876 resultados para feature-based design
Resumo:
Molecular modi. cation is a quite promising strategy in the design and development of drug analogs with better bioavailability, higher intrinsic activity and less toxicity. In the search of new leads with potential antimicrobial activity, a new series of 14 4-substituted [N`-(benzofuroxan-5-yl) methylene] benzohydrazides, nifuroxazide derivatives, were synthesized and tested against standard and multidrug-resistant Staphylococcus aureus strains. The selection of the substituent groups was based on physicochemical properties, such as hydrophobicity and electronic effect. These properties were also evaluated through the lipophilic and electrostatic potential maps, respectively, considering the compounds with better biological pro. le. Twelve compounds exhibited similar bacteriostatic activity against standard and multidrug-resistant strains. The most active compound was the 4-CF(3) substituted derivative, which presented a minimum inhibitory concentration (MIC) value of 14.6-13.1 mu g/mL, and a ClogP value of 1.87. The results highlight the benzofuroxan derivatives as potential leads for designing new future antimicrobial drug candidates. (C) 2009 Elsevier Ltd. All rights reserved.
Resumo:
Phospholipases A(2) (PLA(2)) are enzymes commonly found in snake venoms from Viperidae and Elaphidae families, which are major components thereof. Many plants are used in traditional medicine its active agents against various effects induced by snakebite. This article presents the PLA(2) BthTX-I structure prediction based on homology modeling. In addition, we have performed virtual screening in a large database yielding a set of potential bioactive inhibitors. A flexible docking program was used to investigate the interactions between the receptor and the new ligands. We have performed molecular interaction fields (MIFs) calculations with the phospholipase model. Results confirm the important role of Lys49 for binding ligands and suggest three additional residues as well. We have proposed a theoretically nontoxic, drug-like, and potential novel BthTX-I inhibitor. These calculations have been used to guide the design of novel phospholipase inhibitors as potential lead compounds that may be optimized for future treatment of snakebite victims as well as other human diseases in which PLA(2) enzymes are involved.
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This paper reports on a system for automated agent negotiation, based on a formal and executable approach to capture the behavior of parties involved in a negotiation. It uses the JADE agent framework, and its major distinctive feature is the use of declarative negotiation strategies. The negotiation strategies are expressed in a declarative rules language, defeasible logic, and are applied using the implemented system DR-DEVICE. The key ideas and the overall system architecture are described, and a particular negotiation case is presented in detail.
Resumo:
In recent years, the design flows of many dams were re-evaluated, often resulting in discharges larger than the original design. In many cases, the occurrence of the revised flows could result in dam overtopping because of insufficient storage and spillway capacity. An experimental study was conducted herein to gain a better understanding of the flow properties in stepped chutes with slopes typical of embankment dams. The work was based upon a Froude similitude in large-size experimental facilities. A total of 10 configurations were tested including smooth steps, steps equipped with devices to enhance energy dissipation and rough steps. The present results yield a new design procedure. The design method includes some key issues not foreseen in prior studies : e.g., gradually varied flow, type of flow regime, flow resistance. It is believed that the outcomes are valid for a wide range of chute geometry and flow conditions typical of embankment chutes.
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Extracting human postural information from video sequences has proved a difficult research question. The most successful approaches to date have been based on particle filtering, whereby the underlying probability distribution is approximated by a set of particles. The shape of the underlying observational probability distribution plays a significant role in determining the success, both accuracy and efficiency, of any visual tracker. In this paper we compare approaches used by other authors and present a cost path approach which is commonly used in image segmentation problems, however is currently not widely used in tracking applications.
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Trust is a vital feature for Semantic Web: If users (humans and agents) are to use and integrate system answers, they must trust them. Thus, systems should be able to explain their actions, sources, and beliefs, and this issue is the topic of the proof layer in the design of the Semantic Web. This paper presents the design and implementation of a system for proof explanation on the Semantic Web, based on defeasible reasoning. The basis of this work is the DR-DEVICE system that is extended to handle proofs. A critical aspect is the representation of proofs in an XML language, which is achieved by a RuleML language extension.
Resumo:
A simple design process for the design of elliptical cross-section, transverse gradient coils for use in magnetic resonance imaging (MRI) is presented. This process is based on a flexible stochastic optimization method and results in designs of high linearity and efficiency with low switching times. A design study of a shielded, transverse asymmetric elliptical coil set for use in neural imaging is presented and includes the minimization of the torques experienced by the gradient set.
Resumo:
In this paper, a new v-metric based approach is proposed to design decentralized controllers for multi-unit nonlinear plants that admit a set of plant decompositions in an operating space. Similar to the gap metric approach in literature, it is shown that the operating space can also be divided into several subregions based on a v-metric indicator, and each of the subregions admits the same controller structure. A comparative case study is presented to display the advantages of proposed approach over the gap metric approach. (C) 2000 Elsevier Science Ltd. All rights reserved.
Resumo:
Objectives: To test the acceptability of screening and to identify modifiable risk factors for abdominal aortic aneurysm (AAA) in men. Design: A trial of ultrasound screening for AAA in a population-based random sample of men aged 65-83 years, and a cross-sectional case-control comparison of men in the same sample. Participants: 12203 men who had an ultrasound examination of their abdominal aorta, and completed a questionnaire covering demographic, behavioural and medical factors. Main outcome measures: Prevalence of AAA, and independent associations of AAA with demographic, medical and lifestyle factors. Results: Invitations to screening produced a corrected response of 70.5%. The prevalence of AAAs (> 30 mm) rose from 4.8% in men aged 65-69 years to 10.8% in those aged 80-83 years. The overall prevalence of large (> 50 mm) aneurysms was 0.69%. In a multivariate logistic model Mediterranean-born men had a 40% lower risk of AAA (> 30 mm) compared with men born in Australia (odds ratio [OR], 0.6; 95% CI, 0.4-0.8), while ex-smokers had a significantly increased risk of AAA (OR, 2.3; 95% CI, 1.9-2.8), and current smokers had even higher risks. AAA was significantly associated with established coronary and peripheral arterial disease and a waist:hip ratio greater than 0.9; men who regularly undertook vigorous exercise had a lower risk (OR, 0.8; 95% CI, 0.7-1.0). Conclusion: Ultrasound screening for AAA is acceptable to men in the likely target population. AAA shares some but not all of the risk factors for occlusive vascular disease, but the scope for primary prevention of AAA in later life is limited.
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The simultaneous design of the steady-state and dynamic performance of a process has the ability to satisfy much more demanding dynamic performance criteria than the design of dynamics only by the connection of a control system. A method for designing process dynamics based on the use of a linearised systems' eigenvalues has been developed. The eigenvalues are associated with system states using the unit perturbation spectral resolution (UPSR), characterising the dynamics of each state. The design method uses a homotopy approach to determine a final design which satisfies both steady-state and dynamic performance criteria. A highly interacting single stage forced circulation evaporator system, including control loops, was designed by this method with the goal of reducing the time taken for the liquid composition to reach steady-state. Initially the system was successfully redesigned to speed up the eigenvalue associated with the liquid composition state, but this did not result in an improved startup performance. Further analysis showed that the integral action of the composition controller was the source of the limiting eigenvalue. Design changes made to speed up this eigenvalue did result in an improved startup performance. The proposed approach provides a structured way to address the design-control interface, giving significant insight into the dynamic behaviour of the system such that a systematic design or redesign of an existing system can be undertaken with confidence.
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In this paper we propose a new framework for evaluating designs based on work domain analysis, the first phase of cognitive work analysis. We develop a rationale for a new approach to evaluation by describing the unique characteristics of complex systems and by showing that systems engineering techniques only partially accommodate these characteristics. We then present work domain analysis as a complementary framework for evaluation. We explain this technique by example by showing how the Australian Defence Force used work domain analysis to evaluate design proposals for a new system called Airborne Early Warning and Control. This case study also demonstrates that work domain analysis is a useful and feasible approach that complements standard techniques for evaluation and that promotes a central role for human factors professionals early in the system design and development process. Actual or potential applications of this research include the evaluation of designs for complex systems.
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In this paper, genetic algorithm (GA) is applied to the optimum design of reinforced concrete liquid retaining structures, which comprise three discrete design variables, including slab thickness, reinforcement diameter and reinforcement spacing. GA, being a search technique based on the mechanics of natural genetics, couples a Darwinian survival-of-the-fittest principle with a random yet structured information exchange amongst a population of artificial chromosomes. As a first step, a penalty-based strategy is entailed to transform the constrained design problem into an unconstrained problem, which is appropriate for GA application. A numerical example is then used to demonstrate strength and capability of the GA in this domain problem. It is shown that, only after the exploration of a minute portion of the search space, near-optimal solutions are obtained at an extremely converging speed. The method can be extended to application of even more complex optimization problems in other domains.
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Study objective: To investigate the effect of the voluntary folate fortification policy in Australia on serum folate and total plasma homocysteine (tHcy) concentrations. Design: Population based cohort study. Setting: Perth, Western Australia. Participants: Men and women aged 27 to 77 years (n = 468), who were originally randomly selected from the Perth electoral roll. The cohort was surveyed in 1995/96 before widespread introduction of folate fortification of a variety of foods, and followed up on two occasions, firstly in 1998/99 and again in 2001, when a moderate number of folate fortified foods were available. Subjects with abnormal serum creatinine concentrations at baseline were excluded from this analysis. Main results: Repeated measures analysis of variance was used to determine changes in serum folate and tHcy over the three surveys and to assess whether time trends were related to age, sex, MTHFR C677T genotype, or consumption of folate fortified foods. An increase (38%) in mean serum folate (p < 0.0005) and a decrease (21%) in mean tHcy (p < 0.0005) were seen after introduction of the voluntary folate fortification policy in Australia. Serum folate was consistently higher (p = 0.032) and tHcy was consistently lower (p = 0.001) in subjects who consumed at least one folate fortified food compared with subjects who did not consume any folate fortified foods in the previous week. The time related changes in serum folate and tHcy were affected only by intake of folate fortified foods (p < 0.0005) and not by any other measured variables including age, sex, or MTHFR genotype. Conclusion: Voluntary fortification of foods with folate in Australia has been followed by a substantial increase in serum folate and decrease in tHcy in the general population.
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Background: Condition-dependence is a ubiquitous feature of animal life histories and has important implications for both natural and sexual selection. Mate choice, for instance, is typically based on condition-dependent signals. Theory predicts that one reason why condition-dependent signals may be special is that they allow females to scan for genes that confer high parasite resistance. Such explanations require a genetic link between immunocompetence and body condition, but existing evidence is limited to phenotypic associations. It remains unknown, therefore, whether females selecting males with good body condition simply obtain a healthy mate, or if they acquire genes for their offspring that confer high immunocompetence. Results: Here we use a cross-foster experimental design to partition the phenotypic covariance in indices of body condition and immunocompetence into genetic, maternal and environmental effects in a passerine bird, the zebra finch Taeniopygia guttata. We show that there is significant positive additive genetic covariance between an index of body condition and an index of cell-mediated immune response. In this case, genetic variance in the index of immune response explained 56% of the additive genetic variance in the index of body condition. Conclusion: Our results suggest that, in the context of sexual selection, females that assess males on the basis of condition-dependent signals may gain genes that confer high immunocompetence for their offspring. More generally, a genetic correlation between indices of body condition and imuunocompetence supports the hypothesis that parasite resistance may be an important target of natural selection. Additional work is now required to test whether genetic covariance exists among other aspects of both condition and immunocompetence.
Resumo:
Depression is the most frequent psychiatric disorder in Parkinson`s disease (PD). Although evidence Suggests that depression in PD is related to the degenerative process that underlies the disease, further studies are necessary to better understand the neural basis of depression in this population of patients. In order to investigate neuronal alterations underlying the depression in PD, we studied thirty-six patients with idiopathic PD. Twenty of these patients had the diagnosis of major depression disorder and sixteen did not. The two groups were matched for PD motor severity according to Unified Parkinson Disease Rating Scale (UPDRS). First we conducted a functional magnetic resonance imaging (fMRI) using an event-related parametric emotional perception paradigm with test retest design. Our results showed decreased activation in the left mediodorsal (MD) thalamus and in medial prefrontall cortex in PD patients with depression compared to those without depression. Based upon these results and the increased neuron count in MD thalamus found in previous studies, we conducted a region of interest (ROI) guided voxel-based morphometry (VBM) study comparing the thalamic volume. Our results showed an increased volume in mediodorsal thalamic nuclei bilaterally. Converging morphological changes and functional emotional processing in mediodorsal thalamus highlight the importance of limbic thalamus in PD depression. In addition this data supports the link between neurodegenerative alterations and mood regulation. (C) 2009 Elsevier Inc. All rights reserved.