Best Estimate Method vs Evaluation Method: a comparison of two techniques in evaluating seismic analysis and design

The concept of how two techniques, Best Estimate Method and Evaluation Method, may be applied to the traditional seismic analysis and design of a nuclear power plant is introduced. Only the four links of the seismic analysis and design methodology chain (SMC) - seismic input, soil-structure interaction, major structural response, and subsystem response - are considered. The objective is to evaluate the compounding of conservatisms in the seismic analysis and design of nuclear power plants, to provide guidance for judgments in the SMC, and to concentrate the evaluation on that part of the seismic analysis and design which is familiar to the engineering community. An example applies the effects of three-dimensional excitations on a model of a nuclear power plant structure. The example demonstrates how conservatisms accrue by coupling two links in the SMC and comparing those results to the effects of one link alone. The utility of employing the Best Estimate Method vs the Evaluation Method is also demonstrated

Neurotoxicity with high dose disulfiram and vorinostat used for HIV latency reversal

OBJECTIVE: To examine whether administering both vorinostat and disulfiram to people with HIV (PWH) on antiretroviral therapy (ART) is safe and can enhance HIV latency reversal. DESIGN: Vorinostat and disulfiram, can increase HIV transcription in people with HIV (PWH) on antiretroviral therapy (ART). Together these agents may lead to significant HIV latency reversal. METHODS: Virologically suppressed PWH on ART received disulfiram 2000 mg daily for 28 days and vorinostat 400 mg daily on days 8-10 and 22-24. The primary endpoint was plasma HIV RNA on day 11 relative to baseline using a single copy assay. Assessments included cell-associated (CA) unspliced (US) RNA as a marker of latency reversal, HIV DNA in CD4+ T-cells, plasma HIV RNA and plasma concentrations of ART, vorinostat and disulfiram. RESULTS: The first two participants (P1 and P2) experienced grade 3 neurotoxicity leading to trial suspension. After 24 days, P1 presented with confusion, lethargy, and ataxia having stopped disulfiram and ART. Symptoms resolved by day 29. After 11 days, P2 presented with paranoia, emotional lability, lethargy, ataxia and study drugs were ceased. Symptoms resolved by day 23. CA-US RNA increased by 1.4- and 1.3-fold for P1 and P2 respectively. Plasma HIV RNA was detectable from day 8-37 (peak 81 copies/mL) for P2 but was not increased in P1 Antiretroviral levels were therapeutic and neuronal injury markers were elevated in P1. CONCLUSIONS: The combination of prolonged high dose disulfiram and vorinostat was not safe in PWH on ART and should not be pursued despite evidence of latency reversal

High-angle wave instability and emergent shoreline shapes : 2. Wave climate analysis and comparisons to nature

Author Posting. © American Geophysical Union, 2006. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research 111 (2006): F04012, doi:10.1029/2005JF000423.Recent research has revealed that the plan view evolution of a coast due to gradients in alongshore sediment transport is highly dependant upon the angles at which waves approach the shore, giving rise to an instability in shoreline shape that can generate different types of naturally occurring coastal landforms, including capes, flying spits, and alongshore sand waves. This instability merely requires that alongshore sediment flux is maximized for a given deepwater wave angle, a maximum that occurs between 35° and 50° for several common alongshore sediment transport formulae. Here we introduce metrics that sum over records of wave data to quantify the long-term stability of wave climates and to investigate how wave climates change along a coast. For Long Point, a flying spit on the north shore of Lake Erie, Canada, wave climate metrics suggest that unstable waves have shaped the spit and, furthermore, that smaller-scale alongshore sand waves occur along the spit at the same locations where the wave climate becomes unstable. A shoreline aligned along the trend of the Carolina Capes, United States, would be dominated by high-angle waves; numerical simulations driven by a comparable wave climate develop a similarly shaped cuspate coast. Local wave climates along these simulated capes and the Carolina Capes show similar trends: Shoreline reorientation and shadowing from neighboring capes causes most of the coast to experience locally stable wave climates despite regional instability.This research was funded by the Andrew W. Mellon Foundation and NSF grants DEB-05-07987 and EAR-04-44792

The business of rapid transition

In a context of climate emergency and calls from the IPCC for “transformative systemic change,” we need to revisit the role of business in helping to accelerate responses to climate crisis. The scale and depth of the challenges facing business have intensified in ways which force us to refocus our research on questions of urgency and speed, as well as the growing need for new and alternative business models and a fundamental re‐balancing of the economy. There is a large literature dealing with business responses to climate change from a range of perspectives and disciplines covering issues such as corporate strategy and public policy engagement. But I argue that the question of the nature and speed of change now required, and whether there are historical and contemporary precedents for accelerated transitions within and beyond business, must assume a more central place in our research. This must be alongside growing efforts to understand how business will adapt to climate chaos. This conclusion implies a closer engagement and cross‐fertilization of ideas with scholars of sustainability transitions, for example. Here, there is growing interest in the question of how to accelerate transitions, but where greater attention is required to the role of business actors

Necrotrophism Is a Quorum-Sensing-Regulated Lifestyle in Bacillus thuringiensis

How pathogenic bacteria infect and kill their host is currently widely investigated. In comparison, the fate of pathogens after the death of their host receives less attention. We studied Bacillus thuringiensis (Bt) infection of an insect host, and show that NprR, a quorum sensor, is active after death of the insect and allows Bt to survive in the cadavers as vegetative cells. Transcriptomic analysis revealed that NprR regulates at least 41 genes, including many encoding degradative enzymes or proteins involved in the synthesis of a nonribosomal peptide named kurstakin. These degradative enzymes are essential in vitro to degrade several substrates and are specifically expressed after host death suggesting that Bt has an active necrotrophic lifestyle in the cadaver. We show that kurstakin is essential for Bt survival during necrotrophic development. It is required for swarming mobility and biofilm formation, presumably through a pore forming activity. A nprR deficient mutant does not develop necrotrophically and does not sporulate efficiently in the cadaver. We report that necrotrophism is a highly regulated mechanism essential for the Bt infectious cycle, contributing to spore spreading

‘Sub-Prime’ Water, Low-Security Entitlements and Policy Challenges in Over-Allocated River Basins: the Case of the Murray–Darling Basin

Environmental policy is often implemented using market instruments. In some cases, including carbon taxing, the links between financial products and the environmental objectives, are transparent. In other cases, including water markets, the links are less transparent. In Australia’s Murray–Darling Basin (MDB), financial water products are known as ‘entitlements’, and are similar to traditional financial products, such as shares. The Australian water market includes ‘Low Security’ entitlements, which are similar to ‘sub-prime’ mortgage bonds because they are unlikely to yield an amount equal to their financial worth. Nearly half the water purchased under the Murray–Darling Basin Plan for environmental purposes is ‘Low Security’. We suggest that the current portfolio of water held by the Australian Government for environmental purposes reflects the mortgage market in the lead-up to the global financial crisis. Banks assumed that the future value of the mortgage market would reflect past trends. Similarly, it is assumed that the future value of water products will reflect past trends, without considering climate change. Historic records of allocations to ‘Low Security’ entitlements in the MDB suggest that, in the context of climate change, the Basin Plan water portfolio may fall short of the target annual average yield of 2075 GL by 511 GL. We recommend adopting finance sector methods including ‘hedging’ ‘Low Security’ entitlements by purchasing an additional 322–2755 GL of ‘Low Security’, or 160–511 GL of ‘High Security’ entitlements. Securing reliable environmental water is a global problem. Finance economics present opportunities for increasing the reliability of environmental flows