America’s Marine Highway stakeholders: a system-scale analysis of influence in decision making

This work surveys stakeholders of America’s Marine Highway to identify their perceived influence on each other’s resource allocation decision making. The value/criticality of the resource held by the stakeholder group can be indirectly measured by the influence exerted by the group on its peers and its external stakeholders. The stakeholder map visualizes how the various stakeholder groups influence each other. Survey of the US Marine Highway stakeholders reveals peers as the most dominant influence among shippers, environmental advocates, and regulators. Results suggest that only suppliers and transportation providers exhibit distinct dominance of customer-supplier influence over that of their peers. This snapshot of stakeholder relationships is a powerful tool for both businesses as well as regulators in their pursuit of shared objectives in a network-centric environment. Stakeholder relationship influence results, and their graphical illustration, contribute to understanding the underlying dynamics of a changing value advantage in the current and coming decades of shipping

Systems biology analysis of drivers underlying hallmarks of cancer cell metabolism.

Malignant transformation is often accompanied by significant metabolic changes. To identify drivers underlying these changes, we calculated metabolic flux states for the NCI60 cell line collection and correlated the variance between metabolic states of these lines with their other properties. The analysis revealed a remarkably consistent structure underlying high flux metabolism. The three primary uptake pathways, glucose, glutamine and serine, are each characterized by three features: (1) metabolite uptake sufficient for the stoichiometric requirement to sustain observed growth, (2) overflow metabolism, which scales with excess nutrient uptake over the basal growth requirement, and (3) redox production, which also scales with nutrient uptake but greatly exceeds the requirement for growth. We discovered that resistance to chemotherapeutic drugs in these lines broadly correlates with the amount of glucose uptake. These results support an interpretation of the Warburg effect and glutamine addiction as features of a growth state that provides resistance to metabolic stress through excess redox and energy production. Furthermore, overflow metabolism observed may indicate that mitochondrial catabolic capacity is a key constraint setting an upper limit on the rate of cofactor production possible. These results provide a greater context within which the metabolic alterations in cancer can be understood

Groundwater dynamics in coastal gravel barriers backed by freshwater lagoons and the potential for saline intrusion: Two cases from the UK

“NOTICE: this is the author’s version of a work that was accepted for publication in Journal of Marine Systems. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Journal of Marine Systems, [VOL 123, (01.08.13)] DOI 10.1016/j.jmarsys.2013.04.004". The full text is under embargo until 01.08.15

Transportation Energy Futures Series: Freight Transportation Demand: Energy-Efficient Scenarios for a Low-Carbon Future

Freight transportation demand is projected to grow to 27.5 billion tons in 2040, and to nearly 30.2 billion tons in 2050. This report describes the current and future demand for freight transportation in terms of tons and ton-miles of commodities moved by truck, rail, water, pipeline, and air freight carriers. It outlines the economic, logistics, transportation, and policy and regulatory factors that shape freight demand, the trends and 2050 outlook for these factors, and their anticipated effect on freight demand. After describing federal policy actions that could influence future freight demand, the report then summarizes the capabilities of available analytical models for forecasting freight demand. This is one in a series of reports produced as a result of the Transportation Energy Futures project, a Department of Energy-sponsored multi-agency effort to pinpoint underexplored strategies for reducing GHGs and petroleum dependence related to transportation

Topoisomerase II: a fitted mechanism for the chromatin landscape

The mechanism by which type-2A topoisomerases transport one DNA duplex through a transient double-strand break produced in another exhibits fascinating traits. One of them is the fine coupling between inter-domainal movements and ATP usage; another is their preference to transport DNA in particular directions. These capabilities have been inferred from in vitro studies but we ignore their significance inside the cell, where DNA configurations markedly differ from those of DNA in free solution. The eukaryotic type-2A enzyme, topoisomerase II, is the second most abundant chromatin protein after histones and its biological roles include the decatenation of newly replicated DNA and the relaxation of polymerase-driven supercoils. Yet, topoisomerase II is also implicated in other cellular processes such as chromatin folding and gene expression, in which the topological transformations catalysed by the enzyme are uncertain. Here, some capabilities of topoisomerase II that might be relevant to infer the enzyme performance in the context of chromatin architecture are discussed. Some aspects addressed are the importance of the DNA rejoining step to ensure genome stability, the regulation of the enzyme activity and of its putative structural role, and the selectively of DNA transport in the chromatin milieu

The Impact of the C-Terminal Domain on the Interaction of Human DNA Topoisomerase II α and β with DNA

<b>Background</b> Type II DNA topoisomerases are essential, ubiquitous enzymes that act to relieve topological problems arising in DNA from normal cellular activity. Their mechanism of action involves the ATP-dependent transport of one DNA duplex through a transient break in a second DNA duplex; metal ions are essential for strand passage. Humans have two isoforms, topoisomerase IIα and topoisomerase IIβ, that have distinct roles in the cell. The C-terminal domain has been linked to isoform specific differences in activity and DNA interaction. <b>Methodology/Principal Findings</b> We have investigated the role of the C-terminal domain in the binding of human topoisomerase IIα and topoisomerase IIβ to DNA in fluorescence anisotropy assays using full length and C-terminally truncated enzymes. We find that the C-terminal domain of topoisomerase IIβ but not topoisomerase IIα affects the binding of the enzyme to the DNA. The presence of metal ions has no effect on DNA binding. Additionally, we have examined strand passage of the full length and truncated enzymes in the presence of a number of supporting metal ions and find that there is no difference in relative decatenation between isoforms. We find that calcium and manganese, in addition to magnesium, can support strand passage by the human topoisomerase II enzymes. <b>Conclusions/Significance</b> The C-terminal domain of topoisomerase IIβ, but not that of topoisomerase IIα, alters the enzyme's KD for DNA binding. This is consistent with previous data and may be related to the differential modes of action of the two isoforms in vivo. We also show strand passage with different supporting metal ions for human topoisomerase IIα or topoisomerase IIβ, either full length or C-terminally truncated. They all show the same preferences, whereby Mg > Ca > Mn

The Impact of the Human DNA Topoisomerase II C-Terminal Domain on Activity

Type II DNA topoisomerases (topos) are essential enzymes needed for the resolution of topological problems that occur during DNA metabolic processes. Topos carry out an ATP-dependent strand passage reaction whereby one double helix is passed through a transient break in another. Humans have two topoII isoforms, alpha and beta, which while enzymatically similar are differentially expressed and regulated, and are thought to have different cellular roles. The C-terminal domain (CTD) of the enzyme has the most diversity, and has been implicated in regulation. We sought to investigate the impact of the CTD domain on activity.We have investigated the role of the human topoII C-terminal domain by creating constructs encoding C-terminally truncated recombinant topoIIalpha and beta and topoIIalpha+beta-tail and topoIIbeta+alpha-tail chimeric proteins. We then investigated function in vivo in a yeast system, and in vitro in activity assays. We find that the C-terminal domain of human topoII isoforms is needed for in vivo function of the enzyme, but not needed for cleavage activity. C-terminally truncated enzymes had similar strand passage activity to full length enzymes, but the presence of the opposite C-terminal domain had a large effect, with the topoIIalpha-CTD increasing activity, and the topoIIbeta-CTD decreasing activity.In vivo complementation data show that the topoIIalpha C-terminal domain is needed for growth, but the topoIIbeta isoform is able to support low levels of growth without a C-terminal domain. This may indicate that topoIIbeta has an additional localisation signal. In vitro data suggest that, while the lack of any C-terminal domain has little effect on activity, the presence of either the topoIIalpha or beta C-terminal domain can affect strand passage activity. Data indicates that the topoIIbeta-CTD may be a negative regulator. This is the first report of in vitro data with chimeric human topoIIs

Risk perception influences athletic pacing strategy.

PURPOSE: The objective of this study is to examine risk taking and risk perception associations with perceived exertion, pacing, and performance in athletes. METHODS: Two experiments were conducted in which risk perception was assessed using the domain-specific risk taking (DOSPERT) scale in 20 novice cyclists (experiment 1) and 32 experienced ultramarathon runners (experiment 2). In experiment 1, participants predicted their pace and then performed a 5-km maximum effort cycling time trial on a calibrated Kingcycle mounted bicycle. Split times and perceived exertion were recorded every kilometer. In experiment 2, each participant predicted their split times before running a 100-km ultramarathon. Split times and perceived exertion were recorded at seven checkpoints. In both experiments, higher and lower risk perception groups were created using median split of DOSPERT scores. RESULTS: In experiment 1, pace during the first kilometer was faster among lower risk perceivers compared with higher risk perceivers (t(18) = 2.0, P = 0.03) and faster among higher risk takers compared with lower risk takers (t(18) = 2.2, P = 0.02). Actual pace was slower than predicted pace during the first kilometer in both the higher risk perceivers (t(9) = -4.2, P = 0.001) and lower risk perceivers (t(9) = -1.8, P = 0.049). In experiment 2, pace during the first 36 km was faster among lower risk perceivers compared with higher risk perceivers (t(16) = 2.0, P = 0.03). Irrespective of risk perception group, actual pace was slower than predicted pace during the first 18 km (t(16) = 8.9, P < 0.001) and from 18 to 36 km (t(16) = 4.0, P < 0.001). In both experiments, there was no difference in performance between higher and lower risk perception groups. CONCLUSIONS: Initial pace is associated with an individual's perception of risk, with low perceptions of risk being associated with a faster starting pace. Large differences between predicted and actual pace suggest that the performance template lacks accuracy, perhaps indicating greater reliance on momentary pacing decisions rather than preplanned strategy.This is the author accepted manuscript. The final version is available from Wolters Kluwer via http://dx.doi.org/10.1249/MSS.000000000000050

Phytoplankton Response to Intrusions of Slope Water on the West Florida Shelf: Models and Observations

Previous hypotheses had suggested that upwelled intrusions of nutrient-rich Gulf of Mexico slope water onto the West Florida Shelf (WFS) led to formation of red tides of Karenia brevis. However, coupled biophysical models of (1) wind- and buoyancy-driven circulation, (2) three phytoplankton groups (diatoms, K. brevis, and microflagellates), (3) these slope water supplies of nitrate and silicate, and (4) selective grazing stress by copepods and protozoans found that diatoms won in one 1998 case of no light limitation by colored dissolved organic matter (CDOM). The diatoms lost to K. brevis during another CDOM case of the models. In the real world, field data confirmed that diatoms were indeed the dominant phytoplankton after massive upwelling in 1998, when only a small red tide of K. brevis was observed. Over a 7-month period of the CDOM-free scenario the simulated total primary production of the phytoplankton community was ∼1.8 g C m−2 d−1 along the 40-m isobath of the northern WFS, with the largest accumulation of biomass on the Florida Middle Ground (FMG). Despite such photosynthesis, these models of the WFS yielded a net source of CO2 to the atmosphere during spring and summer and suggested a small sink in the fall. With diatom losses of 90% of their daily carbon fixation to herbivores the simulation supported earlier impressions of a short, diatom-based food web on the FMG, where organic carbon content of the surficial sediments is tenfold those of the surrounding seabeds. Farther south, the simulated near-bottom pools of ammonium were highest in summer, when silicon regeneration was minimal, leading to temporary Si limitation of the diatoms. Termination of these upwelled pulses of production by diatoms and nonsiliceous microflagellates mainly resulted from nitrate exhaustion in the model, however, mimicking most del15PON observations in the field. Yet, the CDOM-free case of the models failed to replicate the observed small red tide in December 1998, tagged with the del15N signature of nitrogen fixation. A large red tide of K. brevis did form in the CDOM-rich case, when estuarine supplies of CDOM favored the growth of the shade-adapted, ungrazed dinoflagellates. The usual formation of large harmful algal blooms of \u3e1 ug chl L−1 (105 cells L−1) in the southern part of the WFS, between Tampa Bay and Charlotte Harbor, must instead depend upon local aeolian and estuarine supplies of nutrients and CDOM sun screen, not those from the shelf break. In the absence of slope water supplies, local upwelling instead focuses nitrate-poor innocula of co-occurring K. brevis and nitrogen fixers at coastal fronts for both aggregation and transfer of nutrients between these phytoplankton groups