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

Proton Nuclear Magnetic Resonance Investigation of the [2Fe-2S]\u3csup\u3e1-\u3c/sup\u3e-Containing “Rieske-Type” Protein from \u3cem\u3eXanthobacter\u3c/em\u3e Strain Py2

Proton NMR spectra of the Rieske-type ferredoxin from Xanthobacter strain Py2 were recorded in both H2O and D2O buffered solutions at pH 7.2. Several well-resolved hyperfine-shifted 1H NMR signals were observed in the 90 to −20 ppm chemical shift range. Comparison of spectra recorded in H2O and D2O buffered solutions indicated that the signals at −11.4 (L) and −15.5 (M) ppm were solvent-exchangeable and thus were assigned to the two histidine Nε2H protons. The remaining observed signals were assigned based upon chemical shift, T1 values, and one-dimensional nuclear Overhauser effect (nOe) saturation transfer experiments to either CβH or CαH protons of cluster cysteinyl or histidine ligands. Upon oxidation of the [2Fe-2S] cluster, only two broad resonances were observed, indicating that the two Fe(III) ions are strongly antiferromagnetically coupled. In addition, the temperature dependence of each observed hyperfine-shifted signal in the reduced state was determined, providing information about the magnetic properties of the [2Fe-2S]1- cluster. Fits of the temperature data observed for each resonance to equations describing the hyperfine shift with their Boltzmann weighting factors provided a ΔEL value of 185 ± 26 cm-1 which, in turn, gives −2J as 124 cm-1. These data indicate that the two iron centers in the reduced [2Fe-2S] Rieske-type center are moderately antiferromagnetically coupled. The combination of these data with the available spectroscopic and crystallographic results for Rieske-type proteins has provided new insights into the role of the Rieske-type protein from Xanthobacter strain Py2 in alkene oxidation

Investigating Hydrologic Alteration as a Mechanism of Fish Assemblage Shifts in Urbanizing Streams

Stream biota in urban and suburban settings are thought to be impaired by altered hydrology; however, it is unknown what aspects of the hydrograph alter fish assemblage structure and which fishes are most vulnerable to hydrologic alterations in small streams. We quantified hydrologic variables and fish assemblages in 30 small streams and their subcatchments (area 8-20 km 2) in the Etowah River Catchment (Georgia, USA). We stratified streams and their subcatchments into 3 landcover categories based on imperviousness (20% of subcatchment), and then estimated the degree of hydrologic alteration based on synoptic measurements of baseflow yield. We derived hydrologic variables from stage gauges at each study site for 1 y (January 2003-2004). Increased imperviousness was positively correlated with the frequency of storm events and rates of the rising and falling limb of the hydrograph (i.e, storm flashiness ) during most seasons. Increased duration of low flows associated with imperviousness only occurred during the autumn low-flow period, and this measure corresponded with increased richness of lentic tolerant species. Altered storm flows in summer and autumn were related to decreased richness of endemic, cosmopolitan, and sensitive fish species, and decreased abundance of lentic tolerant species. Species predicted to be sensitive to urbanization, based on specific life-history or habitat requirements, also were related to stormflow variables and % fine bed sediment in riffles. Overall, hydrologic variables explained 22 to 66% of the variation in fish assemblage richness and abundance Linkages between hydrologic alteration and fish assemblages were potentially complicated by contrasting effects of elevated flows on sediment delivery and scour, and mediating effects of high stream gradient on sediment delivery from elevated flows. However, stormwater management practices promoting natural hydrologic regimes are likely to reduce the impacts of catchment imperviousness on stream fish assemblages. ?? 2005 by The North American Benthological Societ

Markov dynamic models for long-timescale protein motion

Molecular dynamics (MD) simulation is a well-established method for studying protein motion at the atomic scale. However, it is computationally intensive and generates massive amounts of data. One way of addressing the dual challenges of computation efficiency and data analysis is to construct simplified models of long-timescale protein motion from MD simulation data. In this direction, we propose to use Markov models with hidden states, in which the Markovian states represent potentially overlapping probabilistic distributions over protein conformations. We also propose a principled criterion for evaluating the quality of a model by its ability to predict long-timescale protein motions. Our method was tested on 2D synthetic energy landscapes and two extensively studied peptides, alanine dipeptide and the villin headpiece subdomain (HP-35 NleNle). One interesting finding is that although a widely accepted model of alanine dipeptide contains six states, a simpler model with only three states is equally good for predicting long-timescale motions. We also used the constructed Markov models to estimate important kinetic and dynamic quantities for protein folding, in particular, mean first-passage time. The results are consistent with available experimental measurements

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

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

Why are MD simulated protein folding times wrong?

The question of significant deviations of protein folding times simulated using molecular dynamics from experimental values is investigated. It is shown that in the framework of Markov State Model (MSM) describing the conformational dynamics of peptides and proteins, the folding time is very sensitive to the simulation model parameters, such as forcefield and temperature. Using two peptides as examples, we show that the deviations in the folding times can reach an order of magnitude for modest variations of the molecular model. We, therefore, conclude that the folding rate values obtained in molecular dynamics simulations have to be treated with care

Dynamics of N removal over annual time periods in a suburban river network

Author Posting. © American Geophysical Union, 2008. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research 113 (2008): G03038, doi:10.1029/2007JG000660.River systems are dynamic, highly connected water transfer networks that integrate a wide range of physical and biological processes. We used a river network nitrogen (N) removal model with daily temporal resolution to evaluate how elevated N inputs, saturation of the denitrification and total nitrate removal processes, and hydrologic conditions interact to determine the amount, timing and distribution of N removal in the fifth-order river network of a suburban 400 km2 basin. Denitrification parameters were based on results from whole reach 15NO3 tracer additions. The model predicted that between 15 and 33% of dissolved inorganic nitrogen (DIN) inputs were denitrified annually by the river system. Removal approached 100% during low flow periods, even with the relatively low and saturating uptake velocities typical of surface water denitrification. Annual removal percentages were moderate because most N inputs occurred during high flow periods when hydraulic conditions and temperatures are less favorable for removal by channel processes. Nevertheless, the percentage of annual removal occurring during above average flow periods was similar to that during low flow periods. Predicted river network removal proportions are most sensitive to loading rates, spatial heterogeneity of inputs, and the form of the removal process equation during typical base flow conditions. However, comparison with observations indicates that removal by the river network is higher than predicted by the model at moderately high flows, suggesting additional removal processes are important at these times. Further increases in N input to the network will lead to disproportionate increases in N exports due to the limits imposed by process saturation.This work was funded by NSF-DEB- 0614282, NSF-OCE-9726921, NSF-DEB-0111410, and NSF-BCS- 0709685

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