Structure optimization combining soft-core interaction functions, the diffusion equation method, and molecular dynamics

Smoothing the potential energy surface for structure optimization is a general and commonly applied strategy. We propose a combination of soft-core potential energy functions and a variation of the diffusion equation method to smooth potential energy surfaces, which is applicable to complex systems such as protein structures; The performance of the method was demonstrated by comparison with simulated annealing using the refinement of the undecapeptide Cyclosporin A as a test case. Simulations were repeated many times using different initial conditions and structures since the methods are heuristic and results are only meaningful in a statistical sense.

Proton transport model in the ionosphere .1. Multistream approach of the transport equations

The suprathermal particles, electrons and protons, coming from the magnetosphere and precipitating into the high-latitude atmosphere are an energy source of the Earth's ionosphere. They interact with ambient thermal gas through inelastic and elastic collisions. The physical quantities perturbed by these precipitations, such as the heating rate, the electron production rate, or the emission intensities, can be provided in solving the kinetic stationary Boltzmann equation. This equation yields particle fluxes as a function of altitude, energy, and pitch angle. While this equation has been solved through different ways for the electron transport and fully tested, the proton transport is more complicated. Because of charge-changing reactions, the latter is a set of two-coupled transport equations that must be solved: one for protons and the other for H atoms. We present here a new approach that solves the multistream proton/hydrogen transport equations encompassing the collision angular redistributions and the magnetic mirroring effect. In order to validate our model we discuss the energy conservation and we compare with another model under the same inputs and with rocket observations. The influence of the angular redistributions is discussed in a forthcoming paper.

New Specific Equation to Estimate Resting Energy Expenditure in Severely Obese Patients

Calculating the estimated resting energy expenditure (REE) in severely obese patients is useful, but there is controversy concerning the effectiveness of available prediction equations (PE) using body weight (BW). We evaluated the efficacy of REE equations against indirect calorimetry (IC) in severely obese subjects and aimed to develop a new equation based on body composition compartments. One hundred and twenty severely obese patients had their REE measured (MREE) by IC and compared to the most commonly used PE (Harris-Benedict (HB), Ireton-Jones, Owen, and Mifflin St. Jeor). In a random sample (n = 60), a new REE equation based on fat-free mass (FFM) was developed and validated. All PE studied failed to estimate REE in severe obesity (low concordance correlation coefficient (CCC) and limits of agreement of nearly 50% of the sample +/- 10% of MREE). The HB equation using actual BW exhibited good results for all samples when compared to IC (2,117 +/- 518 kcal/day by HB vs. 2,139 +/- 423 kcal/day by MREE, P > 0.01); these results were blunted when patients were separated by gender (2,771 vs. 2,586 kcal/day, P < 0.001 in males and 1,825 vs. 1,939 kcal/day, P < 0.001 in females). A new resting energy expenditure equation prediction was developed using FFM, Horie-Waitzberg, & Gonzalez, expressed as 560.43 + (5.39 x BW) + (14.14 x FFM). The new resting energy expenditure equation prediction, which uses FFM and BW, demonstrates higher accuracy, precision, CCC, and limits of agreement than the standard PE in patients when compared to MREE (2,129 +/- 45 kcal/day vs. 2,139 +/- 423 kcal/day, respectively, P = 0.1). The new equation developed to estimate REE, which takes into account both FFM and BW, provides better results than currently available equations.

Conservation of hepatitis C virus nonstructural protein 3 amino acid sequence in viral isolates during liver transplantation

As a consequence of selective pressure exerted by the immune response during hepatitis C virus (HCV) infection, a high rate of nucleotide mutations in the viral genome is observed which leads to the emergence of viral escape mutants. The aim of this study was to evaluate the evolution of the amino acid (aa) sequence of the HCV nonstructural protein 3 (NS3) in viral isolates after liver transplantation. Six patients with HCV-induced liver disease undergoing liver transplantation (LT) were followed up for sequence analysis. Hepatitis C recurrence was observed in all patients after LT. The rate of synonymous (dS) nucleotide substitutions was much higher than that of nonsynonymous (dN) ones in the NS3 encoding region. The high values of the dS/dN ratios suggest no sustained adaptive evolution selection pressure and, therefore, absence of specific NS3 viral populations. Clinical genotype assignments were supported by phylogenetic analysis. Serial samples from each patient showed lower mean nucleotide genetic distance when compared with samples of the same HCV genotype and subtype. The NS3 samples studied had an N-terminal aa sequence with several differences as compared with reference ones, mainly in genotype 1b-infected patients. After LT, as compared with the sequences before, a few reverted aa substitutions and several established aa substitutions were observed at the N-terminal of NS3. Sites described to be involved in important functions of NS3, notably those of the catalytic triad and zinc binding, remained unaltered in terms of aa sequence. Rare or frequent aa substitutions occurred indiscriminately in different positions. Several cytotoxic T lymphocyte epitopes described for HCV were present in our 1b samples. Nevertheless, the deduced secondary structure of the NS3 protease showed a few alterations in samples from genotype 3a patients, but none were seen in 1b cases. Our data, obtained from patients under important selective pressure during LT, show that the NS3 protease remains well conserved, mainly in HCV 3a patients. It reinforces its potential use as an antigenic candidate for further studies aiming at the development of a protective immune response.

Contributions of Non-consumptive Wildlife Tourism to Conservation

Wildlife tourism has the potential to contribute to conservation through a variety of mechanisms. This chapter presents a preliminary assessment of the extent to which this potential is currently being realised, comparing tourism based on viewing of animals in captive settings (with a focus on federated zoos) with that in free-ranging situations (wildlife watching). The key mechanisms involved are: direct wildlife management and research; use of income derived from wildlife tourism to fund conservation; education of visitors to behave in a more conservation-friendly manner; political lobbying in support of conservation; and provision of a socio-economic incentive for conservation. All of these occur in at least some zoos and wildlife-watching situations, and collectively the contribution of non-consumptive wildlife tourism to conservation is significant, though impossible to quantify. The key strengths of the zoo sector in this regard are its inputs into captive breeding and its potential to educate large numbers of people. in contrast, wildlife watching provides significant socio-economic incentives for conservation of natural habitats. There seem to be significant opportunities for expanding the role of non-consumptive wildlife tourism in conservation.