The myeloproliferative disorder-associated JAK2 V617F mutant escapes negative regulation by suppressor of cytokine signaling 3

The somatic JAK2 valine-to-phenylalanine (V617F) mutation has been detected in up to 90% of patients with polycythemia and in a sizeable proportion of patients with other myeloproliferative disorders such as essential thrombocythemia and idiopathic myelofibrosis. Suppressor of cytokine signaling 3 (SOCS3) is known to be a strong negative regulator of erythropoietin (EPO) signaling through interaction with both the EPO receptor (EPOR) and JAK2. We report here that JAK2 V617F cannot be regulated and that its activation is actually potentiated in the presence of SOCS3. Instead of acting as a suppressor, SOCS3 enhanced the proliferation of cells expressing both JAK2 V617F and EPOR. Additionally, although SOCS1 and SOCS2 are degraded in the presence of JAK2 V617F, turnover of SOCS3 is inhibited by the JAK2 mutant kinase and this correlated with marked tyrosine phosphorylation of SOCS3 protein. We also observed constitutive tyrosine phosphorylation of SOCS3 in peripheral blood mononuclear cells (PBMCs) derived from patients homozygous for the JAK2 V617F mutant. These findings suggest that the JAK2 V617F has overcome normal SOCS regulation by hyperphosphorylating SOCS3, rendering it unable to inhibit the mutant kinase. Thus, JAK2 V617F may even exploit SOCS3 to potentiate its myeloproliferative capacity.

Thresholding of noisy shoeprint images based on pixel context

In a typical shoeprint classification and retrieval system, the first step is to segment meaningful basic shapes and patterns in a noisy shoeprint image. This step has significant influence on shape descriptors and shoeprint indexing in the later stages. In this paper, we extend a recently developed denoising technique proposed by Buades, called non-local mean filtering, to give a more general model. In this model, the expected result of an operation on a pixel can be estimated by performing the same operation on all of its reference pixels in the same image. A working pixel’s reference pixels are those pixels whose neighbourhoods are similar to the working pixel’s neighbourhood. Similarity is based on the correlation between the local neighbourhoods of the working pixel and the reference pixel. We incorporate a special instance of this general case into thresholding a very noisy shoeprint image. Visual and quantitative comparisons with two benchmarking techniques, by Otsu and Kittler, are conducted in the last section, giving evidence of the effectiveness of our method for thresholding noisy shoeprint images.

Stabilization of zinc electrodes with a conducting polymer

The reversibility of zinc anode in alkaline medium was enhanced by electrostatic deposition of a conducting polymer (polypyrrole). Electropolymerization of pyrrole onto zinc in aqueous medium using an organic acid as dopant is feasible and preferred as zinc is less corrosive in this medium. The structure of the polymer film was analyzed by FT-IR spectroscopy and scanning electron microscopy. The effect of the polypyrrole deposit on the zinc electrode was studied by cyclic voltammetry and charge–discharge cycling.