Showing papers by "ETH Zurich published in 1999"

Multiobjective evolutionary algorithms: a comparative case study and the strength Pareto approach

Abstract: Evolutionary algorithms (EAs) are often well-suited for optimization problems involving several, often conflicting objectives. Since 1985, various evolutionary approaches to multiobjective optimization have been developed that are capable of searching for multiple solutions concurrently in a single run. However, the few comparative studies of different methods presented up to now remain mostly qualitative and are often restricted to a few approaches. In this paper, four multiobjective EAs are compared quantitatively where an extended 0/1 knapsack problem is taken as a basis. Furthermore, we introduce a new evolutionary approach to multicriteria optimization, the strength Pareto EA (SPEA), that combines several features of previous multiobjective EAs in a unique manner. It is characterized by (a) storing nondominated solutions externally in a second, continuously updated population, (b) evaluating an individual's fitness dependent on the number of external nondominated points that dominate it, (c) preserving population diversity using the Pareto dominance relationship, and (d) incorporating a clustering procedure in order to reduce the nondominated set without destroying its characteristics. The proof-of-principle results obtained on two artificial problems as well as a larger problem, the synthesis of a digital hardware-software multiprocessor system, suggest that SPEA can be very effective in sampling from along the entire Pareto-optimal front and distributing the generated solutions over the tradeoff surface. Moreover, SPEA clearly outperforms the other four multiobjective EAs on the 0/1 knapsack problem.

SENSE: Sensitivity Encoding for fast MRI

Abstract: The invention relates to a method of parallel imaging for obtaining images by means of magnetic resonance (MR). The method includes the simultaneous measurement of sets of MR singals by an array of receiver coils, and the reconstruction of individual receiver coil images from the sets of MR signals. In order to reduce the acquisition time, the distance between adjacent phase encoding lines in k-space is increased, compared to standard Fourier imaging, by a non-integer factor smaller than the number of receiver coils. This undersampling gives rise to aliasing artifacts in the individual receiver coil images. An unaliased final image with the same field of view as in standard Fourier imaging is formed from a combination of the individual receiver coil images whereby account is taken of the mutually different spatial sensitivities of the receiver coils at the positions of voxels which in the receiver coil images become superimposed by aliasing. This requires the solution of a linear equation by means of the generalised inverse of a sensitivity matrix. The reduction of the number of phase encoding lines by a non-integer factor compared to standard Fourier imaging provides that different numbers of voxels become superimposed (by aliasing) in different regions of the receiver coil images. This effect can be exploited to shift residual aliasing artifacts outside the area of interest.

Rietveld refinement guidelines

Abstract: A set of general guidelines for structure refinement using the Rietveld (whole-profile) method has been formulated by the International Union of Crystallography Commission on Powder Diffraction. The practical rather than the theoretical aspects of each step in a typical Rietveld refinement are discussed with a view to guiding newcomers in the field. The focus is on X-ray powder diffraction data collected on a laboratory instrument, but features specific to data from neutron (both constant-wavelength and time-of-flight) and synchrotron radiation sources are also addressed. The topics covered include (i) data collection, (ii) background contribution, (iii) peak-shape function, (iv) refinement of profile parameters, (v) Fourier analysis with powder diffraction data, (vi) refinement of structural parameters, (vii) use of geometric restraints, (viii) calculation of e.s.d.'s, (ix) interpretation of R values and (x) some common problems and possible solutions.

Peptide Folding: When Simulation Meets Experiment

Abstract: Accurate reproduction of the mechanism of peptide folding in solution and conformational preferences as a function of amino acid sequence is possible with atomic level dynamics simulations. For example, the simulations correctly predict a left-handed 31-helical fold for the β-heptapeptide 1 (the molecular model is shown in the picture) and a right-handed helical fold for the β-hexapeptide 2, as was confirmed by NMR spectroscopy.

Comparison of multiobjective evolutionary algorithms: empirical results

Abstract: In this paper, we provide a systematic comparison of various evolutionary approaches to multiobjective optimization using six carefully chosen test functions. Each test function involves a particular feature that is known to cause difficulty in the evolutionary optimization process, mainly in converging to the Pareto-optimal front (e.g., multimodality and deception). By investigating these different problem features separately, it is possible to predict the kind of problems to which a certain technique is or is not well suited. However, in contrast to what was suspected beforehand, the experimental results indicate a hierarchy of the algorithms under consideration. Furthermore, the emerging effects are evidence that the suggested test functions provide sufficient complexity to compare multiobjective optimizers. Finally, elitism is shown to be an important factor for improving evolutionary multiobjective search.

Channel parameter estimation in mobile radio environments using the SAGE algorithm

Abstract: This study investigates the application potential of the SAGE (space-alternating generalized expectation-maximization) algorithm to jointly estimate the relative delay, incidence azimuth, Doppler frequency, and complex amplitude of impinging waves in mobile radio environments The performance, ie, high-resolution ability, accuracy, and convergence rate of the scheme, is assessed in synthetic and real macro- and pico-cellular channels The results indicate that the scheme overcomes the resolution limitation inherent to classical techniques like the Fourier or beam-forming methods In particular, it is shown that waves which exhibit an arbitrarily small difference in azimuth can be easily separated as long as their delays or Doppler frequencies differ by a fraction of the intrinsic resolution of the measurement equipment Two waves are claimed to be separated when the mean-squared estimation errors (MSEEs) of the estimates of their parameters are close to the corresponding Cramer-Rao lower bounds (CRLBs) derived in a scenario where only a single wave is impinging The adverb easily means that the MSEEs rapidly approach the CLRBs, ie, within less than 20 iteration cycles Convergence of the log-likelihood sequence is achieved after approximately ten iteration cycles when the scheme is applied in real channels In this use, the estimated dominant waves can be related to a scatterer/reflector in the propagation environment The investigations demonstrate that the SAGE algorithm is a powerful high-resolution tool that can be successfully applied for parameter extraction from extensive channel measurement data, especially for the purpose of channel modeling

Engineered glycoforms of an antineuroblastoma IgG1 with optimized antibody-dependent cellular cytotoxic activity

Abstract: The glycosylation pattern of chCE7, an antineuroblastoma chimeric IgG1, was engineered in Chinese hamster ovary cells with tetracycline-regulated expression of beta(1,4)-N-acetylglucosaminyltransferase III (GnTIII), a glycosyltransferase catalyzing formation of bisected oligosaccharides that have been implicated in antibody-dependent cellular cytotoxicity (ADCC). Measurement of the ADCC activity of chCE7 produced at different tetracycline levels showed an optimal range of GnTIII expression for maximal chCE7 in vitro ADCC activity, and this activity correlated with the level of constant region-associated, bisected complex oligosaccharides determined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The new optimized variants of chCE7 exhibit substantial ADCC activity and, hence, may be useful for treatment of neuroblastoma. The strategy presented here should be applicable to optimize the ADCC activity of other therapeutic IgGs.

Carrier-envelope offset phase control: A novel concept for absolute optical frequency measurement and ultrashort pulse generation

Abstract: The shortest pulses periodically emitted directly from a mode-locked Ti:sapphire laser are approaching the two-optical-cycle range. In this region, the phase of the optical carrier with respect to the pulse envelope becomes important in nonlinear optical processes such as high-harmonic generation. Because there are no locking mechanisms between envelope and carrier inside a laser, their relative phase offset experiences random fluctuations. Here, we propose several novel methods to measure and to stabilize this carrier-envelope offset (CEO) phase with sub-femtosecond uncertainty. The stabilization methods are an important prerequisite for attosecond pulse generation schemes. Short and highly periodic pulses of a two-cycle laser correspond to an extremely wide frequency comb of equally spaced lines, which can be used for absolute frequency measurements. Using the proposed phase-measurement methods, it will be possible to phase-coherently link any unknown optical frequency within the comb spectrum to a primary microwave standard. Experimental studies using a sub-6-fs Ti:sapphire laser suggesting the feasibility of carrier-envelope phase control are presented.

Preparation of nucleosome core particle from recombinant histones.

Abstract: Publisher Summary This chapter describes the preparation method of nucleosome core particles (NCPs) from recombinant histones. The ability to make defined NCPs, or arrays of nucleosomes, from histone proteins expressed in bacteria has several advantages over previously used methods using histones isolated from natural sources. The chapter discusses protocols for the overexpression and purification of histones H2A, H2B, H3, and H4, both as full-length proteins and as corresponding trypsin-resistant globular domains. The chapter presents a method for the refolding and purification of a histone octamer from denatured recombinant histone proteins together with a protocol for the assembly and purification of a nucleosome core particle using 146 base pairs of DNA. The purity and homogeneity of the final core-particle preparation are assessed by a high-resolution gel shift assay. The chapter presents a flow chart that describes the procedures involved in the preparation of synthetic nucleosomes.

Impaired myocardial angiogenesis and ischemic cardiomyopathy in mice lacking the vascular endothelial growth factor isoforms VEGF164 and VEGF188.

Abstract: Impaired myocardial angiogenesis and ischemic cardiomyopathy in mice lacking the vascular endothelial growth factor isoforms VEGF 164 and VEGF 188

Nature of the Earth's earliest crust from hafnium isotopes in single detrital zircons

Abstract: Continental crust forms from, and thus chemically depletes, the Earth's mantle. Evidence that the Earth's mantle was already chemically depleted by melting before the formation of today's oldest surviving crust has been presented in the form of Sm–Nd isotope studies of 3.8–4.0 billion years old rocks from Greenland1,2,3,4,5 and Canada5,6,7. But this interpretation has been questioned because of the possibility that subsequent perturbations may have re-equilibrated the neodymium-isotope compositions of these rocks8. Independent and more robust evidence for the origin of the earliest crust and depletion of the Archaean mantle can potentially be provided by hafnium-isotope compositions of zircon, a mineral whose age can be precisely determined by U–Pb dating, and which can survive metamorphisms4. But the amounts of hafnium in single zircon grains are too small for the isotopic composition to be precisely analysed by conventional methods. Here we report hafnium-isotope data, obtained using the new technique of multiple-collector plasma-source mass spectrometry9, for 37 individual grains of the oldest known terrestrial zircons (from the Narryer Gneiss Complex, Australia, with U–Pb ages of up to 4.14 Gyr (10–13). We find that none of the grains has a depleted mantle signature, but that many were derived from a source with a hafnium-isotope composition similar to that of chondritic meteorites. Furthermore, more than half of the analysed grains seem to have formed by remelting of significantly older crust, indicating that crustal preservation and subsequent reworking might have been important processes from earliest times.

Growth, annealing and recrystallization of zircon and preservation of monazite in high-grade metamorphism: conventional and in-situ U-Pb isotope, cathodoluminescence and microchemical evidence

Abstract: Zircon and monazite from granulite- to amphibolite-facies rocks of the Vosges mountains (central Variscan Belt, eastern France) were dated by ion-microprobe and conventional U-Pb techniques. Different granulites of igneous (so-called leptynites) and sedimentary origin (kinzigites) and their leucosomes were dated at 334.9 ± 3.6, 335.4 ± 3.6 and 336.7 ± 3.5 Ma (conventional age 335.4 ± 0.6 Ma). Subsequent growth stages of zircon were distinguished by secondary electron (SEM) and cathodoluminescence (CL) imaging: (1) subsolidus growth producing round anhedral morphologies and sector zoning; (2) appearance of an intergranular fluid or melt phase at incipient dehydration melting that first resulted in resorption of pre-existing zircons, followed by growth of acicular zircons or overgrowths on round zircons consisting of planar growth zoning; (3) advanced melting producing euhedral prismatic zircons with oscillatory zoning overgrowing the sector zones. Two further lithologies, the Kaysersberg granite and the Trois-Epis units, were both formerly considered as migmatites. The intrusion of the Kaysersberg granite was dated at 325.8 ± 4.8 Ma. The Trois-Epis unit was found to be the product of volume recrystallization of a former granulite, which occurred under amphibolite-facies conditions 327.9 ± 4.4 Ma ago. The amphibolite-facies overprint of the Trois-Epis zircons led to the complete rejuvenation of most of the zircon domains by annealing and replacement/recrystallization processes. Annealing is assumed to occur in strained lattice domains, which are possibly disturbed by high trace element contents and/or large differences in decay damage between adjacent growth zones. Investigation of cathodoluminescence structures reveals that the replacement occurs along curved chemical reaction fronts that proceed from the surface towards the interior of the zircon. The monazite U-Pb system still records the age of high-grade metamorphism at around 335 Ma. The chemical reagent responsible for the rejuvenation of zircon obviously left the monazite unaffected.

Elastic model-based segmentation of 3-D neuroradiological data sets

Abstract: This paper presents a new technique for the automatic model-based segmentation of three-dimensional (3-D) objects from volumetric image data. The development closely follows the seminal work of Taylor and Cootes on active shape models, but is based on a hierarchical parametric object description rather than a point distribution model. The segmentation system includes both the building of statistical models and the automatic segmentation of new image data sets via a restricted elastic deformation of shape models. Geometric models are derived from a sample set of image data which have been segmented by experts. The surfaces of these binary objects are converted into parametric surface representations, which are normalized to get an invariant object-centered coordinate system. Surface representations are expanded into series of spherical harmonics which provide parametric descriptions of object shapes. It is shown that invariant object surface parametrization provides a good approximation to automatically determine object homology in terms of sets of corresponding sets of surface points. Gray-level information near object boundaries is represented by 1-D intensity profiles normal to the surface. Considering automatic segmentation of brain structures as their driving application, the authors' choice of coordinates for object alignment was the well-accepted stereotactic coordinate system. Major variation of object shapes around the mean shape, also referred to as shape eigenmodes, are calculated in shape parameter space rather than the feature space of point coordinates. Segmentation makes use of the object shape statistics by restricting possible elastic deformations into the range of the training shapes. The mean shapes are initialized in a new data set by specifying the landmarks of the stereotactic coordinate system. The model elastically deforms, driven by the displacement forces across the object's surface, which are generated by matching local intensity profiles. Elastical deformations are limited by setting bounds for the maximum variations in eigenmode space. The technique has been applied to automatically segment left and right hippocampus, thalamus, putamen, and globus pallidus from volumetric magnetic resonance scans taken from schizophrenia studies. The results have been validated by comparison of automatic segmentation with the results obtained by interactive expert segmentation.

Dendritic asymmetry cannot account for directional responses of neurons in visual cortex.

Abstract: A simple model was proposed to account for the direction selectivity of neurons in the primary visual cortex, area V1. In this model, the temporal asymmetries in the summation of inhibition and excitation that produce directionality were generated by structural asymmetries in the tangential organization of the basal dendritic tree of cortical neurons. We reconstructed dendritic trees of neurons with known direction preferences and found no correlation between the small biases of a neuron's dendritic morphology and its direction preference. Detailed simulations indicated that even when the electrotonic asymmetries in the dendrites were extreme, as in cortical Meynert cells, the biophysical properties of single neurons could contribute only partially to the directionality of cortical neurons.

Nonlinear Predictive Control and Moving Horizon Estimation — An Introductory Overview

Abstract: In the past decade model predictive control (MPC) has become a preferred control strategy for a large number of processes. The main reasons for this preference include the ability to handle constraints in an optimal way and the flexible formulation in the time domain. Linear MPC schemes, i.e. MPC schemes for which the prediction is based on a linear description of the plant, are by now routinely used in a number of industrial sectors and the underlying control theoretic problems, like stability, are well studied. Nonlinear model predictive control (NMPC), i.e. MPC based on a nonlinear plant description, has only emerged in the past decade and the number of reported industrial applications is still fairly low. Because of its additional ability to take process nonlinearities into account, expectations on this control methodology are high.

Fading channels: how perfect need "perfect side information" be?

Abstract: The analysis of flat-fading channels is often performed under the assumption that the additive noise is white and Gaussian, and that the receiver has precise knowledge of the realization of the fading process. These assumptions imply the optimality of Gaussian codebooks and of scaled nearest-neighbor decoding. Here we study the robustness of this communication scheme with respect to errors in the estimation of the fading process. We quantify the degradation in performance that results from such estimation errors, and demonstrate the lack of robustness of this scheme. For some situations we suggest the rule of thumb that, in order to avoid degradation, the estimation error should be negligible compared to the reciprocal of the signal-to-noise ratio (SNR).

Metal fractionation between magmatic brine and vapor, determined by microanalysis of fluid inclusions

Abstract: The major and trace element compositions of individual fluid inclusions from a range of magmatic-hydrothermal ore deposits were analyzed by laser-ablation inductively coupled plasma-mass spectrometry, to explore the behavior of ore-forming components during fluid phase separation (“boiling”) in high-temperature saline fluid systems. Data from 13 samples showing unambiguous evidence for coeval trapping of a liquid brine and a coexisting vapor phase identify two groups of elements with drastically different geochemical behavior. Na, K, Fe, Mn, Zn, Rb, Cs, Ag, Sn, Pb, and Tl preferentially partition into the brine (probably as Cl complexes), whereas Cu, As, Au (probably as HS complexes), and B selectively partition into the vapor. Fluid phase separation is probably a major, previously underestimated process in the chemical differentiation that contributes to the extreme range of selective element enrichments in magmatic-hydrothermal systems, from deep plutons through porphyry-style and greisen deposits to epithermal mineralization and volcanic fumaroles.

The VersaKey framework: versatile group key management

Abstract: Middleware supporting secure applications in a distributed environment faces several challenges. Scalable security in the context of multicasting or broadcasting is especially hard when privacy and authenticity is to be assured to highly dynamic groups where the application allows participants to join and leave at any time. Unicast security is well-known and has widely advanced into production state. But proposals for multicast security solutions that have been published so far are complex, often require trust in network components, or are inefficient. In this paper, we propose a framework of new approaches for achieving scalable security in IP multicasting. Our solutions assure that newly joining members are not able to understand past group traffic and that leaving members may not follow future communication. For versatility, our framework supports a range of closely related schemes for key management, ranging from tightly centralized to fully distributed, and even allows switching between these schemes on-the-fly with low overhead. Operations have low complexity [O(log N) for joins or leaves], thus granting scalability even for very large groups. We also present a novel concurrency-enabling scheme, which was devised for fully distributed key management. In this paper, we discuss the requirements for secure multicasting, present our flexible system, and evaluate its properties based on the existing prototype implementation.

Extreme Value Theory as a Risk Management Tool

Abstract: The financial industry, including banking and insurance, is undergoing major changes. The (re)insurance industry is increasingly exposed to catastrophic losses for which the requested cover is only just available. An increasing complexity of financial instruments calls for sophisticated risk management tools. The securitization of risk and alternative risk transfer highlight the convergence of finance and insurance at the product level. Extreme value theory plays an important methodological role within risk management for insurance, reinsurance, and finance.

Experimental variation in polyandry affects parasite loads and fitness in a bumble-bee

Abstract: In many species of animals, females typically mate with more than one male (polyandry) Some social insects carry this behaviour to extremes1 For example, honeybee queens mate with ten to twenty (or even more) males on their nuptial flights2 The reasons for this behaviour remain unknown, given the obvious costs of time, energy and exposure to predation Several potential benefits of polyandry have been proposed1,3,3,4, but none are well supported yet Here we test the hypothesis that genetic diversity among a female's offspring may offer some protection from parasitism5,6,7 We artificially inseminated queens of a bumble-bee (Bombus terrestris L) with sperm of either low or high genetic diversity The resulting colonies were exposed to parasitism under field conditions High-diversity colonies had fewer parasites and showed greater reproductive success, on average, than did low-diversity colonies We suggest that female mating frequency may be influenced in part by parasites

Inhibition of non-haem iron absorption in man by polyphenolic-containing beverages.

Abstract: The effects of different polyphenol-containing beverages on Fe absorption from a bread meal were estimated in adult human subjects from the erythrocyte incorporation of radio-Fe. The test beverages contained different polyphenol structures and were rich in either phenolic acids (chlorogenic acid in coffee), monomeric flavonoids (herb teas, camomile (Matricaria recutita L.), vervain (Verbena officinalis L.), lime flower (Tilia cordata Mill.), pennyroyal (Mentha pulegium L.) and peppermint (Mentha piperita L.), or complex polyphenol polymerization products (black tea and cocoa). All beverages were potent inhibitors of Fe absorption and reduced absorption in a dose-dependent fashion depending on the content of total polyphenols. Compared with a water control meal, beverages containing 20-50 mg total polyphenols/serving reduced Fe absorption from the bread meal by 50-70%, whereas beverages containing 100-400 mg total polyphenols/serving reduced Fe absorption by 60-90%. Inhibition by black tea was 79-94%, peppermint tea 84%, pennyroyal 73%, cocoa 71%, vervain 59%, lime flower 52% and camomile 47%. At an identical concentration of total polyphenols, black tea was more inhibitory than cocoa, and more inhibitory than herb teas camomile, vervain, lime flower and pennyroyal, but was of equal inhibition to peppermint tea. Adding milk to coffee and tea had little or no influence on their inhibitory nature. Our findings demonstrate that herb teas, as well as black tea, coffee and coca can be potent inhibitors of Fe absorption. This property should be considered when giving dietary advice in relation to Fe nutrition.

Gold concentrations of magmatic brines and the metal budget of porphyry copper deposits

Abstract: Porphyry copper–molybdenum–gold deposits are the most important metal resources formed by hydrothermal processes associated with magmatism. It remains controversial, however, whether the metal content of porphyry-style and other magmatic–hydrothermal deposits is dominantly controlled by metal partitioning between magma and an exsolving magmatic fluid phase1,2 or by scavenging of metals from solid upper-crustal rocks by surface-derived fluids3. It also remains unknown to what degree the metal content in such deposits is affected by selective mineral precipitation from the ore fluid. Extremely saline fluids4, precipitating quartz and ore minerals in veins have been inferred to have a significant magma-derived component, on the basis of geological5, isotopic6,7 and experimental evidence8,9. Here we report gold and copper concentrations of single fluid inclusions in quartz, determined by laser-ablation inductively coupled plasma mass spectrometry. The results show that the Au/Cu ratio of primary high-temperature brines is identical to the bulk Au/Cu ratio in two of the world's largest copper–gold ore bodies. This indicates that the bulk metal budget of such deposits is primarily controlled by the composition of the incoming fluid, which is, in turn, likely to be controlled by the crystallization process in an underlying magma chamber.

Unified modeling of hybrid electric vehicle drivetrains

Abstract: Hybridizing automotive drivetrains, or using more than one type of energy converter, is considered an important step toward very low pollutant emission and high fuel economy. The automotive industry and governments in the United States, Europe, and Japan have formed strategic initiatives with the aim of cooperating in the development of new vehicle technologies. Efforts to meet fuel economy and exhaust emission targets have initiated major advances in hybrid drivetrain system components, including: high-efficiency high-specific power electric motors and controllers; load-leveling devices such as ultracapacitors and fly-wheels; hydrogen and direct-methanol fuel cells; direct injection diesel and Otto cycle engines; and advanced batteries. The design of hybrid electric vehicles is an excellent example of the need for mechatronic system analysis and design methods. If one is to fully realize the potential of using these technologies, a complete vehicle system approach for component selection and optimization over typical driving situations is required. The control problems that arise in connection with hybrid power trains are significant and pose additional challenges to power-train control engineers. The principal aim of the paper is to propose a framework for the analysis, design, and control of optimum hybrid vehicles within the context of energy and power flow analysis. The approaches and results presented in the paper are one step toward the development of a complete toolbox for the analysis and design of hybrid vehicles.

Metabolic flux ratio analysis of genetic and environmental modulations of Escherichia coli central carbon metabolism.

Abstract: The response of Escherichia coli central carbon metabolism to genetic and environmental manipulation has been studied by use of a recently developed methodology for metabolic flux ratio (METAFoR) analysis; this methodology can also directly reveal active metabolic pathways. Generation of fluxome data arrays by use of the METAFoR approach is based on two-dimensional (13)C-(1)H correlation nuclear magnetic resonance spectroscopy with fractionally labeled biomass and, in contrast to metabolic flux analysis, does not require measurements of extracellular substrate and metabolite concentrations. METAFoR analyses of E. coli strains that moderately overexpress phosphofructokinase, pyruvate kinase, pyruvate decarboxylase, or alcohol dehydrogenase revealed that only a few flux ratios change in concert with the overexpression of these enzymes. Disruption of both pyruvate kinase isoenzymes resulted in altered flux ratios for reactions connecting the phosphoenolpyruvate (PEP) and pyruvate pools but did not significantly alter central metabolism. These data indicate remarkable robustness and rigidity in central carbon metabolism in the presence of genetic variation. More significant physiological changes and flux ratio differences were seen in response to altered environmental conditions. For example, in ammonia-limited chemostat cultures, compared to glucose-limited chemostat cultures, a reduced fraction of PEP molecules was derived through at least one transketolase reaction, and there was a higher relative contribution of anaplerotic PEP carboxylation than of the tricarboxylic acid (TCA) cycle for oxaloacetate synthesis. These two parameters also showed significant variation between aerobic and anaerobic batch cultures. Finally, two reactions catalyzed by PEP carboxykinase and malic enzyme were identified by METAFoR analysis; these had previously been considered absent in E. coli cells grown in glucose-containing media. Backward flux from the TCA cycle to glycolysis, as indicated by significant activity of PEP carboxykinase, was found only in glucose-limited chemostat culture, demonstrating that control of this futile cycle activity is relaxed under severe glucose limitation.

Folding-unfolding thermodynamics of a beta-heptapeptide from equilibrium simulations.

Abstract: The thermodynamics of folding and unfolding of a beta-heptapeptide in methanol solution has been studied at four different temperatures, 298 K, 340 K, 350 K, and 360 K, by molecular dynamics simulation. At each of these temperatures, the 50-ns simulations were sufficient to generate an equilibrium distribution between a relatively small number of conformations (approximately 10(2)), showing that, even above the melting temperature (approximately 340 K), the peptide does not randomly sample conformational space. The free energy of folding and the free energy difference between pairs of conformations have been calculated from their relative populations. The experimentally determined folded conformation at 298 K, a left-handed 3(1)-helix, is at each of the four temperatures the predominant conformation, with its probability and average lifetime decreasing with increasing temperature. The most common intermediates of folding and unfolding are also the same at the four temperatures. Paths and rates of interconversion between different conformations have been determined. It has been found that folding can occur through multiple pathways, not necessarily downhill in free energy, although the final step involves a reduced number of intermediates.