Inhibitors of Trypanosoma brucei trypanothione reductase: comparative molecular field analysis modeling and structural basis for selective inhibition

Background: Sleeping sickness is a major cause of death in Africa. Since no secure treatment is available, the development of novel therapeutic agents is urgent. In this context, the enzyme trypanothione reductase (TR) is a prominent molecular target that has been investigated in drug design for sleeping sickness. Results: In this study, comparative molecular field analysis models were generated for a series of Trypanosoma brucei TR inhibitors. Statistically significant results were obtained and the models were applied to predict the activity of external test sets, with good correlation between predicted and experimental results. We have also investigated the structural requirements for the selective inhibition of the parasite's enzyme over the human glutathione reductase. Conclusion: The quantitative structure-activity relationship models provided valuable information regarding the essential molecular requirements for the inhibitory activity upon the target protein, providing important insights into the design of more potent and selective TR inhibitors.

Mechanical analysis and modeling of structural archetypes

This is a research B for the University of Bologna. The course is the civil engineering LAUREA MAGISTRALE at UNIBO. The main purpose of this research is to promote another way of explaining, analyzing and presenting some civil engineering aspects to the students worldwide by theory, modeling and photos. The basic idea is divided into three steps. The first one is to present and analyze the theoretical parts. So a detailed analysis of the theory combined with theorems, explanations, examples and exercises will cover this step. At the second, a model will make clear all these parts that were discussed in the theory by showing how the structures work or fail. The modeling is able to present the behavior of many elements, in scale which we use in the real structures. After these two steps an interesting exhibition of photos from the real world with comments will give the chance to the engineers to observe all these theoretical and modeling-laboratory staff in many different cases. For example many civil engineers in the world may know about the air pressure on the structures but many of them have never seen the extraordinary behavior of the bridge of Tacoma ‘dancing with the air’. At this point I would like to say that what I have done is not a book, but a research of how this ‘3 step’ presentation or explanation of some mechanical characteristics could be helpful. I know that my research is something different and new and in my opinion is very important because it helps students to go deeper in the science and also gives new ideas and inspirations. This way of teaching can be used at all lessons especially at the technical. Hope that one day all the books will adopt this kind of presentation.

Assessment Of Dynamic Properties Of A Crowd Model For Human-Structure Interaction Modeling

As lightweight and slender structural elements are more frequently used in the design, large scale structures become more flexible and susceptible to excessive vibrations. To ensure the functionality of the structure, dynamic properties of the occupied structure need to be estimated during the design phase. Traditional analysis method models occupants simply as an additional mass; however, research has shown that human occupants could be better modeled as an additional degree-of- freedom. In the United Kingdom, active and passive crowd models are proposed by the Joint Working Group as a result of a series of analytical and experimental research. It is expected that the crowd models would yield a more accurate estimation to the dynamic response of the occupied structure. However, experimental testing recently conducted through a graduate student project at Bucknell University indicated that the proposed passive crowd model might be inaccurate in representing the impact on the structure from the occupants. The objective of this study is to provide an assessment of the validity of the crowd models proposed by JWG through comparing the dynamic properties obtained from experimental testing data and analytical modeling results. The experimental data used in this study was collected by Firman in 2010. The analytical results were obtained by performing a time-history analysis on a finite element model of the occupied structure. The crowd models were created based on the recommendations from the JWG combined with the physical properties of the occupants during the experimental study. During this study, SAP2000 was used to create the finite element models and to implement the analysis; Matlab and ME¿scope were used to obtain the dynamic properties of the structure through processing the time-history analysis results from SAP2000. The result of this study indicates that the active crowd model could quite accurately represent the impact on the structure from occupants standing with bent knees while the passive crowd model could not properly simulate the dynamic response of the structure when occupants were standing straight or sitting on the structure. Future work related to this study involves improving the passive crowd model and evaluating the crowd models with full-scale structure models and operating data.

Structure-based modeling of head -related transfer functions towards interactive customization of binaural sound systems

One of the most popular techniques for creating spatialized virtual sounds is based on the use of Head-Related Transfer Functions (HRTFs). HRTFs are signal processing models that represent the modifications undergone by the acoustic signal as it travels from a sound source to each of the listener's eardrums. These modifications are due to the interaction of the acoustic waves with the listener's torso, shoulders, head and pinnae, or outer ears. As such, HRTFs are somewhat different for each listener. For a listener to perceive synthesized 3-D sound cues correctly, the synthesized cues must be similar to the listener's own HRTFs. ^ One can measure individual HRTFs using specialized recording systems, however, these systems are prohibitively expensive and restrict the portability of the 3-D sound system. HRTF-based systems also face several computational challenges. This dissertation presents an alternative method for the synthesis of binaural spatialized sounds. The sound entering the pinna undergoes several reflective, diffractive and resonant phenomena, which determine the HRTF. Using signal processing tools, such as Prony's signal modeling method, an appropriate set of time delays and a resonant frequency were used to approximate the measured Head-Related Impulse Responses (HRIRs). Statistical analysis was used to find out empirical equations describing how the reflections and resonances are determined by the shape and size of the pinna features obtained from 3D images of 15 experimental subjects modeled in the project. These equations were used to yield “Model HRTFs” that can create elevation effects. ^ Listening tests conducted on 10 subjects show that these model HRTFs are 5% more effective than generic HRTFs when it comes to localizing sounds in the frontal plane. The number of reversals (perception of sound source above the horizontal plane when actually it is below the plane and vice versa) was also reduced by 5.7%, showing the perceptual effectiveness of this approach. The model is simple, yet versatile because it relies on easy to measure parameters to create an individualized HRTF. This low-order parameterized model also reduces the computational and storage demands, while maintaining a sufficient number of perceptually relevant spectral cues. ^

A costs structure analysis of the Brazilian sugar and ethanol companies

The Brazil consolidated itself as the largest world producer of sugarcane, sugar and ethanol. The creation of the Programa Nacional do Alcool - PROALCOOL and the growing use of cars with flexible motors were some of the factors that helped to motivate still more the production. Evolutions in the agricultural and industrial research did the Brazilian competitiveness in sugar and ethanol globally elevated, what is evidenced when comparing the amount produced at the country and the production costs, which turned a big one differential. Therefore, the administration of costs is of great relevance to the sugar and ethanol companies, for representing a significant rationalization in the production processes, with economy of resources and the reach of better earnings, besides reducing the operational risk pertinent at the fixed costs of production. Thus, the present work has for objective to analyze the costs structure of sugar and ethanol companies of the Center-south area of the country through an empiric-analytical study based in methodologies and concepts extracted of the costs accounting. It is verified that great part of the costs and operational expenses have variable behavior, a positive factor for the sector reducing the operational risk of the activity. The main restraint of this study is the sample of five years and 10% of the number of plants in Brazil that although they represent 30% of the national production, don`t allow the generalization of the model.

Molecular mobility, composition and structure analysis in glycerol plasticised chitosan films

This study was developed with the purpose to investigate the effect of polysaccharide/plasticiser concentration on the microstructure and molecular dynamics of polymeric film systems, using transmission electron microscope imaging (TEM) and nuclear magnetic resonance (NMR) techniques. Experiments were carried out in chitosan/glycerol films prepared with solutions of different composition. The films obtained after drying and equilibration were characterised in terms of composition, thickness and water activity. Results show that glycerol quantities used in film forming solutions were responsible for films composition; while polymer/total plasticiser ratio in the solution determined the thickness (and thus structure) of the films. These results were confirmed by TEM. NMR allowed understanding the films molecular rearrangement. Two different behaviours for the two components analysed, water and glycerol were observed: the first is predominantly moving free in the matrix, while glycerol is mainly bounded to the chitosan chain. (C) 2013 Elsevier Ltd. All rights reserved.

Genetic and genomic analysis modeling of germline c-MYC overexpression and cancer susceptibility

Background: Germline genetic variation is associated with the differential expression of many human genes. The phenotypic effects of this type of variation may be important when considering susceptibility to common genetic diseases. Three regions at 8q24 have recently been identified to independently confer risk of prostate cancer. Variation at 8q24 has also recently been associated with risk of breast and colorectal cancer. However, none of the risk variants map at or relatively close to known genes, with c-MYC mapping a few hundred kilobases distally. Results: This study identifies cis-regulators of germline c-MYC expression in immortalized lymphocytes of HapMap individuals. Quantitative analysis of c-MYC expression in normal prostate tissues suggests an association between overexpression and variants in Region 1 of prostate cancer risk. Somatic c-MYC overexpression correlates with prostate cancer progression and more aggressive tumor forms, which was also a pathological variable associated with Region 1. Expression profiling analysis and modeling of transcriptional regulatory networks predicts a functional association between MYC and the prostate tumor suppressor KLF6. Analysis of MYC/Myc-driven cell transformation and tumorigenesis substantiates a model in which MYC overexpression promotes transformation by down-regulating KLF6. In this model, a feedback loop through E-cadherin down-regulation causes further transactivation of c-MYC.Conclusion: This study proposes that variation at putative 8q24 cis-regulator(s) of transcription can significantly alter germline c-MYC expression levels and, thus, contribute to prostate cancer susceptibility by down-regulating the prostate tumor suppressor KLF6 gene.

A scaled difference chi-square test statistic for moment structure analysis

A family of scaling corrections aimed to improve the chi-square approximation of goodness-of-fit test statistics in small samples, large models, and nonnormal data was proposed in Satorra and Bentler (1994). For structural equations models, Satorra-Bentler's (SB) scaling corrections are available in standard computer software. Often, however, the interest is not on the overall fit of a model, but on a test of the restrictions that a null model say ${\cal M}_0$ implies on a less restricted one ${\cal M}_1$. If $T_0$ and $T_1$ denote the goodness-of-fit test statistics associated to ${\cal M}_0$ and ${\cal M}_1$, respectively, then typically the difference $T_d = T_0 - T_1$ is used as a chi-square test statistic with degrees of freedom equal to the difference on the number of independent parameters estimated under the models ${\cal M}_0$ and ${\cal M}_1$. As in the case of the goodness-of-fit test, it is of interest to scale the statistic $T_d$ in order to improve its chi-square approximation in realistic, i.e., nonasymptotic and nonnormal, applications. In a recent paper, Satorra (1999) shows that the difference between two Satorra-Bentler scaled test statistics for overall model fit does not yield the correct SB scaled difference test statistic. Satorra developed an expression that permits scaling the difference test statistic, but his formula has some practical limitations, since it requires heavy computations that are notavailable in standard computer software. The purpose of the present paper is to provide an easy way to compute the scaled difference chi-square statistic from the scaled goodness-of-fit test statistics of models ${\cal M}_0$ and ${\cal M}_1$. A Monte Carlo study is provided to illustrate the performance of the competing statistics.

Comparison Structure Analysis

This study presents an automatic, computer-aided analytical method called Comparison Structure Analysis (CSA), which can be applied to different dimensions of music. The aim of CSA is first and foremost practical: to produce dynamic and understandable representations of musical properties by evaluating the prevalence of a chosen musical data structure through a musical piece. Such a comparison structure may refer to a mathematical vector, a set, a matrix or another type of data structure and even a combination of data structures. CSA depends on an abstract systematic segmentation that allows for a statistical or mathematical survey of the data. To choose a comparison structure is to tune the apparatus to be sensitive to an exclusive set of musical properties. CSA settles somewhere between traditional music analysis and computer aided music information retrieval (MIR). Theoretically defined musical entities, such as pitch-class sets, set-classes and particular rhythm patterns are detected in compositions using pattern extraction and pattern comparison algorithms that are typical within the field of MIR. In principle, the idea of comparison structure analysis can be applied to any time-series type data and, in the music analytical context, to polyphonic as well as homophonic music. Tonal trends, set-class similarities, invertible counterpoints, voice-leading similarities, short-term modulations, rhythmic similarities and multiparametric changes in musical texture were studied. Since CSA allows for a highly accurate classification of compositions, its methods may be applicable to symbolic music information retrieval as well. The strength of CSA relies especially on the possibility to make comparisons between the observations concerning different musical parameters and to combine it with statistical and perhaps other music analytical methods. The results of CSA are dependent on the competence of the similarity measure. New similarity measures for tonal stability, rhythmic and set-class similarity measurements were proposed. The most advanced results were attained by employing the automated function generation – comparable with the so-called genetic programming – to search for an optimal model for set-class similarity measurements. However, the results of CSA seem to agree strongly, independent of the type of similarity function employed in the analysis.

Median filtering: structure analysis and application

Median filtering is a simple digital non—linear signal smoothing operation in which median of the samples in a sliding window replaces the sample at the middle of the window. The resulting filtered sequence tends to follow polynomial trends in the original sample sequence. Median filter preserves signal edges while filtering out impulses. Due to this property, median filtering is finding applications in many areas of image and speech processing. Though median filtering is simple to realise digitally, its properties are not easily analysed with standard analysis techniques,

A novel cation induced polymeric chain in Na-8[{Cu(gly)(2)}(2)]{H-2(H2W12O42)}] center dot 24H(2)O: hydrothermal synthesis, spectroscopic characterization and X-ray structure analysis

A novel bis(glycinato) copper(II) paradodecatungstate Na-8[{Cu(gly)(2)}(2)]-{H-2(H2W12O42)}] center dot 24H(2)O (1) has been synthesized under hydrothermal conditions. The crystal structure of 1 reveals an infinite one-dimensional chain along the [100] direction and is built from paradodecatungstate (H2W12O42)(10-) clusters joined through [Cu(gly)(2)] moieties. Parallel chains are interlinked by NaO6 octahedra to generate a two-dimensional network.

The exclusive use of integer-order spots for LEED-IV structure analysis of adsorption systems: p(2×2)-O on Ni{111}

Two different ways of performing low-energy electron diffraction (LEED) structure determinations for the p(2 x 2) structure of oxygen on Ni {111} are compared: a conventional LEED-IV structure analysis using integer and fractional-order IV-curves collected at normal incidence and an analysis using only integer-order IV-curves collected at three different angles of incidence. A clear discrimination between different adsorption sites can be achieved by the latter approach as well as the first and the best fit structures of both analyses are within each other's error bars (all less than 0.1 angstrom). The conventional analysis is more sensitive to the adsorbate coordinates and lateral parameters of the substrate atoms whereas the integer-order-based analysis is more sensitive to the vertical coordinates of substrate atoms. Adsorbate-related contributions to the intensities of integer-order diffraction spots are independent of the state of long-range order in the adsorbate layer. These results show, therefore, that for lattice-gas disordered adsorbate layers, for which only integer-order spots are observed, similar accuracy and reliability can be achieved as for ordered adsorbate layers, provided the data set is large enough.

Secondary structure analysis of the dissimilatory sulphite reductase in Desulfovibrio desulfuricans

The complete sequences of the dsrA and dsrB genes coding for the α− and β−subunits, respectively, of the sulphite reductase enzyme in Desulfovibrio desulfuricans were determined. Analyses of the amino acid sequences indicated a number of serohaem/Fe4S4 binding consensus sequences whilst predictive secondary structure analysis revealed a similar pattern of α−helix and β−strand structures between the two subunits which was indicative of gene duplication.

Towards to the trans-bromination of 2-styrylpyridine with a palladacycle intermediary and structure analysis for trans-1,2-dibromo-2-styrylpyridine

The simple halogenation of alkynes in conventional organic reactions gives a blend of cis and trans isomers. It is proposed then, a synthesis of stereospecific halogenation of alkynes in trans position, using palladacycle as intermediaries. The recrystallization of the compound obtained by bromination of 2-Styrylpyridine, with cyclepalladium intermediary results in a single crystal, which is subjected to X-ray diffraction. The crystal packing is established through weak interactions of three types. The first one is of the type pi x pi interactions, from symmetry operation, between the centroids. The second one is of the type C-X center dot center dot center dot pi interactions. And the last type is an anomalous intermolecular interaction between halogens, C-X center dot center dot center dot X-C, with bond distances smaller than the sum of the van der Waals radii. The conformation on the C=C bond is trans and the dihedral angle between the aromatic rings is (with esd approximate) 18.1(3)degrees. (C) 2010 Elsevier B.V. All rights reserved.