Role of angiopoietin-like protein 3 in sugar-induced dyslipidemia in rhesus macaques: suppression by fish oil or RNAi.

Angiopoietin-like protein 3 (ANGPTL3) inhibits lipid clearance and is a promising target for managing cardiovascular disease. Here we investigated the effects of a high-sugar (high-fructose) diet on circulating ANGPTL3 concentrations in rhesus macaques. Plasma ANGPTL3 concentrations increased ∼30% to 40% after 1 and 3 months of a high-fructose diet (both P < 0.001 vs. baseline). During fructose-induced metabolic dysregulation, plasma ANGPTL3 concentrations were positively correlated with circulating indices of insulin resistance [assessed with fasting insulin and the homeostatic model assessment of insulin resistance (HOMA-IR)], hypertriglyceridemia, adiposity (assessed as leptin), and systemic inflammation [C-reactive peptide (CRP)] and negatively correlated with plasma levels of the insulin-sensitizing hormone adropin. Multiple regression analyses identified a strong association between circulating APOC3 and ANGPTL3 concentrations. Higher baseline plasma levels of both ANGPTL3 and APOC3 were associated with an increased risk for fructose-induced insulin resistance. Fish oil previously shown to prevent insulin resistance and hypertriglyceridemia in this model prevented increases of ANGPTL3 without affecting systemic inflammation (increased plasma CRP and interleukin-6 concentrations). ANGPTL3 RNAi lowered plasma concentrations of ANGPTL3, triglycerides (TGs), VLDL-C, APOC3, and APOE. These decreases were consistent with a reduced risk of atherosclerosis. In summary, dietary sugar-induced increases of circulating ANGPTL3 concentrations after metabolic dysregulation correlated positively with leptin levels, HOMA-IR, and dyslipidemia. Targeting ANGPTL3 expression with RNAi inhibited dyslipidemia by lowering plasma TGs, VLDL-C, APOC3, and APOE levels in rhesus macaques

Multi-objective management of financial risks in food-energy-water systems

Financial risks related to extreme weather are increasingly worrisome for many organizations, from local and national governments to insurers and banks. A case in point is the financial risk posed by hydrologic variability for organizations such as water utilities, hydropower producers, and irrigators, among others. During drought, these organizations often face reduced revenues (e.g., selling less water) and/or increased expenditures (e.g., acquiring expensive replacement water). Furthermore, these organizations generally have large "fixed" costs regardless of hydrology (e.g., debt service, maintenance). Left unmanaged, this combination of highly variable revenues and large fixed costs can lead to budget disruptions, default, and even bankruptcy, threatening these organizations' ability to provide reliable and affordable water, electricity, and food. Many tools exist for managing hydrologic financial risks, including infrastructure (e.g., reservoirs, canals) and financial tools (e.g., reserve funds, borrowing, financial instruments). However, characterizing and managing these risks is challenging due to the complex dynamics of water availability and management within coupled natural-engineered-economic systems. Numerous open questions remain regarding the design of risk management portfolios that meet multiple objectives under uncertainty. This dissertation advances understanding of these issues through three core contributions. First, a snow-based hedging contract is developed for a hydropower producer relying on snowmelt, and combined with other financial tools to form comprehensive portfolios, with multi-objective optimization used to map key tradeoffs between risk and cost. Second, Evolutionary Multi-Objective Direct Policy Search is used develop dynamic policies that adapt the portfolios over time based on changing information (e.g., updating hedging contracts based on power price forecasts). Sensitivity analysis and visual analytics provide decision-makers with insight into how different policies achieve their goals. Lastly, cooperative partnerships for agricultural water supply investments (e.g., canals, groundwater banks) are investigated, using exploratory modeling to identify partnerships that provide supply and financial benefits not only "on average", but for each partner across multiple scenarios to ensure that each receives acceptable benefits from their investment. Overall, this dissertation provides several insights that can help public- and private-sector organizations to build financial resilience against weather- and climate-related risks within natural-engineered-economic systems.Doctor of Philosoph

HST Images and Spectra of the Remnant of SN 1885 in M31

Near UV HST images of the remnant of SN 1885 (S And) in M31 show a 0"70 +- 0"05 diameter absorption disk silhouetted against M31's central bulge, at SN 1885's historically reported position. The disk's size corresponds to a linear diameter of 2.5 +- 0.4 pc at a distance of 725 +- 70 kpc, implying an average expansion velocity of 11000 +- 2000 km/s over 110 years. Low-dispersion FOS spectra over 3200-4800 A; reveal that the absorption arises principally from Ca II H & K (equivalent width ~215 A;) with weaker absorption features of Ca I 4227 A; and Fe I 3720 A;. The flux at Ca II line center indicates a foreground starlight fraction of 0.21, which places SNR 1885 some 64 pc to the near side of the midpoint of the M31 bulge, comparable to its projected 55 pc distance from the nucleus. The absorption line profiles suggest an approximately spherically symmetric, bell-shaped density distribution of supernova ejecta freely expanding at up to 13100 +- 1500 km/s. We estimate Ca I, Ca II, and Fe I masses of 2.9(+2.4,-0.6) x 10^-4 M_o, 0.005(+0.016,-0.002) M_o, and 0.013(+0.010,-0.005) M_o respectively. If the ionization state of iron is similar to the observed ionization state of calcium, M_CaII/M_CaI = 16(+42,-5), then the mass of Fe II is 0.21(+0.74,-0.08) M_o, consistent with that expected for either normal or subluminous SN Ia.Comment: 8 pages, including 4 embedded EPS figures, emulateapj.sty style file. Color image at http://casa.colorado.edu/~mcl/sand.shtml . Submitted to Ap

Transfusion Rates in Emergency General Surgery: High but Modifiable

Background: Transfusion of red blood cells (RBC) increases morbidity and mortality, and emergency general surgery (EGS) cases have increased risk for transfusion and complication given case complexity and patient acuity. Transfusion reduction strategies and blood-conservation technology have been developed to decrease transfusions. This study explores whether transfusion rates in EGS have decreased as these new strategies have been implemented. Methods: This is a retrospective review of the American College of Surgeons\u27 National Surgical Quality Improvement Program (ACS NSQIP) data from three academic medical centers. Operations performed by general surgeons on adults (aged ≥18 years) were selected. Data were analyzed from two periods: 2011-2013 and 2014-2016. Cases were grouped by the first four digits of the primary procedure Current Procedural Terminology code. Transfusion was defined as any RBC transfusion during or within 72 hours following the operation. Composite morbidity was defined as any NSQIP complication within 30 days following the operation. Results: Overall general surgery transfusion rates decreased from 6.4% to 4.8% from period 1 to period 2 (emergent: 16.6%–11.5%; non-emergent 4.9%–3.7%; Fisher’s exact p values \u3c 0.001). Among patients transfused, the number of units received decreased slightly (median 2 U (IQR 2–3) to median 2 U (IQR 1–3), Mann-Whitney U test p = 0.005). Morbidity decreased (overall: 13.8%–12.3%, p = 0.001; emergent: 26.3%–20.6%, p \u3c 0.001) while mortality did not change. Discussion: Rates of RBC transfusion decreased in both emergent and non-emergent cases. Efforts to reduce transfusion may have been successful in the EGS population. Morbidity improved over the time periods while mortality was unchanged. Level of Evidence: Level III

Entropy creation inside black holes points to observer complementarity

Heating processes inside large black holes can produce tremendous amounts of entropy. Locality requires that this entropy adds on space-like surfaces, but the resulting entropy (10^10 times the Bekenstein-Hawking entropy in an example presented in the companion paper) exceeds the maximum entropy that can be accommodated by the black hole's degrees of freedom. Observer complementarity, which proposes a proliferation of non-local identifications inside the black hole, allows the entropy to be accommodated as long as individual observers inside the black hole see less than the Bekenstein-Hawking entropy. In the specific model considered with huge entropy production, we show that individual observers do see less than the Bekenstein-Hawking entropy, offering strong support for observer complementarity.Comment: 13 pages. This is a companion paper to arXiv:0801.4415; Added reference

Coherent electronic transfer in quantum dot systems using adiabatic passage

We describe a scheme for using an all-electrical, rapid, adiabatic population transfer between two spatially separated dots in a triple-quantum dot system. The electron spends no time in the middle dot and does not change its energy during the transfer process. Although a coherent population transfer method, this scheme may well prove useful in incoherent electronic computation (for example quantum-dot cellular automata) where it may provide a coherent advantage to an otherwise incoherent device. It can also be thought of as a limiting case of type II quantum computing, where sufficient coherence exists for a single gate operation, but not for the preservation of superpositions after the operation. We extend our analysis to the case of many intervening dots and address the issue of transporting quantum information through a multi-dot system.Comment: Replaced with (approximately) the published versio

Hubble Space Telescope Images and Spectra of the Remnant of SN 1885 in M31

Near-UV Hubble Space Telescope images of the remnant of SN 1885 (S And) in M31 show a 070±005 diameter absorption disk silhouetted against M31\u27s central bulge, at SN 1885\u27s historically reported position. The disk\u27s size corresponds to a linear diameter of 2.5±0.4 pc at a distance of 725±70 kpc, implying an average expansion velocity of 11,000±2000 km s-1 over 110 yr. Low-dispersion Faint Object Spectrograph spectra over 3200-4800 Å reveal that the absorption arises principally from Ca II H and K (equivalent width 215 Å), with weaker absorption features of Ca I 4227 Å and Fe I 3720 Å. The flux at Ca II line center indicates a foreground starlight fraction of 0.21, which places SNR 1885 some 64 pc to the near side of the midpoint of the M31 bulge, comparable to its projected 55 pc distance from the nucleus. The absorption line profiles suggest an approximately spherically symmetric, bell-shaped density distribution of supernova ejecta freely expanding at up to 13,100±1500 km s-1. We estimate Ca I, Ca II, and Fe I masses of 2.9×10−4 M☉, 0.005 M☉, and 0.013 M☉, respectively. If the ionization state of iron is similar to the observed ionization state of calcium, MCa II/MCa I=16, then the mass of Fe II is 0.21 M☉, consistent with that expected for either normal or subluminous SN Ia