Determining Utility System Value of Demand Flexibility From Grid-interactive Efficient Buildings

This report focuses on ways current methods and practices that establish the value to electric utility systems of distributed energy resource (DER) investments can be enhanced to determine the value of demand flexibility in grid-interactive efficient buildings that can provide grid services. The report introduces key valuation concepts that are applicable to demand flexibility that these buildings can provide and links to other documents that describe these concepts and their implementation in more detail.The scope of this report is limited to the valuation of economic benefits to the utility system. These are the foundational values on which other benefits (and costs) can be built. Establishing the economic value to the grid of demand flexibility provides the information needed to design programs, market rules, and rates that align the economic interest of utility customers with building owners and occupants. By nature, DERs directly impact customers and provide societal benefits external to the utility system. Jurisdictions can use utility system benefits and costs as the foundation of their economic analysis but align their primary cost-effectiveness metric with all applicable policy objectives, which may include customer and societal (non-utility system) impacts.This report suggests enhancements to current methods and practices that state and local policymakers, public utility commissions, state energy offices, utilities, state utility consumer representatives, and other stakeholders might support. These enhancements can improve the consistency and robustness of economic valuation of demand flexibility for grid services. The report concludes with a discussion of considerations for prioritizing implementation of these improvements

Merlin Phosphorylation by p21-activated Kinase 2 and Effects of Phosphorylation on Merlin Localization

The Nf2 tumor suppressor gene product merlin is related to the membrane-cytoskeleton linker proteins of the band 4.1 superfamily, including ezrin, radixin, and moesin (ERMs). Merlin is regulated by phosphorylation in a Rac/cdc42-dependent fashion. We report that the phosphorylation of merlin at serine 518 is induced by the p21-activated kinase PAK2. This is demonstrated by biochemical fractionation, use of active and dominant-negative mutants of PAK2, and immunodepletion. By using wild-type and mutated forms of merlin and phospho-directed antibodies, we show that phosphorylation of merlin at serine 518 leads to dramatic protein relocalization. Neurofibromatosis type 2 (NF2)1 is an inherited disorder characterized by the development of Schwann cell tumors of the eighth cranial nerve. Mutations and loss of heterozygosity of theNF2 gene have been detected in NF2 patients and in various sporadic tumors, including schwannomas, meningiomas, and ependymomas (1). In further support of a role for NF2 in tumor suppression, mice heterozygous for an Nf2 mutation are predisposed to a wide variety of tumors with high metastatic potential (2). In a separate model in which Nf2 is inactivated specifically in Schwann cells, mice develop schwannomas and Schwann cell hyperplasia (3). The longest and predominant splice form of the Nf2gene codes for a 595-amino acid protein highly similar to the band 4.1 family of proteins. It is most closely related to the ERM proteins,moesin, ezrin, and radixin. The ERM proteins are thought to function as cell membrane-cytoskeleton linkers and are localized to cortical actin structures near the plasma membrane such as microvilli, membrane ruffles, and lamellipodia (4, 5). Likewise, merlin is localized to cortical actin structures, in patterns that partially overlap with the ERMs (1). It has been proposed that intramolecular binding of the N-terminal and C-terminal domains conformationally regulates the ERM proteins by masking binding sites for interacting proteins. The ERMs can also form homodimers and heterodimers, among themselves and with merlin, adding an additional level of complexity to the regulation of these proteins (6). The recently solved crystal structure of the moesin N/C-terminal complex strengthens this model of conformational regulation (7). Given the sequence and, most likely, structural similarities of merlin to the ERM proteins, it is possible that merlin itself could be regulated in a similar fashion. Recent studies (8, 9) have implicated additional factors in the regulation of the ERMs, including phospholipids and phosphorylation. Previous work from our group and others (10, 11) has shown that merlin is differentially phosphorylated as well and that merlin protein levels are affected by growth conditions such as cell confluency, loss of adhesion, or serum deprivation. Merlin is found in an hypophosphorylated form when the combination of cellular and environmental conditions are growth-inhibitory (10). ERMs can be phosphorylated by Rho kinase, and this phosphorylation can affect intramolecular association and cellular localization. Phosphorylation and/or phospholipids may promote the transition of the proteins to an active form by “opening” intra- and intermolecular associations. These active monomers can then bind to other interacting proteins and the actin cytoskeleton and induce actin-rich membrane projections (5,8, 12, 13). The induction of merlin phosphorylation by activated alleles of the Rho family GTPases has also been examined. Interestingly, although activated Rho did not induce noticeable phosphorylation of merlin, activated forms of Rac and cdc42 did. The site of Rac-induced phosphorylation was determined to be a serine at position 518; mutation of serine 518 results in reduced basal phosphorylation and eliminated Rac-induced phosphorylation (11). Although Rac and cdc42 are implicated in the regulation of many pathways, they are most associated with regulation of cytoskeleton reorganization and gene expression (for recent reviews see Refs.14-16). In light of the data demonstrating that activated Rac/cdc42 leads to phosphorylation and possible inactivation of merlin, the elucidation of the responsible effector pathways and their effects on merlin function are of major importance. Understanding this regulation of merlin could lead to a more complete appreciation of the effects of merlin loss in tumors

To Fib or Not to Fib: Misdiagnosis of Atrial Fibrillation on Telemetry Case Presentation and Root Cause Analysis

Case presentation, current practices of telemetry management, root cause analysis, goals for improvement, proposed intervention and next steps

Pharmacologic reductions of total tau levels; implications for the role of microtubule dynamics in regulating tau expression

The microtubule-associated protein tau (MAPT) is a pathological component of several neurodegenerative diseases and clinical dementias. Here, we have investigated the effects of a series of commercially available FDA-approved compounds and natural products on total tau protein levels using a cell-based approach that allows for the rapid and efficient measurement of changes in protein expression. RESULTS: The compounds that reduced tau largely fell within 3 functional categories with the largest percentage being microtubule regulators. Several of these candidates were validated in both a human neuroglioma and a human neuroblastoma cell line. While these drugs lead to a rapid reduction in tau protein levels, a selective decrease in MAPT mRNA expression was also observed. CONCLUSION: These findings suggest that the identified compounds that reduce tau levels may act either through direct effects on the MAPT promoter itself or by altering a feedback transcriptional mechanism regulating MAPT transcription. This is particularly interesting in light of recent evidence suggesting that MAPT 5' UTR mutations in late-onset PD and PSP cases alter the expression of tau mRNA. In fact, one of the compounds we identified, rotenone, has been used extensively to model PD in rodents. These observations may provide key insights into the mechanism of tau turnover within the neuron while also providing the first evidence that selectively reducing tau protein levels may be possible using compounds that are FDA-approved for other uses

Extracellular vesicles : where the amyloid precursor protein carboxyl-terminal fragments accumulate and amyloid-β oligomerizes

Pleiotropic roles are proposed for brain extracellular vesicles (EVs) in the development of Alzheimer's disease (AD). Our previous studies have suggested a beneficial role for EVs in AD, where the endosomal system in vulnerable neurons is compromised, contributing to the removal of accumulated material from neurons. However, the involvement of EVs in propagating AD amyloidosis throughout the brain has been considered because the amyloid-β precursor protein (APP), APP metabolites, and key APP cleaving enzymes were identified in association with EVs. Here, we undertook to determine whether the secretase machinery is actively processing APP in EVs isolated from the brains of wild-type and APP overexpressing Tg2576 mice. We found that full-length APP is cleaved in EVs incubated in the absence of cells. The resulting metabolites, both α- and β-APP carboxyl-terminal fragments and APP intracellular domain accumulate in EVs over time and amyloid-β dimerizes. Thus, EVs contribute to the removal from neurons and transport of APP-derived neurotoxic peptides. While this is potentially a venue for propagation of the pathology throughout the brain, it may contribute to efficient removal of neurotoxic peptides from the brain

Performance of cages as large animal-exclusion devices in the deep sea

Sedimentary, deep-sea communities include megafaunal animals (e.g., sea cucumbers, brittle stars, crabs) and demersal fishes, collectively termed the large, motile epifauna (LME). Individuals of the LME are common, and their biomass approximates that of the macrofauna. Based on analogies with shallow-water animals, they are likely to be sources of mortality for the infauna and to create spatial and temporal heterogeneity in the community. Given present theories of deep-sea community organization, such effects could be important. Unfortunately, this hypothesis has not been tested because of the difficulty of conducting experiments in the deep sea and because tools for manipulating the LME have not been developed. We studied the suitability of exclusion cages for this purpose at 780 m depth in San Diego Trough. We placed 16 cages of two mesh sizes for 4.5 months over regions of the seafloor that appeared free of LME. Time-lapse photographs of a cage and a control plot coupled with observations of all cages at the end of the experiment indicated that small (1.27-cm × 1.27-cm square)-mesh cages were effective at excluding LME. Further, the cages were essentially free of cage artifacts that have been reported in shallow-water studies. Large, mobile and disruptive animals (e.g., fishes, crabs) did not establish long-term residence adjacent to or on the cages. Bio-fouling slightly reduced the open surface area of the cage mesh, potentially reducing flow through the cage, but the composition of surface sediments in terms of organic C and N, phytoplankton-derived pigments, and grain size was indistinguishable between cages and control areas. Activities of excess 234Th were significantly higher (average = 37%) inside of small-mesh cages, which might suggest enhanced particulate deposition inside cages. However, this measurement was an artifact of experimental manipulation. Particles that accumulated on the cage during the experiment were dislodged and settled to the seafloor when the cage was opened just prior to sampling. These particles would have been highly enriched in 234Th, and their inclusion in core samples artificially inflated the calculated sediment accumulation rates inside cages. Therefore, the cages performed well; they excluded the targeted LME without causing artifacts and thus should be useful for experimental study of a group of animals that may have substantial impact on the structure and organization of deep-sea communities

Quantum Bubble Nucleation beyond WKB: Resummation of Vacuum Bubble Diagrams

On the basis of Borel resummation, we propose a systematical improvement of bounce calculus of quantum bubble nucleation rate. We study a metastable super-renormalizable field theory, $D$ dimensional O(N) symmetric $\phi^4$ model ($D<4$) with an attractive interaction. The validity of our proposal is tested in D=1 (quantum mechanics) by using the perturbation series of ground state energy to high orders. We also present a result in D=2, based on an explicit calculation of vacuum bubble diagrams to five loop orders.Comment: 19 pages, 5 figures, PHYZZ

Valuation of scleroderma and psoriatic arthritis health states by the general public

<p>Abstract</p> <p>Objective</p> <p>Psoriatic arthritis (PsA) and scleroderma (SSc) are chronic rheumatic disorders with detrimental effects on health-related quality of life. Our objective was to assess health values (utilities) from the general public for health states common to people with PsA and SSc for economic evaluations.</p> <p>Methods</p> <p>Adult subjects from the general population in a Midwestern city (N = 218) completed the SF-12 Health Survey and computer-assisted 0-100 rating scale (RS), time trade-off (TTO, range: 0.0-1.0) and standard gamble (SG, range: 0.0-1.0) utility assessments for several hypothetical PsA and SSc health states.</p> <p>Results</p> <p>Subjects included 135 (62%) females, 143 (66%) Caucasians, and 62 (28%) African-Americans. The mean (SD) scores for the SF-12 Physical Component Summary scale were 52.9 (8.3) and for the SF-12 Mental Component Summary scale were 49.0 (9.1), close to population norms. The mean RS, TTO, and SG scores for PsA health states varied with severity, ranging from 20.2 to 63.7 (14.4-20.3) for the RS 0.29 to 0.78 (0.24-0.31) for the TTO, and 0.48 to 0.82 (0.24-0.34) for the SG. The mean RS, TTO, and SG scores for SSc health states were 25.3-69.7 (15.2-16.3) for the RS, 0.36-0.80 (0.25-0.31) for the TTO, and 0.50-0.81 (0.26-0.32) for the SG, depending on disease severity.</p> <p>Conclusion</p> <p>Health utilities for PsA and SSc health states as assessed from the general public reflect the severity of the diseases. These descriptive findings could have implications regarding comparative effectiveness research for tests and treatments for PsA and SSc.</p

Diversity among Equals: Educational Opportunity and the State of Affirmative Admissions in New England

This report reviews the practice of Affirmative Admissions as a strategy for achieving diversity within New England colleges and universities. It shows how educational leaders perceive Affirmative Admissions, the nature of regional Affirmative Admissions policies, and the numbers of student affected by current enrollment strategies. This report is part of a larger series on educational access and opportunity in New England. Research was organized into five components: (1) analysis of pertinent legal issues related to postsecondary access and equity; (2) interviews with postsecondary campus and state leaders (n=104); (3) interviews with K-12 leaders and educators at state, district, and school levels (n=45); (4) a survey of 221 postsecondary education institutions in New England; and (5) econometric analyses of student data. The focus was on groups of institutions, 18 groups clustered by admissions policies and restrictions. The most compelling conclusion is that there is no significant evidence that colleges have reduced standards to admit greater numbers of minority students. By increasing educational access to a broader segment of the population, the regions higher education institutions have taken crucial steps toward assuring the vitality and vibrancy of New Englands future economy and civic life. The study also indicates that the pool of qualified minority students is much too small, highlighting the need to improve the preparation of minority students. Three appendixes contain details about survey methodology, participating institutions, and regression coefficients. Prepared by the Center for Education Policy (CEP) and Massachusetts Institute for Social and Economic Research (MISER), University of Massachusetts at Amherst. Sponsored by the Nellie Mae Education Foundation

Cost-effectiveness of HBV and HCV screening strategies:a systematic review of existing modelling techniques

Introduction: Studies evaluating the cost-effectiveness of screening for Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) are generally heterogeneous in terms of risk groups, settings, screening intervention, outcomes and the economic modelling framework. It is therefore difficult to compare cost-effectiveness results between studies. This systematic review aims to summarise and critically assess existing economic models for HBV and HCV in order to identify the main methodological differences in modelling approaches. Methods: A structured search strategy was developed and a systematic review carried out. A critical assessment of the decision-analytic models was carried out according to the guidelines and framework developed for assessment of decision-analytic models in Health Technology Assessment of health care interventions. Results: The overall approach to analysing the cost-effectiveness of screening strategies was found to be broadly consistent for HBV and HCV. However, modelling parameters and related structure differed between models, producing different results. More recent publications performed better against a performance matrix, evaluating model components and methodology. Conclusion: When assessing screening strategies for HBV and HCV infection, the focus should be on more recent studies, which applied the latest treatment regimes, test methods and had better and more complete data on which to base their models. In addition to parameter selection and associated assumptions, careful consideration of dynamic versus static modelling is recommended. Future research may want to focus on these methodological issues. In addition, the ability to evaluate screening strategies for multiple infectious diseases, (HCV and HIV at the same time) might prove important for decision makers