Objective
Diabetic subjects are at higher risk of ischemic peripheral vascular disease (PVD). We tested the hypothesis that advanced glycation end products (AGEs) and their receptor (RAGE) block neoangiogenesis and blood flow recovery after hind limb ischemia induced by femoral artery ligation (FAL) through modulation of immune/inflammatory mechanisms.
Approach and Results
Wild type (WT) mice rendered diabetic with streptozotocin and subjected to unilateral FAL displayed increased accumulation and expression of AGEs and RAGE in ischemic muscle. In diabetic WT mice, FAL attenuated neoangiogenesis and impaired blood flow recovery, in parallel with reduced macrophage content in ischemic muscle and suppression of early inflammatory gene expression, including chemokine (C-C motif) ligand 2 (Ccl2) and early growth response gene 1 (Egr1) versus non-diabetic mice. Deletion of Ager or transgenic expression of Glo1 (reduces AGEs) restored adaptive inflammation, neoangiogenesis and blood flow recovery in diabetic mice. In diabetes, deletion of Ager increased circulating Ly6Chi monocytes and augmented macrophage infiltration into ischemic muscle tissue after FAL. In vitro, macrophages grown in high glucose display inflammation that is skewed to expression of tissue damage versus tissue repair gene expression. Further, macrophages grown in high versus low glucose demonstrate blunted macrophage-endothelial cell interactions. In both settings, these adverse effects of high glucose were reversed by Ager deletion in macrophages.
Conclusions
These findings indicate that RAGE attenuates adaptive inflammation in hind limb ischemia; underscore microenvironment-specific functions for RAGE in inflammation in tissue repair versus damage; and illustrate that AGE/RAGE antagonism may fill a critical gap in diabetic PVD.
Abstract-Multiple-voltage is an effective dynamic power reduction design technique. Recent research has shown that testing for resistive bridging faults in such designs requires more than one voltage setting for 100% defect coverage; however switching between several supply voltage settings has a detrimental impact on the overall cost of test. This paper proposes an effective Gate Sizing technique for reducing test cost of multi-Vdd designs with bridge defects. Using synthesized ISCAS benchmarks and a parametric fault model, experimental results show that for all the circuits, the proposed technique achieves 100% defect coverage at a single Vdd setting; in addition it has a lower overhead than the recently proposed Test Point Insertion technique in terms of timing, area and power.
Acute erythroleukemia is characterized by a predominant immature erythroid population and accounts for approximately 2-5 % of all cases of acute leukemia. Two subtypes are recognized based on the presence or absence of a significant myeloid component: erythroleukemia and pure erythroid leukemia. Erythroleukemia is predominantly a disease of adults, while pure erythroid leukemia can be seen in any age including children. Here is a case of pure erythroleukemia presenting mainly as late erythroblasts which was diagnosed on bone marrow examination, cytochemistry and was confirmed on immunophenotyping. Possibly this is the only case so for demonstrating deletion of long arm of chromosome 20 in pure erythroleukemia.
This paper deals with a sequential sampling procedure for selecting from a given multinomial distribution with K .cells,-the cell with the largest probability of occurrence. Observations being taken sequentially from the given distribution, the sampling is terminated when the largest count in any cell is equal to N or when the difference between the largest and the 4 next largest cell counts is equal to r, where r and N are given positive integers. The Cell with the largest count on the termination of sampling is selected as the most probable event. I The probability of a correct selection and the expected total number of observations are given.
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