Real-time in vivo imaging of platelets, tissue factor and fibrin during arterial thrombus formation in the mouse

We have used confocal and widefield microscopy to image thrombus formation in real time in the microcirculation of a living mouse. This system provides high-speed, near-simultaneous acquisition of images of multiple fluorescent probes and of a brightfield channel. Vascular injury is induced with a laser focused through the microscope optics. We observed platelet deposition, tissue factor accumulation and fibrin generation after laser-induced endothelial injury in a single developing thrombus. The initiation of blood coagulation in vivo entailed the initial accumulation of tissue factor on the upstream and thrombus–vessel wall interface of the developing thrombus. Subsequently tissue factor was associated with the interior of the thrombus. Tissue factor was biologically active, and was associated with fibrin generation within the thrombus

Global clinical response in C ushing's syndrome patients treated with mifepristone

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106755/1/cen12332.pd

Biopolymer additives for the reduction of soil erosion losses during irrigation

High molecular weight, synthetic polyacrylamides (PAM) are relatively large, water soluble polymers that are used increasingly by farmers to prevent erosion and increase infiltration during irrigation. A lab-scale erosion test was conducted to screen biopolymer solutions for a similar efficacy in reducing shear-induced erosion. In lab-scale mini-furrow tests, chitosan, starch xanthate, cellulose xanthate, and acid-hydrolyzed cellulose microfibrils, at concentrations of 20, 80, 80, and 120 ppm respectively, reduced suspended solids in the runoff water from test soil. None of these biopolymers, however, exhibited the >90% runoff sediment reduction shown by PAM at concentrations as low as 5 ppm. Preliminary field tests results showed that chitosan solutions were only marginally effective in reducing runoff from a 137m long furrow. There were indications that results were dependent on the length of the furrow. Erosion of some clay-rich soils from Northern California was reduced up to 85% by increasing the concentration of exchangeable calcium to >2.5mMole, with or without the addition of polymer additives

Accumulation of Tissue Factor Into Developing Thrombi In Vivo Is Dependent Upon Microparticle P-Selectin Glycoprotein Ligand 1 And Platelet P-Selectin

Using a laser-induced endothelial injury model, we examined thrombus formation in the microcirculation of wild-type and genetically altered mice by real-time in vivo microscopy to analyze this complex physiologic process in a system that includes the vessel wall, the presence of flowing blood, and the absence of anticoagulants. We observe P-selectin expression, tissue factor accumulation, and fibrin generation after platelet localization in the developing thrombus in arterioles of wild-type mice. However, mice lacking P-selectin glycoprotein ligand 1 (PSGL-1) or P-selectin, or wild-type mice infused with blocking P-selectin antibodies, developed platelet thrombi containing minimal tissue factor and fibrin. To explore the delivery of tissue factor into a developing thrombus, we identified monocyte-derived microparticles in human platelet–poor plasma that express tissue factor, PSGL-1, and CD14. Fluorescently labeled mouse microparticles infused into a recipient mouse localized within the developing thrombus, indicating that one pathway for the initiation of blood coagulation in vivo involves the accumulation of tissue factor– and PSGL-1–containing microparticles in the platelet thrombus expressing P-selectin. These monocyte-derived microparticles bind to activated platelets in an interaction mediated by platelet P-selectin and microparticle PSGL-1. We propose that PSGL-1 plays a role in blood coagulation in addition to its known role in leukocyte trafficking

Accumulation of Tissue Factor into Developing Thrombi In Vivo Is Dependent upon Microparticle P-Selectin Glycoprotein Ligand 1 and Platelet P-Selectin

Using a laser-induced endothelial injury model, we examined thrombus formation in the microcirculation of wild-type and genetically altered mice by real-time in vivo microscopy to analyze this complex physiologic process in a system that includes the vessel wall, the presence of flowing blood, and the absence of anticoagulants. We observe P-selectin expression, tissue factor accumulation, and fibrin generation after platelet localization in the developing thrombus in arterioles of wild-type mice. However, mice lacking P-selectin glycoprotein ligand 1 (PSGL-1) or P-selectin, or wild-type mice infused with blocking P-selectin antibodies, developed platelet thrombi containing minimal tissue factor and fibrin. To explore the delivery of tissue factor into a developing thrombus, we identified monocyte-derived microparticles in human platelet–poor plasma that express tissue factor, PSGL-1, and CD14. Fluorescently labeled mouse microparticles infused into a recipient mouse localized within the developing thrombus, indicating that one pathway for the initiation of blood coagulation in vivo involves the accumulation of tissue factor– and PSGL-1–containing microparticles in the platelet thrombus expressing P-selectin. These monocyte-derived microparticles bind to activated platelets in an interaction mediated by platelet P-selectin and microparticle PSGL-1. We propose that PSGL-1 plays a role in blood coagulation in addition to its known role in leukocyte trafficking

The CuSPED Mission: CubeSat for GNSS Sounding of the Ionosphere-Plasmasphere Electron Density

The CubeSat for GNSS Sounding of Ionosphere-Plasmasphere Electron Density (CuSPED) is a 3U CubeSat mission concept that has been developed in response to the NASA Heliophysics program's decadal science goal of the determining of the dynamics and coupling of the Earth's magnetosphere, ionosphere, and atmosphere and their response to solar and terrestrial inputs. The mission was formulated through a collaboration between West Virginia University, Georgia Tech, NASA GSFC and NASA JPL, and features a 3U CubeSat that hosts both a miniaturized space capable Global Navigation Satellite System (GNSS) receiver for topside atmospheric sounding, along with a Thermal Electron Capped Hemispherical Spectrometer (TECHS) for the purpose of in situ electron precipitation measurements. These two complimentary measurement techniques will provide data for the purpose of constraining ionosphere-magnetosphere coupling models and will also enable studies of the local plasma environment and spacecraft charging; a phenomenon which is known to lead to significant errors in the measurement of low-energy, charged species from instruments aboard spacecraft traversing the ionosphere. This paper will provide an overview of the concept including its science motivation and implementation

Preventing soil erosion with polymer additives

The agricultural use of polyacrylamide, PAM, as an additive in irrigation water has grown rapidly since commercial introduction in 1995, with over l million acres treated in 1998. PAM provides both economic and environmental benefits by improving water infiltration and reducing up to 98% of erosion-induced soil losses — a yearly saving of tons of topsoil per acre. With as little as 5 ppm of PAM in the first irrigation water to run across the field, soil cohesion increases enough to prevent particle detachment and erosion. Stable soil/polymer flocs result from PAM's high molecular weight (typically > 12 million) and its affinity to soil via coulombic and Van der Waals attraction. Although water soluble linear PAM is the only class of commercial polymer presently used to reduce erosion during irrigation, other polymer additives have shown some potential. Biopolymers such as chitosan, starch xanthate, cellulose xanthate, and acid-hydrolyzed cellulose microfibrils reduce shear-induced erosion; however concentrations at least 6-10 times higher than PAM are required to obtain the > 90% runoff sediment reduction shown by commercial PAM. The application of PAM in agricultural irrigation water and potential biopolymer alternatives to PAM are discusse

Platelet PECAM-1 Inhibits Thrombus Formation In Vivo

Platelet endothelial cell adhesion molecule-1 (PECAM-1) is a cell surface glycoprotein receptor expressed on a range of blood cells including platelets, and is also on vascular endothelial cells. PECAM-1 possesses adhesive and signalling properties, the latter being mediated by an Immunoreceptor Tyrosine-based Inhibitory Motif present on the cytoplasmic tail of the protein. Recent studies in vitro have demonstrated that PECAM-1 signalling inhibits the aggregation of platelets. In the present study we have utilised PECAM-1 deficient mice and radiation chimeras to investigate the function of this receptor in the regulation of thrombus formation. Using intravital microscopy and laser induced injury to cremaster muscle arterioles, we show that thrombi formed in PECAM-1 deficient mice were larger, formed more rapidly than in control mice and were more stable. Larger thrombi were also formed in control mice transplanted with PECAM-1 deficient bone marrow, in comparison to control-transplanted mice. A ferric chloride model of thrombosis was used to investigate thrombus formation in carotid arteries. In PECAM-1 deficient mice the time to 75% vessel occlusion was significantly shorter than in control mice. These data provide evidence for the involvement of platelet PECAM-1 in the negative regulation of thrombus formation

Estimating hydrodynamic roughness in a wave-dominated environment with a high-resolution acoustic Doppler profiler

Author Posting. © American Geophysical Union, 2005. 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 110 (2005): C06014, doi:10.1029/2003JC001814.Hydrodynamic roughness is a critical parameter for characterizing bottom drag in boundary layers, and it varies both spatially and temporally due to variation in grain size, bedforms, and saltating sediment. In this paper we investigate temporal variability in hydrodynamic roughness using velocity profiles in the bottom boundary layer measured with a high-resolution acoustic Doppler profiler (PCADP). The data were collected on the ebb-tidal delta off Grays Harbor, Washington, in a mean water depth of 9 m. Significant wave height ranged from 0.5 to 3 m. Bottom roughness has rarely been determined from hydrodynamic measurements under conditions such as these, where energetic waves and medium-to-fine sand produce small bedforms. Friction velocity due to current u *c and apparent bottom roughness z 0a were determined from the PCADP burst mean velocity profiles using the law of the wall. Bottom roughness k B was estimated by applying the Grant-Madsen model for wave-current interaction iteratively until the model u *c converged with values determined from the data. The resulting k B values ranged over 3 orders of magnitude (10−1 to 10−4 m) and varied inversely with wave orbital diameter. This range of k B influences predicted bottom shear stress considerably, suggesting that the use of time-varying bottom roughness could significantly improve the accuracy of sediment transport models. Bedform height was estimated from k B and is consistent with both ripple heights predicted by empirical models and bedforms in sonar images collected during the experiment