Pallet Racking Using Cold-reduced Steel

Codes of practice for the design of cold-formed sections have generally included a requirement for the coil material to possess a specified amount of ductility prior to forming. The scientific basis for such ductility requirements is shrouded in historical mystery but code drafting committees have been reluctant to remove these requirements in the absence of good reason. However, very low ductility steels have been used for the manufacture of cold-formed steel components for many years by the two leading UK manufacturers of storage racks without this lack of ductility giving rise to any problems during either manufacture or service. This relatively hard material is produced by taking conventional coil material and cold-reducing it prior to forming it into beam, column and other components. The advantage gained by this procedure is a significant increase in the yield stress but the penalty is a considerable reduction in the ductility. As, up to the present time, storage racking has not been subject to formal approval procedures, the absence of clauses in UK or European Codes of Practice allowing the use of these hard steels has not caused any problems. However, this situation is now changing and it has become necessary to justify their performance in comparison with material of more usual ductility. It may be noted here that the use of low ductility steel is not unique to storage racking because very hard steels have been also used successfully in Europe for the manufacture of profiled steel cladding. Galvanised coil is available with a guaranteed yield stress of 550 N/mm² and several manufacturers successfully form this material. Indeed, the first author has tested roof sheeting made from material which had a measured yield stress in excess of 700 N/mm² together with zero elongation in a conventional tensile test. The buckling-yielding failure modes observed in both single and two-span tests to failure showed no evidence of the influence of reduced ductility. In this paper, the justification for the use of low-yield stress steel is taken a stage further by describing a series of tests on racking components made from both cold-reduced steel and an equivalent hot-rolled steel of similar yield stress but much greater ductility. It is shown that the use of hard steel has no adverse effect on performance. The paper concludes by describing a test to failure of a full scale rack structure fabricated using components made from cold-reduced steel

Mapping the Hsp90 Genetic Interaction Network in Candida albicans Reveals Environmental Contingency and Rewired Circuitry

The molecular chaperone Hsp90 regulates the folding of diverse signal transducers in all eukaryotes, profoundly affecting cellular circuitry. In fungi, Hsp90 influences development, drug resistance, and evolution. Hsp90 interacts with ∼10% of the proteome in the model yeast Saccharomyces cerevisiae, while only two interactions have been identified in Candida albicans, the leading fungal pathogen of humans. Utilizing a chemical genomic approach, we mapped the C. albicans Hsp90 interaction network under diverse stress conditions. The chaperone network is environmentally contingent, and most of the 226 genetic interactors are important for growth only under specific conditions, suggesting that they operate downstream of Hsp90, as with the MAPK Hog1. Few interactors are important for growth in many environments, and these are poised to operate upstream of Hsp90, as with the protein kinase CK2 and the transcription factor Ahr1. We establish environmental contingency in the first chaperone network of a fungal pathogen, novel effectors upstream and downstream of Hsp90, and network rewiring over evolutionary time

Differential limit on the extremely-high-energy cosmic neutrino flux in the presence of astrophysical background from nine years of IceCube data

We report a quasi-differential upper limit on the extremely-high-energy (EHE) neutrino flux above $5\times 10^{6}$ GeV based on an analysis of nine years of IceCube data. The astrophysical neutrino flux measured by IceCube extends to PeV energies, and it is a background flux when searching for an independent signal flux at higher energies, such as the cosmogenic neutrino signal. We have developed a new method to place robust limits on the EHE neutrino flux in the presence of an astrophysical background, whose spectrum has yet to be understood with high precision at PeV energies. A distinct event with a deposited energy above $10^{6}$ GeV was found in the new two-year sample, in addition to the one event previously found in the seven-year EHE neutrino search. These two events represent a neutrino flux that is incompatible with predictions for a cosmogenic neutrino flux and are considered to be an astrophysical background in the current study. The obtained limit is the most stringent to date in the energy range between $5 \times 10^{6}$ and $5 \times 10^{10}$ GeV. This result constrains neutrino models predicting a three-flavor neutrino flux of $E_\nu^2\phi_{\nu_e+\nu_\mu+\nu_\tau}\simeq2\times 10^{-8}\ {\rm GeV}/{\rm cm}^2\ \sec\ {\rm sr}$at$10^9\ {\rm GeV}$. A significant part of the parameter-space for EHE neutrino production scenarios assuming a proton-dominated composition of ultra-high-energy cosmic rays is excluded.Comment: The version accepted for publication in Physical Review

Functioning of Coastal River-Dominated Ecosystems and Implications for Oil Spill Response: From Observations to Mechanisms and Models

Coastal river-dominated oceans are physically complex, biologically productive, and intimately connected to human socioeconomic activity. The Deepwater Horizon blowout and subsequent advection of oil into coastal waters of the northern Gulf of Mexico (nGOM) highlighted the complex linkages among oceanographic processes within this river-dominated system and knowledge gaps about it that resulted in imprecise information on both oil transport and ecosystem consequences. The interdisciplinary research program implemented through the CONsortium for oil exposure pathways in COastal River-Dominated Ecosystems (CONCORDE) is designed to identify and quantitatively assess key physical, biological, and geochemical processes acting in the nGOM, in order to provide the foundation for implementation of a synthesis model (coupled circulation and biogeochemistry) of the nGOM shelf system that can ultimately aid in prediction of oil spill transport and impacts. CONCORDE field and modeling efforts in 2015–2016 focused on defining the influence of freshwater input from river plumes in the nGOM. In situ observations, combined with field-deployed and simulated drifters, show considerable variability in the spatial extent of freshwater influence that is related to wind direction and strength. Increased primary production and particle abundance (a proxy for secondary production) was observed during the spring when nGOM shelf waters were becoming stratified. Zooplankton and marine snow displayed intense vertical and horizontal patchiness during all seasons, often aggregating near the halocline. Simulations of a neutrally buoyant tracer released offshore of the Mississippi Bight showed surface advection of low tracer concentrations onto the inner shelf under high river discharge, high stratification, and variable wind conditions compared to almost no advection onto the inner shelf under low discharge, negligible stratification, and generally northeasterly winds. The interconnectedness of environmental variables and biological activity indicate that multiple factors can affect the transport of oil and the resulting ecological impacts. The process-oriented understanding provided by CONCORDE is necessary to predict ecosystem-level impacts of oil spills, and these results are applicable to other river-dominated coastal systems worldwide that often support oil extraction activities

Exploring the Trypanosoma brucei Hsp83 Potential as a Target for Structure Guided Drug Design

Human African trypanosomiasis is a neglected parasitic disease that is fatal if untreated. The current drugs available to eliminate the causative agent Trypanosoma brucei have multiple liabilities, including toxicity, increasing problems due to treatment failure and limited efficacy. There are two approaches to discover novel antimicrobial drugs--whole-cell screening and target-based discovery. In the latter case, there is a need to identify and validate novel drug targets in Trypanosoma parasites. The heat shock proteins (Hsp), while best known as cancer targets with a number of drug candidates in clinical development, are a family of emerging targets for infectious diseases. In this paper, we report the exploration of T. brucei Hsp83--a homolog of human Hsp90--as a drug target using multiple biophysical and biochemical techniques. Our approach included the characterization of the chemical sensitivity of the parasitic chaperone against a library of known Hsp90 inhibitors by means of differential scanning fluorimetry (DSF). Several compounds identified by this screening procedure were further studied using isothermal titration calorimetry (ITC) and X-ray crystallography, as well as tested in parasite growth inhibitions assays. These experiments led us to the identification of a benzamide derivative compound capable of interacting with TbHsp83 more strongly than with its human homologs and structural rationalization of this selectivity. The results highlight the opportunities created by subtle structural differences to develop new series of compounds to selectively target the Trypanosoma brucei chaperone and effectively kill the sleeping sickness parasite

A leaky umbrella has little value: evidence clearly indicates the serotonin system is implicated in depression.

A recent “umbrella” review examined various biomarkers relating to the serotonin system, and concluded there was no consistent evidence implicating serotonin in the pathophysiology of depression. We present reasons for why this conclusion is overstated, including methodological weaknesses in the review process, selective reporting of data, over-simplification, and errors in the interpretation of neuropsychopharmacological findings. We use the examples of tryptophan depletion and serotonergic molecular imaging, the two research areas most relevant to the investigation of serotonin, to illustrate this

A leaky umbrella has little value:evidence clearly indicates the serotonin system is implicated in depression

A recent “umbrella” review examined various biomarkers relating to the serotonin system, and concluded there was no consistent evidence implicating serotonin in the pathophysiology of depression. We present reasons for why this conclusion is overstated, including methodological weaknesses in the review process, selective reporting of data, over-simplification, and errors in the interpretation of neuropsychopharmacological findings. We use the examples of tryptophan depletion and serotonergic molecular imaging, the two research areas most relevant to the investigation of serotonin, to illustrate this

The bZIP Transcription Factor Rca1p Is a Central Regulator of a Novel CO2 Sensing Pathway in Yeast

Like many organisms the fungal pathogen Candida albicans senses changes in the environmental CO2 concentration. This response involves two major proteins: adenylyl cyclase and carbonic anhydrase (CA). Here, we demonstrate that CA expression is tightly controlled by the availability of CO2 and identify the bZIP transcription factor Rca1p as the first CO2 regulator of CA expression in yeast. We show that Rca1p upregulates CA expression during contact with mammalian phagocytes and demonstrate that serine 124 is critical for Rca1p signaling, which occurs independently of adenylyl cyclase. ChIP-chip analysis and the identification of Rca1p orthologs in the model yeast Saccharomyces cerevisiae (Cst6p) point to the broad significance of this novel pathway in fungi. By using advanced microscopy we visualize for the first time the impact of CO2 build-up on gene expression in entire fungal populations with an exceptional level of detail. Our results present the bZIP protein Rca1p as the first fungal regulator of carbonic anhydrase, and reveal the existence of an adenylyl cyclase independent CO2 sensing pathway in yeast. Rca1p appears to regulate cellular metabolism in response to CO2 availability in environments as diverse as the phagosome, yeast communities or liquid culture

Primordial Nucleosynthesis with a Decaying Tau Neutrino

A comprehensive study of the effect of an unstable tau neutrino on primordial nucleosynthesis is presented. The standard code for nucleosynthesis is modified to allow for a massive decaying tau neutrino whose daughter products include neutrinos, photons, $e^\pm$ pairs, and/or noninteracting (sterile) daughter products. Tau-neutrino decays influence primordial nucleosynthesis in three distinct ways: (i) the energy density of the decaying tau neutrino and its daughter products affect the expansion rate tending to increase $^4$He, D, and $^3$He production; (ii) electromagnetic (EM) decay products heat the EM plasma and dilute the baryon-to-photon ratio tending to decrease $^4$He production and increase D and $^3$He production; and (iii) electron neutrinos and antineutrinos produced by tau-neutrino decays increase the weak rates that govern the neutron-to-proton ratio, leading to decreased $^4$He production for short lifetimes (\la 30\sec) and masses less than about 10\MeV and increased $^4$He production for long lifetimes or large masses. The precise effect of a decaying tau neutrino on the yields of primordial nucleosynthesis and the mass-lifetime limits that follow depend crucially upon decay mode. We identify four generic decay modes that serve to bracket the wider range of possibilities:Comment: 27 pages, Latex, 12 Figures avaiable on request, FNAL--Pub--93/236-

Young off-axis volcanism along the ultraslow-spreading Southwest Indian Ridge

Author Posting. © The Authors, 2010. This is the author's version of the work. It is posted here by permission of Nature Publishing Group for personal use, not for redistribution. The definitive version was published in Nature Geoscience 3 (2010): 286-292, doi:10.1038/ngeo824.Mid-ocean ridge crustal accretion occurs continuously at all spreading rates through a combination of magmatic and tectonic processes. Fast to slow spreading ridges are largely built by adding magma to narrowly focused neovolcanic zones. In contrast, ultraslow spreading ridge construction significantly relies on tectonic accretion, which is characterized by thin volcanic crust, emplacement of mantle peridotite directly to the seafloor, and unique seafloor fabrics with variable segmentation patterns. While advances in remote imaging have enhanced our observational understanding of crustal accretion at all spreading rates, temporal information is required in order to quantitatively understand mid-ocean ridge construction. However, temporal information does not exist for ultraslow spreading environments. Here, we utilize U-series eruption ages to investigate crustal accretion at an ultraslow spreading ridge for the first time. Unexpectedly young eruption ages throughout the Southwest Indian ridge rift valley indicate that neovolcanic activity is not confined to the spreading axis, and that magmatic crustal accretion occurs over a wider zone than at faster spreading ridges. These observations not only suggest that crustal accretion at ultraslow spreading ridges is distinct from faster spreading ridges, but also that the magma transport mechanisms may differ as a function of spreading rate.This work was supported by the following NSF grants: NSF-OCE 0137325; NSF-OCE 060383800; and NSF-OCE 062705300