Screening for C3 Deficiency in Newborns Using Microarrays

BACKGROUND: Dried blood spot samples (DBSS) from newborns are widely used in neonatal screening for selected metabolic diseases and diagnostic possibilities for additional disorders are continuously being evaluated. Primary immunodeficiency disorders comprise a group of more than one hundred diseases, several of which are fatal early in life. Yet, a majority of the patients are not diagnosed due to lack of high-throughput screening methods. METHODOLOGY/PRINCIPAL FINDINGS: We have previously developed a system using reverse phase protein microarrays for analysis of IgA levels in serum samples. In this study, we extended the applicability of the method to include determination of complement component C3 levels in eluates from DBSS collected at birth. Normal levels of C3 were readily detected in 269 DBSS from healthy newborns, while no C3 was detected in sera and DBSS from C3 deficient patients. CONCLUSIONS/SIGNIFICANCE: The findings suggest that patients with deficiencies of specific serum proteins can be identified by analysis of DBSS using reverse phase protein microarrays.QC 20120213</p

The variable link between PNA and NAO in observations and in multi-century CGCM simulations

The link between the Pacific/North American pattern (PNA) and the North Atlantic Oscillation (NAO) is investigated in reanalysis data (NCEP, ERA40) and multi-century CGCM runs for present day climate using three versions of the ECHAM model. PNA and NAO patterns and indices are determined via rotated principal component analysis on monthly mean 500 hPa geopotential height fields using the varimax criteria. On average, the multi-century CGCM simulations show a significant anti-correlation between PNA and NAO. Further, multi-decadal periods with significantly enhanced (high anti-correlation, active phase) or weakened (low correlations, inactive phase) coupling are found in all CGCMs. In the simulated active phases, the storm track activity near Newfoundland has a stronger link with the PNA variability than during the inactive phases. On average, the reanalysis datasets show no significant anti-correlation between PNA and NAO indices, but during the sub-period 1973–1994 a significant anti-correlation is detected, suggesting that the present climate could correspond to an inactive period as detected in the CGCMs. An analysis of possible physical mechanisms suggests that the link between the patterns is established by the baroclinic waves forming the North Atlantic storm track. The geopotential height anomalies associated with negative PNA phases induce an increased advection of warm and moist air from the Gulf of Mexico and cold air from Canada. Both types of advection contribute to increase baroclinicity over eastern North America and also to increase the low level latent heat content of the warm air masses. Thus, growth conditions for eddies at the entrance of the North Atlantic storm track are enhanced. Considering the average temporal development during winter for the CGCM, results show an enhanced Newfoundland storm track maximum in the early winter for negative PNA, followed by a downstream enhancement of the Atlantic storm track in the subsequent months. In active (passive) phases, this seasonal development is enhanced (suppressed). As the storm track over the central and eastern Atlantic is closely related to the NAO variability, this development can be explained by the shift of the NAO index to more positive values

Determination of Membrane Protein Transporter Oligomerization in Native Tissue Using Spatial Fluorescence Intensity Fluctuation Analysis

Membrane transporter proteins exist in a complex dynamic equilibrium between various oligomeric states that include monomers, dimers, dimer of dimers and higher order oligomers. Given their sub-optical microscopic resolution size, the oligomerization state of membrane transporters is difficult to quantify without requiring tissue disruption and indirect biochemical methods. Here we present the application of a fluorescence measurement technique which combines fluorescence image moment analysis and spatial intensity distribution analysis (SpIDA) to determine the oligomerization state of membrane proteins in situ. As a model system we analyzed the oligomeric state(s) of the electrogenic sodium bicarbonate cotransporter NBCe1-A in cultured cells and in rat kidney. The approaches that we describe offer for the first time the ability to investigate the oligomeric state of membrane transporter proteins in their native state

APEX: Current Status of the Airborne Dispersive Pushbroom Imaging Spectrometer

ABSTRACT Over the past few years, a joint Swiss/Belgium ESA initiative resulted in a project to build a precursor mission of future spaceborne imaging spectrometers, namely APEX (Airborne Prism Experiment). APEX is designed to be an airborne dispersive pushbroom imaging spectrometer operating in the solar reflected wavelength range between 400 and 2500 nm. The system is optimized for land applications including limnology, snow, and soil, amongst others. The instrument is optimized with various steps taken to allow for absolute calibrated radiance measurements. This includes the use of a pre-and post-data acquisition internal calibration facility as well as a laboratory calibration and a performance model serving as a stable reference. The instrument is currently in its breadboarding phase, including some new results with respect to detector development and design optimization for imaging spectrometers. In the same APEX framework, a complete processing and archiving facility (PAF) is developed. The PAF not only includes imaging spectrometer data processing up to physical units, but also geometric and atmospheric correction for each scene, as well as calibration data input. The PAF software includes an Internet based web-server and provides interfaces to data users as well as instrument operators and programmers. The software design, the tools and its life cycle are discussed as well

APEX: Current Status of the Airborne Dispersive Pushbroom Imaging Spectrometer

ABSTRACT Over the past few years, a joint Swiss/Belgium ESA initiative resulted in a project to build a precursor mission of future spaceborne imaging spectrometers, namely APEX (Airborne Prism Experiment). APEX is designed to be an airborne dispersive pushbroom imaging spectrometer operating in the solar reflected wavelength range between 400 and 2500 nm. The system is optimized for land applications including limnology, snow, and soil, amongst others. The instrument is optimized with various steps taken to allow for absolute calibrated radiance measurements. This includes the use of a pre-and post-data acquisition internal calibration facility as well as a laboratory calibration and a performance model serving as a stable reference. The instrument is currently in its breadboarding phase, including some new results with respect to detector development and design optimization for imaging spectrometers. In the same APEX framework, a complete processing and archiving facility (PAF) is developed. The PAF not only includes imaging spectrometer data processing up to physical units, but also geometric and atmospheric correction for each scene, as well as calibration data input. The PAF software includes an Internet based web-server and provides interfaces to data users as well as instrument operators and programmers. The software design, the tools and its life cycle are discussed as well

In Vivo Methods to Study Uptake of Nanoparticles into the Brain

Several in vivo techniques have been developed to study and measure the uptake of CNS compounds into the brain. With these techniques, various parameters can be determined after drug administration, including the blood-to-brain influx constant (Kin), the permeability-surface area (PS) product, and the brain uptake index (BUI). These techniques have been mostly used for drugs that are expected to enter the brain via transmembrane diffusion or by carrier-mediated transcytosis. Drugs that have limitations in entering the brain via such pathways have been encapsulated in nanoparticles (based on lipids or synthetic polymers) to enhance brain uptake. Nanoparticles are different from CNS compounds in size, composition and uptake mechanisms. This has led to different methods and approaches to study brain uptake in vivo. Here we discuss the techniques generally used to measure nanoparticle uptake in addition to the techniques used for CNS compounds. Techniques include visualization methods, behavioral tests, and quantitative methods

Association between traumatic bone marrow abnormalities of the knee, the trauma mechanism and associated soft-tissue knee injuries

OBJECTIVES: To determine the association between traumatic bone marrow abnormalities, the knee injury mechanism, and associated soft tissue injuries in a larger cohort than those in the published literature. METHOD: Retrospective study including 220 patients with traumatic knee injuries. Knee MRIs were evaluated for trauma mechanism, soft tissue injury, and the location of bone marrow abnormalities. The locations of the abnormalities were correlated with trauma mechanisms and soft tissue injuries using the chi-square test with Bonferroni correction. RESULTS: One hundred and forty-four valgus injuries, 39 pivot shift injuries, 25 lateral patellar dislocations, 8 hyperextensions, and 4 dashboard injuries were included. Valgus and pivot shift injuries showed traumatic bone marrow abnormalities in the posterolateral regions of the tibia. Abnormalities after patellar dislocation were found in the anterolateral and centrolateral femur and patella. Hyperextension injuries were associated with abnormalities in almost all regions, and dashboard injuries were associated with changes in the anterior regions of the tibia and femur. CONCLUSIONS: Our study provides evidence of associations between traumatic bone marrow abnormality patterns and different trauma mechanisms in acute knee injury, and reveals some overlap, especially of the two most common trauma mechanisms (valgus and pivot shift), in a large patient cohort. KEY POINTS• Specific bone marrow oedema patterns after knee trauma were confirmed. • New associations between bone marrow oedema patterns and knee trauma were shown. • Bone marrow oedema patterns help in identifying associated soft tissue injuries