How optimization of potential functions affects protein folding.

The relationship between the optimization of the potential function and the foldability of theoretical protein models is studied based on investigations of a 27-mer cubic-lattice protein model and a more realistic lattice model for the protein crambin. In both the simple and the more complicated systems, optimization of the energy parameters achieves significant improvements in the statistical-mechanical characteristics of the systems and leads to foldable protein models in simulation experiments. The foldability of the protein models is characterized by their statistical-mechanical properties--e.g., by the density of states and by Monte Carlo folding simulations of the models. With optimized energy parameters, a high level of consistency exists among different interactions in the native structures of the protein models, as revealed by a correlation function between the optimized energy parameters and the native structure of the model proteins. The results of this work are relevant to the design of a general potential function for folding proteins by theoretical simulations.

Brain localization for arbitrary stimulus categories: a simple account based on Hebbian learning.

A central theme of cognitive neuroscience is that different parts of the brain perform different functions. Recent evidence from neuropsychology suggests that even the processing of arbitrary stimulus categories that are defined solely by cultural conventions (e.g., letters versus digits) can become spatially segregated in the cerebral cortex. How could the processing of stimulus categories that are not innate and that have no inherent structural differences become segregated? We propose that the temporal clustering of stimuli from a given category interacts with Hebbian learning to lead to functional localization. Neural network simulations bear out this hypothesis.

The crystal structure of an N-terminal two-domain fragment of vascular cell adhesion molecule 1 (VCAM-1): a cyclic peptide based on the domain 1 C-D loop can inhibit VCAM-1-alpha 4 integrin interaction.

Vascular cell adhesion molecule 1 (VCAM-1) represents a structurally and functionally distinct class of immunoglobulin superfamily molecules that bind leukocyte integrins and are involved in inflammatory and immune functions. X-ray crystallography defines the three-dimensional structure of the N-terminal two-domain fragment that participates in ligand binding. Residues in domain 1 important for ligand binding reside in the C-D loop, which projects markedly from one face of the molecule near the contact between domains 1 and 2. A cyclic peptide that mimics this loop inhibits binding of alpha 4 beta 1 integrin-bearing cells to VCAM-1. These data demonstrate how crystallographic structural information can be used to design a small molecule inhibitor of biological function.

Síntese de potencial inibidor de acetilcolinesterase para tratamento da Doença de Alzheimer

A doença de Alzheimer (DA) é a forma mais comum de demência, representando cerca de 80% dos casos. A DA é caracterizada por um processo de declínio progressivo e irreversível das funções cognitivas e da memória, que se estende para a desorganização do comportamento. Atualmente, 46,8 milhões de pessoas em todo o mundo foram diagnosticadas com demência. Embora vários fatores tenham sido implicados na DA, sua etiologia ainda não é completamente conhecida. Do ponto de vista neuropatológico, é observado no cérebro de indivíduos com DA atrofia cortical difusa, presença de grande número de placas senis, emaranhados neurofibrilares, processo inflamatório e perda neuronal. A progressão dos sintomas está associada a mudanças estruturais nas sinapses colinérgicas em certas regiões do cérebro, que consequentemente, apresentam neurotransmissão colinérgica reduzida. Os vários eventos patológicos interligados contribuem para o avanço da doença e direcionam diversas pesquisas na busca por tratamentos multialvos com base no processo multifatorial de DA. Assim o presente trabalho descreve a síntese de derivados híbridos dual binding site de donepezila-tacrina (fármacos inibidores de acetilcolinesterase), com potencial para agir em dois alvos terapêuticos pela (i) inibição da acetilcolinesterase em ambos os sítios ativo e periférico, como demonstrado pelos estudos de modelagem molecular, e (ii) na agregação do peptídeo A? neurotóxico induzido pela acetilcolinesterase, na tentativa de interromper a progressão da doença. A estratégia sintética envolveu a condensação da 5,6-dimetóxiindanona com a unidade 4-piperidinil carbaldeído, a qual forneceu o intermediário 5,6- dimetóxindan-1-ona-4-piperidinil-metileno-1-[(4-cloroquinolin-2-il)metil], seguido de redução da dupla ligação, gerada na reação de condensação anterior, e substituição do átomo de cloro-quinolina por amino para obtenção do produto final, ou manutenção da função olefina, seguido de substituição do átomo de cloro-quinolina por azido ou amino, gerando cinco híbridos estruturalmente correlacionados. Os híbridos foram testados em ensaio de inibição de acetilcolinesterase e butirilcolinesterase pelo método de Ellman, e o híbrido insaturado, contendo a função amino-quinolina foi o mais ativo da série com IC50 na faixa de nanomolar (0,014 ?M). Futuramente, os intermediários da reação e produto final serão submetidos ao ensaio de inibição da agregação do peptídeo A? neurotóxico pelo método da tioflavina T. Neste trabalho, também são descritos os testes de predição in vitro para permeação pela barreira hematoencefálica, bem como sua absorção intestinal, pelo método PAMPA.

Particle Swarm Optimization Based Reactive Power Dispatch for Power Networks with Distributed Generation

Reactive power is critical to the operation of the power networks on both safety aspects and economic aspects. Unreasonable distribution of the reactive power would severely affect the power quality of the power networks and increases the transmission loss. Currently, the most economical and practical approach to minimizing the real power loss remains using reactive power dispatch method. Reactive power dispatch problem is nonlinear and has both equality constraints and inequality constraints. In this thesis, PSO algorithm and MATPOWER 5.1 toolbox are applied to solve the reactive power dispatch problem. PSO is a global optimization technique that is equipped with excellent searching capability. The biggest advantage of PSO is that the efficiency of PSO is less sensitive to the complexity of the objective function. MATPOWER 5.1 is an open source MATLAB toolbox focusing on solving the power flow problems. The benefit of MATPOWER is that its code can be easily used and modified. The proposed method in this thesis minimizes the real power loss in a practical power system and determines the optimal placement of a new installed DG. IEEE 14 bus system is used to evaluate the performance. Test results show the effectiveness of the proposed method.

Disipation Functions of Flow Equations in Models of Complex Systems

In an open system, each disequilibrium causes a force. Each force causes a flow process, these being represented by a flow variable formally written as an equation called flow equation, and if each flow tends to equilibrate the system, these equations mathematically represent the tendency to that equilibrium. In this paper, the authors, based on the concepts of forces and conjugated fluxes and dissipation function developed by Onsager and Prigogine, they expose the following hypothesis: Is replaced in Prigogine’s Theorem the flow by its equation or by a flow orbital considering conjugate force as a gradient. This allows to obtain a dissipation function for each flow equation and a function of orbital dissipation.

A Belief System's Organization Based on a Computational Model of the Dynamic Context: First Approximation

In this article we present a model of organization of a belief system based on a set of binary recursive functions that characterize the dynamic context that modifies the beliefs. The initial beliefs are modeled by a set of two-bit words that grow, update, and generate other beliefs as the different experiences of the dynamic context appear. Reason is presented as an emergent effect of the experience on the beliefs. The system presents a layered structure that allows a functional organization of the belief system. Our approach seems suitable to model different ways of thinking and to apply to different realistic scenarios such as ideologies.

Chemical diversity and potential biological functions of the pygidial gland secretions in two species of Neotropical dung roller beetles

Dung roller beetles of the genus Canthon (Coleoptera: Scarabaeinae) emit an odorous secretion from a pair of pygidial glands. To investigate the chemical composition of these secretions, we used stir bar sorptive extraction (SBSE), coupled with gas chromatography–mass spectrometry (GC–MS) for analysis of extracts of pygidial gland secretions secreted by the dung roller beetles Canthon femoralis femoralis and Canthon cyanellus cyanellus. Chemical analyses of volatiles collected from pygidial gland secretions comprise a great diversity of the functional groups. Chemical profile comparisons showed high intra- and interspecific variability. The pygidial gland secretion of Canthon f. femoralis was dominated by sesquiterpene hydrocarbons, whereas the profile of Canthon c. cyanellus was dominated by carboxylic acids. The different pygidial secretions have a high diversity of chemical compounds suggesting a multifunctional nature involving some key functions in the biology. We discuss the biological potential of these compounds found in the pygidial glands of each species with respect to their ecological and behavioral relevance.

An adaptive algorithm for clustering cumulative probability distribution functions using the Kolmogorov–Smirnov two-sample test

This paper proposes an adaptive algorithm for clustering cumulative probability distribution functions (c.p.d.f.) of a continuous random variable, observed in different populations, into the minimum homogeneous clusters, making no parametric assumptions about the c.p.d.f.’s. The distance function for clustering c.p.d.f.’s that is proposed is based on the Kolmogorov–Smirnov two sample statistic. This test is able to detect differences in position, dispersion or shape of the c.p.d.f.’s. In our context, this statistic allows us to cluster the recorded data with a homogeneity criterion based on the whole distribution of each data set, and to decide whether it is necessary to add more clusters or not. In this sense, the proposed algorithm is adaptive as it automatically increases the number of clusters only as necessary; therefore, there is no need to fix in advance the number of clusters. The output of the algorithm are the common c.p.d.f. of all observed data in the cluster (the centroid) and, for each cluster, the Kolmogorov–Smirnov statistic between the centroid and the most distant c.p.d.f. The proposed algorithm has been used for a large data set of solar global irradiation spectra distributions. The results obtained enable to reduce all the information of more than 270,000 c.p.d.f.’s in only 6 different clusters that correspond to 6 different c.p.d.f.’s.

A Quantile-Based Probabilistic Mean Value Theorem

For non-negative random variables with finite means we introduce an analogous of the equilibrium residual-lifetime distribution based on the quantile function. This allows us to construct new distributions with support (0, 1), and to obtain a new quantile-based version of the probabilistic generalization of Taylor's theorem. Similarly, for pairs of stochastically ordered random variables we come to a new quantile-based form of the probabilistic mean value theorem. The latter involves a distribution that generalizes the Lorenz curve. We investigate the special case of proportional quantile functions and apply the given results to various models based on classes of distributions and measures of risk theory. Motivated by some stochastic comparisons, we also introduce the “expected reversed proportional shortfall order”, and a new characterization of random lifetimes involving the reversed hazard rate function.

New hybrid materials based on the grafting of Pd(II)-amino complexes on the graphitic surface of AC: preparation, structures and catalytic properties

A novel procedure for the preparation of solid Pd(II)-based catalysts consisting of the anchorage of designed Pd(II)-complexes on an activated carbon (AC) surface is reported. Two molecules of the Ar–S–F type (where Ar is a plane-pyrimidine moiety, F a Pd(II)-ligand and S an aliphatic linker) differing in F, were grafted on AC by π–π stacking of the Ar moiety and the graphene planes of the AC, thus favouring the retaining of the metal-complexing ability of F. Adsorption of Pd(II) by the AC/Ar–S–F hybrids occurs via Pd(II)-complexation by F. After deep characterization, the catalytic activities of the AC/Ar–S–F/Pd(II) hybrids on the hydrogenation of 1-octene in methanol as a catalytic test were evaluated. 100% conversion to n-octane at T = 323.1 K and P = 15 bar, was obtained with both catalysts and most of Pd(II) was reduced to Pd(0) nanoparticles, which remained on the AC surface. Reusing the catalysts in three additional cycles reveals that the catalyst bearing the F ligand with a larger Pd-complexing ability showed no loss of activity (100% conversion to n-octane) which is assigned to its larger structural stability. The catalyst with the weaker F ligand underwent a progressive loss of activity (from 100% to 79% in four cycles), due to the constant aggregation of the Pd(0) nanoparticles. Milder conditions, T = 303.1 K and P = 1.5 bar, prevent the aggregation of the Pd(0) nanoparticles in this catalyst allowing the retention of the high catalytic efficiency (100% conversion) in four reaction cycles.

Aggregation dynamics and foraging behaviour of striped red mullet Mullus surmuletus in the western Mediterranean Sea

Habitat-related heterogeneity of striped red mullet Mullus surmuletus heterospecific foraging assemblages was examined off the coast of Spain. Video-based focal-follows conducted on 122 M. surmuletus assemblages (446 total individuals) revealed an array of attendant species (n = 7) with composition linked to benthic habitat complexity; bare sandy substrata were characterized by homospecific groups of M. surmuletus, while habitats with rock and vegetation attracted a variety of scrounging labrids and sparids. Although the nature of the relationship between M. surmuletus and attendants requires further exploration, the present study indicates that substratum composition can be a driving factor explaining the dynamics of this heterospecific assemblage.

Analysis of Protein Turnover by Quantitative SNAP-Based Pulse-Chase Imaging

Assessment of protein dynamics in living cells is crucial for understanding their biological properties and functions. The SNAP-tag, a self labeling suicide enzyme, presents a tool with unique features that can be adopted for determining protein dynamics in living cells. Here we present detailed protocols for the use of SNAP in fluorescent pulse-chase and quench-chase-pulse experiments. These time-slicing methods provide powerful tools to assay and quantify the fate and turnover rate of proteins of different ages. We cover advantages and pitfalls of SNAP-tagging in fixed- and live-cell studies and evaluate the recently developed fast-acting SNAPf variant. In addition, to facilitate the analysis of protein turnover datasets, we present an automated algorithm for spot recognition and quantification.

Optimum Design of Electromagnets for Magnetic Levitation of Transport Systems based on the Inverse Problem Solutions

Article is devoted to design of optimum electromagnets for magnetic levitation of transport systems. The method of electromagnets design based on the inverse problem solution of electrical equipment is offered. The method differs from known by introducing a stage of minimization the target functions providing the stated levitation force and magnetic induction in a gap, and also the mass of an electromagnet. Initial values of parameters are received, using approximate formulas of the theory of electric devices and electrical equipment. The example of realization of a method is given. The received results show its high efficiency at design. It is practical to use the offered method and the computer program realizing it as a part of system of the automated design of electric equipment for transport with a magnetic levitation.

Radix 16 division, multiplication, logarithmic and exponential algorithms based on continued product representations,

Thesis (M.S.)--University of Illinois at Urbana-Champaign.