Gamma Prime Precipitate Evolution During Aging of a Model Nickel-Based Superalloy

The microstructural stability of nickel-based superalloys is critical for maintaining alloy performance during service in gas turbine engines. In this study, the precipitate evolution in a model polycrystalline Ni-based superalloy during aging to 1000 hours has been studied via transmission electron microscopy, atom probe tomography and neutron diffraction. Variations in phase composition and precipitate morphology, size and volume fraction were observed during aging, whilst the constrained lattice misfit remained constant at approximately zero. The experimental composition of the γ matrix phase was consistent with thermodynamic equilibrium predictions, whilst significant differences were identified between the experimental and predicted results from the γʹ phase. These results have implications for the evolution of mechanical properties in service and their prediction using modeling methods.The authors wish to acknowledge Mrs. S. Rhodes, Dr. H.T. Pang, Dr. D.M. Collins, and Dr. O.M.D.M. Messé for their assistance with the experiments performed. Funding was provided by the EPSRC/Rolls-Royce Strategic Partnership under EP/M005607/1 and EP/H022309/1. The Oxford Atom Probe facility was funded by the EPSRC under EP/M022803/1. Neutron diffraction beam time was supported through the Canadian Neutron Beam Centre under Experiment number 1258

Universal scaling in highly doped conducting polymer films

Electrical transport of a highly doped disordered conducting polymer, viz. poly-3,4-ethylenedioxythiophene stabilized with poly-4-styrenesulphonic acid, is investigated as a function of bias and temperature. The transport shows universal power-law scaling with both bias and temperature. All measurements constitute a single universal curve, and the complete J(V,T) characteristics are described by a single equation. We relate this scaling to dissipative tunneling processes, such as Coulomb blockade. © 2010 The American Physical Society

Systemic complement activation levels in Stargardt disease

PurposePreclinical research provides evidence for the complement system as a potential common pathway in Stargardt disease (STGD1) and age-related macular degeneration (AMD) leading to retinal pigment epithelium (RPE) loss. However, systemic complement activation has not yet been assessed in STGD1 patients. We conducted a cross-sectional case-control study to assess systemic complement activation in STGD1 patients and its association with disease severity.MethodsSystemic concentrations of complement component C3 and its degradation product C3d were compared between 80 STGD1 patients and 80 controls that were frequency matched for age and sex. The C3d/C3 ratio was used as parameter of systemic complement activation. Within the STGD1 cohort, we additionally examined the association between the C3d/C3 ratio, demographic and behavioural factors (age, sex, smoking and BMI), and measures of disease severity (age at onset, visual acuity, and area of atrophy).ResultsThe C3d/C3 ratio did not significantly differ between patients (mean C3d/C3 ratio 3.5±1.4) and controls (mean C3d/C3 ratio 3.6±1.0), mean difference -0.156 (p = 0.804, independent samples t-test). The overall effect size was 8% (95% confidence interval, 3-15%). Elevated C3d/C3 ratios (>8.1) were found in three patients who all had a concomitant inflammatory condition at the time of blood draw. Within the patient cohort, C3 levels were associated with sex (mean difference -134, p = 0.001, independent samples t-test) and BMI (correlation coefficient 0.463, pConclusionsSystemic complement levels were not elevated in STGD1 patients compared to age and sex matched controls and was not associated with STGD1 severity. Considering the continued absent proof of a systemic contribution of the complement system to RPE loss in STGD1 patients, we hypothesize that complement activation in STGD1 is more likely a local process. In light of upcoming complement-targeted therapies, further studies are needed that measure complement levels in the eye of STGD1 patients

Systemic complement activation levels in Stargardt disease

The datasets contains all raw data and edited_data used for analyses in the research "Systemic complement activation levels in Stargardt disease". ABSTRACT Purpose Preclinical research provides evidence for the complement system as a potential common pathway in Stargardt disease (STGD1) and age-related macular degeneration (AMD) leading to retinal pigment epithelium (RPE) loss. However, systemic activation of the complement system has not yet been assessed in STGD1 patients. We conducted a cross-sectional case-control study to assess systemic complement activation in STGD1 patients and its association with disease severity. Methods Systemic concentrations of complement component C3 and its degradation product C3d were compared between 80 STGD1 patients and 80 controls that were frequency matched for age and sex. The C3d/C3 ratio was used as parameter of systemic complement activation. Within the STGD1 cohort, we additionally examined the association between the C3d/C3 ratio, demographic and behavioural factors (age, sex, smoking and BMI), and measures of disease severity (age at onset, visual acuity, and area of atrophy). Results The C3d/C3 ratio did not significantly differ between patients (mean C3d/C3 ratio 3.5±1.4) and controls (mean C3d/C3 ratio 3.6±1.0), mean difference -0.156, p=0.804, independent samples t-test. Overall effect size was 8% (95% confidence interval, 3-15%). Systemic activation of the complement system (C3d/C3 ratio > 8.1) was found in three patients and none of the controls. These three patients all had a concomitant inflammatory condition at the time of blood draw. Within the patient cohort, C3 levels were associated with sex (mean difference -134, p=0.001, independent samples t-test) and BMI (correlation coefficient 0.463, p<0.001, Spearman’s Correlation), but not with any measures of disease severity, age or smoking status. Conclusions Systemic complement activation was not elevated in STGD1 patients compared to age and sex matched controls and was not associated with STGD1 disease severity. Considering the continued absent proof of a systemic contribution of the complement system to RPE loss in STGD1 patients, we hypothesize that complement activation in STGD1 is more likely a local process. In light of upcoming complement-targeted therapies, further studies are needed that measure complement levels in the eye of STGD1 patients

Direct oral anticoagulants do not inhibit growth and metastasis of human triple negative breast cancer in immunodeficient mice

It has been well-established that cancer results in a hypercoagulable state and an increased risk for venous thromboembolism (VTE). More recently, it has been suggested that coagulation may also affect cancer progression and metastasis. Cancer patients with VTE are currently treated with the anticoagulant low molecular weight heparins (LMWHs). Preclinical studies have shown that LMWHs can inhibit metastasis formation in several types of cancer, but beneficial effects of LMWHs on survival have not been consistently found in clinical trials. Recently, a new class of anticoagulants are available for treatment of VTE, the so-called direct oral anticoagulant (DOACs), which include dabigatran and rivaroxaban, a direct thrombin and FXa inhibitor, respectively. However, the effects of DOACs on cancer are currently under studied.Toxicolog

Systemic complement activation levels in Stargardt disease

The datasets contains all raw data and edited_data used for analyses in the research "Systemic complement activation levels in Stargardt disease". ABSTRACT Purpose Preclinical research provides evidence for the complement system as a potential common pathway in Stargardt disease (STGD1) and age-related macular degeneration (AMD) leading to retinal pigment epithelium (RPE) loss. However, systemic activation of the complement system has not yet been assessed in STGD1 patients. We conducted a cross-sectional case-control study to assess systemic complement activation in STGD1 patients and its association with disease severity. Methods Systemic concentrations of complement component C3 and its degradation product C3d were compared between 80 STGD1 patients and 80 controls that were frequency matched for age and sex. The C3d/C3 ratio was used as parameter of systemic complement activation. Within the STGD1 cohort, we additionally examined the association between the C3d/C3 ratio, demographic and behavioural factors (age, sex, smoking and BMI), and measures of disease severity (age at onset, visual acuity, and area of atrophy). Results The C3d/C3 ratio did not significantly differ between patients (mean C3d/C3 ratio 3.5±1.4) and controls (mean C3d/C3 ratio 3.6±1.0), mean difference -0.156, p=0.804, independent samples t-test. Overall effect size was 8% (95% confidence interval, 3-15%). Systemic activation of the complement system (C3d/C3 ratio > 8.1) was found in three patients and none of the controls. These three patients all had a concomitant inflammatory condition at the time of blood draw. Within the patient cohort, C3 levels were associated with sex (mean difference -134, p=0.001, independent samples t-test) and BMI (correlation coefficient 0.463, p<0.001, Spearman’s Correlation), but not with any measures of disease severity, age or smoking status. Conclusions Systemic complement activation was not elevated in STGD1 patients compared to age and sex matched controls and was not associated with STGD1 disease severity. Considering the continued absent proof of a systemic contribution of the complement system to RPE loss in STGD1 patients, we hypothesize that complement activation in STGD1 is more likely a local process. In light of upcoming complement-targeted therapies, further studies are needed that measure complement levels in the eye of STGD1 patients