Summary Dapsone-induced optic atrophy (OA) is very rare at therapeutic doses. A 43-year-old gentleman on WHO-recommended multibacillary Multi-Drug Therapy (WHO MB-MDT) containing rifampicin, dapsone, ...and clofazimine, presented with bilateral gradual painless diminution of vision after 3 months of medication. He denied any history of trauma, headache, limb weakness, ataxia, diplopia, temporal pain, or weight loss. There was no history of sudden diminution of vision in family members. Fundus examination showed bilateral pale optic discs with well-defined margins. Glucose-6-phosphate dehydrogenase (G6PD) was normal. He was diagnosed with OA secondary to dapsone. There is therefore a possibility of dapsone induced OA even at the therapeutic dose. Hence, we should perform routine eye check-up before starting dapsone. Keywords: Dapsone, optic atrophy, leprosy
Essentials Mechanism of thrombin-induced inflammation is not fully understood. Thrombin induced monocyte adhesion and barrier loss require Angiopoietin-2 (Ang-2). Ang-2 mediates vessel leakage and ...monocyte adhesion through SHP-2/p38MAPK pathway. Calcium dependent SHP2/p38MAPK activation regulates Ang-2 expression through a feedback loop.
Background Thrombin imparts an inflammatory phenotype to the endothelium by promoting increased monocyte adhesion and vascular permeability. However, the molecular players that govern these events are incompletely understood. Objective The aim of this study was to determine whether Angiopoietin-2 (Ang-2) has a role, if any, in regulating inflammatory signals initiated by thrombin. Methods Assessment of vascular leakage by Miles assay was performed by intra-dermal injection on the foot paw. Surface levels of intercellular adhesion molecule-1 (ICAM-1) were determined by flow cytometry. Overexpression, knockdown and phosphorylation of proteins were determined by Western blotting. Results In time-course experiments, thrombin-stimulated Ang-2 up-regulation, peaked prior to the expression of adhesion molecule ICAM-1 in human umbilical vein-derived endothelial cells (HUVECs). Knockdown of Ang-2 blocked both thrombin-induced monocyte adhesion and ICAM-1 expression. In addition, Ang-2(-/-) mice displayed defective vascular leakage when treated with thrombin. Introducing Ang-2 protein in Ang-2(-/-) mice failed to recover a wild-type phenotype. Mechanistically, Ang-2 appears to regulate the thrombin-activated calcium spike that is required for tyrosine phosphatase SHP2 and p38 MAPK activation. Further, down-regulation of SHP2 attenuated both thrombin-induced Ang-2 expression and monocyte adhesion. Down-regulation of the adaptor protein Gab1, a co-activator of SHP2, as well as overexpression of the Gab1 mutant incapable of interacting with SHP2 (YFGab1), inhibited thrombin-mediated effects, including downstream activation of p38 MAPK, which in turn was required for Ang-2 expression. Conclusions The data establish an essential role of the Gab1/SHP2/p38MAPK signaling pathway and Ang-2 in regulating thrombin-induced monocyte adhesion and vascular leakage.
Abstract Background and aims Studies suggest that Gentiana lutea (GL), and its component isovitexin, may exhibit anti-atherosclerotic properties. In this study we sought to investigate the protective ...mechanism of GL aqueous root extract and isovitexin on endothelial inflammation, smooth muscle cell migation, and on the onset and progression of atherosclerosis in streptozotocin (STZ)-induced diabetic rats. Methods and results Our results show that both GL extract and isovitexin, block leukocyte adhesion and generation of reactive oxygen species in human umbilical vein endothelial cells (HUVECs) and rat aortic smooth muscle cells (RASMCs), following TNF-alpha and platelet derived growth factor-BB (PDGF-BB) challenges respectively. Both the extract and isovitexin blocked TNF-α induced expression of ICAM-1 and VCAM-1 in HUVECs. PDGF-BB induced migration of RASMCs and phospholipase C-γ activation, were also abrogated by GL extract and isovitexin. Fura-2 based ratiometric measurements demonstrated that, both the extact, and isovitexin, inhibit PDGF-BB mediated intracellular calcium rise in RASMCs. Supplementation of regular diet with 2% GL root powder for STZ rats, reduced total cholesterol in blood. Oil Red O staining demonstrated decreased lipid accumulation in aortic wall of diabetic animals upon treatment with GL. Medial thickness and deposition of collagen in the aortic segment of diabetic rats were also reduced upon supplementation. Immunohistochemistry demonstrated reduced expression of vascular cell adhesion molecule-1 (VCAM-1), inducible nitric oxide synthase (iNOS), and vascular endothelial cadherin (VE-cadherin) in aortic segments of diabetic rats following GL treatment. Conclusions Thus, our results support that GL root extract/powder and isovitexin exhibit anti-atherosclerotic activities.
Summarizer Koo, Gunjae; Matam, Kiran Kumar; I, Te ...
2017 50th Annual IEEE/ACM International Symposium on Microarchitecture (MICRO),
10/2017
Conference Proceeding
Modern data center solid state drives (SSDs) integrate multiple general-purpose embedded cores to manage flash translation layer, garbage collection, wear-leveling, and etc., to improve the ...performance and the reliability of SSDs. As the performance of these cores steadily improves there are opportunities to repurpose these cores to perform application driven computations on stored data, with the aim of reducing the communication between the host processor and the SSD. Reducing host-SSD bandwidth demand cuts down the I/O time which is a bottleneck for many applications operating on large data sets. However, the embedded core performance is still significantly lower than the host processor, as generally wimpy embedded cores are used within SSD for cost effective reasons. So there is a trade-off between the computation overhead associated with near SSD processing and the reduction in communication overhead to the host system.
In this work, we design a set of application programming interfaces (APIs) that can be used by the host application to offload a data intensive task to the SSD processor. We describe how these APIs can be implemented by simple modifications to the existing Non-Volatile Memory Express (NVMe) command interface between the host and the SSD processor. We then quantify the computation versus communication tradeoffs for near storage computing using applications from two important domains, namely data analytics and data integration. Using a fully functional SSD evaluation platform we perform design space exploration of our proposed approach by varying the bandwidth and computation capabilities of the SSD processor. We evaluate static and dynamic approaches for dividing the work between the host and SSD processor, and show that our design may improve the performance by up to 20% when compared to processing at the host processor only, and 6X when compared to processing at the SSD processor only.
Background: Cauliflower production during the late winter season has major problems including the requirement of long duration for its maturity, lower yield and poor postharvest quality, especially ...in the mid-hill region of Nepal. A field experiment was conducted to access the growth, crop maturity and yield of late-season cauliflower varieties at Puranchaur, Kaski in the mid-hill region of Nepal.Methods: The experiment was arranged in a randomized complete block design (RCBD) with toal eleven late-season cauliflower varieties in which nine were hybrid varieties viz. Freedom, Titan, Ravella, Artica, Bishop, Casper, Indam 9803, NS 106 and Snow Mystique while two were open pollinated varieties viz. Amazing and Snowball 16. The experiment was conducted from November 2016 to March 2017 with four replications.Result: Significantly shorter period for final curd initiation of 76 days was recorded in NS 106 and Indam 9803 which was statistically similar with Amazing. Significantly shorter period for final curd maturation of 90 days was recorded in Amazing which was statistically similar to Bishop and NS 106. Similarly, the highest curd yield of 50 mt/ha was produced by Bishop at 91 days after transplanting (DAT) while the lowest crud yield of 19 mt/ha was recorded in Snowball 16 at 113 DAT. Finally, it was concluded that Bishop found the best hybrid variety for higher curd yield and short duration for maturation while Amazing performed higher yield than Snowball 16 and early maturing variety in the mid-hill region of Nepal.
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•Generating circuits for accelerated life testing of field programmable gate arrays.•The problem involves multi-variable optimization.•Proposed a genetic algorithm for the purpose ...mentioned above.•Proved empirically that particle swarm optimization can be used to enhance the quality of results yielded by a GA.•Showed that GA aided by PSO not only reduces time (from months to hours) but can also yield better results than the hand-crafted SBC.
Accelerated life testing (ALT) of a field programmable gate array (FPGA) requires it to be configured with a circuit that satisfies multiple criteria. Hand-crafting such a circuit is a herculean task as many components of the criteria are orthogonal to each other demanding a complex multivariate optimization. This paper presents an evolutionary algorithm aided by particle swarm optimization methodology to generate synthetic benchmark circuits (SBC) that can be used for ALT of FPGAs. The proposed algorithm was used to generate a SBC for ALT of a commercial FPGA. The generated SBC when compared with a hand-crafted one, demonstrated to be more suitable for ALT, measured in terms of meeting the multiple criteria. The SBC generated by the proposed technique utilizes 8.37% more resources; operates at a maximum frequency which is 40% higher; and has 7.75% higher switching activity than the hand-crafted one reported in the literature. The hand-crafted circuit is very specific to the particular device of that family of FPGAs, whereas the proposed algorithm is device-independent. In addition, it took several man months to hand-craft the SBC, whereas the proposed algorithm took less than half-a-day.
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