3,158 research outputs found
Hereditary and acquired protein S deficiencies are associated with low TFPI levels in plasma.
No full textJ Thromb Haemost. 2010 Feb;8(2):294-300. Epub 2009 Nov 30.
Hereditary and acquired protein S deficiencies are associated with low TFPI
levels in plasma.
Castoldi E, Simioni P, Tormene D, Rosing J, Hackeng TM.
Department of Biochemistry, CARIM, Maastricht University, Maastricht, the
Netherlands. [email protected]
BACKGROUND: Protein S and tissue factor pathway inhibitor (TFPI) act together in
down-regulating coagulation.
OBJECTIVE: To investigate the TFPI/protein S system in hereditary and acquired
protein S deficiency.
METHODS: Plasma antigen levels of protein S and full-length TFPI were determined
in heterozygous type I protein S-deficient individuals (n=35), patients on oral
anticoagulant treatment (OAT) (n=29), oral contraceptive (OC) users (n=10) and
matched controls. Thrombin generation was determined using calibrated automated
thrombography.
RESULTS: Full-length TFPI levels were lower in type I protein S-deficient
individuals (76.8+/-33.8%) than in age- and sex-matched controls (128.0+/-59.4%,
P<0.001). Among protein S-deficient individuals with thrombosis, those on OAT had
not only lower total protein S levels (25.7+/-8.2% vs. 54.7+/-8.2%, P<0.001), but
also lower full-length TFPI levels (52.6+/-15.0% vs. 75.4+/-22.9%, P=0.009) than
those not on OAT. Similarly, OC users had lower protein S (73.8+/-11.5% vs.
87.9+/-10.8%, P=0.005) and full-length TFPI levels (73.7+/-27.7% vs.
106.4+/-29.2%, P=0.007) than non-users. When triggered with tissue factor, plasma
from protein S-deficient individuals generated 3-5-fold more thrombin than
control plasma. The difference was only partially corrected by normalization of
the protein S level, full correction requiring additional normalization of the
TFPI level. Protein S-immunodepletion experiments indicated that free protein S
and full-length TFPI form a complex in plasma, and the protein S/TFPI interaction
was confirmed by surface plasmon resonance analysis.
CONCLUSIONS: Full-length TFPI binds to protein S in plasma and is reduced in
genetic and acquired protein S deficiency. The concomitant TFPI deficiency
substantially contributes to the hypercoagulable state associated with protein S
deficiency.
PMID: 20002538 [PubMed - indexed for MEDLINE
Thrombin generation-based assays to measure the activity of the TFPI-protein S pathway in plasma from normal and protein S-deficient individuals.
No full textSimilar hypercoagulable state and thrombosis risk in type I and type III proteinS-deficient individuals from mixed type I/III families.
No full textHaematologica. 2010 Sep;95(9):1563-71. Epub 2010 Apr 26.
Similar hypercoagulable state and thrombosis risk in type I and type III protein
S-deficient individuals from families with mixed type I/III protein S deficiency.
Castoldi E, Maurissen LF, Tormene D, Spiezia L, Gavasso S, Radu C, Hackeng TM,
Rosing J, Simioni P.
Department of Biochemistry, Maastricht University P.O. Box 616, 6200 Maastricht,
The Netherlands. [email protected]
BACKGROUND: Protein S, which circulates in plasma in both free and bound forms,
is an anticoagulant protein that stimulates activated protein C and tissue factor
pathway inhibitor. Hereditary type I protein S deficiency (low total and low free
protein S) is a well-established risk factor for venous thrombosis, whereas the
thrombosis risk associated with type III deficiency (normal total and low free
protein S) has been questioned.
DESIGN AND METHODS: Kaplan-Meier analysis was performed on 242 individuals from
30 families with protein S deficiency. Subjects were classified as normal, or
having type I or type III deficiency according to their total and free protein S
levels. Genetic and functional studies were performed in 23 families (132
individuals).
RESULTS: Thrombosis-free survival was not different between type I and type III
protein S-deficient individuals. Type III deficient individuals were older and
had higher protein S, tissue factor pathway inhibitor and prothrombin levels than
type I deficient individuals. Thrombin generation assays sensitive to the
activated protein C- and tissue factor pathway inhibitor-cofactor activities of
protein S revealed similar hypercoagulable states in type I and type III protein
S-deficient plasma. Twelve PROS1 mutations and two large deletions were
identified in the genetically characterized families.
CONCLUSIONS: Not only type I, but also type III protein S deficiency is
associated with a hypercoagulable state and increased risk of thrombosis. These
findings may, however, be restricted to type III deficient individuals from
families with mixed type I/III protein S deficiency, as these represented 80% of
type III deficient individuals in our cohort.
PMCID: PMC2930959
PMID: 20421270 [PubMed - in process
Type III protein S deficiency is associated with a hypercoagulable state and an increased risk of venous thrombosis
No full textAntisense-based RNA therapy of factor V deficiency: in vitro and ex vivo rescue of a F5 deep-intronic splicing mutation
No full textAntisense molecules are emerging as a powerful tool to correct splicing defects. Recently, we identified a homozygous deep-intronic mutation (F5 c.1296+268A>G) activating a cryptic donor splice site in a patient with severe coagulation factor V (FV) deficiency and life-threatening bleeding episodes. Here, we assessed the ability of 2 mutation-specific antisense molecules (a morpholino oligonucleotide [MO] and an engineered U7 small nuclear RNA [snRNA]) to correct this splicing defect. COS-1 and HepG2 cells transfected with a F5 minigene construct containing the patient's mutation expressed aberrant messenger RNA (mRNA) in excess of normal mRNA. Treatment with mutation-specific antisense MO (1-5 mu M) or a construct expressing antisense U7snRNA (0.25-2 mu g) dose-dependently increased the relative amount of correctly spliced mRNA by 1 to 2 orders of magnitude, whereas control MO and U7snRNA were ineffective. Patient-derived megakaryocytes obtained by differentiation of circulating progenitor cells did not express FV, but became positive for FV at immunofluorescence staining after administration of antisense MO or U7snRNA. However, treatment adversely affected cell viability, mainly because of the transfection reagents used to deliver the antisense molecules. Our data provide in vitro and ex vivo proof of principle for the efficacy of RNA therapy in severe FV deficiency, but additional cytotoxicity studies are warranted
Similar hypercoagulable state and thrombosis risk in type Iand type III protein S-deficient individuals from families with mixed type I/IIIprotein S deficiency.
No full textBACKGROUND:
Protein S, which circulates in plasma in both free and bound forms, is an anticoagulant protein that stimulates activated protein C and tissue factor pathway inhibitor. Hereditary type I protein S deficiency (low total and low free protein S) is a well-established risk factor for venous thrombosis, whereas the thrombosis risk associated with type III deficiency (normal total and low free protein S) has been questioned.
DESIGN AND METHODS:
Kaplan-Meier analysis was performed on 242 individuals from 30 families with protein S deficiency. Subjects were classified as normal, or having type I or type III deficiency according to their total and free protein S levels. Genetic and functional studies were performed in 23 families (132 individuals).
RESULTS:
Thrombosis-free survival was not different between type I and type III protein S-deficient individuals. Type III deficient individuals were older and had higher protein S, tissue factor pathway inhibitor and prothrombin levels than type I deficient individuals. Thrombin generation assays sensitive to the activated protein C- and tissue factor pathway inhibitor-cofactor activities of protein S revealed similar hypercoagulable states in type I and type III protein S-deficient plasma. Twelve PROS1 mutations and two large deletions were identified in the genetically characterized families.
CONCLUSIONS:
Not only type I, but also type III protein S deficiency is associated with a hypercoagulable state and increased risk of thrombosis. These findings may, however, be restricted to type III deficient individuals from families with mixed type I/III protein S deficiency, as these represented 80% of type III deficient individuals in our cohort
Synthesis optimization and charge carrier transfer mechanism in LiLuSiO<sub>4</sub>:Ce, Tm storage phosphor
No full textLiLuSiO4:Ce and LiLuSiO4:Ce, Tm show very efficient charge carrier storage properties upon beta irradiation after samples have received treatment in vacuum. They outperform the commercial storage phosphor BaFBr(I):Eu2+ in many aspects. The influence of the synthesis conditions, Ce and Tm concentration, nonstoichiometry and codoping with Ca, Hf, Al and Ge are reported. Based on the results of the synthesis optimization, thermoluminescence (TL) emission and TL excitation spectra a mechanism of charge carrier transfer, storage, and recombination during irradiation and thermal or optical readout is proposed.Accepted Author ManuscriptRST/Fundamental Aspects of Materials and EnergyRST/Luminescence Material
GA Landsat 5 TM Analysis Ready Data Collection 3
No full textMaintenance and Update Frequency: asNeededStatement: This product is derived from the USGS Landsat Collection 1 archive.
The Moderate Resolution Imaging Spectroradiometer (MODIS) MCD43A1 Version 6 Bidirectional Reflectance Distribution Function and Albedo (BRDF/Albedo) Model Parameters dataset was provided by the National Aeronautics and Space Administration (NASA). It was produced daily using 16 days of Terra and Aqua MODIS data at 500 m resolution.
The ozone data was provided by Environment Canada.
The Aerosol Optical Thickness data was provided by the Commonwealth Scientific and Industrial Research Organisation (CSIRO).
The Precipitable Water for Entire Atmosphere data was provided by the National Oceanic and Atmospheric Administration (NOAA) / Earth System Research Laboratory (ESRL) / Physical Sciences Division (PSD).
The baseline Digital Surface Model (DSM) data produced from the Shuttle Radar Topography Mission (SRTM) was provided by the National Geospatial-Intelligence Agency (NGA).
Level 1 Collection 1 data was provided by the United States Geological Survey (USGS)'s Earth Resources Observation and Science (EROS) Center.<b>BACKGROUND</b><br/><p><br/><p>The United States Geological Survey's (USGS) Landsat satellite program has been capturing images of the Australian continent for more than 30 years. This data is highly useful for land and coastal mapping studies. <br/><p>In particular, the light reflected from the Earth’s surface (surface reflectance) is important for monitoring environmental resources – such as agricultural production and mining activities – over time. <br/><p>We need to make accurate comparisons of imagery acquired at different times, seasons and geographic locations. However, inconsistencies can arise due to variations in atmospheric conditions, sun position, sensor view angle, surface slope and surface aspect. These need to be reduced or removed to ensure the data is consistent and can be compared over time. <br/><p> </p><br/><b>WHAT THIS PRODUCT OFFERS</b><br/><p><br/><p>GA Landsat 5 TM Analysis Ready Data Collection 3 takes Landsat 5 Thematic Mapper (TM) imagery captured over the Australian continent and corrects for inconsistencies across land and coastal fringes. The result is accurate and standardised surface reflectance data, which is instrumental in identifying and quantifying environmental change. <br/><p><br/><p>The TM instrument is an advanced, multispectral scanning, Earth resources sensor which is designed to categorise the Earth's surface. It is particularly useful for agricultural applications and identification of land use. <br/><p><br/><p>This product is a single, cohesive Analysis Ready Data (ARD) package, which allows you to analyse surface reflectance data as is, without the need to apply additional corrections. <br/><p><br/><p>It contains three sub-products that provide corrections or attribution information:<br/><p><br/><p> 1) GA Landsat 5 TM NBAR Collection 3 <br/><p> 2) GA Landsat 5 TM NBART Collection 3<br/><p> 3) GA Landsat 5 TM OA Collection 3<br/><p><br/><p>The resolution is a 30 m grid based on the USGS Landsat Collection 1 archive
The dependence of light extraction improvement on optimized surface microstructure for AlGaN-based UVC-LEDs considering TM-polarized emission
No full textIn order to improve the light extraction of AlGaN-based short wavelength ultraviolet light emitting diodes (DUC-LEDs), a type of microstructure with high aspect ratio is introduced and optimized on the AlN substrate surface. And, particle swarm optimization (PSO) algorithm is used to inverse design of the surface microstructure to maximize the light extraction efficiency (LEE). Considering that the propagation characteristics of TM-polarized light are different from that of TE-polarized light, the optical field distribution and LEE is analyzed for the UVC-LEDs with different TE-polarized component when the optimized surface microstructure is applied. Furthermore, the preparation process tolerance of the high aspect ratio structure is discussed by calculating the LED's LEE when the structural deviation occurs or morphology changes. Simulation results show that, by using the optimized surface microstructure based on parabola cone array, the LEDs' LEE is increased from 4.4% to 8.7% and from 0.4% to 3.7% for TE-polarized and TM-polarized emission, respectively. In addition, it is demonstrated that the light extraction improvement by the surface microstructure has a good tolerance to the structural deviation and morphology. The results are significant for improving light extraction and realizing high efficient short wavelength AlGaN-based UVC-LEDs by designing surface microstructures.Green Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.ImPhys/Esmaeil Zadeh grou
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