MEGA16 - Computer program for analysis and extrapolation of stress-rupture data

The computerized form of the minimum commitment method of interpolating and extrapolating stress versus time to failure data, MEGA16, is described. Examples are given of its many plots and tabular outputs for a typical set of data. The program assumes a specific model equation and then provides a family of predicted isothermals for any set of data with at least 12 stress-rupture results from three different temperatures spread over reasonable stress and time ranges. It is written in FORTRAN 4 using IBM plotting subroutines and its runs on an IBM 370 time sharing system

Interpolation and Extrapolation of Creep Rupture Data by the Minimum Commitment Method. Part 3: Analysis of Multiheats

The Minimum Commitment Method was applied to two sets of data for which multiple heat information was available. For one alloy, a 304 stainless steel studied in Japan, data on nine well characterized heats were used, while for a proprietary low alloy carbon steel studied in the United Kingdom data were available on seven heats - in many cases to very long rupture times. For this preliminary study no instability factors were used. It was discovered that heat-to-heat variations would be accounted for by introducing heat identifiers in the form A + B log sigma where sigma is the stress and the constants A and B depend only on the heat. With these identifiers all the data could be collapsed onto a single master curve, even though there was considerable scatter among heats. Using these identifiers together with the average behavior of all heats made possible the determination of an accurate constitutive equation for each individual heat. Two basic approaches are discussed for applying the results of the analysis

Turbine engine Hot Section Technology (HOST) project

The Hot Section Technology (HOST) Project is a NASA-sponsored endeavor to improve the durability of advanced gas turbine engines for commercial and military aircraft. Through improvements in the analytical models and life prediction systems, designs for future hot section components , the combustor and turbine, will be more accurately analyzed and will incorporate features required for longer life in the more hostile operating environment of high performance engines

An introduction to NASA's turbine engine hot section technology (HOST) project

An overview of research to develop and improve the accuracy of current analysis methods so that increased durability can be designed into future engines is presented. Emphasis is placed on improved accuracy in life prediction. Component design, including description of the thermal and aerodynamic environments, the material's mechanical response, the interactions between environmental and structural response, and high temperature instrumentation capable of measuring near-engine environment effects are addressed. Component tests, improved modeling of the physical phenomena, and tests to verify the proved models are also discussed

Dominant Folding Pathways of a WW Domain

We investigate the folding mechanism of the WW domain Fip35 using a realistic atomistic force field by applying the Dominant Reaction Pathways (DRP) approach. We find evidence for the existence of two folding pathways, which differ by the order of formation of the two hairpins. This result is consistent with the analysis of the experimental data on the folding kinetics of WW domains and with the results obtained from large-scale molecular dynamics (MD) simulations of this system. Free-energy calculations performed in two coarse-grained models support the robustness of our results and suggest that the qualitative structure of the dominant paths are mostly shaped by the native interactions. Computing a folding trajectory in atomistic detail only required about one hour on 48 CPU's. The gain in computational efficiency opens the door to a systematic investigation of the folding pathways of a large number of globular proteins

Pomeron in diffractive processes γ∗(Q2)p→ρ0p\gamma^*(Q^2)p\to\rho^0 p and γ∗(Q2)p→γ∗(Q2)p\gamma^*(Q^2)p\to\gamma^*(Q^2) p at large Q^2: the onset of pQCD

We study the reactions $\gamma^*(Q^2)p\to\rho^0 p$ and $\gamma^*(Q^2)p\to\gamma^*(Q^2) p$ at large Q^2 and $W^2/Q^2$ and small momentum transfer, $\kappa^2_\perp$, to the nucleon where the pomeron exchange dominates. At large Q^2 the virtual photon selects a hard $q\bar q$ pair, thus selecting the hard pomeron component (the BFKL pomeron). The amplitudes for both transverse and longitudinal polarizations of the initial photon and outgoing $\rho$-meson (photon) are calculated in the framework of the BFKL pomeron exchange. Our calculations show that one cannot expect the early onset of the pure perturbative regime in the discussed diffractive processes: the small interquark distances, $\rho_{q\bar q} <0.2$ fm, start to dominate not earlier than at $Q^2 \simeq 100 GeV^2, W^2/Q^2 \simeq 10^7$ in $\gamma^*(Q^2)p\to\rho^0 p$ and $Q^2 \simeq 50 GeV^2, W^2/Q^2 \simeq 10^6$ in $\gamma^*(Q^2)p\to\gamma^*(Q^2) p$.Comment: 20 pages, LaTeX, epsfig.st

Efficacy and tolerability of bevacizumab plus capecitabine as first-line therapy in patients with advanced hepatocellular carcinoma

Molecularly targeted agents with anti-angiogenic activity, including bevacizumab, have demonstrated clinical activity in patients with advanced /metastatic hepatocellular carcinoma (HCC). This multicentre phase II study involving patients from several Asian countries sought to evaluate the safety and efficacy of bevacizumab plus capecitabine in this population. METHODS: Histologically proven/clinically diagnosed advanced HCC patients received bevacizumab 7.5 mg kg(-1) on day 1 and capecitabine 800 mg m(-2) twice daily on days 1-14 every 3 weeks as first-line therapy. RESULTS: A total of 45 patients were enrolled; 44 (96%) had extrahepatic metastasis and/or major vessel invasion and 30( 67%) had hepatitis B. No grade 3/4 haematological toxicity occurred. Treatment-related grade 3/4 non-haematological toxicities included diarrhoea (n = 2, 4%), nausea/ vomiting ( n = 1, 2%), gastrointestinal bleeding (n = 4, 9%) and hand- foot syndrome (n = 4, 9%). The overall response rate ( RECIST) was 9% and the disease control rate was 52%. Overall , median progression-free survival (PFS) and overall survival(OS) were 2.7 and 5.9 months, respectively. Median PFS and OS were 3.6 and 8.2 months, respectively, for Cancer of the Liver Italian Programme (CLIP) score <= 3 patients, and 1.4 and 3.3 months, respectively, for CLIP score 4 patients. CONCLUSION: The bevacizumab-capecitabine combination shows good tolerability and modest anti-tumour activity in patients with advanced HCC

Using Selectively Applied Accelerated Molecular Dynamics to Enhance Free Energy Calculations

Accelerated molecular dynamics (aMD) has been shown to enhance conformational space sampling relative to classical molecular dynamics; however, the exponential reweighting of aMD trajectories, which is necessary for the calculation of free energies relating to the classical system, is oftentimes problematic, especially for systems larger than small poly peptides. Here, we propose a method of accelerating only the degrees of freedom most pertinent to sampling, thereby reducing the total acceleration added to the system and improving the convergence of calculated ensemble averages, which we term selective aMD. Its application is highlighted in two biomolecular cases. First, the model system alanine dipeptide is simulated with classical MD, all-dihedral aMD, and selective aMD, and these results are compared to the infinite sampling limit as calculated with metadynamics. We show that both forms of aMD enhance the convergence of the underlying free energy landscape by 5-fold relative to classical MD; however, selective aMD can produce improved statistics over all-dihedral aMD due to the improved reweighting. Then we focus on the pharmaceutically relevant case of computing the free energy of the decoupling of oseltamivir in the active site of neuraminidase. Results show that selective aMD greatly reduces the cost of this alchemical free energy transformation, whereas all-dihedral aMD produces unreliable free energy estimates