Mechanisms Underlying Maintenance of Adult Visual Receptive Fields

The establishment of neuronal connections requires a sequence of orchestrated events including neuronal migration, axon guidance, synapse formation and elimination, and circuit fine-tuning. Understanding the molecular signaling pathways that underlie these processes is fundamental to understanding how the nervous system is assembled and how it functions. In this dissertation, I investigated the molecular mechanisms mediating the effects of visual experience in the development and plasticity of the visual pathway. Each neuron receiving visual input responds to a specific area of the visual field- their receptive field (RF). During early development RFs refine in size, an important property of visual acuity. Utilizing the sensory deprivation model of dark rearing (DR) in Syrian hamsters (Mesocricerus auratus), I investigated the signaling mechanisms underlying RF refinement and plasticity. Our lab has previously reported that the developmental refinement of RFs happens independently of visual experience in both superior colliculus (SC) and visual cortex (V1), but fails to be maintained without sufficient visual experience during an early critical period (CP). Using a pharmacological approach, I show that BDNF/TrkB signaling is crucial for the maintenance of RF refinement in SC. DR hamsters treated with a TrkB agonist during the CP for RF refinement maintenance (P33-P40) have mature RFs in adulthood. Hamsters given visual experience, but treated with a TrkB antagonist during the CP have enlarged (unrefined) RFs in adulthood. I also show that refined RFs are essential for enhancing both looming escape behaviors, and spatial discrimination of sinusoidal gratings. How early visual experience prevents plasticity in adulthood (resulting in a loss of RF maintenance) is poorly understood, but reduced GABAergic inhibition is involved. Using a molecular approach I identified several possible mechanisms mediating a loss of inhibition in SC of DR adults. Ultimately it appears that reduced expression of the GABA neurotransmitter is primarily responsible for loss of RF maintenance, rather than any post synaptic modifications. This work provides insight into the mechanisms of development and plasticity in the nervous system and could instruct therapies to prevent maladaptive plasticity in disease and to enhance recovery of function in adults

A Virtual Hydroelectric Power System for Distributable Industrial Control System Security Research

Cyber security for industrial control systems (ICS) has been a rapidly growing area of interest and research for the last several years. The lack of an easily distributable platform on which ICS components can be built for use in security testing and result comparison among researchers presents a major issue. This thesis details the use of a virtual testbed environment to build a representative virtual hydroelectric power system (VHPS). The VHPS generates realistic Modbus/TCP network traffic between two separate ICS devices, a Master and a Slave, located on separate VMs. For security testing purposes, a method of session hijacking has been implemented as well as a Function Code Scan attack and a Setpoint Manipulation attack. The virtual environment, the VHPS, and the attacks have been packaged into an LXDE-based Fedora Spin VM for easy distribution

Strategy, Uncertainty, and the China Challenge

Despite China’s increasing aggressiveness, its intentions are indeterminate, even aligning with U.S. interests in some arenas. Furthermore, China simply may fail in achieving even its foremost national and foreign-policy goals. Given this uncertainty, the United States should not base its policy and strategy on any specific prediction about Chinese intentions or abilities

Experimental study of the properties of the Higgs boson

Measurements of Higgs boson production and decay rates are presented using the proton-proton collision data collected by the ATLAS experiment during LHC Run I, corresponding to 4.5 fb$^-$$^1$ at 7 TeV and 20.3 fb$^-$$^1$ at 8 TeV. Under certain assumptions, the coupling strengths of the Higgs boson to Standard Model particles are also probed. The H -> ZZ$^($$^*$$^)$$_-$$_>$ 4I final state, where I = e, mu, is discussed, and is observed with a significance corresponding to 8.1 standard deviations. The Higgs boson production rate, relative to the Standard Model prediction, is measured to be mu = 1.44$^+$$^0$$^.$$^4$$^0$$_-$$_0$$_.$$_3$$_3$ at the ATLAS best-fit value for the measurement of the Higgs boson mass, m$_H$ = 125.36 GeV. The various Higgs boson production and decay modes studied by the ATLAS experiment are also combined. The couplings of the Higgs boson are probed in a number of benchmark models, where a good agreement with the Standard Model prediction is observed for each model considered. The Higgs boson coupling measurements are also used to place constraints on a number of beyond the Standard Model theories, and are combined with direct searches for invisible Higgs boson decays to place a limit on the Higgs boson branching ratio to invisible final states

People and ground stone tools in the Zagros Neolithic - economic and social interpretations of the assemblage from Bestansur, Iraqi Kurdistan

Recent research into ground stone technology has moved beyond the earlier typological approach of describing and classifying the artefact at the point when it entered the archaeological record, towards a perspective which studies the broader sequences of processes and activities by which people made, used, and deposited the artefacts. Most studies of Neolithic Zagros ground stone assemblages have not, until now, been subjected to these new approaches. My thesis analyses and interprets a ground stone assemblage (424 tools and 412 items of debitage and unworked stone) from the Early Neolithic settlement of Bestansur in the Central Zagros (Iraqu Kurdistan). It uses the 'object biography' approach to address these research aims. These are to find and interpret the whole life-history of the artefacts, to identify the characteristics of the people who made and engaged with them, and third, to explore the role of ground stone in the development of social process and relations in the Early Neolithic of the eastern Fertile Crescent, particularly in quotidian and ritual processes such as commensality and funerary practice. The thesis reviews the development of ground stone research in the Neolithic Zagros. It uses the modern techniques of usewear and residue analysis, and draws on ethnographic studies to interpret the role and significance of ground stone in Neolithic Bestansur. In answering these research questions, it shows how ground stone artefacts afforded technological solutions to many problems associated with the development of settled residential life, exploiting the cultivation of plants and the management of animals, and new and more complex social practice and structures, the key changes of the Neolithic in southwest Asia. It also concludes that the presence or absence of ground stone tools can be used to illustrate past processes of abandonment of buildings and settlements

Explaining Predictive Uncertainty with Information Theoretic Shapley Values

Researchers in explainable artificial intelligence have developed numerous methods for helping users understand the predictions of complex supervised learning models. By contrast, explaining the $\textit{uncertainty}$ of model outputs has received relatively little attention. We adapt the popular Shapley value framework to explain various types of predictive uncertainty, quantifying each feature's contribution to the conditional entropy of individual model outputs. We consider games with modified characteristic functions and find deep connections between the resulting Shapley values and fundamental quantities from information theory and conditional independence testing. We outline inference procedures for finite sample error rate control with provable guarantees, and implement an efficient algorithm that performs well in a range of experiments on real and simulated data. Our method has applications to covariate shift detection, active learning, feature selection, and active feature-value acquisition

Efficacy and Safety of Once-Daily Vibegron for Treatment of Overactive Bladder in Patients Aged ≥65 and ≥75 Years: Subpopulation Analysis from the EMPOWUR Randomized, International, Phase III Study

Background Overactive bladder (OAB) is common among older adults. The efficacy and safety of vibegron for the treatment of OAB were demonstrated in the international, phase III EMPOWUR trial. This subpopulation analysis from EMPOWUR assessed the efficacy and safety of vibegron in patients aged ≥ 65 and ≥ 75 years. Methods In EMPOWUR, patients with OAB were randomly assigned 5:5:4 to receive once-daily vibegron 75 mg, placebo, or tolterodine 4 mg extended release, respectively, once daily for 12 weeks. Coprimary efficacy endpoints were change from baseline at week 12 in average daily number of micturitions and urge urinary incontinence (UUI) episodes; a key secondary efficacy endpoint was change from baseline at week 12 in average daily number of urgency episodes. Safety was assessed through adverse events (AEs). Efficacy analyses compared vibegron with placebo; no efficacy comparisons were made between vibegron and tolterodine. Results Of the 1463 patients with evaluable efficacy data, 628 patients were aged ≥ 65 years, and 179 were aged ≥ 75 years. After 12 weeks, patients treated with once-daily vibegron 75 mg in both age subgroups showed significant improvements from baseline versus placebo in all three symptoms of OAB: daily micturitions (≥ 65 years, P \u3c 0.0001; ≥75 years, P \u3c 0.05), UUI episodes (≥ 65 years, P \u3c 0.001; ≥ 75 years, P \u3c 0.0001), and urgency episodes (≥ 65 years, P \u3c 0.01; ≥ 75 years, P \u3c 0.01). Significant reductions from baseline versus placebo in daily micturitions, UUI episodes, and urgency episodes were observed beginning at week 2 for patients aged ≥ 65 years treated with vibegron. In patients aged ≥ 65 years, 50.0% of those receiving vibegron versus 29.8% receiving placebo experienced a ≥ 75% reduction in UUI episodes at week 12 (P\u3c 0.0001). Rates of cardiovascular-associated AEs were low for patients receiving vibegron ( Conclusions In this subpopulation analysis of patients with OAB aged ≥ 65 and ≥ 75 years from the EMPOWUR study, once-daily vibegron 75 mg showed rapid onset and robust efficacy versus placebo and was generally safe and well tolerated, consistent with results from the overall population