Applying FAIR Principles to Plant Phenotypic Data Management in GnpIS.

GnpIS is a data repository for plant phenomics that stores whole field and greenhouse experimental data including environment measures. It allows long-term access to datasets following the FAIR principles: Findable, Accessible, Interoperable, and Reusable, by using a flexible and original approach. It is based on a generic and ontology driven data model and an innovative software architecture that uncouples data integration, storage, and querying. It takes advantage of international standards including the Crop Ontology, MIAPPE, and the Breeding API. GnpIS allows handling data for a wide range of species and experiment types, including multiannual perennial plants experimental network or annual plant trials with either raw data, i.e., direct measures, or computed traits. It also ensures the integration and the interoperability among phenotyping datasets and with genotyping data. This is achieved through a careful curation and annotation of the key resources conducted in close collaboration with the communities providing data. Our repository follows the Open Science data publication principles by ensuring citability of each dataset. Finally, GnpIS compliance with international standards enables its interoperability with other data repositories hence allowing data links between phenotype and other data types. GnpIS can therefore contribute to emerging international federations of information systems.

Mining Plant Genomic and Genetic Data Using the GnpIS Information System.

GnpIS is an information system designed to help scientists working on plants and fungi to decipher the molecular and genetic architecture of trait variations by facilitating the navigation through genetic, genomic, and phenotypic information. The purpose of the present chapter is to illustrate how users can (1) explore datasets from phenotyping experiments in order to build new datasets for studying genotype × environment interactions in traits, (2) browse into the results of other genetic analysis data such as GWAS to generate or check working hypothesis about candidate genes or to identify important alleles and germplasms for breeding programs, and (3) explore the polymorphism in specific area of the genome using InterMine, JBrowse tools embedded in the GnpIS information system.

Chondrocyte deformation induces mitochondrial distortion and heterogeneous intracellular strain fields.

Chondrocyte mechanotransduction is poorly understood but may involve cell deformation and associated distortion of intracellular structures and organelles. This study quantifies the intracellular displacement and strain fields associated with chondrocyte deformation and in particular the distortion of the mitochondria network, which may have a role in mechanotransduction. Isolated articular chondrocytes were compressed in agarose constructs and simultaneously visualised using confocal microscopy. An optimised digital image correlation technique was developed to calculate the local intracellular displacement and strain fields using confocal images of fluorescently labelled mitochondria. The mitochondria formed a dynamic fibrous network or reticulum, which co-localised with microtubules and vimentin intermediate filaments. Cell deformation induced distortion of the mitochondria, which collapsed in the axis of compression with a resulting loss of volume. Compression generated heterogeneous intracellular strain fields indicating mechanical heterogeneity within the cytoplasm. The study provides evidence supporting the potential involvement of mitochondrial deformation in chondrocyte mechanotransduction, possibly involving strain-mediated release of reactive oxygen species. Furthermore the heterogeneous strain fields, which appear to be influenced by intracellular structure and organisation, may generate significant heterogeneity in mechanotransduction behaviour for cells subjected to identical levels of deformation.

Immunisation of fish by bath immersion using ultrasound.

Ultrasonic irradiations (USI) as a means to open routes in the skin, thus facilitating the transdermal delivery of vaccines that will improve the effectiveness of vaccination by immersion, are reviewed in this paper. Based on our recent results in goldfish and carp it could be summarized that: (i) USI significantly improved the antigen uptake and enhanced antibody response; (ii) the requirements for high antigen concentrations, which are needed for simple bath immersion, could be considerably reduced in presonicated fish; (iii) after bath immersion, the antigen was slowly released from the skin to the blood in which its presence could still be detected 24 hours later. This retardation of the antigen in the skin was suggested to be due to a possible interaction with cells of the local immune system, in which it is processed and recognized. It is concluded that the recent advances in biotechnology of immunization with recombinant DNA and the use of DNA vaccines, together with the improvement of their administration using USI, provide interesting prospects for the further application of vaccines against viral and even parasitic diseases of fish.

Chromate concentration bias in primer paint particles.

Chromate-containing primer paints are used to prevent corrosion on metal surfaces. Chromate contains hexavalent chromium (Cr6+), a human carcinogen. The objective of this research was to determine if there is a bias in the fraction of chromate found in various particle sizes generated during primer painting operations. A solvent-based, aviation primer paint was sprayed using a high-volume, low-pressure spray gun. Paint particles were collected and separated by size with seven-stage cascade impactors. It was determined that particles with a mass aerodynamic diameter < 2.0 microm contained significantly less Cr6+ per dry weight of paint than particles > 2.0 microm (P < 0.001). The median concentration of Cr6+ in particles < 2.0 microm is 18 micro g of Cr/mg of dry paint and the median concentration for particles > 2.0 microm is 70 microg of Cr/mg of dry paint. The mixed paint contains 18.75% strontium chromate, which equates to a ratio of 67 microg of Cr/mg of dry paint. Particles > 2.0 microm are more likely to impact in the upper tracheobronchial regions of the lung where mucociliary clearance is relatively rapid. Additionally, chromate emissions from spraying operations may be overestimated because larger particles, which are more easily trapped on an air filter, contain more chromate than the smaller particles, which are more likely to bypass an air filter.

Acute neurobehavioral effects in rats from exposure to HFC 134a or CFC 12.

1,1,1,2-Tetrafluoroethane (HFC 134a), a chlorine-free hydrofluoroalkane, is internationally replacing billions of pounds of dichlorodifluoromethane (CFC 12) for coolant, refrigerant and aerosol propellant applications. The ALC50 for HFC 134a in rats is 567,000 ppm for 4 h; its potential for cardiac epinephrine sensitization in beagle dogs is acceptable (75,000 ppm); and its capacity to induce carcinogenicity or developmental disorders in animals is minimal. HFC 134a, with a serum half life estimated at 4-11 min, has been accepted for use as a propellant in metered-dose inhalant products, implying a low human toxicity risk from periodic brief exposures. There has been little published human or animal research evaluating possible neurobehavioral toxicity from longer HFC 134a exposures, as may be expected to occur in operational scenarios. In this study, male Wistar rats were exposed to various concentrations of HFC 134a or CFC 12 for up to 30 min while performing in either a rotarod/motorized running wheel apparatus or in an operant chamber The relative neurobehavioral toxicity of CFC 12 and its ozone-depleting substance replacement HFC 134a was assessed by comparing both gross motor system incapacitation and more subtle changes in ability to perform an operant discrimination task. It was shown that exposure to HFC 134a or CFC 12 concentrations from 40,000 to 470,000 ppm, for up to 30 min, induced neurobehavioral deficits in every subject, ranging from reduced operant efficiency to apparent anesthesia. For neurobehavioral endpoints examined in these experiments, HFC 134a inhalation was shown to induce deficits more rapidly, and at lower concentrations when compared to CFC 12 exposure.

Preliminary investigations of ultrasound induced acoustic streaming using particle image velocimetry.

Particle image velocimetry was used to investigate ultrasound-induced acoustic streaming in a system for the enhanced uptake of substances from the aquatic medium into fish. Four distinct regions of the induced streaming in the system were observed and measured. One of the regions was identified as an preferential site for substance uptake, where the highest velocities in proximity to the fish surface were measured. A positive linear relationship was found between the ultrasound intensity and the maximum streaming velocity, where a unitless geometric factor, specific to the system, was calculated for correcting the numerical relationship between the two parameters. The results are part of a comprehensive study aimed at improving mass transdermal administrations of substances (e.g. vaccines, hormones) into fish from the aquatic medium.

Gas bubble pulsation in a semiconfined space subjected to ultrasound.

In the case of ultrasound application in biological tissues, gas bubbles might form and collapse within cells, in the intercellular spaces and on tissue surfaces. In this work the effect of confined space on the behavior of the gas bubble in the presence of ultrasonic field is studied. A numerical model for bubble pulsation in a planar liquid layer, bounded by two rigid walls, is developed. Surface tension at the interface between the host liquid and the gas in the bubble is considered as well. A mathematical statement and solution technique based on the boundary integral method are presented. In some cases, the bubble divides into two symmetrical parts and high-velocity jets are generated, aimed at the walls. The final velocity of the jets strongly depends on the surface tension of the host liquid. Two new parameters that predict the occurrence of jet formation are developed.

A typical path model of tracheobronchial clearance of inhaled particles in rats.

A mathematical description of particle clearance from the ciliated conducting airways (tracheobronchial region) of the lungs in rats was developed, assuming that particles on the mucus blanket behave as a fluid and adhere to principles of fluid flow described by the continuity equation. Effective particle transport velocities for given generations of airways were estimated from reported tracheal mucus velocities. Using typical rat airway geometry and estimated particle transport velocities, solutions of sets of rate equations for transport from each generation of airways were summed to estimate total particle clearance from the tracheobronchial region of the lung as a function of time. Aerosol particle size distribution (MMAD ranging from 0.1 to 4.2 microm, and sigma(g) from 1 to 2.7) and concentration data from several investigators were used to predict short-term, tracheobronchial clearance (retention) in rats up to 24 h following exposure. Comparisons between predicted and observed retention showed an average difference between model predictions, and observed fractional retention of initial lung or body burden was 4.9%, with a tendency toward underprediction of clearance of particles >3.0 microm.

Ultrasound-facilitated transport of silver chloride (AgCl) particles in fish skin.

Electron-dense nano-particles in aqueous suspension were administered by immersion into the epidermis of fish using ultrasound in the therapeutic range. Enhanced permeability of the tissues to the particles was achieved by acoustic cavitation, which induced a controlled level of necrosis in the outer cell layers, and by non-cavitational exposures, which widened intercellular spaces of non-necrosed tissue in deeper regions of the epidermis. Both particle concentration and penetration depth were quantified using transmission electron microscopy. While cavitation-induced perforation was necessary for particles to penetrate into the tissues, non-cavitational exposures during immersions increased the particle flux towards the skin surface, as well as the diffusion rate of the particles within the epidermis and their depth of penetration. The technique described above may potentially be applied for non-stressful, mass-administration of substances into aquatic animals, as well as the relatively new field of ultrasound-facilitated delivery in moist epithelial tissues in humans.

A prospective, randomized, controlled trial of high and low maintenance doses of magnesium sulfate for acute tocolysis.

OBJECTIVE: This study was undertaken to compare a high-dose protocol for magnesium sulfate tocolytic therapy with a low-dose regimen with respect to time needed to achieve tocolysis. STUDY DESIGN: Patients between 24 and 34 weeks' gestation with preterm labor were included. Patients with ruptured membranes or nonreassuring fetal assessments were excluded. Gravid women received a 4-g loading dose of magnesium sulfate and were prospectively randomly assigned to receive a maintenance dose of 2 or 5 g/h. RESULTS: The median times to tocolysis were 120 minutes (semi-interquartile range, 30 minutes) in the low-dose group and 90 minutes (semi-interquartile range, 28 minutes) in the high-dose group (P <.001). CONCLUSION: Patients treated with a higher maintenance dose of magnesium sulfate had a higher frequency of side effects; however, tocolysis was achieved more rapidly and they required shorter admissions to the labor and delivery unit without increased maternal or neonatal morbidity.

Ultrasound-induced intercellular space widening in fish epidermis.

Transmission electron microscopy was employed to determine the effects of therapeutic ultrasound (US) (I(sata) < or =2.2 W cm(-2), 3 MHz), sonicated at different angles and durations, on the external epithelia of fish skin. Sonication at 1.7 W cm(-2) (90 s), where the ultrasonic beam was perpendicular to the skin surface, produced minor intercellular space widening (ICSW), as well as the disruption of desmosomes connecting between the cells. Increasing the intensity to 2.2 W cm(-2) increased ICSW, the extent of which was positively correlated to the duration of exposure (30 to 90 s). Perpendicular sonication produced ICSW, almost exclusively between cells of the two outermost cell layers, parallel to the skin surface. Sonicating at 45 degrees (2.2 W cm(-2), 90 s) produced ICSW in deeper cell layers in the tissues, in which the spaces were at seemingly random orientations. Mucous cells and macrophages were also found to be damaged, as were apoptotic epidermal cells. The suggested mechanism for ICSW is the formation of transverse (shear) waves at the interface between the aquatic medium and the skin surface. The waves, which are damped out within a few cell layers, give rise to shear stresses that, in turn, cause strains that act to separate between cells and damage some of the relatively weaker cells.

Ultrasound-induced cavitation damage to external epithelia of fish skin.

Transmission electron microscopy was used to show the effects of therapeutic ultrasound (< or = 1.0 W/cm2, 1 MHz) on the external epithelia of fish skin. Exposures of up to 90 s produced damage to 5 to 6 of the outermost layers. Negligible temperature elevations and lack of damage observed when using degassed water indicated that the effects were due to cavitation. The minimal intensity was determined for inducing cellular damage, where the extent and depth of damage to the tissues was correlated to the exposure duration. The results may be interpreted as a damage front, advancing slowly from the outer cells inward, presumably in association with the slow replacement of the perforated cell contents with the surrounding water. This study illustrates that a controlled level of microdamage may be induced to the outer layers of the tissues.

Collagen arrangement in hepatic granuloma in mice infected with Schistosoma mansoni: dependence on fiber radiation centers.

The collagen structure of isolated and in situ liver granuloma from Swiss Webster mice infected with Schistosoma mansoni was sequentially and three-dimensionally analyzed during different times of infection (early acute, acute, transitional acute-chronic, and chronic phases) by laser scanning confocal microscopy and electron scanning variable vacuum microscopy. The initial granuloma structure is characterized by vascular collagen residues and by anchorage points (or fiber radiation centers), from where collagenous fibers are angularly shed and self-assembled. During the exudative-productive stage, the self-assembly of these fibers minimizes energy and mass through continuous tension and focal compression. The curvature or angles between collagen fibers probably depends on the fibroblastic or myofibroblastic organization of stress fibers. Gradually, the loose unstable lattice of the exudative-productive stage transforms into a highly packed and stable architecture as a result of progressive compactness. The three-dimensional architecture of granulomas provides increased tissue integrity, efficient distribution of soluble compounds and a haptotactic background to the cells.

A physiological model for predicting carboxyhemoglobin formation from exposure to carbon monoxide in rats.

A time-dependent simulation model, based on the Coburn-Forster-Kane equation, was written in Advanced Continuous Simulation Language to predict carboxyhemoglobin (HbCO) formation and dissociation in F-344 rats during and after exposure to 500 parts/million CO for 1 h. Blood-gas analysis and CO-oximetry were performed on samples collected during exposure and off-gassing of CO. Volume displacement plethysmography was used to measure minute ventilation (VE) during exposure. CO diffusing capacity in the lung (DLCO) was also measured. Other model parameters measured in the animals included blood pH, total blood volume, and Hb concentration. Comparisons between model predictions using values for VE, DLCO, and the Haldane coefficient cited in the literature and predictions using measured VE, DLCO, and calculated Haldane coefficient for individual animals were made. General model predictions using values for model parameters derived from the literature agreed with published HbCO values by a factor of 0.987 but failed to simulate experimental data. On average, the general model overpredicted measured HbCO level by nearly 9%. A specific model using the means of measured variables predicted HbCO concentration within a factor of 0.993. When experimentally observed parameter fluctuations were included, the specific model predictions reflected experimental effects on HbCO formation.

Collagen arrangement in hepatic granuloma in mice infected with Schistosoma mansoni: dependence on fiber radiation centers

The collagen structure of isolated and in situ liver granuloma from Swiss Webster mice infected with Schistosoma mansoni was sequentially and three-dimensionally analyzed during different times of infection (early acute, acute, transitional acute-chronic, and chronic phases) by laser scanning confocal microscopy and electron scanning variable vacuum microscopy. The initial granuloma structure is characterized by vascular collagen residues and by anchorage points (or fiber radiation centers), from where collagenous fibers are angularly shed and self-assembled. During the exudative-productive stage, the self-assembly of these fibers minimizes energy and mass through continuous tension and focal compression. The curvature or angles between collagen fibers probably depends on the fibroblastic or myofibroblastic organization of stress fibers. Gradually, the loose unstable lattice of the exudative-productive stage transforms into a highly packed and stable architecture as a result of progressive compactness. The three-dimensional architecture of granulomas provides increased tissue integrity, efficient distribution of soluble compounds and a haptotactic background to the cells

Breathing zone particle size and lead concentration from sanding operations to remove lead based paints.

The relationship between lead concentration in the dry film of lead based paints applied to steel bulkheads aboard ship, the lead concentration found in the air when the paint is removed by mechanical means, and blood lead concentrations of workers involved in lead based paint removal has not been well characterized. Intuitively a direct relationship must exist but confounding factors confuse the issue. Simultaneous sampling procedures from the same paint removal operation may differ by several orders of magnitude. The process from dried film to aerosol (airborne dust) exposure, and on to dose can be separated into two major phases; (1) generation of the dust and its transport through the air to the worker and (2) uptake and dose related factors within the body. Both phases involve complex interactions and there are a number of factors within each phase that significantly affect the potential lead dose for the worker. This study attempts to clarify the mechanisms involved in the generation and transportation of the dust to the worker by evaluating the relationship of a number of key factors on particle size and lead distribution within the aerosol dust generated when lead based paint is removed by sanding. The study examined the relationship between particle size in the dust and grit size of the abrasive. It also examined the distribution of lead within selected particle sizes. The Mass Median Aerodynamic Diameter (MMAD) was used as an indicator of change in the particle size distribution. Particle size distributions were evaluated using a TSI Aerodynamic Particle Sizer, a five stage cyclone and scanning electron microscopy. Lead distribution was determined using the five stage cyclone, and personal or area samples analyzed using inductively coupled plasma (ICP). Mass concentrations were evaluated using a MIE Mass Concentration Analyzer and gravimetric analysis of filter samples collected in the breathing zone. Student's t-tests were used to evaluate changes in MMADs, mass concentrations and other indices for inter and intra-grit size samples. Correlation coefficients (Pearson's r) were used to determine the relationship between factors. Findings of the research indicated that the particle size distribution in the dust is directly related to the grit size of the abrasive (i.e. inversely related to the abrasive grit number). Particulate mass concentrations of dust varied directly with abrasive grit number. The distribution of lead did not appear to be affected by grit size of the abrasive in that the lead distribution within the particle size ranges remained homogeneous and consistent with the lead concentration in the dried film. Mass concentrations of lead in air samples varied directly with lead concentration in the bulk coating. Results of this project, coordinated with deposition modeling and bioavailability studies will be useful in the development of a model to characterize lead dose to workers based on known parameters within the work specifications.

Acute lung injury, acute respiratory distress syndrome and inhalation injury: an overview.

Acute Lung Injury (ALI) and the Acute Respiratory Distress Syndrome (ARDS) are severe respiratory diseases that have a very poor prognosis and have numerous causes. Despite a great deal of research and investigation since the initial description of ARDS 30 years ago many questions about the pathogenesis, treatment and outcome of the disease remain unanswered. Although there is evidence to suggest that outcome of ALI and ARDS is improving, the reasons why are unknown and there is not yet a well developed treatment for these diseases. Inhalation injury resulting from exposure to pyrolysis and combustion atmospheres is among the causes of ALI/ARDS. Little is known of the mechanisms of fire related inhalation injury that results in the development of ALI/ARDS. There is a paucity of information about fire atmosphere exposure response relationships for smoke-induced inhalation injury. Although there is considerable information about the pulmonary toxicity of many of the more common constituents of fire atmospheres, little is known about the pulmonary toxicity of mixtures of these constituents. Fire related pulmonary health risks are of particular concern to the Navy due to the limited opportunity to escape the inhalation hazards posed by shipboard fires. Consequently the Naval Medical Research Institute Detachment (Toxicology) has undertaken a research program to develop research models of combustion atmosphere induced ALI/ARDS which can be exploited to systematically address some of the questions surrounding fire related ALI/ARDS. ALI/ARDS has been the topic of a vast amount of research, numerous symposia, working groups and their published proceedings, book chapters, and books. Less information is available regarding experimental models of smoke induced lung damage, however the literature on the subject is extensive. Consequently this article is intended to provide the reader with a primer or cursory "overview" of ALI and ARDS from a toxicological perspective and should not be considered comprehensive.

Calculation of exposure chamber leak rate with thermal correction: a measure of chamber integrity.

A method for assessing inhalation exposure chamber integrity by calculation of leak rate was modified to account for temporal changes of temperature in the chamber. In a well-sealed chamber, accounting for thermal effect brought observed leak rates into better agreement with predicted values. Mean estimates of chamber leak rate without thermal correction ranged from 2.9 to 40.6 cm3/min whereas those with thermal correction ranged from 9.6 to 14.3 cm3/min. The average change in estimate of chamber leak rate brought about by correcting for thermal effect was 16.8 cm3/min per K change of temperature in the chamber. Accounting for thermal effect reduced the coefficient of variation for repeated estimates (n = 10) of chamber leak rate from 65 to 15%. The use of temperature-corrected calculation of chamber leak rate minimizes thermal artifact thereby improving decisions about chamber operation based on assessment of chamber integrity.

Histoarchitecture of schistosomal granuloma development and involution: morphogenetic and biomechanical approaches.

The authors present morphogenetic and biomechanical approaches on the concept of the Schistosoma mansoni granulomas, considering them as organoid structures that depend on cellular adhesion and sorting, forming rearrangement into hierarchical concentric layers, creating tension-dependent structures, aiming to acquire round form, since this is the minimal energy form, in which opposing forces pull in equally from all directions and are in balance. From the morphogenetic point of view, the granulomas function as little organs, presenting maturative and involutional stages in their development with final disappearance (pre-granulomatous stages, subdivided in: weakly and/or initial reactive and exudative; granulomatous stages: exudative-productive, productive and involutional). A model for the development of granulomas was suggested, according to the following stages: encapsulating, focal histolysis, fiber production, orientation and compacting and involution and disintegration. The authors concluded that schistosomal granuloma is not a tangled web of individual cells and fibers, but an organized structure composed by host and parasite components, which is not formed to attack the miracidia, but functions as an hybrid interface between two different phylogenetic beings.