An efficient analytical placement algorithm using cell shifting, iterative local refinement and a hybrid net model

In this thesis, we present FastPlace-a fast, iterative, flat placement algorithm for large scale standard cell designs in the fixed-die context. FastPlace is based on the quadratic placement approach. The quadratic approach formulates the wirelength minimization problem as a convex quadratic program, which can be solved analytically by some efficient techniques. However, the quadratic approach in general suffers from some drawbacks. First, the resulting placement has a lot of overlap among cells. Second, the resulting total wirelength may be long as the quadratic wirelength objective is only an indirect measure of the total linear wirelength. Third, existing net models tend to create a lot of non-zero entries in the connectivity matrix while modeling the netlist and this slows down the quadratic program solver. These problems are handled as follows: (1) A Cell Shifting technique is proposed to generate an evenly distribute global placement from the quadratic program solution. This technique is very efficient and produces a high-quality global placement with even cell distribution. (2) An Iterative Local Refinement technique is proposed to reduce the wirelength according to the half-perimeter bounding rectangle measure. This technique is very effective as it makes use of the wirelength and cell distribution information provided by a coarse global placement. (3) A Hybrid Net Model is proposed which is a combination of the traditional clique and star models. This net model significantly reduces the number of non-zero entries in the connectivity matrix. It results in a significant speed-up of the solver as compared to using it with the traditional clique model. Experimental results show that the run-time of FastPlace is of the order O(n1·412), where n is the circuit size given by the number of pins. Also, the current implementation when tested on 18 Standard Cell benchmark circuits is on average 11.0 and 82.7 times faster than existing academic placers Capo and Dragon respectively

Micro-RNA-1 is decreased by hypoxia and contributes to the development of pulmonary vascular remodeling via regulation of sphingosine kinase 1

Sphingosine kinase 1 (SphK1) upregulation is associated with pathologic pulmonary vascular remodeling in pulmonary arterial hypertension (PAH), but the mechanisms controlling its expression are undefined. In this study, we sought to characterize the regulation of SphK1 expression by micro-RNAs (miRs). In silico analysis of the SphK1 3'-untranslated region identified several putative miR binding sites, with miR-1-3p (miR-1) being the most highly predicted target. Therefore we further investigated the role of miR-1 in modulating SphK1 expression and characterized its effects on the phenotype of pulmonary artery smooth muscle cells (PASMCs) and the development of experimental pulmonary hypertension in vivo. Our results demonstrate that miR-1 is downregulated by hypoxia in PASMCs and can directly inhibit SphK1 expression. Overexpression of miR-1 in human PASMCs inhibits basal and hypoxia-induced proliferation and migration. Human PASMCs isolated from PAH patients exhibit reduced miR-1 expression. We also demonstrate that miR-1 is downregulated in mouse lung tissues during experimental hypoxia-mediated pulmonary hypertension (HPH), consistent with upregulation of SphK1. Furthermore, administration of miR-1 mimics in vivo prevented the development of HPH in mice and attenuated induction of SphK1 in PASMCs. These data reveal the importance of miR-1 in regulating SphK1 expression during hypoxia in PASMCs. A pivotal role is played by miR-1 in pulmonary vascular remodeling, including PASMC proliferation and migration, and its overexpression protects from the development of HPH in vivo. These studies improve our understanding of the molecular mechanisms underlying the pathogenesis of pulmonary hypertension

A Techniques for Scalable and Effective Routability Evaluation

Routing congestion has become a critical layout challenge in nanoscale circuits since it is a critical factor in determining the routability of a design. An unroutable design is not useful even though it closes on all other design metrics. Fast design closure can only be achieved by accurately evaluating whether a design is routable or not early in the design cycle. Lately, it has become common to use a “light mode ” version of a global router to quickly evaluate the routability of a given placement. This approach suffers from three weaknesses: (i) it does not adequately model local routing resources, which can cause incorrect routability predictions that are only detected late, during detailed routing, (ii) the congestion maps obtained by it tend to have isolated hot spots surrounded by noncongested spots, called “noisy hot spots”, which further affects the accuracy in routability evaluation, (iii) the metrics used to represent congestion may yield numbers that do not provide sufficient intuition to the designer; moreover, they may often fail to predict the routability accurately. This paper presents solutions to these issues. First, we propose three approaches to model local routing resources. Second, we propose a smoothing technique to reduce the number of noisy hot spots and obtain a more accurate routability evaluation result. Finally, we develop a new metric which represents congestion maps with higher fidelity. We apply the proposed techniques to several industrial circuits and demonstrate that one can better predict and evaluate design routability, and congestion mitigation tools can perform muc

Plasma chemokines are biomarkers of disease severity, higher bacterial burden and delayed sputum culture conversion in pulmonary tuberculosis

Plasma cytokines are biomarkers of disease extent and mycobacterial burden in pulmonary tuberculosis (PTB). Whether chemokines can perform the same role in PTB is not known. We examined the plasma levels of chemokines in individuals with PTB, latent TB (LTB) or healthy controls (HC) and their association with disease severity and mycobacterial burdens in PTB. We also examined the chemokines in PTB individuals at the end of anti-tuberculous chemotherapy (ATT). PTB individuals exhibited significantly higher levels of CCL1, CCL3, CXCL1, CXCL2, CXCL9 and CXCL10 in comparison to LTB and/or HC individuals. PTB individuals with bilateral or cavitary disease displayed significantly elevated levels of CCL1, CCL3, CXCL1, CXCL10 and CXCL11 compared to those with unilateral or non-cavitary disease and also exhibited a significant positive relationship with bacterial burdens. In addition, PTB individuals with slower culture conversion displayed significantly elevated levels of CCL1, CCL3, CXCL1 and CXCL9 at the time of PTB diagnosis and prior to ATT. Finally, the chemokines were significantly reduced following successful ATT. Our data demonstrate that PTB is associated with elevated levels of chemokines, which are partially reversed followed chemotherapy. Our data demonstrate that chemokines are markers of disease severity, predicting increased bacterial burden and delayed culture conversion in PTB

WOUND HEALING ACTIVITY OF JATROPHA TANJORENSIS LEAVES

Objective:  The term “wound” is defined as a disruption of normal anatomical structure. Therefore, “healing” is the complex and dynamic process that results in the restoration of anatomical continuity and function. Methods: Albino Wistar rats (150-180 g) of both sexes were selected. The experiment of Wound Healing Activity by Excision Wound Model and Incision Wound Model by the simple ointment B.P., reference standard drug (0.2% w/w nitrofurazone ointment), stigmasterol ointment (0.2% w/w), hexane, chloroform and methanol extract ointments of 3%, 4% and 5% w/w of leaves in Jatropha tanjorensis in simple ointment base (where 3g, 4g and 5 g of the extracts was incorporated in 100 g of simple ointment separately). Results: The time for wound closure to methanol extract ointment (5% w/w) and stigmasterol (0.2% w/w) was similar to that of standard drug, nitrofurazone ointment (0.2% w/w) 16±2 days in Excision Wound Model. The significant tensile strength at 3%: 4%: 5% w/w methanol extract ointments (p<0.001), followed by chloroform extract and hexane extract. Stigmasterol ointment at 0.2% w/w produced tensile strength comparable with Standard drug, nitrofurazone ointment (0.2% w/w) (p<0.001) in Incision Wound Model. Conclusion: Juice of the Jatropha plant and the pounded leaves are applied to wounds and refractory ulcers. The juice is very successfully used to treat scabies, eczema and ringworm. The present study proved that the leaves have wound healing activity.                  Peer Review History: Received 5 September  2018;   Revised 28 September; Accepted 12 October, Available online 15 November 2018 Academic Editor: Dr. Nuray Arı, Ankara University, Turkiye, [email protected] UJPR follows the most transparent and toughest ‘Advanced OPEN peer review’ system. The identity of the authors and, reviewers will be known to each other. This transparent process will help to eradicate any possible malicious/purposeful interference by any person (publishing staff, reviewer, editor, author, etc) during peer review. As a result of this unique system, all reviewers will get their due recognition and respect, once their names are published in the papers. We expect that, by publishing peer review reports with published papers, will be helpful to many authors for drafting their article according to the specifications. Auhors will remove any error of their article and they will improve their article(s) according to the previous reports displayed with published article(s). The main purpose of it is ‘to improve the quality of a candidate manuscript’. Our reviewers check the ‘strength and weakness of a manuscript honestly’. There will increase in the perfection, and transparency. Received file:        Reviewer's Comments: Average Peer review marks at initial stage: 5.5/10 Average Peer review marks at publication stage: 8.0/10 Reviewer(s) detail: Dr. Mohamed Said Fathy Al-Refaey, University of Sadat City, Menofia, Egypt, [email protected] Prof. Dr. Hüsniye Kayalar, Ege University, Turkey, [email protected] Similar Articles: POTENTIAL OF SNAKEHEAD FISH (OPHIOCEPHALUS STRIATUS) IN ACCELERATING WOUND HEALING ENHANCEMENT OF WOUND HEALING BY TOPICAL APPLICATION OF EPIDERMAL GROWTH FACTOR IN ANIMAL MODE

Role of Nox4 and Nox2 in Hyperoxia-Induced Reactive Oxygen Species Generation and Migration of Human Lung Endothelial Cells

Abstract In vascular endothelium, the major research focus has been on reactive oxygen species (ROS) derived from Nox2. The role of Nox4 in endothelial signal transduction, ROS production, and cytoskeletal reorganization is not well defined. In this study, we show that human pulmonary artery endothelial cells (HPAECs) and human lung microvascular endothelial cells (HLMVECs) express higher levels of Nox4 and p22phox compared to Nox1, Nox2, Nox3, or Nox5. Immunofluorescence microscopy and Western blot analysis revealed that Nox4 and p22phox, but not Nox2 or p47phox, are localized in nuclei of HPAECs. Further, knockdown of Nox4 with siRNA decreased Nox4 nuclear expression significantly. Exposure of HPAECs to hyperoxia (3-24h) enhanced mRNA and protein expression of Nox4, and Nox4 siRNA decreased hyperoxia-induced ROS production. Interestingly, Nox4 or Nox2 knockdown with siRNA upregulated the mRNA and protein expression of the other, suggesting activation of compensatory mechanisms. A similar upregulation of Nox4 mRNA was observed in Nox2 2/ko mice. Downregulation of Nox4, or pretreatment with N-acetylcysteine, attenuated hyperoxia-induced cell migration and capillary tube formation, suggesting that ROS generated by Nox4 regulate endothelial cell motility. These results indicate that Nox4 and Nox2 play a physiological role in hyperoxia-induced ROS production and migration of ECs. Antioxid. Redox Signal. 11, 747-764.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78121/1/ars.2008.2203.pd

NOX Enzymes and Pulmonary Disease

Abstract The primary function of the lung is to facilitate the transfer of molecular oxygen (O2; dioxygen) from the atmosphere to the systemic circulation. In addition to its essential role in aerobic metabolism, O2 serves as the physiologic terminal acceptor of electron transfer catalyzed by the NADPH oxidase (NOX) family of oxidoreductases. The evolution of the lungs and circulatory systems in vertebrates was accompanied by increasing diversification of NOX family enzymes, suggesting adaptive roles for NOX-derived reactive oxygen species in normal physiology. However, this adaptation may paradoxically carry detrimental consequences in the setting of overwhelming/persistent environmental stressors, both infectious and noninfectious, and during the process of aging. Here, we review current understanding of NOX enzymes in normal lung physiology and their pathophysiologic roles in a number of pulmonary diseases, including lung infections, acute lung injury, pulmonary arterial hypertension, obstructive lung disorders, fibrotic lung disease, and lung cancer. Antioxid. Redox Signal. 11, 2505-2516.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78108/1/ars.2009.2599.pd