Dextran sulfate modulates MAP kinase signaling and reduces endothelial injury in a rat aortic clamping model

OBJECTIVE: Mitogen-activated protein kinases (MAPKs), including JNK, p38, and ERK1/2, noticeably influence ischemia/reperfusion injury (IRI). The complement inhibitor dextran sulfate (DXS) associates with damaged endothelium denudated of its heparan sulfate proteoglycan (HSPG) layer. Other glycosaminoglycan analogs are known to influence MAPK signaling. Hypothetically therefore, targeted intravascular cytoprotection by DXS may function in part through influencing MAPK activation to reduce IRI-induced damage of the vasculature. METHODS: IRI of the infrarenal aorta of male Wistar rats was induced by 90 minutes clamping followed by 120 minutes reperfusion. DXS (5 mg/mL) or physiologic saline (NaCl controls) was infused locally into the ischemic aortic segment immediately prior to reperfusion. Ninety minutes ischemia-only and heparinase infusion (maximal damage) experiments, as well as native rat aorta, served as controls. Aortas were excised following termination of the experiments for further analysis. RESULTS: DXS significantly inhibited IRI-induced JNK and ERK1/2 activation (P = .043; P =.005) without influencing the p38 pathway (P =.110). Reduced aortic injury, with significant inhibition of apoptosis (P = .032 for DXS vs NaCl), correlated with decreased nuclear factor kappaB translocation within the aortic wall. DXS treatment clearly reduced C1q, C4b/c, C3b/c, and C9 complement deposition, whilst preserving endothelial cell integrity and reducing reperfusion-induced HSPG shedding. Protection was associated with binding of fluorescein labeled DXS to ischemically damaged tissue. CONCLUSIONS: Local application of DXS into ischemic vasculature immediately prior to reperfusion reduces complement deposition and preserves endothelial integrity, partially through modulating activation of MAPKs and may offer a new approach to tackle IRI in vascular surgical procedures. CLINICAL RELEVANCE: The purpose of the present study was to determine the role of dextran sulfate (DXS), a glycosaminoglycan analog and complement inhibitor, in modulating intracellular MAPK signaling pathways, reducing complement activation and ultimately attenuating ischemia/reperfusion injury (IRI) in a rat aortic-clamping model, in part a surrogate model to study the microvasculature. The study shows a role for DXS in ameliorating endothelial injury by reducing IRI-mediated damage and intravascular, local inflammation in the affected aortic segment. DXS may be envisaged as an endothelial protectant in vascular injury, such as occurs during vascular surgical procedures.

Amalgamation and interpolation in ordered algebras

The first part of this paper provides a comprehensive and self-contained account of the interrelationships between algebraic properties of varieties and properties of their free algebras and equational consequence relations. In particular, proofs are given of known equivalences between the amalgamation property and the Robinson property, the congruence extension property and the extension property, and the flat amalgamation property and the deductive interpolation property, as well as various dependencies between these properties. These relationships are then exploited in the second part of the paper in order to provide new proofs of amalgamation and deductive interpolation for the varieties of lattice-ordered abelian groups and MV-algebras, and to determine important subvarieties of residuated lattices where these properties hold or fail. In particular, a full description is given of all subvarieties of commutative GMV-algebras possessing the amalgamation property.

Modulus method and radial stretch map in the Heisenberg group

We develop a modulus method for surface families inside a domain in the Heisenberg group and we prove that the stretch map between two Heisenberg spherical rings is a minimiser for the mean distortion among the class of contact quasiconformal maps between these rings which satisfy certain boundary conditions.

A bone-thickness map as a guide for bone-anchored port implantation surgery in the temporal bone

The bone-anchored port (BAP) is an investigational implant, which is intended to be fixed on the temporal bone and provide vascular access. There are a number of implants taking advantage of the stability and available room in the temporal bone. These devices range from implantable hearing aids to percutaneous ports. During temporal bone surgery, injuring critical anatomical structures must be avoided. Several methods for computer-assisted temporal bone surgery are reported, which typically add an additional procedure for the patient. We propose a surgical guide in the form of a bone-thickness map displaying anatomical landmarks that can be used for planning of the surgery, and for the intra-operative decision of the implant’s location. The retro-auricular region of the temporal and parietal bone was marked on cone-beam computed tomography scans and tridimensional surfaces displaying the bone thickness were created from this space. We compared this method using a thickness map (n = 10) with conventional surgery without assistance (n = 5) in isolated human anatomical whole head specimens. The use of the thickness map reduced the rate of Dura Mater exposition from 100% to 20% and OPEN ACCESS Materials 2013, 6 5292 suppressed sigmoid sinus exposures. The study shows that a bone-thickness map can be used as a low-complexity method to improve patient’s safety during BAP surgery in the temporal bone.

Human intervertebral disc stiffness correlates better with the Otsu threshold computed from axial T2 map of its posterior annulus fibrosus than with clinical classifications

Degeneration of the intervertebral disc, sometimes associated with low back pain and abnormal spinal motions, represents a major health issue with high costs. A non-invasive degeneration assessment via qualitative or quantitative MRI (magnetic resonance imaging) is possible, yet, no relation between mechanical properties and T2 maps of the intervertebral disc (IVD) has been considered, albeit T2 relaxation time values quantify the degree of degeneration. Therefore, MRI scans and mechanical tests were performed on 14 human lumbar intervertebral segments freed from posterior elements and all soft tissues excluding the IVD. Degeneration was evaluated in each specimen using morphological criteria, qualitative T2 weighted images and quantitative axial T2 map data and stiffness was calculated from the load-deflection curves of in vitro compression, torsion, lateral bending and flexion/extension tests. In addition to mean T2, the OTSU threshold of T2 (TOTSU), a robust and automatic histogram-based method that computes the optimal threshold maximizing the distinction of two classes of values, was calculated for anterior, posterior, left and right regions of each annulus fibrosus (AF). While mean T2 and degeneration schemes were not related to the IVDs' mechanical properties, TOTSU computed in the posterior AF correlated significantly with those classifications as well as with all stiffness values. TOTSU should therefore be included in future degeneration grading schemes.

Precipitation isoscape of high reliefs: interpolation scheme designed and tested for monthly resolved precipitation oxygen isotope records of an Alpine domain

Stable oxygen isotope composition of atmospheric precipitation (δ18Op) was scrutinized from 39 stations distributed over Switzerland and its border zone. Monthly amount-weighted δ18Op values averaged over the 1995–2000 period showed the expected strong linear altitude dependence (−0.15 to −0.22‰ per 100 m) only during the summer season (May–September). Steeper gradients (~ −0.56 to −0.60‰ per 100 m) were observed for winter months over a low elevation belt, while hardly any altitudinal difference was seen for high elevation stations. This dichotomous pattern could be explained by the characteristically shallower vertical atmospheric mixing height during winter season and provides empirical evidence for recently simulated effects of stratified atmospheric flow on orographic precipitation isotopic ratios. This helps explain "anomalous" deflected altitudinal water isotope profiles reported from many other high relief regions. Grids and isotope distribution maps of the monthly δ18Op have been calculated over the study region for 1995–1996. The adopted interpolation method took into account both the variable mixing heights and the seasonal difference in the isotopic lapse rate and combined them with residual kriging. The presented data set allows a point estimation of δ18Op with monthly resolution. According to the test calculations executed on subsets, this biannual data set can be extended back to 1992 with maintained fidelity and, with a reduced station subset, even back to 1983 at the expense of faded reliability of the derived δ18Op estimates, mainly in the eastern part of Switzerland. Before 1983, reliable results can only be expected for the Swiss Plateau since important stations representing eastern and south-western Switzerland were not yet in operation.

A global radiosonde and tracked balloon archive on 16 pressure levels (GRASP) back to 1905 – Part 1: Merging and interpolation to 00:00 and 12:00 GMT

Many observed time series of the global radiosonde or PILOT networks exist as fragments distributed over different archives. Identifying and merging these fragments can enhance their value for studies on the three-dimensional spatial structure of climate change. The Comprehensive Historical Upper-Air Network (CHUAN version 1.7), which was substantially extended in 2013, and the Integrated Global Radiosonde Archive (IGRA) are the most important collections of upper-air measurements taken before 1958. CHUAN (tracked) balloon data start in 1900, with higher numbers from the late 1920s onward, whereas IGRA data start in 1937. However, a substantial fraction of those measurements have not been taken at synoptic times (preferably 00:00 or 12:00 GMT) and on altitude levels instead of standard pressure levels. To make them comparable with more recent data, the records have been brought to synoptic times and standard pressure levels using state-of-the-art interpolation techniques, employing geopotential information from the National Oceanic and Atmospheric Administration (NOAA) 20th Century Reanalysis (NOAA 20CR). From 1958 onward the European Re-Analysis archives (ERA-40 and ERA-Interim) available at the European Centre for Medium-Range Weather Forecasts (ECMWF) are the main data sources. These are easier to use, but pilot data still have to be interpolated to standard pressure levels. Fractions of the same records distributed over different archives have been merged, if necessary, taking care that the data remain traceable back to their original sources. If possible, station IDs assigned by the World Meteorological Organization (WMO) have been allocated to the station records. For some records which have never been identified by a WMO ID, a local ID above 100 000 has been assigned. The merged data set contains 37 wind records longer than 70 years and 139 temperature records longer than 60 years. It can be seen as a useful basis for further data processing steps, most notably homogenization and gridding, after which it should be a valuable resource for climatological studies. Homogeneity adjustments for wind using the NOAA-20CR as a reference are described in Ramella Pralungo and Haimberger (2014). Reliable homogeneity adjustments for temperature beyond 1958 using a surface-data-only reanalysis such as NOAA-20CR as a reference have yet to be created. All the archives and metadata files are available in ASCII and netCDF format in the PANGAEA archive