Chaperonin-facilitated protein folding: optimization of rate and yield by an iterative annealing mechanism.

We develop a heuristic model for chaperonin-facilitated protein folding, the iterative annealing mechanism, based on theoretical descriptions of "rugged" conformational free energy landscapes for protein folding, and on experimental evidence that (i) folding proceeds by a nucleation mechanism whereby correct and incorrect nucleation lead to fast and slow folding kinetics, respectively, and (ii) chaperonins optimize the rate and yield of protein folding by an active ATP-dependent process. The chaperonins GroEL and GroES catalyze the folding of ribulose bisphosphate carboxylase at a rate proportional to the GroEL concentration. Kinetically trapped folding-incompetent conformers of ribulose bisphosphate carboxylase are converted to the native state in a reaction involving multiple rounds of quantized ATP hydrolysis by GroEL. We propose that chaperonins optimize protein folding by an iterative annealing mechanism; they repeatedly bind kinetically trapped conformers, randomly disrupt their structure, and release them in less folded states, allowing substrate proteins multiple opportunities to find pathways leading to the most thermodynamically stable state. By this mechanism, chaperonins greatly expand the range of environmental conditions in which folding to the native state is possible. We suggest that the development of this device for optimizing protein folding was an early and significant evolutionary event.

Toward a mechanism for GroEL.GroES chaperone activity: an ATPase-gated and -pulsed folding and annealing cage.

Free GroEL binds denatured proteins very tightly: it retards the folding of barnase 400-fold and catalyzes unfolding fluctuations in native barnase and its folding intermediate. GroEL undergoes an allosteric transition from its tight-binding T-state to a weaker binding R-state on the cooperative binding of nucleotides (ATP/ADP) and GroES. The preformed GroEL.GroES.nucleotide complex retards the folding of barnase by only a factor of 4, and the folding rate is much higher than the ATPase activity that releases GroES from the complex. Binding of GroES and nucleotides to a preformed GroEL.denatured-barnase complex forms an intermediately fast-folding complex. We propose the following mechanism for the molecular chaperone. Denatured proteins bind to the resting GroEL.GroES.nucleotide complex. Fast-folding proteins are ejected as native structures before ATP hydrolysis. Slow-folding proteins enter chaperoning cycles of annealing and folding after the initial ATP hydrolysis. This step causes transient release of GroES and formation of the GroEL.denatured-protein complexes with higher annealing potential. The intermediately fast-folding complex is formed on subsequent rebinding of GroES. The ATPase activity of GroEL.GroES is thus the gatekeeper that selects for initial entry of slow-folding proteins to the chaperone action and then pumps successive transitions from the faster-folding R-states to the tighter-binding/stronger annealing T-states. The molecular chaperone acts as a combination of folding cage and an annealing machine.

Temperatures at the last interglacial simulated by a coupled ocean-atmosphere climate model

The last interglacial (Eemian, 125,000 years ago) has generally been considered the warmest time period in the last 200,000 years and thus sometimes been used as a reference for greenhouse projections. Herein we report results from a coupled ocean-atmosphere climate model of the surface temperature response to changes in the radiative forcing at the last interglacial. Although the model generates the expected summer warming in the northern hemisphere, winter cooling of a comparable magnitude occurs over North Africa and tropical Asia. The global annual mean temperature for the Eemian run is 0.3 degrees C cooler than the control run. Validation of simulated sea surface temperatures (SSTs) against reconstructed SSTs supports this conclusion and also the assumption that the flux correction, fitted for the present state, operates satisfactorily for modest perturbations. Our results imply that contrary to conventional expectations, Eemian global temperatures may already have been reached by the mid 20th century.

Estimación del movimiento coherente: computación evolutiva como alternativa al annealing determinista

Comunicación presentada en SCETA, Seminario Sobre Computación Evolutiva, celebrado en la VII Conferencia de la Asociación Española para la Inteligencia Artificial, CAEPIA, Málaga, 12-14 noviembre 1997.

Mechanical annealing of metallic electrodes at the atomic scale

The process of creating an atomically defined and robust metallic tip is described and quantified using measurements of contact conductance between gold electrodes and numerical simulations. Our experiments show how the same conductance behavior can be obtained for hundreds of cycles of formation and rupture of the nanocontact by limiting the indentation depth between the two electrodes up to a conductance value of approximately 5G0 in the case of gold. This phenomenon is rationalized using molecular dynamics simulations together with density functional theory transport calculations which show how, after repeated indentations (mechanical annealing), the two metallic electrodes are shaped into tips of reproducible structure. These results provide a crucial insight into fundamental aspects relevant to nanotribology or scanning probe microscopies.

Evaluation of the pathogenicity of multiple isolates of Beauveria bassiana (Hypocreales: Clavicipitaceae) on Rhynchophorus ferrugineus (Coleoptera: Dryophthoridae) for the assessment of a solid formulation under simulated field conditions

A solid state formulation of Beauveria bassiana (Balsamo) Vuillemin has been developed for biological control of the Red Palm Weevil (RPW), Rhynchophorus ferrugineus (Olivier, 1790). Two kinds of bioassays (dry conidia and dipping) using 10 isolates from several coleopterans in Mediterranean environments, identified 2 RPW derived isolates (193 and 203) as most pathogenic to RPW larvae and adults (zero survival within first 4–5 d for dry conidia, and 14 and 23 d for dipping bioassays). Isolate 203 (5.1 × 108 ± 1.9 × 108 conidia g-1) was formulated with fragmented date seed into solid granules and tested in palms infested with RPW under semi-field conditions in Feb, Apr/May and Jun of both 2007 and 2008. Beauveria bassiana significantly reduced RPW adult survival with respect to controls in May 2007 and in the Apr/Jun 2008 experiments. Total RPW adult mortality was achieved within 30 days for all B. bassiana treatments, and was associated with increasing numbers of insects with signs of mycosis in 2008 experiments. Beauveria bassiana formulation reduced RPW multiplication in artificially infested palms compared to controls, and a positive correlation between numbers of larvae and time post-infestation was recorded. The suppression of RPW adult populations by B. bassiana persisted for at least 3 months under semi-field conditions. The Beauveria bassiana solid formulation, which induces great adult mortality and persistence in the field, could be applied as a preventive as well as a curative treatment for the integrated management of RPW.

Simulated magnetic field expulsion in neutron star cores

The study of long-term evolution of neutron star (NS) magnetic fields is key to understanding the rich diversity of NS observations, and to unifying their nature despite the different emission mechanisms and observed properties. Such studies in principle permit a deeper understanding of the most important parameters driving their apparent variety, e.g. radio pulsars, magnetars, X-ray dim isolated NSs, gamma-ray pulsars. We describe, for the first time, the results from self-consistent magnetothermal simulations considering not only the effects of the Hall-driven field dissipation in the crust, but also adding a complete set of proposed driving forces in a superconducting core. We emphasize how each of these core-field processes drive magnetic evolution and affect observables, and show that when all forces are considered together in vectorial form, the net expulsion of core magnetic flux is negligible, and will have no observable effect in the crust (consequently in the observed surface emission) on megayear time-scales. Our new simulations suggest that strong magnetic fields in NS cores (and the signatures on the NS surface) will persist long after the crustal magnetic field has evolved and decayed, due to the weak combined effects of dissipation and expulsion in the stellar core.

Organic distributed feedback laser to monitor solvent extraction upon thermal annealing in solution-processed polymer films

Solution-processed polymer films are used in multiple technological applications. The presence of residual solvent in the film, as a consequence of the preparation method, affects the material properties, so films are typically subjected to post-deposition thermal annealing treatments aiming at its elimination. Monitoring the amount of solvent eliminated as a function of the annealing parameters is important to design a proper treatment to ensure complete solvent elimination, crucial to obtain reproducible and stable material properties and therefore, device performance. Here we demonstrate, for the first time to our knowledge, the use of an organic distributed feedback (DFB) laser to monitor with high precision the amount of solvent extracted from a spin-coated polymer film as a function of the thermal annealing time. The polymer film of interest, polystyrene in the present work, is doped with a small amount of a laser dye as to constitute the active layer of the laser device and deposited over a reusable DFB resonator. It is shown that solvent elimination translates into shifts in the DFB laser wavelength, as a consequence of changes in film thickness and refractive index. The proposed method is expected to be applicable to other types of annealing treatments, polymer-solvent combinations or film deposition methods, thus constituting a valuable tool to accurately control the quality and reproducibility of solution-processed polymer thin films.

Implementation of non-local boundary layer schemes in the Regional Atmospheric Modeling System and its impact on simulated mesoscale circulations

This paper proposes the implementation of different non-local Planetary Boundary Layer schemes within the Regional Atmospheric Modeling System (RAMS) model. The two selected PBL parameterizations are the Medium-Range Forecast (MRF) PBL and its updated version, known as the Yonsei University (YSU) PBL. YSU is a first-order scheme that uses non-local eddy diffusivity coefficients to compute turbulent fluxes. It is based on the MRF, and improves it with an explicit treatment of the entrainment. With the aim of evaluating the RAMS results for these PBL parameterizations, a series of numerical simulations have been performed and contrasted with the results obtained using the Mellor and Yamada (MY) scheme, also widely used, and the standard PBL scheme in the RAMS model. The numerical study carried out here is focused on mesoscale circulation events during the summer, as these meteorological situations dominate this season of the year in the Western Mediterranean coast. In addition, the sensitivity of these PBL parameterizations to the initial soil moisture content is also evaluated. The results show a warmer and moister PBL for the YSU scheme compared to both MRF and MY. The model presents as well a tendency to overestimate the observed temperature and to underestimate the observed humidity, considering all PBL schemes and a low initial soil moisture content. In addition, the bias between the model and the observations is significantly reduced moistening the initial soil moisture of the corresponding run. Thus, varying this parameter has a positive effect and improves the simulated results in relation to the observations. However, there is still a significant overestimation of the wind speed over flatter terrain, independently of the PBL scheme and the initial soil moisture used, even though a different degree of accuracy is reproduced by RAMS taking into account the different sensitivity tests.

Effects of various aging heat treatments and solution-annealing and aging heat treatments on tensile, creep, and stress-rupture strengths of inconel x sheet to temperatures of 1,400 degrees F /

Cover title.

Car-barrier impact response of a computer simulated Mustang. Final report.

Automobile Manufacturers Association, Detroit, Mich.

Development and implementation of a rear vision device test protocol. Volume II - simulated-use testing. Final report.

National Highway Traffic Safety Administration, Washington, D.C.

Response of Enrico Fermi reactor to TNT simulated nuclear accidents /

"Published January 1964."--i.