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In vivo maternal and in vitro BPA exposure effects on hypothalamic neurogenesis and appetite regulators

Highlights: • BPA exposure during fetal period and in vitro BPA treatment alters neurogenesis. • BPA increases hypothalamic neuroprogenitor cell proliferation and differentiation. • BPA increases protein expression of hypothalamic neurogenic bHLH factors. • BPA promotes protein expression of hypothalamic appetite versus satiety neuropeptide. • BPA promotes neuronal versus astroglial lineage. In utero exposure to the ubiquitous plasticizer, bisphenol A (BPA) is associated with offspring obesity. As food intake/appetite is one of the critical elements contributing to obesity, we determined the effects of in vivo maternal BPA and in vitro BPA exposure on newborn hypothalamic stem cells which form the arcuate nucleus appetite center. For in vivo studies, female rats received BPA prior to and during pregnancy via drinking water, and newborn offspring primary hypothalamic neuroprogenitor (NPCs) were obtained and cultured. For in vitro BPA exposure, primary hypothalamic NPCs from healthy newborns were utilized. In both cases, we studied the effects of BPA on NPC proliferation and differentiation, including putative signal and appetite factors. Maternal BPA increased hypothalamic NPC proliferation and differentiation in newborns, in conjunction with increased neuroproliferative (Hes1) and proneurogenic (Ngn3) protein expression. With NPC differentiation, BPA exposure increased appetite peptide and reduced satiety peptide expression. In vitro BPA-treated control NPCs showed results that were consistent with in vivo data (increase appetite vs satiety peptide expression) and further showed a shift towards neuronal versus glial fate as well as an increase in the epigenetic regulator lysine-specific histone demethylase1 (LSD1). These findings emphasize the vulnerability of stem-cell populations that are involved in life-long regulation of metabolic homeostasis to epigenetically-mediated endocrine disruption by BPA during early life.

54 ENVIRONMENTAL SCIENCES↗

Concentrating Solar Power and Water Issues in the U.S. Southwest

Concentrating solar power (CSP) systems utilize the sun's energy to create heat that is used to generate electrical power. CSP systems in the United States are installed primarily in the Southwest, with 92% of plants that are operational, under construction, or under development located in three western states--Arizona, California, and Nevada. This report provides an overview of CSP development in these states, or the 'Southwest' for the purposes of this discussion, with a particular focus on the water supply issues associated with CSP. The Western Governors' Association (WGA) commissioned staff from the Western States Water Council (WSWC) to collaborate with staff from the National Renewable Energy Laboratory (NREL) to prepare this report. The WGA has long supported the effective management of the West's water resources, as well as the development of a clean, diverse, reliable, and affordable energy supply consisting of traditional and renewable energy resources. This report is specifically intended to help inform these goals, especially as WGA continues to underwrite a Regional Transmission Expansion Planning project, undertaken by the WSWC and the Western Electricity Coordinating Council (WECC), to better understand energy development within the existing and future water resource constraints of the West. This report builds upon earlier research conducted by NREL, the University of Colorado-Boulder, and Stanford University that was supported through the Joint Institute for Strategic Energy Analysis (JISEA) and presents information gathered through extensive research and literature reviews, as well as interviews and outreach with state water administrators and energy regulators, WECC and other experts familiar with CSP development in the Southwest.

14 SOLAR ENERGY↗

Damaged Fuel in the United States - 20325

Throughout the history of commercial nuclear power plant operations in the U.S., many fuel assemblies have lost the capability to perform all of their desired functions. Since they can no longer be handled, stored, or transported in accordance with established regulations, they are classified as damaged fuel. The causes of these failed assemblies are diverse and plant-specific. The majority of these failed assemblies are contained in damaged fuel cans to be used in conjunction with storage and/or transportation systems. These systems have a limited number of slots that can be filled with damaged fuel cans. A damaged fuel can is generally a stainless-steel container that confines damaged spent nuclear fuel (SNF) and is closed at one end by mesh endpoints that allow gaseous and liquid media to escape but minimize the dispersal of gross particulate material. Out of extreme caution, a few reactors have loaded high burnup fuel into damaged fuel cans. Damaged fuel is not licensed for storage or transport in the U.S. because relevant regulations do not specify exactly how to classify damaged fuel. Instead, these regulations license/certify packages that specify approved contents. Damaged fuel must be included among the approved contents to be considered acceptable. In many cases, damaged SNF is encapsulated in damaged fuel cans to ensure it can confine gross fuel particles, debris, and/or damaged assemblies to known volumes within loaded casks. A damaged fuel can may then be utilized in the same way as an assembly in a storage and transportation system. Some storage cask systems utilize top and bottom plugs to confine debris in damaged fuel. The most recent domestic documentation on damaged SNF was published by the U.S. Energy Information Administration (EIA), which used data from U.S. reactors compiled from 1968 to June 30, 2013, to produce Form GC-859, 'Nuclear Fuel Data Survey.' According to this form, there were 136,821 boiling water reactor (BWR) SNF assemblies and 104,647 pressurized water reactor (PWR) SNF assemblies, for a combined total of 241,468. Of these, 4,521 were classified as failed. Some were also disassembled and the fuel rods or pieces of fuel rods combined to make consolidated assemblies. These consolidated assemblies may include damaged fuel or were perhaps consolidated as part of a demonstration project. The GC-859 data includes 2,550 consolidated assemblies containing 0 - 264 entire fuel rods. These consolidated assemblies could be placed in single assembly canisters and stored in the spent fuel pool. For dry storage and transportation, a single assembly canister is generally placed in each damaged fuel can. In addition to the consolidated assemblies, 2,391 un-canistered fuel rod pieces exist, which were removed from 494 assemblies. (authors)

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

The Radiation Oncology Job Market: The Economics and Policy of Workforce Regulation

Examinations of the US radiation oncology workforce offer inconsistent conclusions, but recent data raise significant concerns about an oversupply of physicians. Despite these concerns, residency slots continue to expand at an unprecedented pace. Employed radiation oncologists and professional corporations with weak contracts or loose ties to hospital administrators would be expected to suffer the greatest harm from an oversupply. The reduced cost of labor, however, would be expected to increase profitability for equipment owners, technology vendors, and entrenched professional groups. Policymakers must recognize that the number of practicing radiation oncologists is a poor surrogate for clinical capacity. There is likely to be significant opportunity to augment capacity without increasing the number of radiation oncologists by improving clinic efficiency and offering targeted incentives for geographic redistribution. Payment policy changes significantly threaten radiation oncologists' income, which may encourage physicians to care for greater patient loads, thereby obviating more personnel. Furthermore, the implementation of alternative payment models such as Medicare's Oncology Care Model threatens to decrease both the utilization and price of radiation therapy by turning referring providers into cost-conscious consumers. Medicare funds the vast majority of graduate medical education, but the extent to which the expansion in radiation oncology residency slots has been externally funded is unclear. Excess physician capacity carries a significant risk of harm to society by suboptimally allocating intellectual resources and creating comparative shortages in other, more needed disciplines. There are practical concerns associated with a market-based solution in which medical students self-regulate according to job availability, but antitrust law would likely forbid collaborative self-regulation that purports to restrict supply. Because Congress is unlikely to create one central body to govern residency controls for all specialties, we recommend better reporting of program-specific employment metrics and careful, intellectually honest re-evaluation of existing Accreditation Council for Graduate Medical Education accreditation standards.

61 RADIATION PROTECTION AND DOSIMETRY↗

Systemic Microgravity Response: Utilizing GeneLab to Develop Hypotheses for Spaceflight Risks

Biological risks associated with microgravity are a major concern for long-term space travel. Although determination of risk has been a focus for NASA research, data examining systemic (i.e., multi- or pan-tissue) responses to space flight are sparse. To perform our analysis, we utilized the NASA GeneLab database which is a publicly available repository containing a wide array of omics results from experiments conducted with: i) with different flight conditions (space shuttle (STS) missions vs. International Space Station (ISS); ii) a variety of tissues; and 3) assays that measure epigenetic, transcriptional, and protein expression changes. Meta-analysis of the transcriptomic data from 7 different murine and rat data sets, examining tissues such as liver, kidney, adrenal gland, thymus, mammary gland, skin, and skeletal muscle (soleus, extensor digitorum longus, tibialis anterior, quadriceps, and gastrocnemius) revealed for the first time, the existence of potential master regulators coordinating systemic responses to microgravity in rodents. We identified p53, TGF1 and immune related pathways as the highly prevalent pan-tissue signaling pathways that are affected by microgravity. Some variability in the degree of change in their expression across species, strain and time of flight was also observed. Interestingly, while certain skeletal muscle (gastrocnemius and soleus) exhibited an overall down-regulation of these genes, some other muscle types such as the extensor digitorum longus, tibialis anterior and quadriceps, showed an up-regulated expression, indicative of potential compensatory mechanisms to prevent microgravity-induced atrophy. Key genes isolated by unbiased systems analyses displayed a major overlap between tissue types and flight conditions and established TGF1 to be the most connected gene across all data sets. Finally, a set of microgravity responsive miRNA signature was identified and based on their predicted functional state and subsequent impact on health, a theoretical health risk score was calculated. The genes and miRNAs identified from our analyses can be targeted for future research involving efficient countermeasure design. Our study thus exemplifies the utility of GeneLab data repository to aid in the process of performing novel hypothesis based spaceflight research aimed at elucidating the global impact of environmental stressors at multiple biological scales.

GeneLab↗

Metabololipidomic profiling of functional immunoresolvent clusters and eicosanoids in mammalian tissues

Highlights: • New methods for metabololipidomics of specialized proresolving mediators (SPM) and classic eicosanoids. • Illustration from human blood coagulation. • Illustration from solid tumor. • Regulation of SPM biosynthesis by adenosine and adenosine deaminase. Metabolomics enables a systems approach to interrogate the bioactive mediators, their pathways and further metabolites involved in the physiology and pathophysiology of human and animal tissues. New metabololipidomic approaches with mass spectrometry presented in this brief review can now be utilized for the identification and profiling of lipid mediator networks that control inflammation-resolution in human blood and healthy and diseased solid tissues. Coagulation of blood is a protective response that prevents excessive bleeding on injury of blood vessels. Here, we review novel approaches to understand the relationship(s) between coagulation and resolution of inflammation and infection. To determine whether coagulation is involved in host-protective actions by lipid mediators, we used a metabololipidomic-based profiling approach with human whole blood (WB) during coagulation. We identified recently temporal clusters of endogenously produced pro-thrombotic and proinflammatory lipid mediators (eicosanoids), as well as specialized proresolving mediators (SPMs) in this vital process. In addition to the classic eicosanoids (prostaglandins, thromboxanes and leukotrienes), a specific SPM cluster was identified that consists of resolvin E1 (RvE1), RvD1, RvD5, lipoxin B{sub 4}, and maresin 1, each of which present at bioactive concentrations (0.1–1 nM). The removal of adenosine from coagulating blood samples significantly enhances SPM amounts and unleashes the biosynthesis of RvD3, RvD4, and RvD6 evident following rapid snap freezing with centrifugation before extraction and LC-MS-MS. The classic cyclooxygenase inhibitors, celecoxib and indomethacin, that block thromboxanes and prostanoids do not block production of the clot-driven SPM cluster. Unbiased mass cytometry analysis demonstrated that the SPM cluster produced in human blood targets leukocytes at the single-cell level, directly activating extracellular signaling in human neutrophils and monocytes. Human whole blood treated with the components of this SPM cluster enhanced both phagocytosis and killing of Escherichia coli by leukocytes. Thus, we identified a pro-resolving lipid mediator circuit and specific SPM cluster that promotes host defense. This new lipid mediator (LM)-SPM metabololipidomic approach now provides accessible metabolomic profiles in healthy and diseased human tissues, including cancer, for precision and personalized medicine.

60 APPLIED LIFE SCIENCES↗

Common Column Identification for Table Similarity Detection in Electrified Transportation Data Lakes

Electrified transportation often requires researchers and operators to interact with datasets from a wide range of sources and disciplines, such as transportation, power systems, public health, policies, and regulations. These datasets vary in quality and format, making it difficult to understand, preprocess, and identify key columns representing real-world entities or values for indexing and joining, which can negatively impact downstream analysis and operation. Existing solutions are limited, requiring extensive manual customization or data expertise to utilize. In this article, we propose a multi-layered approach to automatically identify key columns to expedite preprocessing and aid in analysis of electrified transportation data. Our method leverages a dynamic ontology to identify common fields and an information theory-based strategy for edge cases that are difficult to generalize. Evaluations on a number of datasets from data.gov and kaggle.com show improved performance of our methods over several baseline techniques, and our ablation analyses illustrate the efficacy of individual components of our method. Our case studies also demonstrate that our methods have the potential to improve analysis of electrified transportation data and aid in automatic integration of such datasets.

33 ADVANCED PROPULSION SYSTEMS↗

Evaluation of performance indicators applied to a material recovery facility fed by mixed packaging waste

Highlights: • Material Flows assessment of a Material Recovery Facility has been realized. • Performance Indicators for a generic MRF have been proposed. • A Dashboard has been utilized to measure the facility performance. • Experimental values of incoming waste and output products composition are reported. - Abstract: Most of the integrated systems for municipal solid waste management aim to increase the recycling of secondary materials by means of physical processes including sorting, shredding and reprocessing. Several restrictions prevent from reaching a very high material recycling efficiency: the variability of the composition of new-marketed materials used for packaging production and its shape and complexity are critical issues. The packaging goods are in fact made of different materials (aluminium, polymers, paper, etc.), possibly assembled, having different shape (flat, cylindrical, one-dimensional, etc.), density, colours, optical properties and so on. These aspects limit the effectiveness and efficiency of the sorting and reprocessing plants. The scope of this study was to evaluate the performance of a large scale Material Recovery Facility (MRF) by utilizing data collected during a long period of monitoring. The database resulted from the measured data has been organized in four sections: (1) data related to the amount and type of inlet waste; (2) amount and composition of output products and waste; (3) operating data (such as worked hours for shift, planned and unscheduled maintenance time, setting parameters of the equipment, and energy consumption for shift); (4) economic data (value of each product, disposal price for the produced waste, penalty for non-compliance of products and waste, etc.). A part of this database has been utilized to build an executive dashboard composed by a set of performance indicators suitable to measure the effectiveness and the efficiency of the MRF operations. The dashboard revealed itself as a powerful tool to support managers and engineers in their decisions in respect to the market demand or compliance regulation variation as well as in the designing of the lay-out improvements. The results indicated that the 40% of the input waste was recovered as valuable products and that a large part of these (88%) complied with the standards of the recycling companies. The evaluation of the indicators led to the decision to modify the layout to improve the interception of some polymers for which the performance indicators were poor. In particular, two additional optical sorters have to be inserted to increase the yield indicator and to the overall performance of the facility. Definitely, the results of the work allowed to: increase the yield and purity of products’ flows; ensure the compliance of waste flows; increase the workability.

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

Coarse-Grained Modeling Elucidates Differential Metabolism of Saccharomyces cerevisiae under Varied Nutrient Limitations

Microorganisms such as Saccharomyces cerevisiae have a native ability to adapt their metabolism to varying nutrient conditions. Understanding their responses to nutrient limitations is critical for decoding cellular physiology and designing strategies for metabolic engineering. While the influence of carbon availability on yeast metabolism has been extensively studied, the role of nitrogen availability remains relatively underexplored. In this study, we utilized a coarse-grained kinetic model to systematically analyze and compare the effects of carbon and nitrogen limitations on yeast metabolism. Our model successfully revealed the differential metabolic characteristics of S. cerevisiae under carbon- and nitrogen-limited chemostat conditions. It also highlighted the significance of protein activity regulation at varying carbon-to-nitrogen ratios, and elucidated distinct strategies employed to maintain ATP homeostasis. Furthermore, this study provides a computational tool for investigating yeast physiology under nutrient limitations and offers quantitative and mechanistic insights into yeast metabolism.

59 BASIC BIOLOGICAL SCIENCES↗

A computationally identified compound antagonizes excess FGF-23 signaling in renal tubules and a mouse model of hypophosphatemia

Fibroblast growth factor–23 (FGF-23) interacts with a binary receptor complex composed of α-Klotho (α-KL) and FGF receptors (FGFRs) to regulate phosphate and vitamin D metabolism in the kidney. Excess FGF-23 production, which causes hypophosphatemia, is genetically inherited or occurs with chronic kidney disease. Among other symptoms, hypophosphatemia causes vitamin D deficiency and the bone-softening disorder rickets. Current therapeutics that target the receptor complex have limited utility clinically. In this paper, using a computationally driven, structure-based, ensemble docking and virtual high-throughput screening approach, we identified four novel compounds predicted to selectively inhibit FGF-23–induced activation of the FGFR/α-KL complex. Additional modeling and functional analysis found that Zinc13407541 bound to FGF-23 and disrupted its interaction with the FGFR1/α-KL complex; experiments in a heterologous cell expression system showed that Zinc13407541 selectivity inhibited α-KL–dependent FGF-23 signaling. Zinc13407541 also inhibited FGF-23 signaling in isolated renal tubules ex vivo and partially reversed the hypophosphatemic effects of excess FGF-23 in a mouse model. Finally, these chemical probes provide a platform to develop lead compounds to treat disorders caused by excess FGF-23.

59 BASIC BIOLOGICAL SCIENCES↗

Next Generation Environmentally-Friendly Driving Feedback Systems Research and Development

The objective of this project is to design, develop, and demonstrate a next-generation, federal safety- and emission-complaint driving feedback system that can be deployed across the existing vehicle fleet and improve fleet average fuel efficiency by at least 2%. The project objective was achieved with the driving feedback system that encourages fuel-efficient vehicle travel and operation through: 1) Eco-Routing Navigation module that suggests the most fuel-efficient route from one stop to the next, 2) Eco-Driving Feedback module that provides sensible information, recommendation, and warning regarding fuel-efficient vehicle operation, and 3) Eco-Score and Eco-Rank module that provides a means for driving performance tracking, self-evaluation, and peer comparison. The system also collects and stores vehicle travel and operation data, which are used by Algorithm Updating module to customize the other modules for specific vehicles and adapts them to specific drivers over time. The driving feedback system was designed and developed as an aftermarket technology that can be retrofitted to vehicles in the existing fleet. It consists of a mobile application for smart devices running Android operating system, a vehicle on-board diagnostics connector, and a data server. While the system receives and utilizes real-time vehicle and engine data from the vehicle’s controller area network bus through the vehicle’s on-board diagnostic connector, it does not modify or interfere with the vehicle’s controller area network bus, and thus, is in compliance with federal safety and emission regulations. The driving feedback system was demonstrated and then installed on 45 vehicles from three different fleets for field operational test. These include 15 private vehicles of the general public, 15 pickup trucks of the California Department of Transportation that are assigned to individual employees for business use, and 15 shuttle buses of the Riverside Transit Agency that are used for paratransit service. Detailed vehicle travel and operation data including route taken, driving speed, acceleration, braking, and the corresponding fuel consumption, were collected both before and during the test period. The data analysis results show that the fleet average fuel efficiency improvements for the three fleets with the use of the driving feedback system are in the range of 2% to 9%. The economic viability of the driving feedback system is high. A fully deployed system would require capital investment in smart device ($150-$350) and on-board diagnostics connector ($50-$100) as well as paying operating costs for wireless data plan and subscription fees ($20-$30 per month) for connecting to the data server and receiving various system services. For individual consumers who already own a smart device (such as smartphone) and commercial fleets that already use some kind of telematics services, the costs for deploying this driving feedback system would be much lower.

33 ADVANCED PROPULSION SYSTEMS↗

Data for "Implications of Zoning Ordinances for Rural Utility-Scale Solar Deployment and Power System Decarbonization in the Great Lakes Region".

This dataset includes the Energy Zoning Database and geographic shapefiles used to identify suitable rural areas for utility-scale solar development. Additionally, it contains the input data required for the capacity expansion model, including information on existing electric generators and their associated costs, solar resource potential, and transmission infrastructure data. These datasets collectively support the analysis presented in the paper, ensuring a comprehensive assessment of zoning regulations, land suitability, and the economic and technical feasibility of solar deployment in rural areas.

Owusu-Obeng, Papa Yaw (ORCID:0000000334385183)↗

Siting solar thermal power experiments

The Small Community Solar Thermal Power Experiment will test a point-focusing, distributed receiver system in a small community, electric utility application. Site planning is becoming increasingly important for solar experiments as well as all kinds of development due to increased competition for desirable sites and increased complexity of regulatory requirements. Siting issues can be categorized as: (1) resources and physical environmental at this site; (2) acquisition, permits and regulations; and (3) development requirements and costs. These issues are addressed with respect to the unique requirements of solar thermal power experiments.

Holbeck, H. J.↗

Developing High-Throughput Organ-On-A-Chip Models to Investigate the Effects of Ionizing Radiation on the Central Nervous System

One of the main health risks in human space exploration is central nervous system (CNS) damage by ionizing radiation. Irradiation with simulated GCRs or their components, or high doses of low-LET radiation such as gamma rays, in animal models has been shown to cause neuronal damage together with glial cell activation and neuroinflammation and has been associated with prolonged cognitive and behavioral dysfunction. The extent of CNS damage in response to any insult, including ionizing radiation, is partially regulated by the blood-brain barrier (BBB), which enables immune cells to enter the CNS. The main cellular regulators of BBB permeability are astrocytes, which also modulate neuronal death, immune responses and oxidative stress, and thus could serve as a robust CNS-specific target for countermeasure development. However, studies on BBB permeability and astrocyte functions in regulating CNS responses to ionizing radiation have been limited, especially in human tissue/organ analogs. Therefore, we have established a high throughput 3D organ-on-a-chip system to study human CNS functions in response to ionizing radiation, with the eventual goal of adapting it to spaceflight missions. We utilized commercially available OrganoPlate system (Mimetas, Inc.) seeded with primary or induced pluripotent stem cell-derived human cells for developing 3D neuronal-astrocytic and BBB models. We investigated both immediate and delayed CNS dose responses to 0.5-1 Gy X-rays by measuring BBB permeability and morphology, and astrocyte activation. We have also quantified secreted markers of oxidative stress and cell viability. In the future, we are planning to monitor dendritic, axonal and synaptic changes in neurons, evaluate the combined exposures to simulated microgravity and ionizing radiation, and compare the responses to low and high-LET ionizing radiation. We anticipate these studies could indicate novel cellular and mechanistic targets for countermeasure developments to improve CNS functions in astronauts.

Malkani, Sherina↗

Super oxidation and solidification of organic solvents, polycyclic aromatic hydrocarbons and pesticides at an abandoned chemical factory site

Large quantities of organic chemical such as VOCs, SVOCs and POPs were found in the soil of land at an abandoned Chemical Plant. Technology of super oxidation was applied to the soil for cleanup. Fenton process was utilized to treat soil contaminated heavily by BHC, benzene, chlorobenzene, dichlorobenzene, hexachlorobenzene, dichloroethane, dichloropropane, trichlorobenzene and dichloroether, etc. Super oxidation was coupled with method of stabilization for this case to enhance the remediation effect, which proved to be successful. Concentration of concerned pollutants was brought down below the national regulation level by approximately 8 folds. To make the treated soil strong and effective layer preventing pollutants breaking through, Iron powder was mixed in the soil, forming PBR (Permeable Barrier Reactor), to lower the risk to human health. The site after enhanced super oxidation above was totally safe to be developed into a residential community and/or commercial area. (authors)

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

Mind the Gap: Building Simulation in the Architectural Design Studio

Building modelling and simulation approaches are increasingly being utilized in architectural design studios to guide and inform the design process and offer evidence-based feedback on proposed building performance. The development of intuitive and simplified simulation interfaces has greatly contributed to achieving this integration. One aspect that is often overlooked is the workflow that governs and regulates integrated design, which can have significant impacts on final design outcomes. Currently there are numerous software packages available for building performance simulations. This makes it challenging to select an appropriate tool that provides accurate results yet allows a designer to make informed architectural decisions with a designer-friendly interface. Furthermore, workflows to incorporate simulations into the design process proved to highly impact student’s project design integration. Yet, it is not clear what type of workflows are successful to achieve this goal, under what conditions, and/or for which building and site typologies. This paper addresses these issues by first reviewing three different workflows for integrating building performance simulation processes and highlighting their strengths and weaknesses. Second, a comparative case study approach was employed to test three of the most common workflows in three different integrated design architectural studios at the senior and vertical studio levels as well as in two courses that run parallel and complementary to the design studios. The workflows, processes, and the resultant student projects were further analyzed based on criteria for better integrated design and architectural excellence as outlined in the American Institute of Architects Committee on the Environment (AIA COTE) Top 10 Student’s Competition. Third, to situate the pedagogical case studies’ results within a larger context, a survey of the AIA COTE Top 10 student competition award recipients over the last five years was conducted. The results are summarized in a pedagogical framework that outlines best strategies of the type of workflows, software, design process used, methods to achieve desired interaction between design process and analytical feedback, and metrics for educators to evaluate the success of this integration and their learning outcomes in the design studio. The goal is to help bridge the gap between the building design and simulation within the design studio’s creative process for more integrated design outcomes.

Elzeyadi, Ihab↗

Access to pedestal pressure relevant to burning plasmas on the high magnetic field tokamak Alcator C-Mod

Experiments on the Alcator C-Mod tokamak have utilized reactor-relevant magnetic fields to sustain substantially higher pedestal pressure than in other devices and allow close approach to the ITER H-mode baseline target pedestal pressure of 90 kPa. The EPED model, which couples the physics of transport driven by kinetic ballooning modes and MHD instabilities arising from peeling-ballooning modes, predicts the pressure profile at the onset of edge-localized modes (ELMs), and yields to lowest order a critical-βN like behavior for the pedestal: p∝Bt×Bp ( ∝Bt^2 for fixed edge q). C-Mod routinely accesses edge plasma pressure in excess of 30 kPa, often by using a high-density (ne>3×10^20 m^-3) approach to high confinement, taking advantage of a regime known as enhanced D-alpha (EDA) H-mode. In the EDA H-mode, plasma transport regulates both the pedestal profiles and the core impurity content, thus holding the pedestal stationary at just below the peeling-ballooning stability boundary. This stationary ELM-suppressed regime has approached the maximum pedestal predicted by EPED at these densities: 60 kPa. This in turn gives rise to volume-averaged core plasma pressure in excess of 0.2MPa, a world record value for a magnetic fusion device. Another approach to achieving high pressure utilizes a pedestal limited by current-driven modes at low collisionality, in which pressure increases with density and which allows access to a higher EPED solution, termed “super-H”. C-Mod experiments at reduced density (ne<2×10^20 m^-3) and strong plasma shaping (δ>0.5) accessed this regime, producing pedestals with pressures up to 80kPa (approximately 90% of the ITER target) and temperatures of nearly 2 keV. In a number of these hot H-modes, we observe strong edge instabilities at low toroidal mode number (n=1) when pedestal pressure approaches predicted values from EPED, showing that current-driven MHD modes can serve as a limit on the pedestal in a metal-walled tokamak at high pressure and low collisionality.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

Systemic Response to Microgravity: Utilizing GeneLab Datasets to Identify Molecular Targets for Future Hypotheses-Driven Spaceflight Studies

Biological risks associated with microgravity are a major concern for long-term space travel. Although determination of risk has been a focus for NASA research, data examining systemic (i.e., multi- or pan-tissue) responses to space flight are sparse. To perform our analysis, we utilized the NASA GeneLab database which is a publicly available repository containing a wide array of omics results from experiments conducted with: i) with different flight conditions (space shuttle (STS) missions vs. International Space Station (ISS); ii) a variety of tissues; and 3) assays that measure epigenetic, transcriptional, and protein expression changes. Meta-analysis of the transcriptomic data from 7 different murine and rat data sets, examining tissues such as liver, kidney, adrenal gland, thymus, mammary gland, skin, and skeletal muscle (soleus, extensor digitorum longus, tibialis anterior, quadriceps, and gastrocnemius) revealed for the first time, the existence of potential master regulators coordinating systemic responses to microgravity in rodents. We identified p53, TGF(beta)1 and immune related pathways as the highly prevalent pan-tissue signaling pathways that are affected by microgravity. Some variability in the degree of change in their expression across species, strain and time of flight was also observed. Interestingly, while certain skeletal muscle (gastrocnemius and soleus) exhibited an overall down-regulation of these genes, some other muscle types such as the extensor digitorum longus, tibialis anterior and quadriceps, showed an up-regulated expression, indicative of potential compensatory mechanisms to prevent microgravity-induced atrophy. Key genes isolated by unbiased systems analyses displayed a major overlap between tissue types and flight conditions and established TGF(beta)1 to be the most connected gene across all data sets. Finally, a set of microgravity responsive miRNA signature was identified and based on their predicted functional state and subsequent impact on health, a theoretical health risk score was calculated. The genes and miRNAs identified from our analyses can be targeted for future research involving efficient countermeasure design. Our study thus exemplifies the utility of GeneLab data repository to aid in the process of performing novel hypothesis based spaceflight research aimed at elucidating the global impact of environmental stressors at multiple biological scales.

GeneLab↗