Systemic Acrolein Elevations in Mice With Experimental Autoimmune Encephalomyelitis and Patients With Multiple Sclerosis

Demyelination and axonal injury are the key pathological processes in multiple sclerosis (MS), driven by inflammation and oxidative stress. Acrolein, a byproduct and instigator of oxidative stress, has been demonstrated as a neurotoxin in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. However, due to the invasive nature of acrolein detection using immunoblotting techniques, the investigation of acrolein in MS has been limited to animal models. Recently, detection of a specific acrolein-glutathione metabolite, 3-HPMA, has been demonstrated in urine, enabling the noninvasive quantification of acrolein for the first time in humans with neurological disorders. In this study, we have demonstrated similar elevated levels of acrolein in both urine (3-HPMA) and in spinal cord tissue (acrolein-lysine adduct) in mice with EAE, which can be reduced through systemic application of acrolein scavenger hydralazine. Furthermore, using this approach we have demonstrated an increase of 3-HPMA in both the urine and serum of MS patients relative to controls. It is expected that this noninvasive acrolein detection could facilitate the investigation of the role of acrolein in the pathology of MS in human. It may also be used to monitor putative therapies aimed at suppressing acrolein levels, reducing severity of symptoms, and slowing progression as previously demonstrated in animal studies

Video Game Cultivation: Sowing the Seeds of Consumer Behavior

George Gerbner (1998) dedicated a significant amount of this life attempting to understand the creation and impact of mass media messages on viewers. Out of this research sprang cultivation theory, which holds viewers\u27 realities can be impacted over time by the media environment they inhabit and its overarching messages. While often applied to television, cultivation theory has largely ignored other mediums, specifically video games. Video games have evolved as a medium since the public arcades of the 1980\u27s and now run on high-powered, internet-enabled consoles. These consoles allow producers into the home of the consumer, saturating them with messages. This thesis advocates video game producer messages are encoded in such a manner as to encourage the consumption of video game content and instill in the consumer a reality constructed by the producer. To interrogate these messages, I conduct a case study of a video game developer, Tacit Games (a pseudonym), and examine how the producer attempts to cultivate consumption in the consumer through approaches like downloadable content and framing the video game experience for the video game consumer. Specifically, I examine messages surrounding the developer\u27s franchise, City Mayhem (also a pseudonym). To do this, I conduct qualitative interviews with five senior employees of the company to ascertain what messages are produced for the consumer in relation to the goals of this thesis. The data collected from these interviews is analyzed through the lens of cultural Marxism, which entails the examination of the limitations and pressures exerted on the formation of culture

Power, Efficiency, and Emissions Optimization of a Single Cylinder Direct-Injected Diesel Engine for Testing of Alternative Fuels through Heat Release Modeling

The increasing dependency of the global economy on mineral fuels necessitates the investigation and future implementation of renewable fuels. Within the spectrum of compression ignition engines, this requires an understanding of the differences in combustion of alternative fuels (including biodiesels) from mineral diesel fuel oil, and requires an environment conducive to the experimentation necessary for future research. This thesis is a work in four parts, and gives much of the perspective necessary to empirically correlate the changes caused by differing fuel inputs. The first chapter provides a background as to the motivation of the work, its component sections, and a description of the work done previously and in parallel with the thesis. Finally, the focus of the thesis is given in order to relate the components to each other. The second chapter takes the form of a thorough review of hydrocarbon emissions from the perspective of compression-ignition engines, including a description of the variance in emissions when switching between diesel fuels from mineral or biological sources. The broad field of hydrocarbon emissions is broken down into subspecies of the group, and a recommendation as the future catalytic aftertreatment modeling using these subspecies is given. In chapter three, the basis of a thermodynamic equilibrium-based heat release model is given. In particular, this model is set up to use an Arrhenius-based rate of combustion calibrated to the emission profile recorded during experimentation. The model is subsequently tested and validated against previously acquired data, in order to highlight the model's ability to cope with varying testing modes, including variable fuels, Exhaust Gas Recirculation, or changing aspiration techniques. The final chapter describes the experimental procedure used to find the proper injection timings to trigger the Maximum Brake Torque condition at a given engine speed as a function of engine load, with the goal of accelerating future calibration of the improved test cell. These timings are also compared to the emissions profile of the engine, with the goal of linking variations in efficiency and emissions composition to variable injection timings

Standing together for reproducibility in large-scale computing: report on reproducibility@XSEDE

This is the final report on reproducibility@xsede, a one-day workshop held in conjunction with XSEDE14, the annual conference of the Extreme Science and Engineering Discovery Environment (XSEDE). The workshop's discussion-oriented agenda focused on reproducibility in large-scale computational research. Two important themes capture the spirit of the workshop submissions and discussions: (1) organizational stakeholders, especially supercomputer centers, are in a unique position to promote, enable, and support reproducible research; and (2) individual researchers should conduct each experiment as though someone will replicate that experiment. Participants documented numerous issues, questions, technologies, practices, and potentially promising initiatives emerging from the discussion, but also highlighted four areas of particular interest to XSEDE: (1) documentation and training that promotes reproducible research; (2) system-level tools that provide build- and run-time information at the level of the individual job; (3) the need to model best practices in research collaborations involving XSEDE staff; and (4) continued work on gateways and related technologies. In addition, an intriguing question emerged from the day's interactions: would there be value in establishing an annual award for excellence in reproducible research? Overvie

Modeling of Compression Ignition Engines for Advanced Engine Operation and Alternative Fuels by the Second Law of Thermodynamics

With the advent of modern engine control strategies, and particularly electronic common-rail injection, the scope and scale of what is achievable and controllable in compression-ignition engines has exploded quite rapidly in recent years. The potential marriage of electronically-controlled and multi-point fuel injection, dual fuel combustion, variable exhaust gas recirculation, exhaust waste heat recovery, low-temperature combustion, and the immense variety of potential liquid and gaseous fuels available means that the older understanding of compression ignition engine combustion is incomplete and inadequate to explain, predict, control, and optimize more novel engine combustion and operational regimes. This mandates that new models, both diagnostic and theoretical, be developed to explore engine combustion and pick apart the various phenomena that result, and includes revisiting models that previously have been sidelined for a lack of usefulness. To that end, this work details the construction, validation, and usage of a diagnostic heat release model focused on the application of the 2nd Law of Thermodynamics and the phenomena associated with entropy generation and availability destruction from the accumulated test data of numerous fuels and engine operational modes. A critical aspect of this research includes the marriage of this model with a suite of emissions analysis technologies, allowing for a complete characterization of engine-out regulated and unregulated emissions species, as well as a thoroughly instrumented and highly modified single-cylinder compression-ignition engine. This combined test apparatus for novel fuels and engine operational modes, in combination with the models described herein, serve as a means to collect and dissect engine performance, in-cylinder pressure, engine knock and noise, emissions, heat release, and availability release and consumption, and the interrelationships between these characteristics The experimental results of this work showcase both the direct usage of the 2nd Law Analysis (both alongside and separate from the more traditional 1st Law Heat Release Analysis), and also the potential usage of this model for the exploration of engine operational modes. In particular, the 2nd Law analysis appears to be of immense importance to the exploration of low temperature combustion regimes, as well as the usage of exhaust waste heat recovery systems

The Smart Grid, A Scale Demonstration Model Incorporating Electrified Vehicles

This article was published in the Spring 2011 issue of the Journal of Undergraduate Researc

Influence of Fuel Injection System and Engine-Timing Adjustments on Regulated Emissions from Four Biodiesel Fuels

The use of biofuels for transportation has grown substantially in the past decade in response to federal mandates and increased concern about the use of petroleum fuels. As biofuels become more common, it is imperative to assess their influence on mobile source emissions of regulated and hazardous pollutants. This assessment cannot be done without first obtaining a basic understanding of how biofuels affect the relationship between fuel properties, engine design, and combustion conditions. Combustion studies were conducted on biodiesel fuels from four feedstocks (palm oil, soybean oil, canola oil, and coconut oil) with two injection systems, mechanical and electronic. For the electronic system, fuel injection timing was adjusted to compensate for physical changes caused by different fuels. The emissions of nitrogen oxides (NOx) and partial combustion products were compared across both engine injection systems. The analysis showed differences in NOx emissions based on hydrocarbon chain length and degree of fuel unsaturation, with little to no NOx increase compared with ultra-low sulfur diesel fuel for most conditions. Adjusting the fuel injection timing provided some improvement in biodiesel emissions for NOx and particulate matter, particularly at lower engine loads. The results indicated that the introduction of biodiesel and biodiesel blends could have widely dissimilar effects in different types of vehicle fleets, depending on typical engine design, age, and the feedstock used for biofuel production

IL-23 drives a pathogenic T cell population that induces autoimmune inflammation

Interleukin (IL)-23 is a heterodimeric cytokine composed of a unique p19 subunit, and a common p40 subunit shared with IL-12. IL-12 is important for the development of T helper (Th)1 cells that are essential for host defense and tumor suppression. In contrast, IL-23 does not promote the development of interferon-γ–producing Th1 cells, but is one of the essential factors required for the expansion of a pathogenic CD4+ T cell population, which is characterized by the production of IL-17, IL-17F, IL-6, and tumor necrosis factor. Gene expression analysis of IL-23–driven autoreactive T cells identified a unique expression pattern of proinflammatory cytokines and other novel factors, distinguishing them from IL-12–driven T cells. Using passive transfer studies, we confirm that these IL-23–dependent CD4+ T cells are highly pathogenic and essential for the establishment of organ-specific inflammation associated with central nervous system autoimmunity

Moral trauma, moral distress, moral injury, and moral injury disorder: definitions and assessments.

We propose new definitions for moral injury and moral distress, encompassing many prior definitions, but broadening moral injury to more general classes of victims, in addition to perpetrators and witnesses, and broadening moral distress to include settings not involving institutional constraints. We relate these notions of moral distress and moral injury to each other, and locate them on a moral trauma spectrum that includes considerations of both persistence and severity. Instances in which moral distress is particularly severe and persistent, and extends beyond cultural and religious norms, might be considered to constitute moral injury disorder. We propose a general assessment to evaluate various aspects of this proposed moral trauma spectrum, and one that can be used both within and outside of military contexts, and for perpetrators, witnesses, victims, or more generally

Skyline: Interactive In-Editor Computational Performance Profiling for Deep Neural Network Training

Training a state-of-the-art deep neural network (DNN) is a computationally-expensive and time-consuming process, which incentivizes deep learning developers to debug their DNNs for computational performance. However, effectively performing this debugging requires intimate knowledge about the underlying software and hardware systems---something that the typical deep learning developer may not have. To help bridge this gap, we present Skyline: a new interactive tool for DNN training that supports in-editor computational performance profiling, visualization, and debugging. Skyline's key contribution is that it leverages special computational properties of DNN training to provide (i) interactive performance predictions and visualizations, and (ii) directly manipulatable visualizations that, when dragged, mutate the batch size in the code. As an in-editor tool, Skyline allows users to leverage these diagnostic features to debug the performance of their DNNs during development. An exploratory qualitative user study of Skyline produced promising results; all the participants found Skyline to be useful and easy to use.Comment: 14 pages, 5 figures. Appears in the proceedings of UIST'2