The FIT Model - Fuel-cycle Integration and Tradeoffs

All mass streams from fuel separation and fabrication are products that must meet some set of product criteria – fuel feedstock impurity limits, waste acceptance criteria (WAC), material storage (if any), or recycle material purity requirements such as zirconium for cladding or lanthanides for industrial use. These must be considered in a systematic and comprehensive way. The FIT model and the “system losses study” team that developed it [Shropshire2009, Piet2010] are an initial step by the FCR&D program toward a global analysis that accounts for the requirements and capabilities of each component, as well as major material flows within an integrated fuel cycle. This will help the program identify near-term R&D needs and set longer-term goals. The question originally posed to the “system losses study” was the cost of separation, fuel fabrication, waste management, etc. versus the separation efficiency. In other words, are the costs associated with marginal reductions in separations losses (or improvements in product recovery) justified by the gains in the performance of other systems? We have learned that that is the wrong question. The right question is: how does one adjust the compositions and quantities of all mass streams, given uncertain product criteria, to balance competing objectives including cost? FIT is a method to analyze different fuel cycles using common bases to determine how chemical performance changes in one part of a fuel cycle (say used fuel cooling times or separation efficiencies) affect other parts of the fuel cycle. FIT estimates impurities in fuel and waste via a rough estimate of physics and mass balance for a set of technologies. If feasibility is an issue for a set, as it is for “minimum fuel treatment” approaches such as melt refining and AIROX, it can help to make an estimate of how performances would have to change to achieve feasibility

The FIT Model - Fuel-cycle Integration and Tradeoffs

All mass streams from fuel separation and fabrication are products that must meet some set of product criteria – fuel feedstock impurity limits, waste acceptance criteria (WAC), material storage (if any), or recycle material purity requirements such as zirconium for cladding or lanthanides for industrial use. These must be considered in a systematic and comprehensive way. The FIT model and the “system losses study” team that developed it [Shropshire2009, Piet2010] are an initial step by the FCR&D program toward a global analysis that accounts for the requirements and capabilities of each component, as well as major material flows within an integrated fuel cycle. This will help the program identify near-term R&D needs and set longer-term goals. The question originally posed to the “system losses study” was the cost of separation, fuel fabrication, waste management, etc. versus the separation efficiency. In other words, are the costs associated with marginal reductions in separations losses (or improvements in product recovery) justified by the gains in the performance of other systems? We have learned that that is the wrong question. The right question is: how does one adjust the compositions and quantities of all mass streams, given uncertain product criteria, to balance competing objectives including cost? FIT is a method to analyze different fuel cycles using common bases to determine how chemical performance changes in one part of a fuel cycle (say used fuel cooling times or separation efficiencies) affect other parts of the fuel cycle. FIT estimates impurities in fuel and waste via a rough estimate of physics and mass balance for a set of technologies. If feasibility is an issue for a set, as it is for “minimum fuel treatment” approaches such as melt refining and AIROX, it can help to make an estimate of how performances would have to change to achieve feasibility

Aberrant substrate engagement of the ER translocon triggers degradation by the Hrd1 ubiquitin ligase

Little is known about quality control of proteins that aberrantly or persistently engage the endoplasmic reticulum (ER)-localized translocon en route to membrane localization or the secretory pathway. Hrd1 and Doa10, the primary ubiquitin ligases that function in ER-associated degradation (ERAD) in yeast, target distinct subsets of misfolded or otherwise abnormal proteins based primarily on degradation signal (degron) location. We report the surprising observation that fusing Deg1, a cytoplasmic degron normally recognized by Doa10, to the Sec62 membrane protein rendered the protein a Hrd1 substrate. Hrd1-dependent degradation occurred when Deg1-Sec62 aberrantly engaged the Sec61 translocon channel and underwent topological rearrangement. Mutations that prevent translocon engagement caused a reversion to Doa10-dependent degradation. Similarly, a variant of apolipoprotein B, a protein known to be cotranslocationally targeted for proteasomal degradation, was also a Hrd1 substrate. Hrd1 therefore likely plays a general role in targeting proteins that persistently associate with and potentially obstruct the translocon

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Kepler and Ground-Based Transits of the exo-Neptune HAT-P-11b

We analyze 26 archival Kepler transits of the exo-Neptune HAT-P-11b, supplemented by ground-based transits observed in the blue (B band) and near-IR (J band). Both the planet and host star are smaller than previously believed; our analysis yields Rp = 4.31 R xor 0.06 R xor and Rs = 0.683 R solar mass 0.009 R solar mass, both about 3 sigma smaller than the discovery values. Our ground-based transit data at wavelengths bracketing the Kepler bandpass serve to check the wavelength dependence of stellar limb darkening, and the J-band transit provides a precise and independent constraint on the transit duration. Both the limb darkening and transit duration from our ground-based data are consistent with the new Kepler values for the system parameters. Our smaller radius for the planet implies that its gaseous envelope can be less extensive than previously believed, being very similar to the H-He envelope of GJ 436b and Kepler-4b. HAT-P-11 is an active star, and signatures of star spot crossings are ubiquitous in the Kepler transit data. We develop and apply a methodology to correct the planetary radius for the presence of both crossed and uncrossed star spots. Star spot crossings are concentrated at phases 0.002 and +0.006. This is consistent with inferences from Rossiter-McLaughlin measurements that the planet transits nearly perpendicular to the stellar equator. We identify the dominant phases of star spot crossings with active latitudes on the star, and infer that the stellar rotational pole is inclined at about 12 deg 5 deg to the plane of the sky. We point out that precise transit measurements over long durations could in principle allow us to construct a stellar Butterfly diagram to probe the cyclic evolution of magnetic activity on this active K-dwarf star

Lipids and bariatric procedures Part 2 of 2: scientific statement from the American Society for Metabolic and Bariatric Surgery (ASMBS), the National Lipid Association (NLA), and Obesity Medicine Association (OMA) 1

Bariatric procedures often improve lipid levels in patients with obesity. This 2-part scientific statement examines the potential lipid benefits of bariatric procedures and represents contributions from authors representing the National Lipid Association, American Society for Metabolic and Bariatric Surgery, and the Obesity Medicine Association. The foundation for this scientific statement was based on data published through June 2015. Part 1 of this 2-part scientific statement provides an overview of: (1) adipose tissue, cholesterol metabolism, and lipids; (2) bariatric procedures, cholesterol metabolism, and lipids; (3) endocrine factors relevant to lipid influx, synthesis, metabolism, and efflux; (4) immune factors relevant to lipid influx, synthesis, metabolism, and efflux; (5) bariatric procedures, bile acid metabolism, and lipids; and (6) bariatric procedures, intestinal microbiota, and lipids, with specific emphasis on how the alterations in the microbiome by bariatric procedures influence obesity, bile acids, and inflammation, which in turn, may all affect lipid levels. Included in part 2 of this comprehensive scientific statement will be a review of: (1) the importance of nutrients (fats, carbohydrates, and proteins) and their absorption on lipid levels; (2) the effects of bariatric procedures on gut hormones and lipid levels; (3) the effects of bariatric procedures on nonlipid cardiovascular disease risk factors; (4) the effects of bariatric procedures on lipid levels; (5) effects of bariatric procedures on cardiovascular disease; and finally (6) the potential lipid effects of vitamin, mineral, and trace element deficiencies that may occur after bariatric procedures. This document represents the executive summary of part 1

TEMPORARY REMOVAL: Lipids and Bariatric Procedures Part 1 of 2: Scientific Statement from the National Lipid Association (NLA), American Society for Metabolic and Bariatric Surgery (ASMBS), and Obesity Medicine Association (OMA)

The publisher regrets that this article has been temporarily removed. A replacement will appear as soon as possible in which the reason for the removal of the article will be specified, or the article will be reinstated. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy

System Losses Study - FIT (Fuel-cycle Integration and Tradeoffs)

This team aimed to understand the broad implications of changes of operating performance and parameters of a fuel cycle component on the entire system. In particular, this report documents the study of the impact of changing the loss of fission products into recycled fuel and the loss of actinides into waste. When the effort started in spring 2009, an over-simplified statement of the objective was “the number of nines” – how would the cost of separation, fuel fabrication, and waste management change as the number of nines of separation efficiency changed. The intent was to determine the optimum “losses” of TRU into waste for the single system that had been the focus of the Global Nuclear Energy Program (GNEP), namely sustained recycle in burner fast reactors, fed by transuranic (TRU) material recovered from used LWR UOX-51 fuel. That objective proved to be neither possible (insufficient details or attention to the former GNEP options, change in national waste management strategy from a Yucca Mountain focus) nor appropriate given the 2009-2010 change to a science-based program considering a wider range of options. Indeed, the definition of “losses” itself changed from the loss of TRU into waste to a generic definition that a “loss” is any material that ends up where it is undesired. All streams from either separation or fuel fabrication are products; fuel feed streams must lead to fuels with tolerable impurities and waste streams must meet waste acceptance criteria (WAC) for one or more disposal sites. And, these losses are linked in the sense that as the loss of TRU into waste is reduced, often the loss or carryover of waste into TRU or uranium is increased. The effort has provided a mechanism for connecting these three Campaigns at a technical level that had not previously occurred – asking smarter and smarter questions, sometimes answering them, discussing assumptions, identifying R&D needs, and gaining new insights. The FIT model has been a forcing function, helping the team in this endeavor. Models don’t like “TBD” as an input, forcing us to make assumptions and see if they matter. A major addition in FY 2010 was exploratory analysis of “modified open fuel” cycles, employing “minimum fuel treatment” as opposed to full aqueous or electrochemical separation treatment. This increased complexity in our analysis and analytical tool development because equilibrium conditions do not appear sustainable in minimum fuel treatment cases, as was assumed in FY 2009 work with conventional aqueous and electrochemical separation. It is no longer reasonable to assume an equilibrium situation exists in all cases