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Algorithms, Architecture, C++, Developer, Development, Exchange, Foundation, ISO, Libraries, Linux, Middleware, Networking, Programming, Protocols, RPC, Software Engineer, TCP/IP, Unix
Full Time
Telecommuting not available Travel not required
C++ Infrastructure Engineer familiar with ISO C++ Standards (200-300k)
SUMMARY:
An Elite technology firm in New York is looking for a C++ infrastructure developer to build the foundation for thousands of fellow engineers, as they create the middleware software infrastructure for large-scale, fault-tolerant applications that run on thousands of machines. Join a team of world class C++ engineers building a complex infrastructure with RPC, publish/subscribe, and message queues.
RESPONSIBILITIES
Two possible teams to join are the RPC or Multicast Team. RPC handles server-side development and message exchange; providing libraries, tools, and processes for a service-oriented architecture based on message-routing.
The Multicast team develops distributed middleware transport libraries and services that support low-latency, high volume applications and middleware services. The team implements reliable multicast and unicast protocols, especially Pragmatic Reliable Multicast, as well as higher level services that include fault tolerance.
REQUIREMENTS:
Gambit Technologies,
Dice Id : 10116662
Position Id : NT669794111108842
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The figure below shows the –time profiles of sildenafil after administration of 50 mg of the drug in the form of slow IV infusion and oral tablet. Determine the absolute bioavailability of the tablets. Determine the Cl from the IV data. Studies with radiolabeled sildenafil have shown that 92% of the drug is absorbed, although much less intact drug is detected in plasma. Can you explain this difference?

The figure below shows the –time profiles of sildenafil after administration of 100 mg of the drug to fasted and fed volunteers. Describe the food effect on the oral bioavailability of sildenafil .

Christopher F. Barnett MD, MPH, Teresa De Marco MD, in Murray and Nadel's Textbook of Respiratory Medicine (Sixth Edition) , 2016

Phosphodiesterase Type 5 Antagonists.

Sildenafil and tadalafil are selective inhibitors of cyclic guanosine monophosphate–specific phosphodiesterase type 5 and cause pulmonary arteriolar smooth muscle cell relaxation and vasodilation. Additionally, sildenafil has antifibrotic activity that has been tested in patients with lung disease.

The acute effects of sildenafil on hemodynamics and oxygenation were studied at rest and with exercise in 20 patients with COPD and mild PH after a single dose of 20 mg or 40 mg of sildenafil . There was a significant 21% reduction in resting 1 hour after sildenafil that was accompanied by worsening gas exchange with a reduction in arterial P o of 9%. A similar reduction in was seen during exercise with no significant change in oxygenation; concomitant studies showed that worsening hypoxemia was related to worsening of ventilation-perfusion matching after sildenafil .

Three studies have attempted to address the effects of sildenafil on exercise tolerance in patients with COPD. In the first, sildenafil was administered to 15 COPD patients for 3 months; compared to baseline, there was no difference in the right ventricular stroke volume measured by MRI or in exercise tolerance measured by cardiopulmonary exercise testing and the 6MWD. The effects of sildenafil on exercise capacity were studied in 10 patients in a randomized double-blind placebo-controlled crossover study. Patients with PH were specifically excluded from this study. After 14 days of sildenafil treatment, there was no difference in exercise capacity, but there was worsening of oxygenation and quality of life with increasing symptoms and adverse events in the sildenafil group. Another study randomized 63 patients with COPD and moderate PH documented by echocardiography to treatment with sildenafil for 3 months during pulmonary rehabilitation; in this study sildenafil had no effect on exercise capacity or oxygenation.

The acute effects of sildenafil have also been evaluated in patients with interstitial lung disease. Sixteen hospitalized patients with pulmonary fibrosis were treated with inhaled NO and then randomized to receive open-label intravenous epoprostenol (mean dose 8 ng/kg/min) or a single dose of oral sildenafil 50 mg. All three agents reduced the PVR index to a similar extent. However, only inhaled NO and sildenafil reduced the PVR-to-SVR ratio. Intravenous epoprostenol also decreased mean systemic arterial pressure and P o values, owing to ventilation-perfusion mismatching. By contrast, during treatment with inhaled NO and sildenafil , ventilation-perfusion matching was maintained. Therefore, among patients in this study, sildenafil exerted a selective pulmonary arterial vasodilatory effect without worsening hypoxemia.

The effects of sildenafil on exercise tolerance in patients with PH-IPF were examined in two studies. In one small open-label study 14 patients with IPF and mild PH received sildenafil 20 to 50 mg three times daily for 12 weeks. At the end of the study, of the 11 patients who completed the 6MWD, 9 demonstrated an improvement in the mean 6MWD of 49 m (90% confidence interval, 17.5 to 84 m). The largest study of sildenafil in patients with IPF to date was STEP-IPF ( Sildenafil Trial of Exercise Performance in Idiopathic Pulmonary Fibrosis). In this study, patients with IPF were randomized to either sildenafil ( = 89) or placebo ( = 91) for 12 weeks of treatment without any assessment for the presence or severity of PH. The primary end point of improvement in 6MWD was not met; however, patients taking sildenafil had improved dyspnea, quality of life, and less deterioration in oxygenation.

Overall, the results of these studies are highly variable but suggest that in certain patients with lung disease sildenafil might confer some early hemodynamic and symptomatic improvement, potentially at the expense of worsening ventilation-perfusion matching and worsening oxygenation and without any clear long-term benefits. Further well-designed studies are needed to determine if there is a role for these agents in PH-LD.

Avinash C. Shukla, ... Francis X. McGowan, in Archerr Ted Baker ML9FeXEO
, 2009

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Ph.D. (2006) University of California at Santa Barbara, Geography and Operations Research

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Middleton, R.S. , Carey, J.W., Currier, R.P., Hyman, J.D., Kang, Q., Karra, S., Jiménez-Martínez, J., Porter, M.L., Viswanathan, H.S., (2015) Shale gas and non-aqueous fracturing fluids: Opportunities and challenges for supercritical CO 2 , Applied Energy 147 , 500-509.

Middleton, R.S.

Middleton, R.S. , Levine, J.S., Bielicki, J.M., Viswanathan, H.S., Carey, J.W., Stauffer, P.H., (2015) Jumpstarting commercial-scale CO 2 capture and storage with ethylene production and enhanced oil recovery in the U.S. Gulf, Greenhouse Gases: Science and Technology , In press.

Dai, Z., Stauffer, P.H., Carey, J.W., Middleton, R.S. , Lu, Z., Jacobs, J.F., Hnottavange-Telleen, K., Spangler, L.H. (2014) Pre-site Characterization Risk Analysis for Commercial-Scale Carbon Sequestration, Environmental Science and Technology 1 , DOI: 10.1021/es405468p.

Dai, Z., Middleton, R.S. , Viswanathan, H., Fessenden-Rahn, J., Bauman, J., Pawar, R., Lee, S.-Y., McPherson, B. (2014) An Integrated framework for optimizing CO 2 sequestration and enhanced oil recovery, Environmental Science and Technology Letters 1 , 49-54.

Bielicki, J.M., Callas, G., Middleton, R.S. , Ha-Duong, M. (2014) National Corridors for Climate Change Mitigation: Managing Industrial CO 2 Emissions in France, Greenhouse Gases: Science and Technology , DOI: 10.1002/ghg.1395.

Middleton, R.S. and Eccles, J.K., (2013). Fracking, renewables, and natural gas power: the complex future of carbon capture and storage, Applied Energy 108 , 66-73.


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