Modeling and Propagation of Noisy Waveforms in Static Timing Analysis

A technique based on the sensitivity of the output to input waveform is presented for accurate propagation of delay information through a gate for the purpose of static timing analysis (STA) in the presence of noise. Conventional STA tools represent a waveform by its arrival time and slope. However, this is not an accurate way of modeling the waveform for the purpose of noise analysis. The key contribution of our work is the development of a method that allows efficient propagation of equivalent waveforms throughout the circuit. Experimental results demonstrate higher accuracy of the proposed sensitivity-based gate delay propagation technique, SGDP, compared to the best of existing approaches. SGDP is compatible with the current level of gate characterization in conventional ASIC cell libraries, and as a result, it can be easily incorporated into commercial STA tools to improve their accuracy.Comment: Submitted on behalf of EDAA (http://www.edaa.com/

ATP-dependent potassium channels are implicated in simvastatin pretreatment-induced inhibition of apoptotic cell death after renal ischemia/reperfusion injury

Background: Simvastatin is a widely used medication in cardiac care. Here we evaluate the role of ATP sensitive potassium (KATP) channels in simvastatin induced renal protection after renal ischemia/reperfusion (I/R) injury. Methods: A total of 81 male Wistar rats, were treated with simvastatin (10 and 20mg/kg/day; gavage, one week). Some groups received glibenclamide (KATP channel inhibitor; 5mg/kg) before ischemia (45min) and reperfusion (24h). Finally the kidneys were processed for histological analysis and measurement of biochemical parameters including tissue malondialdehyde (MDA), blood urea nitrogen (BUN), fractional excretion of sodium (FENa), creatinine clearance rate (CCr) and Bcl2-associated X protein (Bax) expression. Results: IR significantly increased serum Cr (p< 0.01) and BUN levels (p< 0.01), elevated FENa (p<0.01) and tissue MDA (p<0.01), and decreased CCr (p< 0.01) and induced histological damage. Bax pro-apoptotic protein was upregulated in renal tissue after I/R injury and downregulated in simvastatin pretreated group. Simvastatin at doses of 10 and 20mg/kg/day significantly reduced serum Cr and BUN levels (p< 0.05 vs. IR group), tissue MDA contents and FENa (p< 0.05 vs. I/R) and increased CCr (p< 0.05 vs. IR). Renal tissue injury was improved only in simvastatin 20mg/kg/day group (p< 0.05). Glibenclamide significantly abolished protective effects of simvastatin and increased serum Cr and BUN and FENa and decreased CCr (p< 0.05). It also abolished the effects of simvastatin on tissue injury and MDA contents and downregulated the Bax protein after IR injury (p< 0.05). Conclusion: Opening of KATP channels is essential for simvastatin-induced renal protection against I/R injury

Electronic Properties of Topological Materials: Optical Excitations in Moebius Conjugated Polymers

Electronic structures and optical excitations in Moebius conjugated polymers are studied theoretically. Periodic and Moebius boundary conditions are applied to the tight binding model of poly(para-phenylene), taking exciton effects into account. We discuss that oligomers with a few structural units are more effective than polymers for observations of effects of discrete wave numbers that are shifted by the change in boundary condition. Next, calculations of optical absorption spectra are reported. Certain components of optical absorption for an electric field perpendicular to the polymer axis mix with absorption spectra for an electric field parallel to the polymer axis. Therefore, the polarization dependences of an electric field of light enable us to detect whether conjugated polymers have the Moebius boundary.Comment: 10 pages, 6 figures, to be published in J. Phys. Soc. Jpn., Vol. 74 No. 2 (February, 2005), Letter sectio

Plasma oxysterol level in patients with coronary artery stenosis and its changes in response to the treatment with atorvastatin

Background: Considering the increasing incidence of coronary artery stenosis and its related complications, the importance of its etiology and inconsistent reports we aimed to determine the relationship between oxysterol, serum levels and severity of coronary atherosclerosis and effect of statins on oxysterol. Methods: A total of 85 patients referred to Taleghani Hospital, Tehran, Iran during 2011-2012 with coronary artery stenosis more than 75, as determined by angiography, participated in the current study. Their demographic information and history of smoking and taking atorvastatin was carefully recorded. Two milliliters of venous blood was obtained from each patient. The serum oxysterol level of samples was measured using the enzyme-linked immunosorbent assay (ELISA) method. Statistical analysis was performed using SPSS v.19. Results: Eighty five patients completed the study. Mean age of patients was 64.4 years; 51 (60) were male; 55 (68) had acute coronary syndrome and 30 (32) had chronic stable angina. Mean±SD of plasma level of oxysterol was 24.8±0.2 pmol/ml. The normal range of oxysterol level was 13pmol/ml. Mean±SD of plasma oxysterol level in patients under statin therapy was 24.4±2.1 pmol/ml. In patients without receiving statins, plasma oxysterol level was 26.38±1.6pmol/ml. Conclusion: Findings of the present study indicated significant correlation between serum oxysterol and severity of coronary artery stenosis. It also demonstrated that receiving atorvastatin is associated with significant reduction of plasma oxysterol level

Role of morphine preconditioning and nitric oxide following brain ischemia reperfusion injury in mice

Objective(s): Morphine dependence (MD) potently protects heart against ischemia reperfusion (IR) injury through specific signaling mechanisms, which are different from the pathways involved in acute morphine treatment or classical preconditioning. Since opioid receptor density changes post cerebral ischemia strongly correlated with brain histological damage, in the present study, we tried to elucidate the possible role of opioid receptors in IR injury among morphine-dependent mice. Materials and Methods: Accordingly, incremental doses (10 mg/kg/day to 30 mg/kg/day) of morphine sulphate were subcutaneously administered for 5 days before global brain ischemia induction through bilateral common carotid artery occlusion. Animals were received naloxone (5 mg/kg) or L-NAME (20 mg/kg) 30 min after the last morphine dose. Twenty four hr after the ischemia induction, Retention trial of passive avoidance test and western blot analysis were done. histological analysis (TUNEL and NISSL staining) performed 72 hr after ischemia. Results: MD improved post ischemia memory performance (P<0.01) and neuronal survival (P<0.001) and decreased apoptosis (P<0.05) in region I of hippocampus (CA1 region) in mouse. Treatment with naloxone or L-NAME abolished all MD aforementioned effects. Conclusion: Results of the present study suggested that opioid receptors activation in the early hr post ischemia is crucial for MD-induced hippocampus tolerance against IR injury. Opioid receptor-dependent balance of NO production was another key factor in MD-induced protection. Further studies are required to determine the effect of MD on opioid receptor changes after ischemia and its correlation with MD-induced protection. © 2015, Mashhad University of Medical Sciences. All rights reserved

IN VITRO EQUIVALENCE STUDY OF GENERIC METFORMIN HYDROCHLORIDE TABLETS UNDER BIOWAIVER CONDITIONS

Background: Generic drugs are smarter alternative to expensive brands, it is bio- equivalent formula of any branded drug. FDA approved that generic drugs are the safest to consume, the medicines meet the similar manufacturing standards followed while producing an innovator drug, however, the color, shape, taste and packaging of generics is different from the innovator product. In short, a generic drug should be bioequivalent to its brand counterpart. Metformin was initially marketed under the name of Glucophage®, and now the market is loaded by generics of different origin, and price variability. Method: Our study was conducted to determine whether metformin generics are bioequivalent to the innovator drug Glucophage®. In-vitro bioequivalence testing under Biowaiver conditions can predict bioequivalence in a safe, fast, and less expensive method. Thus, study was performed on Metformin tablets to assess whether generics are bioequivalent to the innovator and hence be interchangeable. Results: The quality control results of the thickness, hardness, friability, disintegration, weight uniformity, content uniformity, and assay showed that most metformin tablets complied with the USP 34 NF29 2011 specifications. Dissolution testing under biowaiver conditions showed different results. All tablets of the generics and innovator Glucophage® were able to dissolve by more than 85% within 15 min. Two generics were bioequivalent to the innovator Glucophage® having f2≥ 50 in the three dissolution media. The rest of generics showed variable results. Conclusion: Generics of metformin varied in their bioequivalency to the innovator Gluocophage®. This variation could be explained by different excipients, and manufacturing conditions. In-vivo bioequivalence testing should be conducted to confirm that the innovator could be safely interchangeable with the brand and this variation won’t affect the safety and efficacy of the drug

Improvement of tissue survival of skin flaps by 5α-reductase inhibitors: Possible involvement of nitric oxide and inducible nitric oxide synthase

Background: Skin flap grafting is a popular approach for reconstruction of critical skin and underlying soft tissue injuries. In a previous study, we demonstrated the beneficial effects of two 5α-reductase inhibitors, azelaic acid and finasteride, on tissue survival in a rat model of skin flap grafting. In the current study, we investigated the involvement of nitric oxide and inducible nitric oxide synthase (iNOS) in graft survival mediated by these agents. Methods: A number of 42 male rats were randomly allocated into six groups: 1, normal saline topical application; 2, azelaic acid (100 mg/flap); 3, finasteride (1 mg/flap); 4, injection of L-NG-nitroarginine methyl ester (L-NAME) (i.p., 20 mg/kg); 5, L-NAME (20 mg/kg, i.p.) + azelaic acid (100 mg/flap, topical); 6, L-NAME (20 mg/kg, i.p.) + finasteride (1 mg/flap, topical). Tissue survival, level of nitric oxide, and iNOS expression in groups were measured. Results: Our data revealed that azelaic acid and finasteride significantly increased the expression of iNOS protein and nitric oxide (NO) levels in graft tissue (P &lt; 0.05). These increases in iNOS expression and NO level were associated with higher survival of the graft tissue. Conclusion: It appears that alterations of the NO metabolism are implicated in the azelaic acid- and finasteride-mediated survival of the skin flaps. © 2015, Pasteur Institute of Iran. All rights reserved

How Might Recharge Change Under Projected Climate Change in the Western U.S.?

Although groundwater is a major water resource in the western U.S., little research has been done on the impacts of climate change on groundwater storage and recharge in the West. Here we assess the impact of projected changes in climate on groundwater recharge in the near (2021–2050) and far (2071–2100) future across the western U.S. Variable Infiltration Capacity model was run with RCP 6.0 forcing from 11 global climate models and “subsurface runoff” output was considered as recharge. Recharge is expected to decrease in the West (−5.8 ± 14.3%) and Southwest (−4.0 ± 6.7%) regions in the near future and in the South region (−9.5 ± 24.3%) in the far future. The Northern Rockies region is expected to get more recharge in the near (+5.3 ± 9.2%) and far (+11.8 ± 12.3%) future. Overall, southern portions of the western U.S. are expected to get less recharge in the future and northern portions will get more. Climate change interacts with land surface properties to affect the amount of recharge that occurs in the future. Effects on recharge due to change in vegetation response from projected changes in climate and CO2 concentration, though important, are not considered in this study.Key PointsClimate change interacts with land surface properties to affect the amount of recharge that occurs in the futureSouthern portions of the western U.S. are expected to get less and northern portions more recharge in the futureThe large variability in projected recharge across the GCMs is associated with variability in projected precipitationPeer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139906/1/grl56569.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139906/2/grl56569_am.pd