The Leeway of Shipping Containers at Different Immersion Levels

The leeway of 20-foot containers in typical distress conditions is established through field experiments in a Norwegian fjord and in open-ocean conditions off the coast of France with wind speed ranging from calm to 14 m/s. The experimental setup is described in detail and certain recommendations given for experiments on objects of this size. The results are compared with the leeway of a scaled-down container before the full set of measured leeway characteristics are compared with a semi-analytical model of immersed containers. Our results are broadly consistent with the semi-analytical model, but the model is found to be sensitive to choice of drag coefficient and makes no estimate of the cross-wind leeway of containers. We extend the results from the semi-analytical immersion model by extrapolating the observed leeway divergence and estimates of the experimental uncertainty to various realistic immersion levels. The sensitivity of these leeway estimates at different immersion levels are tested using a stochastic trajectory model. Search areas are found to be sensitive to the exact immersion levels, the choice of drag coefficient and somewhat less sensitive to the inclusion of leeway divergence. We further compare the search areas thus found with a range of trajectories estimated using the semi-analytical model with only perturbations to the immersion level. We find that the search areas calculated without estimates of crosswind leeway and its uncertainty will grossly underestimate the rate of expansion of the search areas. We recommend that stochastic trajectory models of container drift should account for these uncertainties by generating search areas for different immersion levels and with the uncertainties in crosswind and downwind leeway reported from our field experiments.Comment: 25 pages, 11 figures and 5 tables; Ocean Dynamics, Special Issue on Advances in Search and Rescue at Sea (2012

Saccharomyces cerevisiae mutants affected in vacuole assembly or vacuolar H+-ATPase are hypersensitive to lead (Pb) toxicity

Lead is an important environmental pollutant. The role of vacuole, in Pb detoxification, was studied using a vacuolar protein sorting mutant strain (vps16Δ), belonging to class C mutants. Cells disrupted in VPS16 gene, did not display a detectable vacuolar-like structure. Based on the loss of cell proliferation capacity, it was found that cells from vps16Δ mutant exhibited a hypersensitivity to Pb-induced toxicity, compared to wild type (WT) strain. The function of vacuolar H+-ATPase (V-ATPase), in Pb detoxification, was evaluated using mutants with structurally normal vacuoles but defective in subunits of catalytic (vma1Δ or vma2Δ) or membrane domain (vph1Δ or vma3Δ) of V-ATPase. All mutants tested, lacking a functional V-ATPase, displayed an increased susceptibility to Pb, comparatively to cells from WT strain. Modification of vacuolar morphology, in Pb-exposed cells, was visualized using a Vma2p-GFP strain. The treatment of yeast cells with Pb originated the fusion of the medium size vacuolar lobes into one enlarged vacuole. In conclusion, it was found that vacuole plays an important role in the detoxification of Pb in Saccharomyces cerevisiae; in addition, a functional V-ATPase was required for Pb compartmentalization.The authors thank the Fundacao para a Ciencia e a Tecnologia (FCT) through the Portuguese Government for their financial support of this work through the grant PEST-OE/EQB/LA0023/2011 to IBB

The NEWMEDS rodent touchscreen test battery for cognition relevant to schizophrenia.

RATIONALE: The NEWMEDS initiative (Novel Methods leading to New Medications in Depression and Schizophrenia, http://www.newmeds-europe.com ) is a large industrial-academic collaborative project aimed at developing new methods for drug discovery for schizophrenia. As part of this project, Work package 2 (WP02) has developed and validated a comprehensive battery of novel touchscreen tasks for rats and mice for assessing cognitive domains relevant to schizophrenia. OBJECTIVES: This article provides a review of the touchscreen battery of tasks for rats and mice for assessing cognitive domains relevant to schizophrenia and highlights validation data presented in several primary articles in this issue and elsewhere. METHODS: The battery consists of the five-choice serial reaction time task and a novel rodent continuous performance task for measuring attention, a three-stimulus visual reversal and the serial visual reversal task for measuring cognitive flexibility, novel non-matching to sample-based tasks for measuring spatial working memory and paired-associates learning for measuring long-term memory. RESULTS: The rodent (i.e. both rats and mice) touchscreen operant chamber and battery has high translational value across species due to its emphasis on construct as well as face validity. In addition, it offers cognitive profiling of models of diseases with cognitive symptoms (not limited to schizophrenia) through a battery approach, whereby multiple cognitive constructs can be measured using the same apparatus, enabling comparisons of performance across tasks. CONCLUSION: This battery of tests constitutes an extensive tool package for both model characterisation and pre-clinical drug discovery.This work was supported by the Innovative Medicine Initiative Joint Undertaking under grant agreement no. 115008 of which resources are composed of EFPIA in-kind contribution and financial contribution from the European Union’s Seventh Framework Programme (FP7/2007-2013). The authors thank Charlotte Oomen for valuable comments on the manuscript.This is the author accepted manuscript. The final version is available from Springer via http://dx.doi.org/10.1007/s00213-015-4007-

BAKTRAK: Backtracking drifting objects using an iterative algorithm with a forward trajectory model

The task of determining the origin of a drifting object after it has been located is highly complex due to the uncertainties in drift properties and environmental forcing (wind, waves and surface currents). Usually the origin is inferred by running a trajectory model (stochastic or deterministic) in reverse. However, this approach has some severe drawbacks, most notably the fact that many drifting objects go through nonlinear state changes underway (e.g., evaporating oil or a capsizing lifeboat). This makes it difficult to naively construct a reverse-time trajectory model which realistically predicts the earliest possible time the object may have started drifting. We propose instead a different approach where the original (forward) trajectory model is kept unaltered while an iterative seeding and selection process allows us to retain only those particles that end up within a certain time-space radius of the observation. An iterative refinement process named BAKTRAK is employed where those trajectories that do not make it to the goal are rejected and new trajectories are spawned from successful trajectories. This allows the model to be run in the forward direction to determine the point of origin of a drifting object. The method is demonstrated using the Leeway stochastic trajectory model for drifting objects due to its relative simplicity and the practical importance of being able to identify the origin of drifting objects. However, the methodology is general and even more applicable to oil drift trajectories, drifting ships and hazardous material that exhibit non-linear state changes such as evaporation, chemical weathering, capsizing or swamping. The backtracking method is tested against the drift trajectory of a life raft and is shown to predict closely the initial release position of the raft and its subsequent trajectory.Comment: 28 pages, 8 figures, 2 table

High-Throughput Screen for Identifying Small Molecules That Target Fungal Zinc Homeostasis

Resistance to traditional antifungal drugs has increased significantly over the past three decades, making identification of novel antifungal agents and new targets an emerging priority. Based on the extraordinary zinc requirement of several fungal pathogens and their well-established sensitivity to zinc deprivation, we developed an efficient cell-based screen to identify new antifungal drugs that target the zinc homeostasis machinery. The screen is based on the zinc-regulated transcription factor Zap1 of Saccharomyces cerevisiae, which regulates transcription of genes like the high-affinity zinc transporter ZRT1. We generated a genetically modified strain of S. cerevisae that reports intracellular zinc deficiency by placing the coding sequence of green fluorescent protein (GFP) under the control of the Zap1-regulated ZRT1 promoter. After showing that the GFP fluorescence signal correlates with low intracellular zinc concentrations in this strain, a protocol was developed for screening small-molecule libraries for compounds that induce Zap1-dependent GFP expression. Comparison of control compounds and known modulators of metal metabolism from the library reveals a robust screen (Z′ = 0.74) and validates this approach to the discovery of new classes of antifungal compounds that interfere with the intracellular zinc homeostasis. Given that growth of many pathogenic organisms is significantly impaired by zinc limitation; these results identify new types of antifungal drugs that target critical nutrient acquisition pathways

Quality Indicators for Colonoscopy Procedures: A Prospective Multicentre Method for Endoscopy Units

BACKGROUND AND AIMS: Healthcare professionals are required to conduct quality control of endoscopy procedures, and yet there is no standardised method for assessing quality. The topic of the present study was to validate the applicability of the procedure in daily practice, giving physicians the ability to define areas for continuous quality improvement. METHODS: In ten endoscopy units in France, 200 patients per centre undergoing colonoscopy were enrolled in the study. An evaluation was carried out based on a prospectively developed checklist of 10 quality-control indicators including five dependent upon and five independent of the colonoscopy procedure. RESULTS: Of the 2000 procedures, 30% were done at general hospitals, 20% at university hospitals, and 50% in private practices. The colonoscopies were carried out for a valid indication for 95.9% (range 92.5-100). Colon preparation was insufficient in 3.7% (range 1-10.5). Colonoscopies were successful in 95.3% (range 81-99). Adenoma detection rate was 0.31 (range 0.17-0.45) in successful colonoscopies. CONCLUSION: This tool for evaluating the quality of colonoscopy procedures in healthcare units is based on standard endoscopy and patient criteria. It is an easy and feasible procedure giving the ability to detect suboptimal practice and differences between endoscopy-units. It will enable individual units to assess the quality of their colonoscopy techniques

MTF-1-Mediated Repression of the Zinc Transporter Zip10 Is Alleviated by Zinc Restriction

The regulation of cellular zinc uptake is a key process in the overall mechanism governing mammalian zinc homeostasis and how zinc participates in cellular functions. We analyzed the zinc transporters of the Zip family in both the brain and liver of zinc-deficient animals and found a large, significant increase in Zip10 expression. Additionally, Zip10 expression decreased in response to zinc repletion. Moreover, isolated mouse hepatocytes, AML12 hepatocytes, and Neuro 2A cells also respond differentially to zinc availability in vitro. Measurement of Zip10 hnRNA and actinomycin D inhibition studies indicate that Zip10 was transcriptionally regulated by zinc deficiency. Through luciferase promoter constructs and ChIP analysis, binding of MTF-1 to a metal response element located 17 bp downstream of the transcription start site was shown to be necessary for zinc-induced repression of Zip10. Furthermore, zinc-activated MTF-1 causes down-regulation of Zip10 transcription by physically blocking Pol II movement through the gene. Lastly, ZIP10 is localized to the plasma membrane of hepatocytes and neuro 2A cells. Collectively, these results reveal a novel repressive role for MTF-1 in the regulation of the Zip10 zinc transporter expression by pausing Pol II transcription. ZIP10 may have roles in control of zinc homeostasis in specific sites particularly those of the brain and liver. Within that context ZIP10 may act as an important survival mechanism during periods of zinc inadequacy

Multiplicity of cerebrospinal fluid functions: New challenges in health and disease

This review integrates eight aspects of cerebrospinal fluid (CSF) circulatory dynamics: formation rate, pressure, flow, volume, turnover rate, composition, recycling and reabsorption. Novel ways to modulate CSF formation emanate from recent analyses of choroid plexus transcription factors (E2F5), ion transporters (NaHCO3 cotransport), transport enzymes (isoforms of carbonic anhydrase), aquaporin 1 regulation, and plasticity of receptors for fluid-regulating neuropeptides. A greater appreciation of CSF pressure (CSFP) is being generated by fresh insights on peptidergic regulatory servomechanisms, the role of dysfunctional ependyma and circumventricular organs in causing congenital hydrocephalus, and the clinical use of algorithms to delineate CSFP waveforms for diagnostic and prognostic utility. Increasing attention focuses on CSF flow: how it impacts cerebral metabolism and hemodynamics, neural stem cell progression in the subventricular zone, and catabolite/peptide clearance from the CNS. The pathophysiological significance of changes in CSF volume is assessed from the respective viewpoints of hemodynamics (choroid plexus blood flow and pulsatility), hydrodynamics (choroidal hypo- and hypersecretion) and neuroendocrine factors (i.e., coordinated regulation by atrial natriuretic peptide, arginine vasopressin and basic fibroblast growth factor). In aging, normal pressure hydrocephalus and Alzheimer's disease, the expanding CSF space reduces the CSF turnover rate, thus compromising the CSF sink action to clear harmful metabolites (e.g., amyloid) from the CNS. Dwindling CSF dynamics greatly harms the interstitial environment of neurons. Accordingly the altered CSF composition in neurodegenerative diseases and senescence, because of adverse effects on neural processes and cognition, needs more effective clinical management. CSF recycling between subarachnoid space, brain and ventricles promotes interstitial fluid (ISF) convection with both trophic and excretory benefits. Finally, CSF reabsorption via multiple pathways (olfactory and spinal arachnoidal bulk flow) is likely complemented by fluid clearance across capillary walls (aquaporin 4) and arachnoid villi when CSFP and fluid retention are markedly elevated. A model is presented that links CSF and ISF homeostasis to coordinated fluxes of water and solutes at both the blood-CSF and blood-brain transport interfaces