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Sample records for mechanical thrombectomy combined

  1. Septic thrombophlebitis: percutaneous mechanical thrombectomy and thrombolytic therapies.

    PubMed

    Kar, Subrata; Webel, Richard

    2014-01-01

    Suppurative thrombophlebitis (Lemierre's syndrome) of the internal jugular vein is a rare and sometimes fatal complication. It commonly occurs from oropharyngeal infections, peripheral lines, complications from dental procedures, gingivitis, or central venous catheterizations. Empiric antibiotics are the initial treatment of choice followed by thrombolytics or surgical thrombectomy in refractory cases. We present a case of septic thrombophlebitis of the right internal jugular vein from a peripherally inserted central venous catheter. We also review the current percutaneous mechanical thrombectomy and thrombolytics therapies for such a rare disorder. Mechanical thrombectomy includes rotational thrombectomy or rheolytic therapies. Devices include the Amplatz thrombectomy device (Microvena), the Arrow-Trerotola Percutaneous thrombolytic device (Arrow), and the Cragg-Casteneda thrombolytic brush (Microtherapeutics). Rheolytic therapies include Angiojet, the Hydrolyzer, and the Oasis Thrombectomy System. Percutaneous mechanical thrombectomy techniques include rotational fragmentation, aspiration or suction thrombectomy, and hydrodynamic thrombectomy. AngioJet catheters may be used for percutaneous embolectomy in conjunction with pulse spray techniques, which instill thrombolytics locally. Thrombolytics include streptokinase, urokinase, and recombinant-tissue plasminogen activator. Mechanical thrombectomy combined with thrombolytics provide optimal treatment results secondary to their complementary effects. Therefore, patients who are refractory to standard medical therapy and considered poor surgical candidates may benefit from combined percutaneous mechanical thrombectomy with thrombolytics to achieve superior results if no contraindications exist for thrombolytics. PMID:22198069

  2. Mechanical thrombectomy using a combined CT/C-arm X-ray system

    PubMed Central

    Herweh, Christian; Pham, Mirko; Schönenberger, Silvia; Bösel, Julian; Ringleb, Peter A; Heiland, Sabine; Bendszus, Martin; Möhlenbruch, Markus

    2016-01-01

    Background Mechanical thrombectomy (MT) using stent-retrievers has been proven to be a safe and effective treatment in acute ischemic stroke (AIS), particularly in large vessel occlusion. Other than patient characteristics, time to recanalization is the most important factor linked to outcome. MT is usually performed in a dedicated angiography suite using a floor- and/or ceiling-mounted biplane angiographic system. Here we report our first experience of MT with a new combined CT and mobile C-arm X-ray device setup. Methods Patients with AIS underwent stroke imaging (non-contrast enhanced CT, CT perfusion, and CT angiography) using a commercially available 64-slice CT scanner which was modified for combined use with a C-arm system. In patients with large vessel occlusion, MT was conducted without further patient transfer within the CT imaging suite using a mobile C-arm X-ray device equipped with a 30×30 cm (12×12 inch), 1.5×1.5 k full-view flat detector which was positioned between the gantry and patient table. The safety and feasibility of this new system was assessed in preliminary patients. Results Angiographic imaging quality of the mobile C-arm was feasible and satisfactory for diagnostic angiography and MT. Using this setup, time between stroke imaging and groin puncture (picture-to-puncture time) was reduced by up to 35 min (including time for preparation of the patient such as intubation). Conclusions MT using a combined CT/C-arm system is safe and feasible. The potential advantages, particularly time saving and ensuing improvement in patient outcome, need to be assessed in a larger study. PMID:25935925

  3. Mechanical Thrombectomy of Hemodialysis Fistulae and Grafts

    SciTech Connect

    Patel, Aalpen A. Tuite, Catherine M.; Trerotola, Scott O.

    2005-12-15

    In this article, the authors present approaches they use in performing dialysis access intervention-in particular clotted access. It is not meant to be a comprehensive review of dialysis access management. At our institution, mechanical thrombectomy is the primary mode of treatment for clotted hemodialysis access. We will present physical examination findings in clotted dialysis access and contraindications for mechanical thrombectomy in dialysis access. We will also discuss the devices for mechanical thrombectomy and the techniques we use. Finally, we will discuss the difficulties encountered in these procedures and their solutions.

  4. Mechanical Thrombectomy for Stroke After Cardiac Surgery.

    PubMed

    Madeira, Márcio; Martins, Catarina; Koukoulis, Giovanna; Marques, Marta; Reis, João; Abecassis, Miguel

    2016-08-01

    Stroke after cardiac surgery remains a devastating complication and its treatment options are limited. Systemic fibrinolysis is a relative contraindication, because it raises the risk of systemic hemorrhage. Endovascular therapy, mechanical thrombectomy, and intra-arterial fibrinolysis have emerged as safer options. We present three patients who developed strokes following cardiac surgery who underwent successful mechanical thrombectomy and review the literature on this subject. doi: 10.1111/jocs.12776 (J Card Surg 2016;31:517-520). PMID:27282492

  5. Mechanical Thrombectomy of Iliocaval Thrombosis Using a Protective Expandable Sheath

    SciTech Connect

    Truong, Tri H.; Spuentrup, Elmar; Staatz, Gundula; Wildberger, Joachim E.; Schmitz-Rode, Thomas; Nolte-Ernsting, Claus C.A.; Guenther, Rolf W.; Haage, Patrick

    2004-09-15

    We report a case of successful percutaneous treatment of a subacute ilio-caval venous thrombosis in a 64-year-old female patient by using a novel combination of a rotatory fragmentation device (percutaneous thrombectomy device: PTD) and large wire basket (temporary Guenther basket filter) under temporary caval filter protection using an expandable sheath. Because the patient had multiple myeloma with increased risk for contrast media-induced renal failure, the therapeutic angiographic procedure was performed without iodinated contrast medium. Non-contrast-enhanced MR venography (high-resolution True FISP) confirmed the effective thrombus removal by the percutaneous mechanical thrombectomy procedure.

  6. Successful Recanalization of Acute Superior Mesenteric Artery Thromboembolic Occlusion by a Combination of Intraarterial Thrombolysis and Mechanical Thrombectomy with a Carotid Filter

    SciTech Connect

    Zelenak, Kamil; Sinak, Igor; Janik, Jan; Mikolajcik, Anton; Mistuna, Dusan

    2013-06-15

    Acute superior mesenteric artery (SMA) occlusion is a life-threatening disease, and acute intestinal ischemia develops from the sudden decrease in perfusion to the intestines. The key to saving the patient's life is early diagnosis, and prompt revascularization of the SMA can prevent intestinal infarction and decrease the risk of bowel segment necrosis. Computed tomographic angiography may be useful for rapid diagnosis. We report recanalization of an SMA occlusion in an 80-year-old man with a combination of intraarterial thrombolysis and mechanical thrombectomy with a carotid filter.

  7. Mechanical Thrombectomy in Acute Ischemic Stroke: A Systematic Review.

    PubMed

    Lambrinos, Anna; Schaink, Alexis K; Dhalla, Irfan; Krings, Timo; Casaubon, Leanne K; Sikich, Nancy; Lum, Cheemun; Bharatha, Aditya; Pereira, Vitor Mendes; Stotts, Grant; Saposnik, Gustavo; Kelloway, Linda; Xie, Xuanqian; Hill, Michael D

    2016-07-01

    Although intravenous thrombolysis increases the probability of a good functional outcome in carefully selected patients with acute ischemic stroke, a substantial proportion of patients who receive thrombolysis do not have a good outcome. Several recent trials of mechanical thrombectomy appear to indicate that this treatment may be superior to thrombolysis. We therefore conducted a systematic review and meta-analysis to evaluate the clinical effectiveness and safety of new-generation mechanical thrombectomy devices with intravenous thrombolysis (if eligible) compared with intravenous thrombolysis (if eligible) in patients with acute ischemic stroke caused by a proximal intracranial occlusion. We systematically searched seven databases for randomized controlled trials published between January 2005 and March 2015 comparing stent retrievers or thromboaspiration devices with best medical therapy (with or without intravenous thrombolysis) in adults with acute ischemic stroke. We assessed risk of bias and overall quality of the included trials. We combined the data using a fixed or random effects meta-analysis, where appropriate. We identified 1579 studies; of these, we evaluated 122 full-text papers and included five randomized control trials (n=1287). Compared with patients treated medically, patients who received mechanical thrombectomy were more likely to be functionally independent as measured by a modified Rankin score of 0-2 (odds ratio, 2.39; 95% confidence interval, 1.88-3.04; I2=0%). This finding was robust to subgroup analysis. Mortality and symptomatic intracerebral hemorrhage were not significantly different between the two groups. Mechanical thrombectomy significantly improves functional independence in appropriately selected patients with acute ischemic stroke. PMID:27071728

  8. Superior Mesenteric Artery Embolism Treated with Percutaneous Mechanical Thrombectomy

    SciTech Connect

    Popovic, Peter Kuhelj, Dimitrij; Bunc, Matjaz

    2011-02-15

    A case of acute superior mesenteric artery embolism treated with percutaneous thrombus aspiration is described. A 63-year-old man with chronic atrial fibrillation was admitted to the hospital with progressive abdominal pain. Computed tomography angiography revealed an occlusion of the distal part of the superior mesenteric artery. The patient was effectively treated using transaxillary percutaneous mechanical thrombectomy using a 6F Aspirex thrombectomy catheter.

  9. Influence of Thrombus Age on the Mechanical Thrombectomy Efficacy of the Amplatz Thrombectomy Device In Vitro

    SciTech Connect

    Grimm, Jan Jahnke, Thomas; Muhle, Claus; Heller, Martin; Mueller-Huelsbeck, Stefan

    2003-06-15

    Purpose: To determine the efficacy of thrombectomy for the Amplatz Thrombectomy Device (ATD) according to the age of the thrombus. Methods: Thrombectomy was performed with the 7 Fr or 8 Fr ATD. Five-day-old or 8-day-old thrombi were made from porcine blood by clotting within silicone tubes to be used in a flow model. Emboli sizes, weight, remaining thrombus and activation time were evaluated. Results: The age of the thrombus had no influence on the activation time necessary for complete thrombolysis. A significant difference was found in the overall amount of embolization only with the 7 Fr device although a similar trend was shown with the 8 Fr device. The amount of embolized thrombotic material was higher for both devices if older thrombi (i.e., 8 days old) we reprocessed. The overall impression was that the 8 Fr device showed slightly better results (less remaining thrombus and embolization). Conclusion: A tendency toward higher amounts of embolization was observed if older thrombi were used in the model. Therefore the interventional radiologist should be aware of the potentially higher risk of peripheral embolization when performing mechanical thrombectomy(with the ATD) in older thrombotic occlusions, especially since the higher rate of embolization was mainly due to an increased proportion of larger embolic particles (1 mm), which are clinically more significant.

  10. Mechanical Thrombectomy of Occluded Hemodialysis Native Fistulas and Grafts Using a Hydrodynamic Thrombectomy Catheter: Preliminary Experience

    SciTech Connect

    Sahni, Vikram Kaniyur, Sunil; Malhotra, Anmol; Fan, Stanley; Blakeney, Charles; Fotheringham, Tim; Sobeh, Mohammed; Matson, Matthew

    2005-12-15

    The purpose of this study was to evaluate the efficacy and safety of a new hydrodynamic percutaneous thrombectomy catheter in the treatment of thrombosed hemodialysis fistulas and grafts. Twenty-two patients (median age: 47 years; range: 31-79 years) underwent mechanical thrombectomy for thrombosed hemodialysis fistulas or polytetrafluoroethylene (PTFE) grafts. In all cases, an Oasis hydrodynamic catheter was used. Five patients had native fistulas and 17 had PTFE grafts. Six patients required repeat procedures. All patients with native fistulas and 15 of the 17 with PTFE grafts also underwent angioplasty of the venous limb following the thrombectomy. Major outcome measures included technical success, clinical success, primary and secondary patency, and complication rates. Twenty-eight procedures were performed in total. The technical success rate was 100% and 90% and clinical success was 86% and 76% for native fistulas and grafts, respectively. The primary patency at 6 months was 50% and 59% for fistulas and grafts, respectively, and the secondary patency at 6 months was 75% and 70% for fistulas and grafts, respectively. Two patients died of unrelated causes during the follow-up period. The Oasis catheter is an effective mechanical device for the percutaneous treatment of thrombosed hemodialysis access. Our initial success rate showed that the technique is safe in the treatment of both native fistulas and grafts.

  11. A Novel Mechanical Thrombectomy Device for Retrieval of Intravascular Thrombus

    SciTech Connect

    Monsky, Wayne L.; Finitsis, Stephanos; Cicco, Dino De; Brock, John M.; Kucharczyk, John; Latchaw, Richard E.

    2011-04-15

    Purpose: Thrombotic and embolic vascular occlusion represents a leading cause of morbidity and mortality. Currently available thrombectomy devices have limitations, including difficulty removing organized thrombus and clot fragmentation with distal embolization. A novel mechanical thrombectomy device (MTD), designed to remove both hard and soft thrombus without trauma to the blood vessel, was tested in preclinical porcine models evaluating efficacy, safety, and ease of use. Materials and Methods: A total of 26 vessels in 14 pigs underwent mechanical thrombectomy with MTD. Thrombectomy was performed in nine superficial femoral arteries, eight subclavian arteries, five primary branches of the subclavian artery, lateral thoracic artery or the thyrocervical trunk, and four external carotids. Subacute organized fibrin-laden thrombus was injected into the arteries producing vascular occlusion. The MTD was then used for thrombectomy to restore patency and blood flow. Results: Intact thrombus was retrieved from 24 of 26 of the vessels with a single pass of the MTD, resulting in complete restoration of patency in 21 vessels and partial patency in 4 vessels. In 8 cases that used an early design, the embolic material fragmented during withdrawal from the access sheath. In 4 procedures that used an early design, the MTD failed to deploy fully and the embolus was not completely captured. No intraprocedural complications or vascular damage occurred. Conclusions: The present pilot studies demonstrate basic safety and efficacy of a novel MTD with design attributes suitable for retrieval of intact acute and organized chronic thrombus. The device has potential intracranial and peripheral utility.

  12. Mechanical Solitaire Thrombectomy with Low-Dose Booster Tirofiban Injection

    PubMed Central

    Goh, Duck-Ho; Jeong, Hae Woong; Ha, Sam Yeol

    2016-01-01

    Purpose Mechanical thrombectomy using a Solitaire stent has been associated with a high recanalization rate and favorable clinical outcome in intra-arterial thrombolysis. To achieve a higher recanalization rate for mechanical Solitaire thrombectomy, we used an intra-arterial low-dose booster tirofiban injection into the occluded segment after stent deployment. We report the safety and recanalization rates for mechanical Solitaire thrombectomy with a low-dose booster tirofiban injection. Materials and Methods Between February and March 2013, 13 consecutive patients underwent mechanical Solitaire thrombectomy with low-dose booster tirofiban injection. The occlusion sites included the proximal middle cerebral artery (5 patients), the internal carotid artery (5 patients), the top of the basilar artery (2 patients) and the distal middle cerebral artery (M2 segment, 1 patient). Six patients underwent bridge treatment, including intravenous tissue plasminogen activator. Tirofiban of 250 µg was used in all patients except one (500 µg). All occluded vessels were recanalized after 3 attempts at stent retrieval (1 time, n=9; 2 times, n=2; 3 times, n=2). Results Successful recanalization was achieved in all patients (TICI 3, n=8; TICI 2b, n=5). Procedural complications developed in 3 patients (subarachnoid hemorrhage, n=2; hemorrhagic transformation, n=1). Mortality occurred in one patient with a basilar artery occlusion due to reperfusion brain swelling after mechanical Solitaire thrombectomy with low-dose booster tirofiban injection. Favorable clinical outcome (mRS≤2) was observed in 8 patients (61.5%). Conclusion Our modified mechanical Solitaire thrombectomy method using a low-dose booster tirofiban injection might enhance the recanalization rate with no additive hemorrhagic complications. PMID:27621948

  13. Percutaneous rheolytic mechanical thrombectomy in thrombosed direct intrahepatic portosystemic shunt: Report of two cases

    PubMed Central

    Tsetis, Dimitrios; Kehagias, Elias; Samonakis, Dimitrios; Kouroumalis, Elias; Hatzidakis, Adam

    2015-01-01

    We report two patients with Budd–Chiari syndrome, who underwent direct intrahepatic portosystemic shunt complicated by shunt thrombosis. Percutaneous AngioJet mechanical thrombectomy in combination with manual catheter aspiration and balloon disruption of the residual clot was successful, restoring patency of the thrombosed shunt. PMID:26767124

  14. Mechanical Thrombectomy in Patients with Deep Venous Thrombosis

    SciTech Connect

    Delomez, Maxence; Beregi, Jean-Paul; Willoteaux, Serge; Bauchart, Jean-Jacques; D'Othee, Bertrand Janne; Asseman, Philippe; Perez, Nessim; Thery, Claude

    2001-01-15

    Purpose: To report our experience with mechanical thrombectomy in proximal deep vein thrombosis (DVT).Methods: Eighteen patients with a mean ({+-} SD) age of 37.6 {+-} 16.1 years who presented with DVT in the iliac and femoral vein (n = 3), inferior vena cava (n = 5), or inferior vena cava and iliac vein (n = 10), were treated with the Amplatz Thrombectomy Device after insertion of a temporary caval filter.Results: Successful recanalization was achieved in 15 of 18 patients (83%). Overall, the percentage of thrombus removed was 66 {+-} 29%: 73 {+-} 30% at caval level and 55 {+-} 36% at iliofemoral level. Complementary interventions (seven patients) were balloon angioplasty (n = 2), angioplasty and stenting (n = 2), thrombo-aspiration alone (n = 1), thrombo-aspiration, balloon angioplasty, and permanent filter (n = 1), and permanent filter alone (n = 1). There was one in-hospital death. Follow-up was obtained at a mean of 29.6 months; three patients had died (two cancers, one myocardial infarction); 10 had no or minimal sequelae; one had post-phlebitic limb.Conclusion: Mechanical thrombectomy is a potential therapeutic option in patients presenting with proximal DVT.

  15. Mechanical Thrombectomy with Rotarex System in Buerger's Disease

    PubMed Central

    Kilickesmez, Ozgur; Oguzkurt, Levent

    2015-01-01

    We report the case of a patient with 2-month history of chronic thromboembolism of the distal superficial femoral and popliteal arteries with diagnostic features of thromboangiitis obliterans disease. The occlusion could not be crossed by antegrade approach and was achieved retrogradely via dorsalis pedis artery puncture followed by mechanical removal of the thrombus with Rotarex system (Straub Medical AG, Wangs, Switzerland). Subsequent ballooon angioplasties achieved exclusion of the thrombus, and straight-line flow established to the foot through the anterior tibial Artery. The present case report demonstrates the success of mechanical thrombectomy in a patient with Buerger's vasculitis. PMID:25861548

  16. Mechanical Thrombectomy with Rotarex System in Buerger's Disease.

    PubMed

    Kilickesmez, Ozgur; Oguzkurt, Levent

    2015-01-01

    We report the case of a patient with 2-month history of chronic thromboembolism of the distal superficial femoral and popliteal arteries with diagnostic features of thromboangiitis obliterans disease. The occlusion could not be crossed by antegrade approach and was achieved retrogradely via dorsalis pedis artery puncture followed by mechanical removal of the thrombus with Rotarex system (Straub Medical AG, Wangs, Switzerland). Subsequent ballooon angioplasties achieved exclusion of the thrombus, and straight-line flow established to the foot through the anterior tibial Artery. The present case report demonstrates the success of mechanical thrombectomy in a patient with Buerger's vasculitis. PMID:25861548

  17. Mechanical thrombectomy in patients with acute ischemic stroke: a cost-utility analysis

    PubMed Central

    Xie, Xuanqian; Lambrinos, Anna; Chan, Brian; Dhalla, Irfan A.; Krings, Timo; Casaubon, Leanne K.; Lum, Cheemun; Sikich, Nancy; Bharatha, Aditya; Pereira, Vitor Mendes; Stotts, Grant; Saposnik, Gustavo; O'Callaghan, Christina; Kelloway, Linda; Hill, Michael D.

    2016-01-01

    Background: The beneficial effects of endovascular treatment with new-generation mechanical thrombectomy devices compared with intravenous thrombolysis alone to treat acute large-artery ischemic stroke have been shown in randomized controlled trials (RCTs). This study aimed to estimate the cost utility of mechanical thrombectomy compared with the established standard of care. Methods: We developed a Markov decision process analytic model to assess the cost-effectiveness of treatment with mechanical thrombectomy plus intravenous thrombolysis versus treatment with intravenous thrombolysis alone from the public payer perspective in Canada. We conducted comprehensive literature searches to populate model inputs. We estimated the efficacy of mechanical thrombectomy plus intravenous thrombolysis from a meta-analysis of 5 RCTs, and we used data from the Oxford Vascular Study to model long-term clinical outcomes. We calculated incremental cost-effectiveness ratios (ICER) using a 5-year time horizon. Results: The base case analysis showed the cost and effectiveness of treatment with mechanical thrombectomy plus intravenous thrombolysis to be $126 939 and 1.484 quality-adjusted life-years (QALYs), respectively, and the cost and effectiveness of treatment with intravenous thrombolysis alone to be $124 419 and 1.273 QALYs, respectively. The mechanical thrombectomy plus intravenous thrombolysis strategy was associated with an ICER of $11 990 per QALY gained. Probabilistic sensitivity analysis showed that the probability of treatment with mechanical thrombectomy plus intravenous thrombolysis being cost-effective was 57.5%, 89.7% and 99.6% at thresholds of $20 000, $50 000 and $100 000 per QALY gained, respectively. The main factors influencing the ICER were time horizon, extra cost of mechanical thrombectomy treatment and age of the patient. Interpretation: Mechanical thrombectomy as an adjunct therapy to intravenous thrombolysis is cost-effective compared with

  18. In-vitro testing of RF-enabled low force mechanical thrombectomy for ischemic stroke.

    PubMed

    Chi Hang Chon; Zhen Qin; Lam, Alexander K N; Kwok, John C K; Yuen, Matthew M F; Lam, David C C

    2015-08-01

    Mechanical thrombectomy for ischemic stroke has high recanalization rate, long treatment time window and low hemorrhage risk. However, the clot engagement approach of caging the clot against the vessel wall can cause vessel stenosis and stroke recurrence. A device with reduced radial stenting force that reduces vessel wall friction would minimize stenosis and damage. The use of localized Radio Frequency (RF) to enable clot engagement and retrieval with minimal stenting force is explored in this study. New mechanical thrombectomy devices enabled with RF (Patent No.: US 62/172,043) were built and tested on human blood clots in vessels ex vivo. Test results showed that the RF-mechanical thrombectomy successfully and reproducibly captured and retrieved the clots without relying on stent caging of the clot against the vessel wall. Further work will be conducted on animals to compare vessel wall damage between conventional and RF-mechanical thrombectomy. PMID:26736518

  19. Mechanical Thrombectomy for Ischaemic Stroke: The First UK Case Series

    PubMed Central

    Ahmad, Nasar; Nayak, Sanjeev; Jadun, Changez; Natarajan, Indira; Jain, Palbha; Roffe, Christine

    2013-01-01

    Background and Purpose Endovascular treatments have the potential to accelerate reperfusion in acute ischaemic stroke with large vessel occlusion. In the UK only a few stroke centres offer this interventional option. The University Hospital of North Staffordshire (UHNS) has treated the largest number of cases in the UK. Results of the first 106 endovascular treatments (EVT) are presented here. Methods All patients treated with EVT (intra-arterial thrombolysis (IAT), mechanical thrombectomy (MT) or both, or an attempt at intervention) for acute stroke at UHNS, Stoke-on-Trent, UK, were entered into a prospective register. Baseline demographic and clinical data, the National Institutes for Health Stroke Scale (NIHSS), imaging results including Thrombolysis in Cerebral Infarction (TICI) score, and complications were recorded. Mortality, and modified Rankin score (mRS) were assessed at 90 days. Results From December 2009 to January 2013 106 patients (mean age 64 years, median baseline NIHSS 18) were treated with EVT (thrombectomy ± IAT 83%, IAT alone 13%, neither 4%). Seventy-eight per cent of occlusions were in the anterior circulation. Intravenous bridging thrombolysis was performed in 81%. Revascularization was successful (TICI 2b/3) in 84%. The median time from stroke onset to the end of the procedure was 6 h 03 min. A good outcome (mRS≤2) at 90 days was achieved in 48% with a mortality of 15%. Fatal or nonfatal symptomatic intracranial haemorrhage (sICH) within 10 days occurred in 9%. The median length of stay was 14 days (31% discharged home ≤7 days). Conclusions EVT led to good clinical outcomes in almost 50% of patients with severe strokes. PMID:24386090

  20. Mechanical thrombectomy in pediatric acute ischemic stroke: Clinical outcomes and literature review.

    PubMed

    Madaelil, Thomas P; Kansagra, Akash P; Cross, DeWitte T; Moran, Christopher J; Derdeyn, Colin P

    2016-08-01

    There are limited data on outcomes of mechanical thrombectomy for pediatric stroke using modern devices. In this study, we report two cases of pediatric acute ischemic stroke treated with mechanical thrombectomy, both with good angiographic result (TICI 3) and clinical outcome (no neurological deficits at 90 days). In addition, we conducted a literature review of all previously reported cases describing the use of modern thrombectomy devices. Including our two cases, the aggregate rate of partial or complete vessel recanalization was 100% (22/22), and the aggregate rate of favorable clinical outcome was 91% (20/22). This preliminary evidence suggests that mechanical thrombectomy with modern devices may be a safe and effective treatment option in pediatric patients with acute ischemic stroke. PMID:26945589

  1. Primary stentriever versus combined stentriever plus aspiration thrombectomy approaches: in vitro stroke model comparison

    PubMed Central

    Mokin, Maxim; Ionita, Ciprian N; Nagesh, Swetadri Vasan Setlur; Rudin, Stephen; Levy, Elad I; Siddiqui, Adnan H

    2014-01-01

    Background Artificial stroke models can be used for testing various thrombectomy devices. Objective To determine the value of combined stentriever–aspiration thrombectomy compared with the stentriever-alone approach. Methods We designed an in vitro model of the intracranial circulation with a focus on the middle cerebral artery (MCA) that closely resembles the human intracranial circulation. After introducing fresh clot in the MCA, we used conventional biplane angiography and microangiographic fluoroscopy to compare recanalization rates and occurrence of emboli in new, unaffected territory for thrombectomy approaches in which a stentriever (Solitaire flow restoration stentriever, Covidien) was used alone or in combination with continuous manual aspiration through a Navien catheter (Covidien). Results In a total of 22 experiments (11 for each approach), successful clot delivery to the MCA was achieved in all cases. Successful angiographic recanalization (thrombolysis in cerebral infarction score of 2b–3) was achieved more frequently with the combined stentriever–aspiration approach than with the stentriever-alone approach (in 10 vs 4 experiments, p=0.023). Emboli in new territory occurred in three experiments with the stentriever-alone approach, and none were seen with the combined approach (p=0.21). Conclusions The combined stentriever–aspiration approach to thrombectomy leads to better angiographic recanalization rates than use of the stentriever alone. Further experiments are needed to test the value of balloon-guide catheters and aspiration performed using other types of catheters and modes of aspiration. PMID:24789594

  2. Mechanical thrombectomy in cardiac myxoma stroke: a case report and review of the literature.

    PubMed

    Chung, Yoon Sang; Lee, Woong Jae; Hong, Joonhwa; Byun, Jun Soo; Kim, Jae Kyun; Chae, Soo Ahn

    2016-06-01

    Cardiac myxoma is the most common primary tumor of the heart. It is a rare cause of acute ischemic stroke and commonly not detected until after the stroke. There is no current guideline for the treatment of cardiac myxoma stroke and only a few cases of mechanical thrombectomy have been reported. We present a case of cardiac myxoma stroke in a 4-year-old boy treated with a stent-retrieval device and review the literature describing the safety and efficacy of mechanical thrombectomy in cardiac myxoma stroke. We also describe imaging features of the myxoma clot on susceptibility weighted images. PMID:27040551

  3. Adjuvant Tirofiban Injection Through Deployed Solitaire Stent As a Rescue Technique After failed Mechanical Thrombectomy in Acute Stroke

    PubMed Central

    Seo, Jung Hwa; Kim, Sung Tae; Kim, Eun-Gyu

    2015-01-01

    Purpose We present our experiences of intra-arterial tirofiban injection through a deployed Solitaire stent as a rescue therapy after failed mechanical thrombectomy in patients with acute ischemic stroke. Materials and Methods Data on 18 patients treated with adjunctive tirofiban injection through a temporarily deployed Solitaire stent after failed mechanical thrombectomy were retrospectively reviewed. Solitaire stent was used as a primary thrombectomy device in 16 of 18 patients. Two patients received manual aspiration thrombectomy initially. If initial mechanical thrombectomy failed, tirofiban was injected intra-arterially through the deployed Solitaire stent and then subsequent Solitaire thrombectomy was performed. Results Fourteen patients had occlusions in the middle cerebral artery, 2 in the distal internal carotid artery, and 2 in the basilar artery. Successful recanalization was achieved in 14 patients (77.7%) after intra-arterial injection of tirofiban and subsequent Solitaire thrombectomy. Three patients without successful recanalization after rescue method received angioplasty with stenting. Overall, successful recanalization (TICI grades 2b and 3) was achieved in 17 (94.4%) of 18 patients. Periprocedural complications occurred in 5 patients: distal migration of emboli in 5 patients and vessel perforation in 1. Three patients died. Good functional outcome (mRS ≤ 2) was achieved in 9 patients (50.0%) at 3 months. Conclusion Rescue intra-arterial injection of tirofiban through a temporarily deployed Solitaire stent may facilitate further recanalization in cases of failed mechanical thrombectomy in patients with acute ischemic stroke. PMID:25763294

  4. “Missing clot” during mechanical thrombectomy in acute stroke using Solitaire stent retrieval system

    PubMed Central

    Huded, Vikram; Nambiar, Vivek; De Souza, Romnesh; Bohra, Vikram; Ramankutty, Ritesh

    2016-01-01

    Stent retrieval system is an established treatment modality in acute ischemic stroke with large vessel occlusion. Here, we describe a complication which occurred during mechanical thrombectomy in three cases where the clot dislodged during retrieval. There was a possibility of the clot getting reinjected into the artery with possible dire consequences. PMID:27293350

  5. Mechanical Thrombectomy in Patients With Acute Ischemic Stroke: A Health Technology Assessment

    PubMed Central

    2016-01-01

    Background In Ontario, current treatment for eligible patients who have an acute ischemic stroke is intravenous thrombolysis (IVT). However, there are some limitations and contraindications to IVT, and outcomes may not be favourable for patients with stroke caused by a proximal intracranial occlusion. An alternative is mechanical thrombectomy with newer devices, and a number of recent studies have suggested that this treatment is more effective for improving functional independence and clinical outcomes. The objective of this health technology assessment was to evaluate the clinical effectiveness and cost-effectiveness of new-generation mechanical thrombectomy devices (with or without IVT) compared to IVT alone (if eligible) in patients with acute ischemic stroke. Methods We conducted a systematic review of the literature, limited to randomized controlled trials that examined the effectiveness of mechanical thrombectomy using stent retrievers and thromboaspiration devices for patients with acute ischemic stroke. We assessed the quality of the evidence using the GRADE approach. We developed a Markov decision-analytic model to assess the cost-effectiveness of mechanical thrombectomy (with or without IVT) versus IVT alone (if eligible), calculated incremental cost-effectiveness ratios using a 5-year time horizon, and conducted sensitivity analyses to examine the robustness of the estimates. Results There was a substantial, statistically significant difference in rate of functional independence (GRADE: high quality) between those who received mechanical thrombectomy (with or without IVT) and IVT alone (odds ratio [OR] 2.39, 95% confidence interval [CI] 1.88–3.04). We did not observe a difference in mortality (GRADE: moderate quality) (OR 0.80, 95% CI 0.60–1.07) or symptomatic intracerebral hemorrhage (GRADE: moderate quality) (OR 1.11, 95% CI 0.66–1.87). In the base-case cost-utility analysis, which had a 5 year time horizon, the costs and effectiveness for

  6. Intraarterial mechanical thrombectomy for the treatment of postoperative cerebral infarction: a case report

    PubMed Central

    Yun, Jong-Won; Kim, Yong-Ho; Min, Jinhye; Choi, Young Soon; Chae, Young Keun; Lee, Eun Sang; Kang, Yoo

    2014-01-01

    Perioperative ischemic stroke is an uncommon event associated with significant morbidity and mortality. The complexity of the surgical procedure and surgery induced hypercoagulable status also influence the incidence of stroke. The management of stroke involves a decision regarding the quickest suitable revascularization method. Endovascular mechanical thrombectomy, such as intra-arterial mechanical thrombectomy (IAMT), can restore vascular patency of the vessels, providing an alternative or synergistic method to restore blood flow. Although, there are no recommended treatment guidelines, IAMT is eligible to be a treatment of choice for perioperative ischemic stroke. We experienced a case of a patient who demonstrated hemiplegia and aphasia, the early symptom of acute ischemic stroke, in the post-anesthesia care unit and performed IAMT successfully. Thus we report the case with a review of the relevant literature. PMID:24910735

  7. Mechanical Thrombectomy of Iliac Vein Thrombosis in a Pig Model Using the Rotarex and Aspirex Catheters

    SciTech Connect

    Minko, P. Bücker, A.

    2013-06-08

    PurposeTo investigate the efficacy and safety of mechanical thrombectomy for iliac vein thrombosis using Rotarex and Aspirex catheters in a pig model.Materials and MethodsIliac vein thrombosis was induced in six pigs by means of an occlusion-balloon catheter and thrombin injection. The presence of thrombi was verified by digital subtraction angiography (DSA) and computed tomography (CT). Thrombectomy was performed using 6F and 8F Rotarex and 6F, 8F, and 10F Aspirex catheters (Straub Medical AG, Wangs, Switzerland). After intervention, DSA and CT were repeated to evaluate the efficacy of mechanical thrombectomy and to exclude local complications. In addition, pulmonary CT was performed to rule out pulmonary embolism. Finally, all pigs were killed, and iliac veins were dissected to perform macroscopic and histological examination.ResultsThrombus induction was successfully achieved in all animals as verified by DSA and CT. Subsequent thrombectomy lead to incomplete recanalization of the iliac veins with residual thrombi in all cases. However, the use of the 6F and 8F Rotarex catheters caused vessel perforation and retroperitoneal hemorrhage in all cases. Application of the Aspirex device caused one small transmural perforation in a vessel treated with a 10F Aspirex catheter, and this was only seen microscopically. Pulmonary embolism was detected in one animal treated with the Rotarex catheters, whereas no pulmonary emboli were seen in animals treated with the Aspirex catheters.ConclusionThe Aspirex catheter allowed subtotal and safe recanalization of iliac vein thrombosis. In contrast, the use of the Rotarex catheter caused macroscopically obvious vessel perforations in all cases.

  8. Mechanical thrombectomy for acute ischemic stroke in pregnancy using the penumbra system.

    PubMed

    Aaron, Sanjith; Shyamkumar, N K; Alexander, Sunithi; Babu, P Suresh; Prabhakar, A T; Moses, Vinu; Murthy, T V; Alexander, Mathew

    2016-01-01

    Even though intravenous thrombolysis with tissue plasminogen activator (IV tPA) is the standard of care in acute ischemic stroke, its use in pregnancy is not clearly defined. Mechanical thrombectomy devices can be an option; however, literature on the use of such mechanical devices in stroke in pregnancy is lacking. Here we describe two cases that developed acute embolic stroke during pregnancy who were successfully treated by mechanical clot retrieval using the Penumbra system 28 (Penumbra Inc., Alameda, California, USA). To the best of our knowledge, these are the only case reports on the use of the Penumbra device in pregnant patients with acute ischemic stroke. PMID:27293343

  9. Mechanical thrombectomy for acute ischemic stroke in pregnancy using the penumbra system

    PubMed Central

    Aaron, Sanjith; Shyamkumar, N. K.; Alexander, Sunithi; Babu, P. Suresh; Prabhakar, A. T.; Moses, Vinu; Murthy, T. V.; Alexander, Mathew

    2016-01-01

    Even though intravenous thrombolysis with tissue plasminogen activator (IV tPA) is the standard of care in acute ischemic stroke, its use in pregnancy is not clearly defined. Mechanical thrombectomy devices can be an option; however, literature on the use of such mechanical devices in stroke in pregnancy is lacking. Here we describe two cases that developed acute embolic stroke during pregnancy who were successfully treated by mechanical clot retrieval using the Penumbra system 28 (Penumbra Inc., Alameda, California, USA). To the best of our knowledge, these are the only case reports on the use of the Penumbra device in pregnant patients with acute ischemic stroke. PMID:27293343

  10. Efficacy and Safety of Thrombectomy Combined with Intracoronary Administration of Tirofiban in ST-segment Elevation Myocardial Infarction (STEMI)

    PubMed Central

    Gao, Lu; Cao, Zhenhua; Zhang, Hong

    2016-01-01

    Background No/slow reflow gives rise to serious complications in STEMI patients undergoing PCI, and can lead to worse outcomes. Several measures are used to prevent no/slow reflow, including thrombus removal processes and intensive use of anticoagulant agents. Our study was designed to evaluate the efficacy and safety of thrombectomy and intracoronary administration of GPIIb/IIIa inhibitors in STEMI patients undergoing PPCI. Material/Methods We randomly assigned 240 STEMI patients into 3 groups. Before PPCI, patients in group A received thrombectomy and intracoronary administration of tirofiban. Patients in group B received thrombectomy, and patients in group C neither of these 2 treatments. Their demographic data and coronary angiography results were recorded. TIMI grade flow was used to evaluate the effect. After the follow-up, major adverse cardiac events were regarded as study endpoints in evaluating the safety of the combined therapy. Results We found no significant differences among the 3 groups in demographic and clinical characteristics (p>0.05). Patients in group A had better TIMI grade classifications and ST-segment elevation (p=0.005), and lower incidence of no/slow reflow (p=0.031) and MACE. During 6-month follow-up, the MACE rate was lower in group A than in groups B and C (p=0.038). Conclusions The use of thrombectomy combined with intracoronary administration of tirofiban is relatively effective and safe in STEMI patients undergoing PPCI. PMID:27475844

  11. Effective mechanical thrombectomy in a patient with hyperacute ischemic stroke associated with cardiac myxoma.

    PubMed

    Baek, Seol-Hee; Park, Soonchan; Lee, Nam Joon; Kang, Youngjin; Cho, Kyung-Hee

    2014-10-01

    Ischemic stroke is the most common neurologic manifestation of cardiac myxoma. However, there has been no current guideline on the treatment of hyperacute ischemic stroke due to cardiac myxoma. We describe a patient with hyperacute stroke caused by cardiac myxoma who had a good outcome with rapid recanalization through mechanical thrombectomy. A 46-year-old man was admitted with acute symptoms of right side hemiplegia and global aphasia. Brain computed tomography (CT) angiography showed a T occlusion of the left internal carotid artery. Intravenous recombinant tissue plasminogen activator was administered. However, his clinical symptoms did not improve. Thus, we performed endovascular treatment and had a successful outcome. A pathologic examination of the retrieved clot revealed a tumor emboli from a cardiac myxoma. Transthoracic echocardiogram revealed a left atrial myxoma in which a large mass was attached to the posterior wall of the aorta. The patient's neurologic deficits recovered with the exception of left eye blindness. Reperfusion therapy with mechanical thrombectomy might be safe and effective for the rapid revascularization of large vessel occlusions in hyperacute ischemic stroke, from which the tumor thrombi can be retrieved. PMID:25174564

  12. Acute stroke from paradoxical embolism of dense fibrous tissue following pacemaker lead extraction: salvation by mechanical thrombectomy.

    PubMed

    Dayal, Nicolas B; Narata, Ana Paula; Burri, Haran

    2016-02-01

    Systemic embolization is a dreaded complication of transvenous lead extraction (TLE), even without visible vegetations. Preoperative patent foramen ovale evaluation is important, justifying neurological surveillance or consideration of surgical extraction in selected cases. In case of stroke after TLE, mechanical thrombectomy is a successful therapy, and should be readily available. PMID:26862414

  13. [Successful Treatment of Repeated Bilateral Middle Cerebral Artery Occlusion by Performing Mechanical Thrombectomy in a Patient with Trousseau Syndrome].

    PubMed

    Inoue, Satoshi; Fujita, Atsushi; Mizowaki, Takashi; Uchihashi, Yoshito; Kuroda, Ryuichi; Urui, Seishirou; Kurihara, Eiji; Kohmura, Eiji

    2016-06-01

    We report a patient with Trousseau syndrome who presented with repeated acute middle cerebral artery (MCA) occlusion, which was successfully treated by performing mechanical thrombectomy. A 66-year-old man with a lung lesion and abdominal lymph node swelling experienced a sudden onset of left hemiparesis. Magnetic resonance angiography (MRA) revealed a right MCA occlusion. Perfusion-weighted imaging revealed reduced cerebral blood flow in the right MCA territory. Complete recanalization of the occluded vessel was achieved by performing mechanical thrombectomy, and his symptoms remarkably disappeared. Twenty days after the procedure, he experienced right hemiparesis and total aphasia. MRA revealed a left MCA occlusion, which was located on the contralateral side of the first occlusion. The second mechanical thrombectomy was successfully performed, and complete recanalization was successfully achieved. Right hemiparesis improved after the procedure. Histological examination of the retrieved clots revealed coagulated fibrin and platelets. Cytodiagnosis of pleural effusion revealed adenocarcinoma, and he was diagnosed with lung adenocarcinoma and cancerous pleurisy. Trousseau syndrome was the presumed primary cause of the patient's tendency for thrombogenesis. To the best of our knowledge, there were no reports regarding the repeated use of mechanical thrombectomy for patients with bilateral MCA occlusion caused by Trousseau syndrome. Neuroendovascular therapy can offer good neurological outcomes even in patients with malignant lesions. PMID:27270149

  14. Transjugular Intrahepatic Portosystemic Shunt, Mechanical Aspiration Thrombectomy, and Direct Thrombolysis in the Treatment of Acute Portal and Superior Mesenteric Vein Thrombosis

    SciTech Connect

    Ferro, Carlo; Rossi, Umberto G. Bovio, Giulio; Dahamane, M'Hamed; Centanaro, Monica

    2007-09-15

    A patient was admitted because of severe abdominal pain, anorexia, and intestinal bleeding. Contrast-enhanced multidetector computed tomography demonstrated acute portal and superior mesenteric vein thrombosis (PSMVT). The patient was treated percutaneously with transjugular intrahepatic portosystemic shunt (TIPS), mechanical aspiration thrombectomy, and direct thrombolysis, and 1 week after the procedure, complete patency of the portal and superior mesenteric veins was demonstrated. TIPS, mechanical aspiration thrombectomy, and direct thrombolysis together are promising endovascular techniques for the treatment of symptomatic acute PSMVT.

  15. Complex decision-making in stroke: preoperative mechanical thrombectomy of septic embolus for emergency cardiac valve surgery.

    PubMed

    Ladner, Travis R; Davis, Brandon J; He, Lucy; Kirshner, Howard S; Froehler, Michael T; Mocco, J

    2015-12-01

    Stroke is a common and devastating embolic manifestation of infective endocarditis. We report a case of cardioembolic stroke in a patient with enterococcal endocarditis, with National Institutes of Health Stroke Scale score of 3. A middle-aged patient with bacterial endocarditis exhibited mild intermittent left hemiparesis and dysarthria in the setting of severe aortic insufficiency requiring urgent aortic valve replacement. Cerebrovascular imaging revealed a partially occlusive thrombus in the M1 segment of the right middle cerebral artery, which became symptomatic during relative hypotension. Given the expected hypotension during the urgently needed aortic valve replacement, there was a significant risk of infarction of most of the right hemisphere. Thus, mechanical thrombectomy was performed immediately prior to thoracotomy, and the patient awoke neurologically intact. This case demonstrates avoidance of a large stroke due to a subocclusive thrombus and anticipated intraoperative hypotension with preoperative mechanical thrombectomy. PMID:25422318

  16. Complex decision-making in stroke: preoperative mechanical thrombectomy of septic embolus for emergency cardiac valve surgery.

    PubMed

    Ladner, Travis R; Davis, Brandon J; He, Lucy; Kirshner, Howard S; Froehler, Michael T; Mocco, J

    2014-01-01

    Stroke is a common and devastating embolic manifestation of infective endocarditis. We report a case of cardioembolic stroke in a patient with enterococcal endocarditis, with National Institutes of Health Stroke Scale score of 3. A middle-aged patient with bacterial endocarditis exhibited mild intermittent left hemiparesis and dysarthria in the setting of severe aortic insufficiency requiring urgent aortic valve replacement. Cerebrovascular imaging revealed a partially occlusive thrombus in the M1 segment of the right middle cerebral artery, which became symptomatic during relative hypotension. Given the expected hypotension during the urgently needed aortic valve replacement, there was a significant risk of infarction of most of the right hemisphere. Thus, mechanical thrombectomy was performed immediately prior to thoracotomy, and the patient awoke neurologically intact. This case demonstrates avoidance of a large stroke due to a subocclusive thrombus and anticipated intraoperative hypotension with preoperative mechanical thrombectomy. PMID:25410029

  17. Immunohistochemical Analysis of Cerebral Thrombi Retrieved by Mechanical Thrombectomy from Patients with Acute Ischemic Stroke

    PubMed Central

    Schuhmann, Michael K.; Gunreben, Ignaz; Kleinschnitz, Christoph; Kraft, Peter

    2016-01-01

    Mechanical thrombectomy is a novel treatment option for patients with acute ischemic stroke (AIS). Only a few studies have previously suggested strategies to categorize retrieved clots according to their histologic composition. However, these reports did not analyze potential biomarkers that are of importance in stroke-related inflammation. We therefore histopathologically investigated 37 intracerebral thrombi mechanically retrieved from patients with AIS, and focused on the composition of immune cells and platelets. We also conducted correlation analyses of distinctive morphologic patterns (erythrocytic, serpentine, layered, red, white, mixed appearance) with clinical parameters. Most T cells and monocytes were detected in erythrocytic and red clots, in which the distribution of these cells was random. In contrast, von Willebrand factor (vWF)-positive areas co-localized with regions of fibrin and collagen. While clots with huge amounts of vWF seem to be associated with a high National Institute of Health Stroke Scale score at admission, histologic findings could not predict the clinical outcome at discharge. In summary, we provide the first histologic description of mechanically retrieved intracerebral thrombi regarding biomarkers relevant for inflammation in ischemic stroke. PMID:26927082

  18. Immunohistochemical Analysis of Cerebral Thrombi Retrieved by Mechanical Thrombectomy from Patients with Acute Ischemic Stroke.

    PubMed

    Schuhmann, Michael K; Gunreben, Ignaz; Kleinschnitz, Christoph; Kraft, Peter

    2016-01-01

    Mechanical thrombectomy is a novel treatment option for patients with acute ischemic stroke (AIS). Only a few studies have previously suggested strategies to categorize retrieved clots according to their histologic composition. However, these reports did not analyze potential biomarkers that are of importance in stroke-related inflammation. We therefore histopathologically investigated 37 intracerebral thrombi mechanically retrieved from patients with AIS, and focused on the composition of immune cells and platelets. We also conducted correlation analyses of distinctive morphologic patterns (erythrocytic, serpentine, layered, red, white, mixed appearance) with clinical parameters. Most T cells and monocytes were detected in erythrocytic and red clots, in which the distribution of these cells was random. In contrast, von Willebrand factor (vWF)-positive areas co-localized with regions of fibrin and collagen. While clots with huge amounts of vWF seem to be associated with a high National Institute of Health Stroke Scale score at admission, histologic findings could not predict the clinical outcome at discharge. In summary, we provide the first histologic description of mechanically retrieved intracerebral thrombi regarding biomarkers relevant for inflammation in ischemic stroke. PMID:26927082

  19. Advances in interventional neuroradiology: novel use of mechanical thrombectomy in acute ischemic stroke.

    PubMed

    Nayak, Sanjeev; Fitzpatrick, Sean

    2015-05-01

    Dr Sanjeev Nayak speaks to Sean Fitzpatrick, Commissioning Editor: Dr Sanjeev Nayak is a Consultant Neuroradiologist with special interest in Interventional Neuroradiology at the University Hospital of North Midlands, Stoke on Trent. He was responsible for the development of Interventional Stroke Service which he did immediately following his appointment in 2009 and was the lead neuroradiologist from 2010 to 2013. Dr Nayak and his team have pioneered in the field of mechanical thrombectomy and stenting in acute ischemic stroke and treated the largest number of such cases in the UK. His team has produced one of the best clinical outcomes for such patients with the lowest mortality rates in the UK. This work has been nominated for numerous national awards in various categories of BMJ, Patient Safety and Care integration awards. Dr Nayak was the finalist at the HSJ awards under the category of 'Clinical Leader of the Year 2012' and NHS Leadership awards 'NHS Inspirational Leader of the Year 2013. Dr Nayak is also involved in patents and designs involving new stroke interventional devices and is actively involved in stroke research which has led to numerous publications in peer reviewed journals. Dr Nayak has organized national conferences and lectured at various national and international conferences in his field of interest. PMID:26021630

  20. Improvement of Stent Retriever Design and Efficacy of Mechanical Thrombectomy in a Flow Model

    SciTech Connect

    Wenger, Katharina; Nagl, Frank; Wagner, Marlies Berkefeld, Joachim

    2013-02-15

    In vitro experiments were performed to evaluate the efficacy of mechanical intracranial thrombectomy comparing the newly developed Aperio stent retriever and standard devices for stroke treatment. The Aperio (A), with an increased working length of 4 cm and a special cell design for capturing and withholding clots, was compared to three benchmark devices: the Solitaire retrievable stent (B), the Merci X6 (C), and the Merci L5 retriever (D). In a vascular glass model with pulsatile flow, reminiscent of the M1 segment of the middle cerebral artery, we repeatedly induced occlusion by generating thrombi via a modified Chandler loop system. The numbers of recanalization attempts, peripheral embolizations, and recanalizations at the site of occlusion were recorded during 10 retrieval experiments with each device. Eleven devices were able to remove the blood clots from the occluded branch. In 34 of 40 experiments, restoration of flow was obtained in 1-3 attempts. The main differences between the study devices were observed in terms of clot withholding and fragmentation during retrieval. Although there was only one fragmentation recorded for device A, disengagement of the whole clot or peripheral embolization of fragments occurred more frequently (5-7 times) with devices B, C, and D. In a vascular model, the design of device A was best at capturing and withholding thrombi during retrieval. Further study will be necessary to see whether this holds true in clinical applications.

  1. Acute Pancreatitis after Percutaneous Mechanical Thrombectomy: Case Report and Review of the Literature

    SciTech Connect

    Hershberger, Richard C. Bornak, Arash; Aulivola, Bernadette; Mannava, Krishna

    2011-02-15

    Purpose: We describe a case of severe acute pancreatitis after percutaneous mechanical thrombectomy (PMT) and review the literature for the occurrence of this complication. Materials and Methods: A 53-year-old man with a history of bilateral external iliac artery stent placement sought care for acute onset of lifestyle-limiting left claudication. Angiography confirmed left external iliac stent occlusion, and PMT with the AngioJet Xpeedior catheter (Possis Medical, Minneapolis MN) was performed. Results: After PMT of the occluded external iliac artery, a residual in-stent stenosis required the placement of a second iliac stent. The procedure was complicated by severe acute pancreatitis. Other causes of pancreatitis were eliminated during the patient's hospital stay. A literature review revealed nine cases of acute pancreatitis after PMT. Conclusion: Although rare, pancreatitis can be a devastating complication of PMT. The development of pancreatitis seems to be related to the products of extensive hemolysis triggering an inflammatory process. To prevent this complication, we recommend that close attention be paid to the duration and extent of PMT, thereby avoiding extensive hemolysis and subsequent complications.

  2. Mechanical thrombectomy with ‘ADAPT’ technique by transcervical access in acute ischemic stroke

    PubMed Central

    Remollo, Sebastian; García, Maria Rosa; Hidalgo, Cristina; Hernández-Perez, Maria; Ciorba, Mihaela

    2015-01-01

    Background The mechanical thrombectomy (MT) for endovascular clot retrieval has dramatically improved successful revascularization and clinical outcome in selected acute stroke patients. MT is typically performed via a transfemoral approach, but catheterization of the occluded vessel can be problematic in cases of extensive vessel tortuosity. We describe a case of MT with the ‘ADAPT’ technique by direct carotid access due to an inability to catheterize the ICA by a transfemoral approach for acute cerebral ischemia in the setting of left MCA occlusion. Excellent angiographic and good clinical results were obtained without any complications. Case report An 80-year-old woman was admitted with a stroke by occlusion of the left MCA, with an NIHSS: 11, and an ASPECT: 7 in the CT. Under sedation a transfemoral angiography was performed, but after multiple attempts, it was impossible to make a stable catheterization of the left CCA. A transcervical approach was pursued. With ultrasound guidance the CCA was catheterized. Using the ‘ADAPT’ technique, we performed a successful MT. Post-procedure angiography (at 14 minutes) demonstrated recanalization of the entire left MCA (TICI: 3), without complications. The carotid access point was closed with a percutaneous closure. Control TC at 24 h showed a slight hypodensity in the left lenticular nucleus, and loss of gray-white matter differentiation in the adjacent cortex. Neurologically, the patient presented with progressive improvement. At discharge, she had an NIHSS: 0, mRS: 0 and Barthel: 100. Conclusions MT by direct carotid access is an effective alternative technique in those cases where it is not accessible by a transfemoral approach. PMID:26443297

  3. Mechanical thrombectomy in acute ischaemic stroke: a review of the literature, clinical effectiveness and future use.

    PubMed

    Lally, Frank; Grunwald, Iris Q; Sanyal, Ranjan; Natarajan, Indira; Roffe, Christine

    2013-03-01

    The only effective treatment licensed for acute ischaemic stroke is intravenous thrombolysis within 4.5 hours from stroke onset. An alternative method of restoring blood flow is mechanical thrombectomy (MT). Although this is highly effective at recanalization, it remains unclear whether it is more effective than thrombolysis in improving clinical outcomes. This review examines key clinical outcomes from published studies and reviews ongoing studies to identify devices, patient population, and stated outcomes of MT. We discuss the issues when comparing clinical outcomes from different trials and suggest measures to help standardize reporting. We used routine review methodology to search relevant databases for stroke and MT published between 1999 - 2012 and active trials between August 2011 - May 2012. The studies in this review had an overall patient population of 8354. The most widely used primary outcome (94% of studies) was successful recanalization. The mean mortality across the studies was 17% (range 7 - 44), 64% of studies reported neurological improvement and 97% reported functional outcome with 42% (range 15 - 54)] achieving independence in activities of daily living. Mean symptomatic intracerebral haemorrhage was 11% (range 0 - 45%). There were significant differences in outcome reporting between studies. Evidence from published studies shows a strong relationship between recanalization and good outcomes although non-standardization makes comparisons difficult. There is a trend towards higher recanalization, lower mortality, and better functional outcome in more recent studies. To examine effectiveness of MT vs thrombolysis, randomized controlled trials are needed. Several are currently in progress but it remains to be seen if procedures and outcomes are reported in a standardized manner. PMID:23394538

  4. Can the results of treatment of deep venous thrombosis be improved by combining surgical thrombectomy with regional fibrinolysis?

    PubMed

    Nachbur, B B; Beck, E A; Senn, A

    1980-01-01

    A new mode of treatment of extensive acute and subacute deep venous thrombosis of the lower extremities is introduced. For this purpose the beneficial effects of surgical thrombectomy and of thrombolysis with streptokinase are combined during the course of a single surgical intervention. Rapid-flow regional perfusion is the vehicle used for administration of streptokinase and probably represents the third arm of this therapeutic approach by adding a hemodynamic wash-out effect. Because the thrombolytic agent is rinsed out of the circuit at the end of regional perfusion the usual side effects and contra-indications of this drug are avoided. Early and late results of this treatment are assessed clinically and with repeat venograms in a group of 9 patients. Highly satisfactory results were obtained in 6 patients with complete anatomical and functional restoration of deep veins along their entire length in three cases. It is felt that continued use of this method is warranted and that the results of treatment of deep venous thrombosis can thus be improved. PMID:6993494

  5. Comparison of the Effectiveness of Three Methods of Recanalization in a Model of the Middle Cerebral Artery: Thrombus Aspiration via a 4F Catheter, Thrombus Aspiration via the GP Thromboaspiration Device, and Mechanical Thrombectomy Using the Solitaire Thrombectomy Device.

    PubMed

    Tennuci, Christopher; Pearce, Gillian; Wong, Julian; Nayak, Sanjeev; Jones, Tom; Lally, Frank; Roffe, Christine

    2011-01-01

    Introduction. This paper compares different approaches to recanalization in a model of the middle cerebral artery (MCA). Methods. An occlusive thrombus (lamb's blood) was introduced into the MCA of a model of the cerebral circulation perfused with Hartmann's solution (80 pulsations/min, mean pressure 90 mm Hg). Three methods of clot retrieval were tested: thrombus aspiration via a 4F catheter (n = 26), thrombus aspiration via the GP thrombus aspiration device (GPTAD) (n = 30), and mechanical thrombectomy via the Solitaire Device (n = 30). Results. Recanalization rate was similar for all 3 approaches (62%, 77%, and 85%). Time to recanalization was faster with aspiration devices (41 SD 42 s for 4F and 61 SD 21 s for GPTAD) than with the Solitaire (197 SD 64 s P < .05 Kruksal-Wallis). Clot fragmentation was the same in the Solitaire (23%) and the GPTAD (23%), but higher with the 4F (53%, P < .05). Conclusion. In this model, thrombus aspiration was faster than mechanical thrombectomy, and similarly effective at recanalization. These results should be confirmed in vivo. PMID:21603169

  6. Comparison of the Effectiveness of Three Methods of Recanalization in a Model of the Middle Cerebral Artery: Thrombus Aspiration via a 4F Catheter, Thrombus Aspiration via the GP Thromboaspiration Device, and Mechanical Thrombectomy Using the Solitaire Thrombectomy Device

    PubMed Central

    Tennuci, Christopher; Pearce, Gillian; Wong, Julian; Nayak, Sanjeev; Jones, Tom; Lally, Frank; Roffe, Christine

    2011-01-01

    Introduction. This paper compares different approaches to recanalization in a model of the middle cerebral artery (MCA). Methods. An occlusive thrombus (lamb's blood) was introduced into the MCA of a model of the cerebral circulation perfused with Hartmann's solution (80 pulsations/min, mean pressure 90 mm Hg). Three methods of clot retrieval were tested: thrombus aspiration via a 4F catheter (n = 26), thrombus aspiration via the GP thrombus aspiration device (GPTAD) (n = 30), and mechanical thrombectomy via the Solitaire Device (n = 30). Results. Recanalization rate was similar for all 3 approaches (62%, 77%, and 85%). Time to recanalization was faster with aspiration devices (41 SD 42 s for 4F and 61 SD 21 s for GPTAD) than with the Solitaire (197 SD 64 s P < .05 Kruksal-Wallis). Clot fragmentation was the same in the Solitaire (23%) and the GPTAD (23%), but higher with the 4F (53%, P < .05). Conclusion. In this model, thrombus aspiration was faster than mechanical thrombectomy, and similarly effective at recanalization. These results should be confirmed in vivo. PMID:21603169

  7. Initial clinical use of a novel mechanical thrombectomy device, XCOIL™, in hemodialysis graft and fistula declot procedures

    PubMed Central

    Monsky, Wayne L.; Latchaw, Richard E.

    2016-01-01

    PURPOSE We aimed to evaluate the safety and effectiveness of a novel catheter-based mechanical thrombectomy device, XCOIL™, as a first line therapy to restore patency of thrombosed dialysis grafts and fistulae. METHODS In 2010, 18 consecutive/sequential patients (11 male, 7 female; median age, 52 years; age range, 32–69 years) with occluded arteriovenous grafts (n=15) or fistulae (n=3) were treated with XCOIL™ (NexGen Medical Systems Inc.) without adjunctive thrombolytic drugs. XCOIL™ was advanced distal to the thrombus within the outflow vein as well as distal to the arterial inflow platelet thrombin plug, using a 4F angiographic catheter. The percentage of thrombus cleared, primary patency, procedure time, and XCOIL™ performance were documented. RESULTS Thrombosis occurred 1–30 days prior to the procedure. Thrombosed segments of graft/fistula measured 10–50 cm. Pre- and postprocedure angiography demonstrated that in 15 of 18 cases (83%) XCOIL™ removed 80%–100% of the venous outflow thrombus. In 11 of 14 cases (79%), the platelet thrombin plug was also removed. Thrombectomy procedure time averaged 8 min, with one to three passes with the XCOIL™ required. No evidence of distal embolization or graft/vessel injury was found on angiography following clot removal. In four cases in whom patency was not restored with XCOIL™, subsequent use of other clot removal devices also failed to restore patency. In one case with severe venous stenosis, the device failed to deploy and the thrombus was not captured. No intraprocedural complications related to XCOIL™ use occurred. CONCLUSION XCOIL™ is an effective and safe first-line therapy option for the treatment of thrombosed hemodialysis grafts/fistulae. Rapid removal of intact thrombus and platelet thrombin plug can be achieved without adjunctive thrombolytics. PMID:27015445

  8. A Comparison between Mechanical Thrombectomy and Intra-arterial Fibrinolysis in Acute Basilar Artery Occlusion: Single Center Experiences

    PubMed Central

    Jung, Seunguk; Jung, Cheolkyu; Bae, Yun Jung; Choi, Byung Se; Kim, Jae Hyoung; Lee, Sang-Hwa; Chang, Jun Young; Kim, Beom Joon; Han, Moon-Ku; Bae, Hee-Joon; Kwon, Bae Ju; Cha, Sang-Hoon

    2016-01-01

    Background and Purpose Recent advances in intra-arterial techniques and thrombectomy devices lead to high rate of recanalization. However, little is known regarding the effect of the evolvement of endovascular revascularization therapy (ERT) in acute basilar artery occlusion (BAO). We compared the outcome of endovascular mechanical thrombectomy (EMT) versus intra-arterial fibrinolysis (IAF)-based ERT in patients with acute BAO. Methods After retrospectively reviewed a registry of consecutive patients with acute ischemic stroke who underwent ERT from September 2003 to February 2015, 57 patients with acute BAO within 12 hours from stroke onset were enrolled. They were categorized as an IAF group (n=24) and EMT group (n=33) according to the primary technical option. We compared the procedural and clinical outcomes between the groups. Results The time from groin puncture to recanalization was significantly shorter in the EMT group than in the IAF group (48.5 [25.3 to 87.8] vs. 92 [44 to 179] minutes; P=0.02) The rate of complete recanalization was significantly higher in the EMT group than in the IAF group (87.9% vs 41.7%; P<0.01). The good outcome of the modified Rankin Scale score≤2 at 3 months was more frequent in the EMT group than in the IAF group, but it was not statistically significant (39.4% vs 16.7%; P=0.06). Conclusions EMT-based ERT in patients with acute BAO is superior to IAF-based ERT in terms of the reduction of time from groin puncture to recanalization and the improvement of the rate of complete recanalization. PMID:27283281

  9. Acute Superior Mesenteric Venous Thrombosis: Transcatheter Thrombolysis and Aspiration Thrombectomy Therapy by Combined Route of Superior Mesenteric Vein and Artery in Eight Patients

    SciTech Connect

    Yang, Shuofei Liu, Baochen Ding, Weiwei He, Changsheng Wu, Xingjiang Li, Jieshou

    2015-02-15

    PurposeTo assess the feasibility, effectiveness, and safety of catheter-directed thrombolysis and aspiration thrombectomy therapy by combined route of superior mesenteric vein and artery (SMV+SMA) for acute superior mesenteric venous thrombosis (ASMVT).MethodsThis retrospective study reviewed eight ASMVT patients with transcatheter direct thrombolysis and aspiration thrombectomy therapy via SMV and indirect thrombolysis via SMA during a period of 14 months. The demographics, etiology, risk factors, therapeutic effect, complications, mortality, and follow-up of the study population were assessed. Anatomic and imaging classification of location and extent of thrombus at diagnosis and degree of thrombus lysis were described.ResultsTechnical success was achieved with substantial improvement in symptoms and thrombus resolution after thrombolytic therapy in all patients. The local urokinase infusion by SMA and SMV was performed for 5–7 (6.13 ± 0.83) and 7–15 (12 ± 2.51) days. Anticoagulation was performed catheter-directed and then orally throughout hospitalization and after discharge. Four patients required delayed localized bowel resection after thrombolytic therapy with no death. Thrombolytic therapy was not interrupted despite minor bleeding at the puncture site in two patients and sepsis in another two postoperatively. Nearly complete removal of thrombus was demonstrated by contrast-enhanced CT scan and portography before discharge. Patients were discharged in 10–27 (19.25 ± 4.89) days after admission. No recurrence developed during the follow-up of 10–13 (12.13 ± 0.99) months.ConclusionsCatheter-directed thrombolytic and aspiration therapy via SMV+SMA is beneficial for ASMVT in avoiding patient death, efficient resolving thrombus, rapid improving symptoms, reversing extensive intestinal ischemia, averting bowel resection, or localizing infarcted bowel segment and preventing short bowel syndrome.

  10. Mechanical Thrombectomy Using Solitaire in a 6-Year-Old Child.

    PubMed

    Huded, Vikram; Kamath, Vikram; Chauhan, Bhumir; de Souza, Romnesh; Nair, Rithesh; Sapare, Anil; Kekatpure, Minal

    2015-05-01

    A six-year-old boy was diagnosed as recurrent posterior circulation stroke secondary to basilar artery occlusion with rapid progression of symptoms. Etiology of stroke was a dissection of V3 segment of left vertebral artery, which was treated using endovascular technique 26 hours after worsening of symptoms. Since the guidelines for acute revascularization in pediatric stroke are not well established, there is limited experience in the use of mechanical devices for acute ischemic stroke revascularization in children. To our knowledge, this is one of the youngest reported cases of acute ischemic stroke from Asia managed with newer mechanical clot removal devices. PMID:26060522

  11. Presumed Pulmonary Embolism Following Power-Pulse Spray Thrombectomy of Upper Extremity Venous Thrombosis

    SciTech Connect

    Tsai, Jason; Georgiades, Christos S.; Hong, Kelvin; Kim, Hyun S.

    2006-08-15

    To achieve more effective thrombolysis in a shorter treatment time, percutaneous mechanical thrombectomy has been increasingly used in the treatment of deep venous thrombosis (DVT). The power-pulse spray is a new technique to combine chemical and rheolytic effects on clots. We present a case of presumed pulmonary embolism following power-pulse spray treatment for upper extremity DVT which necessitated resuscitation and intubation. The power-pulse spray technique should be used with caution when treating DVT.

  12. Mechanical Thrombectomy-Ready Comprehensive Stroke Center Requirements and Endovascular Stroke Systems of Care: Recommendations from the Endovascular Stroke Standards Committee of the Society of Vascular and Interventional Neurology (SVIN).

    PubMed

    English, Joey D; Yavagal, Dileep R; Gupta, Rishi; Janardhan, Vallabh; Zaidat, Osama O; Xavier, Andrew R; Nogueira, Raul G; Kirmani, Jawad F; Jovin, Tudor G

    2016-03-01

    Five landmark multicenter, prospective, randomized, open-label, blinded end point clinical trials have recently demonstrated significant clinical benefit of endovascular therapy with mechanical thrombectomy in acute ischemic stroke (AIS) patients presenting with proximal intracranial large vessel occlusions. The Society of Vascular and Interventional Neurology (SVIN) appointed an expert writing committee to summarize this new evidence and make recommendations on how these data should guide emergency endovascular therapy for AIS patients. PMID:27051410

  13. Mechanical Thrombectomy-Ready Comprehensive Stroke Center Requirements and Endovascular Stroke Systems of Care: Recommendations from the Endovascular Stroke Standards Committee of the Society of Vascular and Interventional Neurology (SVIN)

    PubMed Central

    English, Joey D.; Yavagal, Dileep R.; Gupta, Rishi; Janardhan, Vallabh; Zaidat, Osama O.; Xavier, Andrew R.; Nogueira, Raul G.; Kirmani, Jawad F.; Jovin, Tudor G.

    2016-01-01

    Five landmark multicenter, prospective, randomized, open-label, blinded end point clinical trials have recently demonstrated significant clinical benefit of endovascular therapy with mechanical thrombectomy in acute ischemic stroke (AIS) patients presenting with proximal intracranial large vessel occlusions. The Society of Vascular and Interventional Neurology (SVIN) appointed an expert writing committee to summarize this new evidence and make recommendations on how these data should guide emergency endovascular therapy for AIS patients. PMID:27051410

  14. Does Mechanical Thrombectomy in Acute Embolic Stroke Have Long-term Side Effects on Intracranial Vessels? An Angiographic Follow-up Study

    SciTech Connect

    Kurre, Wiebke Perez, Marta Aguilar; Horvath, Diana; Schmid, Elisabeth; Baezner, Hansjoerg; Henkes, Hans

    2013-06-15

    Purpose. Mechanical thrombectomy (mTE) proved to be effective treating acute vessel occlusions with an acceptable rate of procedural complications. Potential long-term side effects of the vessel wall trauma caused by mechanical irritation of the endothelium are unknown up to now. Methods. From a retrospectively established database of 640 acute stroke treatments, we selected 261 patients with 265 embolic vessel occlusions treated successfully by mTE without permanent implantation of a stent. Analysis comprised the type of devices used and the number of passes performed. Digital subtraction angiography immediately after treatment was evaluated for vasospasm, dissection, and extravasation. Control angiographic images were evaluated for any morphological change compared to the immediate posttreatment angiographic run. Results. Recanalization was achieved with a median of one (range 1-10) mTE maneuvers. Vasospasm occurred in 69 territories (26.0 %) and was treated with glyceroltrinitrate in three. Dissection was observed in one vessel (0.4 %). Intraprocedural hemorrhage in two patients (0.8 %) was either wire or device induced. Follow-up digital subtraction angiography was available for 117 territories after a median of 107 days, revealing target vessel occlusion in one segment (0.9 %) and a de novo stenosis of four segments (3.4 %). All findings were clinically asymptomatic. Posttreatment vasospasm was more frequent in patients with de novo stenosis and occlusion (p = 0.038). Conclusion. De novo stenoses and occlusions occur in a small proportion of patients after mTE. Because all lesions were clinically asymptomatic, this finding does not affect the overall benefit of the treatment. Vasospasm may predict late vessel wall changes.

  15. Does Preinterventional Flat-Panel Computer Tomography Pooled Blood Volume Mapping Predict Final Infarct Volume After Mechanical Thrombectomy in Acute Cerebral Artery Occlusion?

    SciTech Connect

    Wagner, Marlies; Kyriakou, Yiannis; Mesnil de Rochemont, Richard du; Singer, Oliver C.; Berkefeld, Joachim

    2013-08-01

    PurposeDecreased cerebral blood volume is known to be a predictor for final infarct volume in acute cerebral artery occlusion. To evaluate the predictability of final infarct volume in patients with acute occlusion of the middle cerebral artery (MCA) or the distal internal carotid artery (ICA) and successful endovascular recanalization, pooled blood volume (PBV) was measured using flat-panel detector computed tomography (FPD CT).Materials and MethodsTwenty patients with acute unilateral occlusion of the MCA or distal ACI without demarcated infarction, as proven by CT at admission, and successful Thrombolysis in cerebral infarction score (TICI 2b or 3) endovascular thrombectomy were included. Cerebral PBV maps were acquired from each patient immediately before endovascular thrombectomy. Twenty-four hours after recanalization, each patient underwent multislice CT to visualize final infarct volume. Extent of the areas of decreased PBV was compared with the final infarct volume proven by follow-up CT the next day.ResultsIn 15 of 20 patients, areas of distinct PBV decrease corresponded to final infarct volume. In 5 patients, areas of decreased PBV overestimated final extension of ischemia probably due to inappropriate timing of data acquisition and misery perfusion.ConclusionPBV mapping using FPD CT is a promising tool to predict areas of irrecoverable brain parenchyma in acute thromboembolic stroke. Further validation is necessary before routine use for decision making for interventional thrombectomy.

  16. Sinus thrombectomy for purulent cerebral venous sinus thrombosis utilizing a novel combination of the Trevo stent retriever and the Penumbra ACE aspiration catheter: the stent anchor with mobile aspiration technique.

    PubMed

    Mascitelli, Justin R; Pain, Margaret; Zarzour, Hekmat K; Baxter, Peter; Ghatan, Saadi; Mocco, J

    2015-01-01

    Intracranial complications of sinusitis are rare but life threatening. We present a case of a 17-year-old woman with sinusitis who deteriorated over the course of 12 days from subdural empyema and global purulent cerebral venous sinus thrombosis. The patient was managed with surgery and mechanical thrombectomy utilizing a novel 'stent anchor with mobile aspiration technique', in which a Trevo stent retriever (Stryker) was anchored in the superior sagittal sinus (SSS) while a 5 MAX ACE reperfusion catheter (Penumbra) was passed back and forth from the SSS to the sigmoid sinus with resultant dramatic improvement in venous outflow. The patient was extubated on postoperative day 3 and was discharged with minimal lower extremity weakness on postoperative day 11. This is the first report using the Trevo stent retriever for sinus thrombosis. It is important to keep these rare complications in mind when evaluating patients with oral and facial infections. PMID:26002667

  17. Sinus thrombectomy for purulent cerebral venous sinus thrombosis utilizing a novel combination of the Trevo stent retriever and the Penumbra ACE aspiration catheter: the stent anchor with mobile aspiration technique.

    PubMed

    Mascitelli, Justin R; Pain, Margaret; Zarzour, Hekmat K; Baxter, Peter; Ghatan, Saadi; Mocco, J

    2016-06-01

    Intracranial complications of sinusitis are rare but life threatening. We present a case of a 17-year-old woman with sinusitis who deteriorated over the course of 12 days from subdural empyema and global purulent cerebral venous sinus thrombosis. The patient was managed with surgery and mechanical thrombectomy utilizing a novel 'stent anchor with mobile aspiration technique', in which a Trevo stent retriever (Stryker) was anchored in the superior sagittal sinus (SSS) while a 5 MAX ACE reperfusion catheter (Penumbra) was passed back and forth from the SSS to the sigmoid sinus with resultant dramatic improvement in venous outflow. The patient was extubated on postoperative day 3 and was discharged with minimal lower extremity weakness on postoperative day 11. This is the first report using the Trevo stent retriever for sinus thrombosis. It is important to keep these rare complications in mind when evaluating patients with oral and facial infections. PMID:26019186

  18. Endovascular Mechanical Thrombectomy of an Occluded Superior Division Branch of the Left MCA for Acute Cardioembolic Stroke

    SciTech Connect

    Schumacher, H. C. Meyers, P. M.; Yavagal, D. R.; Harel, N. Y.; Elkind, M. S. V.; Mohr, J. P.; Pile-Spellman, J.

    2003-06-15

    Cardiac embolism accounts for a large proportion of ischemic stroke. Revascularization using systemic or intra-arterial thrombolysis is associated with increasing risks of cerebral hemorrhageas time passes from stroke onset. We report successful mechanicalthrombectomy from a distal branch of the middle cerebral artery (MCA)using a novel technique. A 72-year old man suffered an acute ischemic stroke from an echocardiographically proven ventricular thrombus due toa recent myocardial infarction. Intra-arterial administration of 4 mgrt-PA initiated at 5.7 hours post-ictus failed to recanalize an occluded superior division branch of the left MCA. At 6 hours,symptomatic embolic occlusion persisted. Mechanical extraction of the clot using an Attracter-18 device (Target Therapeutics, Freemont, CA) resulted in immediate recanalization of the MCA branch. Attracter-18 for acute occlusion of MCA branches may be considered in selected patients who fail conventional thrombolysis or are nearing closure of the therapeutic window for use of thrombolytic agents.

  19. Mechanical thrombectomy using Rotarex system and stent-in-stent placement for treatment of distal femoral artery occlusion secondary to stent fracture – a case report and literature review

    PubMed Central

    Dys, Krzysztof; Drelichowska-Durawa, Justyna; Dołega-Kozierowski, Bartosz; Lis, Michał; Sokratous, Kyriakos; Iwanowski, Wojciech; Drelichowski, Stanisław; Witkiewicz, Wojciech

    2013-01-01

    Summary Background: Treatment of peripheral arterial diseases may be distinguished into conservative and interventional management; the latter is divided into surgical and endovascular procedures. Management of peripheral artery stenosis and occlusion with vascular stents is associated with the risk of late complications such as restenosis, stent fracture or dislocation. Case Report: A 62-year-old woman with generalized atherosclerosis, particularly extensive in lower limb arteries, was admitted to the Department of Angiology 11 months after having an endovascular procedure performed due to critical ischemia of left lower limb. Because of stent occlusion, a decision to perform angiographic examination of lower limb arteries was made. Examination revealed occlusion of the superficial femoral artery along its entire length, including previously implanted stents. Distal stent was fractured with slight dislocation of the proximal segment. A decision was made to perform mechanical thrombectomy using a Rotarex system followed by a stent-in-stent placement procedure. Follow-up angiography and ultrasound scan performed 24 hours after the procedure revealed a patent vessel with satisfactory blood flow. Discussion: Nowadays, imaging diagnostics of peripheral artery stenosis involves non-invasive examinations such as ultrasound, minimally invasive examinations such as angio-MRI and MDCT, or invasive examinations such as DSA and IVUS. DSA examinations are used to confirm significant stenosis or occlusion of a vessel, particularly when qualifying a patient for endovascular treatment. Due to their anatomic location, the superficial femoral artery and the popliteal artery are subject to various forces e.g. those exerted by the working muscles. Mechanical thrombectomy and atherectomy are efficient methods of arterial recanalization used in the treatment of acute, subacute or even chronic occlusions or stenosis of peripheral vessels. Conclusions: Frequency of angioplasty and

  20. Emergent Right Coronary Artery Thrombectomy with a Jet Aspiration Thrombectomy Catheter

    SciTech Connect

    Yamauchi, Teiyu; Furui, Shigeru; Isshiki, Takaaki; Toyoizumi, Hideki; Kohtake, Hiroshi; Takeshita, Kohji; Suzuki, Shigeru; Harasawa, Arimi; Sasaki, Yasushi

    1999-07-15

    A saline-jet aspiration thrombectomy (JAT) catheter was used in a patient with acute myocardial infarction. A right coronary arteriogram showed complete thrombotic occlusion at the proximal segment. With this catheter the thrombus was removed without complications in 5 sec. The patient underwent percutaneous transluminal coronary angioplasty and placement of a Palmaz-Schatz stent after successful thrombectomy. Thrombectomy with a JAT catheter was very useful in this patient.0.

  1. Massive Pulmonary Embolism: Treatment with the Rotarex Thrombectomy System

    SciTech Connect

    Liu Sheng; Shi Haibin; Gu Jianping; Yang Zhengqiang; Chen Liang; Lou Wensheng; He Xu; Zhou Weizhong; Zhou Chungao; Zhao Linbo; Xia Jinguo; Li Linsun

    2011-02-15

    This study was designed to evaluate the efficacy and safety of percutaneous mechanical thrombectomy (PMT) for acute massive pulmonary embolism (PE). Fourteen patients (8 men, 6 women) with a mean age of 55.4 (range, 38-71) years with acute massive PE were initially diagnosed by computed tomography (CT) and confirmed by pulmonary angiography. All patients presented with acute PE symptoms and hemodynamic compromise. Each patient was treated with Straub Rotarex thrombectomy device and five patients received additional thrombolysis. Technique success and clinical improvement were achieved in all patients without major complications. The mean pulmonary artery pressure (PAP) decreased from 37.6 {+-} 6.6 to 29 {+-} 6.4 mmHg (P < 0.01) after PMT. Partial arterial pressures of O{sub 2} (PaO{sub 2}) increased from 61.1 {+-} 9.2 to 88 {+-} 5.1 mmHg (P < 0.01). The Miller index was 0.67 {+-} 0.11 and 0.37 {+-} 0.13 (P < 0.01), respectively, before and after PMT (P < 0.01). Eleven patients had no recurrence of PE on a mean follow-up of 28.3 months, whereas the other three patients were lost to follow-up. The preliminary experience in our series suggests that the Straub Rotarex thrombectomy device, which has been utilized in peripheral arteries, also is useful for the treatment of acute massive PE.

  2. The Effectiveness of Additional Treatment Modalities after the Failure of Recanalization by Thrombectomy Alone in Acute Vertebrobasilar Arterial Occlusion

    PubMed Central

    Kim, Seong Mook; Sohn, Sung-Il; Hong, Jeong-Ho; Chang, Hyuk-Won; Lee, Chang-Young

    2015-01-01

    Objective Acute vertebrobasilar artery occlusion (AVBAO) is a devastating disease with a high mortality rate. One of the most important factors affecting favorable clinical outcome is early recanalization. Mechanical thrombectomy is an emerging treatment strategy for achieving a high recanalization rates. However, thrombectomy alone can be insufficient to complete recanalization, especially for acute stroke involving large artery atheromatous disease. The purpose of this study is to investigate the safety and efficacy of mechanical thrombectomy in AVBAO. Methods Fourteen consecutive patients with AVBAO were treated with mechanical thrombectomy. Additional multimodal treatments were intra-arterial (IA) thrombolysis, balloon angioplasty, or permanent stent placement. Recanalization by thrombectomy alone and multimodal treatments were assessed by the Thrombolysis in Cerebral Infarction (TICI) score. Clinical outcome was determined using the National Institutes of Health Stroke Scale (NIHSS) at 7 days and the modified Rankin Scale (mRS) at 3 months. Results Thrombectomy alone and multimodal treatments were performed in 10 patients (71.4%) and 4 patients (28.6%), respectively. Successful recanalization (TICI 2b-3) was achieved in 11 (78.6%). Among these 11 patients, 3 (27.3%) underwent multimodal treatment due to underlying atherosclerotic stenosis. Ten (71.4%) of the 14 showed NIHSS score improvement of >10. Overall mortality was 3 (21.4%) of 14. Conclusion We suggest that mechanical thrombectomy is safe and effective for improving recanalization rates in AVBAO, with low complication rates. Also, in carefully selected patients after the failure of recanalization by thrombectomy alone, additional multimodal treatment such as IA thrombolysis, balloons, or stents can be needed to achieve successful recanalization. PMID:26713141

  3. Percutaneous Venous Thrombectomy Using the Arrow-Trerotola Percutaneous Thrombolytic Device (PTD) with Temporary Caval Filtration: In Vitro Investigations

    SciTech Connect

    Wildberger, Joachim Ernst Haage, Patrick; Bovelander, Jan; Pfeffer, Joachim; Weiss, Claudia; Vorwerk, Dierk; Schmitz-Rode, Thomas; Guenther, Rolf W.

    2005-04-15

    Purpose. To evaluate the size and quantity of downstream emboli after thrombectomy using the Arrow-Trerotola Percutaneous Thrombolytic Device (PTD) with or without temporary filtration for extensive iliofemoral and iliocaval thrombi in an in vitro flow model. Methods. Iliocaval thrombi were simulated by clotted bovine blood in a flow model (semilucent silicone tubings, diameter 12-16 mm). Five experimental set-ups were performed 10 times each; thrombus particles and distribution were measured in the effluent. First, after retrograde insertion, mechanical thrombectomy was performed using the PTD alone. Then a modified self-expanding tulip-shaped temporary vena cava stent filter was inserted additionally at the beginning of each declotting procedure and removed immediately after the intervention without any manipulation within or at the filter itself. In a third step, the filter was filled with thrombus only. Here, two experiments were performed: Careful closure within the flow circuit without any additional fragmentation procedure and running the PTD within the filter lumen, respectively. In the final set-up, mechanical thrombectomy was performed within the thrombus-filled tubing as well as in the filter lumen. The latter was closed at the end of the procedure and both devices were removed from the flow circuit. Results. Running the PTD in the flow circuit without filter protection led to a fragmentation of 67.9% ({+-}7.14%) of the clot into particles {<=}500 {mu}m; restoration of flow was established in all cases. Additional placement of the filter safely allowed maceration of 82.9% ({+-}5.59%) of the thrombus. Controlled closure of the thrombus-filled filter within the flow circuit without additional mechanical treatment broke up 75.2% ({+-}10.49%), while additional mechanical thrombectomy by running the PTD within the occluded filter led to dissolution of 90.4% ({+-}3.99%) of the initial clot. In the final set-up, an overall fragmentation rate of 99.6% ({+-}0

  4. Massive Pulmonary Embolism: Percutaneous Emergency Treatment Using an Aspirex Thrombectomy Catheter

    SciTech Connect

    Popovic, Peter; Bunc, Matjaz

    2010-10-15

    Massive pulmonary embolism (PE) is a life-threatening condition with a high early mortality rate caused by acute right ventricular failure and cardiogenic shock. A 51-year-old woman with a massive PE and contraindication for thrombolytic therapy was treated with percutaneous mechanical thrombectomy using an Aspirex 11F catheter (Straub Medical AG, Wangs, Switzerland). The procedure was successfully performed and showed a good immediate angiographic result. The patient made a full recovery from the acute episode and was discharged on heparin treatment. Our case report indicates that in patients with contraindications to systemic thrombolysis, catheter thrombectomy may constitute a life-saving intervention for massive PE.

  5. Endovascular Treatment of Acute Stroke with Major Vessel Occlusion before Approval of Mechanical Thrombectomy Devices in Japan: Japanese Registry of Neuroendovascular Therapy (JR-NET) and JR-NET 2

    PubMed Central

    HAYAKAWA, Mikito; YAMAGAMI, Hiroshi; SAKAI, Nobuyuki; MATSUMARU, Yuji; YOSHIMURA, Shinichi; TOYODA, Kazunori

    2014-01-01

    The aim of this study was to clarify the general status and historical transition of endovascular therapy (EVT) of acute stroke with major vessel occlusion before approval of mechanical thrombectomy devices in Japan from January 2005 to December 2009. We extracted 1,409 acute ischemic stroke patients receiving EVT (513 women, 69.8 ± 11.8 years) from two nationwide registry studies, the Japanese Registry of Neuroendovascular Therapy (JR-NET) and JR-NET 2. The median baseline National Institutes of Health Stroke Scale (NIHSS) score was 18, and 81.3% of the patients received EVT within 6 hours after symptom onset. The culprit occluded arteries were the internal carotid artery (ICA) in 21.2%, middle cerebral artery (MCA) in 53.0%, and basilar artery (BA) in 20.6%. Intravenous thrombolysis was administered to 6.7% of the patients, and EVT mainly consisted of intra-arterial thrombolysis and percutaneous balloon angioplasty/balloon clot disruption. The final recanalization rate was 82.5%, and the clinical outcome was favorable in 35.8% and fatal in 11.6% at 30 days after onset or at discharge. There was no significant change in neurological severity at baseline throughout the study period, but the onset-to-treatment time became longer and the proportion of ICA or BA occlusion increased annually. Although the final recanalization rate was similar throughout the study period, the incidence of a favorable outcome tended to decreased annually from 41.0% to 29.0%. These results could be considered as baseline data that can be used to validate the beneficial effects of novel EVT devices in Japan. PMID:24292608

  6. Pulling Seton: Combination of mechanisms

    PubMed Central

    Izadpanah, Ahmad; Rezazadehkermani, Mohammad; Hosseiniasl, Seyed Mohammad; Farghadin, Afrouz; Ghahramani, Leila; Bananzadeh, Alimohammad; Roshanravan, Reza; Izadpanah, Ahad

    2016-01-01

    Background: Seton-based techniques are among popular methods for treating high type anal fistula. These techniques are categorized to cutting and noncutting regarding their mechanism of action. In this report we are about to describe a new technique, which is a combination of both mechanisms; we call it Pulling Seton. Materials and Methods: In this technique after determining internal and external orifice of fistula, fistulectomy is done from both ends to the level of external sphincteric muscle. Finally, a remnant of fistula, which remains beneath external sphincteric muscle is excised, and Seton is passed instead of it and tied externally. After the wound heals, patient is asked to pull down the Seton for 3–4 min, 4 times a day. We prospectively enrolled 201 patients with high type anal fistula in this study. Results: Seton gradually passes through external sphincteric muscle till it is displaced outwards or removed by a surgeon via a small incision. 94% of patients treated by this method accomplished their treatment completely without recurrence. None of the patients developed permanent fecal or gas incontinence. Only 5% of patients developed with recurrence of fistula. Since Seton traction is not permanent in this technique, Seton cuts external sphincter slowly, and minimal rate of incontinence is reported. Conclusion: Pulling Seton seems to be an efficient way in treating high type anal fistula with minimal rate of recurrence and complications such as incontinence and authors suggest further randomized studies to compare its efficacy with other Seton-based techniques. PMID:27169099

  7. Safety and Efficacy of Solitaire Stent Thrombectomy

    PubMed Central

    Campbell, Bruce C.V.; Hill, Michael D.; Rubiera, Marta; Menon, Bijoy K.; Demchuk, Andrew; Donnan, Geoffrey A.; Roy, Daniel; Thornton, John; Dorado, Laura; Bonafe, Alain; Levy, Elad I.; Diener, Hans-Christoph; Hernández-Pérez, María; Pereira, Vitor Mendes; Blasco, Jordi; Quesada, Helena; Rempel, Jeremy; Jahan, Reza; Davis, Stephen M.; Stouch, Bruce C.; Mitchell, Peter J.; Jovin, Tudor G.; Saver, Jeffrey L.

    2016-01-01

    Background and Purpose— Recent positive randomized trials of endovascular therapy for ischemic stroke used predominantly stent retrievers. We pooled data to investigate the efficacy and safety of stent thrombectomy using the Solitaire device in anterior circulation ischemic stroke. Methods— Patient-level data were pooled from trials in which the Solitaire was the only or the predominant device used in a prespecified meta-analysis (SEER Collaboration): Solitaire FR With the Intention for Thrombectomy as Primary Endovascular Treatment (SWIFT PRIME), Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times (ESCAPE), Extending the Time for Thrombolysis in Emergency Neurological Deficits—Intra-Arterial (EXTEND-IA), and Randomized Trial of Revascularization With Solitaire FR Device Versus Best Medical Therapy in the Treatment of Acute Stroke Due to Anterior Circulation Large Vessel Occlusion Presenting Within Eight Hours of Symptom Onset (REVASCAT). The primary outcome was ordinal analysis of modified Rankin Score at 90 days. The primary analysis included all patients in the 4 trials with 2 sensitivity analyses: (1) excluding patients in whom Solitaire was not the first device used and (2) including the 3 Solitaire-only trials (excluding ESCAPE). Secondary outcomes included functional independence (modified Rankin Score 0–2), symptomatic intracerebral hemorrhage, and mortality. Results— The primary analysis included 787 patients: 401 randomized to endovascular thrombectomy and 386 to standard care, and 82.6% received intravenous thrombolysis. The common odds ratio for modified Rankin Score improvement was 2.7 (2.0–3.5) with no heterogeneity in effect by age, sex, baseline stroke severity, extent of computed tomography changes, site of occlusion, or pretreatment with alteplase. The number needed to treat to reduce disability was 2.5 and for an extra patient to achieve independent

  8. Midterm Results Following Percutaneous Rotational Thrombectomy for Acute Thrombotic Occlusions of Prosthetic Arteriovenous Access Grafts.

    PubMed

    Karatepe, Celalettin; Aldemir, Mustafa; Çınar, Bayer; Önalan, Akif; Işsever, Halim; Goksel, Onur S

    2015-07-01

    Patent vascular access is critical for patients on regular hemodialysis. Prosthetic grafts are good alternatives when the superficial venous system is of poor quality. However, thrombosis is one of the main drawbacks of synthetic grafts, with reports of 59% to 90% patency rates for 1 year. In cases of thrombotic occlusion of prosthetic arteriovenous fistula grafts, percutaneous mechanical thrombectomy has recently gained clinical popularity as a potential alternative to surgical thrombectomy or pharmacologic thrombolysis. We reviewed our preliminary results from 30 percutaneous rotational thrombectomies performed in a total of 22 patients in the setting of acute dialysis-access prosthetic graft occlusion of the upper extremity. Among the 30 cases of acute occlusion of the arteriovenous graft, immediate success with angiographic flow restoration was observed in all patients except for 2 patients (both females; 6%), with de novo occlusion where reocclusion occurred within 12 hours despite apparent immediate angiographic patency. The mean duration between the initial presentation with acute arteriovenous graft occlusion and the thrombectomy procedure was 27.4 ± 12.4 hours. The mean duration of graft patency was 10.45 ± 0.6 months. A total of 75% of the arteriovenous grafts were patent at the end of 12 months of follow-up. Female gender, diabetes mellitus, and diagnosis to intervention interval were reviewed for midterm graft failure, and the presence of diabetes mellitus yielded significance (P < 0.05). Percutaneous techniques play important roles in the treatment of failed or failing arteriovenous fistulae and grafts. Ongoing analysis of outcomes of both percutaneous and surgical intervention is necessary to continue to identify optimum treatment algorithms. PMID:26595502

  9. Pulmonary Hypertension in Hemodialysis Patients Following Repeated Endovascular Thrombectomy

    PubMed Central

    Hsieh, Mu-Yang; Lin, Lin; Chen, Tsung-Yan; Wang, Ren-Huei; Huang, Su-Chin; Liu, HsiuChiao; Lai, Chao-Lun; Pu, Shih-Yen; Tsai, Kuei-Chin; Wu, Chih-Cheng

    2016-01-01

    Background The prevalence of pulmonary hypertension is unusually high in Taiwanese patients with end-stage renal disease. Thrombosis of hemodialysis grafts is common and pulmonary embolism has been reported after endovascular thrombectomy. The aim of this study was to evaluate the relationship between pulmonary hypertension and endovascular thrombectomy of hemodialysis grafts. Methods One hundred and ten patients on hemodialysis via arteriovenous grafts were enrolled in our study. The mean pulmonary artery pressure (PAP) was measured by right heart catheterization. Clinical information was collected by review of medical records. Comorbid cardiopulmonary disease was evaluated by echocardiography and chest X-ray. The history of patient vascular access thrombosis was reviewed from database, hemodialysis records, and interviews with staff at hemodialysis centers. Results Fifty-two participants (47%) had pulmonary hypertension diagnosed by right heart catheterization. There was no difference in the number of thrombectomy procedures between patients with and without pulmonary hypertension. Based on multivariate analysis, the number of prior endovascular thrombectomy procedures did not correlate with mean PAP (F-value = 1.10, p = 0.30) nor was it associated with pulmonary hypertension (odds ratio = 0.92, p = 0.17). Conclusions Prior endovascular arteriovenous graft thrombectomies were not associated with pulmonary hypertension or increased mean PAP in end-stage renal disease patients on maintenance hemodialysis. PMID:27274170

  10. AngioJet Thrombectomy for Occluded Dialysis Fistulae: Outcome Data

    SciTech Connect

    Littler, Peter Cullen, Nicola; Gould, Derek; Bakran, Ali; Powell, Steven

    2009-03-15

    This study evaluates AngioJet thrombectomy of occluded autogenous dialysis fistulae and polytetrafluoroethylene (PTFE) grafts in a UK hemodialysis population. Comparison is made with published data of alternative percutaneous thrombectomy methods. All patients with occluded dialysis fistulae who sought care at the Royal Liverpool University Hospital between October 2006 and June 2008 were included in the study. All patients were treated with the AngioJet Rheolytic Thrombectomy Device (Possis, Minneapolis, MN). Demographics, time of occlusion, adjunctive therapies, complications, and follow-up data have been prospectively recorded. A total of 64 thrombectomy procedures were performed in 48 patients. Forty-four autogenous fistulas were treated in 34 patients (19 brachiocephalic, 8 radiocephalic, and 7 transposed brachiobasilic). Twenty PTFE grafts were treated in 14 patients (9 brachioaxillary, 3 brachiocephalic loop grafts, 1 brachiobasilic, and 1 femoro-femoral). The average length of occlusion was 24 cm. Average time to intervention was 4 days. Immediate primary patency was 91%. Primary patency at 1, 3, and 6 months, respectively, was 71%, 60%, and 37%. Secondary patency at 3, 6, and 12 months was 87%, 77%, and 62%, respectively. Angioplasty was carried out in all procedures. Patients required stent insertion in 34 of the 64 thrombectomies to treat angioplasty-resistant stenoses. Complications included a puncture-site hematoma, and three angioplasty-related vein ruptures in one patient, all treated with covered stent grafts. Two cases of distal brachial arterial embolization were successfully treated by thrombosuction. AngioJet thrombectomy in dialysis access occlusion is safe and effective, comparing favorably with other methods.

  11. Percutaneous transhepatic thrombectomy and pharmacologic thrombolysis of mesenteric venous thrombosis.

    PubMed

    Zhou, Wei; Choi, Lorraine; Lin, Peter H; Dardik, Alan; Eraso, Andrea; Lumsden, Alan B

    2007-01-01

    Mesenteric venous occlusion is a rare yet highly morbid condition that is traditionally treated with anticoagulation while surgery serves as the last resort. Percutaneous intervention provides an effective option with relatively low mortality and morbidity. We herein describe use of transhepatic percutaneous thrombectomy and pharmacologic thrombolysis in treating two cases of symptomatic mesenteric venous thrombosis. These cases underscore the fact that transhepatic thrombectomy and thrombolysis are a highly effective strategy for treating acute symptomatic mesenteric venous thrombosis. Several percutaneous techniques are also reviewed. PMID:17382054

  12. Mechanical thrombectomy for cerebral venous sinus thrombosis employing a novel combination of Angiojet and Penumbra ACE aspiration catheters: the Triaxial Angiojet technique.

    PubMed

    Bress, Aaron; Hurst, Robert; Pukenas, Bryan; Smith, Michelle; Kung, David

    2016-09-01

    Cerebral venous sinus thrombosis (CVST) can be life threatening. A previously healthy woman in her early forties on oral contraceptives presented with global CVST and rapid clinical deterioration. A novel 'Triaxial Angiojet technique' (KSAW Shuttle [Cook Inc., Bloomington, IN, USA], 5 MAX ACE [Penumbra Inc., Alameda, CA, USA], and Angiojet [Boston Scientific, Marlborough, MA, USA]) was employed to gain access into the superior sagittal sinus. The 5 MAX ACE reperfusion catheter was shortened prior to placing a 4 Fr Angiojet catheter through it. This resulted in markedly improved recanalization with good anterograde flow. The patient was extubated on postoperative day 2 and discharged neurologically intact on postoperative day 10. We report the first case of placing an Angiojet catheter through a larger Penumbra reperfusion catheter when access through a tortuous sigmoid and transverse sinus could not be obtained with a 6 Fr support catheter. PMID:27052259

  13. A New Rotational Thrombectomy Catheter: System Design and First Clinical Experiences

    SciTech Connect

    Schmitt, Hans-Erich; Jaeger, Kurt A.; Jacob, Augustinus L.; Mohr, Helmuth; Labs, Karl-Heinz; Steinbrich, Wolfgang

    1999-11-15

    Purpose: To describe a new catheter for the percutaneous mechanical removal of fresh and organized thrombi, and to assess its efficacy and safety in vitro and in vivo. Methods: The catheter consists of a coated stainless steel spiral that rotates at 40,000 rpm over a guidewire inside the whole length of an 8 Fr, single-lumen, polyurethane catheter, driving a dual-blade cutting crown. Abraded occlusion material is sucked into the catheter head through distal side holes and transported by the spiral into a reservoir at the proximal end. The efficacy of the device was tested in arterial models and fresh bovine carotid arteries (n = 72). In a clinical pilot study 10 patients (8 women, 2 men; mean age 70.6 {+-} 10.1 years) with occlusions of the superficial femoral artery (2-12 cm, mean 5.8 cm), not older than 4 weeks, underwent thrombectomy with the new catheter. Results: In arterial models and bovine cadaver arteries the catheter completely removed fresh thrombi. Occlusion material of higher consistency was cut into particles of 100-500 {mu}m and transported outside. Thrombectomy was successful and vessel patency restored in all 10 patients. The ankle/brachial pressure index significantly (p < 0.0005) increased from 0.41 {+-} 0.18 before intervention to 0.88 {+-} 0.15 after 48 hr and to 0.84 {+-} 0.20 after 3 months. Two reocclusions occurred within 14 days after the intervention. Conclusion: Thrombectomy with the new device appears to be feasible and safe in patients with acute and subacute occlusions of the femoropopliteal artery.

  14. Combined mechanical loading of composite tubes

    NASA Technical Reports Server (NTRS)

    Derstine, Mark S.; Pindera, Marek-Jerzy; Bowles, David E.

    1988-01-01

    An analytical/experimental investigation was performed to study the effect of material nonlinearities on the response of composite tubes subjected to combined axial and torsional loading. The effect of residual stresses on subsequent mechanical response was included in the investigation. Experiments were performed on P75/934 graphite-epoxy tubes with a stacking sequence of (15/0/ + or - 10/0/ -15), using pure torsion and combined axial/torsional loading. In the presence of residual stresses, the analytical model predicted a reduction in the initial shear modulus. Experimentally, coupling between axial loading and shear strain was observed in laminated tubes under combined loading. The phenomenon was predicted by the nonlinear analytical model. The experimentally observed linear limit of the global shear response was found to correspond to the analytically predicted first ply failure. Further, the failure of the tubes was found to be path dependent above a critical load level.

  15. Catheter-Directed Thrombolysis with Percutaneous Rheolytic Thrombectomy Versus Thrombolysis Alone in Upper and Lower Extremity Deep Vein Thrombosis

    SciTech Connect

    Kim, Hyun S. Patra, Ajanta; Paxton, Ben E.; Khan, Jawad; Streiff, Michael B.

    2006-12-15

    Purpose. To compare the efficacy of catheter-directed thrombolysis (CDT) alone versus CDT with rheolytic percutaneous mechanical thrombectomy (PMT) for upper and lower extremity deep vein thrombosis (DVT). Methods. A retrospective cohort of consecutive patients with acute iliofemoral or brachiosubclavian DVT treated with urokinase CDT was identified, and a chart review was conducted. Demographic characteristics, treatment duration, total lytic dose, clot lysis rates and complications were compared in patients treated with urokinase CDT alone or combined CDT and rheolytic PMT. Results. Forty limbs in 36 patients were treated with urokinase CDT alone. Twenty-seven limbs in 21 patients were treated with urokinase CDT and rheolytic PMT. The mean treatment duration for urokinase CDT alone was 48.0 {+-} 27.1 hr compared with 26.3 {+-} 16.6 hr for urokinase CDT and rheolytic PMT (p = 0.0004). The mean urokinase dose required for CDT alone was 5.6 {+-} 5.3 million units compared with 2.7 {+-} 1.8 million units for urokinase CDT with rheolytic PMT (p = 0.008). Complete clot lysis was achieved in 73% (29/40) of DVT treated with urokinase CDT alone compared with 82% (22/27) treated with urokinase CDT with rheolytic PMT. Conclusion. Percutaneous CDT with rheolytic PMT is as effective as CDT alone for acute proximal extremity DVT but requires significantly shorter treatment duration and lower lytic doses. Randomized studies to confirm the benefits of pharmacomechanical thrombolysis in the treatment of acute proximal extremity DVT are warranted.

  16. Prototype fabrication and preliminary in vitro testing of a shape memory endovascular thrombectomy device.

    PubMed

    Small, Ward; Wilson, Thomas S; Buckley, Patrick R; Benett, William J; Loge, Jeffrey M; Hartman, Jonathan; Maitland, Duncan J

    2007-09-01

    An electromechanical microactuator comprised of shape memory polymer (SMP) and shape memory nickel-titanium alloy (nitinol) was developed and used in an endovascular thrombectomy device prototype. The microactuator maintains a straight rod shape until an applied current induces electro-resistive (Joule) heating, causing the microactuator to transform into a corkscrew shape. The straight-to-corkscrew transformation geometry was chosen to permit endovascular delivery through (straight form) and retrieval of (corkscrew form) a stroke-causing thrombus (blood clot) in the brain. Thermal imaging of the microactuator during actuation in air indicated that the steady-state temperature rise caused by Joule heating varied quadratically with applied current and that actuation occurred near the glass transition temperature of the SMP (86 degrees C). To demonstrate clinical application, the device was used to retrieve a blood clot in a water-filled silicone neurovascular model. Numerical modeling of the heat transfer to the surrounding blood and associated thermal effects on the adjacent artery potentially encountered during clinical use suggested that any thermal damage would likely be confined to localized areas where the microactuator was touching the artery wall. This shape memory mechanical thrombectomy device is a promising tool for treating ischemic stroke without the need for infusion of clot-dissolving drugs. PMID:17867358

  17. Early middle cerebral artery stenosis following stent-assisted thrombectomy

    PubMed Central

    Akpınar, Süha

    2015-01-01

    Stent-assisted thrombectomy (SAT) is an extensively used endovascular treatment method for stroke in which the thrombectomy stents come into direct contact with the vascular intimal surface and entrap the thrombus causing the arterial occlusion. Although there are a few studies that demonstrate that the vessel wall changes in the arteries where stroke intervention is performed, we observed progressive stenosis in early follow-up imaging studies in a case. We present a middle cerebral artery (MCA) stroke patient who had four repetitive stent passes during SAT and developed distal MCA stenosis 2 months after SAT at the control magnetic resonance angiography (MRA). Inclusion of early follow-up MRA studies would be helpful in defining the silent vascular changes in patients who have undergone repetitive SAT. PMID:26015531

  18. Delayed Presentation of Endovenous Heat-Induced Thrombosis Treated by Thrombolysis and Subsequent Open Thrombectomy

    PubMed Central

    Kwak, Jung Hak; Min, Sang Il; Kim, Song-Yi; Han, Ahram; Choi, Chanjoong; Ahn, Sanghyun; Ha, Jongwon; Min, Seung-Kee

    2016-01-01

    Although endovenous heat-induced thrombosis (EHIT) is frequently reported after endovenous laser ablation (EVLA), the incidence and timing of occurrence of EHIT are not fully understood. We present a case of EHIT successfully treated with a combination of surgical and endovascular treatments. A 57-year-old woman, two months post bilateral EVLA, presented with a swollen leg. Deep vein thrombosis was diagnosed by Doppler ultrasonography and computerized tomographic venography. We treated the patient with catheter-directed thrombolysis with urokinase after insertion of an inferior vena cava filter. After thrombolytic treatment, we performed surgical venous thrombectomy, due to the presence of a large thrombus in the femoral vein. During the operation, we found organized old thrombus at the great saphenous vein which connected to the deep femoral vein. From these findings, we confirmed the presence of EHIT despite a long time having passed after EVLA. The patient was placed on anticoagulation therapy with oral rivaroxaban for three months. PMID:27386456

  19. Delayed Presentation of Endovenous Heat-Induced Thrombosis Treated by Thrombolysis and Subsequent Open Thrombectomy.

    PubMed

    Kwak, Jung Hak; Min, Sang Il; Kim, Song-Yi; Han, Ahram; Choi, Chanjoong; Ahn, Sanghyun; Ha, Jongwon; Min, Seung-Kee

    2016-06-01

    Although endovenous heat-induced thrombosis (EHIT) is frequently reported after endovenous laser ablation (EVLA), the incidence and timing of occurrence of EHIT are not fully understood. We present a case of EHIT successfully treated with a combination of surgical and endovascular treatments. A 57-year-old woman, two months post bilateral EVLA, presented with a swollen leg. Deep vein thrombosis was diagnosed by Doppler ultrasonography and computerized tomographic venography. We treated the patient with catheter-directed thrombolysis with urokinase after insertion of an inferior vena cava filter. After thrombolytic treatment, we performed surgical venous thrombectomy, due to the presence of a large thrombus in the femoral vein. During the operation, we found organized old thrombus at the great saphenous vein which connected to the deep femoral vein. From these findings, we confirmed the presence of EHIT despite a long time having passed after EVLA. The patient was placed on anticoagulation therapy with oral rivaroxaban for three months. PMID:27386456

  20. Safety and efficacy of the Aperio thrombectomy device when compared to the Solitaire AB/FR and the Revive devices in a pulsatile flow system

    PubMed Central

    Saleh, Mahdi; Spence, John Nathan; Nayak, Sanjeev; Pearce, Gillian; Tennuci, Christopher; Roffe, Christine

    2012-01-01

    Background and Purpose: There are a limited number of studies comparing the Aperio mechanical thrombectomy device to other stent-based devices. In this paper, we compared the Aperio thrombectomy device to the Solitaire AB, FR and Revive devices in a model of the middle cerebral artery (MCA) within a modified pulsatile flow system. Methods: Thrombi made of lamb’s blood were placed into a pulsatile flow system perfused with Hartmann’s solution at 80 bpm with a mean pressure of 90 mm Hg. 30 experiments were run with each device. Results: Recanalization rates were similar for all three devices (90% with the Solitaire AB, FR, 80% with the Revive, and 90% with the Aperio). The mean number of attempts to retrieve the thrombus was also similar for all three devices (1.7 with the Solitaire AB, FR, 2.1 with the Revive, 1.6 with the Aperio). Clot fragmentation and embolization rates revealed no statistical significance but there was a trend towards lower embolization rates with the Aperio (23% compared to 40% with the Solitaire AB, FR and 47% with the Revive). The Aperio was the fastest to recanalize the MCA (mean of 66 seconds compared to 186 seconds for the Solitaire AB, FR and 169 seconds for the Revive). Conclusions: In this in vitro setting, the Aperio device seems to be an efficacious and safe device when compared to other similar clinically used mechanical thrombectomy devices. Larger clinical trials are warranted. PMID:23173104

  1. Combined hydrophobicity and mechanical durability through surface nanoengineering

    DOE PAGESBeta

    Elliott, Paul R.; Stagon, Stephen P.; Huang, Hanchen; Furrer, David U.; Burlatsky, Sergei F.; Filburn, Thomas P.

    2015-04-08

    This paper reports combined hydrophobicity and mechanical durability through the nanoscale engineering of surfaces in the form of nanorod-polymer composites. Specifically, the hydrophobicity derives from nanoscale features of mechanically hard ZnO nanorods and the mechanical durability derives from the composite structure of a hard ZnO nanorod core and soft polymer shell. Experimental characterization correlates the morphology of the nanoengineered surfaces with the combined hydrophobicity and mechanical durability, and reveals the responsible mechanisms. Such surfaces may find use in applications, such as boat hulls, that benefit from hydrophobicity and require mechanical durability.

  2. Combined Hydrophobicity and Mechanical Durability through Surface Nanoengineering

    PubMed Central

    Elliott, Paul R.; Stagon, Stephen P.; Huang, Hanchen; Furrer, David U.; Burlatsky, Sergei F.; Filburn, Thomas P.

    2015-01-01

    This paper reports combined hydrophobicity and mechanical durability through the nanoscale engineering of surfaces in the form of nanorod-polymer composites. Specifically, the hydrophobicity derives from nanoscale features of mechanically hard ZnO nanorods and the mechanical durability derives from the composite structure of a hard ZnO nanorod core and soft polymer shell. Experimental characterization correlates the morphology of the nanoengineered surfaces with the combined hydrophobicity and mechanical durability, and reveals the responsible mechanisms. Such surfaces may find use in applications, such as boat hulls, that benefit from hydrophobicity and require mechanical durability. PMID:25851026

  3. Combined Hydrophobicity and Mechanical Durability through Surface Nanoengineering

    NASA Astrophysics Data System (ADS)

    Elliott, Paul R.; Stagon, Stephen P.; Huang, Hanchen; Furrer, David U.; Burlatsky, Sergei F.; Filburn, Thomas P.

    2015-04-01

    This paper reports combined hydrophobicity and mechanical durability through the nanoscale engineering of surfaces in the form of nanorod-polymer composites. Specifically, the hydrophobicity derives from nanoscale features of mechanically hard ZnO nanorods and the mechanical durability derives from the composite structure of a hard ZnO nanorod core and soft polymer shell. Experimental characterization correlates the morphology of the nanoengineered surfaces with the combined hydrophobicity and mechanical durability, and reveals the responsible mechanisms. Such surfaces may find use in applications, such as boat hulls, that benefit from hydrophobicity and require mechanical durability.

  4. Septic Coronary Artery Embolism Treated with Aspiration Thrombectomy: Case Report and Review of Literature

    PubMed Central

    Sarwar, Nosheen; Eftekhari, Hossein; Lotfi, Amir

    2014-01-01

    Coronary embolization is a potentially fatal sequela of endocarditis. We report a case of Candida endocarditis with septic embolism to the left anterior descending coronary artery. This embolism was successfully treated with aspiration thrombectomy followed by balloon angioplasty. The treatment of acute coronary syndrome in the presence of septic embolism is controversial. Aspiration thrombectomy has been performed in this situation before, and it appears to be safer and more feasible than is thrombolysis or percutaneous transluminal angioplasty. PMID:25120402

  5. Iliocaval Stenosis and Iliac Venous Thrombosis in Retroperitoneal Fibrosis: Percutaneous Treatment by Use of Hydrodynamic Thrombectomy and Stenting

    SciTech Connect

    Vorwerk, Dierk; Guenther, Rolf W.; Wendt, Georg; Neuerburg, Joerg; Schuermann, Karl

    1996-11-15

    A case of bilateral iliac stenosis and caval stenosis due to retroperitoneal fibrosis was treated by caval stenting and iliac balloon angioplasty, but was complicated by subsequent iliac thrombosis. Venous thrombectomy was successfully achieved by hydrodynamic thrombectomy, and iliac patency was stabilized by bilateral stent insertion.

  6. Fascia Iliaca block as the sole anesthesia technique in a patient with recent myocardial infarction for emergency femoral thrombectomy

    PubMed Central

    Parate, Leena Harshad; Channappa, Nagaraj Mungasuvalli; Pujari, Vinayak; Iyer, Sadasivan

    2015-01-01

    Acute limb ischemia is a surgical emergency that precludes prolonged preoperative cardiac evaluation. A 70-year-old female with recent myocardial infarction was posted for emergency transfemoral thrombectomy. We discuss the perioperative anesthetic considerations in these case. Fascia iliaca block can be used as sole anesthesia technique for transfemoral thrombectomy in high-risk patients. PMID:25829911

  7. Elder homicide by unique combination of different mechanisms of asphyxia

    PubMed Central

    Pramanik, Parthasarathi

    2015-01-01

    Elder homicide is a fatal outcome of elder abuse and neglect. Multifactorial homicidal asphyxia in an elderly man by combination of three different mechanisms is an uncommon incident. This following case demonstrates a very unusual murder of 74-year-old man in his own residence. Crime scene visit and postmortem examination revealed that the victim was killed by combined effect of ligature strangulation, traumatic asphyxia and smothering by plastic bag. PMID:25664272

  8. Adenosine triphosphate hydrolysis mechanism in kinesin studied by combined quantum-mechanical/molecular-mechanical metadynamics simulations.

    PubMed

    McGrath, Matthew J; Kuo, I-F Will; Hayashi, Shigehiko; Takada, Shoji

    2013-06-19

    Kinesin is a molecular motor that hydrolyzes adenosine triphosphate (ATP) and moves along microtubules against load. While motility and atomic structures have been well-characterized for various members of the kinesin family, not much is known about ATP hydrolysis inside the active site. Here, we study ATP hydrolysis mechanisms in the kinesin-5 protein Eg5 by using combined quantum mechanics/molecular mechanics metadynamics simulations. Approximately 200 atoms at the catalytic site are treated by a dispersion-corrected density functional and, in total, 13 metadynamics simulations are performed with their cumulative time reaching ~0.7 ns. Using the converged runs, we compute free energy surfaces and obtain a few hydrolysis pathways. The pathway with the lowest free energy barrier involves a two-water chain and is initiated by the Pγ-Oβ dissociation concerted with approach of the lytic water to PγO3-. This immediately induces a proton transfer from the lytic water to another water, which then gives a proton to the conserved Glu270. Later, the proton is transferred back from Glu270 to HPO(4)2- via another hydrogen-bonded chain. We find that the reaction is favorable when the salt bridge between Glu270 in switch II and Arg234 in switch I is transiently broken, which facilitates the ability of Glu270 to accept a proton. When ATP is placed in the ADP-bound conformation of Eg5, the ATP-Mg moiety is surrounded by many water molecules and Thr107 blocks the water chain, which together make the hydrolysis reaction less favorable. The observed two-water chain mechanisms are rather similar to those suggested in two other motors, myosin and F1-ATPase, raising the possibility of a common mechanism. PMID:23751065

  9. To Tube or Not to Tube? The Role of Intubation during Stroke Thrombectomy

    PubMed Central

    Takahashi, Courtney; Liang, Conrad W.; Liebeskind, David S.; Hinman, Jason D.

    2014-01-01

    In the 10 years since the FDA first cleared the use of endovascular devices for the treatment of acute stroke, definitive evidence that such therapy improves outcomes remains lacking. The decision to intubate patients undergoing stroke thrombectomy impacts multiple variables that may influence outcomes after stroke. Three main areas where intubation may deleteriously affect acute stroke management include the introduction of delays in revascularization, fluctuations in peri-procedural blood pressure, and hypocapnia, resulting in cerebral vasoconstriction. In this mini-review, we discuss the evidence supporting these limitations of intubation during stroke thrombectomy and encourage neurohospitalists, neurocritical care specialists, and neurointerventionalists to carefully consider the decision to intubate during thrombectomy and provide strategies to avoid potential complications associated with its use in acute stroke. PMID:25295027

  10. Endovascular therapy including thrombectomy for acute ischemic stroke: A systematic review and meta-analysis with trial sequential analysis.

    PubMed

    Phan, Kevin; Zhao, Dong Fang; Phan, Steven; Huo, Ya Ruth; Mobbs, Ralph J; Rao, Prashanth J; Mortimer, Alex M

    2016-07-01

    One of the primary strategies for the management of acute ischemic stroke is intravenous (IV) thrombolysis with tissue plasminogen activator (t-PA). Over the past decade, endovascular therapies such as the use of stent retrievers to perform mechanical thrombectomy have been found to improve functional outcomes compared to t-PA alone. We aimed to reassess the functional outcomes and complications of IV thrombolysis with and without endovascular treatment for acute ischemic stroke using conventional meta-analysis and trial sequential analysis. Pooled relative risks (RR) and 95% confidence intervals (CI) were calculated for the effect of IV thrombolysis with and without endovascular therapy on functional outcome, mortality and symptomatic intracranial hemorrhage (SICH). Trial sequential analysis was done to strengthen the meta-analysis. We analyzed six randomized controlled trials involving 1943 patients. Patients who received IV thrombolysis with endovascular treatment showed significantly higher rates of excellent functional outcomes (modified Rankin Scale [mRS] 0-1) (RR, 1.75 [95% CI, 1.29-2.39]) compared to those who received IV thrombolysis alone. A similar association was seen for good functional outcomes (mRS 0-2) (RR, 1.56 [95% CI, 1.24-1.96]). Trial sequential analysis demonstrated endovascular treatment increased the RR of a good functional outcome by at least 30% compared to IV thrombolysis alone. There was no significant difference in all-cause mortality for mechanical thrombectomy compared to IV thrombolysis alone or the incidence of SICH at 3month follow-up. Endovascular treatment is more likely to result in a better functional outcome for patients compared to IV thrombolysis alone for acute ischemic stroke. PMID:26947342

  11. Pulmonary Hypertension Among End-Stage Renal Failure Patients Following Hemodialysis Access Thrombectomy

    SciTech Connect

    Harp, Richard J.; Stavropoulos, S. William; Wasserstein, Alan G.; Clark, Timothy W.I.

    2005-01-15

    Purpose: Percutaneous hemodialysis thrombectomy causes subclinical pulmonary emboli without short-term clinical consequence; the long-term effects on the pulmonary arterial vasculature are unknown. We compared the prevalence of pulmonary hypertension between patients who underwent one or more hemodialysis access thrombectomy procedures with controls without prior thrombectomy.Methods: A retrospective case-control study was performed. Cases (n = 88) had undergone one or more hemodialysis graft thrombectomy procedures, with subsequent echocardiography during routine investigation of comorbid cardiovascular disease. Cases were compared with controls without end-stage renal disease (ESRD) (n = 100, group 1), and controls with ESRD but no prior thrombectomy procedures (n = 117, group 2). The presence and velocity of tricuspid regurgitation on echocardiography was used to determine the prevalence and grade of pulmonary hypertension; these were compared between cases and controls using the chi-square test and logistic regression.Results: The prevalence of pulmonary hypertension among cases was 52% (46/88), consisting of mild, moderate and severe in 26% (n = 23), 10% (n = 9) and 16% (n = 14), respectively. Prevalence of pulmonary hypertension among group 1 controls was 26% (26/100), consisting of mild, moderate and severe pulmonary hypertension in 14%, 5% and 7%, respectively. Cases had 2.7 times greater odds of having pulmonary hypertension than group 1 controls (p = 0.002). The prevalence of pulmonary hypertension among group 2 controls was 42% (49/117), consisting of mild, moderate and severe pulmonary arterial hypertension in 25% (n = 49), 10% (n = 12) and 4% (n = 5), respectively. Cases were slightly more likely to have pulmonary hypertension than group 2 controls (OR = 1.5), although this failed to reach statistical significance (p = 0.14).Conclusion: Prior hemodialysis access thrombectomy does not appear to be a risk factor for pulmonary arterial hypertension

  12. View Combination: A Generalization Mechanism for Visual Recognition

    ERIC Educational Resources Information Center

    Friedman, Alinda; Waller, David; Thrash, Tyler; Greenauer, Nathan; Hodgson, Eric

    2011-01-01

    We examined whether view combination mechanisms shown to underlie object and scene recognition can integrate visual information across views that have little or no three-dimensional information at either the object or scene level. In three experiments, people learned four "views" of a two dimensional visual array derived from a three-dimensional…

  13. Randomized Trial of Primary PCI with or without Routine Manual Thrombectomy

    PubMed Central

    Jolly, Sanjit S.; Cairns, John A.; Yusuf, Salim; Meeks, Brandi; Pogue, Janice; Rokoss, Michael J.; Kedev, Sasko; Thabane, Lehana; Stankovic, Goran; Moreno, Raul; Gershlick, Anthony; Chowdhary, Saqib; Lavi, Shahar; Niemelä, Kari; Steg, Philippe Gabriel; Bernat, Ivo; Xu, Yawei; Cantor, Warren J.; Overgaard, Christopher B.; Naber, Christoph K.; Cheema, Asim N.; Welsh, Robert C.; Bertrand, Olivier F.; Avezum, Alvaro; Bhindi, Ravinay; Pancholy, Samir; Rao, Sunil V.; Natarajan, Madhu K.; ten Berg, Jurriën M.; Shestakovska, Olga; Gao, Peggy; Widimsky, Petr; Džavík, Vladimír

    2016-01-01

    BACKGROUND During primary percutaneous coronary intervention (PCI), manual thrombectomy may reduce distal embolization and thus improve microvascular perfusion. Small trials have suggested that thrombectomy improves surrogate and clinical outcomes, but a larger trial has reported conflicting results. METHODS We randomly assigned 10,732 patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary PCI to a strategy of routine upfront manual thrombectomy versus PCI alone. The primary outcome was a composite of death from cardiovascular causes, recurrent myocardial infarction, cardiogenic shock, or New York Heart Association (NYHA) class IV heart failure within 180 days. The key safety outcome was stroke within 30 days. RESULTS The primary outcome occurred in 347 of 5033 patients (6.9%) in the thrombectomy group versus 351 of 5030 patients (7.0%) in the PCI-alone group (hazard ratio in the thrombectomy group, 0.99; 95% confidence interval [CI], 0.85 to 1.15; P = 0.86). The rates of cardiovascular death (3.1% with thrombectomy vs. 3.5% with PCI alone; hazard ratio, 0.90; 95% CI, 0.73 to 1.12; P = 0.34) and the primary outcome plus stent thrombosis or target-vessel revascularization (9.9% vs. 9.8%; hazard ratio, 1.00; 95% CI, 0.89 to 1.14; P = 0.95) were also similar. Stroke within 30 days occurred in 33 patients (0.7%) in the thrombectomy group versus 16 patients (0.3%) in the PCI-alone group (hazard ratio, 2.06; 95% CI, 1.13 to 3.75; P = 0.02). CONCLUSIONS In patients with STEMI who were undergoing primary PCI, routine manual thrombectomy, as compared with PCI alone, did not reduce the risk of cardiovascular death, recurrent myocardial infarction, cardiogenic shock, or NYHA class IV heart failure within 180 days but was associated with an increased rate of stroke within 30 days. (Funded by Medtronic and the Canadian Institutes of Health Research; TOTAL ClinicalTrials.gov number, NCT01149044.) PMID:25853743

  14. Efficacy of Proximal Aspiration Thrombectomy for Using Balloon-Tipped Guide Catheter in Acute Intracranial Internal Carotid Artery Occlusion

    PubMed Central

    Kim, Yong-Won; Hwang, Yang-Ha; Park, Jaechan; Kim, Yong-Sun

    2016-01-01

    Objective Mechanical thrombectomy (MT) for acute intracranial internal carotid artery (ICA) occlusion is often complicated by difficult revascularization and non-involved territory embolization possibly related with larger clot-burden. This study aims to evaluate the efficacy of proximal aspiration thrombectomy (PAT) using a balloon-tipped guide catheter for clot-burden reduction in such cases with period-to-period analysis (period 1 : standard MT without PAT; period 2 : PAT first, then standard MT for the remaining occlusion). Methods Eighty-six patients who underwent MT for acute intracranial ICA occlusion were included in this analysis from the prospectively maintained stroke registry (33 patients in period 1 and 53 in period 2). In period 2, 'responder' was defined as a case where some amount of clot was retrieved by PAT and the following angiography showed partial or full recanalization. Results Fifteen of fifty-three patients in period 2 (28.3%) were 'responders' to PAT. There was a significantly higher incidence of atrial fibrillation in the 'responder' subgroup. Period 2 showed a significantly shorter puncture-to-reperfusion time (94.5 minutes vs. 56.0 minutes; p=0.002), a significantly higher Thrombolysis in Cerebral Infarction of 2b-3 reperfusion (45.5% vs. 73.6%; p=0.009), but only a trend for better 3-month favorable outcome (mRS 0–2; 36.4% vs. 54.7%; p=0.097). There was no increase in the incidence of procedure-related complications or intracranial hemorrhage in period 2. Conclusion A strategy of PAT before standard MT may result in shorter puncture-to-reperfusion time and better angiographic outcome than a strategy of standard MT for acute intracranial ICA occlusion. PMID:27446520

  15. Behavior of cracked cylinders under combined thermal and mechanical loading

    SciTech Connect

    Ignaccolo, S.

    1996-12-01

    Nuclear pressure vessels and pipings can be submitted in their life to severe mechanical and thermal loadings. Engineering methods easy to apply, but sufficiently accurate, are needed to assess the flaws. In the field of non-linear fracture mechanics a lot of work has been achieved for structures submitted to mechanical loadings. But for thermal loadings, and particularly for thermal gradients, only few contributions are available. The authors propose, here, to present the main results of a complete set of finite element computations, conducted in France by CEA, EDF and FRAMATOME, on cracked cylinders submitted to combined mechanical and thermal loads. The interaction between these two types of loads is analyzed in the cases of austenitic and ferritic structures. Moreover, these results are compared to the predictions obtained by simplified engineering methods (R6 procedure, J{sub SA16}, and J{sub EDF} approaches). Their domain of validity is also discussed.

  16. Increasing Efficacy of Thrombectomy by Using Digital Subtraction Angiography to Confirm Stent Retriever Clot Integration.

    PubMed

    Simon, Scott; Langan, Sara; Cooke, Jonathon

    2016-01-01

    Physicians performing thrombectomy for acute stroke have had increasing success as thrombectomy-specific devices have continued to evolve. As the devices evolve, so too must the techniques. The current generation of stent retriever thrombectomy devices requires five minutes of dwell time, regardless of the particularities of the case. We have noticed the presence of flow through the stent immediately prior to removal portends a lower chance of successful thrombus retrieval than when no flow is seen, regardless of dwell time. We hypothesize that interventionalists can use the presence or absence of flow to predict adequacy of seating time and decrease the number of deployments per case. This could significantly decrease time to recanalization by avoiding time-consuming, unsuccessful pulls. This is a technical report of a few cases of stent retriever thrombectomy. We propose using post-deployment digital subtraction angiography to confirm thrombus-device integration and increase the chance of thrombus removal. PMID:27182473

  17. Outcome and periprocedural time management in referred versus directly admitted stroke patients treated with thrombectomy

    PubMed Central

    Weber, Ralph; Reimann, Gernot; Weimar, Christian; Winkler, Angela; Berger, Klaus; Nordmeyer, Hannes; Hadisurya, Jeffrie; Brassel, Friedhelm; Kitzrow, Martin; Krogias, Christos; Weber, Werner; Busch, Elmar W.; Eyding, Jens

    2015-01-01

    Background: After thrombectomy has shown to be effective in acute stroke patients with large vessel occlusion, the potential benefit of secondary referral for such an intervention needs to be validated. Aims: We aimed to compare consecutive stoke patients directly admitted and treated with thrombectomy at a neurointerventional centre with patients secondarily referred for such a procedure from hospitals with a stroke unit. Methods: Periprocedure times and mortality in 300 patients primarily treated in eight neurointerventional centres were compared with 343 patients referred from nine other hospitals in a prospective multicentre study of a German neurovascular network. Data on functional outcome at 3 months was available in 430 (76.4%) patients. Results: In-hospital mortality (14.8% versus 11.7%, p = 0.26) and 3 months mortality (21.9% versus 24.1%, p = 0.53) were not statistically different in both patient groups despite a significant shorter symptom to groin puncture time in directly admitted patients, which was mainly caused by a longer interfacility transfer time. We found a nonsignificant trend for better functional outcome at 3 months in directly admitted patients (modified Rankin Scale 0–2, 44.0% versus 35.7%, p = 0.08). Conclusions: Our results show that a drip-and-ship thrombectomy concept can be effectively organized in a metropolitan stroke network. Every effort should be made to speed up the emergency interfacility transfer to a neurointerventional centre in stroke patients eligible for thrombectomy after initial brain imaging. PMID:27006695

  18. Percutaneous Aspiration Thrombectomy for Arterial Thromboembolism during Infrainguinal Endovascular Recanalization

    PubMed Central

    Wei, Li-Ming; Zhu, Yue-Qi; Liu, Fang; Zhang, Pei-Lei; Li, Xiao-Cong; Zhao, Jun-Gong; Lu, Hai-Tao

    2015-01-01

    Objectives To evaluate the efficacy of percutaneous aspiration thrombectomy (PAT) for infrainguinal arterial thromboembolism in patients undergoing endovascular recanalization (EVR) and to investigate the predictors for thromboembolic complications. Materials and Methods In total, 23 patients (23 limbs) who underwent PAT for thromboembolism (PAT group, PG) during EVR and 237 patients (302 limbs) who underwent successful EVR without thromboembolic complications (control group, CG) were enrolled. Immediate post-operation and follow-up outcomes were compared between the two groups. Multivariate analysis was performed to identify the predictors of thromboembolic complications. Technical success of PAT was defined as achievement of <30% residual stenosis and restoration of mTIMI grade 3. Results The technical success rate was 95.7% in PG. After intervention, the ankle–brachial index (ABI), restoration of blood flow and improvement in dorsal/plantar arterial pulse score showed no significant differences between PG and CG. During follow-up in PG, a sustained ABI improvement was observed in 63.6% (70.9% in CG), an improvement in walking distance in 68.8% (79.9% in CG,), ulcer healing in 75.0% (71.7% in CG) and restenosis/occlusion in 31.8% (25.2% in CG). The limb salvage rate was 100% in PG (96.0% in CG), and pain relief was observed in 66.7% patients with critical limb ischaemia (81.6% in CG). Superficial femoral artery involvement [0.233; 95% confidence interval (CI), 0.108–0.461; P < 0.001], de-novo lesion occlusion (683.8; 95% CI, 36.5–12804.6; P < 0.001) and intraluminal angioplasty (118.4; 95% CI, 8.0–1758.0; P = 0.001) was associated with high incidence of thromboembolism. Conclusion PAT is a safe and effective treatment for thromboembolism during infrainguinal arterial EVR. SFA involvement, de-novo lesion occlusion and intraluminal angioplasty may be predictors of thromboembolic complications. PMID:26484672

  19. [Combined mechanical-cold and mechanical-burn injuries in patients injured in maritime disasters].

    PubMed

    Zakrevskii, Yu N; Shevchenko, A G; Peretechikov, A V; Serdyuk, V I; Arkhangelskii, D A

    2015-06-01

    On the basis of analysis of 372 medical histories and total amount of victims (2691 people) of marine accidents it was revealed that 303 (83.1%) survivors suffered from combined mechanical-cold injuries, combined two-factor mechanical-burn injuries were diagnosed in 115 of wounded (15.7%), combined three-factor mechanical-cold-burn injuries were diagnosed in 162 of wounded (22.5%). It was established that in case of capsizing and shipwrecking chest and abdomen injuries prevail in wounded (22.4%). Pelvic fractures, injuries of the lower extremities and spine traumas prevail in wounded evacuated from the crash area after explosion and fire on the ships (43.3%). The above-mentioned injuries prevail due to mine-blast nature of injuries. Typical injuries in wounded survived in maritime disasters are in non-severe combined mechanical-cold, mechanical-burn, and mechanical-cold-burn injuries, minor and moderate hypothermia, mild burn injuries and mild carbon monoxide poisoning. PMID:26442314

  20. Iliofemoral-popliteal deep vein thrombosis at 35(th) week of pregnancy: treated with cesarean section and vena cava blockage plus thrombectomy.

    PubMed

    Mehmet Burgazlı, K; Altay, Metin M; Akdere, Hakan; Bilgin, Mehmet; Kavukcu, Ethem; Kill, Horst; Päfgen, Werner; Kubilay Ertan, A

    2012-01-01

    Pregnancy, due to its adaptive physiological changes, is a risk factor for deep vein thrombosis. Incidence of thromboembolic complications during pregnancy ranges from 0.76 to 1.72 per 1000 births. We present in this case report a pregnant woman with iliofemoral-popliteal deep vein thrombosis diagnosed at the 35(th) week of her pregnancy, who was treated with vena cava blockage and thrombectomy followed by cesarean section. Unfortunately, a rethrombosis developed in the patient after three days. We determined that the a-v fistula was blocked and not working. We found additionally that the deep vein thrombosis was closing the iliac vein completely on the left side and the blockage descending down through the inferior vena cava inlet with MRI. The patient underwent insertion of a retrievable vena cava filter, two stent implantation to the venous narrowings and surgical iliofemoral venous thrombectomy with concomitant re-creation of a temporary femoral arterio-venous fistula. Anticoagulation therapy with enoxaparine was started after the operation. The patient was discharged with warfarin under control of the INR value, and also with additional compression therapy (compression stockings) from the clinic. Without jeopardizing the mother and the baby, planning a combined surgical procedure, with a multidisciplinary approach is the best way to eliminate the risks of serious complications such as pulmonary embolism and mortality. PMID:24592024

  1. Mechanical properties of roots combined with prefabricated fiber post.

    PubMed

    Kono, Takashi; Yoshinari, Masao; Takemoto, Shinji; Hattori, Masayuki; Kawada, Eiji; Oda, Yutaka

    2009-09-01

    This study examined the mechanical properties of roots combined with prefabricated fiber post. Three types of specimens were evaluated: (1) prefabricated fiber post alone (FP); (2) core composite resin with FP (CFP); and (3) root with CFP (RCFP). The volume fractions of the prefabricated fiber post in the core composite resin (FP/CFP ratio) were set to 0, 0.16, 0.22, 0.28, and 0.48. Bending test for FP and CFP, and diametral compression test for FP, CFP, and RCFP were carried out. The FP/CFP ratio showed no effect on the diametral tensile strength (DTS) of RCFP; and there were no significant differences in DTS with/without FP. The flexural strength of CFP increased with increase in FP/CFP ratio. The DTS of CFP declined in comparison with that of core composite resin only. PMID:19822983

  2. Thrombectomy in posterior circulation stroke through persistent primitive trigeminal artery: A case report.

    PubMed

    Mulder, Mjhl; Lycklama À Nijeholt, G J; Dinkelaar, W; de Rooij, Tpw; van Es, Acgm; van der Kallen, B F; Emmer, B J

    2015-12-01

    We describe a case of intra-arterial treatment (IAT) of acute posterior circulation occlusion in a patient with a persistent primitive trigeminal artery (PPTA). The patient presented with an acute left sided hemiparesis and loss of consciousness (Glasgow coma score of 5). Computed tomography angiography showed an acute occlusion of the right internal carotid artery (ICA), the PPTA, distal basilar artery (BA), right posterior cerebral artery (PCA), and right superior cerebellar artery (SCA). Stent-retriever assisted thrombectomy was not considered possible through the hypoplastic proximal BA. After passage of the proximal ICA occlusion, the right PCA and SCA were recanalized through the PPTA, with a single thrombectomy procedure. Ten days after intervention patient was discharged scoring optimal EMV with only a mild facial and left hand paresis remaining. PPTA is a persistent embryological carotid-basilar connection. Knowledge of existing (embryonic) variants in neurovascular anatomy is essential when planning and performing acute neurointerventional procedures. PMID:26464287

  3. Combination of mechanical athermalization with manual in IR zoom telescope

    NASA Astrophysics Data System (ADS)

    Chen, Ruiyi; Zheng, Dayue; Zhou, Xiuli; Zhang, Xingde

    1991-12-01

    An infrared zoom telescope possessing the lenses made of germanium and working at -10 degree(s) to 40 degree(s)C and at 8 - 12 micrometers has been designed. The main problem to be solved is that the refraction index of Ge changes with the temperature, resulting in decollimation. For the purpose of lower production cost and reduced size and weight, a combination of mechanical passive athermalization by the collimating lens group with manual athermalization by the front lens which is chiefly utilized to focus the object is adopted. The lens mount is made of aluminum alloy. A pair of elements of mechanical passive athermalization, nylon/indium steel, is used to partially compensate the effect of variation of refraction index of Ge and expansion or contraction of aluminum alloy on the distance between the fixed and the collimating lens groups. The manually additional adjustment of the focusing lens, i.e., the front lens, is to partially compensate the distance between the front lens and the second lens group.

  4. Apparent-Strain Correction for Combined Thermal and Mechanical Testing

    NASA Technical Reports Server (NTRS)

    Johnson, Theodore F.; O'Neil, Teresa L.

    2007-01-01

    Combined thermal and mechanical testing requires that the total strain be corrected for the coefficient of thermal expansion mismatch between the strain gage and the specimen or apparent strain when the temperature varies while a mechanical load is being applied. Collecting data for an apparent strain test becomes problematic as the specimen size increases. If the test specimen cannot be placed in a variable temperature test chamber to generate apparent strain data with no mechanical loads, coupons can be used to generate the required data. The coupons, however, must have the same strain gage type, coefficient of thermal expansion, and constraints as the specimen to be useful. Obtaining apparent-strain data at temperatures lower than -320 F is challenging due to the difficulty to maintain steady-state and uniform temperatures on a given specimen. Equations to correct for apparent strain in a real-time fashion and data from apparent-strain tests for composite and metallic specimens over a temperature range from -450 F to +250 F are presented in this paper. Three approaches to extrapolate apparent-strain data from -320 F to -430 F are presented and compared to the measured apparent-strain data. The first two approaches use a subset of the apparent-strain curves between -320 F and 100 F to extrapolate to -430 F, while the third approach extrapolates the apparent-strain curve over the temperature range of -320 F to +250 F to -430 F. The first two approaches are superior to the third approach but the use of either of the first two approaches is contingent upon the degree of non-linearity of the apparent-strain curve.

  5. Feasibility of Crosslinked Acrylic Shape Memory Polymer for a Thrombectomy Device

    PubMed Central

    Muschenborn, Andrea D.; Hearon, Keith; Volk, Brent L.; Conway, Jordan W.; Maitland, Duncan J.

    2014-01-01

    Purpose To evaluate the feasibility of utilizing a system of SMP acrylates for a thrombectomy device by determining an optimal crosslink density that provides both adequate recovery stress for blood clot removal and sufficient strain capacity to enable catheter delivery. Methods Four thermoset acrylic copolymers containing benzylmethacrylate (BzMA) and bisphenol A ethoxylate diacrylate (Mn~512, BPA) were designed with differing thermomechanical properties. Finite element analysis (FEA) was performed to ensure that the materials were able to undergo the strains imposed by crimping, and fabricated devices were subjected to force-monitored crimping, constrained recovery, and bench-top thrombectomy. Results Devices with 25 and 35 mole% BPA exhibited the highest recovery stress and the highest brittle response as they broke upon constrained recovery. On the contrary, the 15 mole % BPA devices endured all testing and their recovery stress (5 kPa) enabled successful bench-top thrombectomy in 2/3 times, compared to 0/3 for the devices with the lowest BPA content. Conclusion While the 15 mole% BPA devices provided the best trade-off between device integrity and performance, other SMP systems that offer recovery stresses above 5 kPa without increasing brittleness to the point of causing device failure would be more suitable for this application. PMID:25414549

  6. Meta-Analysis of the Long-Term Effect of Routine Aspiration Thrombectomy in Patients Undergoing Primary Percutaneous Coronary Intervention.

    PubMed

    Mancini, Joseph G; Filion, Kristian B; Windle, Sarah B; Habib, Bettina; Eisenberg, Mark J

    2016-07-01

    American College of Cardiology Foundation/American Heart Association guidelines no longer recommend the use of routine aspiration thrombectomy during primary percutaneous coronary intervention (PCI). This is based on evidence from recent randomized controlled trials (RCTs) that suggests that the long-term benefits of aspiration thrombectomy were previously overestimated. We conducted a systematic review and meta-analysis of RCTs to examine the effect of routine aspiration thrombectomy during primary PCI versus primary PCI alone on markers of reperfusion immediately after PCI and on clinical outcomes at ≥6 months. We systematically searched Medline, EMBASE, and the Cochrane Library of Clinical trials for RCTs published in English or French with follow-up ≥6 months. Data were pooled using random-effects models. Eighteen publications (containing data from 14 RCTs, n = 20,285) met our inclusion criteria. Aspiration thrombectomy was associated with higher rates of ST-segment resolution (relative risk [RR] 1.22, 95% CI 1.07 to 1.40) and myocardial blush grade 3 (RR 1.30, 95% CI 1.01 to 1.67) and a reduced risk of no reflow immediately after PCI (RR 0.63, 95% CI 0.40 to 0.98). However, thrombectomy was not associated with our primary outcome of all-cause mortality at longest available follow-up (RR 0.92, 95% CI 0.81 to 1.04). Similar results were obtained for myocardial infarction and target vessel/lesion revascularization. Thrombectomy also increased the risk of stroke (RR 1.59, 95% CI 1.07 to 2.35). In conclusion, routine aspiration thrombectomy during primary PCI has some short-term clinical benefits but does not improve outcomes ≥6 months and increases the risk of stroke. PMID:27184168

  7. [Stent-assisted mechanical removal of tromboembolism after embolization of middle cerebral artery aneurysm].

    PubMed

    Poncyljusz, Wojciech; Falkowski, Aleksander; Rać, Monika; Sagan, Leszek; Kojder, Ireneusz

    2012-01-01

    Thrombotic occlusion of the middle cerebral artery's branch occurred just after embolization of a nonruptured cerebral aneurysm. Bail-out stent-assisted mechanical thrombectomy of the clot was performed. DSA revealed normal vessel patency at the end of the procedure. There were no adverse events related to this thrombectomy, and the patient recovered from the embolization with minor neurologic deficit. There was no neurologic deficit after 90 days follow-up. PMID:23276015

  8. [Sorption and mechanism of surfactants on bentonite in combined pollution].

    PubMed

    Sun, Xiao-Hui; Lu, Ying-Ying; Chen, Shu-Guang; Li, Ling-Jian; Shen, Xue-You

    2007-04-01

    Sorption of cationic surfactant cetyl pyridinium chloride (CPC), anionic surfactant sodium dodecylbenzene sulfonate (SDBS) and nonionic surfactant Triton X-100 (TX-100) on bentonite was studied. The influences of cation-exchange capacity (CEC), temperature and salinity on the sorption of CPC were also discussed. The results indicate that the sorption of CPC on Na-bentonite is greater than that of TX-100 and SDBS, and SDBS hardly shows any sorption. CPC is adsorbed to Na-bentonite through a combination of hydrophobic bonding and cation-exchange. While TX-100 is adsorbed to Na-bentonite via the formation of an adsorption layer of twain surfactant molecule and hydrogenolysis of silicon-oxygen surface of bentonite and TX-100. The amount of SDBS adsorbed on Ca-bentonite increases with increasing surfactant concentration, reaching a maximum at 1.5 critical micelle concentration (CMC), and then decreases with increasing surfactant loading. The mechanism of the retention appears to be formation of a sparingly soluble Ca-SDBS species, and dissolution in the micelle. The amount of CPC adsorbed on bentonite decreases with increasing temperature, and increases with increasing CEC. NaCl can enhance the sorption of CPC on bentonite. PMID:17639947

  9. Performance of a thrombectomy device for aspiration of thrombus with various sizes based on a computational fluid dynamic modeling.

    PubMed

    Soleimani, Sajjad; Dubini, Gabriele; Pennati, Giancarlo

    2016-06-01

    It is important to thoroughly remove the thrombus within the course of aspiration thrombectomy; otherwise, it may lead to further embolization. The performance of the aspiration thrombectomy device with a generic geometry is studied through the computational approach. In order to model the thrombus aspiration, a real left coronary artery is chosen while thrombi with various sizes are located at the bifurcation area of the coronary artery and, depending on the size of the thrombus, it is stretched toward the side branches. The thrombus occupies the artery resembling the blood current obstruction in the coronary vessel similar to the situation that leads to heart attack. It is concluded that the aspiration ability of the thrombectomy device is not linked to the thrombus size; it is rather linked to the aspiration pressure and thrombus age (organized versus fresh thrombus). However, the aspiration time period correlates to the thrombus size. The minimum applicable aspiration pressure is also investigated in this study. PMID:26351782

  10. Thrombectomy assisted by carotid stenting in acute ischemic stroke management: benefits and harms.

    PubMed

    Steglich-Arnholm, Henrik; Holtmannspötter, Markus; Kondziella, Daniel; Wagner, Aase; Stavngaard, Trine; Cronqvist, Mats E; Hansen, Klaus; Højgaard, Joan; Taudorf, Sarah; Krieger, Derk Wolfgang

    2015-12-01

    Extracranial carotid artery occlusion or high-grade stenosis with concomitant intracranial embolism causes severe ischemic stroke and shows poor response rates to intravenous thrombolysis (IVT). Endovascular therapy (EVT) utilizing thrombectomy assisted by carotid stenting was long considered risky because of procedural complexities and necessity of potent platelet inhibition-in particular following IVT. This study assesses the benefits and harms of thrombectomy assisted by carotid stenting and identifies factors associated with clinical outcome and procedural complications. Retrospective single-center analysis of 47 consecutive stroke patients with carotid occlusion or high-grade stenosis and concomitant intracranial embolus treated between September 2011 and December 2014. Benefits included early improvement of stroke severity (NIHSS ≥ 10) or complete remission within 72 h and favorable long-term outcome (mRS ≤ 2). Harms included complications during and following EVT. Mean age was 64.3 years (standard deviation ±12.5), 40 (85%) patients received IVT initially. Median NIHSS was 16 (inter-quartile range 14-19). Mean time from stroke onset to recanalization was 311 min (standard deviation ±78.0). Early clinical improvement was detected in 22 (46%) patients. Favorable outcome at 3 months occurred in 32 (68%) patients. Expedited patient management was associated with favorable clinical outcome. Two (4%) patients experienced symptomatic hemorrhage. Eight (17%) patients experienced stent thrombosis. Four (9%) patients died. Thrombectomy assisted by carotid stenting seems beneficial and reasonably safe with a promising rate of favorable outcome. Nevertheless, adverse events and complications call for additional clinical investigations prior to recommendation as clinical standard. Expeditious patient management is central to achieve good clinical outcome. PMID:26345413

  11. Chylous ascites after radical nephrectomy and inferior vena cava thrombectomy. Successful conservative management with somatostatin analogue.

    PubMed

    Leibovitch, Ilan; Mor, Yoram; Golomb, Jacob; Ramon, Jacob

    2002-02-01

    Postoperative chylous ascites is a rare complication of retroperitoneal surgery. The treatment of postoperative chylous ascites is primarily conservative, consisting of repeated paraceteses, medium chain triglyceride (MCT) diet, salt restriction, diuretics and bowel rest with total parenteral nutrition. Occasionally, chylous ascites may take a protracted course which may necessitate insertion of peritoneo-venous shunts or direct surgical lymphostasis. Recently, Somatostatin was shown to be highly effective in closure of refractory lymphatic fistulas. We present a case of refractory chylous ascites following radical nephrectomy with inferior vena caval thrombectomy that failed to respond to conventional conservative measures and resolved rapidly following the administration of Somatostatin. PMID:12074412

  12. Suction Thrombectomy of Thrombotic Occlusion of the Subclavian Artery in a Case of Takayasu's Arteritis

    SciTech Connect

    Purkayastha, Sukalyan; Jayadevan, E.R.; Kapilamoorthy, T.R.; Gupta, A.K. E-mail: gupta@sctimst.ac.in

    2006-04-15

    Takayasu's arteritis, also known as pulseless disease, is a chronic inflammatory arteritis affecting large vessels, predominantly the aorta and its main branches. Vessel inflammation leads to wall thickening, fibrosis, stenosis, and thrombus formation. Percutaneous removal of arterial thrombus with the use of several devices has been reported, with mixed results. We present a case of Takayasu's arteritis with thrombotic occlusion of the subclavian artery in which pulsed urokinase injection and suction thrombectomy were used to revascularize a threatened limb and to establish the sole arterial supply to the brain.

  13. Soluble collagen approach to a combination tannage mechanism

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Although complex salts of Cr(III) sulfate are currently the most effective tanning agents, salts of other metals, including aluminum, have been used either alone or in combination with vegetable tannins or other organic chemicals. In the present study, the interactions of aluminum sulfate, and quebr...

  14. Soluble collagen approach to a combination tannage mechanism

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Although complex salts of Cr(III) sulfate are currently the most effective tanning agents, salts of other metals, including aluminum, have been used either alone or in combination with vegetable tannins or other organic chemicals. In the present study, the interactions of metallic sulfates, and cond...

  15. Manual Aspiration Thrombectomy Using Penumbra Catheter in Patients with Acute M2 Occlusion : A Single-Center Analysis

    PubMed Central

    Park, Jung Soo

    2016-01-01

    Objective The efficacy and safety of manual aspiration thrombectomy using Penumbra in an acute occlusion of large intracranial arteries has been proven in many previous studies. Our study aimed to retrospectively assess the efficacy and safety of manual aspiration thrombectomy using Penumbra in patients with small vessel occlusions (M2 segment of the MCA). Methods We conducted a retrospective review of 32 patients who underwent manual aspiration thrombectomy using the Penumbra 4 MAX Reperfusion Catheter for treatment of an M2 occlusion between January 2013 and November 2014. We evaluated immediate angiographic results and clinical outcomes through review of patient electronic medical records. Results There were slightly more men in this study (M : F=18 : 14) and the median age was 72.5 (age range : 41–90). The rate of successful recanalization (TICI grade ≥2b) was 84% (27/32). NIHSS at discharge and favorable clinical outcomes at 3 months were significantly improved than baseline. Median initial NIHSS score was 10 (range : 4–25) and was 4 (range : 0–14) at discharge. Favorable clinical outcomes (mRS score ≤2 at 3 months) were seen in 25 out of 32 patients (78%). There were no procedure-related symptomatic intracerebral hemorrhages. One patient expired after discharge due to a cardiac problem. Conclusion Manual aspiration thrombectomy might be safe and is capable of achieving a high rate of successful recanalization and favorable clinical outcomes in patients with distal cerebral vessel occlusion (M2). PMID:27446515

  16. Connecting caddisworm silk structure and mechanical properties: combined infrared spectroscopy and mechanical analysis

    PubMed Central

    Ashton, Nicholas N.; Pan, Huaizhong; Stewart, Russell J.

    2016-01-01

    The underwater silk of an aquatic casemaking caddisfly larvae (Hesperophylax occidentalis) is viscoelastic, and displays distinct yield behaviour, large strain cycle hysteresis and near complete recovery of its initial strength and stiffness when unloaded. Yield followed by a stress plateau has been attributed to sequential rupture of serial Ca2+-cross-linked phosphoserine (pS) β-domains. Spontaneous recovery has been attributed to refolding of the Ca2+/pS domains powered by an elastic network. In this study, native Ca2+ ions were exchanged with other metal ions, followed by combined mechanical and FTIR analysis to probe the contribution of pS/metal ion complexes to silk mechanical properties. After exchange of Ca2+ with Na+, the fibres are soft elastomers and the infrared spectra are consistent with Cv3 symmetry of the – groups. Multivalent metal ions decreased the – symmetry and the symmetric stretching modes (vs) split in a manner characteristic of ordered phosphate compounds, such as phosphate minerals and lamellar bilayers of phosphatidic acid lipids. Integrated intensities of the vs bands, indicative of the metal ion's effect on transition dipole moment of the P–O bonds, and thereby the strength of the phosphate metal complex, increased in the order: Na+ < Mg2+ < Sr2+ < Ba2+ < Ca2+ < Eu3+ < La3+ < Zn2+ < Fe2+. With a subset of the metal ion series, the initial stiffness and yield stress of metal ion-exchanged fibres increased in the same order: establishing the link between phosphate transition dipole moments and silk fibre strength. PMID:27278649

  17. Connecting caddisworm silk structure and mechanical properties: combined infrared spectroscopy and mechanical analysis.

    PubMed

    Ashton, Nicholas N; Pan, Huaizhong; Stewart, Russell J

    2016-06-01

    The underwater silk of an aquatic casemaking caddisfly larvae (Hesperophylax occidentalis) is viscoelastic, and displays distinct yield behaviour, large strain cycle hysteresis and near complete recovery of its initial strength and stiffness when unloaded. Yield followed by a stress plateau has been attributed to sequential rupture of serial Ca(2+)-cross-linked phosphoserine (pS) β-domains. Spontaneous recovery has been attributed to refolding of the Ca(2+)/pS domains powered by an elastic network. In this study, native Ca(2+) ions were exchanged with other metal ions, followed by combined mechanical and FTIR analysis to probe the contribution of pS/metal ion complexes to silk mechanical properties. After exchange of Ca(2+) with Na(+), the fibres are soft elastomers and the infrared spectra are consistent with Cv3 symmetry of the -[Formula: see text] groups. Multivalent metal ions decreased the -[Formula: see text] symmetry and the symmetric stretching modes (vs) split in a manner characteristic of ordered phosphate compounds, such as phosphate minerals and lamellar bilayers of phosphatidic acid lipids. Integrated intensities of the vs bands, indicative of the metal ion's effect on transition dipole moment of the P-O bonds, and thereby the strength of the phosphate metal complex, increased in the order: Na(+) < Mg(2+) < Sr(2+) < Ba(2+) < Ca(2+) < Eu(3+) < La(3+) < Zn(2+) < Fe(2+) With a subset of the metal ion series, the initial stiffness and yield stress of metal ion-exchanged fibres increased in the same order: [Formula: see text] [Formula: see text] establishing the link between phosphate transition dipole moments and silk fibre strength. PMID:27278649

  18. Treatment protocol based on assessment of clot quality during endovascular thrombectomy for acute ischemic stroke using the Trevo stent retriever

    PubMed Central

    Ishikawa, Kojiro; Ohshima, Tomotaka; Nishihori, Masahiro; Imai, Tasuku; Goto, Shunsaku; Yamamoto, Taiki; Nishizawa, Toshihisa; Shimato, Shinji; Kato, Kyozo

    2016-01-01

    ABSTRACT The optional endovascular approach for acute ischemic stroke is unclear. The Trevo stent retriever can be used as first-line treatment for fast mechanical recanalization. The authors developed a treatment protocol for acute ischemic stroke based on the assessment of clot quality during clot removal with the Trevo. This prospective single-center study included all patients admitted for acute ischemic stroke between July 2014 and February 2015, who underwent emergency endovascular treatment. According to the protocol, the Trevo was used for first-line treatment. Immediately after the Trevo was deployed, the stent delivery wire was pushed to open the stent by force (ACAPT technique). Clot quality was assessed on the basis of the perfusion status after deployment of the Trevo; continued occlusion or immediate reopening either reoccluded or maintained after the stent retriever had been in place for 5 min. If there was no obvious clot removal after the first pass with the Trevo, according to the quality of the clot, either a second pass was performed or another endovascular device was selected. Twelve consecutive patients with acute major cerebral artery occlusion were analyzed. Thrombolysis in cerebral infarction score 2b and 3 was achieved in 11 patients (91.7%) and 9 (75%) had a good clinical outcome after 90 days based on a modified Rankin scale score ≤ 2. Symptomatic intracranial hemorrhage occurred in 1 patient (8.3%). The overall mortality rate was 8.3%. Endovascular thrombectomy using the Trevo stent retriever for first-line treatment is feasible and effective. PMID:27578909

  19. Treatment protocol based on assessment of clot quality during endovascular thrombectomy for acute ischemic stroke using the Trevo stent retriever.

    PubMed

    Ishikawa, Kojiro; Ohshima, Tomotaka; Nishihori, Masahiro; Imai, Tasuku; Goto, Shunsaku; Yamamoto, Taiki; Nishizawa, Toshihisa; Shimato, Shinji; Kato, Kyozo

    2016-08-01

    The optional endovascular approach for acute ischemic stroke is unclear. The Trevo stent retriever can be used as first-line treatment for fast mechanical recanalization. The authors developed a treatment protocol for acute ischemic stroke based on the assessment of clot quality during clot removal with the Trevo. This prospective single-center study included all patients admitted for acute ischemic stroke between July 2014 and February 2015, who underwent emergency endovascular treatment. According to the protocol, the Trevo was used for first-line treatment. Immediately after the Trevo was deployed, the stent delivery wire was pushed to open the stent by force (ACAPT technique). Clot quality was assessed on the basis of the perfusion status after deployment of the Trevo; continued occlusion or immediate reopening either reoccluded or maintained after the stent retriever had been in place for 5 min. If there was no obvious clot removal after the first pass with the Trevo, according to the quality of the clot, either a second pass was performed or another endovascular device was selected. Twelve consecutive patients with acute major cerebral artery occlusion were analyzed. Thrombolysis in cerebral infarction score 2b and 3 was achieved in 11 patients (91.7%) and 9 (75%) had a good clinical outcome after 90 days based on a modified Rankin scale score ≤ 2. Symptomatic intracranial hemorrhage occurred in 1 patient (8.3%). The overall mortality rate was 8.3%. Endovascular thrombectomy using the Trevo stent retriever for first-line treatment is feasible and effective. PMID:27578909

  20. Combined holographic-mechanical optical tweezers: construction, optimization, and calibration.

    PubMed

    Hanes, Richard D L; Jenkins, Matthew C; Egelhaaf, Stefan U

    2009-08-01

    A spatial light modulator (SLM) and a pair of galvanometer-mounted mirrors (GMM) were combined into an optical tweezers setup. This provides great flexibility as the SLM creates an array of traps, which can be moved smoothly and quickly with the GMM. To optimize performance, the effect of the incidence angle on the SLM with respect to phase and intensity response was investigated. Although it is common to use the SLM at an incidence angle of 45 degrees, smaller angles give a full 2pi phase shift and an output intensity which is less dependent on the magnitude of the phase shift. The traps were calibrated using an active oscillatory technique and a passive probability distribution method. PMID:19725658

  1. Combined holographic-mechanical optical tweezers: Construction, optimization, and calibration

    SciTech Connect

    Hanes, Richard D. L.; Jenkins, Matthew C.; Egelhaaf, Stefan U.

    2009-08-15

    A spatial light modulator (SLM) and a pair of galvanometer-mounted mirrors (GMM) were combined into an optical tweezers setup. This provides great flexibility as the SLM creates an array of traps, which can be moved smoothly and quickly with the GMM. To optimize performance, the effect of the incidence angle on the SLM with respect to phase and intensity response was investigated. Although it is common to use the SLM at an incidence angle of 45 deg., smaller angles give a full 2{pi} phase shift and an output intensity which is less dependent on the magnitude of the phase shift. The traps were calibrated using an active oscillatory technique and a passive probability distribution method.

  2. Combining two proven mechanical tenderness measurements in one steak.

    PubMed

    Callahan, Z D; Belk, K E; Miller, R K; Morgan, J B; Lorenzen, C L

    2013-09-01

    This research was performed to determine the true efficacy of measuring both Warner-Bratzler shear force (WBSF) and slice shear force (SSF) in the same steak. The objectives were to compare cooking methods commonly used in preparing steaks for WBSF and SSF procedures and compare them at different cooling times. United States Department of Agriculture select strip loins (n = 240) were aged for either 7 or 14 d to increase the variation in tenderness. Each strip loin was then frozen and cut into 2.54-cm steaks. Steaks were then cooked to an internal temperature of 71°C using a convection conveyor oven (conveyor), a convection oven, clamshell grill, or an open hearth grill. Steaks were allotted to 4 different cooling times to create the combinations of: WBSF 4 h/SSF 0 h, WBSF 4 h/SSF 4 h, WBSF 24 h/SSF 0 h, WBSF 24 h/SSF 24 h. Five 1.25-cm cores were used for WBSF and one 1- by 5-cm slice for SSF. The WBSF from steaks cooked with conveyor were tougher than convection oven cooked steaks [51.9 Newtons (N) vs. 46.1 N; P < 0.05]. However, SSF were tougher when cooked in oven compared with those cooked in conveyor (267.5 N vs. 237.2 N; P < 0.05). Correlations for WBSF and SSF performed in the same steak ranged from 0.51 to 0.88 (P < 0.0001). The WBSF 24 h/SSF 0 h and WBSF 4 h/SSF 4 h had the strongest relationships (0.88 and 0.82, respectively; P < 0.05) between WBSF and SSF when using clamshell method. Performing WBSF and SSF in the same steak was successful based on moderate to high correlation values but the magnitude of the relationship is dependent on the combination of cooking method and cooling time. PMID:23825326

  3. Discovery, mechanisms of action and combination therapy of artemisinin.

    PubMed

    Cui, Liwang; Su, Xin-zhuan

    2009-10-01

    Despite great international efforts, malaria still inflicts an enormous toll on human lives, especially in Africa. Throughout history, antimalarial medicines have been one of the most powerful tools in malaria control. However, the acquisition and spread of parasite strains that are resistant to multiple antimalarial drugs have become one of the greatest challenges to malaria treatment, and are associated with the increase in morbidity and mortality in many malaria-endemic countries. To deal with this grave situation, artemisinin-based combinatory therapies (ACTs) have been introduced and widely deployed in malarious regions. Artemisinin is a new class of antimalarial compounds discovered by Chinese scientists from the sweet wormwood Artemisia annua. The potential development of resistance to artemisinins by Plasmodium falciparum threatens the usable lifespan of ACTs, and therefore is a subject of close surveillance and extensive research. Studies at the Thai-Cambodian border, a historical epicenter of multidrug resistance, have detected reduced susceptibility to artemisinins as manifested by prolonged parasite-clearance times, raising considerable concerns on resistance development. Despite this significance, there is still controversy on the mode of action of artemisinins. Although a number of potential cellular targets of artemisinins have been proposed, they remain to be verified experimentally. Here, we review the history of artemisinin discovery, discuss the mode of action and potential drug targets, and present strategies to elucidate resistance mechanisms. PMID:19803708

  4. Discovery, mechanisms of action and combination therapy of artemisinin

    PubMed Central

    Cui, Liwang; Su, Xin-zhuan

    2009-01-01

    Despite great international efforts, malaria still inflicts an enormous toll on human lives, especially in Africa. Throughout history, antimalarial medicines have been one of the most powerful tools in malaria control. However, the acquisition and spread of parasite strains that are resistant to multiple antimalarial drugs have become one of the greatest challenges to malaria treatment, and are associated with the increase in morbidity and mortality in many malaria-endemic countries. To deal with this grave situation, artemisinin-based combinatory therapies (ACTs) have been introduced and widely deployed in malarious regions. Artemisinin is a new class of antimalarial compounds discovered by Chinese scientists from the sweet wormwood Artemisia annua. The potential development of resistance to artemisinins by Plasmodium falciparum threatens the usable lifespan of ACTs, and therefore is a subject of close surveillance and extensive research. Studies at the Thai–Cambodian border, a historical epicenter of multidrug resistance, have detected reduced susceptibility to artemisinins as manifested by prolonged parasite-clearance times, raising considerable concerns on resistance development. Despite this significance, there is still controversy on the mode of action of artemisinins. Although a number of potential cellular targets of artemisinins have been proposed, they remain to be verified experimentally. Here, we review the history of artemisinin discovery, discuss the mode of action and potential drug targets, and present strategies to elucidate resistance mechanisms. PMID:19803708

  5. Treating electrostatics with Wolf summation in combined quantum mechanical and molecular mechanical simulations

    SciTech Connect

    Ojeda-May, Pedro; Pu, Jingzhi

    2015-11-07

    The Wolf summation approach [D. Wolf et al., J. Chem. Phys. 110, 8254 (1999)], in the damped shifted force (DSF) formalism [C. J. Fennell and J. D. Gezelter, J. Chem. Phys. 124, 234104 (2006)], is extended for treating electrostatics in combined quantum mechanical and molecular mechanical (QM/MM) molecular dynamics simulations. In this development, we split the QM/MM electrostatic potential energy function into the conventional Coulomb r{sup −1} term and a term that contains the DSF contribution. The former is handled by the standard machinery of cutoff-based QM/MM simulations whereas the latter is incorporated into the QM/MM interaction Hamiltonian as a Fock matrix correction. We tested the resulting QM/MM-DSF method for two solution-phase reactions, i.e., the association of ammonium and chloride ions and a symmetric SN{sub 2} reaction in which a methyl group is exchanged between two chloride ions. The performance of the QM/MM-DSF method was assessed by comparing the potential of mean force (PMF) profiles with those from the QM/MM-Ewald and QM/MM-isotropic periodic sum (IPS) methods, both of which include long-range electrostatics explicitly. For ion association, the QM/MM-DSF method successfully eliminates the artificial free energy drift observed in the QM/MM-Cutoff simulations, in a remarkable agreement with the two long-range-containing methods. For the SN{sub 2} reaction, the free energy of activation obtained by the QM/MM-DSF method agrees well with both the QM/MM-Ewald and QM/MM-IPS results. The latter, however, requires a greater cutoff distance than QM/MM-DSF for a proper convergence of the PMF. Avoiding time-consuming lattice summation, the QM/MM-DSF method yields a 55% reduction in computational cost compared with the QM/MM-Ewald method. These results suggest that, in addition to QM/MM-IPS, the QM/MM-DSF method may serve as another efficient and accurate alternative to QM/MM-Ewald for treating electrostatics in condensed-phase simulations of chemical

  6. Treating electrostatics with Wolf summation in combined quantum mechanical and molecular mechanical simulations

    NASA Astrophysics Data System (ADS)

    Ojeda-May, Pedro; Pu, Jingzhi

    2015-11-01

    The Wolf summation approach [D. Wolf et al., J. Chem. Phys. 110, 8254 (1999)], in the damped shifted force (DSF) formalism [C. J. Fennell and J. D. Gezelter, J. Chem. Phys. 124, 234104 (2006)], is extended for treating electrostatics in combined quantum mechanical and molecular mechanical (QM/MM) molecular dynamics simulations. In this development, we split the QM/MM electrostatic potential energy function into the conventional Coulomb r-1 term and a term that contains the DSF contribution. The former is handled by the standard machinery of cutoff-based QM/MM simulations whereas the latter is incorporated into the QM/MM interaction Hamiltonian as a Fock matrix correction. We tested the resulting QM/MM-DSF method for two solution-phase reactions, i.e., the association of ammonium and chloride ions and a symmetric SN2 reaction in which a methyl group is exchanged between two chloride ions. The performance of the QM/MM-DSF method was assessed by comparing the potential of mean force (PMF) profiles with those from the QM/MM-Ewald and QM/MM-isotropic periodic sum (IPS) methods, both of which include long-range electrostatics explicitly. For ion association, the QM/MM-DSF method successfully eliminates the artificial free energy drift observed in the QM/MM-Cutoff simulations, in a remarkable agreement with the two long-range-containing methods. For the SN2 reaction, the free energy of activation obtained by the QM/MM-DSF method agrees well with both the QM/MM-Ewald and QM/MM-IPS results. The latter, however, requires a greater cutoff distance than QM/MM-DSF for a proper convergence of the PMF. Avoiding time-consuming lattice summation, the QM/MM-DSF method yields a 55% reduction in computational cost compared with the QM/MM-Ewald method. These results suggest that, in addition to QM/MM-IPS, the QM/MM-DSF method may serve as another efficient and accurate alternative to QM/MM-Ewald for treating electrostatics in condensed-phase simulations of chemical reactions.

  7. Thrombosis in ST-elevation myocardial infarction: Insights from thrombi retrieved by aspiration thrombectomy

    PubMed Central

    Ribeiro, Daniel Rios P; Cambruzzi, Eduardo; Schmidt, Marcia Moura; Quadros, Alexandre S

    2016-01-01

    In patients with ST-elevation myocardial infarction, recurrent cardiovascular events still remain the main cause of morbidity and mortality, despite significant improvements in antithrombotic therapy. We sought to review data regarding coronary thrombus analysis provided by studies using manual aspiration thrombectomy (AT), and to discuss how insights from this line of investigation could further improve management of acute coronary disease. Several studies investigated the fresh specimens retrieved by AT using techniques such as traditional morphological evaluation, optical microscopy, scanning electron microscopy, magnetic resonance imaging, and immunohistochemistry. These approaches have provided a better understanding of the composition and dynamics of the human coronary thrombosis process, as well as its relationship with some clinical outcomes. Recent data signaling to new antithrombotic therapeutic targets are still emerging. PMID:27354893

  8. [Open thrombectomy in treatment of acute thromboses of lower-limb deep veins].

    PubMed

    Shaĭdakov, E V; Porembskaia, O Ia; Tsarev, O I; Khmel'niker, S M

    2014-01-01

    Thrombosis of lower-limb deep veins is one of the most common vascular diseases in the world. For a long time the generally accepted treatment policy was conservative therapy with anticoagulants. The article is a review of the literature containing the results of studies carried out over the past two decades and confirming efficacy of surgical treatment for acute venous thrombosis. Presented are the data showing that thrombectomy performed within the first 10-14 days from the onset of the disease, improving quality of life of patients and preventing invalidization thereof. The gained world experience makes it possible to work out the most effective approaches to treatment of acute venous thromboses. PMID:25646547

  9. Radiologic indicators prior to renal cell cancer thrombectomy: Implications for vascular reconstruction and mortality

    PubMed Central

    Overholser, Stephen; Raheem, Omer; Zapata, David; Kaushik, Dharam; Rodriguez, Ronald; Derweesh, Ithaar H.; Liss, Michael A.

    2016-01-01

    Background: Renal cancer may invade the inferior vena cava (IVC) creating more complex surgical intervention. We investigate radiologic findings that may predict vascular reconstruction prior to surgery and future renal cancer-specific mortality. Materials and Methods: Radiologic findings included Mayo Clinic risk factors for vascular reconstruction: Right-sided tumor, anteroposterior diameter of the IVC at the ostium of the renal vein ≥24.0 mm, and radiologic identification of complete occlusion of the IVC. Additional factors included thrombus in the lumen of the hepatic veins and metastasis. Along with other demographic factors, analysis included Chi-squared analysis for vascular reconstruction and logistic regression for mortality. A Kaplan–Meier curve was created for the most significant radiologic factor. Results: Thirty-seven patients underwent IVC tumor thrombectomy at two institutions from April 2007 to February 2015. We found that Mayo risk factors of 0, 1, 2, and 3 and the proportions of vascular reconstruction of 0%, 0%, 12.5%, and 13.6%, respectively (P = 0.788). Hepatic vein involvement was the most significant determinate of renal cell carcinoma-specific mortality in multivariable analysis, controlling for the size of IVC at the hepatic veins, pulmonary metastasis, and Fuhrman grade (P = 0.02, Log-rank P = 0.002). Conclusion: Mayo risk factors did not predict vascular reconstruction in our small cohort of Level II–Level IV IVC thrombus undergoing IVC thrombectomy. Tumor thrombus traveling into the lumen of the hepatic veins was a significant risk factor for accelerated mortality. PMID:27453653

  10. Laparoscopic radical nephrectomy with inferior vena cava thrombectomy: highlight of key surgical steps

    PubMed Central

    Sim, A.; Todenhöfer, T.; Mischinger, J.; Fahmy, O.; Boettge, J.; Rausch, S.; Bier, S.; Aufderklamm, S.; Stenzl, A.; Gakis, G.; Schwentner, C.

    2016-01-01

    ABSTRACT Objective: Vascular involvement in the form of renal vein (RV) or inferior vena cava (IVC) thrombus can be seen in 4-10% of patients presented with RCC. In patients without presence of metastasis, surgical treatment in the form of radical nephrectomy remains the treatment of choice with 5-year survival rates of 45-70%. Open surgery is still the first treatment option of choice at the moment for RCC patients with IVC thrombus. Materials and Methods: In our study, we are reporting a case of patient with RCC and level I IVC thrombus treated with laparoscopy. Our patient is a 72 years old man with underlying co-morbidity of hypertension and chronic kidney disease (CKD) presented with right-sided RCC. The CT scan done showed a large right renal upper pole tumor measuring 8.4x5.2cm with level I IVC thrombus (Figure-1). There were no regional lymphadenopathy and the staging scans were negative. Results: The operative time was 124 minutes and blood loss was minimal. The patient was progressed to diet on POD 1 with bowel movement on POD 2. There was no significant change in the pre and post-operative glomerular filtration rate (GFR). The surgical drain was removed on POD2. The patient was discharged well on POD 5. There were no perioperative complications. The pathology was pT3bN0M0 Fuhrman grade II clear cell RCC. Conclusions: As a conclusion, laparoscopic radical nephrectomy and IVC thrombectomy is a complex and technically demanding surgery. With advancement of surgical skills as well as technology, more cases of minimally invasive laparoscopic radical nephrectomy and IVC thrombectomy can performed to improve the perioperative outcomes of carefully selected patients in a high volume center. PMID:27564306

  11. [Advances in cooperativity and mechanism of combination of Back-shu and Front-mu points].

    PubMed

    Wang, Hao; Shen, Guo-Ming

    2011-09-01

    The articles related with combination of Back-shu and Front-mu points searched in CNKI and Pubmed databases during the past 10 years were studied. The conclusions indicate that the application of combination of Back-shu and Front-mu points has solid theoretical basis and experimental evidence, and it is proved that the combination of Back-shu points and Front-mu points is effective in clinic practice. However, the mechanism study still rest on the level of spinal cord, and the breakthrough of combination of Back-Shu and Front-Mu points study is that whether the superior nerve centre involves on the regulation of zang-fu organs by combination of Back-shu and Front-mu points. The key point in future study is to explore the central control mechanism of combination of Back-shu and Front-mu points. PMID:21972656

  12. 40 CFR 280.94 - Allowable mechanisms and combinations of mechanisms.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... OPERATORS OF UNDERGROUND STORAGE TANKS (UST) Financial Responsibility § 280.94 Allowable mechanisms and... one or more underground storage tanks, and (2) A local government owner or operator may use any one or... under this subpart for one or more underground storage tanks. (b) An owner or operator may use...

  13. 40 CFR 280.94 - Allowable mechanisms and combinations of mechanisms.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... OPERATORS OF UNDERGROUND STORAGE TANKS (UST) Financial Responsibility § 280.94 Allowable mechanisms and... one or more underground storage tanks, and (2) A local government owner or operator may use any one or... under this subpart for one or more underground storage tanks. (b) An owner or operator may use...

  14. 40 CFR 280.94 - Allowable mechanisms and combinations of mechanisms.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... OPERATORS OF UNDERGROUND STORAGE TANKS (UST) Financial Responsibility § 280.94 Allowable mechanisms and... one or more underground storage tanks, and (2) A local government owner or operator may use any one or... under this subpart for one or more underground storage tanks. (b) An owner or operator may use...

  15. 40 CFR 280.94 - Allowable mechanisms and combinations of mechanisms.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... OPERATORS OF UNDERGROUND STORAGE TANKS (UST) Financial Responsibility § 280.94 Allowable mechanisms and... one or more underground storage tanks, and (2) A local government owner or operator may use any one or... under this subpart for one or more underground storage tanks. (b) An owner or operator may use...

  16. 40 CFR 280.94 - Allowable mechanisms and combinations of mechanisms.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... OPERATORS OF UNDERGROUND STORAGE TANKS (UST) Financial Responsibility § 280.94 Allowable mechanisms and... one or more underground storage tanks, and (2) A local government owner or operator may use any one or... under this subpart for one or more underground storage tanks. (b) An owner or operator may use...

  17. Excited States and Photochemistry of Chromophores in the Photoactive Proteins Explored by the Combined Quantum Mechanical and Molecular Mechanical Calculations.

    PubMed

    Liu, Lihong; Cui, Ganglong; Fang, Wei-Hai

    2015-01-01

    A photoactive protein usually contains a unique chromophore that is responsible for the initial photoresponse and functions of the photoactive protein are determined by the interaction between the chromophore and its protein surroundings. The combined quantum mechanical and molecular mechanical (QM/MM) approach is demonstrated to be a very useful tool for exploring structures and functions of a photoactive protein with the chromophore and its protein surroundings treated by the QM and MM methods, respectively. In this review, we summarize the basic formulas of the QM/MM approach and emphasize its applications to excited states and photoreactions of chromophores in rhodopsin protein, photoactive yellow protein, and green fluorescent protein. PMID:26415847

  18. Percutaneous Aspiration Thrombectomy for the Treatment of Arterial Thromboembolic Occlusions Following Percutaneous Transluminal Angioplasty

    SciTech Connect

    Schleder, Stephan; Diekmann, Matthias; Manke, Christoph; Heiss, Peter

    2015-02-15

    PurposeThis study was designed to evaluate the technical success and the early clinical outcome of patients undergoing percutaneous aspiration thrombectomy (PAT) for the treatment of arterial thromboembolism following percutaneous infrainguinal transluminal angioplasty (PTA).MethodsIn this single-center study, during a period of 7 years retrospectively, 47 patients (22 male, 47 %) with a mean age of 73 (range 53–96) years were identified in whom PAT was performed for the treatment of thromboembolic complications of infrainguinal PTA. Primary technical success was defined as residual stenosis of <50 % in diameter after sole PAT, whereas secondary technical success was defined as residual stenosis of <50 % in diameter after PAT and additional PTA and/or stenting. Clinical outcome parameters (e.g., need for further intervention, minor/major amputation) were evaluated for the 30-day postinterventional period.ResultsPrimary technical success was achieved in 64 % of patients (30/47); secondary technical success was obtained in 96 % of patients (45/47). Clinical outcome data were available in 38 patients. In 87 % of patients (33/38), there was no need for further intervention within the 30-day postinterventional period. In three patients, minor amputations were conducted due to preexisting ulcerations (Rutherford Category 5 respectively).ConclusionsPAT enables endovascular treatment of iatrogenic thromboembolic complications after PTA with good technical and early clinical results and minimal morbidity.

  19. In Vitro Evaluation of a New Rotational Thrombectomy Device: The Straub Rotarex Catheter

    SciTech Connect

    Zana, Katalin; Otal, Philippe; Fornet, Bela; Forrai, Gabor; Chabbert, Valerie; Smayra, Tarek; Joffre, Francis; Rousseau, Herve

    2001-09-15

    Purpose: To evaluate the efficacy of a new rotational thrombectomy device, and the procedure-related risk of particle embolization.Methods: The experiments were performed in transparent silicone tubes. The conditions of flow were as close as possible to physiological parameters. Distal embolization was detected by a mesh of nylon filters.Results: The Straub Rotarex catheter was able to remove all clots. The mean number of migrating particles larger than 1000 {mu}m was 0.17 ({+-}0.38), the mean number of 400-1000 {mu}m migrating particles was 1.08 ({+-}1.04). The mean intervention time was 67 ({+-}37) sec. The mean volume of collected liquid was 96.6 ({+-}24.7) ml.Conclusion: The in vitro results suggest that the Straub Rotarex catheter is able to remove large volumes of thrombus with a limited risk of embolization. The main limitation of our model is the absence of adhesion of the clot to the tube.

  20. Adverse effects on PMMA caused by mechanical and combined methods of denture cleansing.

    PubMed

    Sorgini, Danilo Balero; da Silva-Lovato, Cláudia Helena; Muglia, Valdir Antônio; de Souza, Raphael Freitas; de Arruda, Carolina Noronha Ferraz; Paranhos, Helena de Freitas Oliveira

    2015-01-01

    This study evaluated the abrasiveness of mechanical and combined methods of denture hygiene, by the analysis of mass loss and surface roughness. Acrylic resin specimens (Plexiglass) were brushed by a tooth brushing machine (Mavtec) with a soft brush (Tek) and water (control) or four dentifrices (Sorriso, Colgate, Polident and Corega) (Experimental groups) for 50 min, representing one year of brushing (mechanical method). After brushing, the specimens were immersed in 0.5% sodium hypochlorite simulating a daily cleaning of 20 min for one year (combined method). Distilled water (23 ºC) was employed as control. The mass loss (g) was analyzed by an analytical balance and the surface roughness (μm) by a rugosimeter. Data were subjected to ANOVA and Bonferroni test (α=0.05). Polident dentifrice showed lowest values of mass loss for both methods (mechanical: -0.0072±0.0017, combined:-0.011±0.002) and the combined method resulted in greater mass loss than the mechanical, except for Corega. For the surface roughness, after the mechanical method, the lowest values were registered for water (-0.007±0.016) and Polident (0.402±0.378); for the combined method, water (-0.063±0.013) showed the lowest values; there was no statistically significant difference between methods. It was concluded that Polident was the less abrasive dentifrice and the association between chemical and mechanical methods increased the mass loss but did not change the surface roughness of specimens. PMID:26200156

  1. Clinical experience with Angiojet: a comprehensive review.

    PubMed

    Ierardi, A M; Xhepa, G; Piffaretti, G; Bacuzzi, A; Tozzi, M; Carbone, M; Barile, A; Squillaci, E; Fonio, P; Brunese, L; Carrafiello, G

    2015-12-01

    The development of various sophisticated mechanical thrombectomy devices and the amassed experience of physicians in minimal invasive therapy produced a paradigm shift in vascular access management toward percutaneous declotting procedures, using pharmaceutical thrombolysis, mechanical thrombectomy, balloon thrombectomy, and a combination of the above techniques. In this setting, in the last years, AngioJet™ (Possis, Minneapolis, MN, USA) rheolytic thrombectomy (RT) showed an increasing use in emergency and election patients. The purpose of this review is to present the current status of percutaneous rheolytic thrombectomy in different fields of applications. PMID:26498886

  2. Clinical study on VATS combined mechanical ventilation treatment of ARDS secondary to severe chest trauma

    PubMed Central

    Qi, Yongjun

    2016-01-01

    The aim of the study was to investigate the clinical effects of microinvasive video-assisted thoracoscopic surgery (VATS) combined with mechanical ventilation in the treatment of acute respiratory distress syndrome (ARDS) secondary to severe chest trauma. A total of 62 patients with ARDS secondary to severe chest trauma were divided into the observation and control groups. The patients in the observation groups were treated with VATS combined with early mechanical ventilation while patients in the control group were treated using routine open thoracotomy combined with early mechanical ventilation. Compared to the controls, the survival rate of the observation group was significantly higher. The average operation time of the observation group was significantly shorter than that of the control group, and the incidence of complications in the perioperative period of the observation group was significantly lower than that of the control group (p<0.05). The average application time of the observation group was significantly shorter than that of the control group, and the incidence of ventilator-associated complications was significantly lower than that of the control group (p<0.05). In conclusion, a reasonable understanding of the indications and contraindications of VATS, combined with early mechanical treatment significantly improved the success rate of the treatment of ARDS patients secondary to severe chest trauma and reduced the complications. PMID:27446317

  3. Combining quantum mechanical ligand conformation analysis and protein modeling to elucidate GPCR-ligand binding modes.

    PubMed

    Schultes, Sabine; Engelhardt, Harald; Roumen, Luc; Zuiderveld, Obbe P; Haaksma, Eric E J; de Esch, Iwan J P; Leurs, Rob; de Graaf, Chris

    2013-01-01

    SAR beyond protein-ligand interactions: By combining structure-affinity relationships, protein-ligand modeling studies, and quantum mechanical calculations, we show that ligand conformational energies and basicity play critical roles in ligand binding to the histamine H4 receptor, a GPCR that plays a key role in inflammation. PMID:23161844

  4. A procedure for combining acoustically induced and mechanically induced loads (first passage failure design criterion)

    NASA Technical Reports Server (NTRS)

    Crowe, D. R.; Henricks, W.

    1983-01-01

    The combined load statistics are developed by taking the acoustically induced load to be a random population, assumed to be stationary. Each element of this ensemble of acoustically induced loads is assumed to have the same power spectral density (PSD), obtained previously from a random response analysis employing the given acoustic field in the STS cargo bay as a stationary random excitation. The mechanically induced load is treated as either (1) a known deterministic transient, or (2) a nonstationary random variable of known first and second statistical moments which vary with time. A method is then shown for determining the probability that the combined load would, at any time, have a value equal to or less than a certain level. Having obtained a statistical representation of how the acoustic and mechanical loads are expected to combine, an analytical approximation for defining design levels for these loads is presented using the First Passage failure criterion.

  5. Mechanism-independent method for predicting response to multidrug combinations in bacteria

    PubMed Central

    Wood, Kevin; Nishida, Satoshi; Sontag, Eduardo D.; Cluzel, Philippe

    2012-01-01

    Drugs are commonly used in combinations larger than two for treating bacterial infection. However, it is generally impossible to infer directly from the effects of individual drugs the net effect of a multidrug combination. Here we develop a mechanism-independent method for predicting the microbial growth response to combinations of more than two drugs. Performing experiments in both Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria, we demonstrate that for a wide range of drugs, the bacterial responses to drug pairs are sufficient to infer the effects of larger drug combinations. To experimentally establish the broad applicability of the method, we use drug combinations comprising protein synthesis inhibitors (macrolides, aminoglycosides, tetracyclines, lincosamides, and chloramphenicol), DNA synthesis inhibitors (fluoroquinolones and quinolones), folic acid synthesis inhibitors (sulfonamides and diaminopyrimidines), cell wall synthesis inhibitors, polypeptide antibiotics, preservatives, and analgesics. Moreover, we show that the microbial responses to these drug combinations can be predicted using a simple formula that should be widely applicable in pharmacology. These findings offer a powerful, readily accessible method for the rational design of candidate therapies using combinations of more than two drugs. In addition, the accurate predictions of this framework raise the question of whether the multidrug response in bacteria obeys statistical, rather than chemical, laws for combinations larger than two. PMID:22773816

  6. Combined (mechanical and pharmacological) modalities for the prevention of venous thromboembolism in joint replacement surgery.

    PubMed

    Kakkos, S K; Warwick, D; Nicolaides, A N; Stansby, G P; Tsolakis, I A

    2012-06-01

    We performed a systematic review and meta-analysis to compare the efficacy of intermittent mechanical compression combined with pharmacological thromboprophylaxis, against either mechanical compression or pharmacological prophylaxis in preventing deep-vein thrombosis (DVT) and pulmonary embolism in patients undergoing hip or knee replacement. A total of six randomised controlled trials, evaluating a total of 1399 patients, were identified. In knee arthroplasty, the rate of DVT was reduced from 18.7% with anticoagulation alone to 3.7% with combined modalities (risk ratio (RR) 0.27, p = 0.03; number needed to treat: seven). There was moderate, albeit non-significant, heterogeneity (I(2) = 42%). In hip replacement, there was a non-significant reduction in DVT from 8.7% with mechanical compression alone to 7.2% with additional pharmacological prophylaxis (RR 0.84) and a significant reduction in DVT from 9.7% with anticoagulation alone to 0.9% with additional mechanical compression (RR 0.17, p < 0.001; number needed to treat: 12), with no heterogeneity (I(2) = 0%). The included studies had insufficient power to demonstrate an effect on pulmonary embolism. We conclude that the addition of intermittent mechanical leg compression augments the efficacy of anticoagulation in preventing DVT in patients undergoing both knee and hip replacement. Further research on the role of combined modalities in thromboprophylaxis in joint replacement and in other high-risk situations, such as fracture of the hip, is warranted. PMID:22628585

  7. Combination of Universal Mechanical Testing Machine with Atomic Force Microscope for Materials Research.

    PubMed

    Zhong, Jian; He, Dannong

    2015-01-01

    Surface deformation and fracture processes of materials under external force are important for understanding and developing materials. Here, a combined horizontal universal mechanical testing machine (HUMTM)-atomic force microscope (AFM) system is developed by modifying UMTM to combine with AFM and designing a height-adjustable stabilizing apparatus. Then the combined HUMTM-AFM system is evaluated. Finally, as initial demonstrations, it is applied to analyze the relationship among macroscopic mechanical properties, surface nanomorphological changes under external force, and fracture processes of two kinds of representative large scale thin film materials: polymer material with high strain rate (Parafilm) and metal material with low strain rate (aluminum foil). All the results demonstrate the combined HUMTM-AFM system overcomes several disadvantages of current AFM-combined tensile/compression devices including small load force, incapability for large scale specimens, disability for materials with high strain rate, and etc. Therefore, the combined HUMTM-AFM system is a promising tool for materials research in the future. PMID:26265357

  8. Combination of Universal Mechanical Testing Machine with Atomic Force Microscope for Materials Research

    PubMed Central

    Zhong, Jian; He, Dannong

    2015-01-01

    Surface deformation and fracture processes of materials under external force are important for understanding and developing materials. Here, a combined horizontal universal mechanical testing machine (HUMTM)-atomic force microscope (AFM) system is developed by modifying UMTM to combine with AFM and designing a height-adjustable stabilizing apparatus. Then the combined HUMTM-AFM system is evaluated. Finally, as initial demonstrations, it is applied to analyze the relationship among macroscopic mechanical properties, surface nanomorphological changes under external force, and fracture processes of two kinds of representative large scale thin film materials: polymer material with high strain rate (Parafilm) and metal material with low strain rate (aluminum foil). All the results demonstrate the combined HUMTM-AFM system overcomes several disadvantages of current AFM-combined tensile/compression devices including small load force, incapability for large scale specimens, disability for materials with high strain rate, and etc. Therefore, the combined HUMTM-AFM system is a promising tool for materials research in the future. PMID:26265357

  9. Combination of Universal Mechanical Testing Machine with Atomic Force Microscope for Materials Research

    NASA Astrophysics Data System (ADS)

    Zhong, Jian; He, Dannong

    2015-08-01

    Surface deformation and fracture processes of materials under external force are important for understanding and developing materials. Here, a combined horizontal universal mechanical testing machine (HUMTM)-atomic force microscope (AFM) system is developed by modifying UMTM to combine with AFM and designing a height-adjustable stabilizing apparatus. Then the combined HUMTM-AFM system is evaluated. Finally, as initial demonstrations, it is applied to analyze the relationship among macroscopic mechanical properties, surface nanomorphological changes under external force, and fracture processes of two kinds of representative large scale thin film materials: polymer material with high strain rate (Parafilm) and metal material with low strain rate (aluminum foil). All the results demonstrate the combined HUMTM-AFM system overcomes several disadvantages of current AFM-combined tensile/compression devices including small load force, incapability for large scale specimens, disability for materials with high strain rate, and etc. Therefore, the combined HUMTM-AFM system is a promising tool for materials research in the future.

  10. Improved characterization of cartilage mechanical properties using a combination of stress relaxation and creep.

    PubMed

    Chin, Hooi Chuan; Khayat, Ghazaleh; Quinn, Thomas M

    2011-01-01

    Mechanical characterization of cartilage, other soft tissues and gels has become a ubiquitous and essential aspect of biomechanics and biomaterials research. Current progress in theoretical modeling and tools for data analysis often exceed what is required for routine mechanical characterization assays in experimental studies, making selection of methodologies difficult for the nonspecialist. We have therefore developed an approach for measurement of confined compression modulus and hydraulic permeability based on simple poroelasticity theory and requiring only linear regression tools for data analysis. This technique involves a new application of an early-time solution for creep combined with stress relaxation measurements to characterize soft tissue mechanical parameters as a function of compressive strain or water content. This combined methodology allows measurement of hydraulic permeability by two different techniques with only a modest increase in experimental duration, providing a more precise assessment of permeability and associated measurement error. PMID:20869717

  11. Isobolographic analysis of the mechanisms of action of anticonvulsants from a combination effect.

    PubMed

    Matsumura, Nobuko; Nakaki, Toshio

    2014-10-15

    The nature of the pharmacodynamic interactions of drugs is influenced by the drugs׳ mechanisms of action. It has been hypothesized that drugs with different mechanisms are likely to interact synergistically, whereas those with similar mechanisms seem to produce additive interactions. In this review, we describe an extensive investigation of the published literature on drug combinations of anticonvulsants, the nature of the interaction of which has been evaluated by type I and II isobolographic analyses and the subthreshold method. The molecular targets of antiepileptic drugs (AEDs) include Na(+) and Ca(2+) channels, GABA type-A receptor, and glutamate receptors such as NMDA and AMPA/kainate receptors. The results of this review indicate that the nature of interactions evaluated by type I isobolographic analyses but not by the two other methods seems to be consistent with the above hypothesis. Type I isobolographic analyses may be used not only for evaluating drug combinations but also for predicting the targets of new drugs. PMID:25149665

  12. Anesthetic management of right atrial mass removal and pulmonary artery thrombectomy in a patient with primary antiphospholipid antibody syndrome.

    PubMed

    Rawat, S K S; Mehta, Yatin; Vats, Mayank; Mishra, Yugal; Khurana, Poonam; Trehan, Naresh

    2010-01-01

    Antiphospholipid antibody syndrome (APLAS) characterises a clinical condition of arterial and venous thrombosis associated with phospholipids directed antibodies. APLAS occurs in 2% of the general population. However, one study demonstrated that 7.1% of hospitalised patients were tested positive for at least one of the three anticardiolipin antibody idiotype. Antiphospholipid antibodies often inhibit phospholipids dependent coagulation in vitro and interfere with laboratory testing of hemostasis. Therefore, the management of anticoagulation during cardiopulmonary bypass can be quite challenging in these patients. Here, we present a case of right atrial mass removal and pulmonary thrombectomy in a patient of APLAS. PMID:20075534

  13. Combination effect of ultrasound and shake as a mechanical action for textile cleaning.

    PubMed

    Gotoh, Keiko; Harayama, Kokoro; Handa, Keiko

    2015-01-01

    The ultrasonic cleaning of artificially soiled fabrics with and without shake was carried out in an aqueous anionic surfactant solution. The polyester, cotton and polyester/cotton (65/35) fabrics were soiled with oleic acid or carbon black as a model soil, and cleaned together with their original fabrics with applying ultrasound for 5min. The detergency and the soil redeposition were determined from the change in the Kubelka-Munk function of the soiled and original fabric surfaces due to the cleaning. For any fabric, the removal of oleic acid and carbon black from the soiled fabric and their redeposition onto the original fabric increased with increasing electric power consumption of ultrasound. When ultrasound and shake were applied at the same time, the detergency further increased for any electric power consumption. The maximum detergency obtained with combination of ultrasound 340W and shake 160spm was compared with detergency obtained with Wascator, a horizontal axis drum type washer. It was found that the ultrasound/shake combination cleaning enabled efficient removal of both soils from any fabric and the detergency of the polyester fabrics was comparable to that with Wascator. The mechanical action during the washing was evaluated by two mechanical action test pieces commercially available, which indicated that the ultrasound/shake combination cleaning provided gentle mechanical action to the fabric in comparison with the drum type washer. The SEM observations showed the damage of the fabric and fiber surfaces was negligibly small after the ultrasound/shake combination washing. PMID:24910442

  14. Combined optical and mechanical scanning in optical-resolution photoacoustic microscopy

    NASA Astrophysics Data System (ADS)

    Li, Lei; Yeh, Chenghung; Hu, Song; Wang, Lidai; Soetikno, Brian T.; Chen, Ruimin; Zhou, Qifa; Shung, K. Kirk; Maslov, Konstantin I.; Wang, Lihong V.

    2014-03-01

    Combined optical and mechanical scanning (COMS) in optical-resolution photoacoustic microscopy (OR-PAM) has provided five scanning modes with fast imaging speed and wide field of view (FOV). With two-dimensional (2D) galvanometer-based optical scanning, we have achieved a 2 KHz B-scan rate and 50 Hz volumetric-scan rate, which enables real-time tracking of cell activities in vivo. With optical-mechanical hybrid 2D scanning, we are able to image a wide FOV (10×8 mm2) within 150 seconds, which is 20 times faster than the conventional mechanical scan in our second-generation OR-PAM. With three-dimensional mechanical-based contour scanning, we can maintain the optimal signal-to-noise ratio and spatial resolution of OR-PAM while imaging objects with uneven surfaces, which is ideal for fast and quantitative studies of tumors and the brain.

  15. An Opportunistic Routing Mechanism Combined with Long-Term and Short-Term Metrics for WMN

    PubMed Central

    Piao, Xianglan; Qiu, Tie

    2014-01-01

    WMN (wireless mesh network) is a useful wireless multihop network with tremendous research value. The routing strategy decides the performance of network and the quality of transmission. A good routing algorithm will use the whole bandwidth of network and assure the quality of service of traffic. Since the routing metric ETX (expected transmission count) does not assure good quality of wireless links, to improve the routing performance, an opportunistic routing mechanism combined with long-term and short-term metrics for WMN based on OLSR (optimized link state routing) and ETX is proposed in this paper. This mechanism always chooses the highest throughput links to improve the performance of routing over WMN and then reduces the energy consumption of mesh routers. The simulations and analyses show that the opportunistic routing mechanism is better than the mechanism with the metric of ETX. PMID:25250379

  16. Spatial masking does not reveal mechanisms selective to combined luminance and red-green color.

    PubMed

    Stromeyer, C F; Thabet, R; Chaparro, A; Kronauer, R E

    1999-06-01

    Detection thresholds plotted in the L and M cone-contrast plane have shown that there are two primary detection mechanisms, a red-green hue mechanism and a light-dark luminance mechanism. However, previous masking results suggest there may be additional mechanisms, responsive to combined features like bright and red or dark and green. We measured detection thresholds for a 1.2 c deg-1 sine-wave grating in the presence of a spatially matched mask grating which was either stationary, dynamically jittered or flickered. The stimuli could be set to any direction in the L,M plane. The appearance of selectivity for combined hue and luminance arose only in conditions where adding the test to the mask modified the spatial phase offset between the luminance and red-green stimulus components. Sensitivity was very high for detecting this spatial phase offset. When this extra cue was eliminated, masking contours in the L,M plane could be largely described by the classical red-green and luminance mechanisms. PMID:10343793

  17. New combined antifriction treatment of the guides of machines and mechanisms

    NASA Astrophysics Data System (ADS)

    Bishutin, S. G.

    2016-04-01

    The technology description of the combined antifriction treatment, including three stages, is presented. These stages are the following: abrasive rough-down for surface preparation to coating with antifriction material; surface rubbing with antifriction material; surface plastic deformation of the processed surface area. These stages are executed with one instrument. The article presents the technological modes of this treatment allowing the formation of wear resistant surface layers of guides of machines and mechanisms.

  18. Modeling of combined high-temperature creep and cyclic plasticity in components using continuum damage mechanics

    NASA Astrophysics Data System (ADS)

    Dunne, F. P. E.; Hayhurst, D. R.

    1992-06-01

    A computer-based finite-element viscoplastic damage solver is presented to analyze structural components subject to combined cyclic thermal and mechanical loading. The solver is capable of predicting the combined evolution of creep and cyclic plasticity damage by solution of the combined boundary-initial value problem. The solver has been used to predict the high-temperature behavior of a slag tap component subjected to cyclic thermal loading generated by infrared heaters and water cooling ducts. It is found that the initiation of damage and microcracking occur early in the lifetime at about 3000 cycles adjacent to the cooling duct. The propagation of failure zones stabilizes at 60,000 cycles after which no further damage evolution occurs.

  19. Synergistic intracellular iron chelation combinations: mechanisms and conditions for optimizing iron mobilization.

    PubMed

    Vlachodimitropoulou Koumoutsea, Evangelia; Garbowski, Maciej; Porter, John

    2015-09-01

    Iron chelators are increasingly combined clinically but the optimal conditions for cellular iron mobilization and mechanisms of interaction are unclear. Speciation plots for iron(III) binding of paired combinations of the licensed iron chelators desferrioxamine (DFO), deferiprone (DFP) and deferasirox (DFX) suggest conditions under which chelators can combine as 'shuttle' and 'sink' molecules but this approach does not consider their relative access and interaction with cellular iron pools. To address this issue, a sensitive ferrozine-based detection system for intracellular iron removal from the human hepatocyte cell line (HuH-7) was developed. Antagonism, synergism or additivity with paired chelator combinations was distinguished using mathematical isobologram analysis over clinically relevant chelator concentrations. All combinations showed synergistic iron mobilization at 8 h with clinically achievable concentrations of sink and shuttle chelators. Greatest synergism was achieved by combining DFP with DFX, where about 60% of mobilized iron was attributable to synergistic interaction. These findings predict that the DFX dose required for a half-maximum effect can be reduced by 3·8-fold when only 1 μmol/l DFP is added. Mechanisms for the synergy are suggested by consideration of the iron-chelate speciation plots together with the size, charge and lipid solubilities for each chelator. Hydroxypyridinones with low lipid solubilities but otherwise similar properties to DFP were used to interrogate the mechanistic interactions of chelator pairs. These studies confirm that synergistic cellular iron mobilization requires one chelator to have the physicochemical properties to enter cells, chelate intracellular iron and subsequently donate iron to a second 'sink' chelator. PMID:26033030

  20. Synergistic chemoprotective mechanisms of dietary phytoestrogens in a select combination against prostate cancer.

    PubMed

    Kumar, Rajeev; Verma, Vikas; Jain, Ashish; Jain, Rajeev K; Maikhuri, Jagdamba P; Gupta, Gopal

    2011-08-01

    Combination of dietary phytoestrogens with diverse molecular mechanisms may enhance their anticancer efficacy at physiological concentrations, as evidenced in epidemiological studies. A select combination of three dietary phytoestrogens containing 8.33 μM each of genistein (G), quercetin (Q) and biochanin A (B) was found to be more potent in inhibiting the growth of androgen-responsive prostate cancer cells (LNCaP) as well as DU-145 and PC-3 prostate cancer cells in vitro than either 25 μM of G, B or Q or 12.5+12.5 μM of G+Q, Q+B or G+B. Subsequent mechanistic studies in PC-3 cells indicated that the action of phytoestrogens was mediated both through estrogen receptor (ER)-dependent and ER-independent pathways as potent estrogen antagonist ICI-182780 (ICI, 5 μM) could not completely mask the synergistic anticancer effects, which were sustained appreciably in presence of ICI. G+Q+B combination was significantly more effective than individual compounds or their double combinations in increasing ER-β, bax (mRNA expression); phospho-JNK, bax (protein levels); and in decreasing bcl-2, cyclin E, c-myc (mRNA expression); phospho-AKT, phospho-ERK, bcl-2, proliferating cell nuclear antigen (protein levels) in PC-3 cells. Phytoestrogens also synergistically stimulated caspase-3 activity. Our findings suggest that selectively combining anticancer phytoestrogens could significantly increase the efficacy of individual components resulting in improved efficacy at physiologically achievable concentrations. The combination mechanism of multiple anticancer phytochemicals may be indicative of the potential of some vegetarian diet components to elicit chemopreventive effects against prostate cancer at their physiologically achievable concentrations, in vivo. PMID:21062672

  1. Measuring the mechanical properties of plant cells by combining micro-indentation with osmotic treatments

    PubMed Central

    Weber, Alain; Braybrook, Siobhan; Huflejt, Michal; Mosca, Gabriella; Routier-Kierzkowska, Anne-Lise; Smith, Richard S.

    2015-01-01

    Growth in plants results from the interaction between genetic and signalling networks and the mechanical properties of cells and tissues. There has been a recent resurgence in research directed at understanding the mechanical aspects of growth, and their feedback on genetic regulation. This has been driven in part by the development of new micro-indentation techniques to measure the mechanical properties of plant cells in vivo. However, the interpretation of indentation experiments remains a challenge, since the force measures results from a combination of turgor pressure, cell wall stiffness, and cell and indenter geometry. In order to interpret the measurements, an accurate mechanical model of the experiment is required. Here, we used a plant cell system with a simple geometry, Nicotiana tabacum Bright Yellow-2 (BY-2) cells, to examine the sensitivity of micro-indentation to a variety of mechanical and experimental parameters. Using a finite-element mechanical model, we found that, for indentations of a few microns on turgid cells, the measurements were mostly sensitive to turgor pressure and the radius of the cell, and not to the exact indenter shape or elastic properties of the cell wall. By complementing indentation experiments with osmotic experiments to measure the elastic strain in turgid cells, we could fit the model to both turgor pressure and cell wall elasticity. This allowed us to interpret apparent stiffness values in terms of meaningful physical parameters that are relevant for morphogenesis. PMID:25873663

  2. Mechanism of Sporicidal Activity for the Synergistic Combination of Peracetic Acid and Hydrogen Peroxide.

    PubMed

    Leggett, Mark J; Schwarz, J Spencer; Burke, Peter A; McDonnell, Gerald; Denyer, Stephen P; Maillard, Jean-Yves

    2016-02-01

    There is still great interest in controlling bacterial endospores. The use of chemical disinfectants and, notably, oxidizing agents to sterilize medical devices is increasing. With this in mind, hydrogen peroxide (H2O2) and peracetic acid (PAA) have been used in combination, but until now there has been no explanation for the observed increase in sporicidal activity. This study provides information on the mechanism of synergistic interaction of PAA and H2O2 against bacterial spores. We performed investigations of the efficacies of different combinations, including pretreatments with the two oxidizers, against wild-type spores and a range of spore mutants deficient in the spore coat or small acid-soluble spore proteins. The concentrations of the two biocides were also measured in the reaction vessels, enabling the assessment of any shift from H2O2 to PAA formation. This study confirmed the synergistic activity of the combination of H2O2 and PAA. However, we observed that the sporicidal activity of the combination is largely due to PAA and not H2O2. Furthermore, we observed that the synergistic combination was based on H2O2 compromising the spore coat, which was the main spore resistance factor, likely allowing better penetration of PAA and resulting in the increased sporicidal activity. PMID:26637595

  3. Mechanism of Sporicidal Activity for the Synergistic Combination of Peracetic Acid and Hydrogen Peroxide

    PubMed Central

    Leggett, Mark J.; Schwarz, J. Spencer; Burke, Peter A.; McDonnell, Gerald; Denyer, Stephen P.

    2015-01-01

    There is still great interest in controlling bacterial endospores. The use of chemical disinfectants and, notably, oxidizing agents to sterilize medical devices is increasing. With this in mind, hydrogen peroxide (H2O2) and peracetic acid (PAA) have been used in combination, but until now there has been no explanation for the observed increase in sporicidal activity. This study provides information on the mechanism of synergistic interaction of PAA and H2O2 against bacterial spores. We performed investigations of the efficacies of different combinations, including pretreatments with the two oxidizers, against wild-type spores and a range of spore mutants deficient in the spore coat or small acid-soluble spore proteins. The concentrations of the two biocides were also measured in the reaction vessels, enabling the assessment of any shift from H2O2 to PAA formation. This study confirmed the synergistic activity of the combination of H2O2 and PAA. However, we observed that the sporicidal activity of the combination is largely due to PAA and not H2O2. Furthermore, we observed that the synergistic combination was based on H2O2 compromising the spore coat, which was the main spore resistance factor, likely allowing better penetration of PAA and resulting in the increased sporicidal activity. PMID:26637595

  4. Endovascular Treatment of Phlegmasia Cerulea Dolens with Impending Venous Gangrene: Manual Aspiration Thrombectomy as the First-Line Thrombus Removal Method

    SciTech Connect

    Oguzkurt, Levent Ozkan, Ugur; Demirturk, Orhan S.; Gur, Serkan

    2011-12-15

    Purpose: Our purpose was to report the outcome of endovascular treatment with manual aspiration thrombectomy as the first-line thromboablative method for phlegmasia cerulea dolens. Methods: Between October 2006 and May 2010, seven consecutive patients (5 women, 2 men; age range, 31-80 years) with the diagnosis of phlegmasia cerulea dolens secondary to acute iliofemoral deep venous thrombosis had endovascular treatment with manual aspiration thrombectomy. Catheter-directed thrombolysis and stent placement were used as adjunctive procedures. Phlegmasia was left-sided in five and right-sided in two patients. Results: All patients had associated great saphenous vein thrombosis in addition to iliofemoral deep vein thrombosis (DVT). Aspiration thrombectomy completely removed the thrombus from the popliteal vein to the inferior vena cava (IVC) in all cases. Three patients with May-Thurner syndrome had stent placement in the left common iliac vein. Two patients had early recurrences. Repeated aspiration thrombectomy was unsuccessful in one patient. There were no complications related to the procedure. One patient who had been successfully treated died of sepsis and another patient who had unsuccessful repeated interventions had below-the-knee amputation. Overall, the clinical success and survival rates of patients in this study were 86%. On follow-up, three patients with successful treatment were asymptomatic with no deep venous insufficiency. One of these patients died during the 4-month follow-up period. Two patients had mild ankle swelling with deep venous insufficiency. Conclusions: Manual aspiration thrombectomy with adjunctive use of catheter-directed thrombolysis and stent placement is an effective endovascular treatment method with high clinical success and survival rates for phlegmasia cerulean dolens.

  5. COMBINE*: An integrated opto-mechanical tool for laser performance modeling

    NASA Astrophysics Data System (ADS)

    Rehak, M.; Di Nicola, J. M.

    2015-02-01

    Accurate modeling of thermal, mechanical and optical processes is important for achieving reliable, high-performance high energy lasers such as those at the National Ignition Facility [1] (NIF). The need for this capability is even more critical for high average power, high repetition rate applications. Modeling the effects of stresses and temperature fields on optical properties allows for optimal design of optical components and more generally of the architecture of the laser system itself. Stresses change the indices of refractions and induce inhomogeneities and anisotropy. We present a modern, integrated analysis tool that efficiently produces reliable results that are used in our laser propagation tools such as VBL [5]. COMBINE is built on and supplants the existing legacy tools developed for the previous generations of lasers at LLNL but also uses commercially available mechanical finite element codes ANSYS or COMSOL (including computational fluid dynamics). The COMBINE code computes birefringence and wave front distortions due to mechanical stresses on lenses and slabs of arbitrary geometry. The stresses calculated typically originate from mounting support, vacuum load, gravity, heat absorption and/or attending cooling. Of particular importance are the depolarization and detuning effects of nonlinear crystals due to thermal loading. Results are given in the form of Jones matrices, depolarization maps and wave front distributions. An incremental evaluation of Jones matrices and ray propagation in a 3D mesh with a stress and temperature field is performed. Wavefront and depolarization maps are available at the optical aperture and at slices within the optical element. The suite is validated, user friendly, supported, documented and amenable to collaborative development. * COMBINE stands for Code for Opto-Mechanical Birefringence Integrated Numerical Evaluations.

  6. Reaction mechanism of manganese superoxide dismutase studied by combined quantum and molecular mechanical calculations and multiconfigurational methods.

    PubMed

    Srnec, Martin; Aquilante, Francesco; Ryde, Ulf; Rulísek, Lubomír

    2009-04-30

    Manganese superoxide dismutases (MnSODs) are enzymes that convert two molecules of the poisonous superoxide radical into molecular oxygen and hydrogen peroxide. During the reaction, the manganese ion cycles between the Mn(2+) and Mn(3+) oxidation states and accomplishes its enzymatic action in two half-cycles (corresponding to the oxidation and reduction of O(2)(-)). Despite many experimental and theoretical studies dealing with SODs, including quantum chemical active-site-model studies of numerous variants of the reaction mechanisms, several details of MnSOD enzymatic action are still unclear. In this study, we have modeled and compared four reaction pathways (one associative, one dissociative, and two second-sphere) in a protein environment using the QM/MM approach (combined quantum and molecular mechanics calculations) at the density functional theory level. The results were complemented by CASSCF/CASPT2/MM single-point energy calculations for the most plausible models to account properly for the multireference character of the various spin multiplets. The results indicate that the oxidation of O(2)(-) to O(2) most likely occurs by an associative mechanism following a two-state (quartet-octet) reaction profile. The barrier height is estimated to be less than 25 kJ.mol(-1). On the other hand, the conversion of O(2)(-) to H(2)O(2) is likely to take place by a second-sphere mechanism, that is, without direct coordination of the superoxide radical to the manganese center. The reaction pathway involves the conical intersection of two quintet states, giving rise to an activation barrier of approximately 60 kJ.mol(-1). The calculations also indicate that the associative mechanism can represent a competitive pathway in the second half-reaction with the overall activation barrier being only slightly higher than the activation barrier in the second-sphere mechanism. The activation barriers along the proposed reaction pathways are in very good agreement with the

  7. Promise of combined hydrothermal/chemical and mechanical refining for pretreatment of woody and herbaceous biomass.

    PubMed

    Kim, Sun Min; Dien, Bruce S; Singh, Vijay

    2016-01-01

    Production of advanced biofuels from woody and herbaceous feedstocks is moving into commercialization. Biomass needs to be pretreated to overcome the physicochemical properties of biomass that hinder enzyme accessibility, impeding the conversion of the plant cell walls to fermentable sugars. Pretreatment also remains one of the most costly unit operations in the process and among the most critical because it is the source of chemicals that inhibit enzymes and microorganisms and largely determines enzyme loading and sugar yields. Pretreatments are categorized into hydrothermal (aqueous)/chemical, physical, and biological pretreatments, and the mechanistic details of which are briefly outlined in this review. To leverage the synergistic effects of different pretreatment methods, conducting two or more pretreatments consecutively has gained attention. Especially, combining hydrothermal/chemical pretreatment and mechanical refining, a type of physical pretreatment, has the potential to be applied to an industrial plant. Here, the effects of the combined pretreatment (combined hydrothermal/chemical pretreatment and mechanical refining) on energy consumption, physical structure, sugar yields, and enzyme dosage are summarized. PMID:27141232

  8. Biodiesel production from palm oil using combined mechanical stirred and ultrasonic reactor.

    PubMed

    Choedkiatsakul, I; Ngaosuwan, K; Cravotto, G; Assabumrungrat, S

    2014-07-01

    This paper investigates the production of biodiesel from palm oil using a combined mechanical stirred and ultrasonic reactor (MS-US). The incorporation of mechanical stirring into the ultrasonic reactor explored the further improvement the transesterification of palm oil. Initial reaction rate values were 54.1, 142.9 and 164.2 mmol/L min for the mechanical-stirred (MS), ultrasonic (US) and MS-US reactors, respectively. Suitable methanol to oil molar ratio and the catalyst loading values were found to be 6 and 1 of oil, respectively. The effect of ultrasonic operating parameters; i.e. frequency, location, and number of transducer, has been investigated. Based on the conversion yield at the reactor outlet after 1 h, the number of transducers showed a relevant role in the reaction rate. Frequency and transducer location would appear to have no significant effect. The properties of the obtained biodiesel (density, viscosity, pour point, and flash point) satisfy the ASTM standard. The combined MS-US reactors improved the reaction rate affording the methyl esters in higher yield. PMID:24418101

  9. Effect of Combined Treatment Using Wilfortrine and Paclitaxel in Liver Cancer and Related Mechanism

    PubMed Central

    Li, Shuzhen; Zheng, Lei

    2016-01-01

    Background Liver cancer is a common malignant tumor with high mortality. Currently, effective medicines against liver cancer are still lacking. Paclitaxel is a wide-spectrum anti-tumor agent, while wilfortrine has been shown to have an inhibitory effect on the proliferation of liver cancer cells. This study thus investigated the potential effect of paclitaxel combined with wilfortrine on cultured liver cancer cells and related mechanisms, in order to provide evidence for pathogenesis and treatment of liver cancer. Material/Methods Liver cancer cell line HpeG2 was divided into control, paclitaxel, wilfortrine, and combined treatment groups. Cell proliferation was tested by MTT, while invasion was detected in Transwell chamber assay. Apoptotic protein Bcl-2 and Bax expression levels were further quantified using real-time PCR and Western blotting. Results Both of those 2 drugs can effectively inhibit cancer cell proliferation, depress invasion ability, increase Bcl-2 expression, and elevate Bax expression levels (p<0.05 in all cases). The combined therapy had better treatment efficacy compared to either of those drugs alone (p<0.05). Conclusions The combined treatment using wilfortrine and paclitaxel can inhibit proliferation and invasion of liver cancer cells via down-regulating Bcl-2 and up-regulating Bax, with better efficacy than single use of either drug. PMID:27043783

  10. Mechanical Properties of Thermoplastic Polyurethanes Laminated Glass Treated by Acid Etching Combined with Cold Plasma

    NASA Astrophysics Data System (ADS)

    Li, Xibao; Lu, Jinshan; Luo, Junming; Zhang, Jianjun; Ou, Junfei; Xu, Haitao

    2014-10-01

    To overcome the problem of interlaminar delamination of thermoplastic polyurethane laminated glass, silicate glass was etched with hydrofluoric acid and thermoplastic polyurethane was then treated with cold plasma. Compared with the untreated samples, the interlaminar shear strength of acid etching samples, cold plasma-treated samples and acid etching combined with cold plasma-treated samples increased by 97%, 84% and 341%, respectively. Acid etching combined with cold plasma-treated samples exhibited a higher flexural strength and strain as compared with the untreated samples. The impact energy of acid etching samples, cold plasma-treated samples and acid etching combined with cold plasma-treated samples increased by 8.7%, 8.1% and 11.6%, respectively, in comparison with the untreated samples. FT-IR analysis showed that a large number of -C=O, -CO-N and -CO-O-C- groups appeared on the surface of cold plasma-treated thermoplastic polyurethane, which resulted in the formation of hydrogen bonds. SEM results showed that some pittings formed on the surface of the silicate glass treated by acid etching, which resulted in the formation of a three-dimensional interface structure between the silicate glass and polyurethane. Hydrogen bonds combined with the three-dimensional interface between silicate glass and polyurethanes co-improved the mechanical properties of thermoplastic polyurethanes laminated glass.

  11. Quantifying subpopulation synergy for antibiotic combinations via mechanism-based modeling and a sequential dosing design.

    PubMed

    Landersdorfer, Cornelia B; Ly, Neang S; Xu, Hongmei; Tsuji, Brian T; Bulitta, Jürgen B

    2013-05-01

    Quantitative modeling of combination therapy can describe the effects of each antibiotic against multiple bacterial populations. Our aim was to develop an efficient experimental and modeling strategy that evaluates different synergy mechanisms using a rapidly killing peptide antibiotic (nisin) combined with amikacin or linezolid as probe drugs. Serial viable counts over 48 h were obtained in time-kill experiments with all three antibiotics in monotherapy against a methicillin-resistant Staphylococcus aureus USA300 strain (inoculum, 10(8) CFU/ml). A sequential design (initial dosing of 8 or 32 mg/liter nisin, switched to amikacin or linezolid at 1.5 h) assessed the rate of killing by amikacin and linezolid against nisin-intermediate and nisin-resistant populations. Simultaneous combinations were additionally studied and all viable count profiles comodeled in S-ADAPT and NONMEM. A mechanism-based model with six populations (three for nisin times two for amikacin) yielded unbiased and precise (r = 0.99, slope = 1.00; S-ADAPT) individual fits. The second-order killing rate constants for nisin against the three populations were 5.67, 0.0664, and 0.00691 liter/(mg · h). For amikacin, the maximum killing rate constants were 10.1 h(-1) against its susceptible and 0.771 h(-1) against its less-susceptible populations, with 14.7 mg/liter amikacin causing half-maximal killing. After incorporating the effects of nisin and amikacin against each population, no additional synergy function was needed. Linezolid inhibited successful bacterial replication but did not efficiently kill populations less susceptible to nisin. Nisin plus amikacin achieved subpopulation synergy. The proposed sequential and simultaneous dosing design offers an efficient approach to quantitatively characterize antibiotic synergy over time and prospectively evaluate antibiotic combination dosing strategies. PMID:23478962

  12. Structural Stability of a Stiffened Aluminum Fuselage Panel Subjected to Combined Mechanical and Internal Pressure Loads

    NASA Technical Reports Server (NTRS)

    Rouse, Marshall; Young, Richard D.; Gehrki, Ralph R.

    2003-01-01

    Results from an experimental and analytical study of a curved stiffened aluminum panel subjected to combined mechanical and internal pressure loads are presented. The panel loading conditions were simulated using a D-box test fixture. Analytical buckling load results calculated from a finite element analysis are presented and compared to experimental results. Buckling results presented indicate that the buckling load of the fuselage panel is significantly influenced by internal pressure loading. The experimental results suggest that the stress distribution is uniform in the panel prior to buckling. Nonlinear finite element analysis results correlates well with experimental results up to buckling.

  13. Aspiration Thrombectomy and Drug-Eluting Stent Implantation Decrease the Occurrence of Angina Pectoris One Year After Acute Myocardial Infarction.

    PubMed

    Lee, Wei-Chieh; Fang, Chih-Yuan; Chen, Huang-Chung; Hsueh, Shu-Kai; Chen, Chien-Jen; Yang, Cheng-Hsu; Yip, Hon-Kan; Hang, Chi-Ling; Wu, Chiung-Jen; Fang, Hsiu-Yu

    2016-04-01

    Angina pectoris is a treatable symptom that is associated with mortality and decreased quality of life. Angina eradication is a primary care goal of care after an acute myocardial infarction (AMI). Our aim was to evaluate factors influencing angina pectoris 1 year after an AMI.From January 2005 to December 2013, 1547 patient received primary percutaneous intervention in our hospital for an acute ST-segment elevation myocardial infarction (MI). Of these patients, 1336 patients did not experience post-MI angina during a 1-year follow-up, and 211 patients did. Univariate and multivariate logistic regression analyses were performed to identify the factors influencing angina pectoris 1 year after an AMI. Propensity score matched analyses were performed for subgroups analyses.The average age of the patients was 61.08 ± 12.77 years, with a range of 25 to 97 years, and 82.9% of the patients were male. During 1-year follow-up, 13.6% of the patients experienced post-MI angina. There was a longer chest pain-to-reperfusion time in the post-MI angina group (P = 0.01), as well as a higher fasting sugar level, glycohemoglobin (HbA1C), serum creatinine, troponin-I and creatine kinase MB (CK-MB). The post-MI angina group also had a higher prevalence of multiple-vessel disease. Manual thrombectomy, and distal protective device and intracoronary glycoprotein IIb/IIIa inhibitor injection were used frequently in the no post-MI angina group. Antiplatelet agents and post-MI medication usage were similar between the 2 groups. Multivariate logistic regression analyses demonstrated that prior MI was a positive independent predictor of occurrence of post-MI angina. Manual thrombectomy use and drug-eluting stent implantation were negative independent predictors of post-MI angina. Higher troponin-I and longer chest pain-to-reperfusion time exhibited a trend toward predicting post-MI angina.Prior MIs were strong, independent predictors of post-MI angina. Manual thrombectomy and drug

  14. Aspiration Thrombectomy and Drug-Eluting Stent Implantation Decrease the Occurrence of Angina Pectoris One Year After Acute Myocardial Infarction

    PubMed Central

    Lee, Wei-Chieh; Fang, Chih-Yuan; Chen, Huang-Chung; Hsueh, Shu-Kai; Chen, Chien-Jen; Yang, Cheng-Hsu; Yip, Hon-Kan; Hang, Chi-Ling; Wu, Chiung-Jen; Fang, Hsiu-Yu

    2016-01-01

    Abstract Angina pectoris is a treatable symptom that is associated with mortality and decreased quality of life. Angina eradication is a primary care goal of care after an acute myocardial infarction (AMI). Our aim was to evaluate factors influencing angina pectoris 1 year after an AMI. From January 2005 to December 2013, 1547 patient received primary percutaneous intervention in our hospital for an acute ST-segment elevation myocardial infarction (MI). Of these patients, 1336 patients did not experience post-MI angina during a 1-year follow-up, and 211 patients did. Univariate and multivariate logistic regression analyses were performed to identify the factors influencing angina pectoris 1 year after an AMI. Propensity score matched analyses were performed for subgroups analyses. The average age of the patients was 61.08 ± 12.77 years, with a range of 25 to 97 years, and 82.9% of the patients were male. During 1-year follow-up, 13.6% of the patients experienced post-MI angina. There was a longer chest pain-to-reperfusion time in the post-MI angina group (P = 0.01), as well as a higher fasting sugar level, glycohemoglobin (HbA1C), serum creatinine, troponin-I and creatine kinase MB (CK-MB). The post-MI angina group also had a higher prevalence of multiple-vessel disease. Manual thrombectomy, and distal protective device and intracoronary glycoprotein IIb/IIIa inhibitor injection were used frequently in the no post-MI angina group. Antiplatelet agents and post-MI medication usage were similar between the 2 groups. Multivariate logistic regression analyses demonstrated that prior MI was a positive independent predictor of occurrence of post-MI angina. Manual thrombectomy use and drug-eluting stent implantation were negative independent predictors of post-MI angina. Higher troponin-I and longer chest pain-to-reperfusion time exhibited a trend toward predicting post-MI angina. Prior MIs were strong, independent predictors of post-MI angina. Manual thrombectomy

  15. Combined use of nitrogen and coatings to improve the quality of mechanically harvested Manzanilla olives.

    PubMed

    Ramírez, Eva; Sánchez, Antonio H; Romero, Concepción; Brenes, Manuel

    2015-03-15

    The combined effect of an edible coating and a nitrogen atmosphere on the quality of Manzanilla olives mechanically harvested and processed as Spanish-style green olives was assessed. The percentage of olives free of any brown spots ranged between 35-50%, 10-25% and 50-65% for fruit directly processed, storage under nitrogen and coated and storage under nitrogen respectively. Moreover, olives stored in the open air developed brown spots due to the oxidation of oleuropein. By contrast, the anoxic conditions prevented oleuropein from undergoing enzymatic oxidation but not from its enzymatic hydrolysis. Hence, the phenolic derivative HyEDA was formed in olives stored under nitrogen, and this substance was rapidly oxidized in the open air to give rise to brown spots although to a lesser extent in the coated fruit. Therefore, the postharvest storage of coated olives under nitrogen can be a good method to prevent bruise damage in mechanically harvested fruit. PMID:25308641

  16. Surfaces with combined microscale and nanoscale structures: a route to mechanically stable superhydrophobic surfaces?

    PubMed

    Groten, Jonas; Rühe, Jürgen

    2013-03-19

    Materials with superhydrophobic properties are usually generated by covering the surfaces with hydrophobic nanoscale rough features. A major problem, however, for any practical application of such strongly water-repellent surfaces is the mechanical fragility of the nanostructures. Even moderate forces caused by touching or rubbing the surfaces are frequently strong enough to destroy the nanostructures and lead to the loss of the superhydrophobic properties. In this article, we study the mechanical stability of superhydrophobic surfaces with three different topographies: nano- and microscale features and surfaces carrying a combination of both. The surfaces are generated by silicon etching and subsequent coating with a monolayer of a fluoropolymer (PFA). We perform controlled wear tests on the different surfaces and discuss the impact of wear on the wetting properties of the different surfaces. PMID:23363078

  17. Design and fabrication of miniaturized PEM fuel cell combined microreactor with self-regulated hydrogen mechanism

    NASA Astrophysics Data System (ADS)

    Balakrishnan, A.; Frei, M.; Kerzenmacher, S.; Reinecke, H.; Mueller, C.

    2015-12-01

    In this work we present the design and fabrication of the miniaturized PEM fuel cell combined microreactor system with hydrogen regulation mechanism and testing of prototype microreactor. The system consists of two components (i) fuel cell component and (ii) microreactor component. The fuel cell component represents the miniaturized PEM fuel cell system (combination of screen printed fuel cell assembly and an on-board hydrogen storage medium). Hydrogen production based on catalytic hydrolysis of chemical hydride takes place in the microreactor component. The self-regulated hydrogen mechanism based on the gaseous hydrogen produced from the catalytic hydrolysis of sodium borohydride (NaBH4) gets accumulated as bubbles at the vicinity of the hydrophobic coated hydrogen exhaust holes. When the built up hydrogen bubbles pressure exceeds the burst pressure at the hydrogen exhaust holes the bubble collapses. This collapse causes a surge of fresh NaBH4 solution onto the catalyst surface leading to the removal of the reaction by-products formed at the active sites of the catalyst. The catalyst used in the system is platinum deposited on a base substrate. Nickel foam, carbon porous medium (CPM) and ceramic plate were selected as candidates for base substrate for developing a robust catalyst surface. For the first time the platinum layer fabricated by pulsed electrodeposition and dealloying (EPDD) technique is used for hydrolysis of NaBH4. The major advantages of such platinum catalyst layers are its high surface area and their mechanical stability. Prototype microreactor system with self-regulated hydrogen mechanism is demonstrated.

  18. Norcantharidin combined with ABT-737 for hepatocellular carcinoma: Therapeutic effects and molecular mechanisms

    PubMed Central

    Ren, Jing; Li, Gang; Zhao, Wen; Lin, Ling; Ye, Tao

    2016-01-01

    AIM: To study the therapeutic effect of norcantharidin (NCTD) combined with ABT-737 on hepatocellular carcinoma cells and the molecular mechanism. METHODS: Two hepatocellular carcinoma (HCC) cell lines, HepG2 and SMMC-7721, were selected. ABT-737 and NCTD were allocated into groups to be used alone or in combination. HepG2 and SMMC-7721 cells were cultured in vitro. Liver cancer cells in the logarithmic phase of growth were vaccinated and cultured to the cell wall stage; these cells were treated for 48 h with different concentrations of NCTD, or ABT-737, or NCTD combined with ABT-737. The cell proliferation inhibition rate was detected by methyl thiazolyl tetrazolium. The expression of Mcl in HCC cells was detected by Western Blotting, and the cells in each group after treatment had apoptosis detected by flow cytometry. The proliferation inhibition rate, the expression of Mcl-1 in cells and the apoptosis inducing effect of treatment were observed in each group, and the effect of NCTD on ABT-737 in the treatment of HCC and its mechanism of action were analyzed. RESULTS: As the concentration of NCTD increased, the cell proliferation inhibition rate gradually decreased; and the treatment effect of ABT-737 1-3 μm combined with NCTD on cell proliferation inhibition was stronger than that of ABT-737 alone. The difference was statistically significant (P < 0.05). In observing the expression of Mcl-1 in cells after the treatment of different concentrations of NCTD, this was partially inhibited after treatment with NCTD 15 μm, and the expression of Mcl-1 was almost undetectable after treatment with NCTD 30 μm and 60 μm. The effect on inducing apoptosis with the treatment of ABT-737 or NCTD alone for 48 h was lower than that of the control group. The difference was not statistically significant (P > 0.05). The effect on inducing apoptosis in HepG2 and SMMC-7721 cells with the treatment of ABT-737 combined with NCTD for 48 h was greater than that of ABT-737 or NCTD alone

  19. Probabilistic Simulation of Combined Thermo-Mechanical Cyclic Fatigue in Composites

    NASA Technical Reports Server (NTRS)

    Chamis, Christos C.

    2011-01-01

    A methodology to compute probabilistically-combined thermo-mechanical fatigue life of polymer matrix laminated composites has been developed and is demonstrated. Matrix degradation effects caused by long-term environmental exposure and mechanical/thermal cyclic loads are accounted for in the simulation process. A unified time-temperature-stress-dependent multifactor-interaction relationship developed at NASA Glenn Research Center has been used to model the degradation/aging of material properties due to cyclic loads. The fast probability-integration method is used to compute probabilistic distribution of response. Sensitivities of fatigue life reliability to uncertainties in the primitive random variables (e.g., constituent properties, fiber volume ratio, void volume ratio, ply thickness, etc.) computed and their significance in the reliability-based design for maximum life is discussed. The effect of variation in the thermal cyclic loads on the fatigue reliability for a (0/+/-45/90)s graphite/epoxy laminate with a ply thickness of 0.127 mm, with respect to impending failure modes has been studied. The results show that, at low mechanical-cyclic loads and low thermal-cyclic amplitudes, fatigue life for 0.999 reliability is most sensitive to matrix compressive strength, matrix modulus, thermal expansion coefficient, and ply thickness. Whereas at high mechanical-cyclic loads and high thermal-cyclic amplitudes, fatigue life at 0.999 reliability is more sensitive to the shear strength of matrix, longitudinal fiber modulus, matrix modulus, and ply thickness.

  20. Probabilistic Simulation of Combined Thermo-Mechanical Cyclic Fatigue in Composites

    NASA Technical Reports Server (NTRS)

    Chamis, Christos C.

    2010-01-01

    A methodology to compute probabilistically-combined thermo-mechanical fatigue life of polymer matrix laminated composites has been developed and is demonstrated. Matrix degradation effects caused by long-term environmental exposure and mechanical/thermal cyclic loads are accounted for in the simulation process. A unified time-temperature-stress-dependent multifactor-interaction relationship developed at NASA Glenn Research Center has been used to model the degradation/aging of material properties due to cyclic loads. The fast probability-integration method is used to compute probabilistic distribution of response. Sensitivities of fatigue life reliability to uncertainties in the primitive random variables (e.g., constituent properties, fiber volume ratio, void volume ratio, ply thickness, etc.) computed and their significance in the reliability-based design for maximum life is discussed. The effect of variation in the thermal cyclic loads on the fatigue reliability for a (0/+/-45/90)s graphite/epoxy laminate with a ply thickness of 0.127 mm, with respect to impending failure modes has been studied. The results show that, at low mechanical-cyclic loads and low thermal-cyclic amplitudes, fatigue life for 0.999 reliability is most sensitive to matrix compressive strength, matrix modulus, thermal expansion coefficient, and ply thickness. Whereas at high mechanical-cyclic loads and high thermal-cyclic amplitudes, fatigue life at 0.999 reliability is more sensitive to the shear strength of matrix, longitudinal fiber modulus, matrix modulus, and ply thickness.

  1. Quinolinic Acid, an endogenous molecule combining excitotoxicity, oxidative stress and other toxic mechanisms.

    PubMed

    Pérez-De La Cruz, Verónica; Carrillo-Mora, Paul; Santamaría, Abel

    2012-01-01

    Quinolinic acid (QUIN), an endogenous metabolite of the kynurenine pathway, is involved in several neurological disorders, including Huntington's disease, Alzheimer's disease, schizophrenia, HIV associated dementia (HAD) etc. QUIN toxicity involves several mechanisms which trigger various metabolic pathways and transcription factors. The primary mechanism exerted by this excitotoxin in the central nervous system (CNS) has been largely related with the overactivation of N-methyl-D-aspartate receptors and increased cytosolic Ca(2+) concentrations, followed by mitochondrial dysfunction, cytochrome c release, ATP exhaustion, free radical formation and oxidative damage. As a result, this toxic pattern is responsible for selective loss of middle size striatal spiny GABAergic neurons and motor alterations in lesioned animals. This toxin has recently gained attention in biomedical research as, in addition to its proven excitotoxic profile, a considerable amount of evidence suggests that oxidative stress and energetic disturbances are major constituents of its toxic pattern in the CNS. Hence, this profile has changed our perception of how QUIN-related disorders combine different toxic mechanisms resulting in brain damage. This review will focus on the description and integration of recent evidence supporting old and suggesting new mechanisms to explain QUIN toxicity. PMID:22408367

  2. Quinolinic Acid, an Endogenous Molecule Combining Excitotoxicity, Oxidative Stress and Other Toxic Mechanisms

    PubMed Central

    Pérez-De La Cruz, Verónica; Carrillo-Mora, Paul; Santamaría, Abel

    2012-01-01

    Quinolinic acid (QUIN), an endogenous metabolite of the kynurenine pathway, is involved in several neurological disorders, including Huntington’s disease, Alzheimer’s disease, schizophrenia, HIV associated dementia (HAD) etc. QUIN toxicity involves several mechanisms which trigger various metabolic pathways and transcription factors. The primary mechanism exerted by this excitotoxin in the central nervous system (CNS) has been largely related with the overactivation of N-methyl-D-aspartate receptors and increased cytosolic Ca2+ concentrations, followed by mitochondrial dysfunction, cytochrome c release, ATP exhaustion, free radical formation and oxidative damage. As a result, this toxic pattern is responsible for selective loss of middle size striatal spiny GABAergic neurons and motor alterations in lesioned animals. This toxin has recently gained attention in biomedical research as, in addition to its proven excitotoxic profile, a considerable amount of evidence suggests that oxidative stress and energetic disturbances are major constituents of its toxic pattern in the CNS. Hence, this profile has changed our perception of how QUIN-related disorders combine different toxic mechanisms resulting in brain damage. This review will focus on the description and integration of recent evidence supporting old and suggesting new mechanisms to explain QUIN toxicity. PMID:22408367

  3. Examination of turbulent entrainment-mixing mechanisms using a combined approach

    SciTech Connect

    Lu, C.; Liu, Y.; Niu, S.

    2011-10-01

    Turbulent entrainment-mixing mechanisms are investigated by applying a combined approach to the aircraft measurements of three drizzling and two nondrizzling stratocumulus clouds collected over the U.S. Department of Energy's Atmospheric Radiation Measurement Southern Great Plains site during the March 2000 cloud Intensive Observation Period. Microphysical analysis shows that the inhomogeneous entrainment-mixing process occurs much more frequently than the homogeneous counterpart, and most cases of the inhomogeneous entrainment-mixing process are close to the extreme scenario, having drastically varying cloud droplet concentration but roughly constant volume-mean radius. It is also found that the inhomogeneous entrainment-mixing process can occur both near the cloud top and in the middle level of a cloud, and in both the nondrizzling clouds and nondrizzling legs in the drizzling clouds. A new dimensionless number, the scale number, is introduced as a dynamical measure for different entrainment-mixing processes, with a larger scale number corresponding to a higher degree of homogeneous entrainment mixing. Further empirical analysis shows that the scale number that separates the homogeneous from the inhomogeneous entrainment-mixing process is around 50, and most legs have smaller scale numbers. Thermodynamic analysis shows that sampling average of filament structures finer than the instrumental spatial resolution also contributes to the dominance of inhomogeneous entrainment-mixing mechanism. The combined microphysical-dynamical-thermodynamic analysis sheds new light on developing parameterization of entrainment-mixing processes and their microphysical and radiative effects in large-scale models.

  4. Gemcitabine/cannabinoid combination triggers autophagy in pancreatic cancer cells through a ROS-mediated mechanism

    PubMed Central

    Donadelli, M; Dando, I; Zaniboni, T; Costanzo, C; Dalla Pozza, E; Scupoli, M T; Scarpa, A; Zappavigna, S; Marra, M; Abbruzzese, A; Bifulco, M; Caraglia, M; Palmieri, M

    2011-01-01

    Gemcitabine (GEM, 2′,2′-difluorodeoxycytidine) is currently used in advanced pancreatic adenocarcinoma, with a response rate of < 20%. The purpose of our work was to improve GEM activity by addition of cannabinoids. Here, we show that GEM induces both cannabinoid receptor-1 (CB1) and cannabinoid receptor-2 (CB2) receptors by an NF-κB-dependent mechanism and that its association with cannabinoids synergistically inhibits pancreatic adenocarcinoma cell growth and increases reactive oxygen species (ROS) induced by single treatments. The antiproliferative synergism is prevented by the radical scavenger N-acetyl--cysteine and by the specific NF-κB inhibitor BAY 11-7085, demonstrating that the induction of ROS by GEM/cannabinoids and of NF-κB by GEM is required for this effect. In addition, we report that neither apoptotic nor cytostatic mechanisms are responsible for the synergistic cell growth inhibition, which is strictly associated with the enhancement of endoplasmic reticulum stress and autophagic cell death. Noteworthy, the antiproliferative synergism is stronger in GEM-resistant pancreatic cancer cell lines compared with GEM-sensitive pancreatic cancer cell lines. The combined treatment strongly inhibits growth of human pancreatic tumor cells xenografted in nude mice without apparent toxic effects. These findings support a key role of the ROS-dependent activation of an autophagic program in the synergistic growth inhibition induced by GEM/cannabinoid combination in human pancreatic cancer cells. PMID:21525939

  5. Bilateral renal vein thrombosis and pulmonary embolism secondary to membranous glomerulonephritis treated with percutaneous catheter thrombectomy and localized thrombolytic therapy

    PubMed Central

    Janda, S. P.

    2010-01-01

    Renal vein thrombosis (RVT) is a rare event but is prevalent in patients with nephrotic syndrome. Bilateral RVT is even rarer. The literature is relatively sparse in terms of the management of RVT because of its rarity and consists of a few case reports and case series. We present a case with bilateral RVT complicated by a pulmonary embolism in a patient with membranous glomerulonephritis (MGN). A 19-year-old female presented with acute flank pain and worsening renal function after a couple of weeks in hospital while being treated with diuretics for anasarca secondary to MGN. Venography was used for diagnosis. The patient underwent percutaneous catheter thrombectomy and localized thrombolysis achieving resolution of pain and improvement of renal function. The patient was then anticoagulated for life with warfarin. PMID:21072156

  6. Keratinocyte galvanotaxis in combined DC and AC electric fields supports an electromechanical transduction sensing mechanism.

    PubMed

    Hart, Francis X; Laird, Mhairi; Riding, Aimie; Pullar, Christine E

    2013-02-01

    Sedentary keratinocytes at the edge of a skin wound migrate into the wound, guided by the generation of an endogenous electric field (EF) generated by the collapse of the transepithelial potential. The center of the wound quickly becomes more negative than the surrounding tissue and remains the cathode of the endogenous EF until the wound is completely re-epithelialized. This endogenous guidance cue can be studied in vitro. When placed in a direct current (DC) EF of physiological strength, 100 V/m, keratinocytes migrate directionally toward the cathode in a process known as galvanotaxis. Although a number of membrane-bound (e.g., epidermal growth factor receptor (EGFR), integrins) and cytosolic proteins (cAMP, ERK, PI3K) are known to play a role in the downstream signaling mechanisms underpinning galvanotaxis, the initial sensing mechanism for this response is not understood. To investigate the EF sensor, we studied the migration of keratinocytes in a DC EF of 100 V/m, alternating current (AC) EFs of 40 V/m at either 1.6 or 160 Hz, and combinations of DC and AC EFs. In the AC EFs alone, keratinocytes migrated randomly. The 1.6 Hz AC EF combined with the DC EF suppressed the direction of migration but had no effect on speed. In contrast, the 160 Hz AC EF combined with the DC EF did not affect the direction of migration but increased the migration speed compared to the DC EF alone. These results can be understood in terms of an electromechanical transduction model, but not an electrodiffusion/osmosis or a voltage-gated channel model. PMID:22907479

  7. Mechanisms Mediating Enhanced Neutralization Efficacy of Staphylococcal Enterotoxin B by Combinations of Monoclonal Antibodies*

    PubMed Central

    Dutta, Kaushik; Varshney, Avanish K.; Franklin, Matthew C.; Goger, Michael; Wang, Xiaobo; Fries, Bettina C.

    2015-01-01

    Staphylococcal enterotoxin B (SEB) is a superantigen that cross-links the major histocompatibility complex class II and specific V-β chains of the T-cell receptor, thus forming a ternary complex. Developing neutralizing mAb to disrupt the ternary complex and abrogate the resulting toxicity is a major therapeutic challenge because SEB is effective at very low concentrations. We show that combining two SEB-specific mAbs enhances their efficacy, even though one of the two mAbs by itself has no effect on neutralization. Crystallography was employed for fine-mapping conformational epitopes in binary and ternary complexes between SEB and Fab fragments. NMR spectroscopy was used to validate and identify subtle allosteric changes induced by mAbs binding to SEB. The mapping of epitopes established that a combination of different mAbs can enhance efficacy of mAb-mediated protection from SEB induced lethal shock by two different mechanisms: one mAb mixture promoted clearance of the toxin both in vitro and in vivo by FcR-mediated cross-linking and clearance, whereas the other mAb mixture induced subtle allosteric conformational changes in SEB that perturbed formation of the SEB·T-cell receptor·major histocompatibility complex class II trimer. Finally structural information accurately predicted mAb binding to other superantigens that share conformational epitopes with SEB. Fine mapping of conformational epitopes is a powerful tool to establish the mechanism and optimize the action of synergistic mAb combinations. PMID:25572397

  8. Mechanisms mediating enhanced neutralization efficacy of staphylococcal enterotoxin B by combinations of monoclonal antibodies.

    PubMed

    Dutta, Kaushik; Varshney, Avanish K; Franklin, Matthew C; Goger, Michael; Wang, Xiaobo; Fries, Bettina C

    2015-03-13

    Staphylococcal enterotoxin B (SEB) is a superantigen that cross-links the major histocompatibility complex class II and specific V-β chains of the T-cell receptor, thus forming a ternary complex. Developing neutralizing mAb to disrupt the ternary complex and abrogate the resulting toxicity is a major therapeutic challenge because SEB is effective at very low concentrations. We show that combining two SEB-specific mAbs enhances their efficacy, even though one of the two mAbs by itself has no effect on neutralization. Crystallography was employed for fine-mapping conformational epitopes in binary and ternary complexes between SEB and Fab fragments. NMR spectroscopy was used to validate and identify subtle allosteric changes induced by mAbs binding to SEB. The mapping of epitopes established that a combination of different mAbs can enhance efficacy of mAb-mediated protection from SEB induced lethal shock by two different mechanisms: one mAb mixture promoted clearance of the toxin both in vitro and in vivo by FcR-mediated cross-linking and clearance, whereas the other mAb mixture induced subtle allosteric conformational changes in SEB that perturbed formation of the SEB·T-cell receptor·major histocompatibility complex class II trimer. Finally structural information accurately predicted mAb binding to other superantigens that share conformational epitopes with SEB. Fine mapping of conformational epitopes is a powerful tool to establish the mechanism and optimize the action of synergistic mAb combinations. PMID:25572397

  9. Mechanism of Bacterial Inactivation by (+)-Limonene and Its Potential Use in Food Preservation Combined Processes

    PubMed Central

    Espina, Laura; Gelaw, Tilahun K.; de Lamo-Castellví, Sílvia; Pagán, Rafael; García-Gonzalo, Diego

    2013-01-01

    This work explores the bactericidal effect of (+)-limonene, the major constituent of citrus fruits' essential oils, against E. coli. The degree of E. coli BJ4 inactivation achieved by (+)-limonene was influenced by the pH of the treatment medium, being more bactericidal at pH 4.0 than at pH 7.0. Deletion of rpoS and exposure to a sub-lethal heat or an acid shock did not modify E. coli BJ4 resistance to (+)-limonene. However, exposure to a sub-lethal cold shock decreased its resistance to (+)-limonene. Although no sub-lethal injury was detected in the cell envelopes after exposure to (+)-limonene by the selective-plating technique, the uptake of propidium iodide by inactivated E. coli BJ4 cells pointed out these structures as important targets in the mechanism of action. Attenuated Total Reflectance Infrared Microspectroscopy (ATR-IRMS) allowed identification of altered E. coli BJ4 structures after (+)-limonene treatments as a function of the treatment pH: β-sheet proteins at pH 4.0 and phosphodiester bonds at pH 7.0. The increased sensitivity to (+)-limonene observed at pH 4.0 in an E. coli MC4100 lptD4213 mutant with an increased outer membrane permeability along with the identification of altered β-sheet proteins by ATR-IRMS indicated the importance of this structure in the mechanism of action of (+)-limonene. The study of mechanism of inactivation by (+)-limonene led to the design of a synergistic combined process with heat for the inactivation of the pathogen E. coli O157:H7 in fruit juices. These results show the potential of (+)-limonene in food preservation, either acting alone or in combination with lethal heat treatments. PMID:23424676

  10. The Use of the 'Preclosure' Technique for Antegrade Aspiration Thrombectomy with Large Catheters in Acute Limb Ischemia

    SciTech Connect

    Funke, C. Pfiffner, R.; Husmann, M.; Pfammatter, T.

    2013-04-15

    This study was designed to assess retrospectively short- and mid-term outcomes of the use of a suture-mediated closure device to close the antegrade access in patients undergoing percutaneous aspiration thrombectomy with large catheters for acute leg ischemia. Between November 2005 and February 2010, a suture-mediated active closure system (ProGlide{sup Registered-Sign} 6F, Abbott) was placed before arterial sheath (mean 9 F, range 6-12 F) introduction in 101 patients (74 men, 73 %, mean age 70.1 {+-} 12.6 years standard deviation). Data regarding mortality, complications, and factors contributing to vascular complications at the access site was collected for 6 month after the intervention to detect device-related problems. As a coincidence, 77 patients had follow-up visits for a duplex ultrasound. There were a total of 19 vascular complications (19 %) at the puncture site, all of which were of hemorrhagic nature and none of which consisted of vessel occlusion. Two major outcome complications (2 %) occurred. A retroperitoneal hematoma and a serious inguinal bleeding required additive treatment and did not result in permanent sequelae. Nine cases involved death of which eight were not attributable to the closure and one remained unclear. Successful closure was achieved in 95 patients (94 %); additional manual compression was sufficient in the majority of the remaining patients. Numerous factors contributing to vascular complications were encountered. With acceptable short- and mid-term outcomes, the 'preclose' technique can be a reliable option for the closure of a large antegrade femoral access even for patients at a high risk of vascular complications, such as those undergoing aspiration thrombectomy.

  11. Mechanism of red mud combined with Fenton's reagent in sewage sludge conditioning.

    PubMed

    Zhang, Hao; Yang, Jiakuan; Yu, Wenbo; Luo, Sen; Peng, Li; Shen, Xingxing; Shi, Yafei; Zhang, Shinan; Song, Jian; Ye, Nan; Li, Ye; Yang, Changzhu; Liang, Sha

    2014-08-01

    Red mud was evaluated as an alternative skeleton builder combined with Fenton's reagent in sewage sludge conditioning. The results show that red mud combined with Fenton's reagent showed good conditioning capability with the pH of the filtrate close to neutrality, indicating that red mud acted as a neutralizer as well as a skeleton builder when jointly used with Fenton's reagent. Through response surface methodology (RSM), the optimal dosages of Fe(2+), H2O2 and red mud were proposed as 31.9, 33.7 and 275.1 mg/g DS (dry solids), respectively. The mechanism of the composite conditioner could be illuminated as follows: (1) extracellular polymeric substances (EPS), including loosely bound EPS and tightly bound EPS, were degraded into dissolved organics, e.g., proteins and polysaccharides; (2) bound water was released and converted into free water due to the degradation of EPS; and (3) morphology of the conditioned sludge exhibited a porous structure in contrast with the compact structure of raw sludge, and the addition of red mud formed new mineral phases and a rigid lattice structure in sludge, allowing the outflow of free water. Thus, sludge dewatering performance was effectively improved. The economic assessment for a wastewater treatment plant of 370,000 equivalent inhabitants confirms that using red mud conditioning, combined with Fenton's reagent, leads to a saving of approximately 411,000 USD/y or 50.8 USD/t DS comparing with using lime and ordinary Portland cement combined with Fenton's reagent, and approximately 612,000 USD/y or 75.5 USD/t DS comparing with the traditional treatment. PMID:24810740

  12. Mechanically fastened composite laminates subjected to combined bearing-bypass and shear loading

    NASA Technical Reports Server (NTRS)

    Madenci, Erdogan

    1993-01-01

    Bolts and rivets provide a means of load transfer in the construction of aircraft. However, they give rise to stress concentrations and are often the source and location of static and fatigue failures. Furthermore, fastener holes are prone to cracks during take-off and landing. These cracks present the most common origin of structural failures in aircraft. Therefore, accurate determination of the contact stresses associated with such loaded holes in mechanically fastened joints is essential to reliable strength evaluation and failure prediction. As the laminate is subjected to loading, the contact region, whose extent is not known, develops between the fastener and the hole boundary through this contact region, which consists of slip and no-slip zones due to friction. The presence of the unknown contact stress distribution over the contact region between the pin and the composite laminate, material anisotropy, friction between the pin and the laminate, pin-hole clearance, combined bearing-bypass and shear loading, and finite geometry of the laminate result in a complex non-linear problem. In the case of bearing-bypass loading in compression, this non-linear problem is further complicated by the presence of dual contact regions. Previous research concerning the analysis of mechanical joints subjected to combined bearing-bypass and shear loading is non-existent. In the case of bearing-bypass loading only, except for the study conducted by Naik and Crews (1991), others employed the concept of superposition which is not valid for this non-linear problem. Naik and Crews applied a linear finite element analysis with conditions along the pin-hole contact region specified as displacement constraint equations. The major shortcoming of this method is that the variation of the contract region as a function of the applied load should be known a priori. Also, their analysis is limited to symmetric geometry and material systems, and frictionless boundary conditions. Since the

  13. Network bursting dynamics in excitatory cortical neuron cultures results from the combination of different adaptive mechanisms.

    PubMed

    Masquelier, Timothée; Deco, Gustavo

    2013-01-01

    In the brain, synchronization among cells of an assembly is a common phenomenon, and thought to be functionally relevant. Here we used an in vitro experimental model of cell assemblies, cortical cultures, combined with numerical simulations of a spiking neural network (SNN) to investigate how and why spontaneous synchronization occurs. In order to deal with excitation only, we pharmacologically blocked GABAAergic transmission using bicuculline. Synchronous events in cortical cultures tend to involve almost every cell and to display relatively constant durations. We have thus named these "network spikes" (NS). The inter-NS-intervals (INSIs) proved to be a more interesting phenomenon. In most cortical cultures NSs typically come in series or bursts ("bursts of NSs", BNS), with short (~1 s) INSIs and separated by long silent intervals (tens of s), which leads to bimodal INSI distributions. This suggests that a facilitating mechanism is at work, presumably short-term synaptic facilitation, as well as two fatigue mechanisms: one with a short timescale, presumably short-term synaptic depression, and another one with a longer timescale, presumably cellular adaptation. We thus incorporated these three mechanisms into the SNN, which, indeed, produced realistic BNSs. Next, we systematically varied the recurrent excitation for various adaptation timescales. Strong excitability led to frequent, quasi-periodic BNSs (CV~0), and weak excitability led to rare BNSs, approaching a Poisson process (CV~1). Experimental cultures appear to operate within an intermediate weakly-synchronized regime (CV~0.5), with an adaptation timescale in the 2-8 s range, and well described by a Poisson-with-refractory-period model. Taken together, our results demonstrate that the INSI statistics are indeed informative: they allowed us to infer the mechanisms at work, and many parameters that we cannot access experimentally. PMID:24146781

  14. Combined spectroscopic study on the growth mechanism of Diphosphine-stabilized Gold Nanoclusters

    NASA Astrophysics Data System (ADS)

    Bao, Jie; Yang, Lina; Liu, Wei; Huang, Yuanyuan; Huang, Ting; Cao, Yuanjie; Yao, Tao; Sun, Zhihu; Wei, Shiqiang

    2016-05-01

    The formation process of 1,5-Bis(diphenylphosphino) pentane (L5)-protected Au nanocluster through the reduction of precursor Au2L5Cl2 by borane-tert-butylamine (TBAB) is traced by a combination of time-dependent x-ray/UV-vis absorption spectroscopies and mass spectrometry. It is revealed that the initial generation of dual-core basic unit Au4L5 2Cl is a critical step, which allows for a subsequent size-growth process via incorporation of the existing Au monomer (Au(I)-Cl) or Au2L5 to form Au5L5 2, Au8L5 3Cl, Au10L5 4Cl and finally main Au11L5 4Cl2 This work advances one step further toward understanding the mechanism of formation and growth of diphosphine ligands-protected Au NCs.

  15. On combining Thole's induced point dipole model with fixed charge distributions in molecular mechanics force fields.

    PubMed

    Antila, Hanne S; Salonen, Emppu

    2015-04-15

    The Thole induced point dipole model is combined with three different point charge fitting methods, Merz-Kollman (MK), charges from electrostatic potentials using a grid (CHELPG), and restrained electrostatic potential (RESP), and two multipole algorithms, distributed multipole analysis (DMA) and Gaussian multipole model (GMM), which can be used to describe the electrostatic potential (ESP) around molecules in molecular mechanics force fields. This is done to study how the different methods perform when intramolecular polarizability contributions are self-consistently removed from the fitting done in the force field parametrization. It is demonstrated that the polarizable versions of the partial charge models provide a good compromise between accuracy and computational efficiency in describing the ESP of small organic molecules undergoing conformational changes. For the point charge models, the inclusion of polarizability reduced the the average root mean square error of ESP over the test set by 4-10%. PMID:25753482

  16. Antimicrobial Combinations against Pan-Resistant Acinetobacter baumannii Isolates with Different Resistance Mechanisms

    PubMed Central

    Leite, Gleice Cristina; Oliveira, Maura Salaroli; Perdigão-Neto, Lauro Vieira; Rocha, Cristiana Kamia Dias; Guimarães, Thais; Rizek, Camila; Levin, Anna Sara; Costa, Silvia Figueiredo

    2016-01-01

    The study investigated the effect of antibiotic combinations against 20 clinical isolates of A. baumannii (seven colistin-resistant and 13 colistin-susceptible) with different resistance mechanisms. Clinical data, treatment, and patient mortality were evaluated. The following methods were used: MIC, PCRs, and outer membrane protein (OMP) analysis. Synergy was investigated using the checkerboard and time-kill methods. Clonality was evaluated by PFGE. Based on clonality, the whole genome sequence of six A. baumannii isolates was analyzed. All isolates were resistant to meropenem, rifampicin, and fosfomycin. OXA-23 and OXA-143 were the most frequent carbapenemases found. Four isolates showed loss of a 43kDa OMP. The colistin-susceptible isolates belonged to different clones and showed the highest synergistic effect with fosfomycin-amikacin. Among colistin-resistant isolates, the highest synergistic effect was observed with the combinations of colistin-rifampicin followed by colistin-vancomycin. All colistin-resistant isolates harbored blaOXA-23-like and belonged to CC113. Clinical and demographic data were available for 18 of 20 patients. Fourteen received treatment and eight patients died during treatment. The most frequent site of infection was the blood in 13 of 14 patients. Seven patients received vancomycin plus an active drug against A. baumannii; however, mortality did not differ in this group. The synergistic effect was similar for colistin-susceptible isolates of distinct clonal origin presenting with the same resistance mechanism. Overall mortality and death during treatment was high, and despite the high synergism in vitro with vancomycin, death did not differ comparing the use or not of vancomycin plus an active drug against A. baumannii. PMID:26998609

  17. Modulation of oligodendrocyte differentiation and maturation by combined biochemical and mechanical cues

    PubMed Central

    Lourenço, Tânia; Paes de Faria, Joana; Bippes, Christian A.; Maia, João; Lopes-da-Silva, José A.; Relvas, João B.; Grãos, Mário

    2016-01-01

    Extracellular matrix (ECM) proteins play a key role during oligodendrogenesis. While fibronectin (FN) is involved in the maintenance and proliferation of oligodendrocyte progenitor cells (OPCs), merosin (MN) promotes differentiation into oligodendrocytes (OLs). Mechanical properties of the ECM also seem to affect OL differentiation, hence this study aimed to clarify the impact of combined biophysical and biochemical elements during oligodendrocyte differentiation and maturation using synthetic elastic polymeric ECM-like substrates. CG-4 cells presented OPC- or OL-like morphology in response to brain-compliant substrates functionalised with FN or MN, respectively. The expression of the differentiation and maturation markers myelin basic protein — MBP — and proteolipid protein — PLP — (respectively) by primary rat oligodendrocytes was enhanced in presence of MN, but only on brain-compliant conditions, considering the distribution (MBP) or amount (PLP) of the protein. It was also observed that maturation of OLs was attained earlier (by assessing PLP expression) by cells differentiated on MN-functionalised brain-compliant substrates than on standard culture conditions. Moreover, the combination of MN and substrate compliance enhanced the maturation and morphological complexity of OLs. Considering the distinct degrees of stiffness tested ranging within those of the central nervous system, our results indicate that 6.5 kPa is the most suitable rigidity for oligodendrocyte differentiation. PMID:26879561

  18. Combined effects of zooplankton grazing and dispersal on the diversity and assembly mechanisms of bacterial metacommunities.

    PubMed

    Berga, Mercè; Östman, Örjan; Lindström, Eva S; Langenheder, Silke

    2015-07-01

    Effects of dispersal and the presence of predators on diversity, assembly and functioning of bacterial communities are well studied in isolation. In reality, however, dispersal and trophic interactions act simultaneously and can therefore have combined effects, which are poorly investigated. We performed an experiment with aquatic metacommunities consisting of three environmentally different patches and manipulated dispersal rates among them as well as the presence or absence of the keystone species Daphnia magna. Daphnia magna reduced both local and regional diversity, whereas dispersal increased local diversity but decreased beta-diversity having no net effect on regional diversity. Dispersal modified the assembly mechanisms of bacterial communities by increasing the degree of determinism. Additionally, the combination of the D. magna and dispersal increased the importance of deterministic processes, presumably because predator-tolerant taxa were spread in the metacommunity via dispersal. Moreover, the presence of D. magna affected community composition, increased community respiration rates but did not affect bacterial production or abundance, whereas dispersal slightly increased bacterial production. In conclusion, our study suggests that predation by a keystone species such as D. magna and dispersal additively influence bacterial diversity, assembly processes and ecosystem functioning. PMID:25367396

  19. Analysis of Curved Sandwich Panels Subjected to Combined Temperature Gradient and Mechanical Loads

    NASA Technical Reports Server (NTRS)

    Noor, Ahmed K.; Starnes, James H., Jr.; Peters, Jeanne M.

    1998-01-01

    The results of a detailed study of the nonlinear response of curved sandwich panels with composite face sheets and subjected to a temperature gradient through-the-thickness combined with mechanical loadings are presented. The analysis is based on a first-order shear-deformation Sanders-Budiansky type theory with the effects of large displacements, moderate rotations, transverse shear deformation and laminated anisotropic material behavior included. A mixed formulation is used with the fundamental unknowns consisting of the generalized displacements and the stress resultants of the panel. The nonlinear displacements, strain energy, principal strains, transverse shear stresses, transverse shear strain energy density, and their hierarchical sensitivity coefficients are evaluated. The hierarchical sensitivity coefficients measure the sensitivity of the nonlinear response to variations in the panel parameters, the effective properties of the face sheet layers and the core, and the micromechanical parameters. Numerical results are presented for cylindrical panels subjected to combined pressure loading, edge shortening or extension, edge shear and a temperature gradient through the thickness. The results show the effects of variations in the loading and the panel aspect ratio, on the nonlinear response and its sensitivity to changes in the various panel, effective layer and micromechanical parameters.

  20. Structural and Mechanical Properties of Amyloid Beta Fibrils: A Combined Experimental and Theoretical Approach.

    PubMed

    Paul, Thomas J; Hoffmann, Zachary; Wang, Congzhou; Shanmugasundaram, Maruda; DeJoannis, Jason; Shekhtman, Alexander; Lednev, Igor K; Yadavalli, Vamsi K; Prabhakar, Rajeev

    2016-07-21

    In this combined experimental (deep ultraviolet resonance Raman (DUVRR) spectroscopy and atomic force microscopy (AFM)) and theoretical (molecular dynamics (MD) simulations and stress-strain (SS)) study, the structural and mechanical properties of amyloid beta (Aβ40) fibrils have been investigated. The DUVRR spectroscopy and AFM experiments confirmed the formation of linear, unbranched and β-sheet rich fibrils. The fibrils (Aβ40)n, formed using n monomers, were equilibrated using all-atom MD simulations. The structural properties such as β-sheet character, twist, interstrand distance, and periodicity of these fibrils were found to be in agreement with experimental measurements. Furthermore, Young's modulus (Y) = 4.2 GPa computed using SS calculations was supported by measured values of 1.79 ± 0.41 and 3.2 ± 0.8 GPa provided by two separate AFM experiments. These results revealed size dependence of structural and material properties of amyloid fibrils and show the utility of such combined experimental and theoretical studies in the design of precisely engineered biomaterials. PMID:27387853

  1. Investigation of the response of microstructures under the combined effect of mechanical shock and electrostatic forces

    PubMed Central

    Younis, Mohammad I; Miles, Ronald; Jordy, Daniel

    2009-01-01

    There is strong experimental evidence for the existence of strange modes of failure of microelectromechanical systems (MEMS) devices under mechanical shock and impact. Such failures have not been explained with conventional models of MEMS. These failures are characterized by overlaps between moving microstructures and stationary electrodes, which cause electrical shorts. This work presents modeling and simulation of MEMS devices under the combination of shock loads and electrostatic actuation, which sheds light on the influence of these forces on the pull-in instability. Our results indicate that the reported strange failures can be attributed to early dynamic pull-in instability. The results show that the combination of a shock load and an electrostatic actuation makes the instability threshold much lower than the threshold predicted, considering the effect of shock alone or electrostatic actuation alone. In this work, a single-degree-of-freedom model is utilized to investigate the effect of the shock–electrostatic interaction on the response of MEMS devices. Then, a reduced-order model is used to demonstrate the effect of this interaction on MEMS devices employing cantilever and clamped–clamped microbeams. The results of the reduced-order model are verified by comparing with finite-element predictions. It is shown that the shock–electrostatic interaction can be used to design smart MEMS switches triggered at a predetermined level of shock and acceleration. PMID:21720492

  2. Bacterial radiosensitization by using radiation processing in combination with essential oil: Mechanism of action

    NASA Astrophysics Data System (ADS)

    Lacroix, Monique; Caillet, Stéphane; Shareck, Francois

    2009-07-01

    Spice extracts under the form of essential oils were tested for their efficiency to increase the relative radiosensitivity of Listeria monocytogenes and Escherichia coli O157H7 in culture media. The two pathogens were treated by gamma-irradiation alone or in combination with oregano essential oil to evaluate their mechanism of action. The membrane murein composition, and the intracellular and extracellular concentration of ATP was determined. The bacterial strains were treated with two irradiation doses: 1.2 kGy to induce cell damage and 3.5 kGy to cause cell death for L. monocytogenes. A dose of 0.4 kGy to induce cell damages, 1.1 kGy to obtain viable but nonculturable (VBNC) state and 1.3 kGy to obtain a lethal dose was also applied on E. coli O157H7. Oregano essential oil was used at 0.020% and 0.025% (w/v), which is the minimum inhibitory concentration (MIC) for L. monocytogenes. For E. coli O157H7, a concentration of 0.006% and 0.025% (w/v) which is the minimum inhibitory concentration was applied. The use of essential oils in combination with irradiation has permitted an increase of the bacterial radiosensitization by more than 3.1 times. All treatments had also a significant effect ( p⩽0.05) on the murein composition, although some muropeptides did not seem to be affected by the treatment. Each treatment influenced differently the relative percentage and number of muropeptides. There was a significant ( p⩽0.05) correlation between the reduction of intracellular ATP and increase in extracellular ATP following treatment of the cells with oregano oil. The reduction of intracellular ATP was even more important when essential oil was combined with irradiation, but irradiation of L. monocytogenes alone induced a significant decrease ( p⩽0.05) of the internal ATP without affecting the external ATP.

  3. Respiratory mechanics measured by forced oscillation technique in combined pulmonary fibrosis and emphysema.

    PubMed

    Mori, Kazutaka; Shirai, Toshihiro; Mikamo, Masashi; Shishido, Yuichiro; Akita, Takefumi; Morita, Satoru; Asada, Kazuhiro; Fujii, Masato; Hozumi, Hironao; Suda, Takafumi; Chida, Kingo

    2013-01-15

    The coexistence of emphysema and pulmonary fibrosis is known as combined pulmonary fibrosis and emphysema (CPFE). The aim of this study was to compare the lung mechanics measured by multi-frequency forced oscillation technique (FOT) among patients with CPFE, interstitial pneumonia (IP), and chronic obstructive pulmonary disease (COPD). FOT and pulmonary function tests were performed in 41 patients with CPFE, 47 with IP, and 86 with COPD. Whole-breath resistance at 20 Hz was significantly lower in patients with CPFE than in those with IP or COPD, irrespective of the severity of airflow limitation. Within-breath analyses of resistance revealed no difference among the 3 groups; however, the difference between inspiratory and expiratory phases of reactance at 5 Hz, which reflects expiratory flow limitation, in patients with CPFE was significantly higher than in those with IP and lower than in those with COPD. In conclusion, both emphysema and fibrosis affect lung mechanics in CPFE, leading to different findings from IP or COPD alone. PMID:23117106

  4. Combined adsorption and oxidation mechanisms of hydrogen sulfide on granulated coal ash.

    PubMed

    Asaoka, Satoshi; Hayakawa, Shinjiro; Kim, Kyung-Hoi; Takeda, Kazuhiko; Katayama, Misaki; Yamamoto, Tamiji

    2012-07-01

    Hydrogen sulfide is highly toxic to benthic organisms and may cause blue tide with depletion of dissolved oxygen in water column due to its oxidation. The purpose of this study is to reveal the combined adsorption and oxidation mechanisms of hydrogen sulfide on granulated coal ash that is a byproduct from coal electric power stations to apply the material as an adsorbent for hydrogen sulfide in natural fields. Sulfur species were identified in both liquid and solid phases to discuss removal mechanisms of the hydrogen sulfide with the granulated coal ash. Batch experiments revealed that hydrogen sulfide decreased significantly by addition of the granulated coal ash and simultaneously the sulfate ion concentration increased. X-ray absorption fine structure analyses showed hydrogen sulfide was adsorbed onto the granulated coal ash and successively oxidized by manganese oxide (III) contained in the material. The oxidation reaction of hydrogen sulfide was coupling with reduction of manganese oxide. On the other hand, iron containing in the granulated coal ash was not involved in hydrogen sulfide oxidation, because the major species of iron in the granulated coal ash was ferrous iron that is not easily reduced by hydrogen sulfide. PMID:22487226

  5. Combining ibuprofen sodium with cellulosic polymers: a deep dive into mechanisms of prolonged supersaturation.

    PubMed

    Terebetski, Jenna L; Michniak-Kohn, Bozena

    2014-11-20

    The combination of a highly soluble salt form of a drug with a polymeric precipitation inhibitor has the potential to prolong drug supersaturation even following salt disproportionation. In this study, dissolution profiles of ibuprofen sodium in the presence of various cellulosic polymers, including hydroxypropyl methylcellulose (HPMC), methylcellulose (MC), and hydroxypropyl cellulose (HPC), were examined in order to assess degree and duration of supersaturation. In addition, the roles that the polymers played in altering drug solubility, media viscosity, physical form, and particle morphology were also assessed. A deep dive into the mechanisms of supersaturation revealed that intermolecular hydrogen bonding between ibuprofen and HPMC was driving supersaturation through nucleation inhibition and crystal growth modification. Polymer viscosity was proposed as the primary factor prolonging supersaturation of ibuprofen in the presence of MC, while mechanisms other than hydrogen bonding were likely to be attributed to supersaturation with the most hydrophobic polymer evaluated, HPC. Overall, the study suggested that induction of intermolecular interactions between ibuprofen and HPMC were more effective at inhibiting nucleation and maintaining prolonged supersaturation than physical modulation of solution properties, such as viscosity. PMID:25219860

  6. [Mechanism of action of combined extremely weak magnetic field on aqueous solution of amino acid].

    PubMed

    Zhadin, M N; Bakharev, B V; Bobkova, N V

    2014-01-01

    The fundamental physical mechanisms of resonance action of an extremely weak (40 nT) alternating magnetic field at the cyclotron frequency combined with a weak (40 μT) static magnetic field, on living systems are analyzed in the present work. The experimental effects of such sort of magnetic fields were described in different papers: the very narrow resonant peaks in electrical conductivity of the aqueous solutions in the in vitro experiments and the biomedical in vivo effects on living animals of magnetic fields with frequencies tuned to some amino acids. The existing experimental in vitro data had a good repeatability in different laboratories and countries. Unfortunately, for free ions such sort of effects are absolutely impossible because the dimensions of an ion rotation radius should be measured by meters at room temperature and at very low static magnetic fields used in all the above experiments. Even for bound ions these effects should be also absolutely impossible from the positions of classic physics because of rather high viscosity of biological liquid media (blood plasma, cerebrospinal liquid, cytoplasm). Only modern quantum electrodynamics of condensed media opens the new ways for solving these problems. The proposed article is devoted to analysis of quantum mechanisms of these effects. PMID:25707253

  7. Characterization of the mechanical properties of skin by inverse analysis combined with the indentation test.

    PubMed

    Delalleau, Alexandre; Josse, Gwendal; Lagarde, Jean-Michel; Zahouani, Hassan; Bergheau, Jean-Michel

    2006-01-01

    This study proposes a new method to determine the mechanical properties of human skin by the use of the indentation test [Pailler-Mattei, 2004. Caractérisation mécanique et tribologique de la peau humaine in vivo, Ph.D. Thesis, ECL-no. 2004-31; Pailler-Mattei, Zahouani, 2004. Journal of Adhesion Science and Technology 18, 1739-1758]. The principle of the measurements consists in applying an in vivo compressive stress [Zhang et al., 1994. Proceedings of the Institution of Mechanical Engineers 208, 217-222; Bosboom et al., 2001. Journal of Biomechanics 34, 1365-1368; Oomens et al., 1984. Selected Proceedings of Meetings of European Society of Biomechanics, pp. 227-232; Oomens et al., 1987. Journal of Biomechanics 20(9), 877-885] on the skin tissue of an individual's forearm. These measurements show an increase in the normal contact force as a function of the indentation depth. The interpretation of such results usually requires a long and tedious phenomenological study. We propose a new method to determine the mechanical parameters which control the response of skin tissue. This method is threefold: experimental, numerical, and comparative. It consists combining experimental results with a numerical finite elements model in order to find out the required parameters. This process uses a scheme of extended Kalman filters (EKF) [Gu et al., 2003. Materials Science and Engineering A345, 223-233; Nakamura et al., 2000. Acta Mater 48, 4293-4306; Leustean and Rosu, 2003. Certifying Kalman filters. RIACS Technical Report 03.02, 27pp. http://gureni.cs.uiuc.edu/~grosu/download/luta + leo.pdf; Welch and Bishop, An introduction to Kalman filter, University of North Carolina at Chapel Hill, 16p. http://www.cs.unc.edu/~welch/kalman/]. The first results presented in this study correspond to a simplified numerical modeling of the global system. The skin is assumed to be a semi-infinite layer with an isotropic linear elastic mechanical behavior [Zhang et al., 1994. Proceedings of

  8. Combined exposure to big endothelin-1 and mechanical loading in bovine sternal cores promotes osteogenesis.

    PubMed

    Meyer, Luisa A; Johnson, Michael G; Cullen, Diane M; Vivanco, Juan F; Blank, Robert D; Ploeg, Heidi-Lynn; Smith, Everett L

    2016-04-01

    , 19 and 23. The data suggest that combined exposure to big ET1 and mechanical loading results in increased osteogenesis as measured in biomechanical, histomorphometric and biochemical responses. PMID:26855374

  9. Modelling late-orogenic collapse: A combined thermo-mechanical and chemical approach

    NASA Astrophysics Data System (ADS)

    Kaislaniemi, Lars; van Hunen, Jeroen; Bouilhol, Pierre; Allen, Mark B.

    2015-04-01

    We have explored the geodynamics of late-orogenic collapse via numerical models to study the effects of lithospheric thinning on mantle and lower crustal melting. Our goal is to better understand the formation of migmatitic terrains and the role of mantle melt in generating the geochemical spectrum of granitoids observed during the lithospheric re-equilibration. These numerical models combine finite elements thermo-mechanical modelling coupled with a Gibbs free energy minimization strategy that allow tracking melt composition. Our models assume a "jelly sandwich" strength profile of the lithosphere and the existence of sub-lithospheric small-scale convection caused by the increased post-subductional mantle water contents. The models take into account the viscosity lowering effects of water and partial melts, and dynamically adjust the composition of the mantle and crustal residue after extraction of partial melts. Effects of mantle magmas underplating the crust have been studied. Using Gibbs energy minimization allows for precise tracking of the crustal melt composition (major oxides) as a function of time and location. Our results show that minor lithosphere thinning causing low degree lower crustal melting can grow into large scale lithospheric mantle delamination via a positive feedback mechanism between the thinning of the lithosphere and the strength weakening by the partial melts in the lower crust. The melt percolation threshold (percentage of melt at which melts are extracted) affects this feedback mechanism: Extracting melts disable the weakening effect by the partial melts, but also removes most of the water in the source, leaving behind a depleted high viscosity residue layer. For this reason we also found that underplating of mantle melts below the crust initially enhances the positive feedback in lithosphere thinning, but overall has no major - or has even negative - impact on the lithosphere thinning and crustal melting. If asthenospheric melts are

  10. Mechanisms of resistance to combinations of vincristine, etoposide and doxorubicin in Chinese hamster ovary cells.

    PubMed Central

    Souès, S.; Laval, F.; Charcosset, J. Y.

    1995-01-01

    We have isolated from Chinese hamster ovary cells, 30 sublines resistant to vincristine, doxorubicin or etoposide and 43 sublines evading treatment with a pair of these drugs. Isolated in one step and under low selective pressure, sublines were 3- to 25-fold more resistant to their selecting drug(s) than the parental cells. Possible P-glycoprotein-associated multidrug resistance was investigated through pgp gene copy number and mRNA expression level. DNA topoisomerase II alteration was evaluated from the ability of nuclear extracts to form cleavable complexes. Vincristine (all sublines) and doxorubicin (6/7 sublines) preferentially selected for pgp gene amplification and mRNA overexpression, whereas selection with etoposide resulted in a decrease of cleavable complex formation in 11 out of 13 sublines. A common pgp gene-mediated resistance was found in the 13 doxorubicin plus vincristine-selected sublines, whereas all but one of the 12 etoposide plus vincristine-resistant sublines displayed both pgp mRNA overexpression and decreased ability to form cleavable complexes. Among the 18 doxorubicin plus etoposide selected sublines, five exhibited a decreased ability to form cleavable complexes only, six exhibited pgp mRNA overexpression only and six exhibited both alterations. Overall, drug resistance could not be attributed to either mechanism in three of the 73 sublines. We conclude that under low selective pressure it is possible to find a combination of drugs which require simultaneous selection of more than one resistance mechanism; such cells emerge with very low frequency. Images Figure 1 Figure 2 Figure 4 Figure 5 Figure 6 PMID:7880729

  11. Opioid Mechanism Involvement in the Synergism Produced by the Combination of Diclofenac and Caffeine in the Formalin Model

    PubMed Central

    Flores-Ramos, José María; Díaz-Reval, M. Irene

    2013-01-01

    Analgesics can be administered in combination with caffeine for improved analgesic effectiveness in a process known as synergism. The mechanisms by which these combinations produce synergism are not yet fully understood. The aim of this study was to analyze whether the administration of diclofenac combined with caffeine produced antinociceptive synergism and whether opioid mechanisms played a role in this event. The formalin model was used to evaluate the antinociception produced by the oral administration of diclofenac, caffeine, or their combination. Opioid involvement was analyzed through intracerebroventricular (i.c.v.) administration of naloxone followed by the oral administration of the study drugs. Diclofenac presented a dose-dependent effect, with a mean effective dose (ED50) of 6.7 mg/kg. Caffeine presented an analgesic effect with a 17–36% range. The combination of subeffective doses of each of the two drugs presented the greatest synergism with an effect of 57.7 ± 5.6%. The maximal antinociceptive effect was obtained with the combination of 10.0 mg/kg diclofenac and 1.0 mg/kg of caffeine, with an effect of 76.7 ± 5.6%. The i.c.v. administration of naloxone inhibited the effect of diclofenac, both separately and combined. In conclusion, caffeine produces antinociceptive synergism when administered in combination with diclofenac, and this synergism is partially mediated by opioid mechanisms at the central level. PMID:27335871

  12. Mechanical behavior of twinned SiC nanowires under combined tension-torsion and compression-torsion strain

    SciTech Connect

    Li, Zhijie; Wang, Shengjie; Wang, Zhiguo; Zu, Xiaotao T.; Gao, Fei; Weber, William J.

    2010-07-01

    The mechanical behavior of twinned silicon carbide (SiC) nanowires under combined tension-torsion and compression-torsion is investigated using molecular dynamics simulations with an empirical potential. The simulation results show that both the tensile failure stress and buckling stress decrease under combined tension-torsional and combined compression-torsional strain, and they decrease with increasing torsional rate under combined loading. The torsion rate has no effect on the elastic properties of the twinned SiC nanowires. The collapse of the twinned nanowires takes place in a twin stacking fault of the nanowires.

  13. Combined decellularisation and dehydration improves the mechanical properties of tissue-engineered sinews

    PubMed Central

    Lebled, Claire; Grover, Liam M

    2014-01-01

    Novel sources of replacement sinews are needed to repair damaged tissue after injury. The current methods of repair ultilise autografts, allografts or xenografts, although each method has distinct disadvantages that limit their success. Decellularisation of harvested tissues has been previously investigated for sinew repair with the long-term aim of repopulating the structure with autologous cells. Although this procedure shows promise, the demand for donor scaffolds will always outweigh supply. Here, we report the fabrication of fibrin-based tissue-engineered sinews, which can be decellularised, dehydrated and stored. The sinews may then be rehydrated and repopulated with an autologous cell population. In addition to enabling production of patient-specific implants, interestingly, the process of combined decellularisation, dehydration and rehydration enhanced the mechanical properties of the sinew. The treated sinews exhibited a 2.6-fold increase in maximum load and 8-fold increase in ultimate tensile strength when compared with the control group (p < 0.05 in both cases). PMID:24904729

  14. Enhancing combined biological nitrogen and phosphorus removal from wastewater by applying mechanically disintegrated excess sludge.

    PubMed

    Zubrowska-Sudol, Monika; Walczak, Justyna

    2015-06-01

    The goal of the study was to evaluate the possibility of applying disintegrated excess sludge as a source of organic carbon to enhance biological nitrogen and phosphorus removal. The experiment, performed in a sequencing batch reactor, consisted of two two-month series, without and with applying mechanically disintegrated excess sludge, respectively. The effects on carbon, nitrogen and phosphorus removal were observed. It was shown that the method allows enhancement of combined nitrogen and phosphorus removal. After using disintegrated sludge, denitrification effectiveness increased from 49.2 ± 6.8% to 76.2 ± 2.3%, which resulted in a decline in the NOx-N concentration in the effluent from the SBR by an average of 21.4 mg NOx-N/L. Effectiveness of biological phosphorus removal increased from 28.1 ± 11.3% to 96.2 ± 2.5%, thus resulting in a drop in the [Formula: see text] concentration in the effluent by, on average, 6.05 mg PO4(3-)-P/L. The application of disintegrated sludge did not deteriorate effluent quality in terms of COD and NH4(+)-N. The concentration of NH4(+)-N in both series averaged 0.16 ± 0.11 mg NH4(+)-N/L, and the concentration of COD was 15.36 ± 3.54 mg O2/L. PMID:25776916

  15. Heat flux reduction mechanism induced by a combinational opposing jet and cavity concept in supersonic flows

    NASA Astrophysics Data System (ADS)

    Huang, Wei; Jiang, Yan-ping; Yan, Li; Liu, Jun

    2016-04-01

    The thermal protection on the surface of hypersonic vehicles attracts an increasing attention worldwide, especially when the vehicle enters the atmosphere at high speed. In the current study, the Reynolds-averaged Navier-Stokes (RANS) equations coupled with the Menter's shear stress transport (SST) model have been employed to investigate the heat flux reduction mechanism induced by the variations of the cavity configuration, the jet pressure ratio and the injectant molecular weight in the combinational opposing jet and cavity concept. The length of the cavity is set to be 6 mm, 8 mm and 10 mm in order to make sure that the cavity configuration is the "open" cavity, and the jet pressure ratio is set to be 0.4, 0.6 and 0.8 in order to make sure that the flow field is steady. The injectant is set to be nitrogen and helium. The obtained results show that the aft angle of the cavity only has a slight impact on the heat flux reduction, and the heat flux peak decreases with the decrease of the length of the cavity. The design of the thermal protection system for the hypersonic blunt body is a multi-objective design exploration problem, and the heat flux distribution depends on the jet pressure ratio, the aft wall of the cavity and the injectant molecular weight. The heat flux peak decreases with the increase of the jet pressure ratio when the aft angle of the cavity is large enough, and this value is 45°.

  16. Mechanism-based corrector combination restores ΔF508-CFTR folding and function.

    PubMed

    Okiyoneda, Tsukasa; Veit, Guido; Dekkers, Johanna F; Bagdany, Miklos; Soya, Naoto; Xu, Haijin; Roldan, Ariel; Verkman, Alan S; Kurth, Mark; Simon, Agnes; Hegedus, Tamas; Beekman, Jeffrey M; Lukacs, Gergely L

    2013-07-01

    The most common cystic fibrosis mutation, ΔF508 in nucleotide binding domain 1 (NBD1), impairs cystic fibrosis transmembrane conductance regulator (CFTR)-coupled domain folding, plasma membrane expression, function and stability. VX-809, a promising investigational corrector of ΔF508-CFTR misprocessing, has limited clinical benefit and an incompletely understood mechanism, hampering drug development. Given the effect of second-site suppressor mutations, robust ΔF508-CFTR correction most likely requires stabilization of NBD1 energetics and the interface between membrane-spanning domains (MSDs) and NBD1, which are both established primary conformational defects. Here we elucidate the molecular targets of available correctors: class I stabilizes the NBD1-MSD1 and NBD1-MSD2 interfaces, and class II targets NBD2. Only chemical chaperones, surrogates of class III correctors, stabilize human ΔF508-NBD1. Although VX-809 can correct missense mutations primarily destabilizing the NBD1-MSD1/2 interface, functional plasma membrane expression of ΔF508-CFTR also requires compounds that counteract the NBD1 and NBD2 stability defects in cystic fibrosis bronchial epithelial cells and intestinal organoids. Thus, the combination of structure-guided correctors represents an effective approach for cystic fibrosis therapy. PMID:23666117

  17. Synaptic mechanisms shaping delay-tuned combination-sensitivity in the auditory thalamus of mustached bats.

    PubMed

    Butman, John A; Suga, Nobuo

    2016-01-01

    For the processing of target-distance information, delay-tuned auditory neurons of the mustached bat show facilitative responses to a combination of signal elements of a biosonar pulse-echo pair with a specific echo delay. They are initially produced in the inferior colliculus by facilitative responses based on the coincidence of the rebound response following glycinergic inhibition to the first harmonic of the pulse and a short-latency response to the 2nd-4th harmonics of its echo. Here, we report that further facilitative responses to pulse-echo pairs of thalamic delay-tuned neurons are mediated by glutamate receptors (NMDA and non-NMDA receptors), and that GABAergic inhibition shortens the duration of facilitative responses mediated by NMDA-receptors, without changing the delay tuning of thalamic delay-tuned neurons. Different from collicular delay-tuned neurons, thalamic ones respond much more to pulse-echo pairs than individual signal elements. The neural mechanisms involved in shaping thalamic delay-tuning support a model of hierarchical signal processing in the auditory system. PMID:26519094

  18. The heterotrophic-combined-with-autotrophic denitrification process: performance and interaction mechanisms.

    PubMed

    Xu, Guihua; Feng, Cuijie; Fang, Fang; Chen, Shaohua; Xu, Yuanjian; Wang, Xingzu

    2015-01-01

    In this work, the interaction mechanisms between an autotrophic denitrification (AD) and heterotrophic denitrification (HD) process in a heterotrophic-autotrophic denitrification (HAD) system were investigated, and the performance of the HAD system under different S/Ac(-) molar ratios was also evaluated. The results demonstrated that the heterotrophic-combined-with-autotrophic denitrification process is a promising technology which can remove chemical oxygen demand (COD), sulfide and nitrate simultaneously. The reduction rate of NO(3)(-) to NO(2)(-) by the HD process was much faster than that of reducing NO(2)(-) to N₂, while the reduction rate of NO(3)(-) to NO(2)(-) by the AD process was slower than that of NO(2)(-) to N₂. Therefore, the AD process could use the surplus NO(2)(-) produced by the HD process. This could alleviate the NO(2)(-)-N accumulation and increase the denitrification rate. In addition, the inhibition effects of acetate on AD bacteria and sulfide on HD were observed, and the inhibition was compensated by the promotion effects on NO(2)(-). Therefore, the processes of AD and HD seem to react in parallel, without disturbing each other, in our HAD system. PMID:25909732

  19. Electrostatic vibration energy harvester with combined effect of electrical nonlinearities and mechanical impact

    NASA Astrophysics Data System (ADS)

    Basset, P.; Galayko, D.; Cottone, F.; Guillemet, R.; Blokhina, E.; Marty, F.; Bourouina, T.

    2014-03-01

    This paper presents an advanced study including the design, characterization and theoretical analysis of a capacitive vibration energy harvester. Although based on a resonant electromechanical device, it is intended for operation in a wide frequency band due to the combination of stop-end effects and a strong biasing electrical field. The electrostatic transducer has an interdigited comb geometry with in-plane motion, and is obtained through a simple batch process using two masks. A continuous conditioning circuit is used for the characterization of the transducer. A nonlinear model of the coupled system ‘transduce-conditioning circuit’ is presented and analyzed employing two different semi-analytical techniques together with precise numerical modelling. Experimental results are in good agreement with results obtained from numerical modelling. With the 1 g amplitude of harmonic external acceleration at atmospheric pressure, the system transducer-conditioning circuit has a half-power bandwidth of more than 30% and converts more than 2 µW of the power of input mechanical vibrations over the range of 140 and 160 Hz. The harvester has also been characterized under stochastic noise-like input vibrations.

  20. Mechanism-based corrector combination restores ΔF508-CFTR folding and function

    PubMed Central

    Okiyoneda, Tsukasa; Veit, Guido; Dekkers, Johanna F.; Bagdany, Miklos; Soya, Naoto; Xu, Haijin; Roldan, Ariel; Verkman, Alan S.; Kurth, Mark; Simon, Agnes; Hegedus, Tamas; Beekman, Jeffrey M.; Lukacs, Gergely L.

    2013-01-01

    The most common cystic fibrosis (CF) mutation, ΔF508 in the nucleotide binding domain-1 (NBD1), impairs CFTR coupled-domain folding, plasma membrane (PM) expression, function and stability. VX-809, a promising investigational corrector of ΔF508-CFTR misprocessing, has limited clinical benefit and incompletely understood mechanism, hampering drug development. Based on the effect of second site suppressor mutations, robust ΔF508-CFTR correction likely requires stabilization of NBD1 and the membrane spanning domains (MSDs)-NBD1 interface, both established primary conformational defects. Here, we elucidated the molecular targets of available correctors; class-I stabilizes the NBD1-MSD1/2 interface, class-II targets NBD2, and only chemical chaperones, surrogates of class-III correctors, stabilize the human ΔF508-NBD1. While VX-809 can correct missense mutations primarily destabilizing the NBD1-MSD1/2 interface, functional PM expression of ΔF508-CFTR also requires compounds that counteract the NBD1 and NBD2 stability defects in CF bronchial epithelial cells and intestinal organoids. Thus, structure-guided corrector combination represents an effective approach for CF therapy. PMID:23666117

  1. Unravelling the mechanism of glycerol hydrogenolysis over rhodium catalyst through combined experimental-theoretical investigations.

    PubMed

    Auneau, Florian; Michel, Carine; Delbecq, Françoise; Pinel, Catherine; Sautet, Philippe

    2011-12-01

    We report herein a detailed and accurate study of the mechanism of rhodium-catalysed conversion of glycerol into 1,2-propanediol and lactic acid. The first step of the reaction is particularly debated, as it can be either dehydration or dehydrogenation. It is expected that these elementary reactions can be influenced by pH variations and by the nature of the gas phase. These parameters were consequently investigated experimentally. On the other hand, there was a lack of knowledge about the behaviour of glycerol at the surface of the metallic catalyst. A theoretical approach on a model Rh(111) surface was thus implemented in the framework of density functional theory (DFT) to describe the above-mentioned elementary reactions and to calculate the corresponding transition states. The combination of experiment and theory shows that the dehydrogenation into glyceraldehyde is the first step for the glycerol transformation on the Rh/C catalyst in basic media under He or H(2) atmosphere. PMID:22069214

  2. The neural dynamic mechanisms of asymmetric switch costs in a combined Stroop-task-switching paradigm.

    PubMed

    Wu, Shanshan; Hitchman, Glenn; Tan, Jinfeng; Zhao, Yuanfang; Tang, Dandan; Wang, Lijun; Chen, Antao

    2015-01-01

    Switch costs have been constantly found asymmetrical when switching between two tasks of unequal dominance. We used a combined Stroop-task-switching paradigm and recorded electroencephalographic (EEG) signals to explore the neural mechanism underlying the phenomenon of asymmetrical switch costs. The results revealed that a fronto-central N2 component demonstrated greater negativity in word switch (cW) trials relative to word repeat (wW) trials, and both First P3 and P3b components over the parieto-central region exhibited greater positivity in color switch (wC) trials relative to color repeat (cC) trials, whereas a contrasting switch-related fronto-central SP effect was found to have an opposite pattern for each task. Moreover, the time-frequency analysis showed a right-frontal lower alpha band (9-11 Hz) modulation in the word task, whereas a fronto-central upper alpha band (11-13 Hz) modulation was exclusively found in the color task. These results provide evidence for dissociable neural processes, which are related to inhibitory control and endogenous control, contributing to the generation of asymmetrical switch costs. PMID:25989933

  3. MECHANISMS IN ENDOCRINOLOGY: An update in the genetic aetiologies of combined pituitary hormone deficiency.

    PubMed

    Castinetti, Frederic; Reynaud, Rachel; Saveanu, Alexandru; Jullien, Nicolas; Quentien, Marie Helene; Rochette, Claire; Barlier, Anne; Enjalbert, Alain; Brue, Thierry

    2016-06-01

    Over the last 5 years, new actors involved in the pathogenesis of combined pituitary hormone deficiency in humans have been reported: they included a member of the immunoglobulin superfamily glycoprotein and ciliary G protein-coupled receptors, as well as new transcription factors and signalling molecules. New modes of inheritance for alterations of genes encoding transcription factors have also been described. Finally, actors known to be involved in a very specific phenotype (hypogonadotroph hypogonadism for instance) have been identified in a wider range of phenotypes. These data thus suggest that new mechanisms could explain the low rate of aetiological identification in this heterogeneous group of diseases. Taking into account the fact that several reviews have been published in recent years on classical aetiologies of CPHD such as mutations of POU1F1 or PROP1, we focused the present overview on the data published in the last 5 years, to provide the reader with an updated review on this rapidly evolving field of knowledge. PMID:26733480

  4. Combination of fluid and solid mechanical stresses contribute to cell death and detachment in a microfluidic alveolar model.

    PubMed

    Douville, Nicholas J; Zamankhan, Parsa; Tung, Yi-Chung; Li, Ran; Vaughan, Benjamin L; Tai, Cheng-Feng; White, Joshua; Christensen, Paul J; Grotberg, James B; Takayama, Shuichi

    2011-02-21

    Studies using this micro-system demonstrated significant morphological differences between alveolar epithelial cells (transformed human alveolar epithelial cell line, A549 and primary murine alveolar epithelial cells, AECs) exposed to combination of solid mechanical and surface-tension stresses (cyclic propagation of air-liquid interface and wall stretch) compared to cell populations exposed solely to cyclic stretch. We have also measured significant differences in both cell death and cell detachment rates in cell monolayers experiencing combination of stresses. This research describes new tools for studying the combined effects of fluid mechanical and solid mechanical stress on alveolar cells. It also highlights the role that surface tension forces may play in the development of clinical pathology, especially under conditions of surfactant dysfunction. The results support the need for further research and improved understanding on techniques to reduce and eliminate fluid stresses in clinical settings. PMID:21152526

  5. [Procedural aspects in primary PCI: arterial access, stent selection, thrombectomy and treatment of non-culprit lesions].

    PubMed

    Boeder, N F; Hamm, C W; Nef, H M

    2014-09-01

    Acute myocardial infarction was one of the most common causes of death in Germany in 2011. According to the guidelines of the European Society for Cardiology, systemic fibrinolysis and primary percutaneous coronary intervention (PCI) are the methods of choice for acute treatment. Primary PCI should be given priority due to its superiority. The transradial access should be preferred due to the lower bleeding complication rate. In the selection of stents the new generation of drug-eluting stents (DES) are superior to the first generation of bare metal stents (BMS). It has now been demonstrated that the incident rates of DES (e.g. mortality, target vessel revascularization, early and late stent thrombosis and myocardial infarction) are significantly lower. For bioresorbable scaffolds (BRS) long-term results for the use in treatment of ST-elevation myocardial infarction (STEMI) are not yet available but initial results are very promising. However, the selection of a stent needs to be done on an individual basis in order to do justice to all aspects. Data with respect to thrombectomy in acute treatment are heterogeneous. Currently, a thorough consideration of all aspects is necessary because thrombus aspiration can also be associated with an increased rate of incidents. In a state of hemodynamic stability only so-called culprit lesions should currently be treated with a stent. Elective interventions on further stenoses should be carried out after consideration of individual factors and if necessary evaluation of the hemodynamic relevance. PMID:25070211

  6. Effect of salmeterol/fluticasone combination on the dynamic changes of lung mechanics in mechanically ventilated COPD patients: a prospective pilot study

    PubMed Central

    Chen, Wei-Chih; Chen, Hung-Hsing; Chiang, Chi-Huei; Lee, Yu-Chin; Yang, Kuang-Yao

    2016-01-01

    Background The combined therapy of inhaled corticosteroids and long-acting beta-2 agonists for mechanically ventilated patients with COPD has never been explored. Therefore, the aim of this study was to investigate their dynamic effects on lung mechanics and gas exchange. Materials and methods Ten mechanically ventilated patients with resolution of the causes of acute exacerbations of COPD were included. Four puffs of salmeterol 25 μg/fluticasone 125 μg combination therapy were administered. Lung mechanics, including maximum resistance of the respiratory system (Rrs), end-inspiratory static compliance, peak inspiratory pressure (PIP), plateau pressure, and mean airway pressure along with gas exchange function were measured and analyzed. Results Salmeterol/fluticasone produced a significant improvement in Rrs and PIP after 30 minutes. With regard to changes in baseline values, salmeterol/fluticasone inhalation had a greater effect on PIP than Rrs. However, the therapeutic effects seemed to lose significance after 3 hours of inhaled corticosteroid/long-acting beta-2 agonist administration. Conclusion The combination of salmeterol/fluticasone-inhaled therapy in mechanically ventilated patients with COPD had a significant benefit in reducing Rrs and PIP. PMID:26869782

  7. Effects and mechanisms of the combined pollution of lanthanum and acid rain on the root phenotype of soybean seedlings.

    PubMed

    Sun, Zhaoguo; Wang, Lihong; Zhou, Qing; Huang, Xiaohua

    2013-09-01

    Rare earth pollution and acid rain pollution are both important environmental issues worldwide. In regions which simultaneously occur, the combined pollution of rare earth and acid rain becomes a new environmental issue, and the relevant research is rarely reported. Accordingly, we investigated the combined effects and mechanisms of lanthanum ion (La(3+)) and acid rain on the root phenotype of soybean seedlings. The combined pollution of low-concentration La(3+) and acid rain exerted deleterious effects on the phenotype and growth of roots, which were aggravated by the combined pollution of high-concentration La(3+) and acid rain. The deleterious effects of the combined pollution were stronger than those of single La(3+) or acid rain pollution. These stronger deleterious effects on the root phenotype and growth of roots were due to the increased disturbance of absorption and utilization of mineral nutrients in roots. PMID:23726884

  8. Quantum Mechanics/Molecular Mechanics Method Combined with Hybrid All-Atom and Coarse-Grained Model: Theory and Application on Redox Potential Calculations.

    PubMed

    Shen, Lin; Yang, Weitao

    2016-04-12

    We developed a new multiresolution method that spans three levels of resolution with quantum mechanical, atomistic molecular mechanical, and coarse-grained models. The resolution-adapted all-atom and coarse-grained water model, in which an all-atom structural description of the entire system is maintained during the simulations, is combined with the ab initio quantum mechanics and molecular mechanics method. We apply this model to calculate the redox potentials of the aqueous ruthenium and iron complexes by using the fractional number of electrons approach and thermodynamic integration simulations. The redox potentials are recovered in excellent accordance with the experimental data. The speed-up of the hybrid all-atom and coarse-grained water model renders it computationally more attractive. The accuracy depends on the hybrid all-atom and coarse-grained water model used in the combined quantum mechanical and molecular mechanical method. We have used another multiresolution model, in which an atomic-level layer of water molecules around redox center is solvated in supramolecular coarse-grained waters for the redox potential calculations. Compared with the experimental data, this alternative multilayer model leads to less accurate results when used with the coarse-grained polarizable MARTINI water or big multipole water model for the coarse-grained layer. PMID:26930454

  9. Cardiopulmonary bypass (CPB) has no significant impact on survival in patients undergoing nephrectomy and level III-IV inferior vena cava thrombectomy; a multi-institutional analysis

    PubMed Central

    Dall'Era, Marc A.; Durbin-Johnson, Blythe; Carballido, Joaquín A.; Chandrasekar, Thenappan; Chromecki, Thomas; Ciancio, Gaetano; Daneshmand, Siamak; Gontero, Paolo; Gonzalez, Javier; Haferkamp, Axel; Hohenfellner, Markus; Huang, William C.; Espinós, Estefania Linares; Mandel, Philipp; Martinez-Salamanca, Juan I.; Master, Viraj A.; McKiernan, James M.; Montorsi, Francesco; Novara, Giacomo; Pahernik, Sascha; Palou, Juan; Pruthi, Raj S.; Rodriguez-Faba, Oscar; Russo, Paul; Scherr, Douglas S.; Shariat, Shahrokh F.; Spahn, Martin; Terrone, Carlo; Vergho, Daniel; Wallen, Eric M.; Xylinas, Evanguelos; Zigeuner, Richard; Libertino, John A.; Evans, Christopher P.

    2016-01-01

    Purpose The impact of cardiopulmonary bypass (CPB) usage in level III-IV tumor thrombectomy on surgical and oncologic outcomes is unknown. We sought to determine the impact of cardiopulmonary bypass (CPB) on overall and cancer specific survival, as well as surgical complication rates, and immediate outcomes in patients undergoing nephrectomy and level III-IV tumor thrombectomy with or without CPB. Patients and Methods We retrospectively analyzed 362 patients with RCC and with level III or IV tumor thrombus from 1992 to 2012 in 22 US and European centers. Cox proportional hazards models were used to compare overall and cancer-specific survival between patients with and without CPB. Perioperative mortality and complications rates were assessed using logistic regression analyses. Results The median overall survival was 24.6 months in non-CPB patients and 26.6 months in CPB patients. Overall survival and cancer-specific survival (CSS) did not differ significantly in both groups, neither in univariate analysis nor when adjusting for known risk factors. In multivariate analysis, no significant differences were seen in hospital LOS, Clavien 1-4 complication rate, intraoperative or 30 day mortality, and CSS between both groups. Limitations include the retrospective nature of the study. Conclusions In our multi-institutional analysis, the use of cardiopulmonary bypass did not significantly impact cancer specific survival or overall survival in patients undergoing nephrectomy and level III or IV tumor thrombectomy. Neither approach was independently associated with increased mortality in the multivariate analysis. Higher surgical complications were not independently associated with the use of CPB. PMID:25797392

  10. CH 2 Cl 2 + OH - Reaction in Aqueous Solution: A Combined Quantum Mechanical and Molecular Mechanics Study

    SciTech Connect

    Wang, Dunyou; Valiev, Marat; Garrett, Bruce C.

    2011-03-03

    The CH2Cl2 + OH- reaction in aqueous solution was investigated using combined quantum mechanical and molecular mechanics approach. We present analysis of the reactant, transition, and product state structures, and calculate the free energy reaction profile through the CCSD(T) level of the theory for the reactive region. Our results show that the aqueous environment has a significant impact on the reaction process raising the reaction barrier by ~17 kcal/mol and the reaction energy by ~20 kcal/mol. While solvation effects play a predominant role, we also find sizable contributions from solvent-induced polarization effects.

  11. Combined probabilistic and principal component analysis approach for multivariate sensitivity evaluation and application to implanted patellofemoral mechanics.

    PubMed

    Fitzpatrick, Clare K; Baldwin, Mark A; Rullkoetter, Paul J; Laz, Peter J

    2011-01-01

    Many aspects of biomechanics are variable in nature, including patient geometry, joint mechanics, implant alignment and clinical outcomes. Probabilistic methods have been applied in computational models to predict distributions of performance given uncertain or variable parameters. Sensitivity analysis is commonly used in conjunction with probabilistic methods to identify the parameters that most significantly affect the performance outcome; however, it does not consider coupled relationships for multiple output measures. Principal component analysis (PCA) has been applied to characterize common modes of variation in shape and kinematics. In this study, a novel, combined probabilistic and PCA approach was developed to characterize relationships between multiple input parameters and output measures. To demonstrate the benefits of the approach, it was applied to implanted patellofemoral (PF) mechanics to characterize relationships between femoral and patellar component alignment and loading and the resulting joint mechanics. Prior studies assessing PF sensitivity have performed individual perturbation of alignment parameters. However, the probabilistic and PCA approach enabled a more holistic evaluation of sensitivity, including identification of combinations of alignment parameters that most significantly contributed to kinematic and contact mechanics outcomes throughout the flexion cycle, and the predictive capability to estimate joint mechanics based on alignment conditions without requiring additional analysis. The approach showed comparable results for Monte Carlo sampling with 500 trials and the more efficient Latin Hypercube sampling with 50 trials. The probabilistic and PCA approach has broad applicability to biomechanical analysis and can provide insight into the interdependencies between implant design, alignment and the resulting mechanics. PMID:20825941

  12. Shared and unique responses of plants to multiple individual stresses and stress combinations: physiological and molecular mechanisms

    PubMed Central

    Pandey, Prachi; Ramegowda, Venkategowda; Senthil-Kumar, Muthappa

    2015-01-01

    In field conditions, plants are often simultaneously exposed to multiple biotic and abiotic stresses resulting in substantial yield loss. Plants have evolved various physiological and molecular adaptations to protect themselves under stress combinations. Emerging evidences suggest that plant responses to a combination of stresses are unique from individual stress responses. In addition, plants exhibit shared responses which are common to individual stresses and stress combination. In this review, we provide an update on the current understanding of both unique and shared responses. Specific focus of this review is on heat–drought stress as a major abiotic stress combination and, drought–pathogen and heat–pathogen as examples of abiotic–biotic stress combinations. We also comprehend the current understanding of molecular mechanisms of cross talk in relation to shared and unique molecular responses for plant survival under stress combinations. Thus, the knowledge of shared responses of plants from individual stress studies and stress combinations can be utilized to develop varieties with broad spectrum stress tolerance. PMID:26442037

  13. Transcriptome Analysis of Sunflower Genotypes with Contrasting Oxidative Stress Tolerance Reveals Individual- and Combined- Biotic and Abiotic Stress Tolerance Mechanisms

    PubMed Central

    Ramu, Vemanna S.; Paramanantham, Anjugam; Ramegowda, Venkategowda; Mohan-Raju, Basavaiah; Udayakumar, Makarla

    2016-01-01

    In nature plants are often simultaneously challenged by different biotic and abiotic stresses. Although the mechanisms underlying plant responses against single stress have been studied considerably, plant tolerance mechanisms under combined stress is not understood. Also, the mechanism used to combat independently and sequentially occurring many number of biotic and abiotic stresses has also not systematically studied. From this context, in this study, we attempted to explore the shared response of sunflower plants to many independent stresses by using meta-analysis of publically available transcriptome data and transcript profiling by quantitative PCR. Further, we have also analyzed the possible role of the genes so identified in contributing to combined stress tolerance. Meta-analysis of transcriptomic data from many abiotic and biotic stresses indicated the common representation of oxidative stress responsive genes. Further, menadione-mediated oxidative stress in sunflower seedlings showed similar pattern of changes in the oxidative stress related genes. Based on this a large scale screening of 55 sunflower genotypes was performed under menadione stress and those contrasting in oxidative stress tolerance were identified. Further to confirm the role of genes identified in individual and combined stress tolerance the contrasting genotypes were individually and simultaneously challenged with few abiotic and biotic stresses. The tolerant hybrid showed reduced levels of stress damage both under combined stress and few independent stresses. Transcript profiling of the genes identified from meta-analysis in the tolerant hybrid also indicated that the selected genes were up-regulated under individual and combined stresses. Our results indicate that menadione-based screening can identify genotypes not only tolerant to multiple number of individual biotic and abiotic stresses, but also the combined stresses. PMID:27314499

  14. Combination Regimens of Radiation Therapy and Therapeutic Cancer Vaccines: Mechanisms and Opportunities

    PubMed Central

    Garnett-Benson, Charlie; Hodge, James W.; Gameiro, Sofia R.

    2014-01-01

    Radiation therapy is widely used with curative or palliative intent in the clinical management of multiple cancers. Although mainly aimed at direct tumor cell killing, mounting evidence suggests that radiation can alter the tumor to become an immunostimulatory milieu. Data suggest that the immunogenic effects of radiation can be exploited to promote synergistic antitumor effects in combination with immunotherapeutic agents. Here we review concepts associated with the immunogenic consequences of radiation therapy, and highlight how preclinical findings are translating into clinical benefit for patients receiving combination regimens of radiation therapy and therapeutic cancer vaccines. PMID:25481266

  15. Combined Enzymatic and Mechanical Cell Disruption and Lipid Extraction of Green Alga Neochloris oleoabundans

    PubMed Central

    Wang, Dongqin; Li, Yanqun; Hu, Xueqiong; Su, Weimin; Zhong, Min

    2015-01-01

    Microalgal biodiesel is one of the most promising renewable fuels. The wet technique for lipids extraction has advantages over the dry method, such as energy-saving and shorter procedure. The cell disruption is a key factor in wet oil extraction to facilitate the intracellular oil release. Ultrasonication, high-pressure homogenization, enzymatic hydrolysis and the combination of enzymatic hydrolysis with high-pressure homogenization and ultrasonication were employed in this study to disrupt the cells of the microalga Neochloris oleoabundans. The cell disruption degree was investigated. The cell morphology before and after disruption was assessed with scanning and transmission electron microscopy. The energy requirements and the operation cost for wet cell disruption were also estimated. The highest disruption degree, up to 95.41%, assessed by accounting method was achieved by the combination of enzymatic hydrolysis and high-pressure homogenization. A lipid recovery of 92.6% was also obtained by the combined process. The combined process was found to be more efficient and economical compared with the individual process. PMID:25853267

  16. Combined enzymatic and mechanical cell disruption and lipid extraction of green alga Neochloris oleoabundans.

    PubMed

    Wang, Dongqin; Li, Yanqun; Hu, Xueqiong; Su, Weimin; Zhong, Min

    2015-01-01

    Microalgal biodiesel is one of the most promising renewable fuels. The wet technique for lipids extraction has advantages over the dry method, such as energy-saving and shorter procedure. The cell disruption is a key factor in wet oil extraction to facilitate the intracellular oil release. Ultrasonication, high-pressure homogenization, enzymatic hydrolysis and the combination of enzymatic hydrolysis with high-pressure homogenization and ultrasonication were employed in this study to disrupt the cells of the microalga Neochloris oleoabundans. The cell disruption degree was investigated. The cell morphology before and after disruption was assessed with scanning and transmission electron microscopy. The energy requirements and the operation cost for wet cell disruption were also estimated. The highest disruption degree, up to 95.41%, assessed by accounting method was achieved by the combination of enzymatic hydrolysis and high-pressure homogenization. A lipid recovery of 92.6% was also obtained by the combined process. The combined process was found to be more efficient and economical compared with the individual process. PMID:25853267

  17. Optical-mechanical system for on-combine segregation of wheat by grain protein concentration

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Grain segregation by grain protein concentration (GPC) may help growers maximize revenues in markets that offer protein premiums. Our objective was to develop an on-combine system for automatically segregating wheat (Triticum aestivum L.) by GPC during harvest. A multispectral optical sensor scans...

  18. Drink Refusal Training as Part of a Combined Behavioral Intervention: Effectiveness and Mechanisms of Change

    ERIC Educational Resources Information Center

    Witkiewitz, Katie; Donovan, Dennis M.; Hartzler, Bryan

    2012-01-01

    Objective: Many trials have demonstrated the effectiveness of cognitive behavioral interventions for alcohol dependence, yet few studies have examined why particular treatments are effective. This study was designed to evaluate whether drink refusal training was an effective component of a combined behavioral intervention (CBI) and whether change…

  19. Control of a simulated arm using a novel combination of Cerebellar learning mechanisms

    NASA Technical Reports Server (NTRS)

    Assad, C.; Hartmann, M.; Paulin, M. G.

    2001-01-01

    We present a model of cerebellar cortex that combines two types of learning: feedforward predicitve association based on local Hebbian-type learning between granule cell ascending branch and parallel fiber inputs, and reinforcement learning with feedback error correction based on climbing fiber activity.

  20. Combining constitutive materials modeling with atomic force microscopy to understand the mechanical properties of living cells

    PubMed Central

    McElfresh, Mike; Baesu, Eveline; Balhorn, Rod; Belak, James; Allen, Michael J.; Rudd, Robert E.

    2002-01-01

    The goal of this work is to study the properties of living cells and cell membranes by using atomic force microscopy. During atomic force microscopy (AFM) measurement, there is a strong mechanical coupling between the AFM tip and the cell. The purpose of this paper is to present a model of the overall mechanical response of the cell that allows us to separate out the mechanical response of the cell from the local surface interactions we wish to quantify. These local interactions include recognition (or binding) events between molecules bound to an AFM tip (e.g., an antibody) and molecules or receptors on the cell surface (e.g., the respective antigen). The computational model differs from traditional Hertzian contact models by explicitly taking into account the mechanics of the biomembrane and cytoskeleton. The model also accounts for the mechanical response of the living cell during arbitrary deformation. The indentation of a bovine sperm cell is used to test the validity of this model, and further experiments are proposed to fully parameterize the model. PMID:11983924

  1. The Interaction Between Statins and Exercise: Mechanisms and Strategies to Counter the Musculoskeletal Side Effects of This Combination Therapy

    PubMed Central

    Deichmann, Richard E.; Lavie, Carl J.; Asher, Timothy; DiNicolantonio, James J.; O'Keefe, James H.; Thompson, Paul D.

    2015-01-01

    Background Broad indications for the use of statin medications are resulting in more patients using these therapies. Simultaneously, healthcare professionals are strongly advocating recommendations to increase exercise training (ET) as a means of decreasing cardiovascular disease (CVD) risk and improving other parameters of fitness. Methods We review the literature to explore mechanisms that may increase the risk of statin/ET interactions, examine the benefits and risks of combining ET and statin use, and offer strategies to minimize the hazards of this combination therapy. Results The combined use of statins and ET can result in health gains and decreased CVD risk; however, multiple factors may increase the risk of adverse events. Some of the events that have been reported with the combination of statins and ET include decreased athletic performance, muscle injury, myalgia, joint problems, decreased muscle strength, and fatigue. The type of statin, the dose, drug interactions, genetic variants, coenzyme Q10 deficiency, vitamin D deficiency, and underlying muscle diseases are among the factors that may predispose patients to intolerance of this combined therapy. Conclusion Effective strategies exist to help patients who may be intolerant of combined statin therapy and ET so they may benefit from this proven therapy. Careful attention to identifying high-risk groups and strategies to prevent or treat side effects that may occur should be employed. PMID:26730228

  2. Simulation of chemical reactions in solution by a combination of classical and quantum mechanical approach

    NASA Astrophysics Data System (ADS)

    Onida, Giovanni; Andreoni, Wanda

    1995-09-01

    A classical trajectory mapping method was developed to study chemical reactions in solution and in enzymes. In this method, the trajectories were calculated on a classical potential surface and the free energy profile was obtained by mapping the classical surface to the quantum mechanical surface obtained by the semiempirical AM1 method. There is no need to perform expensive quantum mechanical calculations at each iteration step. This method was applied to proton transfer reactions both in aqueous solution and in papain. The results are encouraging, indicating the applicability of this hybrid method to chemical reactions both in solution and in enzymes.

  3. Effects and mechanism analysis of combined infusion by levosimendan and vasopressin on acute lung injury in rats septic shock.

    PubMed

    Wang, Xuebing; Ma, Shaolin; Liu, Yang; Xu, Wei; Li, Zhanxia

    2014-12-01

    This research is aimed to discover the influence and underling mechanism of combined infusion of arginine vasopressin with levosimendan on acute lung injury in rat septic shock with norepinephrine supplemented. The traditional fecal peritonitis-induced septic shock model was undergone in rats for study. It is observed that the combined infusion supplemented with norepinephrine brought about a lower mean pulmonary artery pressure; lower high-mobility group box 1 levels, pulmonary levels of interleukin-6, and arterial total nitrate/nitrite; lower apoptotic cells scores and total histological scores; but higher pulmonary gas exchange when compared with the separate infusion group and norepinephrine group. This therapy shows potential clinical beneficial assistance in sepsis-induced acute lung injury. The results suggest the mechanism of such effect is through abating pulmonary artery pressure, and more importantly suppressing inflammatory responses in lung when compared with norepinephrine infusion group and the separate infusion of levosimendan or vasopressin alone. PMID:25002345

  4. Multi-Drug Resistance Transporters and a Mechanism-Based Strategy for Assessing Risks of Pesticide Combinations to Honey Bees.

    PubMed

    Guseman, Alex J; Miller, Kaliah; Kunkle, Grace; Dively, Galen P; Pettis, Jeffrey S; Evans, Jay D; vanEngelsdorp, Dennis; Hawthorne, David J

    2016-01-01

    Annual losses of honey bee colonies remain high and pesticide exposure is one possible cause. Dangerous combinations of pesticides, plant-produced compounds and antibiotics added to hives may cause or contribute to losses, but it is very difficult to test the many combinations of those compounds that bees encounter. We propose a mechanism-based strategy for simplifying the assessment of combinations of compounds, focusing here on compounds that interact with xenobiotic handling ABC transporters. We evaluate the use of ivermectin as a model substrate for these transporters. Compounds that increase sensitivity of bees to ivermectin may be inhibiting key transporters. We show that several compounds commonly encountered by honey bees (fumagillin, Pristine, quercetin) significantly increased honey bee mortality due to ivermectin and significantly reduced the LC50 of ivermectin suggesting that they may interfere with transporter function. These inhibitors also significantly increased honey bees sensitivity to the neonicotinoid insecticide acetamiprid. This mechanism-based strategy may dramatically reduce the number of tests needed to assess the possibility of adverse combinations among pesticides. We also demonstrate an in vivo transporter assay that provides physical evidence of transporter inhibition by tracking the dynamics of a fluorescent substrate of these transporters (Rhodamine B) in bee tissues. Significantly more Rhodamine B remains in the head and hemolymph of bees pretreated with higher concentrations of the transporter inhibitor verapamil. Mechanism-based strategies for simplifying the assessment of adverse chemical interactions such as described here could improve our ability to identify those combinations that pose significantly greater risk to bees and perhaps improve the risk assessment protocols for honey bees and similar sensitive species. PMID:26840460

  5. Multi-Drug Resistance Transporters and a Mechanism-Based Strategy for Assessing Risks of Pesticide Combinations to Honey Bees

    PubMed Central

    Guseman, Alex J.; Miller, Kaliah; Kunkle, Grace; Dively, Galen P.; Pettis, Jeffrey S.; Evans, Jay D.; vanEngelsdorp, Dennis; Hawthorne, David J.

    2016-01-01

    Annual losses of honey bee colonies remain high and pesticide exposure is one possible cause. Dangerous combinations of pesticides, plant-produced compounds and antibiotics added to hives may cause or contribute to losses, but it is very difficult to test the many combinations of those compounds that bees encounter. We propose a mechanism-based strategy for simplifying the assessment of combinations of compounds, focusing here on compounds that interact with xenobiotic handling ABC transporters. We evaluate the use of ivermectin as a model substrate for these transporters. Compounds that increase sensitivity of bees to ivermectin may be inhibiting key transporters. We show that several compounds commonly encountered by honey bees (fumagillin, Pristine, quercetin) significantly increased honey bee mortality due to ivermectin and significantly reduced the LC50 of ivermectin suggesting that they may interfere with transporter function. These inhibitors also significantly increased honey bees sensitivity to the neonicotinoid insecticide acetamiprid. This mechanism-based strategy may dramatically reduce the number of tests needed to assess the possibility of adverse combinations among pesticides. We also demonstrate an in vivo transporter assay that provides physical evidence of transporter inhibition by tracking the dynamics of a fluorescent substrate of these transporters (Rhodamine B) in bee tissues. Significantly more Rhodamine B remains in the head and hemolymph of bees pretreated with higher concentrations of the transporter inhibitor verapamil. Mechanism-based strategies for simplifying the assessment of adverse chemical interactions such as described here could improve our ability to identify those combinations that pose significantly greater risk to bees and perhaps improve the risk assessment protocols for honey bees and similar sensitive species. PMID:26840460

  6. Effect of utilization of veno-venous bypass vs. cardiopulmonary bypass on complications for high level inferior vena cava tumor thrombectomy and concomitant radical nephrectomy

    PubMed Central

    Simon, Ross M.; Kim, Timothy; Espiritu, Patrick; Kurian, Tony; Sexton, Wade J.; Pow-Sang, Julio M.; Sverrisson, Einar; Spiess, Philippe E.

    2015-01-01

    ABSTRACT Purpose: To determine if patients with renal cell carcinoma (RCC) with levels III and IV tumor thrombi are receive any reduction in complication rate utilizing veno-venous bypass (VVB) over cardiopulmonary bypass (CPB) for high level (III/IV) inferior vena cava (IVC) tumor thrombectomy and concomitant radical nephrectomy. Materials and Methods: From May 1990 to August 2011, we reviewed 21 patients that had been treated for RCC with radical nephrectomy and concomitant IVC thrombectomy employing either CPB (n =16) or VVB (n=5). We retrospectively reviewed our study population for complication rates and perioperative characteristics. Results: Our results are reported using the validated Dindo-Clavien Classification system comparing the VVB and CPB cohorts. No significant difference was noted in minor complication rate (60.0% versus 68.7%, P=1.0), major complication rate (40.0% versus 31.3%, P=1.0), or overall complication rate (60.0% versus 62.5%, P=1.0) comparing VVB versus CPB. We also demonstrated a trend towards decreased time on bypass (P=0.09) in the VVB cohort. Conclusion: The use of VVB over CPB provides no decrease in minor, major, or overall complication rate. The use of VVB however, can be employed on an individualized basis with final decision on vascular bypass selection left to the discretion of the surgeon based on specifics of the individual case. PMID:26689516

  7. Simultaneous mechanical stiffness and electrical potential measurements of living vascular endothelial cells using combined atomic force and epifluorescence microscopy

    NASA Astrophysics Data System (ADS)

    Callies, Chiara; Schön, Peter; Liashkovich, Ivan; Stock, Christian; Kusche-Vihrog, Kristina; Fels, Johannes; Sträter, Alexandra S.; Oberleithner, Hans

    2009-04-01

    The degree of mechanical stiffness of vascular endothelial cells determines the endogenous production of the vasodilating gas nitric oxide (NO). However, the underlying mechanisms are not yet understood. Experiments on vascular endothelial cells suggest that the electrical plasma membrane potential is involved in this regulatory process. To test this hypothesis we developed a technique that simultaneously measures the electrical membrane potential and stiffness of vascular endothelial cells (GM7373 cell line derived from bovine aortic endothelium) under continuous perfusion with physiological electrolyte solution. The cellular stiffness was determined by nano-indentation using an atomic force microscope (AFM) while the electrical membrane potential was measured with bis-oxonol, a voltage-reporting fluorescent dye. These two methods were combined using an AFM attached to an epifluorescence microscope. The electrical membrane potential and mechanical stiffness of the same cell were continuously recorded for a time span of 5 min. Fast fluctuations (in the range of seconds) of both the electrical membrane potential and mechanical stiffness could be observed that were not related to each other. In contrast, slow cell depolarizations (in the range of minutes) were paralleled by significant increases in mechanical stiffness. In conclusion, using the combined AFM-fluorescence technique we monitored for the first time simultaneously the electrical plasma membrane potential and mechanical stiffness in a living cell. Vascular endothelial cells exhibit oscillatory non-synchronized waves of electrical potential and mechanical stiffness. The sustained membrane depolarization, however, is paralleled by a concomitant increase of cell stiffness. The described method is applicable for any fluorophore, which opens new perspectives in biomedical research.

  8. Combined effects of chemical priming and mechanical stimulation on mesenchymal stem cell differentiation on nanofiber scaffolds

    PubMed Central

    Subramony, Siddarth D.; Su, Amanda; Yeager, Keith; Lu, Helen H.

    2014-01-01

    Functional tissue engineering of connective tissues such as the anterior cruciate ligament (ACL) remains a significant clinical challenge, largely due to the need for mechanically competent scaffold systems for grafting, as well as a reliable cell source for tissue formation. We have designed an aligned, polylactide-co-glycolide (PLGA) nanofiber-based scaffold with physiologically relevant mechanical properties for ligament regeneration. The objective of this study is to identify optimal tissue engineering strategies for fibroblastic induction of human mesenchymal stem cells (hMSC), testing the hypothesis that basic fibroblast growth factor (bFGF) priming coupled with tensile loading will enhance hMSC-mediated ligament regeneration. It was observed that compared to the unloaded, as well as growth factor-primed but unloaded controls, bFGF stimulation followed by physiologically relevant tensile loading enhanced hMSC proliferation, collagen production and subsequent differentiation into ligament fibroblast-like cells, upregulating the expression of types I and III collagen, as well as tenasin-C and tenomodulin. The results of this study suggest that bFGF priming increases cell proliferation, while mechanical stimulation of the hMSCs on the aligned nanofiber scaffold promotes fibroblastic induction of these cells. In addition to demonstrating the potential of nanofiber scaffolds for hMSC-mediated functional ligament tissue engineering, this study yields new insights into the interactive effects of chemical and mechanical stimuli on stem cell differentiation. PMID:24267271

  9. Combination of different molecular mechanisms leading to fluconazole resistance in a Candida lusitaniae clinical isolate.

    PubMed

    Reboutier, David; Piednoël, Mathieu; Boisnard, Stéphanie; Conti, Audrey; Chevalier, Virginie; Florent, Martine; Gibot-Leclerc, Stéphanie; Da Silva, Bruno; Chastin, Christiane; Fallague, Karim; Favel, Anne; Noël, Thierry; Ruprich-Robert, Gwenaël; Chapeland-Leclerc, Florence; Papon, Nicolas

    2009-02-01

    We report on the underlying molecular mechanisms likely responsible for the high-level fluconazole resistance in a Candida lusitaniae clinical isolate. Fluconazole resistance correlated with overexpression of ERG11 and of several efflux pump genes, in particular, the orthologs of the Candida albicans MDR1, PDR16, CDR1, CDR2, and YOR1. PMID:19070454

  10. Combined Pan-RAF and MEK Inhibition Overcomes Multiple Resistance Mechanisms to Selective RAF Inhibitors.

    PubMed

    Whittaker, Steven R; Cowley, Glenn S; Wagner, Steve; Luo, Flora; Root, David E; Garraway, Levi A

    2015-12-01

    RAF and MEK inhibitors are effective in BRAF-mutant melanoma but not in BRAF-mutant colorectal cancer. To gain additional insights into this difference, we performed a genome-scale pooled shRNA enhancer screen in a BRAF-mutant, RAF inhibitor-resistant colorectal cancer cell line exposed to the selective RAF inhibitor PLX4720. We identified multiple genes along the receptor tyrosine kinase (RTK)/mitogen-activated protein kinase (MAPK) signaling axis that, when suppressed, either genetically or pharmacologically, sensitized cells to the selective RAF inhibitor through sustained inhibition of MAPK signaling. Strikingly, CRAF was a key mediator of resistance that could be overcome by the use of pan-RAF inhibitors in combination with a MEK inhibitor. Furthermore, the combination of pan-RAF and MEK inhibitors displayed strong synergy in melanoma and colorectal cancer cell lines with RAS-activating events such as RTK activation, KRAS mutation, or NF1 loss-of-function mutations. Combinations of selective RAF inhibitors, such as PLX4720 or dabrafenib, with MEK inhibitors did not incur such profound synergy, suggesting that inhibition of CRAF by pan-RAF inhibitors plays a key role in determining cellular response. Importantly, in contrast to the modest activity seen with single-agent treatment, dual pan-RAF and MEK inhibition results in the induction of apoptosis, greatly enhancing efficacy. Notably, combined pan-RAF and MEK inhibition can overcome intrinsic and acquired resistance to single-agent RAF/MEK inhibition, supporting dual pan-RAF and MEK inhibition as a novel therapeutic strategy for BRAF- and KRAS-mutant cancers. PMID:26351322

  11. Midgut epithelial responses of different mosquito–Plasmodium combinations: The actin cone zipper repair mechanism in Aedes aegypti

    PubMed Central

    Gupta, Lalita; Kumar, Sanjeev; Han, Yeon Soo; Pimenta, Paulo F. P.; Barillas-Mury, Carolina

    2005-01-01

    In vivo responses of midgut epithelial cells to ookinete invasion of three different vector–parasite combinations, Aedes aegypti–Plasmodium gallinaceum, Anopheles stephensi–Plasmodium berghei, and A. stephensi–P. gallinaceum, were directly compared by using enzymatic markers and immunofluorescence stainings. Our studies indicate that, in A. aegypti and A. stephensi ookinetes traverse the midgut via an intracellular route and inflict irreversible damage to the invaded cells. These two mosquito species differ, however, in their mechanisms of epithelial repair. A. stephensi detaches damaged cells by an actin-mediated budding-off mechanism when invaded by either P. berghei or P. gallinaceum. In A. aegypti, the midgut epithelium is repaired by a unique actin cone zipper mechanism that involves the formation of a cone-shaped actin aggregate at the base of the cell that closes sequentially, expelling the cellular contents into the midgut lumen as it brings together healthy neighboring cells. Invasion of A. stephensi by P. berghei induced expression of nitric oxide synthase and peroxidase activities, which mediate tyrosine nitration. These enzymes and nitrotyrosine, however, were not induced in the other two vector–parasite combinations examined. These studies indicate that the epithelial responses of different mosquito–parasite combinations are not universal. The implications of these observations to validate animal experimental systems that reflect the biology of natural vectors of human malarias are discussed. PMID:15753303

  12. Midgut epithelial responses of different mosquito-Plasmodium combinations: the actin cone zipper repair mechanism in Aedes aegypti.

    PubMed

    Gupta, Lalita; Kumar, Sanjeev; Han, Yeon Soo; Pimenta, Paulo F P; Barillas-Mury, Carolina

    2005-03-15

    In vivo responses of midgut epithelial cells to ookinete invasion of three different vector-parasite combinations, Aedes aegypti-Plasmodium gallinaceum, Anopheles stephensi-Plasmodium berghei, and A. stephensi-P. gallinaceum, were directly compared by using enzymatic markers and immunofluorescence stainings. Our studies indicate that, in A. aegypti and A. stephensi ookinetes traverse the midgut via an intracellular route and inflict irreversible damage to the invaded cells. These two mosquito species differ, however, in their mechanisms of epithelial repair. A. stephensi detaches damaged cells by an actin-mediated budding-off mechanism when invaded by either P. berghei or P. gallinaceum. In A. aegypti, the midgut epithelium is repaired by a unique actin cone zipper mechanism that involves the formation of a cone-shaped actin aggregate at the base of the cell that closes sequentially, expelling the cellular contents into the midgut lumen as it brings together healthy neighboring cells. Invasion of A. stephensi by P. berghei induced expression of nitric oxide synthase and peroxidase activities, which mediate tyrosine nitration. These enzymes and nitrotyrosine, however, were not induced in the other two vector-parasite combinations examined. These studies indicate that the epithelial responses of different mosquito-parasite combinations are not universal. The implications of these observations to validate animal experimental systems that reflect the biology of natural vectors of human malarias are discussed. PMID:15753303

  13. Top triangle moose: Combining Higgsless and topcolor mechanisms for mass generation

    NASA Astrophysics Data System (ADS)

    Chivukula, R. Sekhar; Christensen, Neil D.; Coleppa, Baradhwaj; Simmons, Elizabeth H.

    2009-08-01

    We present the details of a deconstructed model that incorporates both Higgsless and top-color mechanisms. The model alleviates the tension between obtaining the correct top quark mass and keeping Δρ small that exists in many Higgsless models. It does so by singling out the top quark mass generation as arising from a Yukawa coupling to an effective top Higgs which develops a small vacuum expectation value, while electroweak symmetry breaking results largely from a Higgsless mechanism. As a result, the heavy partners of the SM fermions can be light enough to be seen at the LHC. After presenting the model, we detail the phenomenology, showing that for a broad range of masses, these heavy fermions are discoverable at the LHC.

  14. Top triangle moose: Combining Higgsless and topcolor mechanisms for mass generation

    SciTech Connect

    Chivukula, R. Sekhar; Christensen, Neil D.; Coleppa, Baradhwaj; Simmons, Elizabeth H.

    2009-08-01

    We present the details of a deconstructed model that incorporates both Higgsless and top-color mechanisms. The model alleviates the tension between obtaining the correct top quark mass and keeping {delta}{rho} small that exists in many Higgsless models. It does so by singling out the top quark mass generation as arising from a Yukawa coupling to an effective top Higgs which develops a small vacuum expectation value, while electroweak symmetry breaking results largely from a Higgsless mechanism. As a result, the heavy partners of the SM fermions can be light enough to be seen at the LHC. After presenting the model, we detail the phenomenology, showing that for a broad range of masses, these heavy fermions are discoverable at the LHC.

  15. Controller design for flexible, distributed parameter mechanical arms via combined state space and frequency domain techniques

    NASA Technical Reports Server (NTRS)

    Book, W. J.; Majett, M.

    1982-01-01

    The potential benefits of the ability to control more flexible mechanical arms are discussed. A justification is made in terms of speed of movement. A new controller design procedure is then developed to provide this capability. It uses both a frequency domain representation and a state variable representation of the arm model. The frequency domain model is used to update the modal state variable model to insure decoupled states. The technique is applied to a simple example with encouraging results.

  16. Cellular graphene aerogel combines ultralow weight and high mechanical strength: A highly efficient reactor for catalytic hydrogenation

    NASA Astrophysics Data System (ADS)

    Zhang, Bingxing; Zhang, Jianling; Sang, Xinxin; Liu, Chengcheng; Luo, Tian; Peng, Li; Han, Buxing; Tan, Xiuniang; Ma, Xue; Wang, Dong; Zhao, Ning

    2016-05-01

    The construction of three-dimensional graphene aerogels (GAs) is of great importance owing to their outstanding properties for various applications. Up to now, the combination of ultralow weight and super mechanical strength for GA remains a great challenge. Here we demonstrate the fabrication of cellular GAs by a facile, easily controlled and versatile route, i.e. the chemical reduction of graphene oxide assemblies at oil-water interface under a mild condition (70 °C). The GA is ultralight (with density <3 mg cm‑3) yet mechanically resilient because the walls of the cell closely pack in a highly ordered manner to maximize mechanical strength. The GA has been utilized as an appealing reactor for catalytic hydrogenation, which exhibited great advantages such as large oil absorption capability, exceptional catalytic activity, ease of product separation and high stability.

  17. Cellular graphene aerogel combines ultralow weight and high mechanical strength: A highly efficient reactor for catalytic hydrogenation

    PubMed Central

    Zhang, Bingxing; Zhang, Jianling; Sang, Xinxin; Liu, Chengcheng; Luo, Tian; Peng, Li; Han, Buxing; Tan, Xiuniang; Ma, Xue; Wang, Dong; Zhao, Ning

    2016-01-01

    The construction of three-dimensional graphene aerogels (GAs) is of great importance owing to their outstanding properties for various applications. Up to now, the combination of ultralow weight and super mechanical strength for GA remains a great challenge. Here we demonstrate the fabrication of cellular GAs by a facile, easily controlled and versatile route, i.e. the chemical reduction of graphene oxide assemblies at oil-water interface under a mild condition (70 °C). The GA is ultralight (with density <3 mg cm−3) yet mechanically resilient because the walls of the cell closely pack in a highly ordered manner to maximize mechanical strength. The GA has been utilized as an appealing reactor for catalytic hydrogenation, which exhibited great advantages such as large oil absorption capability, exceptional catalytic activity, ease of product separation and high stability. PMID:27174450

  18. Cellular graphene aerogel combines ultralow weight and high mechanical strength: A highly efficient reactor for catalytic hydrogenation.

    PubMed

    Zhang, Bingxing; Zhang, Jianling; Sang, Xinxin; Liu, Chengcheng; Luo, Tian; Peng, Li; Han, Buxing; Tan, Xiuniang; Ma, Xue; Wang, Dong; Zhao, Ning

    2016-01-01

    The construction of three-dimensional graphene aerogels (GAs) is of great importance owing to their outstanding properties for various applications. Up to now, the combination of ultralow weight and super mechanical strength for GA remains a great challenge. Here we demonstrate the fabrication of cellular GAs by a facile, easily controlled and versatile route, i.e. the chemical reduction of graphene oxide assemblies at oil-water interface under a mild condition (70 °C). The GA is ultralight (with density <3 mg cm(-3)) yet mechanically resilient because the walls of the cell closely pack in a highly ordered manner to maximize mechanical strength. The GA has been utilized as an appealing reactor for catalytic hydrogenation, which exhibited great advantages such as large oil absorption capability, exceptional catalytic activity, ease of product separation and high stability. PMID:27174450

  19. How Changes in Extracellular Matrix Mechanics and Gene Expression Variability Might Combine to Drive Cancer Progression

    PubMed Central

    Bischof, Ashley G.; Mannix, Robert J.; Tobin, Heather; Bar-Yam, Yaneer; Bellin, Robert M.; Ingber, Donald E.

    2013-01-01

    Changes in extracellular matrix (ECM) structure or mechanics can actively drive cancer progression; however, the underlying mechanism remains unknown. Here we explore whether this process could be mediated by changes in cell shape that lead to increases in genetic noise, given that both factors have been independently shown to alter gene expression and induce cell fate switching. We do this using a computer simulation model that explores the impact of physical changes in the tissue microenvironment under conditions in which physical deformation of cells increases gene expression variability among genetically identical cells. The model reveals that cancerous tissue growth can be driven by physical changes in the microenvironment: when increases in cell shape variability due to growth-dependent increases in cell packing density enhance gene expression variation, heterogeneous autonomous growth and further structural disorganization can result, thereby driving cancer progression via positive feedback. The model parameters that led to this prediction are consistent with experimental measurements of mammary tissues that spontaneously undergo cancer progression in transgenic C3(1)-SV40Tag female mice, which exhibit enhanced stiffness of mammary ducts, as well as progressive increases in variability of cell-cell relations and associated cell shape changes. These results demonstrate the potential for physical changes in the tissue microenvironment (e.g., altered ECM mechanics) to induce a cancerous phenotype or accelerate cancer progression in a clonal population through local changes in cell geometry and increased phenotypic variability, even in the absence of gene mutation. PMID:24098430

  20. Combined quantum mechanics (TDDFT) and classical electrodynamics (Mie theory) methods for calculating surface enhanced Raman and hyper-Raman spectra.

    PubMed

    Mullin, Jonathan; Valley, Nicholas; Blaber, Martin G; Schatz, George C

    2012-09-27

    Multiscale models that combine quantum mechanics and classical electrodynamics are presented, which allow for the evaluation of surface-enhanced Raman (SERS) and hyper-Raman scattering spectra (SEHRS) for both chemical (CHEM) and electrodynamic (EM) enhancement mechanisms. In these models, time-dependent density functional theory (TDDFT) for a system consisting of the adsorbed molecule and a metal cluster fragment of the metal particle is coupled to Mie theory for the metal particle, with the surface of the cluster being overlaid with the surface of the metal particle. In model A, the electromagnetic enhancement from plasmon-excitation of the metal particle is combined with the chemical enhancement associated with a static treatment of the molecule-metal structure to determine overall spectra. In model B, the frequency dependence of the Raman spectrum of the isolated molecule is combined with the enhancements determined in model A to refine the enhancement estimate. An equivalent theory at the level of model A is developed for hyper-Raman spectra calculations. Application to pyridine interacting with a 20 nm diameter silver sphere is presented, including comparisons with an earlier model (denoted G), which combines plasmon enhanced fields with gas-phase Raman (or hyper-Raman) spectra. The EM enhancement factor for spherical particles at 357 nm is found to be 10(4) and 10(6) for SERS and SEHRS, respectively. Including both chemical and electromagnetic mechanisms at the level of model A leads to enhancements on the order of 10(4) and 10(9) for SERS and SEHRS. PMID:22946645

  1. Thrombosis of a Superior Mesenteric Vein Aneurysm: Transarterial Thrombolysis and Transhepatic Aspiration Thrombectomy

    SciTech Connect

    Hechelhammer, L.; Crook, D.W.; Widmer, U.; Wildermuth, S.; Pfammatter, T.

    2004-09-15

    We report the case of a 31-year-old woman presenting with abdominal pain due to acute thrombosis of a superior and inferior mesenteric vein aneurysm, which was treated by a combination of arterial thrombolysis and transhepatic thrombus aspiration. At the last follow-up CT, 21 months following this procedure, there was no evidence of rethrombosis, and the patient continues to do well under oral anticoagulation. The literature regarding these uncommon mesenteric vein aneurysms without portal vein involvement, as well as their treatment options, is reviewed.

  2. A combined experimental-numerical approach for determining mechanical properties of aluminum subjects to nanoindentation

    PubMed Central

    Liu, Mao; Lu, Cheng; Tieu, Kiet Anh; Peng, Ching-Tun; Kong, Charlie

    2015-01-01

    A crystal plasticity finite element method (CPFEM) model has been developed to investigate the mechanical properties and micro-texture evolution of single-crystal aluminum induced by a sharp Berkovich indenter. The load-displacement curves, pile-up patterns and lattice rotation angles from simulation are consistent with the experimental results. The pile-up phenomenon and lattice rotation have been discussed based on the theory of crystal plasticity. In addition, a polycrystal tensile CPFEM model has been established to explore the relationship between indentation hardness and yield stress. The elastic constraint factor C is slightly larger than conventional value 3 due to the strain hardening. PMID:26464128

  3. Structural and conformational investigation of nemorosone: A combined X-ray and quantum mechanical study

    NASA Astrophysics Data System (ADS)

    Pagano, Bruno; Pavone, Michele; Piccinelli, Anna Lisa; Rastrelli, Luca; Cuesta-Rubio, Osmany; Mattia, Carlo A.; Barone, Vincenzo

    2008-09-01

    Here we report the X-ray crystal structure of nemorosone, a polyprenylated benzophenone derivative that presents biological activity and potential use as antimicrobial, cytotoxic and antioxidant drug. On the basis of crystallographic data, we carried out a theoretical investigation based on state-of-the-art density functional approaches. A remarkable agreement has been found between experimental findings and quantum mechanical results. Furthermore, the theoretical calculations allowed us to dissect the structural and energetic features of the nemorosone molecule, thus paving the route toward the design of new synthetic drugs.

  4. Rapid diffusion of magic-size islands by combined glide and vacancy mechanisms

    SciTech Connect

    Perez, D; Voter, A F; Uche, O U; Hamilton, J C

    2009-01-01

    Using molecular dynamics, nudged elastic band, and embedded atom methods, we show that certain 2D Ag islands undergo extremely rapid one-dimensional diffusion on Cu(001) surfaces. Indeed, below 300K, hopping rates for 'magic-size' islands are orders of magnitude faster than hopping rates for single Ag adatoms. This rapid diffusion requires both the c(10 x 2) hexagonally-packed superstructure typical of Ag on Cu(001) and appropriate 'magic-sizes' for the islands. The novel highly-cooperative diffusion mechanism presented here couples vacancy diffusion with simultaneous core glide.

  5. Battling resistance mechanisms in antihormonal prostate cancer treatment: Novel agents and combinations.

    PubMed

    De Maeseneer, Daan Joost; Van Praet, Charles; Lumen, Nicolaas; Rottey, Sylvie

    2015-07-01

    Prostate cancer (PCa) is a hormone-sensitive disease. Androgen deprivation therapy lowers serum testosterone levels (castration) or blocks the androgen receptor (AR) ligand-binding domain. Especially in metastatic disease, hormonal therapy has been able to delay disease progression, reduce symptoms, and improve overall survival. Despite subsequent disease progression and development of castration resistance, PCa remains AR driven. Secondary hormonal treatments such as abiraterone acetate or enzalutamide have demonstrated increased overall survival. However, new resistance mechanisms to these agents have been identified, and systemic chemotherapy is still needed especially in fast-progressing castration-resistant PCa. Several promising androgen synthesis inhibitors (orteronel and galeterone), AR inhibitors (ARN-509, EPI-001, AZD3514, and ODM-201), and heat shock protein modulators (AT11387, 17-DMAG, STA-9090, and OGX-427) are currently under investigation. The wide variety in upcoming systemic agents underlines the molecular heterogeneity of castration-resistant PCa. This article reviews antihormonal therapy in PCa and resistance mechanisms and focuses on novel and upcoming agents currently in clinical testing. PMID:25708954

  6. Investigation of the mechanical properties of a low-shrinkage liquid crystalline matrix combined with nano-hydroxyapatite.

    PubMed

    Liu, Wen Wen; He, Xiao Ping; Mo, An Chun; Yao, Qian Qian; Ye, Jun; Jing, Nie

    2011-01-01

    The objective of this study was to investigate the mechanical properties of a low-shrinkage acrylate liquid crystalline resin matrix (ALCRM), (4-3-(acryloyloxy)-2-hydroxypropoxy) phenyl 4-(3-(acryloyloxy)-2-hydroxypropoxy) benzoate, combined with nano-hydroxyapatite (na-HA). The ALCRM monomer and diluent monomer triethylene glycol dimethacrylate (TEGDMA) were mixed at a mass ratio of 7:3 to prepare the resin matrix. The volume shrinkage of the ALCRM/TEGDMA and the traditional resin matrix Bis-GMA (2, 2-bis [4-(3-methacryloxy-2-hydroxypropoxy) phenyl] propane)/TEGDMA were measured. Then 20%, 30%, and 40% na-HA were added to ALCRM/TEGDMA and Bis-GMA/TEGDMA, respectively. Compressive strength (CS) and Vickers hardness (VHN) were tested to identify mechanical properties of the composites. The volume shrinkage of the ALCRM/TEGDMA was 3.60% ± 0.36%, which was lower than that of the traditional resin matrix. Moreover, with the same amount of na-HA filler, the mechanical properties of the ALCRM-based composites were superior to those of Bis-GMA-based composites. ALCRM-based composites exhibited the highest CS and VHN values when the filler content was 30%. These results indicate that the low-shrinkage liquid crystalline resin matrix has strong mechanical properties after incorporating the na-HA. The experimental ALCRM-based composites have promising potential for the development of novel low-shrinkage dental resins with strong mechanical properties. PMID:21980241

  7. The use of combined cathodoluminescence and EBSD analysis: a case study investigating grain boundary migration mechanisms in quartz.

    PubMed

    Piazolo, S; Prior, D J; Holness, M D

    2005-02-01

    Grain boundary migration is an important mechanism of microstructural modification both in rocks and in metals. Combining detailed cathodoluminescence (CL) and electron backscatter diffraction (EBSD) analysis offers the opportunity to relate directly changes in crystallographic orientation to migrating boundaries. We observe the following features in naturally heated quartz grains from the thermal aureole of the Ballachulish Igneous Complex (Scotland, U.K.): (a) propagation of substructures and twin boundaries in swept areas both parallel and at an angle to the growth direction, (b) development of slightly different crystallographic orientations and new twin boundaries at both the growth interfaces and within the swept area and (c) a gradual change in crystallographic orientation in the direction of growth. All these features are compatible with a growth mechanism in which single atoms are attached and detached both at random and at preferential sites, i.e. crystallographically controlled sites or kinks in boundary ledges. Additionally, strain fields caused by defects and/or trace element incorporation may facilitate nucleation sites for new crystallographic orientations at distinct growth interfaces but also at continuously migrating boundaries. This study illustrates the usefulness of combined CL and EBSD in microprocess analysis. Further work in this direction may provide detailed insight into both the mechanism of static grain growth and the energies and mobilities of boundaries in terms of misorientation and grain boundary plane orientation. PMID:15683412

  8. Structured material combined HMO-silica fibers: preparation, optical and mechanical behavior

    NASA Astrophysics Data System (ADS)

    Schuster, K.; Kobelke, J.; Litzkendorf, D.; Schwuchow, A.; Lindner, F.; Kirchhof, J.; Bartelt, H.; Auguste, J.-L.; Humbert, G.; Blondy, J.-M.

    2011-03-01

    We report about preparation technique and characterization of structured fibers composed of HMO core glasses and silica cladding. Two processes as material preparation techniques have been developed based on glasses prepared by melting of SAL (e.g. 70SiO2-20Al2O3-10La2O3) glasses and the reactive powder sintering (REPUSIL) method. The melted glasses have been characterized by dilatometrical methods to find Tg values of 827-875°C and expansion coefficients between 4.3 and 7.0×10-6 K-1. The latter is one order of magnitude higher than the expansion coefficient of pure silica glass. Structured fibers (SAL core, silica cladding) were fabricated following the Rod-in-Tube (RIT) and Granulate-in-Tube (GIT) process. The HMO glasses were chosen due du their high lanthanum content and the expected high nonlinearity, suitable for nonlinear applications (e.g. supercontinuum sources). The partial substitution of lanthanum by other rare earth elements (e.g. Ytterbium) allows the preparation of fibers with extremely high rare earth concentration up to 5 mol% Yb2O3. The concentration of alumina in the HMO glasses as "solubilizer" for lanthanide was adjusted to about 20 mol%. So we overcame the concentration limits of rare earth doping of MCVD (maximum ca. 2 mol% RE2O3). Nevertheless, the investigated HMO glasses show their limits by integration in structured silica based fibers: Optical losses are typically in the dB/m range, best value of this work is about 600 dB/km. The mechanical stability of fibers is influenced by mechanical strain caused by the high thermal expansion of the core material and the lower network bonding stability of the HMO glasses, but partially compensated by the silica cladding.

  9. Central pain mechanisms following combined acid and capsaicin perfusion of the human oesophagus.

    PubMed

    Brock, Christina; Andresen, Trine; Frøkjaer, Jens Brøndum; Gale, Jeremy; Olesen, Anne Estrup; Arendt-Nielsen, Lars; Drewes, Asbjørn Mohr

    2010-03-01

    Visceral afferents originating from different gut-segments converge at the spinal level. We hypothesized that chemically-induced hyperalgesia in the oesophagus could provoke widespread visceral hypersensitivity and also influence descending modulatory pain pathways. Fifteen healthy volunteers were studied at baseline, 30, 60 and 90 min after randomized perfusion of the distal oesophagus with either saline or 180 ml 0.1M HCl+2mg capsaicin. Electro-stimulation of the oesophagus, 8 cm proximal to the perfusion site, rectosigmoid electrical stimulation and rectal mechanical and heat stimulations were used. Evoked brain potentials were recorded after electrical stimulations before and after oesophageal perfusion. After the perfusion, rectal hyperalgesia to heat (P<0.01, 37%) and mechanical (P=0.01, 11%) stimulations were demonstrated. In contrast, hypoalgesia to electro-stimulation was observed in both the oesophagus (P<0.03, 23%) and the sigmoid colon (P<0.001, 18%). Referred pain areas to electro-stimulation in oesophagus were reduced by 13% after perfusion (P=0.01). Evoked brain potentials to rectosigmoid stimulations showed decreased latencies and amplitudes of P1, N1 and P2 (P<0.05), whereas oesophagus-evoked brain potentials were unaffected after perfusion. In conclusion, modality-specific hyperalgesia was demonstrated in the lower gut following chemical sensitization of the oesophagus, reflecting widespread central hyperexcitability. Conversely, hypoalgesia to electrical stimulation, decreases in referred pain and latencies of evoked brain potentials was seen. This outcome may reflect a counterbalancing activation of descending inhibitory pathways. As these findings are also seen in the clinical setting, the model may be usable for future basic and pharmacological studies. PMID:19541517

  10. Overexpression of Heat Shock Protein 72 Attenuates NF-κB Activation Using a Combination of Regulatory Mechanisms in Microglia

    PubMed Central

    Khammash, Mustafa; Giffard, Rona G.

    2014-01-01

    Overexpression of the inducible heat shock protein 70, Hsp72, has broadly cytoprotective effects and improves outcome following stroke. A full understanding of how Hsp72 protects cells against injury is elusive, though several distinct mechanisms are implicated. One mechanism is its anti-inflammatory effects. We study the effects of Hsp72 overexpression on activation of the transcription factor NF-κB in microglia combining experimentation and mathematical modeling, using TNFα to stimulate a microglial cell line stably overexpressing Hsp72. We find that Hsp72 overexpression reduces the amount of NF-κB DNA binding activity, activity of the upstream kinase IKK, and amount of IκBα inhibitor phosphorylated following TNFα application. Simulations evaluating several proposed mechanisms suggest that inhibition of IKK activation is an essential component of its regulatory activities. Unexpectedly we find that Hsp72 overexpression reduces the initial amount of the RelA/p65 NF-κB subunit in cells, contributing to the attenuated response. Neither mechanism in isolation, however, is sufficient to attenuate the response, providing evidence that Hsp72 relies upon multiple mechanisms to attenuate NF-κB activation. An additional observation from our study is that the induced expression of IκBα is altered significantly in Hsp72 expressing cells. While the mechanism responsible for this observation is not known, it points to yet another means by which Hsp72 may alter the NF-κB response. This study illustrates the multi-faceted nature of Hsp72 regulation of NF-κB activation in microglia and offers further clues to a novel mechanism by which Hsp72 may protect cells against injury. PMID:24516376

  11. Cerebral vasodilator properties of Danshen and Gegen: a study of their combined efficacy and mechanisms of actions.

    PubMed

    Deng, Y; Ng, E S K; Kwan, Y W; Lau, C B S; Cheung, D W S; Koon, J C M; Zhang, Z; Zuo, Z; Leung, P C; Fung, K P; Lam, F F Y

    2014-03-15

    Danshen and Gegen are two commonly used Chinese herbal medicines for treatment of cardiovascular diseases. The aim of the present study was to elucidate the combination effects of these two herbs on cerebral vascular tone and their underlying mechanisms of actions. Basilar artery rings were obtained from rats and precontracted with U46619. Cumulative administrations of aqueous extracts of Danshen, Gegen, or the two herbs combined (DG; ratio 7:3) produced concentration-dependent relaxation of the artery rings. Statistical analysis on these findings produced a combination index (CI) of 1.041 at ED50, which indicates the two herbs produced additive vasodilator effects when used as a combined decoction. Removal of the endothelium had no effect on the vasodilator properties of Danshen, Gegen, and DG. However, their maximum effects (Imax) were significantly blunted by a KATP channel inhibitor glibenclamide, a non-selective K(+) channel inhibitor tetraethylammonium (TEA), and by a combination of K(+) channel inhibitors (glibenclamide+TEA+iberiotoxin+4-aminopyridine+barium chloride). In addition, Danshen, Gegen, and DG produced augmentation of KATP currents and inhibited Ca(2+) influx in vascular smooth muscle cells isolated from rat basilar arteries. Furthermore, these agents inhibited CaCl2-induced contraction in the artery rings. In conclusion, the present study showed that Danshen and Gegen produced additive vasodilator effects on rat cerebral basilar arteries. These effects were independent of endothelium-derived relaxant factors (EDRF), but required the opening of KATP channels and inhibition of Ca(2+) influx in the vascular smooth muscle cells. It is suspected that the cerebral vasodilator effects of Danshen and Gegen produced either on their own or in combination, can help patients with obstructive cerebrovascular diseases. PMID:24192211

  12. Reaction path determination for quantum mechanical/molecular mechanical modeling of enzyme reactions by combining first order and second order ``chain-of-replicas'' methods

    NASA Astrophysics Data System (ADS)

    Cisneros, G. Andrés; Liu, Haiyan; Lu, Zhenyu; Yang, Weitao

    2005-03-01

    A two-step procedure for the determination of reaction paths in enzyme systems is presented. This procedure combines two chain-of-states methods: a quantum mechanical/molecular mechanical (QM/MM) implementation of the nudged elastic band (NEB) method and a second order parallel path optimizer method both recently developed in our laboratory. In the first step, a reaction path determination is performed with the NEB method, along with a restrained minimization procedure for the MM environment to obtain a first approximation to the reaction path. In the second step, the calculated path is refined with the parallel path optimizer method. By combining these two methods the reaction paths are determined accurately, and in addition, the number of path optimization iterations are significantly reduced. This procedure is tested by calculating both steps of the isomerization of 2-oxo-4-hexenedioate by 4-oxalocrotonate tautomerase, which have been previously determined by our group. The calculated paths agree with the previously reported results and we obtain a reduction of 45%-55% in the number of path optimization cycles.

  13. Combination of Mechanical and Molecular Filtration for Enhanced Enrichment of Circulating Tumor Cells.

    PubMed

    Meunier, Anne; Hernández-Castro, Javier Alejandro; Turner, Kate; Li, Kebin; Veres, Teodor; Juncker, David

    2016-09-01

    Circulating tumor cells (CTCs) have been linked to cancer progression but are difficult to isolate, as they are very rare and heterogeneous, covering a range of sizes and expressing different molecular receptors. Filtration has emerged as a simple and powerful method to enrich CTCs but only captures cells above a certain size regardless of molecular characteristics. Here, we introduce antibody-functionalized microfilters to isolate CTCs based on both size and surface receptor expression. We present a 3D printed filtration cartridge with microfabricated polymer filters with 8, 10, 12, 15, or 20 μm-diameter pores. Pristine filters were used to optimize sample dilution, rinsing protocol, flow rate, and pore size, leading to >80% for the recovery of spiked cancer cells with very low white blood cell contamination (<1000). Then, filters were functionalized with antibodies against either epithelial cell adhesion molecule (EpCAM) or epidermal growth factor receptor (EGFR) and the cartridges were used to enrich breast (MDA-MB-231, MCF-7) and renal (786-O, A-498) cancer cells expressing various levels of EpCAM and EGFR. Cancer cells were spiked into human blood, and when using filters with antibodies specific to a molecular receptor expressed on a cell, efficiency was increased to >96%. These results suggest that filtration can be optimized to target specific CTC characteristics such as size and receptor expression and that a diverse range of CTCs may be captured using particular combinations of pore size, filtration parameters, and antibody functionalization. PMID:27442305

  14. Decoding the mechanisms of gait generation in salamanders by combining neurobiology, modeling and robotics.

    PubMed

    Bicanski, Andrej; Ryczko, Dimitri; Knuesel, Jérémie; Harischandra, Nalin; Charrier, Vanessa; Ekeberg, Örjan; Cabelguen, Jean-Marie; Ijspeert, Auke Jan

    2013-10-01

    Vertebrate animals exhibit impressive locomotor skills. These locomotor skills are due to the complex interactions between the environment, the musculo-skeletal system and the central nervous system, in particular the spinal locomotor circuits. We are interested in decoding these interactions in the salamander, a key animal from an evolutionary point of view. It exhibits both swimming and stepping gaits and is faced with the problem of producing efficient propulsive forces using the same musculo-skeletal system in two environments with significant physical differences in density, viscosity and gravitational load. Yet its nervous system remains comparatively simple. Our approach is based on a combination of neurophysiological experiments, numerical modeling at different levels of abstraction, and robotic validation using an amphibious salamander-like robot. This article reviews the current state of our knowledge on salamander locomotion control, and presents how our approach has allowed us to obtain a first conceptual model of the salamander spinal locomotor networks. The model suggests that the salamander locomotor circuit can be seen as a lamprey-like circuit controlling axial movements of the trunk and tail, extended by specialized oscillatory centers controlling limb movements. The interplay between the two types of circuits determines the mode of locomotion under the influence of sensory feedback and descending drive, with stepping gaits at low drive, and swimming at high drive. PMID:23430277

  15. Combination of magnetic and enhanced mechanical properties for copolymer-grafted magnetite composite thermoplastic elastomers.

    PubMed

    Jiang, Feng; Zhang, Yaqiong; Wang, Zhongkai; Wang, Wentao; Xu, Zhaohua; Wang, Zhigang

    2015-05-20

    Composite thermoplastic elastomers (CTPEs) of magnetic copolymer-grafted nanoparticles (magnetite, Fe3O4) were synthesized and characterized to generate magnetic CTPEs, which combined the magnetic property of Fe3O4 nanoparticles and the thermoplastic elasticity of the grafted amorphous polymer matrix. Fe3O4 nanoparticles served as stiff, multiple physical cross-linking points homogeneously dispersed in the grafted poly(n-butyl acrylate-co-methyl methacrylate) rubbery matrix synthesized via the activators regenerated by electron transfer for atom transfer radical polymerization method (ARGET ATRP). The preparation technique for magnetic CTPEs opened a new route toward developing a wide spectrum of magnetic elastomeric materials with strongly enhanced macroscopic properties. Differential scanning calorimetry (DSC) was used to measure the glass transition temperatures, and thermogravimetric analysis (TGA) was used to examine thermal stabilities of these CTPEs. The magnetic property could be conveniently tuned by adjusting the content of Fe3O4 nanoparticles in CTPEs. Compared to their linear copolymers, these magnetic CTPEs showed significant increases in tensile strength and elastic recovery. In situ small-angle X-ray scattering measurement was conducted to reveal the microstructural evolution of CTPEs during tensile deformation. PMID:25954980

  16. [Mechanism of inhibiting the cell growth in diffuse large B-cell lymphoma by valproic acid combined with temsirolimus].

    PubMed

    Zheng, Zhong; Zhao, Yan; Dong, Li-Hua; Wang, Li; Cheng, Shu; Zhao, Wei-Li

    2013-12-01

    The aim of this study was to illustrate the mechanism of inhibiting the cell growth in diffuse large B-cell lymphoma by histone deacetylase inhibitor valproic acid (VPA) combined with mTOR inhibitor temsirolimus (TEM). MTT assay and Wright's stain were used to assess cell growth inhibition and to detect the cell morphological changes respectively. The cell apoptosis, cell cycle and cell autophagy were determined by flow cytometry. Ultrastructure changes were confirmed by electron microscopy. Protein changes were detected by Western blot. The results showed that both VPA and TEM alone inhibited cell proliferation and the effect was more obvious in the combination group. VPA combined with TEM induced cell arrest in G0/G1 phase and upregulated the expression of autophagy-related protein LC3, without cell apoptosis. Moreover, typical autophagosomes were observed, further confirming the presence of autophagy. Western blot showed the changes of proteins involved in autophagy signaling pathway. VPA decreased HDAC1 and HDAC3 expression and increased histone acetylation, suggesting that VPA also affected lymphoma cell proliferation through epigenetic modification. It is concluded that the combined treatment of VPA and TEM induces cell cycle arrest and cell autophagy, which provides a new clue for their clinical application in diffuse large B-cell lymphoma. PMID:24370026

  17. [Apoptosis-inducing effect of valproic acid combined with arsenic trioxide on RPMI 8226 cells and its mechanism].

    PubMed

    Wang, Xiao-Ning; Zhang, Mei

    2014-08-01

    This study was aimed to investigate the apoptosis-inducing effect of valproic acid (VPA) combined with arsenic trioxide (ATO) on human multiple myeloma RPMI 8226 cells and its mechanism. The cell proliferation of RPMI 8226 cells was assayed by CCK-8 method. The cell apoptosis were detected by flow cytometry. Semiquantitative RT-PCR and Western blot were applied respectively to detect the mRNA and protein expression level of BCL-2, BAX, caspase-8 and caspase-9 gene. The results showed that both the VPA and ATO inhibited RPMI 8226 cell proliferation. The combination of ATO and VPA has synergistic effect (Q values greater than 1.15). The RPMI 8226 cell apoptosis rate in combined drug group was significantly higher than that in single drug group (P < 0.05). The mRNA and protein expressions of BCL-2 gene in combined drug group decreased, while the mRNA and protein expressions of BAX, caspase-8 and caspase-9 significantly increased, compared with single drug group (P < 0.05) . It is concluded that VPA can enhance the sensitivity of RPMI 8226 cells to ATO-induced apoptosis, which may be associated with decreasing the BCL-2 expression and increasing the BAX, caspase-8 and caspase-9 gene expression. PMID:25130820

  18. Combining 3D printed forms with textile structures - mechanical and geometrical properties of multi-material systems

    NASA Astrophysics Data System (ADS)

    Sabantina, L.; Kinzel, F.; Ehrmann, A.; Finsterbusch, K.

    2015-07-01

    The 3D printing belongs to the rapidly emerging technologies which have the chance to revolutionize the way products are created. In the textile industry, several designers have already presented creations of shoes, dresses or other garments which could not be produced with common techniques. 3D printing, however, is still far away from being a usual process in textile and clothing production. The main challenge results from the insufficient mechanical properties, especially the low tensile strength, of pure 3D printed products, prohibiting them from replacing common technologies such as weaving or knitting. Thus, one way to the application of 3D printed forms in garments is combining them with textile fabrics, the latter ensuring the necessary tensile strength. This article reports about different approaches to combine 3D printed polymers with different textile materials and fabrics, showing chances and limits of this technique.

  19. Research on the mechanical properties of a glass fiber reinforced polymer-steel combined truss structure.

    PubMed

    Liu, Pengfei; Zhao, Qilin; Li, Fei; Liu, Jinchun; Chen, Haosen

    2014-01-01

    An assembled plane truss structure used for vehicle loading is designed and manufactured. In the truss, the glass fiber reinforced polymer (GFRP) tube and the steel joint are connected by a new technology featuring a pretightened tooth connection. The detailed description for the rod and node design is introduced in this paper, and a typical truss panel is fabricated. Under natural conditions, the short-term load test and long-term mechanical performance test for one year are performed to analyze its performance and conduct a comparative analysis for a reasonable FEM model. The study shows that the design and fabrication for the node of an assembled truss panel are convenient, safe, and reliable; because of the creep control design of the rods, not only does the short-term structural stiffness meet the design requirement but also the long-term creep deformation tends towards stability. In addition, no significant change is found in the elastic modules, so this structure can be applied in actual engineering. Although the safety factor for the strength of the composite rods is very large, it has a lightweight advantage over the steel truss for the low density of GFRP. In the FEM model, simplifying the node as a hinge connection relatively conforms to the actual status. PMID:25247203

  20. Research on the Mechanical Properties of a Glass Fiber Reinforced Polymer-Steel Combined Truss Structure

    PubMed Central

    Liu, Pengfei; Zhao, Qilin; Li, Fei; Liu, Jinchun; Chen, Haosen

    2014-01-01

    An assembled plane truss structure used for vehicle loading is designed and manufactured. In the truss, the glass fiber reinforced polymer (GFRP) tube and the steel joint are connected by a new technology featuring a pretightened tooth connection. The detailed description for the rod and node design is introduced in this paper, and a typical truss panel is fabricated. Under natural conditions, the short-term load test and long-term mechanical performance test for one year are performed to analyze its performance and conduct a comparative analysis for a reasonable FEM model. The study shows that the design and fabrication for the node of an assembled truss panel are convenient, safe, and reliable; because of the creep control design of the rods, not only does the short-term structural stiffness meet the design requirement but also the long-term creep deformation tends towards stability. In addition, no significant change is found in the elastic modules, so this structure can be applied in actual engineering. Although the safety factor for the strength of the composite rods is very large, it has a lightweight advantage over the steel truss for the low density of GFRP. In the FEM model, simplifying the node as a hinge connection relatively conforms to the actual status. PMID:25247203

  1. VUV treatment combined with mechanical strain of stretchable polymer foils resulting in cell alignment

    NASA Astrophysics Data System (ADS)

    Barb, R.-A.; Magnus, B.; Innerbichler, S.; Greunz, T.; Wiesbauer, M.; Marksteiner, R.; Stifter, D.; Heitz, J.

    2015-01-01

    Cell-alignment along a defined direction can have a direct effect on the cell functionality and differentiation. Oriented micro- or nanotopographic structures on cell culture substrates can induce cell-alignment. Surface chemistry, wettability, and stiffness of the substrate are also important material features as they strongly influence the cell-substrate interactions. For improved bio-compatibility, highly elastic polyurethane (PU) foils were exposed to the vacuum-UV (VUV) light of a Xe2* excimer lamp at 172 nm in a nitrogen containing atmosphere (N2 or NH3). The irradiation resulted in a change in the chemical surface composition. Additionally, the formation of regular parallel microgrooves was observed on the irradiated surfaces after strong uni-axial deformation (i.e., more than about 50% strain) of the photo-modified PU foils. Cell seeding experiments demonstrated that the VUV modified polymer foils strongly enhance cell adhesion and proliferation. Cells seeded onto microgrooves aligned their shapes and elongated in the direction of the grooves. A similar effect was observed for cells seeded on photo-modified PU foils subjected to cyclic mechanical stretching at lower strain levels (i.e., typically 10% strain) without groove-formation. The cells had also here an elongated shape, however they not always align in a defined direction relative to the stretching.

  2. Mechanism of Reversible Peptide-Bilayer Attachment: Combined Simulation and Experimental Single-Molecule Study.

    PubMed

    Schwierz, Nadine; Krysiak, Stefanie; Hugel, Thorsten; Zacharias, Martin

    2016-01-26

    The binding of peptides and proteins to lipid membrane surfaces is of fundamental importance for many membrane-mediated cellular processes. Using closely matched molecular dynamics simulations and atomic force microscopy experiments, we study the force-induced desorption of single peptide chains from phospholipid bilayers to gain microscopic insight into the mechanism of reversible attachment. This approach allows quantification of desorption forces and decomposition of peptide-membrane interactions into energetic and entropic contributions. In both simulations and experiments, the desorption forces of peptides with charged and polar side chains are much smaller than those for hydrophobic peptides. The adsorption of charged/polar peptides to the membrane surface is disfavored by the energetic components, requires breaking of hydrogen bonds involving the peptides, and is favored only slightly by entropy. By contrast, the stronger adsorption of hydrophobic peptides is favored both by energy and by entropy and the desorption forces increase with increasing side-chain hydrophobicity. Interestingly, the calculated net adsorption free energies per residue correlate with experimental results of single residues, indicating that side-chain free energy contributions are largely additive. This observation can help in the design of peptides with tailored adsorption properties and in the estimation of membrane binding properties of peripheral membrane proteins. PMID:26717083

  3. Combining Laser Microsurgery and Finite Element Modeling to Assess Cell-Level Epithelial Mechanics

    PubMed Central

    Hutson, M. Shane; Veldhuis, J.; Ma, Xiaoyan; Lynch, Holley E.; Cranston, P. Graham; Brodland, G. Wayne

    2009-01-01

    Abstract Laser microsurgery and finite element modeling are used to determine the cell-level mechanics of the amnioserosa—a morphogenetically crucial epithelium on the dorsal surface of fruit fly embryos (Drosophila melanogaster). In the experiments, a tightly focused laser ablates a subcellular hole (1 μm in diameter) that passes clean through the epithelium. The surrounding cells recoil from the wound site with a large range of initial recoil velocities. These depend on the embryo's developmental stage and the subcellular wound site. The initial recoil (up to 0.1 s) is well reproduced by a base finite element model, which assumes a uniform effective viscosity inside the cells, a constant tension along each cell-cell boundary, and a large, potentially anisotropic, far-field stress—one that far exceeds the stress equivalent of the cell-edge tensions. After 0.1 s, the experimental recoils slow dramatically. This observation can be reproduced by adding viscoelastic rods along cell edges or as a fine prestressed mesh parallel to the apical and basal membranes of the cell. The mesh also reproduces a number of double-wounding experiments in which successive holes are drilled in a single cell. PMID:20006944

  4. Combining classical and molecular approaches elaborates on the complexity of mechanisms underpinning anterior regeneration.

    PubMed

    Evans, Deborah J; Owlarn, Suthira; Tejada Romero, Belen; Chen, Chen; Aboobaker, A Aziz

    2011-01-01

    The current model of planarian anterior regeneration evokes the establishment of low levels of Wnt signalling at anterior wounds, promoting anterior polarity and subsequent elaboration of anterior fate through the action of the TALE class homeodomain PREP. The classical observation that decapitations positioned anteriorly will regenerate heads more rapidly than posteriorly positioned decapitations was among the first to lead to the proposal of gradients along an anteroposterior (AP) axis in a developmental context. An explicit understanding of this phenomenon is not included in the current model of anterior regeneration. This raises the question what the underlying molecular and cellular basis of this temporal gradient is, whether it can be explained by current models and whether understanding the gradient will shed light on regenerative events. Differences in anterior regeneration rate are established very early after amputation and this gradient is dependent on the activity of Hedgehog (Hh) signalling. Animals induced to produce two tails by either Smed-APC-1(RNAi) or Smed-ptc(RNAi) lose anterior fate but form previously described ectopic anterior brain structures. Later these animals form peri-pharyngeal brain structures, which in Smed-ptc(RNAi) grow out of the body establishing a new A/P axis. Combining double amputation and hydroxyurea treatment with RNAi experiments indicates that early ectopic brain structures are formed by uncommitted stem cells that have progressed through S-phase of the cell cycle at the time of amputation. Our results elaborate on the current simplistic model of both AP axis and brain regeneration. We find evidence of a gradient of hedgehog signalling that promotes posterior fate and temporarily inhibits anterior regeneration. Our data supports a model for anterior brain regeneration with distinct early and later phases of regeneration. Together these insights start to delineate the interplay between discrete existing, new, and then

  5. Analysis of Reaction Mechanisms in Flames Using Combined - and Lif-Spectroscopy

    NASA Astrophysics Data System (ADS)

    Brockhinke, Andreas; Nau, Patrick; Köhler, Markus; Kohse-Höinghaus, Katharina

    2009-06-01

    Laser-based non-intrusive diagnostic techniques are firmly established as the most versatile tools to study high-temperature gas-phase reactions in general and combustion processes in particular. While fossil fuels remain the most important primary energy carriers, alternative fuels gain in importance. Usually, these fuels contain significant amounts of oxygen, nitrogen and sulphur, leading to different reaction pathways than in the established combustion of hydrocarbons. In order to minimize the formation of pollutants and hazardous compounds (soot, CO, NO_{x}) and increase efficiency, a deeper understanding of these reaction processes is essential. Optical measurements, in particular Cavity Ring-Down Spectroscopy (CRDS) and Laser Induced Fluorescence spectroscopy (LIF), have proven to be well suited for quantitative radical measurements in flames (e.g. OH, ^1CH_2, C_2, HCO). Both techniques provide high sensitivity and selectivity. Our revised experimental setup is designed for quasi-simultaneous measurements, combining the positive features of both complementary techniques. In addition, invasive methods like mass-spectrometry are performed in order to gain a complete understanding of the flame species. In this contribution, we will focus on the quantitative determination of important minor species such as CN, NH_2, CH and formaldehyde in low-pressure flat flames. In addition to investigations of flames with hydrocarbon fuels, we present the first optical measurements in morpholine- and ethylamine-flames. Aim of these measurements is to study the conversion of fuel nitrogen to NO_{x}. Experimental results will be compared with numerical CHEMKIN-II simulations.

  6. Antibiotic prescription patterns in the empiric therapy of severe sepsis: combination of antimicrobials with different mechanisms of action reduces mortality

    PubMed Central

    2012-01-01

    Introduction Although early institution of adequate antimicrobial therapy is lifesaving in sepsis patients, optimal antimicrobial strategy has not been established. Moreover, the benefit of combination therapy over monotherapy remains to be determined. Our aims are to describe patterns of empiric antimicrobial therapy in severe sepsis, assessing the impact of combination therapy, including antimicrobials with different mechanisms of action, on mortality. Methods This is a Spanish national multicenter study, analyzing all patients admitted to ICUs who received antibiotics within the first 6 hours of diagnosis of severe sepsis or septic shock. Antibiotic-prescription patterns in community-acquired infections and nosocomial infections were analyzed separately and compared. We compared the impact on mortality of empiric antibiotic treatment, including antibiotics with different mechanisms of action, termed different-class combination therapy (DCCT), with that of monotherapy and any other combination therapy possibilities (non-DCCT). Results We included 1,372 patients, 1,022 (74.5%) of whom had community-acquired sepsis and 350 (25.5%) of whom had nosocomial sepsis. The most frequently prescribed antibiotic agents were β-lactams (902, 65.7%) and carbapenems (345, 25.1%). DCCT was administered to 388 patients (28.3%), whereas non-DCCT was administered to 984 (71.7%). The mortality rate was significantly lower in patients administered DCCTs than in those who were administered non-DCCTs (34% versus 40%; P = 0.042). The variables independently associated with mortality were age, male sex, APACHE II score, and community origin of the infection. DCCT was a protective factor against in-hospital mortality (odds ratio (OR), 0.699; 95% confidence interval (CI), 0.522 to 0.936; P = 0.016), as was urologic focus of infection (OR, 0.241; 95% CI, 0.102 to 0.569; P = 0.001). Conclusions β-Lactams, including carbapenems, are the most frequently prescribed antibiotics in empiric

  7. Characterization of mechanical properties of hybrid contrast agents by combining atomic force microscopy with acoustic/optic assessments.

    PubMed

    Guo, Gepu; Tu, Juan; Guo, Xiasheng; Huang, Pintong; Wu, Junru; Zhang, Dong

    2016-02-01

    Multi-parameter fitting algorithms, which are currently used for the characterization of coated-bubbles, inevitably introduce uncertainty into the results. Therefore, a better technique that can accurately determine the microbubbles׳ mechanical properties is urgently needed. A comprehensive technology combining atomic force microscopy, optical, and acoustic measurements with simulations of coated-bubble dynamics was developed. Using this technique, the mechanical parameters (size distribution, shell thickness, elasticity, and viscosity) of hybrid (ultrasound/magnetic-resonance-imaging) contrast microbubbles and their structure-property relationship were determined. The measurements indicate that when more superparamagnetic iron oxide nanoparticles are embedded in the microbubbles׳ shells, their mean diameter and effective viscosity increase, and their elastic modulus decreases. This reduces the microbubbles׳ resonance frequency and thus enhances acoustic scattering and attenuation effects. PMID:26726783

  8. Dynamics of associating polymers and the sticky Rouse model: a study by combined dielectric and dynamic mechanical techniques

    NASA Astrophysics Data System (ADS)

    Wang, Yangyang; Cosby, Tyler; Sangoro, Joshua

    Reversible association through non-covalent bonding is ubiquitous in the soft matter world. Despite decades of studies, the dynamics of associating polymers have not been well understood. Here we examine the dynamics of butadiene- and isoprene-based model polymeric systems with pairwise association through hydrogen bonding. Compared to ionomers, where reversible crosslinks are typically not well defined, these hydrogen bonding polymers are associated through strictly binary contacts and thus provide a better opportunity to test theoretical ideas. By combining dielectric spectroscopy and dynamic mechanical measurement, we are able to identify both chain and junction dynamics and analyze their motional coupling mechanism. The results are discussed in the context of the sticky Rouse model.

  9. Enhanced correlation between quantitative ultrasound and structural and mechanical properties of bone using combined transmission-reflection measurement

    PubMed Central

    Lin, Liangjun; Lin, Wei; Qin, Yi-Xian

    2015-01-01

    Quantitative ultrasound (QUS) is capable of predicting the principal structural orientation of trabecular bone; this orientation is highly correlated with the mechanical strength of trabecular bone. Irregular shape of bone, however, would increase variation in such a prediction, especially under human in vivo measurement. This study was designed to combine transmission and reflection modes of QUS measurement to improve the prediction for the structural and mechanical properties of trabecular bone. QUS, mechanical testing, and micro computed tomography (μCT) scanning were performed on 24 trabecular bone cubes harvested from a bovine distal femur to obtain the mechanical and structural parameters. Transmission and reflection modes of QUS measurement in the transverse and frontal planes were performed in a confined 60° angle range with 5° increment. The QUS parameters, attenuation (ATT) and velocity (UV), obtained from transmission mode, were normalized to the specimen thickness acquired from reflection mode. Analysis of covariance showed that the combined transmission-reflection modes improved prediction for the structural and Young's modulus of bone in comparison to the traditional QUS measurement performed only in the medial-lateral orientation. In the transverse plane, significant improvement between QUS and μCT was found in ATT vs bone surface density (BS/BV) (p < 0.05), ATT vs trabecular thickness (Tb.Th) (p < 0.01), ATT vs degree of anisotropy (DA) (p < 0.05), UV vs trabecular bone number (Tb.N) (p < 0.05), and UV vs Tb.Th (p < 0.001). In the frontal plane, significant improvement was found in ATT vs structural model index (SMI) (p < 0.01), ATT vs bone volume fraction (BV/TV) (p < 0.01), ATT vs BS/BV (p < 0.001), ATT vs Tb.Th (p < 0.001), ATT vs DA (p < 0.001), and ATT vs modulus (p < 0.001), UV vs SMI (p < 0.01), UV vs BV/TV (p < 0.05), UV vs BS/BV (p < 0.05), UV vs Tb.Th (p < 0.01), UV vs

  10. Combined solid-state and mechanically-switched transformer tap-changer

    SciTech Connect

    Eitzmann, M.A.; Hill, A.T.

    1995-04-18

    Disclosed is an End-Turn Solid-State Switching (ETSS) transformer tap which makes use of a high-speed solid-state switching network to select either the end-turn lead or one of a number of non-isolated taps on a transformer regulating winding, and connects the selected tap to, while disconnecting the previously selected tap from, a single output conductor carrying the transformer load current. ETSS effectively changes the reference to one of the possible taps interfaced to a solid-state switching network. The same transformer regulating winding connected to ETSS can also be connected in series with a slow-speed mechanically-switched tap-changer (LTC). ETSS selects one connection point on the regulating winding while LTC operation selects the second point. A difference voltage is produced, depending on the number of turns between the ETSS selected tap and the LTC selected tap. The sign of the difference in voltage depends on whether the ETSS selected tap is higher or lower than the LTC selected tap. The difference or tap selected voltage is in series with the transformer load current. In one embodiment, the high-speed solid-state switching network uses a ``Staggered Progression of Solid-State Switches`` (SPSS) to select one of a number of non-isolated taps on a transformer regulating winding and connect the selected tap in series with the load circuit. A switching network arranged according to the method SPSS reduces the necessary total switch power rating, and steady-state losses. ETSS can accomplish modulation of the tap-selected voltage about the nominal value established by the LTC. 9 figs.

  11. Metabolic and Target-Site Mechanisms Combine to Confer Strong DDT Resistance in Anopheles gambiae

    PubMed Central

    Mitchell, Sara N.; Rigden, Daniel J.; Dowd, Andrew J.; Lu, Fang; Wilding, Craig S.; Weetman, David; Dadzie, Samuel; Jenkins, Adam M.; Regna, Kimberly; Boko, Pelagie; Djogbenou, Luc; Muskavitch, Marc A. T.; Ranson, Hilary; Paine, Mark J. I.; Mayans, Olga; Donnelly, Martin J.

    2014-01-01

    The development of resistance to insecticides has become a classic exemplar of evolution occurring within human time scales. In this study we demonstrate how resistance to DDT in the major African malaria vector Anopheles gambiae is a result of both target-site resistance mechanisms that have introgressed between incipient species (the M- and S-molecular forms) and allelic variants in a DDT-detoxifying enzyme. Sequencing of the detoxification enzyme, Gste2, from DDT resistant and susceptible strains of An. gambiae, revealed a non-synonymous polymorphism (I114T), proximal to the DDT binding domain, which segregated with strain phenotype. Recombinant protein expression and DDT metabolism analysis revealed that the proteins from the susceptible strain lost activity at higher DDT concentrations, characteristic of substrate inhibition. The effect of I114T on GSTE2 protein structure was explored through X-ray crystallography. The amino acid exchange in the DDT-resistant strain introduced a hydroxyl group nearby the hydrophobic DDT-binding region. The exchange does not result in structural alterations but is predicted to facilitate local dynamics and enzyme activity. Expression of both wild-type and 114T alleles the allele in Drosophila conferred an increase in DDT tolerance. The 114T mutation was significantly associated with DDT resistance in wild caught M-form populations and acts in concert with target-site mutations in the voltage gated sodium channel (Vgsc-1575Y and Vgsc-1014F) to confer extreme levels of DDT resistance in wild caught An. gambiae. PMID:24675797

  12. The mechanical properties of stored red blood cells measured by a convenient microfluidic approach combining with mathematic model.

    PubMed

    Wang, Ying; You, Guoxing; Chen, Peipei; Li, Jianjun; Chen, Gan; Wang, Bo; Li, Penglong; Han, Dong; Zhou, Hong; Zhao, Lian

    2016-03-01

    The mechanical properties of red blood cells (RBCs) are critical to the rheological and hemodynamic behavior of blood. Although measurements of the mechanical properties of RBCs have been studied for many years, the existing methods, such as ektacytometry, micropipette aspiration, and microfluidic approaches, still have limitations. Mechanical changes to RBCs during storage play an important role in transfusions, and so need to be evaluated pre-transfusion, which demands a convenient and rapid detection method. We present a microfluidic approach that focuses on the mechanical properties of single cell under physiological shear flow and does not require any high-end equipment, like a high-speed camera. Using this method, the images of stretched RBCs under physical shear can be obtained. The subsequent analysis, combined with mathematic models, gives the deformability distribution, the morphology distribution, the normalized curvature, and the Young's modulus (E) of the stored RBCs. The deformability index and the morphology distribution show that the deformability of RBCs decreases significantly with storage time. The normalized curvature, which is defined as the curvature of the cell tail during stretching in flow, suggests that the surface charge of the stored RBCs decreases significantly. According to the mathematic model, which derives from the relation between shear stress and the adherent cells' extension ratio, the Young's moduli of the stored RBCs are also calculated and show significant increase with storage. Therefore, the present method is capable of representing the mechanical properties and can distinguish the mechanical changes of the RBCs during storage. The advantages of this method are the small sample needed, high-throughput, and easy-use, which make it promising for the quality monitoring of RBCs. PMID:27014397

  13. Effects of provinol and its combinations with clinically used antiasthmatics on airway defense mechanisms in experimental allergic asthma.

    PubMed

    Kazimierová, I; Jošková, M; Pecháňová, O; Šutovská, M; Fraňová, S

    2015-01-01

    Our previous studies show that provinol, a polyphenolic compound, has anti-inflammatory activity during allergic inflammation. In the present study we investigated the effects of provinol and its combinations with clinically used antiasthmatics: budesonide or theophylline on airway defense mechanisms during experimental allergic asthma. Separate groups of guinea pigs were treated during the course of 21-day ovalbumin sensitization with provinol (20 mg/kg/day, p.o.), or budesonide (1 mM by inhalation), or theophylline (10 mg/kg/day, i.p.), and with a half-dose combination of provinol+budesonide or provinol+theophylline. Airways defense mechanisms: cough reflex and specific airway resistance (sRaw) were evaluated in vivo. Tracheal smooth muscle reactivity and mucociliary clearance were examined in vitro. The findings were that provinol caused significant decreases in sRaw and in tracheal smooth muscle contractility, a suppression of cough reflex, and positively modulated ciliary beat frequency. The bronchodilatory and antitussive effects of provinol were comparable with those of budesonide and theophylline. Provinol given as add-on treatment significantly potentiated the effects of budesonide or theophylline, although the doses of each were halved. We conclude that provinol not only has bronchodilatory and antitussive effects, but also potentiates similar effects exerted by budesonide and theophylline. PMID:25315622

  14. Midterm Results of a Combined Biological and Mechanical Approach for the Treatment of a Complex Knee Lesion

    PubMed Central

    Filardo, G.; Di Martino, A.; Delcogliano, M.; Marcacci, M.

    2012-01-01

    Objective: Complex fractures of the tibial plateau are difficult to treat and present a high complication rate. The goal of this report is to describe a combined biological and mechanical approach to restore all morphological and functional knee properties. Methods: We treated a 50-year-old woman, who was affected by a posttraumatic osteochondral lesion and depression of the lateral tibial plateau with knee valgus deviation. The mechanical axis was corrected with a lateral tibial plateau elevation osteotomy, the damaged joint surface was replaced by a recently developed biomimetic osteochondral scaffold, and a hinged dynamic external fixator was applied to protect the graft and at the same time to allow postoperative joint mobilization. Results: A marked clinical improvement was documented at 12 months and further improved up to 5 years, with pain-free full range of motion and return to previous activities. The MRI evaluation at 12 and 24 months showed that the implant remained in site with a hyaline-like signal and restoration of the articular surface. Conclusion: This case report describes a combined surgical approach for complex knee lesions that could represent a treatment option to avoid or at least delay posttraumatic osteoarthritis and more invasive procedures. PMID:26069639

  15. Mechanical competence of ovariectomy-induced compromised bone after single or combined treatment with high-frequency loading and bisphosphonates

    PubMed Central

    Camargos G. V.; Bhattacharya P.; van Lenthe G. H.; Del Bel Cury A. A.; Naert I.; Duyck J.; Vandamme K.

    2015-01-01

    Osteoporosis leads to increased bone fragility, thus effective approaches enhancing bone strength are needed. Hence, this study investigated the effect of single or combined application of high-frequency (HF) loading through whole body vibration (WBV) and alendronate (ALN) on the mechanical competence of ovariectomy-induced osteoporotic bone. Thirty-four female Wistar rats were ovariectomized (OVX) or sham-operated (shOVX) and divided into five groups: shOVX, OVX-shWBV, OVX-WBV, ALN-shWBV and ALN-WBV. (Sham)WBV loading was applied for 10 min/day (130 to 150 Hz at 0.3g) for 14 days and ALN at 2 mg/kg/dose was administered 3x/week. Finite element analysis based on micro-CT was employed to assess bone biomechanical properties, relative to bone micro-structural parameters. HF loading application to OVX resulted in an enlarged cortex, but it was not able to improve the biomechanical properties. ALN prevented trabecular bone deterioration and increased bone stiffness and bone strength of OVX bone. Finally, the combination of ALN with HF resulted in an increased cortical thickness in OVX rats when compared to single treatments. Compared to HF loading, ALN treatment is preferred for improving the compromised mechanical competence of OVX bone. In addition, the association of ALN with HF loading results in an additive effect on the cortical thickness. PMID:26027958

  16. The molecular mechanism of action of aspirin, curcumin and sulforaphane combinations in the chemoprevention of pancreatic cancer

    PubMed Central

    THAKKAR, ARVIND; SUTARIA, DHRUVITKUMAR; GRANDHI, B. KARTHIK; WANG, JEFFREY; PRABHU, SUNIL

    2013-01-01

    Pancreatic cancer ranks as the fourth most deadly form of cancer in the United States with ~37,000 deaths each year. The present study evaluated the chemopreventive potential of a combination of aspirin (ASP), curcumin (CUR) and sulforaphane (SFN) in low doses to human pancreatic cancer cells, MIA PaCa-2 and Panc-1. Results demonstrated that low doses of ASP (1 mM), CUR (10 μM) and SFN (5 μM) (ACS) combination reduced cell viability by ~70% (P<0.001), and also induced cell apoptosis by ~51% (P<0.001) accompanied by activation of caspase-3 and Poly(ADP-ribose) polymerase (PARP) proteins. The NF-κB DNA binding activity was inhibited by ~45% (P<0.01) and ~75% (P<0.001) in MIA PaCa-2 and Panc-1 cells, respectively. Mechanistic studies revealed that ACS promoted increase expression of phospho extracellular signal-regulated kinase 1/2 (P-ERK1/2), c-Jun, p38 MAPK and p53 proteins. Furthermore, the cells pretreated with U0126 (ERK1/2 inhibitor) partially abolished the effect of ACS on cell viability. Data from this study demonstrate that a low-dose ACS combination inhibits cell growth by inducing cell apoptosis, and proposes sustained activation of the ERK1/2 signaling pathway as one of the possible mechanisms. PMID:23404329

  17. A bifurcation study to guide the design of a landing gear with a combined uplock/downlock mechanism.

    PubMed

    Knowles, James A C; Lowenberg, Mark H; Neild, Simon A; Krauskopf, Bernd

    2014-12-01

    This paper discusses the insights that a bifurcation analysis can provide when designing mechanisms. A model, in the form of a set of coupled steady-state equations, can be derived to describe the mechanism. Solutions to this model can be traced through the mechanism's state versus parameter space via numerical continuation, under the simultaneous variation of one or more parameters. With this approach, crucial features in the response surface, such as bifurcation points, can be identified. By numerically continuing these points in the appropriate parameter space, the resulting bifurcation diagram can be used to guide parameter selection and optimization. In this paper, we demonstrate the potential of this technique by considering an aircraft nose landing gear, with a novel locking strategy that uses a combined uplock/downlock mechanism. The landing gear is locked when in the retracted or deployed states. Transitions between these locked states and the unlocked state (where the landing gear is a mechanism) are shown to depend upon the positions of two fold point bifurcations. By performing a two-parameter continuation, the critical points are traced to identify operational boundaries. Following the variation of the fold points through parameter space, a minimum spring stiffness is identified that enables the landing gear to be locked in the retracted state. The bifurcation analysis also shows that the unlocking of a retracted landing gear should use an unlock force measure, rather than a position indicator, to de-couple the effects of the retraction and locking actuators. Overall, the study demonstrates that bifurcation analysis can enhance the understanding of the influence of design choices over a wide operating range where nonlinearity is significant. PMID:25484601

  18. A bifurcation study to guide the design of a landing gear with a combined uplock/downlock mechanism

    PubMed Central

    Knowles, James A. C.; Lowenberg, Mark H.; Neild, Simon A.; Krauskopf, Bernd

    2014-01-01

    This paper discusses the insights that a bifurcation analysis can provide when designing mechanisms. A model, in the form of a set of coupled steady-state equations, can be derived to describe the mechanism. Solutions to this model can be traced through the mechanism's state versus parameter space via numerical continuation, under the simultaneous variation of one or more parameters. With this approach, crucial features in the response surface, such as bifurcation points, can be identified. By numerically continuing these points in the appropriate parameter space, the resulting bifurcation diagram can be used to guide parameter selection and optimization. In this paper, we demonstrate the potential of this technique by considering an aircraft nose landing gear, with a novel locking strategy that uses a combined uplock/downlock mechanism. The landing gear is locked when in the retracted or deployed states. Transitions between these locked states and the unlocked state (where the landing gear is a mechanism) are shown to depend upon the positions of two fold point bifurcations. By performing a two-parameter continuation, the critical points are traced to identify operational boundaries. Following the variation of the fold points through parameter space, a minimum spring stiffness is identified that enables the landing gear to be locked in the retracted state. The bifurcation analysis also shows that the unlocking of a retracted landing gear should use an unlock force measure, rather than a position indicator, to de-couple the effects of the retraction and locking actuators. Overall, the study demonstrates that bifurcation analysis can enhance the understanding of the influence of design choices over a wide operating range where nonlinearity is significant. PMID:25484601

  19. Mechanical energy profiles of the combined ankle-foot system in normal gait: insights for prosthetic designs.

    PubMed

    Takahashi, Kota Z; Stanhope, Steven J

    2013-09-01

    Over the last half-century, the field of prosthetic engineering has continuously evolved with much attention being dedicated to restoring the mechanical energy properties of ankle joint musculatures during gait. However, the contributions of 'distal foot structures' (e.g., foot muscles, plantar soft tissue) have been overlooked. Therefore, the purpose of this study was to quantify the total mechanical energy profiles (e.g., power, work, and work-ratio) of the natural ankle-foot system (NAFS) by combining the contributions of the ankle joint and all distal foot structures during stance in level-ground steady state walking across various speeds (0.4, 0.6, 0.8 and 1.0 statures/s). The results from eleven healthy subjects walking barefoot indicated ankle joint and distal foot structures generally performed opposing roles: the ankle joint performed net positive work that systematically increased its energy generation with faster walking speeds, while the distal foot performed net negative work that systematically increased its energy absorption with faster walking speeds. Accounting for these simultaneous effects, the combined ankle-foot system exhibited increased work-ratios with faster walking. Most notably, the work-ratio was not significantly greater than 1.0 during the normal walking speed of 0.8 statures/s. Therefore, a prosthetic design that strategically exploits passive-dynamic properties (e.g., elastic energy storage and return) has the potential to replicate the mechanical energy profiles of the NAFS during level-ground steady-state walking. PMID:23628408

  20. Combined Recording of Mechanically Stimulated Afferent Output and Nerve Terminal Labelling in Mouse Hair Follicle Lanceolate Endings.

    PubMed

    Bewick, Guy S; Cahusac, Peter M B; Banks, Robert W

    2016-01-01

    A novel dissection and recording technique is described for monitoring afferent firing evoked by mechanical displacement of hairs in the mouse pinna. The technique is very cost-effective and easily undertaken with materials commonly found in most electrophysiology laboratories, or easily purchased. The dissection is simple and fast, with the mechanical displacement provided by a generic electroceramic wafer controlled by proprietary software. The same software also records and analyses the electroneurogram output. The recording of the evoked nerve activity is through a commercial differential amplifier connected to fire-polished standard glass microelectrodes. Helpful tips are given for improving the quality of the preparation, the stimulation and the recording conditions to optimize recording quality. The system is suitable for assaying the electrophysiological and optical properties of lanceolate terminals of palisade endings of hair follicles, as well as the outcomes from their pharmacological and/or genetic manipulation. An example of combining electrical recording with mechanical stimulation and labeling with a styryl pyridinium vital dye is given. PMID:27213522

  1. Estimation of coefficient of friction for a mechanical system with combined rolling-sliding contact using vibration measurements

    NASA Astrophysics Data System (ADS)

    Sundar, Sriram; Dreyer, Jason T.; Singh, Rajendra

    2015-06-01

    A new dynamic experiment is proposed to estimate the coefficient of friction for a mechanical system with a combined rolling-sliding contact under a mixed lubrication regime. The experiment is designed and instrumented based on an analogous contact mechanics model, taking into consideration the constraints to ensure no impact and no sliding velocity reversal. The system consists of a cam (rotating with a constant speed) having a point contact with a follower that oscillates about a frictionless pivot, while maintaining contact with the cam with the help of a well-designed translational spring. The viscous damping elements for contact are identified for two different lubricants from an impulse test using the half-power bandwidth method. Dynamic responses (with the cam providing an input to the system) are measured in terms of the follower acceleration and the reaction forces at the follower pivot. A frequency domain based signal processing technique is proposed to estimate the coefficient of friction using the complex-valued Fourier amplitudes of the measured forces and acceleration. The coefficient of friction is estimated for the mechanical system with different surface roughnesses using two lubricants; these are also compared with similar values for both dry and lubricated cases as reported in the literature. An empirical relationship for the coefficient of friction is suggested based on a prior model under a mixed lubrication regime. Possible sources of errors in the estimation procedure are identified and quantified.

  2. Identifying protein aggregation mechanisms and quantifying aggregation rates from combined monomer depletion and continuous scattering.

    PubMed

    Barnett, Gregory V; Drenski, Michael; Razinkov, Vladimir; Reed, Wayne F; Roberts, Christopher J

    2016-10-15

    Parallel temperature initial rates (PTIR) from chromatographic separation of aggregating protein solutions are combined with continuous simultaneous multiple sample light scattering (SMSLS) to make quantitative deductions about protein aggregation kinetics and mechanisms. PTIR determines the rates at which initially monomeric proteins are converted to aggregates over a range of temperatures, under initial-rate conditions. Using SMSLS for the same set of conditions provides time courses of the absolute Rayleigh scattering ratio, IR(t), from which a potentially different measure of aggregation rates can be quantified. The present report compares these measures of aggregation rates across a range of solution conditions that result in different aggregation mechanisms for anti-streptavidin (AS) immunoglobulin gamma-1 (IgG1). The results illustrate how the two methods provide complementary information when deducing aggregation mechanisms, as well as cases where they provide new mechanistic details that were not possible to deduce in previous work. Criteria are presented for when the two techniques are expected to give equivalent results for quantitative rates, the potential limitations when solution non-idealities are large, as well as a comparison of the temperature dependence of AS-IgG1 aggregation rates with published data for other antibodies. PMID:27510552

  3. Responses to combined abiotic and biotic stress in tomato are governed by stress intensity and resistance mechanism.

    PubMed

    Kissoudis, Christos; Sunarti, Sri; van de Wiel, Clemens; Visser, Richard G F; van der Linden, C Gerard; Bai, Yuling

    2016-09-01

    Stress conditions in agricultural ecosystems can occur at variable intensities. Different resistance mechanisms against abiotic stress and pathogens are deployed by plants. Thus, it is important to examine plant responses to stress combinations under different scenarios. Here, we evaluated the effect of different levels of salt stress ranging from mild to severe (50, 100, and 150mM NaCl) on powdery mildew resistance and overall performance of tomato introgression lines with contrasting levels of partial resistance, as well as near-isogenic lines (NILs) carrying the resistance gene Ol-1 (associated with a slow hypersensitivity response; HR), ol-2 (an mlo mutant associated with papilla formation), and Ol-4 (an R gene associated with a fast HR). Powdery mildew resistance was affected by salt stress in a genotype- and stress intensity-dependent manner. In susceptible and partial resistant lines, increased susceptibility was observed under mild salt stress (50mM) which was accompanied by accelerated cell death-like senescence. In contrast, severe salt stress (150mM) reduced disease symptoms. Na(+) and Cl(-) accumulation in the leaves was linearly related to the decreased pathogen symptoms under severe stress. In contrast, complete resistance mediated by ol-2 and Ol-4 was unaffected under all treatment combinations, and was associated with a decreased growth penalty. Increased susceptibility and senescence under combined stress in NIL-Ol-1 was associated with the induction of ethylene and jasmonic acid pathway genes and the cell wall invertase gene LIN6. These results highlight the significance of stress severity and resistance type on the plant's performance under the combination of abiotic and biotic stress. PMID:27436279

  4. Developmentally Inspired Combined Mechanical and Biochemical Signaling Approach on Zonal Lineage Commitment of Mesenchymal Stem Cells in Articular Cartilage Regeneration

    PubMed Central

    Karimi, Tahereh; Barati, Danial; Karaman, Ozan; Moeinzadeh, Sina; Jabbari, Esmaiel

    2014-01-01

    Articular cartilage is organized into multiple zones including superficial, middle and calcified zones with distinct cellular and extracellular components to impart lubrication, compressive strength, and rigidity for load transmission to bone, respectively. During native cartilage tissue development, changes in biochemical, mechanical, and cellular factors direct the formation of stratified structure of articular cartilage. The objective of this work was to investigate the effect of combined gradients in cell density, matrix stiffness, and zone-specific growth factors on the zonal organization of articular cartilage. Human mesenchymal stem cells (hMSCs) were encapsulated in acrylate-functionalized lactide-chain-extended polyethylene glycol (SPELA) gels simulating cell density and stiffness of the superficial, middle and calcified zones. The cell-encapsulated gels were cultivated in medium supplemented with growth factors specific to each zone and the expression of zone-specific markers was measured with incubation time. Encapsulation of 60×106 cells/mL hMSCs in a soft gel (80 kPa modulus) and cultivation with a combination of TGF-β1 (3 ng/mL) and BMP-7 (100 ng/mL) led to the expression of markers for the superficial zone. Conversely, encapsulation of 15×106 cells/mL hMSCs in a stiff gel (320 MPa modulus) and cultivation with a combination of TGF-β1 (30 ng/mL) and hydroxyapatite (3%) led to the expression of markers for the calcified zone. Further, encapsulation of 20×106 cells/mL hMSCs in a gel with 2.1 MPa modulus and cultivation with a combination of TGF-β1 (30 ng/mL) and IGF-1 (100 ng/mL) led to up-regulation of the middle zone markers. Results demonstrate that a developmental approach with gradients in cell density, matrix stiffness, and zone-specific growth factors can potentially regenerate zonal structure of the articular cartilage. PMID:25387395

  5. Responses to combined abiotic and biotic stress in tomato are governed by stress intensity and resistance mechanism

    PubMed Central

    Kissoudis, Christos; Sunarti, Sri; van de Wiel, Clemens; Visser, Richard G.F.; van der Linden, C. Gerard; Bai, Yuling

    2016-01-01

    Stress conditions in agricultural ecosystems can occur at variable intensities. Different resistance mechanisms against abiotic stress and pathogens are deployed by plants. Thus, it is important to examine plant responses to stress combinations under different scenarios. Here, we evaluated the effect of different levels of salt stress ranging from mild to severe (50, 100, and 150mM NaCl) on powdery mildew resistance and overall performance of tomato introgression lines with contrasting levels of partial resistance, as well as near-isogenic lines (NILs) carrying the resistance gene Ol-1 (associated with a slow hypersensitivity response; HR), ol-2 (an mlo mutant associated with papilla formation), and Ol-4 (an R gene associated with a fast HR). Powdery mildew resistance was affected by salt stress in a genotype- and stress intensity-dependent manner. In susceptible and partial resistant lines, increased susceptibility was observed under mild salt stress (50mM) which was accompanied by accelerated cell death-like senescence. In contrast, severe salt stress (150mM) reduced disease symptoms. Na+ and Cl− accumulation in the leaves was linearly related to the decreased pathogen symptoms under severe stress. In contrast, complete resistance mediated by ol-2 and Ol-4 was unaffected under all treatment combinations, and was associated with a decreased growth penalty. Increased susceptibility and senescence under combined stress in NIL-Ol-1 was associated with the induction of ethylene and jasmonic acid pathway genes and the cell wall invertase gene LIN6. These results highlight the significance of stress severity and resistance type on the plant’s performance under the combination of abiotic and biotic stress. PMID:27436279

  6. Response mechanisms of antioxidants in bryophyte (Hypnum plumaeforme) under the stress of single or combined Pb and/or Ni.

    PubMed

    Sun, Shou-Qin; He, Ming; Cao, Tong; Zhang, You-Chi; Han, Wei

    2009-02-01

    The short-term responses and mechanisms of antioxidants in moss Hypnum plumaeforme subjected to single or combined Pb and/or Ni stress has been revealed in this study, in order to clarify (1) the relationship between the stress intensity and antioxidant fluctuation, (2) the difference between single and combined stress, and (3) the possibility of biomonitoring by the application of antioxidant fluctuation under stress. The results showed that the stress induced dose dependent formation of reactive oxygen species (ROS) and subsequent lipid peroxidation. Total chlorophyll (Chl) content and superoxide dismutase (SOD) activity were initiated under lower stress but were inhibited under higher stress. Both single and combined stress decreased catalase (CAT) activity but increased peroxidase (POD) activity, indicating POD in the moss played an important role in resisting the oxidative stress induced by Pb and Ni. The accumulation of (.)O2(-) and H2O2 in H. plumaeforme was respectively related to the low activity of SOD and the decreased activity of CAT. The study indicated that Pb and Ni had synergistic effect in inducing the oxidative stress in moss H. plumaeforme, especially under the combination of high concentration of Ni (0.1, 1.0 mM) and Pb. POD and CAT activity, as well as H2O2 and MDA content, which increased or decreased regularly with a dose dependent under Pb and Ni stress, could be used as an effective indicator in moss biomonitoring, especially in the case of light pollution caused by heavy metals without the changes in the appearance of mosses. PMID:18274872

  7. Molecular mechanisms for inhibition of colon cancer cells by combined epigenetic-modulating epigallocatechin gallate and sodium butyrate

    SciTech Connect

    Saldanha, Sabita N.; Kala, Rishabh; Tollefsbol, Trygve O.

    2014-05-15

    Bioactive compounds are considered safe and have been shown to alter genetic and epigenetic profiles of tumor cells. However, many of these changes have been reported at molecular concentrations higher than physiologically achievable levels. We investigated the role of the combinatorial effects of epigallocatechin gallate (EGCG), a predominant polyphenol in green tea, and sodium butyrate (NaB), a dietary microbial fermentation product of fiber, in the regulation of survivin, which is an overexpressed anti-apoptotic protein in colon cancer cells. For the first time, our study showed that the combination treatment induced apoptosis and cell cycle arrest in RKO, HCT-116 and HT-29 colorectal cancer cells. This was found to be regulated by the decrease in HDAC1, DNMT1, survivin and HDAC activity in all three cell lines. A G2/M arrest was observed for RKO and HCT-116 cells, and G1 arrest for HT-29 colorectal cancer cells for combinatorial treatment. Further experimentation of the molecular mechanisms in RKO colorectal cancer (CRC) cells revealed a p53-dependent induction of p21 and an increase in nuclear factor kappa B (NF-κB)-p65. An increase in double strand breaks as determined by gamma-H2A histone family member X (γ-H2AX) protein levels and induction of histone H3 hyperacetylation was also observed with the combination treatment. Further, we observed a decrease in global CpG methylation. Taken together, these findings suggest that at low and physiologically achievable concentrations, combinatorial EGCG and NaB are effective in promoting apoptosis, inducing cell cycle arrest and DNA-damage in CRC cells. - Highlights: • EGCG and NaB as a combination inhibits colorectal cancer cell proliferation. • The combination treatment induces DNA damage, G2/M and G1 arrest and apoptosis. • Survivin is effectively down-regulated by the combination treatment. • p21 and p53 expressions are induced by the combination treatment. • Epigenetic proteins DNMT1 and HDAC1 are

  8. Compression creep rupture of an E-glass/vinyl ester composite subjected to combined mechanical and fire loading conditions

    NASA Astrophysics Data System (ADS)

    Boyd, Steven Earl

    Polymer matrix composites are seeing increasing use in structural systems (e.g. ships, bridges) and require a quantitative basis for describing their performance under combined mechanical load and fire. Although much work has been performed to characterize the flammability, fire resistance and toxicity of these composite systems, an understanding of the structural response of sandwich type structures and laminate panels under combined mechanical and thermal loads (simulating fire conditions) is still largely unavailable. Therefore a research effort to develop a model to describe the structural response of these glass/vinyl esters systems under fire loading conditions is relevant to the continuing and future application of polymer matrix composites aboard naval ships. The main goal of the effort presented here is to develop analytical models and finite element analysis methods and tools to predict limit states such as local compression failures due to micro-buckling, residual strength and times to failure for composite laminates at temperatures in the vicinity of the glass transition where failure is controlled by viscoelastic effects. Given the importance of compression loading to a structure subject to fire exposure, the goals of this work are succinctly stated as the: (a) Characterization of the non-linear viscoelastic and viscoplastic response of the E-glass/vinyl ester composite above Tg. (b) Description of the laminate compression mechanics as a function of stress and temperature including viscoelasticity. (c) Viscoelastic stress analysis of a laminated panel ([0/+45/90/-45/0] S) using classical lamination theory (CLT). Three manuscripts constitute this dissertation which is representative of the three steps listed above. First, a detailed characterization of the nonlinear thermoviscoelastic response of Vetrotex 324/Derakane 510A--40 through Tg was conducted using the Time--Temperature--Stress--Superposition Principle (TTSSP) and Zapas--Crissman model. Second

  9. A possible mechanism of action of danazol and an ethinylestradiol/norgestrel combination used as postcoital contraceptive agents.

    PubMed

    Rowlands, S; Kubba, A A; Guillebaud, J; Bounds, W

    1986-06-01

    Twenty-seven women requesting postcoital contraception were randomly allocated to take an ethinylestradiol/dl-norgestrel combination or danazol. Urine specimens were assayed for luteinising hormone (LH) and pregnanediol-3-glucuronide (P3G) levels from the day of the postcoital treatment to the next period. In addition, the urine samples of these recruits and 12 additional women were assayed for the Beta-subunit of human chorionic gonadotropin (B-hCG). A consistent pattern of alteration in urinary steroids was lacking, indicating a heterogeneous effect on ovarian function. There was no evidence of early pregnancy in successfully treated cases. We suggest that the main mechanism of action of these drugs is at the endometrial level. PMID:3533419

  10. Increasing reliability of gas-air systems of piston and combined internal combustion engines by improving thermal and mechanic flow characteristics

    NASA Astrophysics Data System (ADS)

    Brodov, Yu. M.; Grigor'ev, N. I.; Zhilkin, B. P.; Plotnikov, L. V.; Shestakov, D. S.

    2015-12-01

    Results of experimental study of thermal and mechanical characteristics of gas exchange flow in piston and combined engines are presented. Ways for improving intake and exhaust processes to increase reliability of gas-air engine systems are proposed.

  11. Plasma metabolomics combined with lipidomics profiling reveals the potential antipyretic mechanisms of Qingkailing injection in a rat model.

    PubMed

    Qin, Lingling; Zhang, Zhixin; Guo, Mingxing; Zhang, Qingqing; Wang, Qing; Lu, Zhiwei; Zhao, Huizhen; Liu, Yuehong; Fu, Shuang; Wang, Meiling; Gao, Xiaoyan

    2016-07-25

    Qingkailing injection (QKLI) has a notable antipyretic effect and is widely used in China as a clinical emergency medicine. To elucidate the pharmacological action thoroughly, following the investigation of the urine metabolome and hypothalamus metabolome, plasma metabolomics combined with lipidomics profiling of the QKLI antipyretic effect in a rat model is described in this paper. Compared with pure metabolomics profiling, this non-targeted plasma metabolomics combined with lipidomics profiling based on ultra-performance liquid chromatography-coupled with quadrupole time-of-flight mass spectrometry (UPLC Q-TOF/MS) could be used for a large-scale detection of features in plasma samples. The results showed that 15 metabolites at the 1 h time point and 19 metabolites at the 2 h time point after QKLI administration were associated with the antipyretic effect of QKLI, including amino acid, phosphatidylcholine and lysophosphatidylcholine. The metabolism pathway analysis revealed that the potential biomarkers, which were important for the antipyretic mechanism of QKLI, were closely responsible for correcting the perturbed pathways of amino acid metabolism and lipid metabolism. In conclusion, the use of complementary UPLC Q-TOF/MS based metabolomics and lipidomics allows for the discovery of new potential plasma biomarkers in the QKLI antipyretic process and the associated pathways, and aided in advancing the understanding of the holism and synergism of the Chinese drug. PMID:27208622

  12. Survival mechanism of Escherichia coli O157:H7 against combined treatment with acetic acid and sodium chloride.

    PubMed

    Lee, Sun-Young; Kang, Dong-Hyun

    2016-05-01

    The combination of salt and acid is commonly used in the production of many foods, including pickles and fermented foods. However, in our previous studies, the addition of salt significantly reduced the inhibitory effect of acetic acid on Escherichia coli O157:H7 in laboratory media and pickled cucumbers. Therefore, this study was conducted to determine the mechanism by which salt confers resistance against acetic acid in E. coli O157:H7. The addition of high concentrations (up to 9% or 15% [w/v]) of salt increased the resistance of E. coli O157:H7 to acetic acid treatment. Combined treatment with acetic acid and salt showed varying results among different bacterial strains (an antagonistic effect for E. coli O157:H7 and Shigella and a synergistic effect for Listeria monocytogenes and Staphylococcus aureus). The addition of salt increased the cytoplasmic pH of E. coli O157:H7, but decreased the cytoplasmic pH of L. monocytogenes and S. aureus on treatment with acetic acid. Therefore, the addition of salt increases the acid resistance of E. coli O157:H7 possibly by increasing its acid resistance response and consequently preventing the acidification of its cytoplasm by organic acids. PMID:26742620

  13. [THE ENVIRONMENTAL BASES AND MECHANISM FOR NATURAL OPISTHORCHIASIS FOCUS PULSATION IN THE COMBINED FOCUS OF OPISTHORCHIASIS AND TULAREMIA].

    PubMed

    Ushakov, A V

    2015-01-01

    A cyclic change in the epizootic activity of a tularemia activity underlies the mechanism of natural opisthorchiasis focus pulsation in the combined focus of opisthorchiasis and tularemia in the ecosystem of the Konda River. This is due to mass breeding and depression in the water vole (Arvicola terrestris) population. The mass breeding is predetermined by high population reproduction constants. The rodents' potential fecundity occurs with the high capacity of lands, which is caused by the hydrological regime of rivers. The size depression is predetermined by the epizootics of tularemia. The water vole is a host of the pathogens of opisthorchiasis and tularemia. So the mass rodent breeding in the combined infection and invasion focus causes an increase in the number of real invasion sources. The epizootic of tularemia is responsible for elimination of these invasion sources and for decreases in the flow of invasion material, the infection rate of Codiella and hence the amount of their produced cercarae, the extensive and intensive indicators of fish contamination, and the intensity of an epizootic process in the opisthorchiasis focus. PMID:26152031

  14. Separation of atmospheric, oceanic and hydrological polar motion excitation mechanisms based on a combination of geometric and gravimetric space observations

    NASA Astrophysics Data System (ADS)

    Göttl, F.; Schmidt, M.; Seitz, F.; Bloßfeld, M.

    2015-04-01

    The goal of our study is to determine accurate time series of geophysical Earth rotation excitations to learn more about global dynamic processes in the Earth system. For this purpose, we developed an adjustment model which allows to combine precise observations from space geodetic observation systems, such as Satellite Laser Ranging (SLR), Global Navigation Satellite Systems, Very Long Baseline Interferometry, Doppler Orbit determination and Radiopositioning Integrated on Satellite, satellite altimetry and satellite gravimetry in order to separate geophysical excitation mechanisms of Earth rotation. Three polar motion time series are applied to derive the polar motion excitation functions (integral effect). Furthermore we use five time variable gravity field solutions from Gravity Recovery and Climate Experiment to determine not only the integral mass effect but also the oceanic and hydrological mass effects by applying suitable filter techniques and a land-ocean mask. For comparison the integral mass effect is also derived from degree 2 potential coefficients that are estimated from SLR observations. The oceanic mass effect is also determined from sea level anomalies observed by satellite altimetry by reducing the steric sea level anomalies derived from temperature and salinity fields of the oceans. Due to the combination of all geodetic estimated excitations the weaknesses of the individual processing strategies can be reduced and the technique-specific strengths can be accounted for. The formal errors of the adjusted geodetic solutions are smaller than the RMS differences of the geophysical model solutions. The improved excitation time series can be used to improve the geophysical modeling.

  15. Characterization of carbapenem resistance mechanisms in Klebsiella pneumoniae and in vitro synergy of the colistin-meropenem combination.

    PubMed

    Krishnappa, Lakshmana Gowda; Marie, Mohammed Ali M; Al Sheikh, Yazeed A

    2015-10-01

    In this prospective study, consecutive isolates of Klebsiella pneumoniae were tested for different mechanisms of carbapenem resistance using the modified Hodge test (MHT), Rosco Neo-Sensitabs (ROSCO). Phenylalanine arginine beta-naphthylamide assay (PABN) inhibitor-based test was done on isolates in which the mechanism of resistance was not identifiable by the ROSCO. Among 105 selected isolates, carbapenemase production was noted in 100 (95%) by MHT and ROSCO showed 97 (92·4%) inhibition with dipicolinic acid signifying the production of MBL. PCR amplification was positive in 90 (86%) isolates for bla(NDM-1) and 46 (44%) isolates for bla(OXA-48). 54 (51%) isolates were positive for bla(CTX-M) and all belonged to bla(CTX-M) group 1. Isolates co produced bla(OXA-48) (31/105, 30%) and bla(CTX-M) (40/105, 38%) in combination with the carbapenemase (bla(NDM-1)) gene. Five colistin-resistant isolates were positive for bla(OXA-48). Eight isolates did not show inhibition with any of the inhibitor containing disks and found to be positive for bla(OXA-48). Isolates were tested for colistin-meropenem synergy and detection rate was higher by the checkerboard (48%) than E-test method (35%). Our study necessitates continuous surveillance to recognize the predominant machinery of resistance in a particular geographical region to formulate effective control measures. PMID:24871673

  16. Combined effects of proinflammatory cytokines and intermittent cyclic mechanical strain in inhibiting osteogenicity in human periodontal ligament cells.

    PubMed

    Sun, Chaofan; Chen, Lijiao; Shi, Xinlian; Cao, Zhensheng; Hu, Bibo; Yu, Wenbin; Ren, Manman; Hu, Rongdang; Deng, Hui

    2016-09-01

    Mechanical strain plays an important role in bone formation and resorption during orthodontic tooth movement. The mechanism has not been fully studied, and the process becomes complex with increased amounts of periodontal patients seeking orthodontic care. Our aims were to elucidate the combined effects of proinflammatory cytokines and intermittent cyclic strain (ICS) on the osteogenic capacity of human periodontal ligament cells. Cultured human periodontal ligament cells were exposed to proinflammatory cytokines (interleukin-1β 5 ng/mL and tumor necrosis factor-α 10 ng/mL) for 1 and 5 days, and ICS (0.5 Hz, 12% elongation) was applied for 4 h per day. The autocrine of inflammatory cytokines was measured by enzyme-linked immunosorbent assay. The expression of osteoblast markers runt-related transcription factor 2 and rabbit collagen type I was determined using real-time polymerase chain reaction and Western blot. The osteogenic capacity was also detected by alkaline phosphatase (ALP) staining, ALP activity, and alizarin red staining. We demonstrated that ICS impaired the osteogenic capacity of human periodontal ligament cells when incubated with proinflammatory cytokines, as evidenced by the low expression of ALP staining, low ALP activity, reduced alizarin red staining, and reduced osteoblast markers. These data, for the first time, suggest that ICS has a negative effect on the inductive inhibition of osteogenicity in human PDL cells mediated by proinflammatory cytokines. PMID:27357508

  17. A combined cryo-EM and molecular dynamics approach reveals the mechanism of ErmBL-mediated translation arrest

    PubMed Central

    Arenz, Stefan; Bock, Lars V.; Graf, Michael; Innis, C. Axel; Beckmann, Roland; Grubmüller, Helmut; Vaiana, Andrea C.; Wilson, Daniel N.

    2016-01-01

    Nascent polypeptides can induce ribosome stalling, regulating downstream genes. Stalling of ErmBL peptide translation in the presence of the macrolide antibiotic erythromycin leads to resistance in Streptococcus sanguis. To reveal this stalling mechanism we obtained 3.6-Å-resolution cryo-EM structures of ErmBL-stalled ribosomes with erythromycin. The nascent peptide adopts an unusual conformation with the C-terminal Asp10 side chain in a previously unseen rotated position. Together with molecular dynamics simulations, the structures indicate that peptide-bond formation is inhibited by displacement of the peptidyl-tRNA A76 ribose from its canonical position, and by non-productive interactions of the A-tRNA Lys11 side chain with the A-site crevice. These two effects combine to perturb peptide-bond formation by increasing the distance between the attacking Lys11 amine and the Asp10 carbonyl carbon. The interplay between drug, peptide and ribosome uncovered here also provides insight into the fundamental mechanism of peptide-bond formation. PMID:27380950

  18. A combined cryo-EM and molecular dynamics approach reveals the mechanism of ErmBL-mediated translation arrest.

    PubMed

    Arenz, Stefan; Bock, Lars V; Graf, Michael; Innis, C Axel; Beckmann, Roland; Grubmüller, Helmut; Vaiana, Andrea C; Wilson, Daniel N

    2016-01-01

    Nascent polypeptides can induce ribosome stalling, regulating downstream genes. Stalling of ErmBL peptide translation in the presence of the macrolide antibiotic erythromycin leads to resistance in Streptococcus sanguis. To reveal this stalling mechanism we obtained 3.6-Å-resolution cryo-EM structures of ErmBL-stalled ribosomes with erythromycin. The nascent peptide adopts an unusual conformation with the C-terminal Asp10 side chain in a previously unseen rotated position. Together with molecular dynamics simulations, the structures indicate that peptide-bond formation is inhibited by displacement of the peptidyl-tRNA A76 ribose from its canonical position, and by non-productive interactions of the A-tRNA Lys11 side chain with the A-site crevice. These two effects combine to perturb peptide-bond formation by increasing the distance between the attacking Lys11 amine and the Asp10 carbonyl carbon. The interplay between drug, peptide and ribosome uncovered here also provides insight into the fundamental mechanism of peptide-bond formation. PMID:27380950

  19. Subchromoplast Sequestration of Carotenoids Affects Regulatory Mechanisms in Tomato Lines Expressing Different Carotenoid Gene Combinations[C][W

    PubMed Central

    Nogueira, Marilise; Mora, Leticia; Enfissi, Eugenia M.A.; Bramley, Peter M.; Fraser, Paul D.

    2013-01-01

    Metabolic engineering of the carotenoid pathway in recent years has successfully enhanced the carotenoid contents of crop plants. It is now clear that only increasing biosynthesis is restrictive, as mechanisms to sequestrate these increased levels in the cell or organelle should be exploited. In this study, biosynthetic pathway genes were overexpressed in tomato (Solanum lycopersicum) lines and the effects on carotenoid formation and sequestration revealed. The bacterial Crt carotenogenic genes, independently or in combination, and their zygosity affect the production of carotenoids. Transcription of the pathway genes was perturbed, whereby the tissue specificity of transcripts was altered. Changes in the steady state levels of metabolites in unrelated sectors of metabolism were found. Of particular interest was a concurrent increase of the plastid-localized lipid monogalactodiacylglycerol with carotenoids along with membranous subcellular structures. The carotenoids, proteins, and lipids in the subchromoplast fractions of the transgenic tomato fruit with increased carotenoid content suggest that cellular structures can adapt to facilitate the sequestration of the newly formed products. Moreover, phytoene, the precursor of the pathway, was identified in the plastoglobule, whereas the biosynthetic enzymes were in the membranes. The implications of these findings with respect to novel pathway regulation mechanisms are discussed. PMID:24249831

  20. Material combinations and parametric study of thermal and mechanical performance of pyramidal core sandwich panels used for hypersonic aircrafts

    NASA Astrophysics Data System (ADS)

    Zhang, Ruiping; Zhang, Xiaoqing; Lorenzini, Giulio; Xie, Gongnan

    2016-07-01

    A novel kind of lightweight integrated thermal protection system, named pyramidal core sandwich panel, is proposed to be a good safeguard for hypersonic aircrafts in the current study. Such system is considered as not only an insulation structure but also a load-bearing structure. In the context of design for hypersonic aircrafts, an efficient optimization should be paid enough attention. This paper concerns with the homogenization of the proposed pyramidal sandwich core panel using two-dimensional model in subsequent research for material selection. According to the required insulation performance and thermal-mechanical properties, several suitable material combinations are chosen as candidates for the pyramidal core sandwich panel by adopting finite element analysis and approximate response surface. To obtain lightweight structure with an excellent capability of heat insulation and load-bearing, an investigation on some specific design variables, which are significant for thermal-mechanical properties of the structure, is performed. Finally, a good balance between the insulation performance, the capability of load-bearing and the lightweight has attained.

  1. Biocatalysis mechanism for p-fluoronitrobenzene degradation in the thermophilic bioelectrocatalysis system: Sequential combination of reduction and oxidation.

    PubMed

    Wang, Yanfeng; Zhang, Xueqin; Feng, Huajun; Liang, Yuxiang; Shen, Dongsheng; Long, Yuyang; Zhou, Yuyang; Dai, Qizhou

    2016-09-01

    To verify the potentially synthetic anodic and cathodic biocatalysis mechanism in bioelectrocatalysis systems (BECSs), a single-chamber thermophilic bioelectrocatalysis system (R3) was operated under strictly anaerobic conditions using the biocathode donated dual-chamber (R1) and bioanode donated dual-chamber (R2) BECSs as controls. Direct bioelectrocatalytic oxidation was found to be infeasible while bioelectrocatalytic reduction was the dominant process for p-Fluoronitrobenzene (p-FNB) removal, with p-FNB removal of 0.188 mM d(-1) in R1 and 0.182 mM d(-1) in R3. Cyclic voltammetry experiments confirmed that defluorination in the BECSs was an oxidative metabolic process catalyzed by bioanodes following the reductive reaction, which explained the 0.034 mM d(-1) defluorination in R3, but negligible defluorination in controls. Taken together, these results revealed a sequentially combined reduction and oxidation mechanism in the thermophilic BECS for p-FNB removal. Moreover, the enrichment of Betaproteobacteria and uniquely selected Bacilli in R3 were probably functional populations for p-FNB degradation. PMID:27268793

  2. A combined cryo-EM and molecular dynamics approach reveals the mechanism of ErmBL-mediated translation arrest

    NASA Astrophysics Data System (ADS)

    Arenz, Stefan; Bock, Lars V.; Graf, Michael; Innis, C. Axel; Beckmann, Roland; Grubmüller, Helmut; Vaiana, Andrea C.; Wilson, Daniel N.

    2016-07-01

    Nascent polypeptides can induce ribosome stalling, regulating downstream genes. Stalling of ErmBL peptide translation in the presence of the macrolide antibiotic erythromycin leads to resistance in Streptococcus sanguis. To reveal this stalling mechanism we obtained 3.6-Å-resolution cryo-EM structures of ErmBL-stalled ribosomes with erythromycin. The nascent peptide adopts an unusual conformation with the C-terminal Asp10 side chain in a previously unseen rotated position. Together with molecular dynamics simulations, the structures indicate that peptide-bond formation is inhibited by displacement of the peptidyl-tRNA A76 ribose from its canonical position, and by non-productive interactions of the A-tRNA Lys11 side chain with the A-site crevice. These two effects combine to perturb peptide-bond formation by increasing the distance between the attacking Lys11 amine and the Asp10 carbonyl carbon. The interplay between drug, peptide and ribosome uncovered here also provides insight into the fundamental mechanism of peptide-bond formation.

  3. Effect of Temperature on Damage Evolution of Cr25Ni35Nb Alloy Subjected to Combined Mechanical and Environmental Degradation

    NASA Astrophysics Data System (ADS)

    Shen, Limin; Liu, Huansheng; Gong, Jianming; Geng, Luyang

    2015-07-01

    Due to combined mechanical and environmental degradation, i.e. coupled creep and carburization, Cr25Ni35Nb alloy often fails prior to the expected design life. In the present paper, based on the continuum damage mechanics, the constitutive model of coupled multi-damage factors for computing the damage evolution of Cr25Ni35Nb alloy was proposed. The damage prediction was carried out by using finite element method based on ABAQUS code. And then damage evolution processes at different operating temperatures (950 °C and 1050 °C) were simulated and the effect of service temperature on the damage evolution was discussed. The results showed that the rate of damage increased obviously with operating temperature increasing. The location with maximum damage is along the inner surface of tube, which implies that fracture begins along the inner surface of tube under the action of coupled creep and carburization damage and this is coincident with the actual observation of the failure of furnace tube.

  4. Separation of atmospheric, oceanic and hydrological polar motion excitation mechanisms by a combination of geometric and gravimetric space observations

    NASA Astrophysics Data System (ADS)

    Göttl, Franziska; Schmidt, Michael; Seitz, Florian; Blossfeld, Mathis

    2014-05-01

    Redistribution and motion of masses within and between the individual subsystems of the Earth cause variations of the orientation of the Earth axis with respect to an Earth-fixed reference frame (polar motion and length-of-day variations). Whereas the integral effect of Earth rotation is precisely measured by geometric space techniques, such as Satellite Laser Ranging (SLR), Very Long Baseline Interferometry (VLBI), Global Navigation Satellite Systems (GNSS) and Doppler Orbit determination and Radiopositioning Integrated on Satellite (DORIS), the separation into individual excitation mechanisms remains a challenge. Commonly, individual geophysical excitation mechanisms of Earth rotation are derived from geophysical models. Due to the fact that geophysical models are afflicted with uncertainties, results derived from different model show large discrepancies. Here we present an adjustment model which allows to combine precise observations from space geodetic observation systems (SLR, VLBI, GNSS, DORIS, satellite altimetry and satellite gravimetry) in order to separate geophysical excitation mechanisms of the Earth rotation. Time variable gravity field solutions from GRACE (Gravity Recovery and Climate Experiment) are used to determine not only the integral mass effect but also the oceanic and hydrological mass effects by applying suitable filter techniques and land-ocean-masks. Furthermore the oceanic mass effect is determined from sea level anomalies as observed by cross-calibrated multi-mission altimetry. Due to the fact that sea level anomalies are not only caused by mass variations but also by volume changes (steric effect), these steric sea level anomalies need to be reduced using appropriate models. We show that through the combination weaknesses of the individual processing strategies can be compensated and the technique specific strengths can be optimally accounted for. This way, excitation functions of atmospheric, oceanic and hydrological mass effects and

  5. Mechanical Revascularization for Acute Ischemic Stroke: A Single-Center, Retrospective Analysis

    SciTech Connect

    Jeromel, Miran Milosevic, Z. V. Kocijancic, I. J. Lovric, D.; Svigelj, V. Zvan, B.

    2013-04-15

    BackgroundEndovascular mechanical revascularization (thrombectomy) is an increasingly used method for intracranial large vessel recanalization in acute stroke. The purpose of the study was to analyze the recanalization rate, clinical outcome, and complication rate in our stroke patients treated with mechanical revascularization. A total of 57 patients with large vessel stroke (within 3 h for anterior and 12 h for posterior circulation) were treated with mechanical revascularization at a single center during 24 months. The primary goal of endovascular treatment using different mechanical devices was recanalization of the occluded vessel. Recanalization rate (reported as thrombolysis in cerebral infarction [TICI] score), clinical outcome (reported as National Institutes of Health Stroke Scale [NIHSS] score and modified Rankin scale [mRS] score), as well as periprocedural complications were analyzed. The mean age of the patients was 63.1 {+-} 12.9 years, with baseline median NIHSS score of 14 (interquartile range, 9.5-19). Successful recanalization (TICI 2b or 3) was achieved in 41 (72 %) patients. Twenty patients (35 %) presented with favorable outcome (mRS {<=}2) 30 days after stroke. Overall, significant neurological improvement ({>=}4 NIHSS point reduction) occurred in 36 (63 %) patients. A clinically significant procedure-related adverse events (vessel disruption, peri/postprocedural intracranial bleeding) defined with decline in NIHSS of {>=}4 or death occurred in three (5 %) patients. The study showed a high recanalization rate with improved clinical outcome and a low rate of periprocedural complications in our stroke patients treated with mechanical revascularization. Therefore, we could conclude that endovascular revascularization (primary or in combination with a bridging thrombolysis) was an effective and safe procedure for intracranial large vessel recanalization in acute stroke.

  6. Molecular mechanisms for inhibition of colon cancer cells by combined epigenetic-modulating epigallocatechin gallate and sodium butyrate

    PubMed Central

    Saldanha, Sabita N.; Kala, Rishabh; Tollefsbol, Trygve O.

    2014-01-01

    Bioactive compounds are considered safe and have been shown to alter genetic and epigenetic profiles of tumor cells. However, many of these changes have been reported at molecular concentrations higher than physiologically achievable levels. We investigated the role of the combinatorial effects of epigallocatechin gallate (EGCG), a predominant polyphenol in green tea, and sodium butyrate (NaB), a dietary microbial fermentation product of fiber, in the regulation of survivin, which is an overexpressed anti-apoptotic protein in colon cancer cells. For the first time, our study showed that the combination treatment induced apoptosis and cell cycle arrest in RKO, HCT-116 and HT-29 colorectal cancer cells. This was found to be regulated by the decrease in HDAC1, DNMT1, survivin and HDAC activity in all three cell lines. A G2/M arrest was observed for RKO and HCT-116 cells, and G1 arrest for HT-29 colorectal cancer cells for combinatorial treatment. Further experimentation of the molecular mechanisms in RKO colorectal cancer cells revealed a p53-dependent induction of p21 and an increase in nuclear factor kappa B (NF-κB)-p65. An increase in double strand breaks as determined by gamma-H2A histone family member X (γ-H2AX) protein levels and induction of histone H3 hyperacetylation was also observed with combination treatment. Further, we observed a decrease in global CpG methylation. Taken together, these findings suggest that at low and physiologically achievable concentrations, combinatorial EGCG and NaB are effective in promoting apoptosis, inducing cell cycle arrest and DNA-damage in colorectal cancer cells. PMID:24518414

  7. The clinical effect and relevant mechanism of combined sorafenib and radiofrequency ablation in the treatment of early small hepatocellular carcinoma

    PubMed Central

    Yan, Shi-Yan; Zhang, Yi; Sun, Chao; Cao, Hai-Xia; Li, Guang-Ming; Wang, Yu-Qin; Fan, Jian-Gao

    2016-01-01

    The number of cases with hepatocellular carcinoma (HCC) are on the increase. The aim of the present study was to investigate the clinical effect and relevant mechanism of combined sorafenib and radiofrequency ablation (RFA) in the treatment of the early small HCC. A total of 120 cases of patients with small HCC that presented during the period of May 2007 to June 2010 were selected and divided into the surgery (n=60) and RF (n=60) groups according to the treatment method employed. The surgery group was treated with a laparotomy resection and the RF group was treated with combined sorafenib and RFA, and a comparative analysis was made between the two groups with regard to recurrence rates, adverse reactions, and survival rates. After treatment of 1 month, the radical effective rate of the surgery and RF groups was 100%. Contrast-enhanced ultrasound images of the patients in the RF group were taken. During the 5-year follow-up, the tumor recurrence rate in the surgery group was 18.3%, significantly lower than that in the RF group where the tumor recurrence rate was 38.3% (P<0.05). The occurrence rate of postoperative pain, fever, abdominal bleeding, infection, and other complications of patients in the surgery group was significantly higher than the complication occurrence rate (P<0.05) of the patients in the RF group. The average survival time of the patients in the surgery group was 51.2±1.5 months and the survival rates during the first, third and fifth year were 90.7, 71.5 and 56.7%, respectively. Additionally, the average survival time of the patients in the RF group was 64.6±2.4 months and the survival rates during the first, third and fifth year were 91.1, 72.8 and 57.5%, respectively. The difference between the two groups was not statistically significant. The tumor-free survival rates in the surgery group during the first, third and fifth year were 87.8, 44.3 and 33.2%, respectively, while the tumor-free survival rates in the RF group during the first

  8. [High frequency jet ventilation combined with conventional mechanical ventilation in the treatment of adult respiratory distress syndrome].

    PubMed

    Roustan, J P

    1995-01-01

    Better understanding of the physiopathology of ventilatory mechanisms associated with ARDS and the recent re-evaluation of the iatrogenic potential of mechanical ventilation (MV) brings us closer to the best suited ventilatory mode for these patients. In severely ill ARDS patients, only a small lung volume is ventilated, and remains available for the totality of the gas exchanges (baby lung concept). The goal of MV is to restore and maintain an optimal exchange volume while limiting mechanical agression of the lung tissue. Analysis of the ARDS related pressure-volume relationship (P/V) is helpful in specifying the tolerable limits of the ventilatory pressure regimen. The lower limit (end expiratory pressure) must be kept above the lower inflexion point of the curve, in order to increase the ventilated lung volume and avoid distal airway collapse. Under this limit, gas exchanges are altered by the shunt effect, and shear stress lesions result from the repeated opening and closing of the distal airways. The upper limit (end inspiratory pressure) must be situated below the upper inflexion point of the curve, in order to avoid lesions resulting from surdistension of the alveolocapillary membranes and barotraumatisms. The only way to position MV in such a narrow pressure window, is to greatly reduce the tidal volume (VT). Though CO2 retention would inevitably occur under conventional MV conditions, high frequency ventilation (HFV) seems better adapted to these theoreotical objectives; small VT's are injected under a limited amplitude pressure regimen and a satisfactory CO2 clearance is maintained. This ventilatory mode, existing since more than 15 years, has recently benefited from many technical improvements as well as the concept of oscillating the ventilation around a selected mean pressure in the central region of the P/V curve. In the past, HFV was applied using low pressure regimens, situated below the lower inflexion point of the curve. The resulting failures are

  9. Combining Atomic Force Microscopy and Depth-Sensing Instruments for the Nanometer-Scale Mechanical Characterization of Soft Matter

    NASA Astrophysics Data System (ADS)

    Tranchida, Davide; Piccarolo, Stefano

    Complex materials exhibit a hierarchical structure where a gradient of features on nanometer scale is induced by the synthetic route eventually enhanced by the loading condition. The nanometer scale at which individual components arrange, determining their properties, is a current challenge of mechanical testing. In this work, a survey on nanoindentation is outlined based on the comparison of results obtained by Atomic Force Microscopy and Depth-Sensing Instruments and their combination. An Atomic Force Microscope equipped with a Force Transducer gives indeed the possibility to scan the sample surface in contact mode, thereby allowing one to choose a suitable position for the nanoindentation, as well as imaging the residual imprint left on the sample. The analysis of the applied load vs. penetration depth curve, also called force curve, shows the limitations of current approaches to determine elastic moduli of compliant viscoelastic materials. Significant deviations from the expected values are observed even after optimizing testing conditions, so as to minimize the artifacts like viscoelastic effects or pile-up. As rigorous approaches are yet to be applied to the interpretation of force curves accounting also of viscoelastic material behavior, an empirical calibration recently proposed by the authors is verified against a set of data on model samples spanning a range of moduli, typical of compliant materials and close to each other, so as to challenge the resolution potential of this method, as well as others in use in the literature.

  10. Concepts and mechanisms underlying chemotherapy induced immunogenic cell death: impact on clinical studies and considerations for combined therapies

    PubMed Central

    Gebremeskel, Simon; Johnston, Brent

    2015-01-01

    Chemotherapy has historically been thought to induce cancer cell death in an immunogenically silent manner. However, recent studies have demonstrated that therapeutic outcomes with specific chemotherapeutic agents (e.g. anthracyclines) correlate strongly with their ability to induce a process of immunogenic cell death (ICD) in cancer cells. This process generates a series of signals that stimulate the immune system to recognize and clear tumor cells. Extensive studies have revealed that chemotherapy-induced ICD occurs via the exposure/release of calreticulin (CALR), ATP, chemokine (C–X–C motif) ligand 10 (CXCL10) and high mobility group box 1 (HMGB1). This review provides an in-depth look into the concepts and mechanisms underlying CALR exposure, activation of the Toll-like receptor 3/IFN/CXCL10 axis, and the release of ATP and HMGB1 from dying cancer cells. Factors that influence the impact of ICD in clinical studies and the design of therapies combining chemotherapy with immunotherapy are also discussed. PMID:26486085

  11. A Combination of Chemometrics and Quantum Mechanics Methods Applied to Analysis of Femtosecond Transient Absorption Spectrum of Ortho-Nitroaniline

    PubMed Central

    Yi, Jing; Xiong, Ying; Cheng, Kemei; Li, Menglong; Chu, Genbai; Pu, Xuemei; Xu, Tao

    2016-01-01

    A combination of the advanced chemometrics method with quantum mechanics calculation was for the first time applied to explore a facile yet efficient analysis strategy to thoroughly resolve femtosecond transient absorption spectroscopy of ortho-nitroaniline (ONA), served as a model compound of important nitroaromatics and explosives. The result revealed that the ONA molecule is primarily excited to S3 excited state from the ground state and then ultrafast relaxes to S2 state. The internal conversion from S2 to S1 occurs within 0.9 ps. One intermediate state S* was identified in the intersystem crossing (ISC) process, which is different from the specific upper triplet receiver state proposed in some other nitroaromatics systems. The S1 state decays to the S* one within 6.4 ps and then intersystem crossing to the lowest triplet state within 19.6 ps. T1 was estimated to have a lifetime up to 2 ns. The relatively long S* state and very long-lived T1 one should play a vital role as precursors to various nitroaromatic and explosive photoproducts. PMID:26781083

  12. A Combination of Chemometrics and Quantum Mechanics Methods Applied to Analysis of Femtosecond Transient Absorption Spectrum of Ortho-Nitroaniline.

    PubMed

    Yi, Jing; Xiong, Ying; Cheng, Kemei; Li, Menglong; Chu, Genbai; Pu, Xuemei; Xu, Tao

    2016-01-01

    A combination of the advanced chemometrics method with quantum mechanics calculation was for the first time applied to explore a facile yet efficient analysis strategy to thoroughly resolve femtosecond transient absorption spectroscopy of ortho-nitroaniline (ONA), served as a model compound of important nitroaromatics and explosives. The result revealed that the ONA molecule is primarily excited to S3 excited state from the ground state and then ultrafast relaxes to S2 state. The internal conversion from S2 to S1 occurs within 0.9 ps. One intermediate state S* was identified in the intersystem crossing (ISC) process, which is different from the specific upper triplet receiver state proposed in some other nitroaromatics systems. The S1 state decays to the S* one within 6.4 ps and then intersystem crossing to the lowest triplet state within 19.6 ps. T1 was estimated to have a lifetime up to 2 ns. The relatively long S* state and very long-lived T1 one should play a vital role as precursors to various nitroaromatic and explosive photoproducts. PMID:26781083

  13. Low temperature plasma enhanced chemical vapor deposition of thin films combining mechanical stiffness, electrical insulation, and homogeneity in microcavities

    SciTech Connect

    Peter, S.; Guenther, M.; Hauschild, D.; Richter, F.

    2010-08-15

    The deposition of hydrogenated amorphous carbon (a-C:H) as well as hydrogenated amorphous silicon carbonitride (SiCN:H) films was investigated in view of a simultaneous realization of a minimum Young's modulus (>70 GPa), a high electrical insulation ({>=}1 MV/cm), a low permittivity and the uniform coverage of microcavities with submillimeter dimensions. For the a-C:H deposition the precursors methane (CH{sub 4}) and acetylene (C{sub 2}H{sub 2}) were used, while SiCN:H films were deposited from mixtures of trimethylsilane [SiH(CH{sub 3}){sub 3}] with nitrogen and argon. To realize the deposition of micrometer thick films with the aforementioned complex requirements at substrate temperatures {<=}200 deg. C, several plasma enhanced chemical vapor deposition methods were investigated: the capacitively coupled rf discharge and the microwave electron cyclotron resonance (ECR) plasma, combined with two types of pulsed substrate bias. SiCN:H films deposited at about 1 Pa from ECR plasmas with pulsed high-voltage bias best met the requirements. Pulsed biasing with pulse periods of about 1 {mu}s and amplitudes of about -2 kV was found to be most advantageous for the conformal low temperature coating of the microtrenches, thereby ensuring the required mechanical and insulating film properties.

  14. The mechanism of pollinator specificity between two sympatric fig varieties: a combination of olfactory signals and contact cues

    PubMed Central

    Wang, Gang; Compton, Stephen G.; Chen, Jin

    2013-01-01

    Background and Aims Pollinator specificity facilitates reproductive isolation among plants, and mechanisms that generate specificity influence species boundaries. Long-range volatile attractants, in combination with morphological co-adaptations, are generally regarded as being responsible for maintaining extreme host specificity among the fig wasps that pollinate fig trees, but increasing evidence for breakdowns in specificity is accumulating. The basis of host specificity was examined among two host-specific Ceratosolen fig wasps that pollinate two sympatric varieties of Ficus semicordata, together with the consequences for the plants when pollinators entered the alternative host variety. Methods The compositions of floral scents from receptive figs of the two varieties and responses of their pollinators to these volatiles were compared. The behaviour of the wasps once on the surface of the figs was also recorded, together with the reproductive success of figs entered by the two Ceratosolen species. Key Results The receptive-phase floral scents of the two varieties had different chemical compositions, but only one Ceratosolen species displayed a preference between them in Y-tube trials. Specificity was reinforced at a later stage, once pollinators were walking on the figs, because both species preferred to enter figs of their normal hosts. Both pollinators could enter figs of both varieties and pollinate them, but figs with extra-varietal pollen were more likely to abort and contained fewer seeds. Hybrid seeds germinated at normal rates. Conclusions Contact cues on the surface of figs have been largely ignored in previous studies of fig wasp host preferences, but together with floral scents they maintain host specificity among the pollinators of sympatric F. semicordata varieties. When pollinators enter atypical hosts, post-zygotic factors reduce but do not prevent the production of hybrid offspring, suggesting there may be gene flow between these varieties. PMID

  15. A novel testing platform for assessing knee joint mechanics: a parallel robotic system combined with an instrumented spatial linkage.

    PubMed

    Atarod, Mohammad; Rosvold, Joshua M; Frank, Cyril B; Shrive, Nigel G

    2014-05-01

    Assessing joint function following trauma and its inter-relation with degenerative changes requires an understanding of the normal state of structural loading in the joint. Very few studies have attempted to reproduce joint specific in vivo motions in vitro to quantify the actual loads carried by different tissues within the knee joint. The most significant challenge in this area is the very high sensitivity of the loads in joint structures to motion reproduction accuracy. A novel testing platform for assessing knee joint mechanics is described, comprised of a highly accurate (0.3 ± 0.1 mm, 0.3 ± 0.1°) six-degree-of-freedom (6-DOF) instrumented spatial linkage (ISL) for in vivo joint kinematic assessments and a unique 6-DOF parallel robotic manipulator. A position feedback system (ISL and position controller) is used for accurate reproduction of in vivo joint motions and estimation of "in situ" joint/tissue loads. The parallel robotic manipulator provides excellent stiffness and repeatability in reproducing physiological motions in 6-DOF, compared to the commonly used serial robots. The position feedback system provides real-time feedback data to the robot to reproduce in vivo motions and significantly enhances motion reproduction accuracy by adjusting for robot end-effector movements. Using this combined robot-ISL system, in vivo motions can be reproduced in vitro with very high accuracy (0.1 mm, 0.1°). Our results indicate that this level of accuracy is essential for meaningful estimation of tissue loads during gait. Using this novel testing platform, we have determined the normal load-carrying characteristics of different tissues within the ovine knee joint. The application of this testing system will continue to increase our understanding of normal and pathological joint states. PMID:24519725

  16. Experimental study of ultra-thin films mechanical integrity by combined nanoindentation and nano-acoustic emission

    NASA Astrophysics Data System (ADS)

    Zhang, Zihou

    Advancement of interconnect technology has imposed significant challenge on interface characterization and reliability for blurred interfaces between layers. There is a need for material properties and these miniaturized length scales and assessment of reliability; including the intrinsic film fracture toughness and the interfacial fracture toughness. The nano-meter range of film thicknesses currently employed, impose significant challenges on evaluating these physical quantities and thereby impose significant challenge on the design cycle. In this study we attempted to use a combined nano-indentation and nano-acoustic emission to qualitatively and quantitatively characterize the failure modes in ultra-thin blanket films on Si substrates or stakes of different characteristics. We have performed and analyzed an exhaustive group of testes that cove many diverge combination of film-substrate combination, provided by both Intel and IBM. When the force-indentation depth curve shows excursion, a direct measure of the total energy release rate is estimated. The collected acoustic emission signal is then used to partition the total energy into two segments, one associated with the cohesive fracture toughness of the film and the other is for the adhesive fracture toughness of the interface. The acoustic emission signal is analyzed in both the time and frequency domain to achieve such energy division. In particular, the signal time domain analysis for signal skewness, time of arrival and total energy content are employed with the proper signal to noise ratio. In the frequency domain, an expansive group of acoustic emission signals are utilized to construct the details of the power spectral density. A bank of band-pass filters are designed to sort the individual signals to those associated with adhesive interlayer cracking, cohesive channel cracking, or other system induced noise. The attenuation time and the energy content within each spectral frequency were the key elements

  17. A combined stretching-tilting mechanism produces negative, zero and positive linear thermal expansion in a semi-flexible Cd(II)-MOF.

    PubMed

    Lama, Prem; Das, Raj Kumar; Smith, Vincent J; Barbour, Leonard J

    2014-06-21

    A novel semi-flexible Cd(II)-MOF has been synthesized and characterized by variable temperature powder and single-crystal X-ray diffraction. The material displays an unusual combination of thermal expansion (TE) i.e. negative, zero and positive, which is an extremely rare finding, especially for metal-organic frameworks as a result of a combined stretching-tilting mechanism. PMID:24809630

  18. As(III) immobilization on gibbsite: Investigation of the complexation mechanism by combining EXAFS analyses and DFT calculations

    NASA Astrophysics Data System (ADS)

    Duarte, Graziele; Ciminelli, Virginia S. T.; Dantas, Maria S. S.; Duarte, Helio A.; Vasconcelos, Igor F.; Oliveira, Augusto F.; Osseo-Asare, Kwadwo

    2012-04-01

    The complexation of aqueous As(III) species on gibbsite was investigated as a function of pH. Theoretical calculations and X-ray absorption fine structure spectroscopy (XAFS) were combined to elucidate the structure of arsenite surface complexes on synthetic gibbsite. Several adsorption sites were evaluated using the self-consistent charge corrected density-functional based tight-binding (SCC-DFTB) method. The formation of bidentate-binuclear, bidentate-mononuclear, monodentate-mononuclear, and monodentate-binuclear complexes by means of both acid-base and non-dissociative mechanisms was studied in detail. The SCC-DFTB calculations showed the bidentate-binuclear/acid-base complex as the most thermodynamically stable geometry for As(III) bonding to gibbsite surface, estimating As-O and As-Al distances of 1.75 and 3.24 Å, respectively. EXAFS results also demonstrated As(III) complexation to three oxygen atoms in the first shell, at a distance of 1.77 Å, and to aluminum in the second shell at a distance of 3.21 Å, characteristic of bidentate-binuclear configuration, at pH 5.0, 7.0 and 9.0. Another As-Al interaction, attributed to the monodentate-binuclear complex due to its distance of 3.49 Å, was shown from EXAFS results to provide a minor contribution to As(III) sorption on gibbsite. Therefore, results from theoretical calculations and experimental measurements confirmed the occurrence of inner-sphere complexation during the As(III) adsorption on gibbsite, in a pH range of 5-9. Hence, the higher As(III) mobility in the environment, when compared to As(V), was suggested to be related to the protonation of the As(III) adsorbed complexes. This protonation would restore the neutral H3AsO3 molecule, which could be then released from the mineral surface. These results might be useful to predict and control arsenic mobility in aqueous environments, particularly where Al oxy-hydroxides are often found.

  19. Effect of fluticasone/salmeterol combination on dyspnea and respiratory mechanics in mild-to-moderate COPD.

    PubMed

    Guenette, Jordan A; Webb, Katherine A; O'Donnell, Denis E

    2013-05-01

    The purpose of this exploratory physiological study was to evaluate the effects of inhaled fluticasone/salmeterol combination (FSC) on sensory and physiological responses to exercise in subjects with mild-to-moderate COPD. In a randomized, double-blind, placebo-controlled, crossover study, subjects underwent 6-week treatments with FSC or placebo (PLA). Detailed pulmonary function and constant-work rate cycle exercise tests were performed following each treatment period. Fifteen subjects completed the study (mean ± SD): age 64 ± 10 years; smoking history 47 ± 29 pack-years; post-bronchodilator forced expiratory volume in 1 s 86 ± 15 %predicted (10 mild and 5 moderate COPD); peak incremental oxygen uptake 71 ± 16 %predicted. Compared with PLA, FSC treatment was associated with improved: FEV1 by 0.23 ± 0.18 L; inspiratory capacity by 0.18 ± 0.23 L; functional residual capacity by -0.28 ± 0.30 L; and specific airways resistance by -4.6 ± 4.5 cmH2O s (all p < 0.01). There were no significant changes in dyspnea intensity throughout exercise and endurance time did not change significantly (1.2 ± 3.0 min, p = 0.149). Following FSC, inspiratory capacity at rest and throughout exercise increased by 0.2-0.3 L with concomitant increases in tidal volume and ventilation (p < 0.05). Compared with PLA, the work of breathing and the ratio of respiratory muscle effort to tidal volume improved with FSC during exercise (p < 0.05). In mild-to-moderate COPD, FSC was associated with significant improvements in airway function at rest and during exercise. Despite important mechanical improvements, there were no significant effects on dyspnea intensity and exercise endurance. PMID:23421968

  20. IM-133N - A Useful Herbal Combination for Eradicating Disease-triggering Pathogens in Mice via Immunotherapeutic Mechanisms

    PubMed Central

    Firashathulla, Syed; Inamdar, Mohammed Naseeruddin; Rafiq, Mohamed; Viswanatha, Gollapalle Lakshminarayanashastry; Sharath Kumar, Lakkavalli Mohan; Babu, Uddagiri Venkanna; Ramakrishnan, Shyam; Paramesh, Rangesh

    2016-01-01

    Objectives: The present study was undertaken to evaluate the immunomodulatory (IM) activity of IM-133N, a herbal combination in various immunotherapeutic experimental models. Methods: The IM activity of IM-133N was evaluated against three experimental models namely, effect of IM- 133N against Escherichia coli (E. coli)-induced abdominal sepsis in mice, and carbon clearance test was performed in Wistar albino rats to evaluated the phagocytic potential of IM-133N, in addition IM-133N was evaluated for its immunoglobulin enhancing potential in rats, where the immunoglobulin levels were measured by zinc sulphate turbity (ZST) test. Further, IM-133N was subjected for detailed liquid chromatography-mass spectrometry (LC-MS)/MS analysis to identify the probable active constituents present in it. Results: The findings of the present study has demonstrated very promising IM property of IM-133N in all the experimental models. Briefly, pretreatment with IM-133N at 125, 250, 500 and 1,000 mg/kg, p.o. doses had protected the mice against E. coli-induced abdominal sepsis and mortality, further the effect of IM- 133N was found to be significant and dose-dependent. In support of this, in another study administration of IM-133N showed a significant and dose-dependent increase in serum immunoglobulin levels, estimated by ZST test. In line with the above findings, in the carbon clearance test the low doses (125 and 250 mg/ kg, p.o.) of IM-133N increased the rate of carbon clearance, whereas the higher doses (500 and 1,000 mg/kg, p.o.) did not sustain the response, and saturation effect was considered as one of the possible reason for futility of higher doses for IM-133N. In addition, A detailed LC-MS/MS analysis of IM-133N showed 17 bioactive phytochemical constituents: namely, apigenin, chaulmoogric acid, mesquitol, quercetin, symphoxanthone, salireposide, β-sitosterol, nonaeicosanol, β-amyrin, betulic acid, oleanolic acid, symplososide, symponoside, symploveroside, symplocomoside

  1. Multi-drug resistance transporters and a mechanism-based strategy for assessing risks of pesticide combinations to honey bees

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Annual losses of honey bee colonies remain high and pesticide exposure is one possible cause. Dangerous combinations of pesticides, plant-produced compounds and antibiotics added to hives may cause or contribute to losses, but it is very difficult to test the many combinations of those compounds tha...

  2. Determination of adhesion between thermoplastic and liquid silicone rubbers in hard-soft-combinations via mechanical peeling test

    NASA Astrophysics Data System (ADS)

    Kühr, C.; Spörrer, A.; Altstädt, V.

    2014-05-01

    The production of hard-soft-combinations via multi injection molding gained more and more importance in the last years. This is attributed to different factors. One principle reason is that the use of two-component injection molding technique has many advantages such as cancelling subsequent and complex steps and shortening the process chain. Furthermore this technique allows the combination of the properties of the single components like the high stiffness of the hard component and the elastic properties of the soft component. Because of the incompatibility of some polymers the adhesion on the interface has to be determined. Thereby adhesion is not only influenced by the applied polymers, but also by the injection molding parameters and the characteristics of the mold. Besides already known combinations of thermoplastics with thermoplastic elastomers (TPE), there consists the possibility to apply liquid silicone rubber (LSR) as soft component. A thermoplastic/LSR combination gains in importance due to the specific advantages of LSR to TPE. The faintly adhesion between LSR and thermoplastics is currently one of the key challenges when dealing with those combinations. So it is coercively necessary to improve adhesion between the two components by adding an adhesion promoter. To determine the promoters influence, it is necessary to develop a suitable testing method to investigate e.g. the peel resistance. The current German standard "VDI Richtlinie 2019', which is actually only employed for thermoplastic/TPE combinations, can serve as a model to determine the adhesion of thermoplastic/LSR combinations.

  3. Mechanical responses of the periodontal ligament based on an exponential hyperelastic model: a combined experimental and finite element method.

    PubMed

    Huang, Huixiang; Tang, Wencheng; Yan, Bin; Wu, Bin; Cao, Dan

    2016-01-01

    The V-W exponential hyperelastic model is adopted to describe the instantaneous elastic response of the periodontal ligament (PDL). The general theoretical framework of constitutive modeling is described based on nonlinear continuum mechanics, and the elasticity tensor used to develop UMAT subroutine is formulated. Nanoindentation experiment is performed to characterize mechanical properties of an adult pig PDL specimen. Then the experiment is simulated by using the finite element (FE) analysis. Meanwhile, the optimized material parameters are identified by the inverse FE method. The good agreement between the simulated results and experimental data demonstrates that the V-W model is capable of describing the mechanical behavior of the PDL. Therefore, the model and its implementation into FE code are validated. By using the model, we simulate the tooth movement under orthodontic loading to predict the mechanical responses of the PDL. The results show that local concentrations of stress and strain in the PDL are found. PMID:25648914

  4. Mechanical Removal of Migrated Onyx Due to Microcatheter Rupture During AVM Embolization: A Technical Case Report.

    PubMed

    Senturk, Cagin

    2015-12-01

    We report a case where migrated Onyx could be removed safely with a mechanical thrombectomy device after withdrawal of the damaged microcatheter. A microcatheter was retained in the superior cerebellar artery with attached Onyx fragments on its tip during embolization of a bled cerebellar AVM. During retrieval maneuvers microcatheter shaft was ruptured and Onyx fragments were released into the vertebrobasilar system causing occlusion. Finally, Onyx fragment on tip of the microcatheter could be detached with dimethyl sulfoxide injection and the microcatheter could be withdrawn. A Merci retriever device (Concentric Medical, Mountain View, CA, USA) was successfully used to retrieve most of the dislodged Onyx material and recanalize the vertebrobasilar circulation. PMID:25910968

  5. Structure of Low-Lying Excited States of Guanine in DNA and Solution: Combined Molecular Mechanics and High-Level Coupled Cluster Studies

    DOE PAGESBeta

    Kowalski, Karol; Valiev, Marat

    2007-01-01

    High-level ab-initio equation-of-motion coupled-cluster methods with singles, doubles, and noniterative triples are used, in conjunction with the combined quantum mechanical molecular mechanics approach, to investigate the structure of low-lying excited states of the guanine base in DNA and solvated environments. Our results indicate that while the excitation energy of the first excited state is barely changed compared to its gas-phase counterpart, the excitation energy of the second excited state is blue-shifted by 0.24 eV.

  6. Damage Detection Based on Power Dissipation Measured with PZT Sensors through the Combination of Electro-Mechanical Impedances and Guided Waves.

    PubMed

    Sevillano, Enrique; Sun, Rui; Perera, Ricardo

    2016-01-01

    The use of piezoelectric ceramic transducers (such as Lead-Zirconate-Titanate-PZT) has become more and more widespread for Structural Health Monitoring (SHM) applications. Among all the techniques that are based on this smart sensing solution, guided waves and electro-mechanical impedance techniques have found wider acceptance, and so more studies and experimental works can be found containing these applications. However, even though these two techniques can be considered as complementary to each other, little work can be found focused on the combination of them in order to define a new and integrated damage detection procedure. In this work, this combination of techniques has been studied by proposing a new integrated damage indicator based on Electro-Mechanical Power Dissipation (EMPD). The applicability of this proposed technique has been tested through different experimental tests, with both lab-scale and real-scale structures. PMID:27164104

  7. Damage Detection Based on Power Dissipation Measured with PZT Sensors through the Combination of Electro-Mechanical Impedances and Guided Waves

    PubMed Central

    Sevillano, Enrique; Sun, Rui; Perera, Ricardo

    2016-01-01

    The use of piezoelectric ceramic transducers (such as Lead-Zirconate-Titanate—PZT) has become more and more widespread for Structural Health Monitoring (SHM) applications. Among all the techniques that are based on this smart sensing solution, guided waves and electro-mechanical impedance techniques have found wider acceptance, and so more studies and experimental works can be found containing these applications. However, even though these two techniques can be considered as complementary to each other, little work can be found focused on the combination of them in order to define a new and integrated damage detection procedure. In this work, this combination of techniques has been studied by proposing a new integrated damage indicator based on Electro-Mechanical Power Dissipation (EMPD). The applicability of this proposed technique has been tested through different experimental tests, with both lab-scale and real-scale structures. PMID:27164104

  8. Overall non-linear correction of phase shifting mechanism in white light interferometry system based on displacement feedback control combined with fuzzy PID control

    NASA Astrophysics Data System (ADS)

    Song, Ningfang; Luo, Xinkai; Li, Huipeng; Li, Jiao

    2015-10-01

    The non-linearity of the phase shifting mechanism in white light interferometry system can seriously affect the measuring accuracy of the system. In this paper, the correcting method is to combine the displacement feedback control technology with the fuzzy PID control technology. Displacement feedback control mechanism and fuzzy PID controller are designed and then try to figure it out through Matlab simulation and experiment.. The result shows that combining the displacement feedback control technology with the fuzzy PID control technology can fulfill decent overall non-linear correction in the white light interferometry measuring system. Meanwhile, the accuracy of the correction is high and the non-linearity drop from 2% to 0.1%.

  9. Biomechanical aspects of segmented arch mechanics combined with power arm for controlled anterior tooth movement: A three-dimensional finite element study

    PubMed Central

    Ozaki, Hiroya; Tominaga, Jun-ya; Hamanaka, Ryo; Sumi, Mayumi; Chiang, Pao-Chang; Tanaka, Motohiro; Koga, Yoshiyuki

    2015-01-01

    The porpose of this study was to determine the optimal length of power arms for achieving controlled anterior tooth movement in segmented arch mechanics combined with power arm. A three-dimensional finite element method was applied for the simulation of en masse anterior tooth retraction in segmented power arm mechanics. The type of tooth movement, namely, the location of center of rotation of the maxillary central incisor in association with power arm length, was calculated after the retraction force was applied. When a 0.017 × 0.022-in archwire was inserted into the 0.018-in slot bracket, bodily movement was obtained at 9.1 mm length of power arm, namely, at the level of 1.8 mm above the center of resistance. In case a 0.018 × 0.025-in full-size archwire was used, bodily movement of the tooth was produced at the power arm length of 7.0 mm, namely, at the level of 0.3 mm below the center of resistance. Segmented arch mechanics required shorter length of power arms for achieving any type of controlled anterior tooth movement as compared to sliding mechanics. Therefore, this space closing mechanics could be widely applied even for the patients whose gingivobuccal fold is shallow. The segmented arch mechanics combined with power arm could provide higher amount of moment-to-force ratio sufficient for controlled anterior tooth movement without generating friction, and vertical forces when applying retraction force parallel to the occlusal plane. It is, therefore, considered that the segmented power arm mechanics has a simple appliance design and allows more efficient and controllable tooth movement. PMID:25610497

  10. Combined first-order reversal curve and x-ray microscopy investigation of magnetization reversal mechanisms in hexagonal antidot lattices

    NASA Astrophysics Data System (ADS)

    Gräfe, Joachim; Weigand, Markus; Stahl, Claudia; Träger, Nick; Kopp, Michael; Schütz, Gisela; Goering, Eberhard J.; Haering, Felix; Ziemann, Paul; Wiedwald, Ulf

    2016-01-01

    The magnetization reversal in nanoscaled antidot lattices is widely investigated to understand the tunability of the magnetic anisotropy and the coercive field through nanostructuring of thin films. By investigating highly ordered focused ion beam milled antidot lattices with a combination of first-order reversal curves and magnetic x-ray microscopy, we fully elucidate the magnetization reversal along the distinct orientations of a hexagonal antidot lattice. This combination proves especially powerful as all partial steps of this complex magnetization reversal can be identified and subsequently imaged. Through this approach we discovered several additional steps that were neglected in previous studies. Furthermore, by imaging the microscopic magnetization state during each reversal step, we were able to link the coercive and interaction fields determined by the first-order reversal curve method to true microscopic magnetization configurations and determine their origin.

  11. A Novel Mechanism of PPAR Gamma Induction via EGFR Signalling Constitutes Rational for Combination Therapy in Bladder Cancer

    PubMed Central

    Mansure, Jose Joao; Nassim, Roland; Chevalier, Simone; Szymanski, Konrad; Rocha, Joice; Aldousari, Saad; Kassouf, Wassim

    2013-01-01

    Background Two signalling molecules that are attractive for targeted therapy are the epidermal growth factor receptor (EGFR) and the peroxisome proliferator-activated receptor gamma (PPARγ). We investigated possible crosstalk between these 2 pathways, particularly in light of the recent evidence implicating PPARγ for anticancer therapy. Principal Findings As evaluated by MTT assays, gefitinib (EGFR inhibitor) and DIM-C (PPARγ agonist) inhibited growth of 9 bladder cancer cell lines in a dose-dependent manner but with variable sensitivity. In addition, combination of gefitinib and DIM-C demonstrated maximal inhibition of cell proliferation compared to each drug alone. These findings were confirmed in vivo, where combination therapy maximally inhibited tumor growth in contrast to each treatment alone when compared to control (p<0.04). Induction of PPARγ expression along with nuclear accumulation was observed in response to increasing concentrations of gefitinib via activation of the transcription factor CCAT/enhancer-binding protein-β (CEBP-β). In these cell lines, DIM-C significantly sensitized bladder cancer cell lines that were resistant to EGFR inhibition in a schedule-specific manner. Conclusion These results suggest that PPARγ agonist DIM-C can be an excellent alternative to bladder tumors resistant to EGFR inhibition and combination efficacy might be achieved in a schedule-specific manner. PMID:23409107

  12. Combined Effects of Ventilation Mode and Positive End-Expiratory Pressure on Mechanics, Gas Exchange and the Epithelium in Mice with Acute Lung Injury

    PubMed Central

    Thammanomai, Apiradee; Hamakawa, Hiroshi; Bartolák-Suki, Erzsébet; Suki, Béla

    2013-01-01

    The accepted protocol to ventilate patients with acute lung injury is to use low tidal volume (VT) in combination with recruitment maneuvers or positive end-expiratory pressure (PEEP). However, an important aspect of mechanical ventilation has not been considered: the combined effects of PEEP and ventilation modes on the integrity of the epithelium. Additionally, it is implicitly assumed that the best PEEP-VT combination also protects the epithelium. We aimed to investigate the effects of ventilation mode and PEEP on respiratory mechanics, peak airway pressures and gas exchange as well as on lung surfactant and epithelial cell integrity in mice with acute lung injury. HCl-injured mice were ventilated at PEEPs of 3 and 6 cmH2O with conventional ventilation (CV), CV with intermittent large breaths (CVLB) to promote recruitment, and a new mode, variable ventilation, optimized for mice (VVN). Mechanics and gas exchange were measured during ventilation and surfactant protein (SP)-B, proSP-B and E-cadherin levels were determined from lavage and lung homogenate. PEEP had a significant effect on mechanics, gas exchange and the epithelium. The higher PEEP reduced lung collapse and improved mechanics and gas exchange but it also down regulated surfactant release and production and increased epithelial cell injury. While CVLB was better than CV, VVN outperformed CVLB in recruitment, reduced epithelial injury and, via a dynamic mechanotransduction, it also triggered increased release and production of surfactant. For long-term outcome, selection of optimal PEEP and ventilation mode may be based on balancing lung physiology with epithelial injury. PMID:23326543

  13. Combined effects of ventilation mode and positive end-expiratory pressure on mechanics, gas exchange and the epithelium in mice with acute lung injury.

    PubMed

    Thammanomai, Apiradee; Hamakawa, Hiroshi; Bartolák-Suki, Erzsébet; Suki, Béla

    2013-01-01

    The accepted protocol to ventilate patients with acute lung injury is to use low tidal volume (V(T)) in combination with recruitment maneuvers or positive end-expiratory pressure (PEEP). However, an important aspect of mechanical ventilation has not been considered: the combined effects of PEEP and ventilation modes on the integrity of the epithelium. Additionally, it is implicitly assumed that the best PEEP-V(T) combination also protects the epithelium. We aimed to investigate the effects of ventilation mode and PEEP on respiratory mechanics, peak airway pressures and gas exchange as well as on lung surfactant and epithelial cell integrity in mice with acute lung injury. HCl-injured mice were ventilated at PEEPs of 3 and 6 cmH(2)O with conventional ventilation (CV), CV with intermittent large breaths (CV(LB)) to promote recruitment, and a new mode, variable ventilation, optimized for mice (VV(N)). Mechanics and gas exchange were measured during ventilation and surfactant protein (SP)-B, proSP-B and E-cadherin levels were determined from lavage and lung homogenate. PEEP had a significant effect on mechanics, gas exchange and the epithelium. The higher PEEP reduced lung collapse and improved mechanics and gas exchange but it also down regulated surfactant release and production and increased epithelial cell injury. While CV(LB) was better than CV, VV(N) outperformed CV(LB) in recruitment, reduced epithelial injury and, via a dynamic mechanotransduction, it also triggered increased release and production of surfactant. For long-term outcome, selection of optimal PEEP and ventilation mode may be based on balancing lung physiology with epithelial injury. PMID:23326543

  14. A new water absorbable mechanical Epidermal skin equivalent: the combination of hydrophobic PDMS and hydrophilic PVA hydrogel.

    PubMed

    Morales-Hurtado, M; Zeng, X; Gonzalez-Rodriguez, P; Ten Elshof, J E; van der Heide, E

    2015-06-01

    Research on human skin interactions with healthcare and lifestyle products is a topic continuously attracting scientific studies over the past years. It is possible to evaluate skin mechanical properties based on human or animal experimentation, yet in addition to possible ethical issues, these samples are hard to obtain, expensive and give rise to highly variable results. Therefore, the design of a skin equivalent is essential. This paper describes the design and characterization of a new Epidermal Skin Equivalent (ESE). The material resembles the properties of epidermis and is a first approach to mimic the mechanical properties of the human skin structure, variable with the length scale. The ESE is based on a mixture of Polydimethyl Siloxane (PDMS) and Polyvinyl Alcohol (PVA) hydrogel cross-linked with Glutaraldehyde (GA). It was chemically characterized by XPS and FTIR measurements and its cross section was observed by macroscopy and cryoSEM. Confocal Microscope analysis on the surface of the ESE showed an arithmetic roughness (Ra) between 14-16 μm and contact angle (CA) values between 50-60°, both of which are close to the values of in vivo human skins reported in the literature. The Equilibrium Water Content (ECW) was around 33.8% and Thermo Gravimetric Analysis (TGA) confirmed the composition of the ESE samples. Moreover, the mechanical performance was determined by indentation tests and Dynamo Thermo Mechanical Analysis (DTMA) shear measurements. The indentation results were in good agreement with that of the target epidermis reported in the literature with an elastic modulus between 0.1-1.5 MPa and it showed dependency on the water content. According to the DTMA measurements, the ESE exhibits a viscoelastic behavior, with a shear modulus between 1-2.5MPa variable with temperature, frequency and the hydration of the samples. PMID:25840121

  15. A New Animal Model for Investigation of Mechanical Unloading in Hypertrophic and Failing Hearts: Combination of Transverse Aortic Constriction and Heterotopic Heart Transplantation

    PubMed Central

    Stenzig, Justus; Biermann, Daniel; Jelinek, Marisa; Reichenspurner, Hermann; Eschenhagen, Thomas; Ehmke, Heimo; Schwoerer, Alexander P.

    2016-01-01

    Objectives Previous small animal models for simulation of mechanical unloading are solely performed in healthy or infarcted hearts, not representing the pathophysiology of hypertrophic and dilated hearts emerging in heart failure patients. In this article, we present a new and economic small animal model to investigate mechanical unloading in hypertrophic and failing hearts: the combination of transverse aortic constriction (TAC) and heterotopic heart transplantation (hHTx) in rats. Methods To induce cardiac hypertrophy and failure in rat hearts, three-week old rats underwent TAC procedure. Three and six weeks after TAC, hHTx with hypertrophic and failing hearts in Lewis rats was performed to induce mechanical unloading. After 14 days of mechanical unloading animals were euthanatized and grafts were explanted for further investigations. Results 50 TAC procedures were performed with a survival of 92% (46/50). When compared to healthy rats left ventricular surface decreased to 5.8±1.0 mm² (vs. 9.6± 2.4 mm²) (p = 0.001) after three weeks with a fractional shortening (FS) of 23.7± 4.3% vs. 28.2± 1.5% (p = 0.01). Six weeks later, systolic function decreased to 17.1± 3.2% vs. 28.2± 1.5% (p = 0.0001) and left ventricular inner surface increased to 19.9±1.1 mm² (p = 0.0001). Intraoperative graft survival during hHTx was 80% with 46 performed procedures (37/46). All transplanted organs survived two weeks of mechanical unloading. Discussion Combination of TAC and hHTx in rats offers an economic and reproducible small animal model enabling serial examination of mechanical unloading in a truly hypertrophic and failing heart, representing the typical pressure overloaded and dilated LV, occurring in patients with moderate to severe heart failure. PMID:26841021

  16. [Mechanisms for the increased fertilizer nitrogen use efficiency of rice in wheat-rice rotation system under combined application of inorganic and organic fertilizers].

    PubMed

    Liu, Yi-Ren; Li, Xiang; Yu, Jie; Shen, Qi-Rong; Xu, Yang-Chun

    2012-01-01

    A pot experiment was conducted to study the effects of combined application of organic and inorganic fertilizers on the nitrogen uptake by rice and the nitrogen supply by soil in a wheat-rice rotation system, and approach the mechanisms for the increased fertilizer nitrogen use efficiency of rice under the combined fertilization from the viewpoint of microbiology. Comparing with applying inorganic fertilizers, combined application of organic and inorganic fertilizers decreased the soil microbial biomass carbon and nitrogen and soil mineral nitrogen contents before tillering stage, but increased them significantly from heading to filling stage. Under the combined fertilization, the dynamics of soil nitrogen supply matched best the dynamics of rice nitrogen uptake and utilization, which promoted the nitrogen accumulation in rice plant and the increase of rice yield and biomass, and increased the fertilizer nitrogen use efficiency of rice significantly. Combined application of inorganic and organic fertilizers also promoted the propagation of soil microbes, and consequently, more mineral nitrogen in soil was immobilized by the microbes at rice early growth stage, and the immobilized nitrogen was gradually released at the mid and late growth stages of rice, being able to better satisfy the nitrogen demand of rice in its various growth and development stages. PMID:22489483

  17. Mechanical Thrombectomy Using the Solitaire FR system for Occlusion of the Top of the Basilar Artery: Intentional Detachment of the Device after Partial Retrieval

    PubMed Central

    Siu, Kwong Lok; Lee, Dong-Geun; Shim, Jae Ho; Suh, Dae Chul

    2014-01-01

    Acute, distal, basilar artery occlusion is a challenging neurovascular emergency. There have been several reports regarding the successful application of the Solitaire FR device for treating this lesion. However, due to the lack of a suitable, balloon-tipped, guiding catheter for the vertebral artery, during this procedure we frequently experience the occurrence of clot fragmentation and distal migration. There may be some technical solutions to solve this problem. The purpose of this report is to present a technical variation of using the Solitaire FR, and which is referred to as the 'intentional device detachment technique.' As a clot tends to re-embolize during its passage through the tortuous cranio-cervical junction level of the vertebral artery or its passage through the tip of the guiding catheter, due to the lack of proximal flow arrest, we thought that not removing the stent segment of the device which is capturing the clot could avoid this problem. We were able to successfully apply this technique in two cases. We believe that this technique can be a possible technical option for using the Solitaire FR device when a patient has little concern regarding the subsequent use of antiplatelets. PMID:24642915

  18. Rice and Bean Targets for Biofortification Combined with High Carotenoid Content Crops Regulate Transcriptional Mechanisms Increasing Iron Bioavailability

    PubMed Central

    Dias, Desirrê Morais; de Castro Moreira, Maria Eliza; Gomes, Mariana Juste Contin; Lopes Toledo, Renata Celi; Nutti, Marilia Regini; Pinheiro Sant’Ana, Helena Maria; Martino, Hércia Stampini Duarte

    2015-01-01

    Iron deficiency affects thousands of people worldwide. Biofortification of staple food crops aims to support the reduction of this deficiency. This study evaluates the effect of combinations of common beans and rice, targets for biofortification, with high carotenoid content crops on the iron bioavailability, protein gene expression, and antioxidant effect. Iron bioavailability was measured by the depletion/repletion method. Seven groups were tested (n = 7): Pontal bean (PB); rice + Pontal bean (R + BP); Pontal bean + sweet potato (PB + SP); Pontal bean + pumpkin (PB + P); Pontal bean + rice + sweet potato (PB + R + P); Pontal bean + rice + sweet potato (PB + R + SP); positive control (Ferrous Sulfate). The evaluations included: hemoglobin gain, hemoglobin regeneration efficiency (HRE), gene expression of divalente metal transporter 1 (DMT-1), duodenal citocromo B (DcytB), ferroportin, hephaestin, transferrin and ferritin and total plasma antioxidant capacity (TAC). The test groups, except the PB, showed higher HRE (p < 0.05) than the control. Gene expression of DMT-1, DcytB and ferroportin increased (p < 0.05) in the groups fed with high content carotenoid crops (sweet potato or pumpkin). The PB group presented lower (p < 0.05) TAC than the other groups. The combination of rice and common beans, and those with high carotenoid content crops increased protein gene expression, increasing the iron bioavailability and antioxidant capacity. PMID:26610564

  19. Drag and heat reduction mechanism induced by a combinational novel cavity and counterflowing jet concept in hypersonic flows

    NASA Astrophysics Data System (ADS)

    Sun, Xi-wan; Guo, Zhen-yun; Huang, Wei; Li, Shi-bin; Yan, Li

    2016-09-01

    The drag and heat reduction problem of hypersonic reentry vehicles has always attracted the attention worldwide, and many novel schemes have been proposed recently. In the current study, the research progress of the combinational configuration of the forward-facing cavity and the counterflowing jet has been reviewed, and the conventional cavity configuration has been substituted by an approximate maximum thrust nozzle contour for better heat and surface pressure reduction efficiency. The Reynolds-average of Navier-Stokes (RANS) equations coupled with the SST k-ω turbulence model have been employed to calculate its surrounding flow fields. A validation metric and the grid convergence index (GCI) have been employed to conduct the turbulence model assessment and the grid independence analysis respectively. The axisymmetric assumption has been verified by three-dimensional computational results as well. The obtained results show that the SST k-ω model is more suitable for the novel drag and heat flux reduction scheme proposed in this article, and the axisymmetric assumption is approximately reasonable. After investigating the influence of jet pressure ratio, the novel combinational configuration has been verified to be more effective in heat and surface pressure reduction, and this is because the approximate maximum thrust nozzle contour contributes to better expansion and avoids total pressure loss of the jet.

  20. Cathepsin S attenuates endosomal EGFR signalling: A mechanical rationale for the combination of cathepsin S and EGFR tyrosine kinase inhibitors

    PubMed Central

    Huang, Chien-Chang; Lee, Cheng-Che; Lin, Hsiao-Han; Chang, Jang-Yang

    2016-01-01

    EGF-mediated EGFR endocytosis plays a crucial role in the attenuation of EGFR activation by sorting from early endosomes to late endosomes and transporting them into lysosomes for the final proteolytic degradation. We previously observed that cathepsin S (CTSS) inhibition induces tumour cell autophagy through the EGFR-mediated signalling pathway. In this study, we further clarified the relationship between CTSS activities and EGFR signalling regulation. Our results revealed that CTSS can regulate EGFR signalling by facilitating EGF-mediated EGFR degradation. CTSS inhibition delayed the EGFR degradation process and caused EGFR accumulation in the late endosomes at the perinuclear region, which provides spatial compartments for prolonged EGFR and sustained downstream signal transducer and activator of transcription 3 and AKT signalling. Notably, cellular apoptosis was markedly enhanced by combining treatment with the EGFR inhibitor Iressa and CTSS inhibitor 6r. The data not only reveal a biological role of CTSS in EGFR signalling regulation but also evidence a rationale for its clinical evaluation in the combination of CTSS and EGFR tyrosine kinase inhibitors. PMID:27387133

  1. Rice and Bean Targets for Biofortification Combined with High Carotenoid Content Crops Regulate Transcriptional Mechanisms Increasing Iron Bioavailability.

    PubMed

    Dias, Desirrê Morais; de Castro Moreira, Maria Eliza; Gomes, Mariana Juste Contin; Lopes Toledo, Renata Celi; Nutti, Marilia Regini; Pinheiro Sant'Ana, Helena Maria; Martino, Hércia Stampini Duarte

    2015-11-01

    Iron deficiency affects thousands of people worldwide. Biofortification of staple food crops aims to support the reduction of this deficiency. This study evaluates the effect of combinations of common beans and rice, targets for biofortification, with high carotenoid content crops on the iron bioavailability, protein gene expression, and antioxidant effect. Iron bioavailability was measured by the depletion/repletion method. Seven groups were tested (n = 7): Pontal bean (PB); rice + Pontal bean (R + BP); Pontal bean + sweet potato (PB + SP); Pontal bean + pumpkin (PB + P); Pontal bean + rice + sweet potato (PB + R + P); Pontal bean + rice + sweet potato (PB + R + SP); positive control (Ferrous Sulfate). The evaluations included: hemoglobin gain, hemoglobin regeneration efficiency (HRE), gene expression of divalente metal transporter 1 (DMT-1), duodenal citocromo B (DcytB), ferroportin, hephaestin, transferrin and ferritin and total plasma antioxidant capacity (TAC). The test groups, except the PB, showed higher HRE (p < 0.05) than the control. Gene expression of DMT-1, DcytB and ferroportin increased (p < 0.05) in the groups fed with high content carotenoid crops (sweet potato or pumpkin). The PB group presented lower (p < 0.05) TAC than the other groups. The combination of rice and common beans, and those with high carotenoid content crops increased protein gene expression, increasing the iron bioavailability and antioxidant capacity. PMID:26610564

  2. Modification mechanism of praseodymium doping for the photocatalytic performance of TiO2: a combined experimental and theoretical study.

    PubMed

    Duan, Zhi-Gang; Zhao, Zong-Yan; Shi, Qing-Nan

    2015-07-15

    Impurity doping is a simple and efficient modification method to improve the photocatalytic performance of wide band gap photocatalysts. However, some basic and important issues about the mechanism of impurity doping modification still need to be further confirmed and explained. In the present work, Pr-doped TiO2 with a mono-phase crystal structure was prepared by a sol-gel method. Then, the crystal structure, binding information, optical absorption, and photocatalytic activity were systematically investigated. The experimental results show that Pr doping could significantly enhance the photocatalytic activity of TiO2, and the effects of modification on rutile TiO2 are more obvious than for anatase TiO2. In order to understand the underlying mechanism, density functional theory was utilized to calculate the crystal structure and electronic structure of pure and Pr-doped TiO2. The differences in electronic structure between anatase and rutile phases lead to the above photocatalytic performance. The experimental measurements and theoretical calculations mutually support each other in the present work. Two points are confirmed: the position of the band edge determines the redox activity of the photocatalyst, and the shallow energy bands induced by impurity doping could improve the photocatalytic performance. PMID:26130404

  3. Correlating mechanical properties and anti-wear performance of tribofilms formed by ionic liquids, ZDDP and their combinations

    DOE PAGESBeta

    Landauer, Alexander K.; Barnhill, William C.; Qu, Jun

    2016-03-10

    Here we examine the elasticity, hardness, and resistance-to-plastic-deformation (P/S2) measured via nanoindentation of several tribofilms and correlates these properties to friction and wear behavior. The tribofilms were generated by ball-on-plate reciprocating sliding lubricated by a base oil containing an ionic liquid, phosphonium-organophosphate or ammonium-organophosphate, zinc dialkyldithiophosphate (ZDDP), or combination of IL and ZDDP. Nanoindentation was conducted at room and elevated temperatures. While there seems little correlation between the tribofilm hardness and tribological behavior, a higher modulus generally leads to better friction and wear performance. Interestingly, a lower P/S2 ratio tends to reduce friction and improve wear protection, which is inmore » an opposite trend as reported for bulk materials. Ultimately, this is likely attributable to the dynamic, self-healing characteristics of tribofilms.« less

  4. Use of Percutaneous Aspiration Thrombectomy vs. Anticoagulation Therapy to Treat Acute Iliofemoral Venous Thrombosis: 1-year Follow-up Results of a Randomised, Clinical Trial

    SciTech Connect

    Cakir, Volkan; Gulcu, Aytac; Akay, Emrah; Capar, Ahmet E.; Gencpinar, Tugra; Kucuk, Banu; Karabay, Ozalp; Goktay, A. Yigit

    2014-08-15

    PurposeThe purpose of this study was to compare the efficacy of percutaneous aspiration thrombectomy (PAT) followed by standard anticoagulant therapy, with anticoagulation therapy alone, for the treatment of acute proximal lower extremity deep vein thrombosis.MethodsIn this randomised, prospective study, 42 patients with acute proximal iliofemoral deep vein thrombosis documented via Doppler ultrasound examination, were separated into an interventional treatment group (16 males, 5 females, average age 51 years) and a medical treatment group (13 males, 8 females, average age 59 years). In the interventional group, PAT with large-lumen 9-F diameter catheterisation was applied, after initiation of standard anticoagulant therapy. Balloon angioplasty (n 19) and stent implementation (n: 14) were used to treat patients with residual stenosis (>50 %) after PAT. Prophylactic IVC filters were placed in two patients. The thrombus clearance status of the venous system was evaluated by venography. In both the medical and interventional groups, venous patency rates and clinical symptom scores were evaluated at months 1, 3, and 12 after treatment.ResultsDeep venous systems became totally cleared of thrombi in 12 patients treated with PAT. The venous patency rates in month 12 were 57.1 and 4.76 % in the interventional and medical treatment groups, respectively. A statistically significant improvement was observed in clinical symptom scores of the interventional group (PAT) with or without stenting (4.23 ± 0.51 before treatment; 0.81 ± 0.92 at month 12) compared with the medical treatment group (4.00 ± 0.63 before treatment; 2.43 ± 0.67 at month 12). During follow-up, four patients in the medical treatment and one in the interventional group developed pulmonary embolisms.ConclusionsFor treatment of acute deep vein thrombosis, PAT with or without stenting is superior to anticoagulant therapy alone in terms of both ensuring venous patency and improving clinical

  5. Design and validation of a novel bioreactor principle to combine online micro-computed tomography monitoring and mechanical loading in bone tissue engineering

    NASA Astrophysics Data System (ADS)

    Hagenmüller, Henri; Hitz, Marco; Merkle, Hans P.; Meinel, Lorenz; Müller, Ralph

    2010-01-01

    Mechanical loading plays an important role in bone remodeling in vivo and, therefore, has been suggested as a key parameter in stem cell-based engineering of bone-like tissue in vitro. However, the optimization of loading protocols during stem cell differentiation and subsequent bone-like tissue formation is challenged by multiple input factors, which are difficult to control and validate. These include the variable cellular performance of cells harvested from different patients, nonstandardized culture media components, the choice of the biomaterial forming the scaffold, and its morphology, impacting a broader validity of mechanical stimulation regimens. To standardize the cell culture of bone-like tissue constructs, we suggest the involvement of time-lapsed feedback loops. For this purpose we present a prototype bioreactor that combines online, nondestructive monitoring using micro-computed tomography and direct mechanical loading of three-dimensional tissue engineering constructs. Validation of this system showed displacement steps down to 1 μm and cyclic sinusoidal loadings of up to 10 Hz. Load detection resolution was 0.01 N, and micro-computed tomography data were of high quality. For the first time, the developed bioreactor links time-lapsed, nondestructive, and dynamic imaging with mechanical stimulation, designed for cell culture under sterile conditions. This system is believed to substantially improve today's experimental options to study and optimize osteogenic stem cell culture and differentiation at the interface with mechanical stimulation.

  6. Analysis of CO2 convection mechanisms associated to surface heating, by combining remote sensing data and in situ measurements

    NASA Astrophysics Data System (ADS)

    Tello, Marivi; Curcoll, Roger; Font, Anna; Morgu, Josep Anton; Rod, Xavier

    Assessing the mechanisms involved in the variability of carbon fluxes is crucial for the under-standing of the changing earth dynamics. In that sense, the aim of this work is to analyze CO2 convection mechanisms at a regional scale in the boundary layer and the lower troposphere by means of cross correlation of land surface temperature data, radio-soundings, wind speeds and in situ measurements of CO2 atmospheric mixing ratios. Since data is easier to acquire, ground level horizontal CO2 fluxes have been widely studied. In the contrary, vertical ones are still subject to uncertainties, even if they are necessary to understand 3D CO2 variability in the atmosphere. In particular, this paper focuses on the relationship between surface heating, convection and CO2 concentrations at different heights and, more generally, on the energy transfer between the surface and the air. The monitored area corresponds to a region on the North Eastern Iberian Peninsula, mainly devoted to agricultural activities. Different types of land covers are observed. On the one hand, in situ data has been collected by several flights during 2007 along the parallel 42o N following the "Crown" aircraft sampling approach [1] that integrates CO2 data obtained through horizontal transects and vertical profiles. This particular configuration is especially well suited for the evaluation of both horizontal and vertical CO2 fluxes. On the other hand, the radiometric land surface temperatures are obtained from the MODIS instrument onboard the Terra and the Aqua satellites. Besides, a flight campaign with an airborne sensor along the same transect in the parallel 42o N has been proposed in the scope of the MIDAS-6 project recently submitted. This project plans to improve soil moisture and ocean salinity products of the SMOS sensor recently launched and to demonstrate its applications. This will allow the study of moisture patterns in the monitored area at two different scales: that of the data collected

  7. Combined Spectroscopic and Calorimetric Studies to Reveal Absorption Mechanisms and Conformational Changes of Protein on Nanoporous Biomaterials

    PubMed Central

    Ahmadi, Saharnaz; Farokhi, Maryam; Padidar, Parisa; Falahati, Mojtaba

    2015-01-01

    In this study the effect of surface modification of mesoporous silica nanoparticles (MSNs) on its adsorption capacities and protein stability after immobilization of beta-lactoglobulin B (BLG-B) was investigated. For this purpose, non-functionalized (KIT-6) and aminopropyl-functionalized cubic Ia3d mesoporous silica ([n-PrNH2-KIT-6]) nanoparticles were used as nanoporous supports. Aminopropyl-functionalized mesoporous nanoparticles exhibited more potential candidates for BLG-B adsorption and minimum BLG leaching than non-functionalized nanoparticles. It was observed that the amount of adsorbed BLG is dependent on the initial BLG concentration for both KIT-6 and [n-PrNH2-KIT-6] mesoporous nanoparticles. Also larger amounts of BLG-B on KIT-6 was immobilized upon raising the temperature of the medium from 4 to 55 °C while such increase was undetectable in the case of immobilization of BLG-B on the [n-PrNH2-KIT-6]. At temperatures above 55 °C the amounts of adsorbed BLG on both studied nanomaterials decreased significantly. By Differential scanning calorimetry or DSC analysis the heterogeneity of the protein solution and increase in Tm may indicate that immobilization of BLG-B onto the modified KIT-6 results in higher thermal stability compared to unmodified one. The obtained results provide several crucial factors in determining the mechanism(s) of protein adsorption and stability on the nanostructured solid supports and the development of engineered nano-biomaterials for controlled drug-delivery systems and biomimetic interfaces for the immobilization of living cells. PMID:26230687

  8. Combined use of two biocontrol agents with different biocontrol mechanisms most likely results in less than expected efficacy in controlling foliar pathogens under fluctuating conditions: a modeling study.

    PubMed

    Xu, X-M; Jeger, M J

    2013-02-01

    Effective use of biocontrol agents (BCAs) is a potentially important component of sustainable agriculture; recently, there has been a trend for combined use of several BCAs, with an expectation of synergistic interactions among them. A previous numerical study suggested that, under homogenous conditions in which two BCAs occupied the same host tissue as the pathogen, combined use of two BCAs with different biocontrol mechanisms resulted, in most cases, in efficacies similar to using the more efficacious one alone; this result is consistent with published experimental results. The present study investigates whether combined use of a mycoparasitic and a competitive BCA leads to greater efficacy than that expected when the model is modified to allow for fluctuating temperature regimes and the effects of temperature on the pathogen and BCAs. Within the range of parameter values considered, combined use of two BCAs is shown to be less effective than that expected under the assumption of Bliss independence, and to result in a level of efficacy similar to that achieved by the more efficacious component used alone, indicating antagonistic interactions between the two BCAs. Nevertheless, combined use of two BCAs resulted in a slightly longer delay in epidemic development than did individual use of BCAs. Stochastic variability in simulated hourly temperatures did not result in a high level of variability in efficacy among replicates; nevertheless, the among-replicate variability appeared to be greater for the combined use of BCAs than for individual BCAs used alone. In contrast, there were greater effects of varying BCA-temperature relationships and application time (reflected in the temperature profile) on efficacy, suggesting the importance of characterizing the relationship between BCA activity and environmental conditions in future research. PMID:23095466

  9. Indentation and self-healing mechanisms of a self-assembled monolayer--a combined experimental and modeling study.

    PubMed

    Meltzer, Christian; Paul, Jonas; Dietrich, Hanno; Jäger, Christof M; Clark, Timothy; Zahn, Dirk; Braunschweig, Björn; Peukert, Wolfgang

    2014-07-30

    A combination of in situ vibrational sum-frequency generation (SFG) spectroscopy and molecular-dynamics (MD) simulations has allowed us to study the effects of indentation of self-assembled octadecylphosphonic acid (ODPA) monolayers on α-Al2O3(0001). Stress-induced changes in the vibrational signatures of C-H stretching vibrations in SFG spectra and the results of MD simulations provide clear evidence for an increase in gauche-defect density in the monolayer as a response to indentation. A stress-dependent analysis indicates that the defect density reaches saturation at approximately 155 MPa. After stress is released, the MD simulations show an almost instantaneous healing of pressure-induced defects in good agreement with experimental results. The lateral extent of the contact areas was studied with colocalized SFG spectroscopy and compared to theoretical predictions for pressure gradients from Hertzian contact theory. SFG experiments reveal a gradual increase in gauche-defect density with pressure before saturation close to the contact center. Furthermore, our MD simulations show a spatial anisotropy of pressure-induced effects within ODPA domains: molecules tilted in the direction of the pressure gradient increase in tilt angle while those on the opposite side form gauche-defects. PMID:25054614

  10. Mechanisms behind injecting the combination of nano-clay particles and polymer solution for enhanced oil recovery

    NASA Astrophysics Data System (ADS)

    Khalili Nezhad, Seyyed Shahram; Cheraghian, Goshtasp

    2015-09-01

    Laboratory investigations and field applications have proved injection of polymer solution to be an effective means to improve oil recovery for reservoirs of medium oil viscosity. The incremental oil produced in this case is the result of an increase in areal and vertical sweep efficiencies. Biopolymers and synthetic polymers are the major categories used in the petroleum industry for specific reasons. Biopolymers like xanthan are limited in their application as they are more susceptible to biodegradation. Synthetic polymers like Hydrolyzed PolyAcrylaMide (HPAM) have a much wider application as they are less susceptible to biodegradation. Furthermore, development of nanotechnology has successfully provided technical and economical viable alternatives for present materials. The objective of this study is to investigate the effect of combining clay nanoparticles with polymer solution on oil recovery. This paper includes a history match of both one-dimensional and two-dimensional polymer floods using a three-dimensional numerical model for fluid flow and mass transport. Results indicated that the amount of polymer adsorption decreased when clay nanoparticles were added to the PolyAcrylaMide solution; however, mobility ratio improvement is believed to be the main contributor for the proposed method in order to enhance much oil recovery compared to xanthan flood and HPAM flood.

  11. Mechanisms behind injecting the combination of nano-clay particles and polymer solution for enhanced oil recovery

    NASA Astrophysics Data System (ADS)

    Khalili Nezhad, Seyyed Shahram; Cheraghian, Goshtasp

    2016-08-01

    Laboratory investigations and field applications have proved injection of polymer solution to be an effective means to improve oil recovery for reservoirs of medium oil viscosity. The incremental oil produced in this case is the result of an increase in areal and vertical sweep efficiencies. Biopolymers and synthetic polymers are the major categories used in the petroleum industry for specific reasons. Biopolymers like xanthan are limited in their application as they are more susceptible to biodegradation. Synthetic polymers like Hydrolyzed PolyAcrylaMide (HPAM) have a much wider application as they are less susceptible to biodegradation. Furthermore, development of nanotechnology has successfully provided technical and economical viable alternatives for present materials. The objective of this study is to investigate the effect of combining clay nanoparticles with polymer solution on oil recovery. This paper includes a history match of both one-dimensional and two-dimensional polymer floods using a three-dimensional numerical model for fluid flow and mass transport. Results indicated that the amount of polymer adsorption decreased when clay nanoparticles were added to the PolyAcrylaMide solution; however, mobility ratio improvement is believed to be the main contributor for the proposed method in order to enhance much oil recovery compared to xanthan flood and HPAM flood.

  12. Molecular mechanisms and time-dependent dynamics of hormesis, antagonism and radioprotective effects at combined ionizing irradiation of biological systems

    NASA Astrophysics Data System (ADS)

    Vysotskii, Vladimir I.; Pinchuk, Anatolii A.; Kornilova, Alla A.; Samoylenko, Igor I.

    2002-11-01

    We study the time-dependent dynamics of formation, relaxation and self-reparation of DNA double-strand breaks at combined irradiation and the nonradiation degradation processes. The self-repairing process of DNA double-strand breaks is related with the peculiarities of long-range interaction of nucleotides within the breakage area. The properties of an intracellular liquid and the characteristics of the long-range interaction between the end pairs of nucleotides in the area of DNA double-strand break are changed during irradiation. Each kind of irradiation is characterized by certain effectiveness of double-strand breaks formation but on the other hand, the irradiation creates the conditions for their liquidation. Based on the analysis and correlation of these phenomena the time-dependent theory for DNA degradation was created, including hormesis phenomenon, radiation antagonism, the validity of anomaly influence of low and large doses at sharp and chronic irradiation and other effects. A qualitative and quantitative agreement of the theory and experimental results was obtained.

  13. A Genetic Susceptibility Mechanism for Major Depression: Combinations of polymorphisms Defined the Risk of Major Depression and Subpopulations.

    PubMed

    Wang, Yanfang; Sun, Ning; Li, Suping; Du, Qiaorong; Xu, Yong; Liu, Zhifeng; Zhang, Kerang

    2015-06-01

    Major Depression (MD) is a highly inherited psychiatric disorder. The norepinephrine transporter (NET) gene plays important role in pathophysiology of MD. This study attempted to examine the relationship between polymorphisms of NET gene and MD. Patients with MD and healthy controls were recruited and subgrouped. The T-182C and G1287A polymorphisms of NET gene were genotyped by direct sequencing. The genotypic and allelic frequencies were compared using the Pearson χ2 analysis. The linkage disequilibrium was analyzed using the UNPHASED program. Significant differences in genotypic and allelic frequencies of T-182C polymorphism were observed between MD subgroups and controls. When referenced by TT genotype, the OR value increased gradient from TC to CC genotype; when referenced by T allele, the odds ratio value of C allele also increased. Compared with those having both -182 T/T and 1287 G/G genotypes, in patients with MD, early-onset MD, and MD with suicide concept group, the -182 C/C and 1287 G/A combinatorial genotype has significant risk; yet in patients with MD family history, the -182 C/C and 1287 A/A combinatorial genotype has significant risk. Different combinations of T-182C and the G1287A polymorphisms of NET gene might increase morbidity risk of MD subpopulations. PMID:26061302

  14. Reaction Mechanism of N-Acetylneuraminic Acid Lyase Revealed by a Combination of Crystallography, QM/MM Simulation, and Mutagenesis

    PubMed Central

    2014-01-01

    N-Acetylneuraminic acid lyase (NAL) is a Class I aldolase that catalyzes the reversible condensation of pyruvate with N-acetyl-d-mannosamine (ManNAc) to yield the sialic acid N-acetylneuraminic acid (Neu5Ac). Aldolases are finding increasing use as biocatalysts for the stereospecific synthesis of complex molecules. Incomplete understanding of the mechanism of catalysis in aldolases, however, can hamper development of new enzyme activities and specificities, including control over newly generated stereocenters. In the case of NAL, it is clear that the enzyme catalyzes a Bi-Uni ordered condensation reaction in which pyruvate binds first to the enzyme to form a catalytically important Schiff base. The identity of the residues required for catalysis of the condensation step and the nature of the transition state for this reaction, however, have been a matter of conjecture. In order to address, this we crystallized a Y137A variant of the E. coli NAL in the presence of Neu5Ac. The three-dimensional structure shows a full length sialic acid bound in the active site of subunits A, B, and D, while in subunit C, discontinuous electron density reveals the positions of enzyme-bound pyruvate and ManNAc. These ‘snapshot’ structures, representative of intermediates in the enzyme catalytic cycle, provided an ideal starting point for QM/MM modeling of the enzymic reaction of carbon–carbon bond formation. This revealed that Tyr137 acts as the proton donor to the aldehyde oxygen of ManNAc during the reaction, the activation barrier is dominated by carbon–carbon bond formation, and proton transfer from Tyr137 is required to obtain a stable Neu5Ac-Lys165 Schiff base complex. The results also suggested that a triad of residues, Tyr137, Ser47, and Tyr110 from a neighboring subunit, are required to correctly position Tyr137 for its function, and this was confirmed by site-directed mutagenesis. This understanding of the mechanism and geometry of the transition states along the C

  15. Development of a 3D parallel mechanism robot arm with three vertical-axial pneumatic actuators combined with a stereo vision system.

    PubMed

    Chiang, Mao-Hsiung; Lin, Hao-Ting

    2011-01-01

    This study aimed to develop a novel 3D parallel mechanism robot driven by three vertical-axial pneumatic actuators with a stereo vision system for path tracking control. The mechanical system and the control system are the primary novel parts for developing a 3D parallel mechanism robot. In the mechanical system, a 3D parallel mechanism robot contains three serial chains, a fixed base, a movable platform and a pneumatic servo system. The parallel mechanism are designed and analyzed first for realizing a 3D motion in the X-Y-Z coordinate system of the robot's end-effector. The inverse kinematics and the forward kinematics of the parallel mechanism robot are investigated by using the Denavit-Hartenberg notation (D-H notation) coordinate system. The pneumatic actuators in the three vertical motion axes are modeled. In the control system, the Fourier series-based adaptive sliding-mode controller with H(∞) tracking performance is used to design the path tracking controllers of the three vertical servo pneumatic actuators for realizing 3D path tracking control of the end-effector. Three optical linear scales are used to measure the position of the three pneumatic actuators. The 3D position of the end-effector is then calculated from the measuring position of the three pneumatic actuators by means of the kinematics. However, the calculated 3D position of the end-effector cannot consider the manufacturing and assembly tolerance of the joints and the parallel mechanism so that errors between the actual position and the calculated 3D position of the end-effector exist. In order to improve this situation, sensor collaboration is developed in this paper. A stereo vision system is used to collaborate with the three position sensors of the pneumatic actuators. The stereo vision system combining two CCD serves to measure the actual 3D position of the end-effector and calibrate the error between the actual and the calculated 3D position of the end-effector. Furthermore, to

  16. Chemoprotective epigenetic mechanisms in a colorectal cancer model: Modulation by n-3 PUFA in combination with fermentable fiber

    PubMed Central

    Triff, Karen; Kim, Eunjoo; Chapkin, Robert S.

    2015-01-01

    Colorectal cancer is the third major cause of cancer-related mortality in both men and women worldwide. The beneficial role of n-3 polyunsaturated fatty acids (PUFA) in preventing colon cancer is substantiated by experimental, epidemiological, and clinical data. From a mechanistic perspective, n-3 PUFA are pleiotropic and multifaceted with respect to their molecular mechanisms of action. For example, this class of dietary lipid uniquely modulates membrane and nuclear receptors, sensors/ion channels, and membrane structure/cytoskeletal function, thereby regulating signaling processes that influence patterns of gene expression and cell phenotype. In addition, n-3 PUFA can synergize with other potential chemoprotective agents known to reprogram the chromatin landscape, such as the fermentable fiber product, butyrate. Nutri-epigenomics is an emerging field of research that is focused on the interaction between nutrition and epigenetics. Epigenetics refers to a group of heterogeneous processes that regulate transcription without changing the DNA coding sequence, ranging from DNA methylation, to histone tail modifications and transcription factor activity. One implication of the nutri-epigenome is that it may be possible to reprogram epigenetic marks that are associated with increased disease risk by nutritional or lifestyle interventions. This review will focus on the nutri-epigenomic role of n-3 PUFA, particularly DHA, as well as the combinatorial effects of n-3 PUFA and fermentable fiber in relation to colon cancer. PMID:25938013

  17. Enhancing specificity in the Janus kinases: a study on the thienopyridine JAK2 selective mechanism combined molecular dynamics simulation.

    PubMed

    Li, Jiao Jiao; Cheng, Peng; Tu, Jing; Zhai, Hong Lin; Zhang, Xiao Yun

    2016-02-01

    The selective inhibition for JAK2 over the other JAK family kinases (JAK1, JAK3 and TYK2) has shared an immense challenge due to high conservatism. In this paper, the highly JAK2 selective mechanism of the thienopyridine derivative was identified at the molecular level, based on insights into the inhibitory effects of compound on four JAK kinases by molecular docking, molecular dynamic simulations, free energy calculation and decomposition. The results clearly indicated that the nonpolar contribution and the H-bond network in the hinge region played a critical selective role in stabilizing ligand JAK2, and the residues Glu930, Leu932 and Gly935 in JAK2 kinase were the key differences compared to the equivalence residues of JAK1, JAK3 and TYK2, which were further verified by simulating four complexes of JAK kinases with another highly selective thienopyridine JAK2 inhibitor . Finally, several novel molecules were designed according to above findings and further verified by the same comprehensive modeling protocol. The obtained results not only demonstrated the rationality of our models and analyses, but also suggested that the designed molecules with higher JAK2 selectivity and bioactivity potential would provide an update of JAK2 inhibitors. PMID:26687880

  18. Unfolding the mechanism of the AAA+ unfoldase VAT by a combined cryo-EM, solution NMR study.

    PubMed

    Huang, Rui; Ripstein, Zev A; Augustyniak, Rafal; Lazniewski, Michal; Ginalski, Krzysztof; Kay, Lewis E; Rubinstein, John L

    2016-07-19

    The AAA+ (ATPases associated with a variety of cellular activities) enzymes play critical roles in a variety of homeostatic processes in all kingdoms of life. Valosin-containing protein-like ATPase of Thermoplasma acidophilum (VAT), the archaeal homolog of the ubiquitous AAA+ protein Cdc48/p97, functions in concert with the 20S proteasome by unfolding substrates and passing them on for degradation. Here, we present electron cryomicroscopy (cryo-EM) maps showing that VAT undergoes large conformational rearrangements during its ATP hydrolysis cycle that differ dramatically from the conformational states observed for Cdc48/p97. We validate key features of the model with biochemical and solution methyl-transverse relaxation optimized spectroscopY (TROSY) NMR experiments and suggest a mechanism for coupling the energy of nucleotide hydrolysis to substrate unfolding. These findings illustrate the unique complementarity between cryo-EM and solution NMR for studies of molecular machines, showing that the structural properties of VAT, as well as the population distributions of conformers, are similar in the frozen specimens used for cryo-EM and in the solution phase where NMR spectra are recorded. PMID:27402735

  19. Combined approach to damaged wire ropes life-time assessment based on NDT results and rope mechanics

    NASA Astrophysics Data System (ADS)

    Vorontsov, A.; Volokhovsky, V.; Slesarev, D.

    2011-07-01

    Principles of strength assessment and life-time prediction of deteriorated wire ropes based on magnetic NDT technique are presented. The measured loss of metallic cross-section area due to abrasion, corrosion etc. and local wire breaks are treated as input data for mechanical model of rope structure. The rope is interpreted as a system with two degrees of freedom that enables to calculate the strains and stresses in each wire when the rope is subjected to tension, torsion and bending. Stress safety factor is considered as a generalized parameter that specifies the rope degradation and may be used for predicting the instant lifetimes during the rope operating history. The rope discard criterion refers to residual life-time calculated with respect to minimal allowable strength factor. Examples of integrity analysis of mine hoisting rope and jib crane rope under tension-bending fatigue loading are demonstrated. The residual strength estimates give the rope inspector further information that helps to make a valid decision on testing policy.

  20. Mechanical and fracture behaviors of defective silicon nanowires: combined effects of vacancy clusters, temperature, wire size, and shape

    NASA Astrophysics Data System (ADS)

    Kuo, Jenn-Kun; Huang, Pei-Hsing; Wu, Wei-Te; Lu, Chi-Ming

    2014-03-01

    Abstract The coupled effects of vacancy clusters (VCs), temperature, wire size, and geometry on the mechanical and fracture behaviors of defective silicon nanowires (Si NWs) were investigated using molecular dynamics modeling with Tersoff potential. The formation energies ( E v ) of a monovacancy (3.933 eV) and a tetrahedron vacancy (10.189 eV) obtained in this study agree well with experimental results and ab initio calculation. Simulation results show that the slip deformations of defective Si NWs are triggered at the wire's surface and edge due to the number of dangling bonds on the wire's surface being much greater than that inside a vacancy defect. VC defects barely affect to the value of Young's modulus, but substantially weaken the ultimate strength of wires with a small cross-sectional size. With decreasing wire size and increasing operation temperature, significant reductions in Young's modulus and fracture strength were observed. The average Young's modulus for square NWs was about 3.7 % higher than that of wires with a circular shape due to the surface facet effect. A brittle-to-ductile transition (BDT) occurred for [001]-oriented Si NWs with a lateral size≤5.43 nm and an operation temperature T≥300 K.

  1. High-resolution structure of the nitrile reductase QueF combined with molecular simulations provide insight into enzyme mechanism.

    SciTech Connect

    Kim, Y.; Zhou, M.; Moy, S.; Morales, J.; Cunningham, M.; Joachimiak, A.; Biosciences Division; Univ. of Texas-Pan American

    2010-01-01

    Here, we report the 1.53-{angstrom} crystal structure of the enzyme 7-cyano-7-deazaguanine reductase (QueF) from Vibrio cholerae, which is responsible for the complete reduction of a nitrile (C {triple_bond} N) bond to a primary amine (H{sub 2}C-NH{sub 2}). At present, this is the only example of a biological pathway that includes reduction of a nitrile bond, establishing QueF as particularly noteworthy. The structure of the QueF monomer resembles two connected ferrodoxin-like domains that assemble into dimers. Ligands identified in the crystal structure suggest the likely binding conformation of the native substrates NADPH and 7-cyano-7-deazaguanine. We also report on a series of numerical simulations that have shed light on the mechanism by which this enzyme affects the transfer of four protons (and electrons) to the 7-cyano-7-deazaguanine substrate. In particular, the simulations suggest that the initial step of the catalytic process is the formation of a covalent adduct with the residue Cys194, in agreement with previous studies. The crystal structure also suggests that two conserved residues (His233 and Asp102) play an important role in the delivery of a fourth proton to the substrate.

  2. Kinetic analysis of acid orange 7 degradation by pulsed discharge plasma combined with activated carbon and the synergistic mechanism exploration.

    PubMed

    Guo, He; Wang, Huijuan; Wu, Qiangshun; Zhou, Guangshun; Yi, Chengwu

    2016-09-01

    The synergistic technique of pulsed discharge plasma (PDP) and activated carbon (AC) was built to investigate the kinetics of acid orange 7 (AO7) degradation under different conditions of AC addition, electrode gap, initial pH value of solution, gas variety and gas flow rate. Emission spectra of OH and O, UV-vis absorption spectra of the AO7 solution and TOC removal were measured to illustrate the synergistic mechanism of the PDP and the AC. The obtained results indicated that the kinetic constant of AO7 degradation increased from 0.00947 min(-1) to 0.01419 min(-1) when 4 g AC was added into the PDP system; AO7 degradation was higher in the case of alkaline solution when oxygen was used as the flow gas in the PDP/AC system, 2 L/min oxygen flow was more favorable for the degradation. Results of the relative emission intensities of OH and O indicated the catalytic effect of the AC on the active species formation as well as the important role of the two radicals for the AO7 degradation. There was no new peaks appeared by the UV-vis analysis of the AO7 solution after 60 min treatment. The highest TOC removal in the PDP/AC system was 30.3%, which was achieved under the condition of 4 L/min air flow rate and 3 initial pH value. PMID:27295438

  3. Combined effect of pulse electron beam treatment and thin hydroxyapatite film on mechanical features of biodegradable AZ31 magnesium alloy

    NASA Astrophysics Data System (ADS)

    Surmeneva, M. A.; Tyurin, A. I.; Teresov, A. D.; Koval, N. N.; Pirozhkova, T. S.; Shuvarin, I. A.; Surmenev, R. A.

    2015-11-01

    The morphology, elemental, phase composition, nanohardness, and Young's modulus of the hydroxyapatite (HA) coating deposited via radio frequency (RF) magnetron sputtering onto the AZ31 surface were investigated by atomic force microscopy (AFM), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD), and nanoindentationtechniques. The calcium phosphate (Ca/P) molar ratio of the HA coating deposited via RF-magnetron sputtering onto AZ31 substrates according to EDX was 1.57+0.03. The SEM experiments revealed significant differences in the morphology of the HA film deposited on untreated and treated with the pulsed electron beam (PEB) AZ31 substrate. Nanoindentation studies demonstrated significant differences in the mechanical responses of the HA film deposited on the initial and PEB-modified AZ31 substrates. The nanoindentation hardness and the Young's modulus of the HA film on the magnesium alloy modified using the PEB treatment were higher than that of the HA layer on the untreated substrate. Moreover, the HA film fabricated onto the PEB-treated surface was more resistant to plastic deformation than the same film on the untreated AZ31 surface.

  4. Combined electromagnetic and permanent magnet undulator to achieve higher field and easier field variation without mechanical movement

    SciTech Connect

    Bogachenkov, V.A.; Papadichev, V.A.

    1995-12-31

    Hybrid or pure permanent magnet undulators (PMU) are widely used because they have high field quality, allow easy field correction and do not consume power. Their main drawback is the necessity of moving one half of the magnet relative to the other to change field value, which requires a high precision, remotely controlled (and thus costly) driving system On the other hand, electromagnetic undulatory (EMU) have no problem with field variation, but consume too much power (100 - 400 kW) for high fields. Adding permanent magnets to EMU results in a considerable decrease of power consumption, while retaining the advantage of easily changing field level. A model of a CW combined EM+PM plane undulator having a 4.8 cm period and 8 periods long is described. It is simple in design and cheap in manufacturing: magnet yokes are made of soft steel rings in which 1.6 cm air gaps were cut to form pole faces. Odd yokes are placed to one side of the undulator axis and even yokes to the other with the air gaps on the axis. Each set of yokes is excited by its own separate winding of simple racetrack shape. Undulator deflection parameter K = 1.1 (B = 2.4 kG) can be reached at a 0.78kW power level, i.e., less than 100 W per period, while without PM only a maximum K = 0.8 can be obtained and requires 4 kW power. No water cooling is needed, which greatly simplifies undulator design. The undulator was not optimized relative to the axial-air-gap to ring-width ratio: one might expect some increase in field level for thinner rings. Field amplitude depends also on relative transverse position of odd and even pole faces.

  5. A Framework for Local Mechanical Characterization of Atherosclerotic Plaques: Combination of Ultrasound Displacement Imaging and Inverse Finite Element Analysis.

    PubMed

    Akyildiz, Ali C; Hansen, Hendrik H G; Nieuwstadt, Harm A; Speelman, Lambert; De Korte, Chris L; van der Steen, Antonius F W; Gijsen, Frank J H

    2016-04-01

    Biomechanical models have the potential to predict plaque rupture. For reliable models, correct material properties of plaque components are a prerequisite. This study presents a new technique, where high resolution ultrasound displacement imaging and inverse finite element (FE) modeling is combined, to estimate material properties of plaque components. Iliac arteries with plaques were excised from 6 atherosclerotic pigs and subjected to an inflation test with pressures ranging from 10 to 120 mmHg. The arteries were imaged with high frequency 40 MHz ultrasound. Deformation maps of the plaques were reconstructed by cross correlation of the ultrasound radiofrequency data. Subsequently, the arteries were perfusion fixed for histology and structural components were identified. The histological data were registered to the ultrasound data to construct FE model of the plaques. Material properties of the arterial wall and the intima of the atherosclerotic plaques were estimated using a grid search method. The computed displacement fields showed good agreement with the measured displacement fields, implying that the FE models were able to capture local inhomogeneities within the plaque. On average, nonlinear stiffening of both the wall and the intima was observed, and the wall of the atheroslcerotic porcine iliac arteries was markedly stiffer than the intima (877 ± 459 vs. 100 ± 68 kPa at 100 mmHg). The large spread in the data further illustrates the wide variation of the material properties. We demonstrated the feasibility of a mixed experimental-numerical framework to determine the material properties of arterial wall and intima of atherosclerotic plaques from intact arteries, and concluded that, due to the observed variation, plaque specific properties are required for accurate stress simulations. PMID:26399991

  6. Combining displacement field and grip force information to determine mechanical properties of planar tissue with complicated geometry.

    PubMed

    Nagel, Tina M; Hadi, Mohammad F; Claeson, Amy A; Nuckley, David J; Barocas, Victor H

    2014-11-01

    Performing planar biaxial testing and using nominal stress-strain curves for soft-tissue characterization is most suitable when (1) the test produces homogeneous strain fields, (2) fibers are aligned with the coordinate axes, and (3) strains are measured far from boundaries. Some tissue types [such as lamellae of the annulus fibrosus (AF)] may not allow for these conditions to be met due to their natural geometry and constitution. The objective of this work was to develop and test a method utilizing a surface displacement field, grip force-stretch data, and finite-element (FE) modeling to facilitate analysis of such complex samples. We evaluated the method by regressing a simple structural model to simulated and experimental data. Three different tissues with different characteristics were used: Superficial pectoralis major (SPM) (anisotropic, aligned with axes), facet capsular ligament (FCL) (anisotropic, aligned with axes, bone attached), and a lamella from the AF (anisotropic, aligned off-axis, bone attached). We found that the surface displacement field or the grip force-stretch data information alone is insufficient to determine a unique parameter set. Utilizing both data types provided tight confidence regions (CRs) of the regressed parameters and low parameter sensitivity to initial guess. This combined fitting approach provided robust characterization of tissues with varying fiber orientations and boundaries and is applicable to tissues that are poorly suited to standard biaxial testing. The structural model, a set of C++ finite-element routines, and a Matlab routine to do the fitting based on a set of force/displacement data is provided in the on-line supplementary material. PMID:25103887

  7. Communication: Slow supramolecular mode in amine and thiol derivatives of 2-ethyl-1-hexanol revealed by combined dielectric and shear-mechanical studies

    NASA Astrophysics Data System (ADS)

    Adrjanowicz, K.; Jakobsen, B.; Hecksher, T.; Kaminski, K.; Dulski, M.; Paluch, M.; Niss, K.

    2015-11-01

    In this paper, we present results of dielectric and shear-mechanical studies for amine (2-ethyl-1-hexylamine) and thiol (2-ethyl-1-hexanethiol) derivatives of the monohydroxy alcohol, 2-ethyl-1-hexanol. The amine and thiol can form hydrogen bonds weaker in strength than those of the alcohol. The combination of dielectric and shear-mechanical data enables us to reveal the presence of a relaxation mode slower than the α-relaxation. This mode is analogous to the Debye mode seen in monohydroxy alcohols and demonstrates that supramolecular structures are present for systems with lower hydrogen bonding strength. We report some key features accompanying the decrease in the strength of the hydrogen bonding interactions on the relaxation dynamics close to the glass-transition. This includes changes (i) in the amplitude of the Debye and α-relaxations and (ii) the separation between primary and secondary modes.

  8. Combination of hypoxia and RNA-interference targeting VEGF induces apoptosis in hepatoma cells via autocrine mechanisms.

    PubMed

    Raskopf, Esther; Vogt, Annabelle; Decker, Georges; Hirt, Sarah; Daskalow, Katjana; Cramer, Thorsten; Standop, Jens; Gonzalez-Carmona, Maria-Angeles; Sauerbruch, Tilman; Schmitz, Volker

    2012-09-01

    Control of VEGF signaling is an intense objective of pre-clinical and clinical studies in HCC disease with steadily increasing clinical application. Despite its emerging role, several aspects of anti-VEGF based treatments are poorly investigated, like the impact on tumor cells themselves, such as the effect on intracellular signaling and apoptosis induction in hepatoma cells. Effects of siRNA-VEGF on VEGF, VEGF-receptor expression and VEGF-A signaling such as AKT and JNK phosphorylation were determined under normoxic or hypoxic conditions in murine hepatoma cells. Apoptosis induction was analyzed by SubG1-fraction, JC1-staining and caspase-8 activation. VEGF receptor expression was analysed by semiquantitative real time PCR. Independent of oxygen status, siRNA-VEGF reduced VEGF levels resulting in decreased AKT and increased JNK phosphorylation in Hepa129 cells. The VEGF-receptors neuropilin-1 (Nrp1) and neuropilin-2 (Nrp2) were downregulated following siRNA-VEGF treatment or hypoxia induction respectively. Functionally, hypoxia significantly increased the apoptosis rate (as analyzed by SubG1-fraction, JC1-staining and JNKphosphorylation) which was further stimulated by siRNA-VEGF treatment. Our data indicate that antitumoral efficacy of an anti-VEGF based treatment with siRNA is partly based on negative autocrine feedback mechanisms which are even enhanced under hypoxic conditions. This observation helps to understand why antitumoral efficacy can be maintained despite of counteracting stimulation of tumoral VEGF secretion due to hypoxia. The direct impact on tumor cells further underscores the attractiveness of an anti-VEGF based siRNA treatment. PMID:21605070

  9. Combining biochemical with (1)H NMR-based metabolomics approach unravels the antidiabetic activity of genipin and its possible mechanism.

    PubMed

    Shen, Xiao-Li; Liu, Huan; Xiang, Huan; Qin, Xue-Mei; Du, Guan-Hua; Tian, Jun-Sheng

    2016-09-10

    Diabetes mellitus is a typical heterogeneous metabolic disorder characterized by abnormal metabolism of carbohydrates, lipids and proteins. Genipin possesses a wide spectrum of biological activities including ameliorating effects on diabetes, but the definite mechanism of this effect remains unknown. To investigate the antidiabetic activities of genipin and explore the biochemical changes of serum endogenous metabolites on diabetic rats induced by alloxan, (1)H NMR spectroscopy coupled with multivariate data analysis was used to. All rats were randomly divided into six groups including negative control (NC) group, diabetic mellitus (DM) group, metformin hydrochloride group, high dose group of genipin, middle dose group of genipin and low dose group of genipin. Diabetes was induced by a single intraperitoneal injection of 120mg/kg body weight of alloxan. Serum samples were collected for the (1)H NMR-based metabolomics and clinical biochemical analysis. Daily oral administration of genipin (25, 50 and 100mg/kg body weight) and metformin hydrochloride (125mg/kg) for two weeks showed beneficial effects on blood glucose level (P<0.01). Significant differences in the metabolic profile as well as the result of biochemical parameters between the diabetic group and the control group were observed. The PLS-DA scores and corresponding loading plots demonstrated that genipin significantly restored the abnormal metabolic state. Detailed analysis of the altered metabolite levels indicated that genipin significantly ameliorated the disturbance in glucose metabolism, tricarboxylic acid cycle, lipid metabolism and amino acid metabolism. Genipin showed the best anti-diabetic effects at a dose of 100mg/kg in rats. This finding indicates that chemical and metabolomic approaches could be powerful tools for the investigation of the biochemical changes in pathological conditions or drug treatment. PMID:27411170

  10. Investigating the complex mechanism of B migration in a magnetic-tunnel-junction trilayer structure—a combined study using XPS and TOF-SIMS

    NASA Astrophysics Data System (ADS)

    Ying, Ji-Feng; Ji, Rong; Ter Lim, Sze; Tran, Michael N.; Wang, Chen Chen; Ernult, Franck

    2016-02-01

    The magnetic-tunnel-junction (MTJ) structure is the core of many important devices, such as magnetic recording head and STT-RAM. CoFeB/MgO/CoFeB tri-layer thin-film stack is a widely researched MTJ structure. In this tri-layer, the functional property of the MTJ, i.e. its TMR ratio, is critically dependent on the crystal orientation of the CoFe grains. In order for the desired (1 0 0) out of plane texture to develop in the CoFeB layers, B needs to be engineered to be expelled out of these CoFeB layers, and diffuse or migrate into the adjacent layers. Ta is usually used as a seed layer adjacent to the MTJ structure. In this work, we investigated the important B-migration mechanisms within this MTJ structure through a combined XPS/TOF-SIMS study. Specifically, we tried to elucidate the possible physical/chemical interactions between the B and Ta that could happen with different film stack designs. Previous works have shown that there might be two possible B-migration mechanisms. One mechanism is direct B diffusion into the adjacent Ta layer during annealing. The other B-migration mechanism is through the formation of TaBOx species, in which B could be carried out by the Ta diffusion. In particular, through studying a series of film stacks, we discussed the circumstances under which one of these B-migration mechanisms becomes dominant. Furthermore, we discussed how these B-migration mechanisms facilitated the B expulsion in a common MTJ structure.

  11. Combined modification of intracellular and extracellular loci on human gonadotropin-releasing hormone receptor provides a mechanism for enhanced expression.

    PubMed

    Maya-Núñez, G; Janovick, J A; Conn, P M

    2000-12-01

    The mammalian gonadotropin-releasing hormone (GnRH) receptor (GnRH-R) has been a therapeutic target for human and animal medicine. This receptor is a unique G-protein-coupled receptor that lacks the intracellular C-terminal domain commonly associated with this family. Development of highthrough put screens for agents active in humans has been hampered by low expression levels of the hGnRH-R in cellular models. Two sites have attracted the interest of laboratories studying regulation of expression. The chimeric addition of the C-terminal tail from catfish GnRH-R (cfGnRH-R) to the rat GnRH-R significantly augmented receptor expression in GH3 cells. In addition, rodent GnRH-R contains 327 amino acids, but cow, sheep, and human GnRH-R (hGnRH-R) contain 328 residues, the "additional" residue being a Lys 191. Deletion of Lys 191 (del 191) from the hGnRH-R resulted in increased receptor expression levels and decreased internalization rates in both COS-7 and HEK 293 cells. In this study, the combined effect of the addition of the C-tail from cfGnRH-R and deletion of the Lys 191 from the hGnRH-R was compared to expression of the wild-type (WT) or either alteration alone in a transient expression system using primate cells. The altered receptor (hGnRH-R[del 191]-C-tail) showed significantly increased receptor expression at the cell surface compared with the WT or either modification alone. The inositol phosphate response to stimulation was also significantly elevated in response to GnRH agonist. After treatment with a GnRH agonist, the altered receptors showed a slower internalization rate. The homologous steady-state regulation of the WT and the altered receptors was similar, although the response of the altered receptors was significantly decreased. These results suggest that the conformational change in the receptor as a result of the deletion of Lys 191 and the addition of the C-terminus tail substantially increased the steady-state receptor expression and decreased

  12. An in vitro and in vivo study on the synergistic effect and mechanism of itraconazole or voriconazole alone and in combination with tetrandrine against Aspergillus fumigatus.

    PubMed

    Li, Shui-Xiu; Song, Yan-Jun; Zhang, Ling-Ling; Shi, Jian-Ping; Ma, Zheng-Lai; Guo, Hui; Dong, Hui-Yu; Li, Yi-Ming; Zhang, Hong

    2015-09-01

    In this study, we investigated the in vitro antifungal effects of itraconazole/voriconazole (ITR/VRC) alone and in combination with tetrandrine (TET) against 23 clinical isolates of A. fumigatus using a chequerboard microdilution method. The dynamic antifungal effects of TET with ITR/VRC against A. fumigatus were assessed in vivo using time-kill curves following systemic infection of mice with A. fumigatus. After treatment, efflux pump activity was determined by the efflux of rhodamine 6G (R6G). When ITR was combined with TET, ITR MICs were reduced from 0.125-32 to 0.0625-2 μg ml(-1), and TET MICs were reduced from 256-512 to 8-64 μg ml(-1). When VRC was combined with TET, VRC MICs were reduced from 0.125-2 to 0.03125-0.5 μg ml(-1), and TET MICs were reduced from 256-512 to 8-256 μg ml(-1). Time-kill curves revealed that A. fumigatus viability was reduced after treatment with ITR/VRC combined with TET versus ITR/VRC alone. ITR/VRC combined with TET significantly prolonged mouse survival and reduced kidney and brain tissue burdens versus ITR/VRC alone (P < 0.05). Moreover, TET inhibited R6G efflux of A. fumigatus. Thus, in vitro and in vivo, TET acted synergistically with ITR/VRC against A. fumigatus, and the synergistic mechanism was related to inhibition of the drug efflux pump. PMID:26296880

  13. Alpha-lipoic acid alone and combined with clozapine reverses schizophrenia-like symptoms induced by ketamine in mice: Participation of antioxidant, nitrergic and neurotrophic mechanisms.

    PubMed

    Vasconcelos, Germana Silva; Ximenes, Naiara Coelho; de Sousa, Caren Nádia Soares; Oliveira, Tatiana de Queiroz; Lima, Laio Ladislau Lopes; de Lucena, David Freitas; Gama, Clarissa Severino; Macêdo, Danielle; Vasconcelos, Silvânia Maria Mendes

    2015-07-01

    Oxidative stress has important implications in schizophrenia. Alpha-lipoic acid (ALA) is a natural antioxidant synthesized in human tissues with clinical uses. We studied the effect of ALA or clozapine (CLZ) alone or in combination in the reversal of schizophrenia-like alterations induced by ketamine (KET). Adult male mice received saline or KET for 14 days. From 8th to 14th days mice were additionally administered saline, ALA (100 mg/kg), CLZ 2.5 or 5 mg/kg or the combinations ALA+CLZ2.5 or ALA+CLZ5. Schizophrenia-like symptoms were evaluated by prepulse inhibition of the startle (PPI) and locomotor activity (positive-like), social preference (negative-like) and Y maze (cognitive-like). Oxidative alterations (reduced glutathione - GSH and lipid peroxidation - LP) and nitrite in the prefrontal cortex (PFC), hippocampus (HC) and striatum (ST) and BDNF in the PFC were also determined. KET caused deficits in PPI, working memory, social interaction and hyperlocomotion. Decreased levels of GSH, nitrite (HC) and BDNF and increased LP were also observed in KET-treated mice. ALA and CLZ alone reversed KET-induced behavioral alterations. These drugs also reversed the decreases in GSH (HC) and BDNF and increase in LP (PFC, HC and ST). The combination ALA+CLZ2.5 reversed behavioral and some neurochemical parameters. However, ALA+CLZ5 caused motor impairment. Therefore, ALA presented an antipsychotic-like profile reversing KET-induced positive- and negative-like symptoms. The mechanism partially involves antioxidant, neurotrophic and nitrergic pathways. The combination of ALA+CLZ2.5 improved most of the parameters evaluated in this study without causing motor impairment demonstrating, thus, that possibly when combined with ALA a lower dose of CLZ is required. PMID:25937462

  14. COMBINED THEORETICAL AND EXPERIMENTAL INVESTIGATION OF MECHANISMS AND KINETICS OF VAPOR-PHASE MERCURY UPTAKE BY CARBONACOUES SURFACES

    SciTech Connect

    Radisav D. Vidic

    2002-05-01

    The first part of this study evaluated the application of a versatile optical technique to study the adsorption and desorption of model adsorbates representative of volatile polar (acetone) and non-polar (propane) organic compounds on a model carbonaceous surface under ultra high vacuum (UHV) conditions. The results showed the strong correlation between optical differential reflectance (ODR) and adsorbate coverage determined by temperature programmed desorption (TPD). ODR technique was proved to be a powerful tool to investigate surface adsorption and desorption from UHV to high pressure conditions. The effects of chemical functionality and surface morphology on the adsorption/desorption behavior of acetone, propane and mercury were investigated for two model carbonaceous surfaces, namely air-cleaved highly oriented pyrolytic graphite (HOPG) and plasma-oxidized HOPG. They can be removed by thermal treatment (> 500 K). The presence of these groups almost completely suppresses propane adsorption at 90K and removal of these groups leads to dramatic increase in adsorption capacity. The amount of acetone adsorbed is independent of surface heat treatment and depends only on total exposure. The effects of morphological heterogeneity is evident for plasma-oxidized HOPG as this substrate provides greater surface area, as well as higher energy binding sites. Mercury adsorption at 100 K on HOPG surfaces with and without chemical functionalities and topological heterogeneity created by plasma oxidation occurs through physisorption. The removal of chemical functionalities from HOPG surface enhances mercury physisorption. Plasma oxidation of HOPG provides additional surface area for mercury adsorption. Mercury adsorption by activated carbon at atmospheric pressure occurs through two distinct mechanisms, physisorption below 348 K and chemisorption above 348 K. No significant impact of oxygen functionalities was observed in the chemisorption region. The key findings of this study

  15. Resolving the mechanism of bacterial inhibition by plant secondary metabolites employing a combination of whole-cell biosensors.

    PubMed

    Chan, Andrea C; Ager, Duane; Thompson, Ian P

    2013-06-01

    Tightening regulations regarding the use of biocides have stimulated interest in investigating alternatives to current antimicrobial strategies. Plant essential oils and their constituent compounds are promising candidates as novel antimicrobial agents because of their excellent ability in killing microbes while being non-toxic to humans at antimicrobially-active concentrations. Allyl isothiocyanate (AIT), carvacrol, cinnamaldehyde (CNAD), citral, and thymol were investigated for their antibacterial activity against Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. The five compounds were screened via disc diffusion assay and broth microdilution method, by which inhibition zone diameters, minimum inhibitory concentrations (MICs), and minimum bactericidal concentrations (MBCs) were determined. AIT and CNAD displayed the greatest inhibitory effects against all species tested, with AIT yielding MICs of 156.25mg/L and MBCs of 156.25 to 312.5mg/L, and CNAD yielding MICs of 78.125 to 156.25mg/L and MBCs of 78.125 to 312.5mg/L. Based on these results, AIT and CNAD were selected for closer examination of their toxic effects. Two complementary bioluminescence-based bacterial biosensors, E. coli HB101_pUCD607_lux and Acinetobacter baylyi ADP1_recA_lux, were employed to examine the dose-response relationships and mechanism of action of AIT and CNAD. This is the first reported study to employ a lux-based biosensor assay coupled with parallel plate count experiments to demonstrate that AIT and CNAD not only damaged cell membranes, but also disrupted cellular metabolism and energy production in bacteria. It is also the first to use genotoxicity-sensing whole-cell bioreporters to demonstrate that neither AIT nor CNAD induced expression of the universal DNA repair gene, recA. This suggests that AIT and CNAD were not genotoxic. As an antimicrobial agent, it is advantageous that the compound be genetically non-damaging so that toxicity towards

  16. Mechanical and chemical processes affecting the chalk during burial, insights from combined reflection seismics, well data and field work

    NASA Astrophysics Data System (ADS)

    Moreau, Julien; Boussaha, Myriam; Nielsen, Lars; Thibault, Nicolas; Stemmerik, Lars

    2014-05-01

    The chalk must undergo several phases of grain reorganisation and chemical reactions during its diagenetic evolution from a carbonaceous ooze to a sedimentary rock. Some of these transformations could be observed on structures from the kilometre- to the micrometre-scale with seismic reflection and cores analyses, respectively. However, few sites allow to combine all the different scale of observation for chalk diagenesis. Onshore and offshore high resolution seismics, two fully cored >350 m wells with wireline logging tools and very high quality exposures from a coastal cliff and a quarry form such an exceptional dataset in the Stevns peninsula area, eastern Danish Basin (Denmark). The studied chalk interval in the area is of Maastrichtian to Danian age. The chalk has been divided in 4 lithofacies, chalk-marl alternations, white chalk, white chalk with flint layers and bryozoan chalk. Advanced stratigraphic works have been performed with astronomical calibration based on stable isotope stratigraphy, wireline logs as well as several palaeontological proxies and detailed sedimentological analysis. Since a couple of decades, a specific kind of fractures has been described in the Chalk of Denmark, the so-called hairline fractures. They have recently been interpreted as compaction bands associated with the pore collapse of the chalk. We have observed these fractures on the field and on the cores in specific intervals. At depth, these fractures are in genetic relation with the formation of some stylolithes. The pressure-solution allows the formation of carbonate seams in the hairline fractures. At larger scale, on the field are observed faults which are sealed with flint precipitations. They slightly offset (<1 m) strata underlined by flint bands. On the onshore and offshore seismic reflection profiles, numerous strata-bound faults form noisy intervals as well as amplitude anomalies. Their normal offsets are less than 25 m. Their branching patterns, and their restriction

  17. Probability of pipe fracture in the primary coolant loop of a PWR plant. Volume 5. Probabilistic fracture mechanics analysis. Load Combination Program Project I final report

    SciTech Connect

    Harris, D.O.; Lim, E.Y.; Dedhia, D.D.

    1981-06-01

    The primary purpose of the Load Combination Program covered in this report is to estimate the probability of a seismic induced LOCA in the primary piping of a commercial pressurized water reactor (PWR). Best estimates, rather than upper bound results are desired. This was accomplished by use of a fracture mechanics model that employs a random distribution of initial cracks in the piping welds. Estimates of the probability of cracks of various sizes initially existing in the welds are combined with fracture mechanics calculations of how these cracks would grow during service. This then leads to direct estimates of the probability of failure as a function of time and location within the piping system. The influence of varying the stress history to which the piping is subjected is easily determined. Seismic events enter into the analysis through the stresses they impose on the pipes. Hence, the influence of various seismic events on the piping failure probability can be determined, thereby providing the desired information.

  18. Study of the mechanism of acetonitrile stacking and its application for directly combining liquid-phase microextraction with micellar electrokinetic chromatography.

    PubMed

    Sun, Jingru; Feng, Jing; Shi, Ludi; Liu, Laping; He, Hui; Fan, Yingying; Hu, Shibin; Liu, Shuhui

    2016-08-26

    Acetonitrile stacking is an online concentration method that is distinctive due to its inclusion of a high proportion of organic solvent in sample matrices. We previously designed a universal methodology for the combination of liquid-phase microextraction (LPME) and capillary electrophoresis (CE) using acetonitrile stacking and micellar electrokinetic chromatography (MEKC) mode, thereby achieving large-volume injection of the diluted LPME extractant and the online concentration. In this report, the methodology was extended to the analysis of highly substituted hydrophobic chlorophenols in wines using diethyl carbonate as the extractant. Additionally, the mechanism of acetonitrile stacking was studied. The results indicated that the combination of LPME and MEKC exhibited good analytical performance: with ∼40-fold concentration by LPME, a 20-cm (33% of the total length) sample plug injection of an eight-fold dilution of diethyl carbonate with the organic solvent-saline solution produced enrichments higher by a factor of 260-791. Limits of qualification ranged from 5.5 to 16.0ng/mL. Acceptable reproducibilities of lower than 1.8% for migration time and 8.6% for peak areas were obtained. A dual stacking mechanism of acetonitrile stacking was revealed, involving transient isotachophoresis plus pH-junction stacking. The latter was associated with a pH shift induced by the presence of acetonitrile. The pseudo-stationary phase (Brij-35) played an important role in reducing the CE running time by weakening the isotachophoretic migration of the analyte ions following Cl(-) ions. The combination of acetonitrile stacking and nonionic micelle-based MEKC appears to be a perfect match for introducing water-immiscible LPME extractants into an aqueous CE system and can thus significantly expand the application of LPME-CE in green analytical chemistry. PMID:27451260

  19. Mechanisms of large Stokes shift and aggregation-enhanced emission of osmapentalyne cations in solution: combined MD simulations and QM/MM calculations.

    PubMed

    Sun, Guang-Xu; Ju, Ming-Gang; Zang, Hang; Zhao, Yi; Liang, WanZhen

    2015-10-01

    Osmapentalyne cations synthesized recently show remarkable optical properties, such as near-infrared emission, unusual large Stokes shift and aggregation-enhanced emission. Here, the mechanisms behind those novel optical behaviors are revealed from the combined molecular dynamics simulations and hybrid quantum mechanics/molecular mechanics calculations. The results demonstrate that the large Stokes shift in the gas phase comes from a photoexcitation-induced deformation of the osmium plane, whereas in solution it corresponds to the variation of osmium ring symmetry. Although the central chromophore ring dominates the absorption and emission processes, the protecting groups PPh3 join the emission. As osmapentalyne cations are aggregated together in solution, the radical distribution functions of their mass-central distances display several peaks immersed in a broad envelope due to different aggregation pathways. However, the chromophore centers are protected by the PPh3 groups, the aggregation structures do not affect the Stokes shift too much, and the calculated aggregate-enhanced emission is consistent with experimental measurements. PMID:26339695

  20. Interionic hydration structures of NaCl in aqueous solution: a combined study of quantum mechanical cluster calculations and QM/EFP-MD simulations.

    PubMed

    Ghosh, Manik K; Re, Suyong; Feig, Michael; Sugita, Yuji; Choi, Cheol Ho

    2013-01-10

    The association process of NaCl in aqueous solution was studied by a combination of quantum mechanical calculations on NaCl(H(2)O)(n) (n = 1-6) clusters and quantum mechanical/effective fragment potential-molecular dynamics (QM/EFP-MD) simulations for NaCl in 292 EFP waters. The interionic hydration structures (IHSs) were topologically classified as "ring" (R), "half-bridge" (H), and "full-bridge" (F) types on the basis of the quantum mechanical calculations. Subsequent IHS analysis on QM/EFP-MD simulations revealed that the NaCl contact ion pair (CIP) mainly involved R type hydration structures while the solvent-separated ion pair (SSIP) was composed of two different groups of F-type hydration structures. Our IHS analysis also discovered H type hydration even at large separation interionic distances (∼7 Å), which is denoted as a dissociating ion pair (DIP). The analysis was able to reveal the most complete interionic structures and their reorganizations of the association process. A strong correlation between the IHSs and interionic distance suggests that not only the solvent reorganization but also the local IHS changes are equally important. Mechanistically, it is suggested that the conversion between ring-type and full-bridge hydration structures is the main rate-determining step of ion-pair association. PMID:23231378

  1. Combinations Therapies.

    PubMed

    Reinmuth, Niels; Reck, Martin

    2015-01-01

    Immunotherapy of cancer encompasses different strategies that elicit or enhance the immune response against tumors. The first results from clinical studies have provided promising data for the treatment of lung cancer patients with immunomodulating monotherapies. To improve the potential benefit of cancer immunotherapy, synergistic combinations of the various immunotherapy approaches or of different elements within each of the immunotherapy approaches are being explored. The rationale typically involves different but complementary mechanisms of action, eventually impinging on more than one immune system mechanism. As a prominent example, the simultaneous blockade of PD-1 and CTLA-4 is giving rise to therapeutic synergy, while still offering room for efficacy improvement. Moreover, combinations of immunomodulating agents with chemotherapy or targeted molecules are being tested. Animal models suggest that immunotherapies in combination with these various options offer evidence for synergistic effects and are likely to radically change cancer treatment paradigms. However, data obtained so far indicate that toxic side effects are also potentiated, which may even restrict the selection of patients that are suitable for these combinational approaches. Advancing the field of combinatorial immunotherapy will require changes in the way investigational agents are clinically developed as well as novel experimental end-points for efficacy evaluation. However, this combined therapeutic manipulation of both tumor and stromal cells may lead to a dramatic change in the therapeutic options of lung cancer patients in any disease stage that can only grossly be appreciated by the current studies. PMID:26384009

  2. Mechanisms that Trigger a Good Health-Care Response to Intimate Partner Violence in Spain. Combining Realist Evaluation and Qualitative Comparative Analysis Approaches

    PubMed Central

    Goicolea, Isabel; Vives-Cases, Carmen; Hurtig, Anna-Karin; Marchal, Bruno; Briones-Vozmediano, Erica; Otero-García, Laura; García-Quinto, Marta; San Sebastian, Miguel

    2015-01-01

    Background Health care professionals, especially those working in primary health-care services, can play a key role in preventing and responding to intimate partner violence. However, there are huge variations in the way health care professionals and primary health care teams respond to intimate partner violence. In this study we tested a previously developed programme theory on 15 primary health care center teams located in four different Spanish regions: Murcia, C Valenciana, Castilla-León and Cantabria. The aim was to identify the key combinations of contextual factors and mechanisms that trigger a good primary health care center team response to intimate partner violence. Methods A multiple case-study design was used. Qualitative and quantitative information was collected from each of the 15 centers (cases). In order to handle the large amount of information without losing familiarity with each case, qualitative comparative analysis was undertaken. Conditions (context and mechanisms) and outcomes, were identified and assessed for each of the 15 cases, and solution formulae were calculated using qualitative comparative analysis software. Results The emerging programme theory highlighted the importance of the combination of each team’s self-efficacy, perceived preparation and women-centredness in generating a good team response to intimate partner violence. The use of the protocol and accumulated experience in primary health care were the most relevant contextual/intervention conditions to trigger a good response. However in order to achieve this, they must be combined with other conditions, such as an enabling team climate, having a champion social worker and having staff with training in intimate partner violence. Conclusions Interventions to improve primary health care teams’ response to intimate partner violence should focus on strengthening team’s self-efficacy, perceived preparation and the implementation of a woman-centred approach. The use of the

  3. Combined effects of moisture, temperature, fiber architecture, and sustained load on the mechanical and microstructural properties of notched and unnotched e-glass/vinyl ester composite materials

    NASA Astrophysics Data System (ADS)

    Buck, Stephanie E.

    Structural composite materials are being investigated for use in applications which will require long-term durability in the presence of various environments and external loading conditions. Flaws may be created in these composite materials during manufacturing, machining, or use. Adverse use conditions may result in significantly reduced mechanical properties and changes in the microstructural properties and damage mechanisms of composites with seemingly minor flaws. E-glass/vinyl ester composite coupons, some with a preexisting flaw, have been conditioned in a wet environment for periods of up to nearly 8000 hours at several temperatures, mostly with a sustained tensile load, to determine the changes in the mechanical properties and damage mechanisms which occur with the introduction of a flaw. The fiber architectures used for the unnotched coupons were [0/90/+/-45]2s, [0/90/+/-45]3s, and [90/0]2s, all containing a chopped strand mat in each set, while those used for the notched coupons were [90/0]2s, [0] 16, [0/90]8, and [0/90]f8, with only the first containing the random mat. The combination of moisture and temperature was found to degrade the mechanical properties of the unnotched materials, particularly the tensile strength. The addition of a sustained load was found to further degrade these properties. During conditioning, the damage mechanisms were found to change from matrix microcracking, fiber damage, and occasional edge delaminations for unnotched specimens to the growth of a significant transverse crack from the notch tip and longitudinal tow debonding for notched specimens. Moisture and elevated temperature were found to affect the extent of damage, but not the dual nature of damage, in the vicinity of the notch tip, while the fiber architecture affected some of the patterns of damage. The unidirectional samples, not loaded during conditioning, were tested in load cycles to determine the strain energy release rates for increments of growth of

  4. Formation of a nanodispersed metal-matrix structure during a combined high-energy mechanical alloying of powders of aluminum-based SiC-containing alloys

    NASA Astrophysics Data System (ADS)

    Popov, V. A.; Cherdyntsev, V. V.

    2009-01-01

    Phase and structural state of composite materials produced by combined mechanical alloying of the AK12M2 and D16 powder alloys with silicon carbide in high-energy planetary mills with the use of ball charging and quasi-cylindrical bodies have been studied. It has been found out that the type of bodies substantially affects the mutual solubility of components in the systems investigated, as well as the perfection of the crystal lattice of the material treated, and its adhesion to the bodies and to the inner surface of the drum. It is shown that the use of balls favors an enhanced mutual solubility of the components and stipulates higher deformation of the crystal lattice of the product in comparison with the quasi-cylinder grinding bodies. The differences observed are discussed based on the calculated data obtained earlier for the ratio of normal and tangential components of energy consumption for different types of grinding bodies.

  5. Atomic-scale and pit-free flattening of GaN by combination of plasma pretreatment and time-controlled chemical mechanical polishing

    SciTech Connect

    Deng, Hui; Endo, Katsuyoshi; Yamamura, Kazuya

    2015-08-03

    Chemical mechanical polishing (CMP) combined with atmospheric-pressure plasma pretreatment was applied to a GaN (0001) substrate. The irradiation of a CF{sub 4}-containing plasma was proven to be very useful for modifying the surface of GaN. When CMP was conducted on a plasma-irradiated surface, a modified layer of GaF{sub 3} acted as a protective layer on GaN by preventing the formation of etch pits. Within a short duration (8 min) of CMP using a commercially available CeO{sub 2} slurry, an atomically flat surface with a root mean square (rms) roughness of 0.11 nm was obtained. Moreover, etch pits, which are inevitably introduced in conventional CMP, could not be observed at the dislocation sites on the polished GaN surface. It was revealed that CMP combined with the plasma pretreatment was very effective for obtaining a pit-free and atomically flat GaN surface.

  6. Combined Pharmacomechanical Thrombolysis of Complete Portomesenteric Thrombosis in a Liver Transplant Recipient

    SciTech Connect

    Lorenz, Jonathan M. Bennett, Shelby; Patel, Jay; Ha, Thuong G. Van; Funaki, Brian

    2013-01-30

    Treatment options for portomesenteric venous thrombosis range from anticoagulation to surgery, depending on chronicity, severity of symptoms, extent of thrombosis, and the availability of local expertise. For acute and subacute cases, a variety of endovascular options have been described in limited published series and case reports, including thrombolysis and mechanical thrombectomy. We report what is to our knowledge the first case in which the Trellis pharmacomechanical thrombolysis device was used successfully to treat complete acute thrombosis of the entire superior mesenteric vein and the entire portal vein with extension into all segmental intrahepatic portal branches in a young adult after liver transplantation. This device, coupled with adjunctive techniques using balloon catheters, facilitated complete restoration of flow, resulting in graft salvage and long-term patency.

  7. Reduction in adipose tissue volume using a new high-power radiofrequency technology combined with infrared light and mechanical manipulation for body contouring.

    PubMed

    Adatto, Maurice A; Adatto-Neilson, Robyn M; Morren, Grietje

    2014-09-01

    them were satisfied with the results at the follow-up visit. The application of high-power RF energy combined with infrared (IR), mechanical massage, and vacuum appears to be an effective modality for the reduction in circumferences of the abdomen/flank, buttock and thigh regions, and the improvement of skin appearance. The present study performed with a new device suggests that the underlying mechanism of action is reduction in the subcutaneous adipose tissue volume and intensification of dermal matrix density. PMID:24687404

  8. Elucidating the degradation mechanism of the cathode catalyst of PEFCs by a combination of electrochemical methods and X-ray fluorescence spectroscopy.

    PubMed

    Monzó, J; van der Vliet, D F; Yanson, A; Rodriguez, P

    2016-08-10

    In this study, we report a methodology which enables the determination of the degradation mechanisms responsible for catalyst deterioration under different accelerated stress protocols (ASPs) by combining measurements of the electrochemical surface area (ECSA) and Pt content (by X-ray fluorescence). The validation of this method was assessed on high surface area unsupported Pt nanoparticles (Pt-NPs), Pt nanoparticles supported on TaC (Pt/TaC) and Pt nanoparticles supported on Vulcan carbon (Pt/Vulcan). In the load cycle protocol, the degradation of Pt-NPs and Pt/Vulcan follows associative processes (e.g. agglomeration) in the first 2000 cycles, however, in successive cycles the degradation goes through dissociative processes such as Pt dissolution, as is evident from a similar decay of ECSA and Pt content. In contrast, the degradation mechanism for Pt nanoparticles dispersed on TaC occurs continuously through the dissociative processes (e.g. Pt dissolution or particle detachment), with similar decay rates of both Pt content and ECSA. In the start-up/shut-down protocol, high surface area Pt-NPs follow associative processes (e.g. Ostwald ripening) in the first 4000 cycles, after which the degradation continues through dissociative processes. On the other hand, dissociative mechanisms always govern the degradation of Pt/TaC under start-up/shut-down protocol conditions. Finally, we report that Pt nanoparticles supported on TaC exhibit the highest catalytic activity and long term durability of the three nanoparticle systems tested. This makes Pt/TaC a potentially valuable catalyst system for application in polymer electrolyte fuel cell cathodes. PMID:27464340

  9. Stepwise Catalytic Mechanism via Short-Lived Intermediate Inferred from Combined QM/MM MERP and PES Calculations on Retaining Glycosyltransferase ppGalNAcT2

    PubMed Central

    Trnka, Tomáš; Kozmon, Stanislav; Tvaroška, Igor; Koča, Jaroslav

    2015-01-01

    The glycosylation of cell surface proteins plays a crucial role in a multitude of biological processes, such as cell adhesion and recognition. To understand the process of protein glycosylation, the reaction mechanisms of the participating enzymes need to be known. However, the reaction mechanism of retaining glycosyltransferases has not yet been sufficiently explained. Here we investigated the catalytic mechanism of human isoform 2 of the retaining glycosyltransferase polypeptide UDP-GalNAc transferase by coupling two different QM/MM-based approaches, namely a potential energy surface scan in two distance difference dimensions and a minimum energy reaction path optimisation using the Nudged Elastic Band method. Potential energy scan studies often suffer from inadequate sampling of reactive processes due to a predefined scan coordinate system. At the same time, path optimisation methods enable the sampling of a virtually unlimited number of dimensions, but their results cannot be unambiguously interpreted without knowledge of the potential energy surface. By combining these methods, we have been able to eliminate the most significant sources of potential errors inherent to each of these approaches. The structural model is based on the crystal structure of human isoform 2. In the QM/MM method, the QM region consists of 275 atoms, the remaining 5776 atoms were in the MM region. We found that ppGalNAcT2 catalyzes a same-face nucleophilic substitution with internal return (SNi). The optimized transition state for the reaction is 13.8 kcal/mol higher in energy than the reactant while the energy of the product complex is 6.7 kcal/mol lower. During the process of nucleophilic attack, a proton is synchronously transferred to the leaving phosphate. The presence of a short-lived metastable oxocarbenium intermediate is likely, as indicated by the reaction energy profiles obtained using high-level density functionals. PMID:25849117

  10. Development of Combined Dry Heat and Chlorine Dioxide Gas Treatment with Mechanical Mixing for Inactivation of Salmonella enterica Serovar Montevideo on Mung Bean Seeds.

    PubMed

    Annous, Bassam A; Burke, Angela

    2015-05-01

    Foodborne outbreaks have been associated with the consumption of fresh sprouted beans. The sprouting conditions of mung bean seeds provide optimal conditions of temperature and relative humidity for any potential pathogenic contaminant on the seeds to grow. The lack of a kill step postsprouting is a major safety concern. Thus, the use of a kill step on the seeds prior to a sprouting step would enhance the safety of fresh sprouts. The objective of this work was to evaluate the effectiveness of the combined thermal and chlorine dioxide gas (3.5 mg/liter of air) treatment with mechanical mixing (tumbling) to eliminate Salmonella on artificially inoculated mung bean seeds. Although no viable Salmonella was recovered from seeds treated in hot water at 60°C for 2 h, these treated seeds failed to germinate. Dry heat treatments (55, 60, or 70°C) for up to 8 h reduced Salmonella populations in excess of 3 log CFU/g. The use of tumbling, while treating the seeds, resulted in up to 1.6 log CFU/g reduction in Salmonella populations compared with no tumbling. Dry heat treatment at 65°C for 18 h with tumbling resulted in a complete inactivation of Salmonella populations on inoculated seeds with low inoculum levels (2.83 log CFU/g) as compared with high inoculum levels (4.75 log CFU/g). The increased reductions in pathogenic populations on the seeds with the use of tumbling could be attributed to increased uniformity of heat transfer and exposure to chlorine dioxide gas. All treated seeds were capable of germinating, as well as the nontreated controls. These results suggest that this combined treatment would be a viable process for enhancing the safety of fresh sprouts. PMID:25951379

  11. Alterations in glucocorticoid negative feedback following maternal Pb, prenatal stress and the combination: A potential biological unifying mechanism for their corresponding disease profiles

    SciTech Connect

    Rossi-George, A.; Virgolini, M.B.; Weston, D.; Cory-Slechta, D.A.

    2009-01-01

    Combined exposures to maternal lead (Pb) and prenatal stress (PS) can act synergistically to enhance behavioral and neurochemical toxicity in offspring. Maternal Pb itself causes permanent dysfunction of the body's major stress system, the hypothalamic pituitary adrenal (HPA) axis. The current study sought to determine the potential involvement of altered negative glucocorticoid feedback as a mechanistic basis of the effects in rats of maternal Pb (0, 50 or 150 ppm in drinking water beginning 2 mo prior to breeding), prenatal stress (PS; restraint on gestational days 16-17) and combined maternal Pb + PS in 8 mo old male and female offspring. Corticosterone changes were measured over 24 h following an i.p. injection stress containing vehicle or 100 or 300 {mu}g/kg (females) or 100 or 150 {mu}g/kg (males) dexamethasone (DEX). Both Pb and PS prolonged the time course of corticosterone reduction following vehicle injection stress. Pb effects were non-monotonic, with a greater impact at 50 vs. 150 ppm, particularly in males, where further enhancement occurred with PS. In accord with these findings, the efficacy of DEX in suppressing corticosterone was reduced by Pb and Pb + PS in both genders, with Pb efficacy enhanced by PS in females, over the first 6 h post-administration. A marked prolongation of DEX effects was found in males. Thus, Pb, PS and Pb + PS, sometimes additively, produced hypercortisolism in both genders, followed by hypocortisolism in males, consistent with HPA axis dysfunction. These findings may provide a plausible unifying biological mechanism for the reported links between Pb exposure and stress-associated diseases and disorders mediated via the HPA axis, including obesity, hypertension, diabetes, anxiety, schizophrenia and depression. They also suggest broadening of Pb screening programs to pregnant women in high stress environments.

  12. Early Detection of Left Atrial Energy Loss and Mechanics Abnormalities in Diabetic Patients with Normal Left Atrial Size: A Study Combining Vector Flow Mapping and Tissue Tracking Echocardiography

    PubMed Central

    Wang, Yi; Hou, Dailun; Ma, Rongchuan; Ding, Geqi; Yin, Lixue; Zhang, Mei

    2016-01-01

    Background Whether left atrial (LA) functional abnormalities already exist when the LA is of normal size is unknown. The aim of this study was to explore LA energy loss and mechanics changes using vector flow mapping (VFM) and two-dimensional tissue tracking (2DTT) echocardiography in patients with diabetes and normal LA size. Material/Methods This study included 47 normotensive patients with diabetes and 45 controls. The following indexes were measured: LA energy loss during systole (LAELs), early diastole (LAELed), and atrial contraction (LAELac); atrial longitudinal strain during systole (SLAs), early diastole (SLAed) and late diastole (SLAac); and peak LA strain rate during systole (SRLAs), early diastole (SRLAed), and atrial contraction (SRLAac). Results The LAELs and LAELed decreased in diabetic patients compared with controls (P=0.002, P<0.01, respectively), whereas the LAELac increased in diabetic patients (P<0.001). The SLAs, SLAed, SRLAs, and SRLAed (all P<0.01) were all lower in diabetic patients than in controls. However, there was no difference in the SLAac and SRLAac between the two groups. Multivariate regression analysis showed that the LAELs, LAELac, and SRLAs were independently associated with HbA1c in the whole study population. Conclusions LA energy loss and deformation mechanics are already impaired in diabetic patients with normal LA size and the long-term parameter of glycemic control was correlated with them. VFM combined with 2DTT might be a promising tool for the early detection of LA dysfunction caused by impaired glucose metabolism. PMID:27005947

  13. Insights into the mechanisms underlying mercury-induced oxidative stress in gills of wild fish (Liza aurata) combining (1)H NMR metabolomics and conventional biochemical assays.

    PubMed

    Cappello, Tiziana; Brandão, Fátima; Guilherme, Sofia; Santos, Maria Ana; Maisano, Maria; Mauceri, Angela; Canário, João; Pacheco, Mário; Pereira, Patrícia

    2016-04-01

    Oxidative stress has been described as a key pathway to initiate mercury (Hg) toxicity in fish. However, the mechanisms underlying Hg-induced oxidative stress in fish still need to be clarified. To this aim, environmental metabolomics in combination with a battery of conventional oxidative stress biomarkers were applied to the gills of golden grey mullet (Liza aurata) collected from Largo do Laranjo (LAR), a confined Hg contaminated area, and São Jacinto (SJ), selected as reference site (Aveiro Lagoon, Portugal). Higher accumulation of inorganic Hg and methylmercury was found in gills of fish from LAR relative to SJ. Nuclear magnetic resonance (NMR)-based metabolomics revealed changes in metabolites related to antioxidant protection, namely depletion of reduced glutathione (GSH) and its constituent amino acids, glutamate and glycine. The interference of Hg with the antioxidant protection of gills was corroborated through oxidative stress endpoints, namely the depletion of glutathione peroxidase and superoxide dismutase activities at LAR. The increase of total glutathione content (reduced glutathione+oxidized glutathione) at LAR, in parallel with GSH depletion aforementioned, indicates the occurrence of massive GSH oxidation under Hg stress, and an inability to carry out its regeneration (glutathione reductase activity was unaltered) or de novo synthesis. Nevertheless, the results suggest the occurrence of alternative mechanisms for preventing lipid peroxidative damage, which may be associated with the enhancement of membrane stabilization/repair processes resulting from depletion in the precursors of phosphatidylcholine (phosphocholine and glycerophosphocholine), as highlighted by NMR spectroscopy. However, the observed decrease in taurine may be attributable to alterations in the structure of cell membranes or interference in osmoregulatory processes. Overall, the novel concurrent use of metabolomics and conventional oxidative stress endpoints demonstrated to be

  14. Microstructure and mechanical properties of BFe10 cupronickel alloy tubes fabricated by a horizontal continuous casting with heating-cooling combined mold technology

    NASA Astrophysics Data System (ADS)

    Mei, Jun; Liu, Xin-hua; Xie, Jian-xin

    2012-04-01

    A new horizontal continuous casting method with heating-cooling combined mold (HCCM) technology was explored for fabricating high-quality thin-wall cupronickel alloy tubes used for heat exchange pipes. The microstructure and mechanical properties of BFe10 cupronickel alloy tubes fabricated by HCCM and traditional continuous casting (cooling mold casting) were comparatively investigated. The results show that the tube fabricated by HCCM has smooth internal and external surfaces without any defects, and its internal and external surface roughnesses are 0.64 μm and 0.85 μm, respectively. The tube could be used for subsequent cold processing without other treatments such as surface planning, milling and acid-washing. This indicates that HCCM can effectively reduce the process flow and improve the production efficiency of a BFe10 cupronickel alloy tube. The tube has columnar grains along its axial direction with a major casting texture of left\\{ {012} right\\}left< {6bar 21} rightrangle. Compared with cooling mold casting ( δ = 36.5%), HCCM can improve elongation ( δ = 46.3%) by 10% with a slight loss of strength, which indicates that HCCM remarkably improves the cold extension performance of a BFe10 cupronickel alloy tube.

  15. Toward the complete utilization of rice straw: Methane fermentation and lignin recovery by a combinational process involving mechanical milling, supporting material and nanofiltration.

    PubMed

    Sasaki, Kengo; Okamoto, Mami; Shirai, Tomokazu; Tsuge, Yota; Fujino, Ayami; Sasaki, Daisuke; Morita, Masahiko; Matsuda, Fumio; Kikuchi, Jun; Kondo, Akihiko

    2016-09-01

    Rice straw was mechanically milled using a process consuming 1.9MJ/kg-biomass, and 10g/L of unmilled or milled rice straw was used as the carbon source for methane fermentation in a digester containing carbon fiber textile as the supporting material. Milling increased methane production from 226 to 419mL/L/day at an organic loading rate of 2180mg-dichromate chemical oxygen demand/L/day, corresponding to 260mLCH4/gVS. Storage of the fermentation effluent at room temperature decreased the weight of the milled rice straw residue from 3.81 to 1.00g/L. The supernatant of the effluent was subjected to nanofiltration. The black concentrates deposited on the nanofiltration membranes contained 53.0-57.9% lignin. Solution nuclear magnetic resonance showed that lignin aromatic components such as p-hydroxyphenyl (H), guaiacyl (G), and syringyl (S) were retained primarily, and major lignin interunit structures such as the β-O-4-H/G unit were absent. This combinational process will aid the complete utilization of rice straw. PMID:27318161

  16. Mechanical Properties of Thermoelectric Ba8Al15Si31 Clathrate Prepared by Combining Arc Melting and Spark Plasma Sintering Techniques

    NASA Astrophysics Data System (ADS)

    Anno, Hiroaki; Ueda, Takahiro; Hirata, Shusaku; Kameyama, Tomoki; Iida, Tsutomu; Kogo, Yasuo

    2016-03-01

    The mechanical properties (the elastic moduli, hardness, and fracture toughness) were investigated for polycrystalline Ba8Al15Si31 clathrate as one of useful thermoelectric materials on a phonon glass and electron crystal concept. Samples were prepared by combining arc melting and spark plasma sintering techniques. The Young's modulus E = 96.88 GPa, shear modulus G = 38.61 GPa, bulk modulus K = 65.77 GPa, and Poisson's ratio ν = 0.2545 were calculated from longitudinal sound velocity v L = 6105 m/s and transverse sound velocity v T = 3503 m/s, measured by an ultrasonic test. The elastic constants c 11 = 78.64 GPa, c 12 = 40.03 GPa, and c 44 = 38.61 GPa were calculated from E and G. The Vickers hardness HV and Young's modulus E were simultaneously determined to be 634 and 109.7 GPa, respectively, by a nanoindentation test. The fracture toughness K IC was determined to be 1.1 MPa m1/2, which was comparable to typical values 1.1-1.2 MPa m1/2 for thermoelectric silicide Mg2Si, by a Vickers indentation fracture test.

  17. Understanding the adsorption of CuPc and ZnPc on noble metal surfaces by combining quantum-mechanical modelling and photoelectron spectroscopy.

    PubMed

    Huang, Yu Li; Wruss, Elisabeth; Egger, David A; Kera, Satoshi; Ueno, Nobuo; Saidi, Wissam A; Bucko, Tomas; Wee, Andrew T S; Zojer, Egbert

    2014-01-01

    Phthalocyanines are an important class of organic semiconductors and, thus, their interfaces with metals are both of fundamental and practical relevance. In the present contribution we provide a combined theoretical and experimental study, in which we show that state-of-the-art quantum-mechanical simulations are nowadays capable of treating most properties of such interfaces in a quantitatively reliable manner. This is shown for Cu-phthalocyanine (CuPc) and Zn-phthalocyanine (ZnPc) on Au(111) and Ag(111) surfaces. Using a recently developed approach for efficiently treating van der Waals (vdW) interactions at metal/organic interfaces, we calculate adsorption geometries in excellent agreement with experiments. With these geometries available, we are then able to accurately describe the interfacial electronic structure arising from molecular adsorption. We find that bonding is dominated by vdW forces for all studied interfaces. Concomitantly, charge rearrangements on Au(111) are exclusively due to Pauli pushback. On Ag(111), we additionally observe charge transfer from the metal to one of the spin-channels associated with the lowest unoccupied π-states of the molecules. Comparing the interfacial density of states with our ultraviolet photoelectron spectroscopy (UPS) experiments, we find that the use of a hybrid functionals is necessary to obtain the correct order of the electronic states. PMID:24609018

  18. PD-L1 (B7-H1) and PD-1 pathway blockade for cancer therapy: Mechanisms, response biomarkers, and combinations.

    PubMed

    Zou, Weiping; Wolchok, Jedd D; Chen, Lieping

    2016-03-01

    PD-L1 and PD-1 (PD) pathway blockade is a highly promising therapy and has elicited durable antitumor responses and long-term remissions in a subset of patients with a broad spectrum of cancers. How to improve, widen, and predict the clinical response to anti-PD therapy is a central theme in the field of cancer immunology and immunotherapy. Oncologic, immunologic, genetic, and biological studies focused on the human cancer microenvironment have yielded substantial insight into this issue. Here, we focus on tumor microenvironment and evaluate several potential therapeutic response markers including the PD-L1 and PD-1 expression pattern, genetic mutations within cancer cells and neoantigens, cancer epigenetics and effector T cell landscape, and microbiota. We further clarify the mechanisms of action of these markers and their roles in shaping, being shaped, and/or predicting therapeutic responses. We also discuss a variety of combinations with PD pathway blockade and their scientific rationales for cancer treatment. PMID:26936508

  19. Combined and Independent Action of Proteins SP-B and SP-C in the Surface Behavior and Mechanical Stability of Pulmonary Surfactant Films

    PubMed Central

    Schürch, David; Ospina, Olga L.; Cruz, Antonio; Pérez-Gil, Jesús

    2010-01-01

    The hydrophobic proteins SP-B and SP-C are essential for pulmonary surfactant function, even though they are a relatively minor component (<2% of surfactant dry mass). Despite countless studies, their specific differential action and their possible concerted role to optimize the surface properties of surfactant films have not been completely elucidated. Under conditions kept as physiologically relevant as possible, we tested the surface activity and mechanical stability of several surfactant films of varying protein composition in vitro using a captive bubble surfactometer and a novel (to our knowledge) stability test. We found that in the naturally derived surfactant lipid mixtures, surfactant protein SP-B promoted film formation and reextension to lower surface tensions than SP-C, and in particular played a vital role in sustaining film stability at the most compressed states, whereas SP-C produced no stabilization. Preparations containing both proteins together revealed a slight combined effect in enhancing film formation. These results provide a qualitative and quantitative framework for the development of future synthetic therapeutic surfactants, and illustrate the crucial need to include SP-B or an efficient SP-B analog for optimal function. PMID:21081077

  20. Cellular and Molecular Mechanisms Underlie the Anti-Tumor Activities Exerted by Walterinnesia aegyptia Venom Combined with Silica Nanoparticles against Multiple Myeloma Cancer Cell Types

    PubMed Central

    Badr, Gamal; Al-Sadoon, Mohamed K.; Abdel-Maksoud, Mostafa A.; Rabah, Danny M.; El-Toni, Ahmed M.

    2012-01-01

    Multiple myeloma (MM) is a clonal disease of plasma cells that remains incurable despite the advent of several novel therapeutics. In this study, we aimed to delineate the impact of snake venom extracted from Walterinnesia aegyptia (WEV) alone or in combination with silica nanoparticles (WEV+NP) on primary MM cells isolated from patients diagnosed with MM as well as on two MM cell lines, U266 and RPMI 8226. The IC50 values of WEV and WEV+NP that significantly decreased MM cell viability without affecting the viability of normal peripheral mononuclear cells (PBMCs) were determined to be 25 ng/ml and 10 ng/ml, respectively. Although both WEV (25 ng/ml) and WEV+NP (10 ng/ml) decreased the CD54 surface expression without affecting the expression of CXCR4 (CXCL12 receptor) on MM cells, they significantly reduced the ability of CXC chemokine ligand 12 (CXCL12) to induce actin cytoskeleton rearrangement and the subsequent reduction in chemotaxis. It has been established that the binding of CXCL12 to its receptor CXCR4 activates multiple intracellular signal transduction pathways that regulate MM cell chemotaxis, adhesion, and proliferation. We found that WEV and WEV+NP clearly decreased the CXCL12/CXCR4-mediated activation of AKT, ERK, NFκB and Rho-A using western blot analysis; abrogated the CXCL12-mediated proliferation of MM cells using the CFSE assay; and induced apoptosis in MM cell as determined by PI/annexin V double staining followed by flow cytometry analysis. Monitoring the expression of B-cell CCL/Lymphoma 2 (Bcl-2) family members and their role in apoptosis induction after treatment with WEV or WEV+NP revealed that the combination of WEV with NP robustly decreased the expression of the anti-apoptotic effectors Bcl-2, BclXL and Mcl-1; conversely increased the expression of the pro-apoptotic effectors Bak, Bax and Bim; and altered the mitochondrial membrane potential in MM cells. Taken together, our data reveal the biological effects of WEV and WEV+NP and the

  1. Cellular and molecular mechanisms underlie the anti-tumor activities exerted by Walterinnesia aegyptia venom combined with silica nanoparticles against multiple myeloma cancer cell types.

    PubMed

    Badr, Gamal; Al-Sadoon, Mohamed K; Abdel-Maksoud, Mostafa A; Rabah, Danny M; El-Toni, Ahmed M

    2012-01-01

    Multiple myeloma (MM) is a clonal disease of plasma cells that remains incurable despite the advent of several novel therapeutics. In this study, we aimed to delineate the impact of snake venom extracted from Walterinnesia aegyptia (WEV) alone or in combination with silica nanoparticles (WEV+NP) on primary MM cells isolated from patients diagnosed with MM as well as on two MM cell lines, U266 and RPMI 8226. The IC(50) values of WEV and WEV+NP that significantly decreased MM cell viability without affecting the viability of normal peripheral mononuclear cells (PBMCs) were determined to be 25 ng/ml and 10 ng/ml, respectively. Although both WEV (25 ng/ml) and WEV+NP (10 ng/ml) decreased the CD54 surface expression without affecting the expression of CXCR4 (CXCL12 receptor) on MM cells, they significantly reduced the ability of CXC chemokine ligand 12 (CXCL12) to induce actin cytoskeleton rearrangement and the subsequent reduction in chemotaxis. It has been established that the binding of CXCL12 to its receptor CXCR4 activates multiple intracellular signal transduction pathways that regulate MM cell chemotaxis, adhesion, and proliferation. We found that WEV and WEV+NP clearly decreased the CXCL12/CXCR4-mediated activation of AKT, ERK, NFκB and Rho-A using western blot analysis; abrogated the CXCL12-mediated proliferation of MM cells using the CFSE assay; and induced apoptosis in MM cell as determined by PI/annexin V double staining followed by flow cytometry analysis. Monitoring the expression of B-cell CCL/Lymphoma 2 (Bcl-2) family members and their role in apoptosis induction after treatment with WEV or WEV+NP revealed that the combination of WEV with NP robustly decreased the expression of the anti-apoptotic effectors Bcl-2, Bcl(XL) and Mcl-1; conversely increased the expression of the pro-apoptotic effectors Bak, Bax and Bim; and altered the mitochondrial membrane potential in MM cells. Taken together, our data reveal the biological effects of WEV and WEV+NP and

  2. Antibiotic Trapping by Plasmid-Encoded CMY-2 β-Lactamase Combined with Reduced Outer Membrane Permeability as a Mechanism of Carbapenem Resistance in Escherichia coli

    PubMed Central

    van der Bij, Akke K.; van Boxtel, Ria; Pitout, Johann D. D.; van Ulsen, Peter; Melles, Damian C.; Tommassen, Jan

    2013-01-01

    A liver transplant patient was admitted with cholangitis, for which meropenem therapy was started. Initial cultures showed a carbapenem-susceptible (CS) Escherichia coli strain, but during admission, a carbapenem-resistant (CR) E. coli strain was isolated. Analysis of the outer membrane protein profiles showed that both CS and CR E. coli lacked the porins OmpF and OmpC. Furthermore, PCR and sequence analysis revealed that both CS and CR E. coli possessed blaCTX-M-15 and blaOXA-1. The CR E. coli strain additionally harbored blaCMY-2 and demonstrated a >15-fold increase in β-lactamase activity against nitrocefin, but no hydrolysis of meropenem was detected. However, nitrocefin hydrolysis appeared strongly inhibited by meropenem. Furthermore, the CMY-2 enzyme demonstrated lower electrophoretic mobility after its incubation either in vitro or in vivo with meropenem, indicative of its covalent modification with meropenem. The presence of the acyl-enzyme complex was confirmed by mass spectrometry. By transformation of the CMY-2-encoding plasmid into various E. coli strains, it was established that both porin deficiency and high-level expression of the enzyme were needed to confer meropenem resistance. In conclusion, carbapenem resistance emerged by a combination of elevated β-lactamase production and lack of porin expression. Due to the reduced outer membrane permeability, only small amounts of meropenem can enter the periplasm, where they are trapped but not degraded by the large amount of the β-lactamase. This study, therefore, provides evidence that the mechanism of “trapping” by CMY-2 β-lactamase plays a role in carbapenem resistance. PMID:23733461

  3. Mechanism of enhanced responses after combination photodynamic therapy (cPDT) in carcinoma cells involves C/EBP-mediated transcriptional upregulation of the coproporphyrinogen oxidase (CPO) gene

    NASA Astrophysics Data System (ADS)

    Anand, Sanjay; Hasan, Tayyaba; Maytin, Edward V.

    2013-03-01

    Photodynamic therapy (PDT) with aminolevulinate (ALA) is widely accepted as an effective treatment for superficial carcinomas and pre-cancers. However, PDT is still suboptimal for deeper tumors, mainly due to inadequate ALA penetration and subsequent conversion to PpIX. We are interested in improving the effectiveness of photodynamic therapy (PDT) for deep tumors, using a combination approach (cPDT) in which target protoporphyrin (PpIX) levels are significantly enhanced by differentiation caused by giving Vitamin D or methotrexate (MTX) for 3 days prior to ALAPDT. In LNCaP and MEL cells, a strong correlation between inducible differentiation and expression of C/EBP transcription factors, as well as between differentiation and mRNA levels of CPO (a key heme-synthetic enzyme), indicates the possibility of CPO transcriptional regulation by the C/EBPs. Sequence analysis of the first 1300 base pairs of the murine CPO upstream region revealed 15 consensus C/EBP binding sites. Electrophoretic Mobility Shift Assays (EMSA) proved that these sites form specific complexes that have strong, moderate or weak affinities for C/EBPs. However, in the context of the full-length CPO promoter, inactivation of any type of site (strong or weak) reduced CPO promoter activity (luciferase assay) to nearly the same extent, suggesting cooperative interactions. A comparative analysis of murine and human CPO promoters revealed possible protein-protein interactions between C/EBPs and several neighboring transcription factors such as NFkB, Sp1, AP-1, CBP/p300 and CREB (an enhanceosome complex). Overall, these results confirm that C/EBP's are important for CPO expression via complex mechanisms which upregulate PpIX and enhance the outcome of cPDT.

  4. [The role of adenosine Al receptors and mitochondrial K+ATP channels in the mechanism of increasing the resistance to acute hypoxia in the combined effects of hypoxia and hypercapnia].

    PubMed

    Tregub, P P; Kulikov, V P; Stepanova, L A; Zabrodina, A S; Nagibaeva, M E

    2014-01-01

    We studied the role of the role of mitoK+ATp channels and Al-adenosine receptor in the mechanism of increasing the resistance to acute hypoxia after hypoxic, hypercapnic and hypercapnic-hypoxic preconditioning. It is shown that mitochondrial ATP-sensitive potassium channels and Al-adenosine receptors, an important mechanism of preconditioning have a high value to increase the resistance to acute hypoxia/ischemia in the combined effect of hypoxia and hypercapnia. However, with regard to the adenosine receptor, this mechanism is realized without the participation hypercapnic component, which apparently starts neuroprotection without activation of the adenosine Al receptors. PMID:25980226

  5. Mechanism of Chemoprevention against Colon Cancer Cells Using Combined Gelam Honey and Ginger Extract via mTOR and Wnt/β-catenin Pathways.

    PubMed

    Wee, Lee Heng; Morad, Noor Azian; Aan, Goon Jo; Makpol, Suzana; Wan Ngah, Wan Zurinah; Mohd Yusof, Yasmin Anum

    2015-01-01

    The PI3K-Akt-mTOR, Wnt/β-catenin and apoptosis signaling pathways have been shown to be involved in genesis of colorectal cancer (CRC). The aim of this study was to elucidate whether combination of Gelam honey and ginger might have chemopreventive properties in HT29 colon cancer cells by modulating the mTOR, Wnt/β-catenin and apoptosis signaling pathways. Treatment with Gelam honey and ginger reduced the viability of the HT29 cells dose dependently with IC50 values of 88 mg/ml and 2.15 mg/ml respectively, their while the combined treatment of 2 mg/ml of ginger with 31 mg/ml of Gelam honey inhibited growth of most HT29 cells. Gelam honey, ginger and combination induced apoptosis in a dose dependent manner with the combined treatment exhibiting the highest apoptosis rate. The combined treatment downregulated the gene expressions of Akt, mTOR, Raptor, Rictor, β-catenin, Gsk3β, Tcf4 and cyclin D1 while cytochrome C and caspase 3 genes were shown to be upregulated. In conclusion, the combination of Gelam honey and ginger may serve as a potential therapy in the treatment of colorectal cancer through inhibiton of mTOR, Wnt/β catenin signaling pathways and induction of apoptosis pathway. PMID:26434873

  6. Mechanism underlying the effect of combined therapy using glucosamine and low-dose cyclosporine A on the development of atopic dermatitis-like skin lesions in NC/Nga mice.

    PubMed

    Kim, Chang-Hyun; Choi, Yun-Seok; Cheong, Kyung Ah; Lee, Ai-Young

    2013-02-01

    Combination therapy is often used in the treatment of atopic dermatitis (AD) to improve clinical efficacy or to spare the dose of each drug. Cyclosporine A (CsA) is a calcineurin inhibitor that was developed for the treatment of AD. Glucosamine (Glu) is a potent immunosuppressant that inhibits Th2-mediated immunity. We previously reported that Glu has an ameliorative effect on the development of the pathology in NC/Nga mice. The aims of our study were to investigate the therapeutic efficacy of combination of Glu and low-dose CsA in dermatophagoides farina (Df)-induced AD-like skin lesions in NC/Nga mice and to determine the underlying therapeutic mechanisms. The Df-induced NC/Nga mice with a clinical score of 7 were used for treatment with Glu (500mg/kg) alone, low-dose CsA (2, 5, and 10mg/kg) or in combination. The clinical scores were reduced significantly by the combination treatment with Glu and low-dose CsA. The suppression of dermatitis by combined therapy was accompanied by decrease in the plasma level of IgE and in the splenic level of IL-4, IL-5, IL-13, TARC and eotaxin. Histological analysis of the skin also revealed that combination treatment significantly reduced the inflammatory cellular infiltrate, including mast cells and eosinophils. Particularly, immunological evaluation reveals an increase of CD4(+)CD25(+) Treg cells in the combined treatment. The induction of TSLP, which leads to systemic Th2 response, was reduced in the skin on combination treatment. The protein expression of filaggrin and involucrin was recovered by combination treatment in the skin lesions, whereas the protein expression of keratin-10 and keratin-14 decreased in the combination treatment. Collectively, our findings suggest that combination treatment of Glu and low-dose CsA leads to the therapeutic effects in Df-induced AD-like skin lesion in NC/Nga mice through inhibition of IgE, inflammatory cellular infiltrate, and recovery of skin barrier function via a mechanism that may

  7. The effect of a combined biological and thermo-mechanical pretreatment of wheat straw on energy yields in coupled ethanol and methane generation.

    PubMed

    Theuretzbacher, Franz; Blomqvist, Johanna; Lizasoain, Javier; Klietz, Lena; Potthast, Antje; Horn, Svein Jarle; Nilsen, Paal J; Gronauer, Andreas; Passoth, Volkmar; Bauer, Alexander

    2015-10-01

    Ethanol and biogas are energy carriers that could contribute to a future energy system independent of fossil fuels. Straw is a favorable bioenergy substrate as it does not compete with food or feed production. As straw is very resistant to microbial degradation, it requires a pretreatment to insure efficient conversion to ethanol and/or methane. This study investigates the effect of combining biological pretreatment and steam explosion on ethanol and methane yields in order to improve the coupled generation process. Results show that the temperature of the steam explosion pretreatment has a particularly strong effect on possible ethanol yields, whereas combination with the biological pretreatment showed no difference in overall energy yield. The highest overall energy output was found to be 10.86 MJ kg VS(-1) using a combined biological and steam explosion pretreatment at a temperature of 200°C. PMID:26176820

  8. Impact and mechanism of non-steroidal anti-inflammatory drugs combined with chemotherapeutic drugs on human lung cancer-nude mouse transplanted tumors

    PubMed Central

    SUN, WEIYI; CHEN, GANG

    2016-01-01

    The present study aimed to investigate the impact of indomethacin treatment combined with oxaliplatin treatment on the expression of cluster of differentiation 44 variant 6 (CD44v6), matrix metalloproteinase-2 (MMP-2) and survivin in human lung cancer-nude mouse transplanted tumors. The human lung adenocarcinoma (A549)-nude mouse transplanted tumor model was established, and the mice were divided into a control group, an indomethacin treatment group, an oxaliplatin treatment group and an indomethacin-oxaliplatin combination treatment group. The tumor inhibition rate was calculated following sacrificing of the mice. Immunohistochemical staining and fluorescence reverse transcription-quantitative polymerase chain reaction were utilized to detect the protein and messenger (m)RNA expression of CD44v6, MMP-2 and survivin. The tumor inhibition rates of the indomethacin group, the oxaliplatin group and the combination group were 26.67, 47.70 and 68.88%, respectively. The protein and mRNA expression levels of CD44v6, MMP-2 and survivin in the transplanted tumors of each treatment group were reduced compared with the control group (P<0.05), and those of the combination group were lower compared with the single-drug treatment groups (P<0.05). Survivin and MMP-2, MMP-2 and CD44v6, and MMP-2 and CD44v6 all exhibited linear positive correlation. The present study provides evidence that the administration of indomethacin alone, or in combination with oxaliplatin, may significantly inhibit the growth of lung cancer-nude mouse transplanted tumors and the expression of CD44v6, MMP-2 and survivin inside the tumor. The combination of non-steroidal anti-inflammatory drugs with chemotherapeutic drugs may improve the antitumor effects. PMID:27313765

  9. Investigation of epothilone B-induced cell death mechanisms in human epithelial cancer cells -in consideration of combined treatment with ionizing radiation.

    PubMed

    Baumgart, Tonja; Kriesen, Stephan; Neels, Oliver; Hildebrandt, Guido; Manda, Katrin

    2015-07-01

    Epothilone B was shown to have promising chemo- and radiosensitizing effects on cells, but the mechanisms underlying cell death remain ambiguous. The aim of the study was to examine selected cell death pathways on the basis of FaDu and A549 cells. Western blot analyses were used for investigation of specific apoptotic markers. Immunofluorescence imaging and flow cytometry were utilized for examination of cell death mechanisms. DNA-staining was used for studying influence of epothilone B on micronucleus rate. We showed that epothilone B can initiate cell death via apoptosis and mitotic catastrophe, but induction of cell death was cell type specific. PMID:25919223

  10. Investigation of mechanism of bone regeneration in a porous biodegradable calcium phosphate (CaP) scaffold by a combination of a multi-scale agent-based model and experimental optimization/validation

    NASA Astrophysics Data System (ADS)

    Zhang, Le; Qiao, Minna; Gao, Hongjie; Hu, Bin; Tan, Hua; Zhou, Xiaobo; Li, Chang Ming

    2016-08-01

    Herein, we have developed a novel approach to investigate the mechanism of bone regeneration in a porous biodegradable calcium phosphate (CaP) scaffold by a combination of a multi-scale agent-based model, experimental optimization of key parameters and experimental data validation of the predictive power of the model. The advantages of this study are that the impact of mechanical stimulation on bone regeneration in a porous biodegradable CaP scaffold is considered, experimental design is used to investigate the optimal combination of growth factors loaded on the porous biodegradable CaP scaffold to promote bone regeneration and the training, testing and analysis of the model are carried out by using experimental data, a data-mining algorithm and related sensitivity analysis. The results reveal that mechanical stimulation has a great impact on bone regeneration in a porous biodegradable CaP scaffold and the optimal combination of growth factors that are encapsulated in nanospheres and loaded into porous biodegradable CaP scaffolds layer-by-layer can effectively promote bone regeneration. Furthermore, the model is robust and able to predict the development of bone regeneration under specified conditions.

  11. Investigation of mechanism of bone regeneration in a porous biodegradable calcium phosphate (CaP) scaffold by a combination of a multi-scale agent-based model and experimental optimization/validation.

    PubMed

    Zhang, Le; Qiao, Minna; Gao, Hongjie; Hu, Bin; Tan, Hua; Zhou, Xiaobo; Li, Chang Ming

    2016-08-21

    Herein, we have developed a novel approach to investigate the mechanism of bone regeneration in a porous biodegradable calcium phosphate (CaP) scaffold by a combination of a multi-scale agent-based model, experimental optimization of key parameters and experimental data validation of the predictive power of the model. The advantages of this study are that the impact of mechanical stimulation on bone regeneration in a porous biodegradable CaP scaffold is considered, experimental design is used to investigate the optimal combination of growth factors loaded on the porous biodegradable CaP scaffold to promote bone regeneration and the training, testing and analysis of the model are carried out by using experimental data, a data-mining algorithm and related sensitivity analysis. The results reveal that mechanical stimulation has a great impact on bone regeneration in a porous biodegradable CaP scaffold and the optimal combination of growth factors that are encapsulated in nanospheres and loaded into porous biodegradable CaP scaffolds layer-by-layer can effectively promote bone regeneration. Furthermore, the model is robust and able to predict the development of bone regeneration under specified conditions. PMID:27460959

  12. Theoretical analysis of geometry and NMR isotope shift in hydrogen-bonding center of photoactive yellow protein by combination of multicomponent quantum mechanics and ONIOM scheme

    SciTech Connect

    Kanematsu, Yusuke; Tachikawa, Masanori

    2014-11-14

    Multicomponent quantum mechanical (MC-QM) calculation has been extended with ONIOM (our own N-layered integrated molecular orbital + molecular mechanics) scheme [ONIOM(MC-QM:MM)] to take account of both the nuclear quantum effect and the surrounding environment effect. The authors have demonstrated the first implementation and application of ONIOM(MC-QM:MM) method for the analysis of the geometry and the isotope shift in hydrogen-bonding center of photoactive yellow protein. ONIOM(MC-QM:MM) calculation for a model with deprotonated Arg52 reproduced the elongation of O–H bond of Glu46 observed by neutron diffraction crystallography. Among the unique isotope shifts in different conditions, the model with protonated Arg52 with solvent effect reasonably provided the best agreement with the corresponding experimental values from liquid NMR measurement. Our results implied the availability of ONIOM(MC-QM:MM) to distinguish the local environment around hydrogen bonds in a biomolecule.

  13. Combined meso-scale modeling and experimental investigation of the effect of mechanical damage on the transport properties of cementitious composites

    NASA Astrophysics Data System (ADS)

    Raghavan, Balaji; Niknezhad, Davood; Bernard, Fabrice; Kamali-Bernard, Siham

    2016-09-01

    The transport properties of cementitious composites such as concrete are important indicators of their durability, and are known to be heavily influenced by mechanical loading. In the current work, we use meso-scale hygro-mechanical modeling with a morphological 3D two phase mortar-aggregate model, in conjunction with experimentally obtained properties, to investigate the coupling between mechanical loading and damage and the permeability of the composite. The increase in permeability of a cylindrical test specimen at 28% aggregate fraction during a uniaxial displacement-controlled compression test at 85% of the peak load was measured using a gas permeameter. The mortar's mechanical behavior is assumed to follow the well-known compression damaged plasticity (CDP) model with isotropic damage, at varying thresholds, and obtained from different envelope curves. The damaged intrinsic permeability of the mortar evolves according to a logarithmic matching law with progressive loading. We fit the matching law parameters to the experimental result for the test specimen by inverse identification using our meso-scale model. We then subject a series of virtual composite specimens to quasi-static uniaxial compressive loading with varying boundary conditions to obtain the simulated damage and strain evolutions, and use the damage data and the previously identified parameters to determine the evolution of the macroscopic permeability tensor for the specimens, using a network model. We conduct a full parameter study by varying aggregate volume fraction, granulometric distribution, loading/boundary conditions and "matching law" parameters, as well as for different strain-damage thresholds and uniaxial loading envelope curves. Based on this study, we propose Avrami equation-based upper and lower bounds for the evolution of the damaged permeability of the composite.

  14. Combining systems pharmacology, transcriptomics, proteomics, and metabolomics to dissect the therapeutic mechanism of Chinese herbal Bufei Jianpi formula for application to COPD

    PubMed Central

    Zhao, Peng; Yang, Liping; Li, Jiansheng; Li, Ya; Tian, Yange; Li, Suyun

    2016-01-01

    Bufei Jianpi formula (BJF) has long been used as a therapeutic agent in the treatment of COPD. Systems pharmacology identified 145 active compounds and 175 potential targets of BJF in a previous study. Additionally, BJF was previously shown to effectively prevent COPD and its comorbidities, such as ventricular hypertrophy, by inhibition of inflammatory cytokine production, matrix metalloproteinases expression, and other cytokine production, in vivo. However, the system-level mechanism of BJF for the treatment of COPD is still unclear. The aim of this study was to gain insight into its system-level mechanisms by integrating transcriptomics, proteomics, and metabolomics together with systems pharmacology datasets. Using molecular function, pathway, and network analyses, the genes and proteins regulated in COPD rats and BJF-treated rats could be mainly attributed to oxidoreductase activity, antioxidant activity, focal adhesion, tight junction, or adherens junction. Furthermore, a comprehensive analysis of systems pharmacology, transcript, protein, and metabolite datasets is performed. The results showed that a number of genes, proteins, metabolites regulated in BJF-treated rats and potential target proteins of BJF were involved in lipid metabolism, cell junction, oxidative stress, and inflammatory response, which might be the system-level therapeutic mechanism of BJF treatment. PMID:27042044

  15. The combination of antitumor drugs, exemestane and erlotinib, induced resistance mechanism in H358 and A549 non-small cell lung cancer (NSCLC) cell lines.

    PubMed

    Kritikou, Ismini; Giannopoulou, Efstathia; Koutras, Angelos K; Labropoulou, Vassiliki T; Kalofonos, Haralabos P

    2013-11-01

    Abstract Context: Estrogens in non-small-cell lung cancer (NSCLC) are important, and their interaction with epidermal growth factor receptor (EGFR) might be crucial. Objective: This study investigates the effect of exemestane, an aromatase inhibitor, and erlotinib, an EGFR inhibitor, on human NSCLC cell lines; H23, H358 and A549. Materials and methods: A cell proliferation assay was used for measuring cell number, apoptosis assay for detecting apoptosis and necrosis and immunoblotting for beclin-1 and Bcl-2 proteins detection. An immunofluorescence assay was used for EGFR localization. A migration assay and zymography were used for cell motility and metalloproteinases (MMPs) expression, respectively. Results: Exemestane, erlotinib or their combination decreased cell proliferation and increased apoptosis. Exemestane's half maximal inhibitory concentration (IC50) was 50 μM for H23 and H358 cells and 20 μM for A549. The IC50 of erlotinib was 25 μM for all cell lines. Apoptosis increase induced by exemestane was 58.0 (H23), 186.3 (H358) and 34.7% (A549) and by erlotinib was 16.7 (H23), 65.3 (H358) and 66.3% (A549). A synergy effect was observed only in H23 cells. Noteworthy, the combination of exemestane and erlotinib decreased beclin-1 protein levels (32.3 ± 19.2%), an indicator of autophagy, in H23 cells. The combination of exemestane and erlotinib partially reversed the EGFR translocation to mitochondria and decreased MMP levels and migration. Discussion and conclusions: The benefit from a dual targeting of aromatase and EGFR seems to be regulated by NSCLC cell content. The diverse responses of cells to agents might be influenced by the dominance of certain molecular pathways. PMID:24192333

  16. [Movement-adsorption and its mechanism of Cd in soil under combining effects of electrokinetics and a new type of bamboo charcoal].

    PubMed

    Ma, Jian-Wei; Wang, Hui; Luo, Qi-Shi

    2007-08-01

    The characteristics of migration and its influencing factor of cadmium in sandy loam soil by uniform electrokinetics as well as the adsorption property by a new material-bamboo charcoal were investigated through bench-scale experiments, and the feasibility of using electrokinetic technique combined with the newly developed bamboo charcoal for remediation of cadmium contaminated soils was analyzed as well. The results show that the bamboo charcoal is good adsorption material which has comparably strong adsorption effect on Cd, bearing potential in future use, which could be simulated by both Freundlich and Langmuir models (R2 > 0.96). The migration rates of cadmium in sandy loam were high up to 0. 6786 - 0.6875cm/h under an electric gradient of 1.0V/cm, depending upon the concentration of cadmium and the distribution of electric field density. Electrokinetics effectively transported the heavy metal in the soil. In the new electrokinetic tech combining the bamboo charcoal with the same electric gradient above under the polarity reversal period of 48 hours, the cadmium in the soil could be wiped off with high efficiency (removal efficiency 79.6% in 12 days) and the pH together with water content could be well retained. The electric current in the process changed periodically according to the reversal. As a new technique, the electrokinetic movement-bamboo charcoal adsorption holds high potential in future use. PMID:17926419

  17. Application and possible mechanisms of combining LLLT (low level laser therapy), infrared hyperthermia and ionizing radiation in the treatment of cancer

    NASA Astrophysics Data System (ADS)

    Abraham, Edward H.; Woo, Van H.; Harlin-Jones, Cheryl; Heselich, Anja; Frohns, Florian

    2014-02-01

    Benefit of concomitant infrared hyperthermia and low level laser therapy and ionizing radiation is evaluated in this study. The purpose/objectives: presentation with locally advanced bulky superficial tumors is clinically challenging. To enhance the efficacy of chemotherapy and IMRT (intensity-modulated radiation therapy) and/or electron beam therapy we have developed an inexpensive and clinically effective infrared hyperthermia approach that combines black-body infrared radiation with halogen spectrum radiation and discrete wave length infrared clinical lasers LLLT. The goal is to produce a composite spectrum extending from the far infrared to near infrared and portions of the visible spectrum with discrete penetrating wavelengths generated by the clinical infrared lasers with frequencies of 810 nm and/or 830 nm. The composite spectrum from these sources is applied before and after radiation therapy. We monitor the surface and in some cases deeper temperatures with thermal probes, but use an array of surface probes as the limiting safe thermal constraint in patient treatment while at the same time maximizing infrared entry to deeper tissue layers. Fever-grade infrared hyperthermia is produced in the first centimeters while non-thermal infrared effects act at deeper tissue layers. The combination of these effects with ionizing radiation leads to improved tumor control in many cancers.

  18. Investigation of the Degradation Mechanisms of a Variety of Organic Photovoltaic Devices by Combination of Imaging Techniques—the ISOS-3Inter-laboratory Collaboration

    SciTech Connect

    Germack D.; Rosch, R.; Tanenbaum, D.M.; Jorgensen, M.; Seeland, M.; Barenklau, M.; Hermenau, M.; Voroshazi, E.; Lloyd, M.T.; Galagan, Y.; Zimmermann, B.; Wurfel, U.; Hosel, M.; Dam, H.F.; Gevorgyan, S.A.; Kudret, S.; Maes, W.; Lutsen, L.; Vanderzande, D.; Andriessen, R.; Teran-Escobar, G.; Lira-Cantu, M.; Rivaton, A.; Uzunoglu, G.Y.; Andreasen, B.; Madsen, M.V.; Norrman, K.; Hoppe, H.; Krebs, F.C.

    2012-04-01

    The investigation of degradation of seven distinct sets (with a number of individual cells of n {ge} 12) of state of the art organic photovoltaic devices prepared by leading research laboratories with a combination of imaging methods is reported. All devices have been shipped to and degraded at Risoe DTU up to 1830 hours in accordance with established ISOS-3 protocols under defined illumination conditions. Imaging of device function at different stages of degradation was performed by laser-beam induced current (LBIC) scanning; luminescence imaging, specifically photoluminescence (PLI) and electroluminescence (ELI); as well as by lock-in thermography (LIT). Each of the imaging techniques exhibits its specific advantages with respect to sensing certain degradation features, which will be compared and discussed here in detail. As a consequence, a combination of several imaging techniques yields very conclusive information about the degradation processes controlling device function. The large variety of device architectures in turn enables valuable progress in the proper interpretation of imaging results - hence revealing the benefits of this large scale cooperation in making a step forward in the understanding of organic solar cell aging and its interpretation by state-of-the-art imaging methods.

  19. Spinal Mechanisms May Provide a Combination of Intermittent and Continuous Control of Human Posture: Predictions from a Biologically Based Neuromusculoskeletal Model

    PubMed Central

    Elias, Leonardo Abdala; Watanabe, Renato Naville; Kohn, André Fabio

    2014-01-01

    Several models have been employed to study human postural control during upright quiet stance. Most have adopted an inverted pendulum approximation to the standing human and theoretical models to account for the neural feedback necessary to keep balance. The present study adds to the previous efforts in focusing more closely on modelling the physiological mechanisms of important elements associated with the control of human posture. This paper studies neuromuscular mechanisms behind upright stance control by means of a biologically based large-scale neuromusculoskeletal (NMS) model. It encompasses: i) conductance-based spinal neuron models (motor neurons and interneurons); ii) muscle proprioceptor models (spindle and Golgi tendon organ) providing sensory afferent feedback; iii) Hill-type muscle models of the leg plantar and dorsiflexors; and iv) an inverted pendulum model for the body biomechanics during upright stance. The motor neuron pools are driven by stochastic spike trains. Simulation results showed that the neuromechanical outputs generated by the NMS model resemble experimental data from subjects standing on a stable surface. Interesting findings were that: i) an intermittent pattern of muscle activation emerged from this posture control model for two of the leg muscles (Medial and Lateral Gastrocnemius); and ii) the Soleus muscle was mostly activated in a continuous manner. These results suggest that the spinal cord anatomy and neurophysiology (e.g., motor unit types, synaptic connectivities, ordered recruitment), along with the modulation of afferent activity, may account for the mixture of intermittent and continuous control that has been a subject of debate in recent studies on postural control. Another finding was the occurrence of the so-called “paradoxical” behaviour of muscle fibre lengths as a function of postural sway. The simulations confirmed previous conjectures that reciprocal inhibition is possibly contributing to this effect, but on the

  20. Spinal mechanisms may provide a combination of intermittent and continuous control of human posture: predictions from a biologically based neuromusculoskeletal model.

    PubMed

    Elias, Leonardo Abdala; Watanabe, Renato Naville; Kohn, André Fabio

    2014-11-01

    Several models have been employed to study human postural control during upright quiet stance. Most have adopted an inverted pendulum approximation to the standing human and theoretical models to account for the neural feedback necessary to keep balance. The present study adds to the previous efforts in focusing more closely on modelling the physiological mechanisms of important elements associated with the control of human posture. This paper studies neuromuscular mechanisms behind upright stance control by means of a biologically based large-scale neuromusculoskeletal (NMS) model. It encompasses: i) conductance-based spinal neuron models (motor neurons and interneurons); ii) muscle proprioceptor models (spindle and Golgi tendon organ) providing sensory afferent feedback; iii) Hill-type muscle models of the leg plantar and dorsiflexors; and iv) an inverted pendulum model for the body biomechanics during upright stance. The motor neuron pools are driven by stochastic spike trains. Simulation results showed that the neuromechanical outputs generated by the NMS model resemble experimental data from subjects standing on a stable surface. Interesting findings were that: i) an intermittent pattern of muscle activation emerged from this posture control model for two of the leg muscles (Medial and Lateral Gastrocnemius); and ii) the Soleus muscle was mostly activated in a continuous manner. These results suggest that the spinal cord anatomy and neurophysiology (e.g., motor unit types, synaptic connectivities, ordered recruitment), along with the modulation of afferent activity, may account for the mixture of intermittent and continuous control that has been a subject of debate in recent studies on postural control. Another finding was the occurrence of the so-called "paradoxical" behaviour of muscle fibre lengths as a function of postural sway. The simulations confirmed previous conjectures that reciprocal inhibition is possibly contributing to this effect, but on the

  1. Mechanical characterization of articular cartilage by combining magnetic resonance imaging and finite-element analysis—a potential functional imaging technique

    NASA Astrophysics Data System (ADS)

    Julkunen, P.; Korhonen, R. K.; Nissi, M. J.; Jurvelin, J. S.

    2008-05-01

    Magnetic resonance imaging (MRI) provides a method for non-invasive characterization of cartilage composition and structure. We aimed to see whether T1 and T2 relaxation times are related to proteoglycan (PG) and collagen-specific mechanical properties of articular cartilage. Specifically, we analyzed whether variations in the depthwise collagen orientation, as assessed by the laminae obtained from T2 profiles, affect the mechanical characteristics of cartilage. After MRI and unconfined compression tests of human and bovine patellar cartilage samples, fibril-reinforced poroviscoelastic finite-element models (FEM), with depthwise collagen orientations implemented from quantitative T2 maps (3 laminae for human, 3-7 laminae for bovine), were constructed to analyze the non-fibrillar matrix modulus (PG specific), fibril modulus (collagen specific) and permeability of the samples. In bovine cartilage, the non-fibrillar matrix modulus (R = -0.64, p < 0.05) as well as the initial permeability (R = 0.70, p < 0.05) correlated with T1. In bovine cartilage, T2 correlated positively with the initial fibril modulus (R = 0.62, p = 0.05). In human cartilage, the initial fibril modulus correlated negatively (R = -0.61, p < 0.05) with T2. Based on the simulations, cartilage with a complex collagen architecture (5 or 7 laminae), leading to high bulk T2 due to magic angle effects, provided higher compressive stiffness than tissue with a simple collagen architecture (3 laminae). Our results suggest that T1 reflects PG-specific mechanical properties of cartilage. High T2 is characteristic to soft cartilage with a classical collagen architecture. Contradictorily, high bulk T2 can also be found in stiff cartilage with a multilaminar collagen fibril network. By emerging MRI and FEM, the present study establishes a step toward functional imaging of articular cartilage.

  2. Possible Mechanism of Therapeutic Effect of 3-Methyl-1-phenyl-2-pyrazolin-5-one and Bone Marrow Stromal Cells Combination Treatment in Rat Ischemic Stroke Model

    PubMed Central

    Shen, Li-Hua; Chen, Jin; Shen, Hua-Chao; Ye, Min; Liu, Xiao-Fei; Ding, Wen-Sen; Sheng, Ya-Feng; Ding, Xin-Sheng

    2016-01-01

    Background: The functional improvement following bone marrow stromal cells (BMSCs) transplantation after stroke is directly related to the number of engrafted cells and neurogenesis in the injured brain. Here, we tried to evaluate whether 3-methyl-1-phenyl-2-pyrazolin-5-one (MCI-186), a free radical scavenger, might influence BMSCs migration to ischemic brain, which could promote neurogenesis and thereby enhance treatment effects after stroke. Methods: Rat transient middle cerebral artery occlusion (MCAO) model was established. Two separate MCAO groups were administered with either MCI-186 or phosphate-buffered saline (PBS) solution to evaluate the expression of stromal cell-derived factor-1 (SDF-1) in ischemic brain, and compared to that in sham group (n = 5/group/time point[at 1, 3, and 7 days after operation]). The content of chemokine receptor-4 (CXCR4, a main receptor of SDF-1) at 7 days after operation was also observed on cultured BMSCs. Another four MCAO groups were intravenously administered with either PBS, MCI-186, BMSCs (2 × 106), or a combination of MCI-186 and BMSCs (n = 10/group). 5-bromo-2-deoxyuridine (BrdU) and Nestin double-immunofluorescence staining was performed to identify the engrafted BMSCs and neuronal differentiation. Adhesive-removal test and foot-fault evaluation were used to test the neurological outcome. Results: MCI-186 upregulated the expression of SDF-1 in ischemic brain and CXCR4 content in BMSCs was enhanced after hypoxic stimulation. When MCAO rats were treated with either MCI-186, BMSCs, or a combination of MCI-186 and BMSCs, the neurologic function was obviously recovered as compared to PBS control group (P < 0.01 or 0.05, respectively). Combination therapy represented a further restoration, increased the number of BMSCs and Nestin+ cells in ischemic brain as compared with BMSCs monotherapy (P < 0.01). The number of engrafted-BMSCs was correlated with the density of neuronal cells in ischemic brain (r = 0.72, P < 0.01) and

  3. A combined experimental and computational study of the catalytic dehydration of glycerol on microporous zeolites: an investigation of the reaction mechanism and acrolein selectivity.

    PubMed

    Lin, Xufeng; Lv, Yanhong; Qu, Yuanyuan; Zhang, Guodong; Xi, Yanyan; Phillips, David L; Liu, Chenguang

    2013-12-14

    The catalytic activity and the acrolein selectivity for liquid phase glycerol dehydration on β zeolites (HNa-β-k) were found to be dependent on the reaction temperature as well as on the amount of acid sites on the zeolites. An increase in the reaction temperature favors the acrolein selectivity. The acrolein selectivity increases with the Na(+)/H(+) ratio and the glycerol conversion decreases with it so that a maximum acrolein yield is obtained when a certain amount of acidic sites are replaced by non-active Na(+) sites. The computational results indicate that 3-hydoxylpropanal (HPA) is an important intermediate that determines the final product selectivity. The relative rates of the different reaction pathways for HAP can be affected by the amount of water molecules involved in its homogeneous reaction. Based on the reaction mechanism proposed, it was hypothesized that smaller pores reduce activity but increase selectivity to acrolein, and results of the H-MFI zeolite were consistent with this hypothesis. Our work provides important insight into the overall landscape of the reaction mechanism and can be used to help design reaction systems that have good acrolein selectivity for the liquid phase glycerol dehydration reactions. PMID:24158544

  4. Investigation of the Abstraction and Dissociation Mechanism in the Nitrogen Trifluoride Channels: Combined Post-Hartree-Fock and Transition State Theory Approaches.

    PubMed

    Claudino, D; Gargano, R; Carvalho-Silva, Valter H; E Silva, Geraldo M; da Cunha, W F

    2016-07-21

    The present paper concludes our series of kinetics studies on the reactions involved in the complex mechanism of nitrogen trifluoride decomposition. Two other related reactions that, along with this mechanism, take part in an efficient boron nitride growth process are also investigated. We report results concerning two abstraction reactions, namely NF2 + N ⇄ 2NF and NF3 + NF ⇄ 2NF2, and two dissociations, N2F4 ⇄ 2NF2 and N2F3 ⇄ NF2 + NF. State-of-the-art electronic structure calculations at the CCSD(T)/cc-pVTZ level of theory were considered to determine geometries and frequencies of reactants, products, and transition states. Extrapolation of the energies to the complete basis set limit was used to obtain energies of all the species. We applied transition state theory to compute thermal rate constants including Wigner, Eckart, Bell, and deformed theory corrections in order to take tunneling effects into account. The obtained results are in good agreement with the experimental data available in the literature and are expected to provide a better phenomenological understanding of the NF3 decomposition role in the boron nitride growth for a wide range of temperature values. PMID:27355487

  5. Ordering mechanism of stacked CdSe/ZnS{sub x}Se{sub 1-x} quantum dots: A combined reciprocal-space and real-space approach

    SciTech Connect

    Schmidt, Th.; Roventa, E.; Clausen, T.; Flege, J. I.; Alexe, G.; Rosenauer, A.; Hommel, D.; Falta, J.; Bernstorff, S.; Kuebel, C.

    2005-11-15

    The vertical and lateral ordering of stacked CdSe quantum dot layers embedded in ZnS{sub x}Se{sub 1-x} has been investigated by means of grazing incidence small angle x-ray scattering and transmission electron microscopy. Different growth parameters have been varied in order to elucidate the mechanisms leading to quantum dot correlation. From the results obtained for different numbers of quantum dot layers, we conclude on a self-organized process which leads to increasing ordering for progressive stacking. The dependence on the spacer layer thickness indicates that strain induced by lattice mismatch drives the ordering process, which starts to break down for too thick spacer layers in a thickness range from 45 to 80 A. Typical quantum dot distances in a range from about 110 to 160 A have been found. A pronounced anisotropy of the quantum dot correlation has been observed, with the strongest ordering along the [110] direction. Since an increased ordering is found with increasing growth temperature, the formation of stacking faults as an additional mechanism for quantum dot alignment can be ruled out.

  6. Large-Scale Quantum-Mechanical Molecular Dynamics Simulations Using Density-Functional Tight-Binding Combined with the Fragment Molecular Orbital Method.

    PubMed

    Nishimoto, Yoshio; Nakata, Hiroya; Fedorov, Dmitri G; Irle, Stephan

    2015-12-17

    The fully analytic gradient is developed for density-functional tight-binding (DFTB) combined with the fragment molecular orbital (FMO) method (FMO-DFTB). The response terms arising from the coupling of the electronic state to the embedding potential are derived, and the gradient accuracy is demonstrated on water clusters and a polypeptide. The radial distribution functions (RDFs) obtained with FMO-DFTB are found to be similar to those from conventional DFTB, while the computational cost is greatly reduced; for 256 water molecules one molecular dynamics (MD) step takes 73.26 and 0.68 s with full DFTB and FMO-DFTB, respectively, showing a speed-up factor of 108. FMO-DFTB/MD is applied to 100 ps MD simulations of liquid hydrogen halides and is found to reproduce experimental RDFs reasonably well. PMID:26623658

  7. NUCLEAR CROSS-SECTION CALCULATIONS IN THE 1 MEV TO 5 GEV RANGE WITH COMBINED SEMI-CLASSICAL AND QUANTUM MECHANICAL MODELS

    SciTech Connect

    Guimaraes, F.B.

    2002-03-07

    In this work we describe neutron and proton induced reaction cross-sections for iron produced by the codes TNG and CEM95 in the 5 to 300 MeV energy range. TNG calculations cover the 5-90 MeV range, while CEM95 covers the 50-300 MeV high energy range. The two codes show some disagreements in the overlap energy range, both among themselves and with the experimental data, which are presently being addressed. The experimental data used are from NNDC and/or from LA150 NSE references. We also describe some developments for combining TNG and CEM95 into a new code called CETNG (Cascade Exciton TNG).

  8. A hybrid approach to determining cornea mechanical properties in vivo using a combination of nano-indentation and inverse finite element analysis.

    PubMed

    Abyaneh, M H; Wildman, R D; Ashcroft, I A; Ruiz, P D

    2013-11-01

    An analysis of the material properties of porcine corneas has been performed. A simple stress relaxation test was performed to determine the viscoelastic properties and a rheological model was built based on the Generalized Maxwell (GM) approach. A validation experiment using nano-indentation showed that an isotropic GM model was insufficient for describing the corneal material behaviour when exposed to a complex stress state. A new technique was proposed for determining the properties, using a combination of nano-indentation experiment, an isotropic and orthotropic GM model and inverse finite element method. The good agreement using this method suggests that this is a promising technique for measuring material properties in vivo and further work should focus on the reliability of the approach in practice. PMID:23816808

  9. Accurate rates of the complex mechanisms for growth and dissolu-tion of minerals using a combination of rare event theories

    SciTech Connect

    Stack, Andrew G; Raiten, Paolo; Gale, Julian D.

    2012-01-01

    Mineral growth and dissolution are often treated as occurring via a single, reversible process that governs the rate of reaction. We show that multiple, distinct intermediate states can occur during both growth and dissolution. Specifically, we have used metadynamics, a method to efficiently explore the free energy landscape of a system, coupled to umbrella sampling and reactive flux calculations, to examine the mechanism and rates of attachment and detachment of a barium ion onto a stepped, barite (BaSO4) surface. The activation energies calculated for the rate limiting reactions, which are different for attachment and detachment, precisely match those measured experimentally during both growth and dissolution. These results can potentially explain anomalous, non-steady state mineral reaction rates observed experimentally, and will enable the design of more efficient growth inhibitors and facilitate an understanding of the effect of impurities.

  10. Solvent-dependent "turn-on" fluorescence chemosensor for Mg2+ based on combination of Cdbnd N isomerization and inhibition of ESIPT mechanisms

    NASA Astrophysics Data System (ADS)

    Liu, Zhaodi; Xu, Huajie; Chen, Shuisheng; Sheng, Liangquan; Zhang, Hong; Hao, Fuying; Su, Pengfei; Wang, Wenlong

    2015-10-01

    A fluorescent chemosensor (L) for Mg2+ has been synthesized and characterized, which exhibits turn-on fluorescence response for Mg2+ only in alcohol solvent (methanol or ethanol) with high sensitivity and selectivity. But in both nonpolar and polar solvents (cyclohexane, DCM, DMSO or MeCN), L showed negligible fluorescent response for Mg2+. In order to discover the unique phenomenon, optical measurements, liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) and a high performance liquid chromatography with a fluorescence detector (HPLC-FLD) of L and L with Mg2+ ions in solvents were studied. In alcohol solvent, [L + alcohol molecule] was formed and the mechanism aspect of L concerning the remarkable fluorescence response for Mg2+ has been discussed.

  11. Ligand-exchange mechanism: new insight into solid-phase extraction of uranium based on a combined experimental and theoretical study.

    PubMed

    Tian, Yin; Fu, Jia; Zhang, Yi; Cao, Kecheng; Bai, Chiyao; Wang, Dongqi; Li, Shoujian; Xue, Ying; Ma, Lijian; Zheng, Chong

    2015-03-21

    In numerous reports on selective solid-phase extraction (SPE) of uranium, the extraction of uranium is generally accepted as a direct coordination of the ligands on the solid matrix with the uranyl, in which the critical effect of the hydration shell on the uranyl is neglected. The related mechanism in the extraction process remains unclear. Herein, the detailed calculation of activation energy and the geometry of the identified transition states reveal that the uranium extraction by a newly-synthesized urea-functionalized graphite oxide (Urea-GO) is in essence an exchange process between the ligands on Urea-GO and the coordinated water molecules in the first hydration shell of the uranyl. Moreover, we demonstrate that it is the ketone oxygen in the urea ligand to displace the coordinated water molecule of uranyl due to its stronger bonding ability and lower steric-hindrance, whereas the nitrogen atom in the same ligand is proved to be an electron donor that enables the oxygen atom to have stronger affinity for uranium through electron delocalization effects evaluated on the basis of calculations of the second-order interaction energy between donor and acceptor orbitals. We therefore propose a new ligand-exchange mechanism for the SPE process. This study advances the fundamental understanding of uranium extraction, and provides theoretical and practical guidance on ligand design for selective complexation of uranium(VI) and other metal ions in aqueous solution. Finally, the effect of nitrate ions on the extraction of uranyl was successfully explained based on the experimental and theoretical study. PMID:25690182

  12. Insight into the Intermolecular Recognition Mechanism between Keap1 and IKKβ Combining Homology Modelling, Protein-Protein Docking, Molecular Dynamics Simulations and Virtual Alanine Mutation

    PubMed Central

    Jiang, Zheng-Yu; Chu, Hong-Xi; Xi, Mei-Yang; Yang, Ting-Ting; Jia, Jian-Min; Huang, Jing-Jie; Guo, Xiao-Ke; Zhang, Xiao-Jin; You, Qi-Dong; Sun, Hao-Peng

    2013-01-01

    Degradation of certain proteins through the ubiquitin-proteasome pathway is a common strategy taken by the key modulators responsible for stress responses. Kelch-like ECH-associated protein-1(Keap1), a substrate adaptor component of the Cullin3 (Cul3)-based ubiquitin E3 ligase complex, mediates the ubiquitination of two key modulators, NF-E2-related factor 2 (Nrf2) and IκB kinase β (IKKβ), which are involved in the redox control of gene transcription. However, compared to the Keap1-Nrf2 protein-protein interaction (PPI), the intermolecular recognition mechanism of Keap1 and IKKβ has been poorly investigated. In order to explore the binding pattern between Keap1 and IKKβ, the PPI model of Keap1 and IKKβ was investigated. The structure of human IKKβ was constructed by means of the homology modeling method and using reported crystal structure of Xenopus laevis IKKβ as the template. A protein-protein docking method was applied to develop the Keap1-IKKβ complex model. After the refinement and visual analysis of docked proteins, the chosen pose was further optimized through molecular dynamics simulations. The resulting structure was utilized to conduct the virtual alanine mutation for the exploration of hot-spots significant for the intermolecular interaction. Overall, our results provided structural insights into the PPI model of Keap1-IKKβ and suggest that the substrate specificity of Keap1 depend on the interaction with the key tyrosines, namely Tyr525, Tyr574 and Tyr334. The study presented in the current project may be useful to design molecules that selectively modulate Keap1. The selective recognition mechanism of Keap1 with IKKβ or Nrf2 will be helpful to further know the crosstalk between NF-κB and Nrf2 signaling. PMID:24066166

  13. Multinuclear diffusion NMR spectroscopy and DFT modeling: a powerful combination for unraveling the mechanism of phosphoester bond hydrolysis catalyzed by metal-substituted polyoxometalates.

    PubMed

    Luong, Thi Kim Nga; Shestakova, Pavletta; Mihaylov, Tzvetan T; Absillis, Gregory; Pierloot, Kristine; Parac-Vogt, Tatjana N

    2015-03-01

    A detailed reaction mechanism is proposed for the hydrolysis of the phosphoester bonds in the DNA model substrate bis(4-nitrophenyl) phosphate (BNPP) in the presence of the Zr(IV)-substituted Keggin type polyoxometalate (Et2NH2)8[{α-PW11O39Zr(μ-OH)(H2O)}2]⋅7 H2O (ZrK 2:2) at pD 6.4. Low-temperature (31)P DOSY spectra at pD 6.4 gave the first experimental evidence for the presence of ZrK 1:1 in fast equilibrium with ZrK 2:2 in purely aqueous solution. Moreover, theoretical calculations identified the ZrK 1:1 form as the potentially active species in solution. The reaction intermediates involved in the hydrolysis were identified by means of (1)H/(31)P NMR studies, including EXSY and DOSY NMR spectroscopy, which were supported by DFT calculations. This experimental/theoretical approach enabled the determination of the structures of four intermediate species in which the starting compound BNPP, nitrophenyl phosphate (NPP), or the end product phosphate (P) is coordinated to ZrK 1:1. In the proposed reaction mechanism, BNPP initially coordinates to ZrK 1:1 in a monodentate fashion, which results in hydrolysis of the first phosphoester bond in BNPP and formation of NPP. EXSY NMR studies showed that the bidentate complex between NPP and ZrK 1:1 is in equilibrium with monobound and free NPP. Subsequently, hydrolysis of NPP results in P, which is in equilibrium with its monobound form. PMID:25652658

  14. Combined capillary electrophoresis and high performance liquid chromatography studies on the kinetics and mechanism of the hydrogen peroxide-thiocyanate reaction in a weakly alkaline solution.

    PubMed

    Hu, Ying; Song, Yanan; Horváth, Attila K; Cui, Yin; Ji, Chen; Zhao, Yuemin; Gao, Qingyu

    2014-03-01

    The hydrogen peroxide-thiocyanate reaction has been reinvestigated by means of capillary electrophoresis and high performance liquid chromatography under weakly alkaline conditions at 25.0±0.1 °C. Concentration-time series of thiocyanate, sulfate and cyanate have been followed by capillary electrophoresis as well as that of thiocyanate and hydrogen peroxide by HPLC. It has been clearly demonstrated that OxSCN(-) (where x=1, 2 and 3) cannot be accumulated in detectable amount in contrast to the results of Christy and Egeberg, hence these species can only be regarded as short-lived intermediates. It has been shown that the overall rate law is first-order with respect to both reactants, but no pH-dependence was observed within the pH range of 8.86-10.08. A simple kinetic model has been proposed to fit all the concentration-time curves simultaneously at five different pHs demonstrating the powerful combination of the experimental techniques CE and HPLC with simultaneous evaluation of kinetic curves. It is also enlightened that the quality of the buffer strongly affects the rate of the overall reaction that increases in the order of application of ammonia, phosphate, carbonate and borate, respectively at a constant ionic strength and pH. PMID:24468335

  15. Performance enhancement of polymer electrolyte fuel cells by combining liquid removal mechanisms of a gas diffusion layer with wettability distribution and a gas channel with microgrooves

    NASA Astrophysics Data System (ADS)

    Utaka, Yoshio; Koresawa, Ryo

    2016-08-01

    Although polymer electrolyte fuel cells (PEFCs) are commercially available, there are still many problems that need to be addressed to improve their performance and increase their usage. At a high current density, generated water accumulates in the gas diffusion layer and in the gas channels of the cathode. This excess water obstructs oxygen transport, and as a result, cell performance is greatly reduced. To improve the cell performance, the effective removal of the generated water and the promotion of oxygen diffusion in the gas diffusion layer (GDL) are necessary. In this study, two functions proposed in previous reports were combined and applied to a PEFC: a hybrid GDL to form an oxygen diffusion path using a wettability distribution and a gas separator with microgrooves to enhance liquid removal. For a PEFC with a hybrid GDL and a gas separator with microgrooves, the concentration overvoltage of the PEFC was reduced, and the current density limit and maximum power density were increased compared with a conventional PEFC. Moreover, the stability of the cell voltage was markedly improved.

  16. Power combiner

    DOEpatents

    Arnold, Mobius; Ives, Robert Lawrence

    2006-09-05

    A power combiner for the combining of symmetric and asymmetric traveling wave energy comprises a feed waveguide having an input port and a launching port, a reflector for reflecting launched wave energy, and a final waveguide for the collection and transport of launched wave energy. The power combiner has a launching port for symmetrical waves which comprises a cylindrical section coaxial to the feed waveguide, and a launching port for asymmetric waves which comprises a sawtooth rotated about a central axis.

  17. Determination of the mechanism of action of repetitive halothane exposure on rat brain tissues using a combined method of microarray gene expression profiling and bioinformatics analysis.

    PubMed

    Wang, Jiansheng; Yang, Xiaojun; Xiao, Huan; Kong, Jianqiang; Bing, Miao

    2015-12-01

    The present study aimed to investigate the gene expression profiles of rats brain tissues treated with halothane compared with untreated controls to improve current understanding of the mechanism of action of the inhaled anesthetic. The GSE357 gene expression profile was dowloaded from the Gene Expression Omnibus database, and included six gene chips of samples repeatedly exposed to halothane and 12 gene chips of untreated controls. The differentially expressed genes (DEGs) between these two groups were identified using the Limma package in R language. Subsequently, the Database for Annotation, Visualization and Integrated Discovery was used to annotate the function of these DEGs. In addition, the most significantly upregulated gene and downregulated gene were annotated, to reveal the functional interactions with other associated genes, in FuncBase database. A total of 44 DEGs were obtained between The control and halothane exposure samples. Following Gene Ontology functional classification, these DEGs were found to be involved predominantly in the circulatory system, regulation of cell proliferation and response to endogenous stimulus and corticosteroid stimulus processes. KRT31 and HMGCS2, which were identified as the most significantly downregulated and upregulated DEGs, respectively, were associated with the lipid metabolic process and T cell activation, respectively. These results provided a basis for the development of improved inhalational anesthetics with minimal side effects and are essential for optimization of inhaled anesthetic techniques for advanced surgical procedures. PMID:26497548

  18. Feeling safe in the plane: neural mechanisms underlying superior action control in airplane pilot trainees--a combined EEG/MRS study.

    PubMed

    Yildiz, Ali; Quetscher, Clara; Dharmadhikari, Shalmali; Chmielewski, Witold; Glaubitz, Benjamin; Schmidt-Wilcke, Tobias; Edden, Richard; Dydak, Ulrike; Beste, Christian

    2014-10-01

    In day-to-day life, we need to apply strategies to cascade different actions for efficient unfolding of behavior. While deficits in action cascading are examined extensively, almost nothing is known about the neuronal mechanisms mediating superior performance above the normal level. To examine this question, we investigate action control in airplane pilot trainees. We use a stop-change paradigm that is able to estimate the efficiency of action cascading on the basis of mathematical constraints. Behavioral and EEG data is analyzed along these constraints and integrated with neurochemical data obtained using Magnetic Resonance Spectroscopy (MRS) from the striatal gamma-aminobutyric acid (GABA) -ergic system. We show that high performance in action cascading, as exemplified in airplane pilot trainees, can be driven by intensified attentional processes, circumventing response selection processes. The results indicate that the efficiency of action cascading and hence the speed of responding as well as attentional gating functions are modulated by striatal GABA and Glutamate + Glutamine concentrations. In superior performance in action cascading similar increases in the concentrations of GABA and Glutamate + Glutamine lead to stronger neurophysiological and behavioral effects as compared to subjects with normal performance in action cascading. PMID:24753040

  19. Understanding the thermal decomposition mechanism of a halogen-free chelated orthoborate-based ionic liquid: a combined computational and experimental study.

    PubMed

    Golets, M; Shimpi, M R; Wang, Y-L; Antzutkin, O N; Glavatskih, S; Laaksonen, A

    2016-08-10

    In the last few decades, ionic liquids (ILs) have gained significant attention as lubricants and lubricant additives due to their polar nature, low vapour pressure and tunable physicochemical properties. In this work, quantum chemistry calculations and atomistic Molecular Dynamics (MD) simulations were employed to predict thermal degradation mechanisms of a potential lubricating agent - the tributyloctylphosphonium bis(oxalato)borate ([P4,4,4,8][BOB]) IL. It was found that the onset of decomposition of the studied IL coincides with a cleavage of the B-O bonds in the [BOB](-) anion. Consequently, a series of chemical reactions of the [P4,4,4,8](+) cation with the [BOB](-) anion was triggered yielding alkylboranes, alkenes, trialkylphosphines, CO and CO2. Another ionic system, consisting of [P4,4,4,8][Cl], was also tested for a comparison. Thermogravimetric measurements have shown a higher thermal stability of [P4,4,4,8][BOB] compared to that of [P4,4,4,8][Cl] at least at the initial stage of decomposition, in accord with the presented calculations. Quantum chemical frequency calculations also agreed with the experimental Fourier Transform Infrared (FTIR) spectroscopy results. PMID:27465515

  20. [Effects and mechanisms of inorganic anions in water on degradation of LAS by UV/H2 O2 combination process].

    PubMed

    Pan, Jing; Sun, Tie-Heng; Li, Hai-Bo

    2007-11-01

    Experiments are carried out to study the effects and mechanisms of inorganic anions in water on the degradation of linear alkyl benzene sulfonate (LAS) in UV/H2 O2 process. The results show that UV/H2 O2 process could remove LAS effectively, and the rate of photodegradation follows first-order reaction kinetics model. Under the condition that H2 O2 concentration was 8 mg x L(-1) and a 14 W low pressure mercury vapor discharge lamp irradiated samples, the first-order photodegradation rate constant of LAS in distilled water and tap water were 0.018 0 min(-1) and 0.012 2 min(-1) respectively. NO3-, Cl-, SO4(2-) and HCO3- have inhibitory action on LAS photodegradation. The higher inorganic anions concentration was, the stronger inhibitory action. When their concentrations were 5, 10 and 15 mmol x L(-1) respectively, their inhibitory action order was HCO3- > NO3- > Cl- > SO4(2-) all the time. It was anions synthetical effect that caused photodegradation rate constant of LAS in tap water lower than distilled water. PMID:18290479

  1. Examine the characterization of biofilm formation and inhibition by targeting SrtA mechanism in Bacillus subtilis: a combined experimental and theoretical study.

    PubMed

    Selvaraj, Chandrabose; Sivakamavalli, Jeyachandran; Vaseeharan, Baskaralingam; Singh, Poonam; Singh, Sanjeev Kumar

    2014-08-01

    Bacillus subtilis is one of the well-known biofilm-forming organisms associated with plants, animals, and also used as a model organism for all Bacillus sp. In B. subtilis, SrtA enzyme plays the imperative roles in mechanism of signaling pathway and microbial adherence toward the host. SrtA is highly considered as a universal drug target for all Gram positive pathogens. Because of unresolved 3D structure of SrtA in Gram positive bacteria including B. subtilis, we developed a homology model protein using structural alignments of similar SrtA from B. anthracis. While the structural model of SrtA is analyzed because of its significance in biofilm formation by screening the suitable active site based compounds and analyzing the ability of bacterial biofilm inhibition. Druggability site based screening able to retrieve the active compounds against SrtA and checked the activity of the screened compounds through experimental biochemical assays and in situ microscopic analysis. Here in this study we concluded the computationally screened SrtA inhibitors showed high level of biofilm inhibition despite difficulties in bacterial membrane rigidification. Hence this study leads a way to the new compounds that may be useful to treat the bacterial infections. PMID:25038633

  2. Degradation of the biocide 4-chloro-3,5-dimethylphenol in aqueous medium with ozone in combination with ultraviolet irradiation: operating conditions influence and mechanism.

    PubMed

    Song, Shuang; Liu, Zhiwu; He, Zhiqiao; Li, Yu; Chen, Jianmeng; Li, Chaolin

    2009-11-01

    Biocides usually persist during municipal sewage treatment and are subsequently distributed into aquatic environments. To explore the capability of advanced oxidation processes for the rapid removal of biocides, we examined the total organic carbon (TOC) reduction of 4-chloro-3,5-dimethylphenol (PCMX) with a combination of UV/O(3). Moreover, the related important parameters, including the mass transfer coefficient and light utilization efficiency, in PCMX degradation were determined. The UV/O(3) experimental results showed a pronounced synergistic effect, leading to the nearly complete elimination of TOC within 75 min. Thus, the effect of operating variables was investigated as a function of pH, ozone dosage, bulk temperature and the initial concentration of PCMX. The efficiency of PCMX mineralization increased with an increase in ozone dose up to 3.1 gh(-1), and a decrease in the initial concentration from 250 to 100mg L(-1). The optimal pH value was 4.0, and the preferred bulk temperature was 20 degrees C on the basis of the influence of temperature on reaction rate and ozone solubility. The major aromatic intermediates identified by gas chromatography/mass spectrometry were 2,6-dimethylbenzene-1,4-diol, 2,6-dimethylbenzo-1,4-quinone, 2,6-bis(hydroxymethyl)benzo-1,4-quinone, and 2,6-dimethylbenzo-1,4-aldehyde. Quantitative determination of related carboxylic acid and inorganic anions was done by ion chromatography. On the basis of the identified reaction products, a possible degradation pathway for the UV/O(3) oxidation of PCMX in aqueous media is proposed. PMID:19818989

  3. Combined valence bond-molecular mechanics potential-energy surface and direct dynamics study of rate constants and kinetic isotope effects for the H +C2H6 reaction

    NASA Astrophysics Data System (ADS)

    Chakraborty, Arindam; Zhao, Yan; Lin, Hai; Truhlar, Donald G.

    2006-01-01

    This article presents a multifaceted study of the reaction H +C2H6→H2+C2H5 and three of its deuterium-substituted isotopologs. First we present high-level electronic structure calculations by the W1, G3SX, MCG3-MPWB, CBS-APNO, and MC-QCISD/3 methods that lead to a best estimate of the barrier height of 11.8±0.5kcal/mol. Then we obtain a specific reaction parameter for the MPW density functional in order that it reproduces the best estimate of the barrier height; this yields the MPW54 functional. The MPW54 functional, as well as the MPW60 functional that was previously parametrized for the H +CH4 reaction, is used with canonical variational theory with small-curvature tunneling to calculate the rate constants for all four ethane reactions from 200 to 2000 K. The final MPW54 calculations are based on curvilinear-coordinate generalized-normal-mode analysis along the reaction path, and they include scaled frequencies and an anharmonic C-C bond torsion. They agree with experiment within 31% for 467-826 K except for a 38% deviation at 748 K; the results for the isotopologs are predictions since these rate constants have never been measured. The kinetic isotope effects (KIEs) are analyzed to reveal the contributions from subsets of vibrational partition functions and from tunneling, which conspire to yield a nonmonotonic temperature dependence for one of the KIEs. The stationary points and reaction-path potential of the MPW54 potential-energy surface are then used to parametrize a new kind of analytical potential-energy surface that combines a semiempirical valence bond formalism for the reactive part of the molecule with a standard molecular mechanics force field for the rest; this may be considered to be either an extension of molecular mechanics to treat a reactive potential-energy surface or a new kind of combined quantum-mechanical/molecular mechanical (QM/MM) method in which the QM part is semiempirical valence bond theory; that is, the new potential

  4. Enhanced anti-tumor activity of trichosanthin after combination with a human-derived cell-penetrating peptide, and a possible mechanism of activity.

    PubMed

    Lu, Ye-Zhou; Li, Peng-Fei; Li, Yan-Zhong; Luo, Fan; Guo, Chao; Lin, Bin; Cao, Xue-Wei; Zhao, Jian; Wang, Fu-Jun

    2016-07-01

    Trichosanthin (TCS), a type I ribosome-inactivating protein (RIP-I) and renowned Chinese traditional medicine, displays a broad spectrum of biological and pharmacological properties. Particularly, its anti-tumor activity has received a great deal of attention. However, the cellular mechanism for TCS uptake varies with different tumor cell lines, leading to discrepancies in its reported ability to penetrate cells. In this study, HBD, a human derived cell-penetrating peptide (CPP), was used to improve the delivery of TCS into several types of tumor cells, including HeLa cells. Recombinant TCS (rTCS) with or without the fused HBD peptide was expressed in Escherichia coli cells and successfully purified by Ni-NTA affinity chromatography. The cellular uptake efficiency of FITC-labelled-rTCS-HBD was observed in HeLa cells and compared with the uptake efficiency of non-HBD conjugated rTCS under the same conditions using laser confocal microscopy. Moreover, the IC50 value of rTCS-HBD in the tested tumor cells was much lower than that of rTCS, indicating that HBD could efficiently deliver the rTCS into tumor cells. When compared with rTCS, rTCS-HBD induced higher rates of apoptosis in HeLa cells as analyzed by flow cytometry. Furthermore, the apoptotic events observed in HeLa cells incubated with HBD-fused rTCS included activation of Caspase-9, decrease in the Bcl-2/Bax ratio, and cleavage of PARP. These results strongly suggest the participation of mitochondria in apoptosis. This report illustrates one possible method for achieving the efficient transport of TCS into cells using a CPP as a vector, and increases the likelihood that TCS can be used in the clinic. PMID:27050721

  5. The inhibitory and combinative mechanism of HZ08 with P-glycoprotein expressed on the membrane of Caco-2 cell line

    SciTech Connect

    Zhang, Yanyan; Hu, Yahui; Feng, Yidong; Kodithuwakku, Nandani Darshika; Fang, Weirong; Li, Yunman; Huang, Wenlong

    2014-01-15

    Recently, the research and development of agents to reverse the phenomenon of multidrug resistance has been an attractive goal as well as a key approach to elevating the clinical survival of cancer patients. Although three generations of P-glycoprotein modulators have been identified, poor clearance and metabolism render these agents too toxic to be used in clinical application. HZ08, which has been under investigation for several years, shows a dramatic reversal effect with low cytotoxicity. For the first time, we aimed to describe the interaction between HZ08 and P-glycoprotein in Caco-2 cell line in which P-glycoprotein is overexpressed naturally. Cytotoxicity and multidrug resistance reversal assays, together with flow cytometry, fluorescence microscopy and siRNA interference as well as Caco-2 monolayer transport model were employed in this study to evaluate the interaction between HZ08 and P-glycoprotein. This study revealed that HZ08 was capable of reversing adriamycin resistance mediated by P-glycoprotein as a result of intracellular enhancement of adriamycin accumulation, which was found to be superior to verapamil. In addition, we confirmed that HZ08 suppressed the transport of Rhodamine123 in the Caco-2 monolayer model but had little effect on P-glycoprotein expression. The transport of HZ08 was diminished by P-glycoprotein inhibitors (verapamil and LY335979) and its accumulation was increased via siRNA targeting MDR1 in Caco-2 cells. Furthermore, considering the binding site of P-glycoprotein, verapamil performed as a competitive inhibitor with HZ08. In conclusion, as a P-glycoprotein substrate, HZ08 inhibited P-glycoprotein activity and may share the same binding site of verapamil to P-glycoprotein. - Highlights: • The cytotoxicity and reversing effect of HZ08 was measured in Caco-2 cell line. • HZ08 inhibited the transport of Rhodamine123 across Caco-2 cell monolayer. • The efflux ratio of HZ08 was dropped when combined with P

  6. A combined experimental and DFT study of active structures and self-cycle mechanisms of mononuclear tungsten peroxo complexes in oxidation reactions

    NASA Astrophysics Data System (ADS)

    Jin, Peng; Wei, Donghui; Wen, Yiqiang; Luo, Mengfei; Wang, Xiangyu; Tang, Mingsheng

    2011-04-01

    Tungsten peroxo complexes have been widely used in olefin epoxidation, alcohol oxidation, Baeyer-Villiger oxidation and other oxidation reactions, however, there is still not a unanimous viewpoint for the active structure of mononuclear tungsten peroxo complex by now. In this paper, the catalysis of mononuclear tungsten peroxo complexes 0- 5 with or without acidic ligands for the green oxidation of cyclohexene to adipic acid in the absence of organic solvent and phase-transfer catalyst has been researched in experiment. Then we have suggested two possible kinds of active structures of mononuclear tungsten peroxo complexes including peroxo ring ( nA, n = 0-1) and hydroperoxo ( nB, n = 0-1) structures, which have been investigated using density functional theory (DFT). Moreover, the calculations on self-cycle mechanisms involving the two types of active structures of tungsten peroxo complexes with and without oxalic acid ligand have also been carried out at the B3LYP/[LANL2DZ/6-31G(d, p)] level. The highest energy barrier are 26.17 kcal/mol ( 0A, peroxo ring structure without oxalic acid ligand), 23.91 kcal/mol ( 1A, peroxo ring structure with oxalic acid ligand), 18.19 kcal/mol ( 0B, hydroperoxo structure without oxalic acid ligand) and 13.10 kcal/mol ( 1B, hydroperoxo structure with oxalic acid ligand) in the four potential energy profiles, respectively. The results indicate that both the energy barriers of active structure self-cycle processes with oxalic acid ligands are lower than those without oxalic acid ligands, so the active structures with oxalic acid ligands should be easier to recycle, which is in good agreement with our experimental results. However, due to the higher energy of product than that of the reactant, the energy profile of the self-cycle process of 1B shows that the recycle of 1B could not occur at all in theory. Moreover, the crystal data of peroxo ring structure with oxalic acid ligand could be found in some experimental references. Thus

  7. Determining the mechanical constitutive properties of metals as a function of strain rate and temperature: A combined experimental and modeling approach

    SciTech Connect

    I. M. Robertson; A. Beaudoin; J. Lambros

    2004-01-05

    observation of specific mechanisms of micro-plasticity, as these will indicate the boundary value problem that should be addressed. This focus on the pre-yield region in the quasi-static effort (the elasto-plastic transition) is also a tractable one from an experimental and modeling viewpoint. In addition, our approach will minimize the need to fit model parameters to experimental data to obtain convergence. These are critical steps to reach the primary objective of simulating and modeling material performance under extreme loading conditions. In this annual report, we describe the progress made in the first year of this program.

  8. Study on the interaction mechanism between the special geological environment and their extreme geo-microbes in Dagang Oilfield by combined methods

    NASA Astrophysics Data System (ADS)

    Yao, Jun

    2010-05-01

    . According to these research work listed above, we can reveal the mechanism of interaction between the special geological environment of Dagang Oilfield and the extreme geo-microbes, so as to clarify the effects of oil field environment on the extreme geo-microbes and especially the adverse effect of these geo-microbes to the geological environment, which may provide a practical foundation of theoretical basis for the reasons why the Dagang Oilfield can produce oil. Acknowledgement This work was supported in part by grants from National Outstanding Youth Research Foundation of China (40925010), International Joint Key Project from National Natural Science Foundation of China (40920134003), National Natural Science Foundation of China (40873060), and International Joint Key Project from Chinese Ministry of Science and Technology (2009DFA92830), and the 111 Project (08030).

  9. Determining the mechanical constitutive properties of metals as a function of strain rate and temperature: A combined experimental and modeling approach; Progress Report for 2004

    SciTech Connect

    I. Robertson; A. Beaudoin; J. Lambros

    2005-01-31

    of specific mechanisms of micro-plasticity, as these will indicate the boundary value problem that should be addressed. This focus on the pre-yield region in the quasi-static effort (the elasto-plastic transition) is also a tractable one from an experimental and modeling viewpoint. In addition, our approach will minimize the need to fit model parameters to experimental data to obtain convergence. These are critical steps to reach the primary objective of simulating and modeling material performance under extreme loading conditions. To achieve these goals required assembling a multidisciplinary team, see Table 1, with key collaborators at the National Laboratories. One of the major issues for the team members was to learn about the expertise available and how to communicate across disciplines. The communication issue is a challenging one and is being addressed in part with weekly meetings in which the graduate students present lectures on the fundamentals of their respective areas to the entire group. Breakthroughs in science are presented but these, by necessity, assume a tutorial nature; examples of student led meetings can be found at our website http://hrdg.mse.uiuc.edu/. For example, interpreting electron micrographs and understanding what can be achieved by using electron microscopy is challenging for the modeling expert as is comprehending the input and limitations of crystal plasticity codes for an electron microscopist. Significant progress has been made at dissolving these barriers and the students are able to work across the disciplines.

  10. Enhanced inactivation of food-borne pathogens in ready-to-eat sliced ham by near-infrared heating combined with UV-C irradiation and mechanism of the synergistic bactericidal action.

    PubMed

    Ha, Jae-Won; Kang, Dong-Hyun

    2015-01-01

    The objective of the study described in this article was, first, to investigate the effect of the simultaneous application of near-infrared (NIR) heating and UV irradiation on inactivation of Escherichia coli O157:H7, Salmonella enterica serovar Typhimurium, and Listeria monocytogenes in ready-to-eat (RTE) sliced ham and as well as its effect on product quality and, second, to elucidate the underlying mechanisms of the synergistic bactericidal action of NIR heating and UV irradiation. With the inoculation amounts used, simultaneous NIR-UV combined treatment for 70 s achieved 3.62, 4.17, and 3.43 log CFU reductions of E. coli O157:H7, S. Typhimurium, and L. monocytogenes, respectively. For all three pathogens, the simultaneous application of both technologies resulted in an additional log unit reduction as a result of their synergism compared to the sum of the reductions obtained after the individual treatments. To investigate the mechanisms of NIR-UV synergistic injury for a particular microorganism in a food base, we evaluated the effect of four types of metabolic inhibitors using the overlay method and confirmed that damage to cellular membranes and the inability of cells to repair these structures due to ribosomal damage were the primary factors related to the synergistic lethal effect. Additionally, NIR-UV combined treatment for a maximum of 70 s did not alter the color values or texture parameters of ham slices significantly (P > 0.05). These results suggest that a NIR-UV combined process could be an innovative antimicrobial intervention for RTE meat products. PMID:25107964

  11. Enhanced Inactivation of Food-Borne Pathogens in Ready-To-Eat Sliced Ham by Near-Infrared Heating Combined with UV-C Irradiation and Mechanism of the Synergistic Bactericidal Action

    PubMed Central

    Ha, Jae-Won

    2014-01-01

    The objective of the study described in this article was, first, to investigate the effect of the simultaneous application of near-infrared (NIR) heating and UV irradiation on inactivation of Escherichia coli O157:H7, Salmonella enterica serovar Typhimurium, and Listeria monocytogenes in ready-to-eat (RTE) sliced ham and as well as its effect on product quality and, second, to elucidate the underlying mechanisms of the synergistic bactericidal action of NIR heating and UV irradiation. With the inoculation amounts used, simultaneous NIR-UV combined treatment for 70 s achieved 3.62, 4.17, and 3.43 log CFU reductions of E. coli O157:H7, S. Typhimurium, and L. monocytogenes, respectively. For all three pathogens, the simultaneous application of both technologies resulted in an additional log unit reduction as a result of their synergism compared to the sum of the reductions obtained after the individual treatments. To investigate the mechanisms of NIR-UV synergistic injury for a particular microorganism in a food base, we evaluated the effect of four types of metabolic inhibitors using the overlay method and confirmed that damage to cellular membranes and the inability of cells to repair these structures due to ribosomal damage were the primary factors related to the synergistic lethal effect. Additionally, NIR-UV combined treatment for a maximum of 70 s did not alter the color values or texture parameters of ham slices significantly (P > 0.05). These results suggest that a NIR-UV combined process could be an innovative antimicrobial intervention for RTE meat products. PMID:25107964

  12. Recanalization of Acute and Subacute Venous and Synthetic Bypass-Graft Occlusions With a Mechanical Rotational Catheter

    SciTech Connect

    Wissgott, Christian Kamusella, Peter; Andresen, Reimer

    2013-08-01

    PurposePercutaneous mechanical thrombectomy (PMT) is now established as an alternative treatment of acute arterial occlusions in addition to fibrinolysis and surgical thrombectomy. The objective of this retrospective study was the investigation of a rotational atherothrombectomy catheter in terms of safety and efficacy in the treatment of acute and subacute femoropopliteal bypass occlusions.Materials and MethodsForty-two patients (average age 65.8 {+-} 9.1 years) with acute (<14 days [n = 31]) and subacute (14-42 days [n = 11]) femoropopliteal bypass occlusions were treated consecutively with a rotational debulking and removal catheter (Straub Rotarex). The average occlusion length was 28.4 {+-} 2.9 (24-34) cm. Thirty-four (81 %) patients underwent venous bypass, and 8 (19 %) patients underwent polytetrafluoroethylene bypass.ResultsThe technical success rate was 97.6 % (41 of 42). In 1 patient, blood flow could not be restored despite the use of the atherothrombectomy system. The average catheter intervention time was 6.9 {+-} 2.1 (4-9) min. Ankle-brachial index increased from 0.39 {+-} 0.13 to 0.83 {+-} 0.11 at discharge and to 0.82 {+-} 0.17 after 1 month (p < 0.05). There were a total of 2 (4.8 %) peri-interventional complications: One patient developed a distal embolism, which was successfully treated with local lysis, and another patient had a small perforation at the distal anastomosis, which was successfully treated with a stent.ConclusionPMT with the Rotarex atherothrombectomy catheter represents a safe and effective option in the treatment of acute and subacute femoropopliteal bypass occlusions because it can quickly restore blood flow.

  13. Transplantation of mesenchymal stem cells, recombinant human BMP-2,and their combination in accelerating the union after osteotomy and increasing, the mechanical strength of extracorporeally irradiated femoral autograft in rat models

    PubMed Central

    Fauzi Kamal, Achmad; Hadisoebroto Dilogo, Ismail; Untung Hutagalung, Errol; Iskandriati, Diah; Susworo, R.; Chaerani Siregar, Nurjati; Aulia Yusuf, Achmad; Bachtiar, Adang

    2014-01-01

    Background: Delayed union, nonunion, and mechanical failure is still problems encountered in limb salvage surgery (LSS) using extracorporeal irradiation (ECI). This study aimed to determine whether bone marrow mesenchymal stem cells (MSC) and recombinant human bone morphogenetic protein-2 (rhBMP-2) improve hostgraft union after osteotomy and also increase its mechanical strength. Methods: Thirty Sprague Dawley rats were randomly divided into five groups. Group I (control) underwent LSS using ECI method with 150 Gy single doses. Similar procedures were applied to other groups. Group II received hydroxyapatite (HA) scaffold. Group III received HA scaffold and MSC. Group IV received HA scaffold and rhBMP-2. Group V received HA scaffolds, MSC, and rhBMP-2. Radiograph were taken at week-2, 4, 6, and 8; serum alkaline phosphatase and osteocalcin were measured at week-2 and 4. Histopathological evaluation and biomechanical study was done at week-8. Results: The highest radiological score was found in group IV and V Similar result was obtained in histological score and ultimate bending force. These results were found to be statistically significant. There was no significant difference among groups in serum alkaline phosphatase and osteocalcin level. Conclusion: Combination of MSC and rhBMP-2 was proven to accelerate union and improve mechanical strength of ECI autograft. PMID:25679008

  14. Effect of combined administration of transforming growth factor-b1 and insulin-like growth factor I on the mechanical properties of a patellar tendon defect model in rabbits.

    PubMed

    Lyras, Dimitrios N; Kazakos, Konstantinos; Verettas, Dionysios; Chronopoulos, Efstathios; Folaranmi, Semiu; Agrogiannis, George

    2010-06-01

    The aim of this study was to test the hypothesis that combined administration of TGF-b1 and IGF-I in a patellar tendon defect model could enhance the mechanical properties of the healed tendon. Twenty four New Zealand white rabbits were used for this purpose. In each animal, the right knee was used for the application of the growth factors, whereas the left knee served as an untreated control. The growth factors were mixed with fibrin sealant as a delivery vehicle. Two groups of rabbits were sacrificed after 2 weeks and 6 weeks respectively. Application of the growth factors resulted in a significant increase in force at failure, ultimate stress, stiffness, and energy uptake at 2 weeks, whereas none of the parameters revealed any significant difference between the two groups at 6 weeks. This study provides valuable information on the effect of the two growth factors on this patellar tendon defect model. PMID:20698461

  15. A combined kick-out and dissociative diffusion mechanism of grown-in Be in InGaAs and InGaAsP. A new finite difference-Bairstow method for solution of the diffusion equations

    SciTech Connect

    Koumetz, Serge D. Martin, Patrick; Murray, Hugues

    2014-09-14

    Experimental results on the diffusion of grown-in beryllium (Be) in indium gallium arsenide (In{sub 0.53}Ga{sub 0.47}As) and indium gallium arsenide phosphide (In{sub 0.73}Ga{sub 0.27}As{sub 0.58}P{sub 0.42}) gas source molecular beam epitaxy alloys lattice-matched to indium phosphide (InP) can be successfully explained in terms of a combined kick-out and dissociative diffusion mechanism, involving neutral Be interstitials (Be{sub i}{sup 0}), singly positively charged gallium (Ga), indium (In) self-interstitials (I{sub III}{sup +}) and singly positively charged Ga, In vacancies (V{sub III}{sup +}). A new numerical method of solution to the system of diffusion equations, based on the finite difference approximations and Bairstow's method, is proposed.

  16. AB117. Efficacy and mechanism of combination therapy using Icariin and daily sildenafil citrate for the treatment of erectile dysfunction in a rat model of bilateral cavernous nerves injury

    PubMed Central

    Xu, Yongde; Guan, Ruili; Lei, Hongen; Yang, Yong; Xin, Zhongcheng

    2016-01-01

    The commonly utilized phosphodiesterase type 5 (PDE5) inhibitors does not lead to satisfactory penile erection after radical prostatectomy due to lack of nitric oxide (NO) released from the damaged cavernous nerves (CNs). Of particular interest is that Icariin (ICA) has been demonstrated to increase the expression of neuronal NO synthase (nNOS) in our previous work. In this study, the efficacy and mechanisms ICA in combination with daily sildenafil for the treatment of neurogenic erectile dysfunction (ED) was investigated in a rat model of bilateral CNs injury (BCNI). Sixty male Sprague-Dawley rats injected with 5-ethynyl-2-deoxyuridine (EdU; 50 mg/kg) at newborn were used to track endogenous stem cells (SCs). Fourty-eight rats of BCNI were randomized equally into gavage feeding of vehicle, sildenafil, ICA and sildenafil+ICA, respectively. Twelve sham-operated rats received vehicle treatment and served as control. Interestingly, ICA in combination with sildenafil resulted in better erectile function and effectively preserved the penile size compared with the control and sildenafil groups (P<0.05). In addition, the numbers of nNOS-positive nerves and EdU-positive cells coexpressing Schwann cell marker S100 in the ICA-treated groups were greater compared with the control group (P<0.05). These results indicate that ICA promotes endogenous SCs to differentiate into Schwann cells, which is essential for the regeneration of nNOS-positive ne