The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

Political parties, motivated reasoning, and public opinion formation

A key characteristic of democratic politics is competition between groups, first of all political parties. Yet, the unavoidably partisan nature of political conflict has had too little influence on scholarship on political psychology. Despite more than 50 years of research on political parties and citizens, we continue to lack a systematic understanding of when and how political parties influence public opinion. We suggest that alternative approaches to political parties and public opinion can be best reconciled and examined through a richer theoretical perspective grounded in motivated reasoning theory. Clearly, parties shape citizens' opinions by mobilizing, influencing, and structuring choices among political alternatives. But the answer to when and how parties influence citizens' reasoning and political opinions depends on an interaction between citizens' motivations, effort, and information generated from the political environment (particularly through competition between parties). The contribution of motivated reasoning, as we describe it, is to provide a coherent theoretical framework for understanding partisan influence on citizens' political opinions. We review recent empirical work consistent with this framework. We also point out puzzles ripe for future research and discuss how partisan-motivated reasoning provides a useful point of departure for such work

Discovery of small molecule inhibitors of xyloglucan endotransglucosylase (XET) activity by high-throughput screening

AbstractSmall molecules (xenobiotics) that inhibit cell-wall-localised enzymes are valuable for elucidating the enzymes’ biological roles. We applied a high-throughput fluorescent dot-blot screen to search for inhibitors of Petroselinum xyloglucan endotransglucosylase (XET) activity in vitro. Of 4216 xenobiotics tested, with cellulose-bound xyloglucan as donor-substrate, 18 inhibited XET activity and 18 promoted it (especially anthraquinones and flavonoids). No compounds promoted XET in quantitative assays with (cellulose-free) soluble xyloglucan as substrate, suggesting that promotion was dependent on enzyme–cellulose interactions. With cellulose-free xyloglucan as substrate, we found 22 XET-inhibitors – especially compounds that generate singlet oxygen (1O2) e.g., riboflavin (IC50 29μM), retinoic acid, eosin (IC50 27μM) and erythrosin (IC50 36μM). The riboflavin effect was light-dependent, supporting 1O2 involvement. Other inhibitors included tannins, sulphydryl reagents and triphenylmethanes. Some inhibitors (vulpinic acid and brilliant blue G) were relatively specific to XET, affecting only two or three, respectively, of nine other wall-enzyme activities tested; others [e.g. (−)-epigallocatechin gallate and riboflavin] were non-specific. In vivo, out of eight XET-inhibitors bioassayed, erythrosin (1μM) inhibited cell expansion in Rosa and Zea cell-suspension cultures, and 40μM mycophenolic acid and (−)-epigallocatechin gallate inhibited Zea culture growth. Our work showcases a general high-throughput strategy for discovering wall-enzyme inhibitors, some being plant growth inhibitors potentially valuable as physiological tools or herbicide leads

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Unraveling the Complexity of Amyotrophic Lateral Sclerosis Survival Prediction

Objective: The heterogeneity of amyotrophic lateral sclerosis (ALS) survival duration, which varies from <1 year to >10 years, challenges clinical decisions and trials. Utilizing data from 801 deceased ALS patients, we: (1) assess the underlying complex relationships among common clinical ALS metrics; (2) identify which clinical ALS metrics are the “best” survival predictors and how their predictive ability changes as a function of disease progression.Methods: Analyses included examination of relationships within the raw data as well as the construction of interactive survival regression and classification models (generalized linear model and random forests model). Dimensionality reduction and feature clustering enabled decomposition of clinical variable contributions. Thirty-eight metrics were utilized, including Medical Research Council (MRC) muscle scores; respiratory function, including forced vital capacity (FVC) and FVC % predicted, oxygen saturation, negative inspiratory force (NIF); the Revised ALS Functional Rating Scale (ALSFRS-R) and its activities of daily living (ADL) and respiratory sub-scores; body weight; onset type, onset age, gender, and height. Prognostic random forest models confirm the dominance of patient age-related parameters decline in classifying survival at thresholds of 30, 60, 90, and 180 days and 1, 2, 3, 4, and 5 years.Results: Collective prognostic insight derived from the overall investigation includes: multi-dimensionality of ALSFRS-R scores suggests cautious usage for survival forecasting; upper and lower extremities independently degenerate and are autonomous from respiratory decline, with the latter associating with nearer-to-death classifications; height and weight-based metrics are auxiliary predictors for farther-from-death classifications; sex and onset site (limb, bulbar) are not independent survival predictors due to age co-correlation.Conclusion: The dimensionality and fluctuating predictors of ALS survival must be considered when developing predictive models for clinical trial development or in-clinic usage. Additional independent metrics and possible revisions to current metrics, like the ALSFRS-R, are needed to capture the underlying complexity needed for population and personalized forecasting of survival

A framework for blue energy enabled energy storage in reverse osmosis processes

Reverse osmosis (RO) is perhaps the most promising desalination technology, but it is facing growing economic challenges when coupled to an intermittent energy supply, such as renewable energy-based grids. A technology with similar components to reverse osmosis is pressure retarded osmosis (PRO), which produces energy from differences in salt concentration (blue energy). However, with the increasing cost-competitiveness of wind and solar photovoltaic renewable energy, PRO faces severe technoeconomic challenges as a stand-alone energy technology. To address cost and energy challenges of both RO and PRO, we propose a framework to intermittently operate RO with an instantaneous, electricity-producing PRO mode by taking advantage of the component overlap and existing infrastructure. Here, we analyze the process and component efficiencies associated with a hybridized RO-PRO system and outline the associated technoeconomic limitations. This approach considered operating PRO by mixing seawater RO brine with either RO permeate or a cheap low salinity water source. The results show that a hybridized system may make PRO viable in a niche subset of conditions, including a combination of relatively cheap water (\u3c$1/m3), pricier electricity (\u3e$0.15/kWh), and with electricity pricing schemes having large differences between lowest and highest prices. This hybridization may effectively allow a hybrid PRO-mode system to act as a cheaper, yet less efficient, salinity gradient energy storage mechanism. However, the economics are extremely challenging unless there is inexpensive, or even free, low salinity water source (e.g. treated wastewater) available