diagnostics for OH and H2O, various H2/O2 systems were studied to obtain more accurate rate constants for several important reactions at combustion temperatures, including: H + O2 = OH + O; H2O2 + M = 2OH + M; OH + H2O2 = HO2 + H2O; and O2 + H2O = OH + HO2. 3) An improved H2/O2 reaction mechanism was compiled that incorporated the aforementioned rate constant determinations, as well as recent studies from other laboratories. The new mechanism was tested against OH and H2O species time-histories in various H2/O2 systems, such as H2 oxidation, H2O2 decomposition, and shock-heated H2O/O2 mixtures, and was found to be in very good agreement. In addition, the current mechanism was validated against a wide range of more standard H2/O2 kinetic targets, including ignition delay times, flow reactor species time-histories, laminar flame speeds, and burner-stabilized flame structures.
Improving the discrimination of unexploded ordnances [electronic resource]
Keywords: Aeronautics and Astronautics

Unexploded ordnances, UXOs, are a significant safety and economic problem in the US and worldwide. Typically, they consist of munitions such as rockets, artillery shells, and missiles. They are buried in unknown locations and present a danger due to both their explosive nature and their environmental impact. Across the US, UXOs are suspected to infest over 15 million acres of land consisting of troop training areas, weapons testing sites, and munitions storage facilities. One of the difficult challenges facing UXO clearance work is discriminating whether a detected target is an UXO and needs to be excavated or an inert object that can be left in the ground. An electromagnetic induction, EMI, sensor is commonly used in UXO clearance work. This research introduces two strategies that change the way the EMI sensor is used in order to improve discrimination. The first strategy is to use more target specific sensor swaths and to use an odometer based positioning system. This research shows that this can improve discrimination over the traditional GPS-based approach because there is less relative error in the sensor position estimates. The next strategy is to use an adaptive sensing algorithm to determine where to move and how to orient an EMI sensor. Allowing the sensor to rotate increases the directions at which the target can be illuminated. The adaptive sensing algorithm exploits this new flexibility to maximize the information obtained during a sensor run, thereby improving UXO discrimination.
Improving the practicality of transactional memory [electronic resource]
Keywords: Electrical Engineering

Transactional Memory (TM) simplifies parallel programming by transferring responsibility for concurrency management from the programmer to the system. Nevertheless, a number of challenges must be addressed for TM to be widely adopted. This dissertation presents work towards improving the practicality of TM across three dimensions: improving programmability, supporting nested parallel transactions, and checking the correctness of TM systems.
Improving the reliability and performance of impact-ionization based transistors for low power logic applications [electronic resource]
Keywords: Electrical Engineering.

Standby power dissipation is becoming an increasingly significant problem for integrated circuits due to the non-scaling behavior of the transistor leakage currents. Underlying this problem is the concept of subthreshold slope (S), which is a measure of switching abruptness in transistors. For MOSFETs, S is fundamentally limited at 60 mV/decade by the drift-diffusion based transport. This leads to an exponential increase in the off-state leakage with feature size scaling. This thesis starts with an overview of several innovative device concepts that have demonstrated proof of S < 60 mV/decade operation. Among these novel devices, Impact-Ionization MOS (IMOS) transistor is highlighted as an attractive candidate, due to its all-electrical operation and extremely abrupt switching behavior. The major obstacles before IMOS are identified to be poor reliability and high operating voltage. Subsequent chapters are devoted to a through study of IMOS reliability. Experimental and simulation-based characterization of the device points to several structural problems that lead to severe hot carrier induced damage and poor repeatability. In order to address these problems, a novel device structure called depletion IMOS (DIMOS) is proposed. DIMOS operating principles and electrical characteristics are studied via simulations and experiments. Experimental results of the DIMOS show suppression of hot carrier injection into the gate and feature repeatable steep subthreshold slope switching for the first time. This work concludes with a discussion of circuit design issues surrounding IMOS and DIMOS devices.
In vivo high-resolution magnetic resonance imaging [electronic resource]
Keywords: Electrical Engineering

Magnetic resonance imaging is a powerful, non-invasive modality that provides excellent soft-tissue contrast, but it suffers from a relatively low signal-to-noise ratio and is inherently prone to artifacts. Although technological progress over the last few decades has dramatically enhanced the resolution and quality of magnetic resonance images, specific clinical challenges highlight the need for further improvements. First, patients with peripheral arterial disease are at high risk for developing skin ulcers, which are often detected at a late stage, when amputation is the only treatment option. High-resolution imaging might detect changes in skin early enough to enable alternative treatments. Second, higher-resolution larynx imaging is highly desirable for the exact assessment of cartilage invasion, which is a critical step in cancer staging and in the selection of the appropriate treatment. High-resolution skin and larynx magnetic resonance imaging poses specific engineering challenges. The resolution of magnetic resonance images is first hampered by insufficient signal-to-noise ratio. Dedicated surface coils and/or higher field strengths overcome this limitation. Receive-only and transmit/receive 1-inch-diameter coils are shown to be suitable for skin imaging at 1.5 T, 3 T, and 7 T, and a dedicated three-channel array for larynx imaging provides a dramatic increase in resolution over the conventionally used 8-channel neurovascular array. The next engineering challenge involves eliminating artifacts from high-resolution images. Chemical shift artifacts are a concern in skin imaging, especially at higher field strengths, because the hypodermis is a fat layer. A multi-echo sequence is introduced that separates fat and water and provides good signal-to-noise ratio for all skin layers. Motion artifacts affect both skin and larynx images. In skin, where motion is usually rigid-body, navigator-based motion correction proves effective, and navigators can be integrated into the multi-echo sequence that separates fat and water. In larynx, where motion is complex, a new real-time algorithm combining a reacquisition strategy with navigator-based motion correction accounts for the different types of motion. One additional concern with skin imaging at higher field strengths is the increase in the spin-lattice relaxation time T1, which compromises the signal-to-noise ratio. Robust T1 mapping requires the use of a 4-parameter model. A novel nonlinear Least-Squares algorithm reduces the complex minimization problem to a straightforward 1D search, making the fitting procedure much faster. T1 mapping performed in skin at 1.5 T, 3 T, and 7 T shows that the increase in T1 slightly attenuates the benefits of higher field strengths but does not offset them.
Incorporating the dynamic nature of molecules improves performance of structure-based function prediction methods [electronic resource]
Keywords: Genetics

Structural Genomics consortia aim to determine the structure of proteins with novel folds. In order to interpret their biological significance, it is critical to annotate the functions of these structures. Most structures are solved by X-ray crystallography experiments and represent static snapshots of the molecules. Structure-based function prediction methods do not perform well when the snapshots fail to display the relevant functional conformations. We show that coupling structure-based function prediction methods to molecular dynamics simulations considerably improves their performance in locating calcium binding sites. Our approach can be easily extended to other functions of interest. In particular, we generated short- to medium- scale molecular simulation trajectories (1ns -- 10ns) using GROMACS, a software suite developed for creating molecular dynamics simulations. Gromos 43a5, Gromos 53a6, AMBER '96, AMBER '99SB, AMBER '03, and OPLS-AA force fields were used to generate trajectories for 11 pairs of PDB structures, HOLO and APO form for the presence of calcium ions in the structures (22 structrures in total). Extracting structures at various time points over the course of the simulations we created structural ensembles which inform about the dynamic nature of each of the simulation systems. Using FEATURE, a machine learning algorithm that evaluates the presence of enriched physico-chemical properties around a site of interest, we analyzed the structural ensembles for the presence of calcium binding sites. We devised a clustering algorithm which allowed for definitive determination of the similarity of the local environments around the points identified by FEATURE as potential calcium binding site centers in different structural ensembles for each of the 22 PDB structures. Our results indicate that short scale simulations with 2 or 3 different force fields generate sufficient structural diversity to allow for improved identification of calcium binding sites. Furthermore, inclusion of calcium ions in the simulation systems does not significantly improve the performance of FEATURE. This result highlights the need for improved force fields, such that the dynamic nature of calcium binding sites can be accurately reproduced.