Optimization of Solutions for the One Plant Protection Problem

Plant protection problems are simulated by a system of ordinary differential equations with given initial conditions. The sensitivity and resistance of pathogen subpopulations to fungicide mixtures, fungicide weathering, plant growth, etc. are taken into consideration. The system of equations is solved numerically for each set of initial conditions and parameters of the disease and fungicide applications. Optimization algorithms were investigated and a computer program was developed for optimization of these solutions. 14 typical cases of the disease were simulated and optimized in order to determine optimal fungicide treatments. The optimized strategy for fungicide application differs considerably from the commonly used method and seems to be an important new principle in plant protection. The approach developed in this study may be useful for a wide spectrum of purposes in the simulation of leaf diseases. It may also help the biologist to decrease or pinpoint experimental work and analyze its results and is perspective for plant disease control.     

Minimizing model fitting objectives that contain spurious local minima by bootstrap restarting

Objective functions that arise when fitting nonlinear models often contain local minima that are of little significance except for their propensity to trap minimization algorithms. The standard methods for attempting to deal with this problem treat the objective function as fixed and employ stochastic minimization approaches in the hope of randomly jumping out of local minima. This article suggests a simple trick for performing such minimizations that can be employed in conjunction with most conventional nonstochastic fitting methods. The trick is to stochastically perturb the objective function by bootstrapping the data to be fit. Each bootstrap objective shares the large-scale structure of the original objective but has different small-scale structure. Minimizations of bootstrap objective functions are alternated with minimizations of the original objective function starting from the parameter values with which minimization of the previous bootstrap objective terminated. An example is presented, fitting a nonlinear population dynamic model to population dynamic data and including a comparison of the suggested method with simulated annealing. Convergence diagnostics are discussed.     

A single ancient origin of brood parasitism in African finches: implications for host-parasite coevolution

Robust phylogenies for brood-parasitic birds, their hosts, and nearest nesting relatives provide the framework to address historical questions about host-parasite coevolution and the origins of parasitic behavior. We tested phylogenetic hypotheses for the two genera of African brood-parasitic finches, Anomalospiza and Vidua, using mitochondrial DNA sequence data from 43 passeriform species. Our analyses strongly support a sister relationship between Vidua and Anomalospiza, leading to the conclusion that obligate brood parasitism evolved only once in African finches rather than twice, as has been the conventional view. In addition, the parasitic finches (Viduidae) are not recently derived from either weavers (Ploceidae) or grassfinches (Estrildidae), but represent a third distinct lineage. Among these three groups, the parasitic finches and estrildids, which includes the hosts of all 19 Vidua species, are sister taxa in all analyses of our full dataset. Many characters shared by Vidua and estrildids, including elaborate mouth markings in nestlings, unusual begging behavior, and immaculate white eggs, can therefore be attributed to common ancestry rather than convergent evolution. The host-specificity of mouth mimicry in Vidua species, however, is clearly the product of subsequent host-parasite coevolution. The lineage leading to Anomalospiza switched to parasitizing more distantly related Old World warblers (Sylviidae) and subsequently lost these characteristics. Substantial sequence divergence between Vidua and Anomalospiza indicates that the origin of parasitic behavior in this clade is ancient (approximately 20 million years ago), a striking contrast to the recent radiation of extant Vidua. We suggest that the parasitic finch lineage has experienced repeated cycles of host colonization, speciation, and extinction through their long history as brood parasites and that extant Vidua species represent only the latest iterations of this process. This dynamic process may account for a significantly faster rate of DNA sequence evolution in parasitic finches as compared to estrildids and other passerines. Our study reduces by one the tally of avian lineages in which obligate brood parasitism has evolved and suggests an origin of parasitism that involved relatively closely related species likely to accept and provide appropriate care to parasitic young. Given the ancient origin of parasitism in African finches, ancestral estrildids must have been parasitized well before the diversification of extant Vidua, suggesting a long history of coevolution between these lineages preceding more recent interactions between specific hosts and parasites.     

l-Arginine Effects on Na+ Transport in M-1 Mouse Cortical Collecting Duct Cells—A Cationic Amino Acid Absorbing Epithelium

The effect of l-arginine on transepithelial ion transport was examined in cultured M-1 mouse renal cortical collecting duct (CCD) cells using continuous short circuit current (I _SC ) measurements in HCO₃ ⁻/CO₂ buffered solution. Steady state I _SC averaged 73.8 ± 3.2 μA/cm² (n= 126) and was reduced by 94 ± 0.6% (n= 16) by the apical addition of 100 μm amiloride. This confirms that the predominant electrogenic ion transport in M-1 cells is Na⁺ absorption via the epithelial sodium channel (ENaC). Experiments using the cationic amino acid l-lysine (radiolabeled) as a stable arginine analogue show that the combined activity of an apical system y⁺ and a basal amino acid transport system y⁺L are responsible for most cationic amino acid transport across M-1 cells. Together they generate net absorptive cationic amino acid flux. Application of l-arginine (10 mm) either apically or basolaterally induced a transient peak increase in I _SC averaging 36.6 ± 5.4 μA/cm² (n= 19) and 32.0 ± 7.2 μA/cm² (n= 8), respectively. The response was preserved in the absence of bath Cl⁻ (n= 4), but was abolished either in the absence of apical Na⁺ (n= 4) or by apical addition of 100 μm amiloride (n= 6). l-lysine, which cannot serve as a precursor of NO, caused a response similar to that of l-arginine (n= 4); neither L-NMMA (100 μm; n= 3) nor L-NAME (1 mm; n= 4) (both NO-synthase inhibitors) affected the I _SC response to l-arginine. The effects of arginine or lysine were replicated by alkalinization that mimicked the transient alkalinization of the bath solution upon addition of these amino acids. We conclude that in M-1 cells l-arginine stimulates Na⁺ absorption via a pH-dependent, but NO-independent mechanism. The observed net cationic amino acid absorption will counteract passive cationic amino acid leak into the CCD in the presence of electrogenic Na⁺ transport, consistent with reports of stimulated expression of Na⁺ and cationic amino acid transporters by aldosterone. Received: 11 September 2000/Revised: 6 December 2000     

Balance control during an arm raising movement in bipedal stance: which biomechanical factor is controlled?

In order to obtain new insight into the control of balance during arm raising movements in bipedal stance, we performed a biomechanical analysis of kinematics and dynamical aspects of arm raising movements by combining experimental work, large-scale models of the body, and techniques simulating human behavior. A comparison between experimental and simulated joint kinematics showed that the minimum torque change model yielded realistic trajectories. We then performed an analysis based on computer simulations. Since keeping the center of pressure (CoP) and the projection of the center of mass (CoM) inside the support area is essential for equilibrium, we modeled an arm raising movement where displacement of one or the other variable is limited. For this optimization model, the effects of adding equilibrium constraints on movement trajectories were investigated. The results show that: (a) the choice of the regulated variable influences the strategy adopted by the system and (b) the system was not able to regulate the CoM for very fast movements without compromising its balance. Consequently, we suggest that the system is able to maintain balance while raising the arm by only controlling the CoP. This may be done mainly by using hip mechanisms and controlling net ankle torque.     

Domain swapping of CD4 upon dimerization

It has recently been shown that disulfide bond Cys130-Cys159 in domain 2 of monomeric CD4 is involved in the formation of CD4 disulfide-bonded dimers on cell surfaces and that it can influence the permissiveness of cells to HIV infection. Because this disulfide bond is buried in the monomer, a large conformational change must take place in order to allow for such disulfide exchange. Using standard optimization techniques, whose efficiency was first checked in the well-documented CD2 case, we have shown that 3D domain swapping is a likely candidate for the conformational change, the hinge loop, or linker, being loop E-F. Indeed, as a consequence of domain swapping, because Cys130 and Cys159 belong to beta-strands C and F, respectively, two disulfide bonds become established between Cys130 in one monomer and Cys159 in the other one. Such a disulfide exchange has already been observed when the nuclear magnetic resonance (NMR) structure of the prion protein was compared to the crystallographic, dimeric one. In both cases, domain swapping implies disulfide exchange because the linker is located in the sequence between two disulfide-bonded cysteines. As in the CD2 case, the proposed configuration of the CD4 dimer is found as a pair of neighboring monomers in the crystallographic unit cell. Moreover, because in this configuration the epitope of monoclonal antibody MT151, which does not compete with Gp120 for CD4 binding, is in the cleft between the pair of CD4 monomers, it is suggested that MT151 achieves its HIV-blocking activity by interfering with the formation of CD4 domain-swapped dimers on cell surface.     

All-atom folding of the three-helix HIV accessory protein with an adaptive parallel tempering method

All-atom protein structure prediction from the amino acid sequence alone remains an important goal of biophysical chemistry. Recent progress in force field development and validation suggests that the PFF01 free-energy force field correctly predicts the native conformation of various helical proteins as the global optimum of its free-energy surface. Reproducible protein structure prediction requires the availability of efficient optimization methods to locate the global minima of such complex potentials. Here we investigate an adapted version of the parallel tempering method as an efficient parallel stochastic optimization method for protein structure prediction. Using this approach we report the reproducible all-atom folding of the three-helix 40 amino acid HIV accessory protein from random conformations to within 2.4 A backbone RMS deviation from the experimental structure with modest computational resources.     

Prediction of protein tertiary structure using PROFESY, a novel method based on fragment assembly and conformational space annealing

A novel method for ab initio prediction of protein tertiary structures, PROFESY (PROFile Enumerating SYstem), is proposed. This method utilizes the secondary structure prediction information of a query sequence and the fragment assembly procedure based on global optimization. Fifteen-residue-long fragment libraries are constructed using the secondary structure prediction method PREDICT, and fragments in these libraries are assembled to generate full-length chains of a query protein. Tertiary structures of 50 to 100 conformations are obtained by minimizing an energy function for proteins, using the conformational space annealing method that enables one to sample diverse low-lying local minima of the energy. We apply PROFESY for benchmark tests to proteins with known structures to demonstrate its feasibility. In addition, we participated in CASP5 and applied PROFESY to four new-fold targets for blind prediction. The results are quite promising, despite the fact that PROFESY was in its early stages of development. In particular, PROFESY successfully provided us the best model-one structure for the target T0161.     

Emerging technologies in therapeutic ultrasound: Thermal ablation to gene delivery

Ultrasound is used today in medicine as a modality for diagnostic imaging. Recently, there have been numerous reports on the application of thermal and nonthermal ultrasound energy for treating various diseases. In addition to thermal ablation of tumors, non-thermal ultrasound combined with drugs and genes have led to much excitement especially for cancer treatment, vascular diseases, and regenerative medicine. Ultrasound energy can enhance the effects of thrombolytic agents such as urokinase for treatment of stroke and acute myocardial infarction. New ultrasound technologies have resulted in advanced devices such as a) ultrasound catheters, b) Non-invasive methods as high intensity focused ultrasound (HIFU) in conjunction with MRI and CT is already being applied in the clinical field, c) Chemical activation of drugs by ultrasound energy for treatment of tumors is another new field recently termed "Sonodynamic Therapy", and d) Combination of genes and microbubble have induced great hopes for ideal gene therapy (sonoporation). Various examples of ultrasound combined modalities are under investigation which could lead to revolutionary therapy.     

Sampling Plan Optimization: A Data Review and Sampling Frequency Evaluation Process

Lawrence Livermore National Laboratory (LLNL) uses a cost-effective sampling (CES) methodology to evaluate and review ground water contaminant data and optimize the site's ground water monitoring plan. The CES methodology is part of LLNL's regulatory approved compliance monitoring plan (Lamarre et al., 1996 Lamarre, A. L., Nichols, E. M., Berg, L. L., Dresen, M. D., Gelinas, R. J., Bainer, R. W. and Folsom, E. N. 1996. Compliance monitoring plan for the Lawrence Livermore National Laboratory Livermore Site UCRL-AR-120936 [Google Scholar]). It allows LLNL to adjust the ground water sampling plan every quarter in response to changing conditions at the site. Since the use of the CES methodology has been approved by the appropriate regulatory agencies, such adjustments do not need additional regulatory approval. This permits LLNL to respond more quickly to changing conditions. The CES methodology bases the sampling frequency for each location on trend, variability, and magnitude statistics describing the contaminants at that location, and on the input of the technical staff (hydrologists, chemists, statisticians, and project leaders). After initial setup is complete, each application of CES takes only a few days for as many as 400 wells. Effective use of the CES methodology requires sufficient data, an understanding of contaminant transport at the site, and an adequate number of monitoring wells downgradient of the contamination. The initial implementation of CES at LLNL in 1992 produced a 40% reduction in the required number of annual routine ground water samples at LLNL. This has saved LLNL $390,000 annually in sampling, analysis, and data management costs.