Boundary and internal conditions for adjoint fluid-flow problems

The ever-increasing robustness and reliability of flow-simulation methods have consolidated CFD as a major tool in virtually all branches of fluid mechanics. Traditionally, those methods have played a crucial role in the analysis of flow physics. In more recent years, though, the subject has broadened considerably, with the development of optimization and inverse design applications. Since then, the search for efficient ways to evaluate flow-sensitivity gradients has received the attention of numerous researchers. In this scenario, the adjoint method has emerged as, quite possibly, the most powerful tool for the job, which heightens the need for a clear understanding of its conceptual basis. Yet, some of its underlying aspects are still subject to debate in the literature, despite all the research that has been carried out on the method. Such is the case with the adjoint boundary and internal conditions, in particular. The present work aims to shed more light on that topic, with emphasis on the need for an internal shock condition. By following the path of previous authors, the quasi-1D Euler problem is used as a vehicle to explore those concepts. The results clearly indicate that the behavior of the adjoint solution through a shock wave ultimately depends upon the nature of the objective functional.

Design of a Modern Liposome and Bee Venom Formulation for the Traditional VIT-Venom Immunotherapy

Traditional venom immunotherapy uses injections of whole bee venom in buffer or adsorbed in Al (OH)(3) in an expensive, time-consuming way. New strategies to improve the safety and efficacy of this treatment with a reduction of injections would, therefore, be of general interest. It would improve patient compliance and provide socio-economic benefits. Liposomes have a long tradition in drug delivery because they increase the therapeutic index and avoid drug degradation and secondary effects. However, bee venom melittin (Mel) and phospholipase (PLA(2)) destroy the phospholipid membranes. Our central idea was to inhibit the PLA(2) and Mel activities through histidine alkylation and or tryptophan oxidation (with pbb, para-bromo-phenacyl bromide, and/or NBSN-bromosuccinimide, respectively) to make their encapsulations possible within stabilized liposomes. We strongly believe that this formulation will be nontoxic but immunogenic. In this paper, we present the whole bee venom conformation characterization during and after chemical modification and after interaction with liposome by ultraviolet, circular dichroism, and fluorescence spectroscopies. The PLA(2) and Mel activities were, measured indirectly by changes in turbidity at 400(nm), rhodamine leak-out, and hemolysis. The native whole bee venom (BV) presented 78.06% of alpha-helical content. The alkylation (A-BV) and succynilation (S-BV) of BV increased 0.44 and 0.20% of its alpha-helical content. The double-modified venom (S-A-BV) had a 0.74% increase of alpha-helical content. The BV chemical modification induced another change on protein conformations observed by Trp that became buried with respect to the native whole BV. It was demonstrated that the liposomal membranes must contain pbb (SPC:Cho:pbb, 26:7:1) as a component to protect them from aggregation and/or fusion. The membranes containing pbb maintained the same turbidity (100%) after incubation with modified venom, in contrast with pbb-free membranes that showed a 15% size decrease. This size decrease was interpreted as membrane degradation and was corroborated by a 50% rhodamine leak-out. Another fact that confirmed our interpretation was the observed 100% inhibition of the hemolytic activity after venom modification with pbb and NBS (S-A-BV). When S-A-BV interacted with liposomes, other protein conformational changes were observed and characterized by the increase of 1.93% on S-A-BV alpha-helical content and the presence of tryptophan residues in a more hydrophobic environment. In other words, the S-A-BV interacted with liposomal membranes, but this interaction was not effective to cause aggregation, leak-out, or fusion. A stable formulation composed by S-A-BV encapsulated within liposomes composed by SPC:Cho:pbb, at a ratio of 26:7:1, was devised. Large unilamellar vesicles of 202.5 nm with a negative surface charge (-24.29 mV) encapsulated 95% of S-A-BV. This formulation can, now, be assayed on VIT.

Approaches for multicopper oxidases in the design of electrochemical sensors for analytical applications

We report an effective approach for the construction of a biomimetic sensor of multicopper oxidases by immobilizing a cyclic-tetrameric copper(II) species, containing the ligand (4-imidazolyl)ethylene-2-amino-1-ethylpyridine (apyhist), in the Nafion (R) membrane on a vitreous carbon electrode surface. This complex provides a tetranuclear arrangement of copper ions that allows an effective reduction of oxygen to water, in a catalytic cycle involving four electrons. The electrochemical reduction of oxygen was studied at pH 9.0 buffer solution by using cyclic voltammetry, chronoamperometry, rotating disk electrode voltammetry and scanning electrochemical microscopy techniques. The mediator shows good electrocatalytic ability for the reduction of O(2) at pH 9.0, with reduction of overpotential (350 mV) and increased current response in comparison with results obtained with a bare glassy carbon electrode. The heterogeneous rate constant (k(ME)`) for the reduction of O(2) at the modified electrode was determined by using a Koutecky-Levich plot. In addition, the charge transport rate through the coating and the apparent diffusion coefficient of O(2) into the modifier film were also evaluated. The overall process was found to be governed by the charge transport through the coating, occurring at the interface or at a finite layer at the electrode/coating interface. The proposed study opens up the way for the development of bioelectronic devices based on molecular recognition and self-organization. (C) 2010 Elsevier Ltd. All rights reserved.

Synthesis Optimization of Hydroxymethylnitrofurazone, an Antichagasic Candidate, Using 3(2) Factorial Design

Hydroxymethylnitrofurazone presents in vitro activity against Trypanosoma cruzi. The optimization of the synthesis of this compound was performed through a 3(2) factorial statistical design. Quadratic model produced the best response surface predicting a maximum yield (82%) close to the center design point with a seven hours reaction and a 1:1.5 (NF:K(2)CO(3)) ratio.

Design of novel antituberculosis compounds using graph-theoretical and substructural approaches

The increasing resistance of Mycobacterium tuberculosis to the existing drugs has alarmed the worldwide scientific community. In an attempt to overcome this problem, two models for the design and prediction of new antituberculosis agents were obtained. The first used a mixed approach, containing descriptors based on fragments and the topological substructural molecular design approach (TOPS-MODE) descriptors. The other model used a combination of two-dimensional (2D) and three-dimensional (3D) descriptors. A data set of 167 compounds with great structural variability, 72 of them antituberculosis agents and 95 compounds belonging to other pharmaceutical categories, was analyzed. The first model showed sensitivity, specificity, and accuracy values above 80% and the second one showed values higher than 75% for these statistical indices. Subsequently, 12 structures of imidazoles not included in this study were designed, taking into account the two models. In both cases accuracy was 100%, showing that the methodology in silico developed by us is promising for the rational design of antituberculosis drugs.

Metal transport parameters of a gneiss saprolitic silty soil for liner design

Diffusion coefficients and retardation factors of two metal cations (Cd2+ and Pb2+) were measured for a compacted Brazilian saprolitic soil derived from gneiss, aiming to assess its geoenvironmental performance as a liner for waste disposal sites. This soil occurs extensively all over the country in very thick layers, but has not been used in liners because of its hydraulic conductivity, higher than 10(-9) m/s when compacted at optimum water content of standard Proctor energy, but which can be reduced by means of appropriate compaction techniques or additives. Batch, column, and diffusion tests were carried out with monospecies synthetic solutions at pH 1, 3, and 5.5. Measured diffusion coefficients varied between 0.5 and 4 X 10(-10) m(2)/s. Retardation factors show that cadmium, a very mobile cation, is not adsorbed at pH I but is significantly retained at pH 3 and pH 5.5, whereas lead is retained at all tested pH values though slightly at pH 1. Estimated retardation factors from batch tests were 1.3-2.3 times those resulting from column tests and at its highest when obtained by diffusion tests; whereas batch tests allow a more complete exposure of the soil grains to the solution, time-dependent nonspecific adsorption may take longer to occur. The importance of contact time was observed and should be considered in further investigations. Its significant retention of metals suggests a promising utilization of this soil as a bottom liner for wastes landfills.

Use of Experimental Design for the Optimization of the Production of New Secondary Metabolites by Two Penicillium Species

A fractional factorial design approach has been used to enhance secondary metabolite production by two Penicillium strains. The method was initially used to improve the production of bioactive extracts as a whole and subsequently to optimize the production of particular bioactive metabolites. Enhancements of over 500% in secondary metabolite production were observed for both P. oxalicum and P. citrinum. Two new alkaloids, citrinalins A (5) and B (6), were isolated and identified from P. citrinum cultures optimized for production of minor metabolites.

Computer-aided design decision support: interfacing knowledge and information

Computer-aided design decision support has proved to be an elusive and intangible project for many researchers as they seek to encapsulate information and knowledge-based systems as useful multifunctional data structures. Definitions of ‘knowledge', ‘information', ‘facts', and ‘data' become semantic footballs in the struggle to identify what designers actually do, and what level of support would suit them best, and how that support might be offered. The Construction Primer is a database-drivable interactive multimedia environment that provides readily updated access to many levels of information aimed to suit students and practitioners alike. This is hardly a novelty in itself. The innovative interface and metadata structures, however, combine with the willingness of national building control legislators, standards authorities, materials producers, building research organisations, and specification services to make the Construction Primer a versatile design decision support vehicle. It is both compatible with most working methodologies while remaining reasonably future-proof. This paper describes the structure of the project and highlights the importance of sound planning and strict adhesion to library-standard metadata protocols as a means to avoid the support becoming too specific or too paradigmatic.

Energy efficient envelope design for high-rise apartments

The energy required to create a comfortable living environment in  high-density cities in hot and humid climates usually demands a substantial electricity usage with an associated environmental burden. This paper describes an integrated passive design approach to reduce the cooling requirement for high-rise apartments through an improved building envelope design. The results show that a saving of 31.4% in annual required cooling energy and 36.8% in the peak cooling load for the BASECASE apartment can be achieved with this approach. However, all the passive strategies have marginal effect on latent cooling load, often less than 1%.

Design of reduced-order scalar functional observers

In the existing literature, the existence conditions and design procedures for scalar functional observers are available for the cases where the observers’ order p is either p=1 or p=(v-1), where v is the observability index of the matrix pair (C,A). Therefore, if an observer with an order p=1 does not exist, the other available option is to use a higher order observer with p=(v-1). This paper shows that there exists another option that can be used to design scalar linear functional observers of the order lower than the well-known upper bound (v-1). The paper provides the existence conditions and a design procedure for scalar functional observers of order 0≤ p ≤2, and demonstrates the presented results with a numerical example.

Existence and design of reduced-order scalar functional observers

In the existing literature, the existence conditions and design procedures for scalar functional observers are available for the cases where the observers’ order p is either p=1 or p=(v-1), where v is the observability index of the matrix pair (C,A). Therefore, if an observer with an order p=1 does not exist, the other option is to use a high-order observer with p=(v-1). This paper provides the existence conditions and a design procedure for scalar functional observers of order 0≤p≤2, and demonstrates the presented results with a numerical example. where K, M, E, H and G are constant matrices to be designed. The problem of observing a scalar functional or multi functionals (z(t)∈Rk , k>1) of the state vector has been the subject of numerous papers, and different algorithms have been proposed (see, [1]-[13] and references therein). There are also papers that deal with the order reduction of multi-dimensional functional observers [9,10,12,13]. For scalar functional observers, a well-known Luenberger’s classic result [1] provides an upper bound on the order with p=(v-1). It is interesting to note here that, except for a recent result of Darouach [12,13], little results have been reported on the order reduction for scalar functional observers.

Role of multi-tenure reserve networks in improving reserve design and connectivity

Multi-tenure reserve networks aim to connect areas managed for biodiversity conservation across public and private land. This paper seeks to determine to what extent multi-tenure reserve networks improve the reserve design and connectivity of the public protected area estate, using three networks in southeastern Australia as case studies. Network configuration varied considerably and those networks with generally larger parcels tended to be better connected. On average, public land components were larger than private land components in all networks. Two networks had 18 components physically adjoining other network components while another had only 6 components adjoining. Importantly for two of the networks, the average distance between the nearest neighbouring component was significantly less than average distances between public protected areas in the subregion. Thus these multi-tenure reserve networks acted to enhance the existing public protected area estate by increasing the potential linkages in the landscape and therefore the viability of individual public protected areas.

A review of cashmere nutrition experiments with suggestions for improving their design and conduct

The scientific literature contains divergent views about the effects of nutrition on cashmere. The consequences of ignoring nutrition will be an increase in the number of goats suffering lower production, increased welfare risks and premature mortality. This review evaluated published reports to identify current knowledge and best practice in regard to the design and management of cashmere nutrition experiments. The ability of experiments to distinguish between treatments was evaluated based on their statistical evidence. Many experiments had serious deficiencies in their design, conduct and reporting. Six of 16 papers did not provide statistical information that would enable a reader to verify differences between treatments. For most experiments to detect nutrition affects at P < 0.05, they required a difference between treatments of 0.2–0.8 μm in cashmere mean fibre diameter and 15–42 g in clean cashmere production. Government Research Institutes research was characterised by more experienced authors conducting longer (P < 0.05) and larger (P < 0.05) experiments than those conducted by Universities. Much of the “debate” regarding the affects of nutrition on cashmere production arises from the misinterpretation of both experiments that did not detect statistically significant effects and of experiments that did detect statistically significant effects. Based on a comparison between experiments reporting responses to nutrition with those reporting no response, 13 design and management features were identified that are related to the ability of experiments to detect significant treatment affects. Methods must be adopted to reduce the variance in cashmere production within treatments, by using sufficient animals per treatment, and having replication to provide sufficient degrees of freedom to reduce error terms in analysis. The power of experimental designs should be evaluated before experiments commence. Cashmere production records from a previous full production year could be used as co-variants during statistical analyses but this requires that potential experimental goats are managed in one flock, without variations resulting from different grazing, reproduction or other management for a year prior to an experiment. It is preferable to use more productive and older goats, and goats that are used to handling, and to the conditions and feed to be used. Allocation of animals to treatments must take into account live weight. Nutrition treatments need to be sufficiently different to produce different growth curves. An appropriate control is needed such as live weight maintenance. Evidence of both nutrition intake and growth curves must be published with cashmere production data so the claims made can be verified by the actual responses. As cashmere production is an order of magnitude less than fibre production of Merino sheep or Angora goats and is more difficult to measure, the requirements for measurement, sampling and testing cashmere fleeces are summarised. The use of mid side cashmere patches to determine cashmere growth and quality is seriously biased and must be avoided, preferably by shearing goats prior to and at the end of experiments. In order to obtain higher fleece growth responses and improve the ability of experiments to detect treatment effects it is preferable to start cashmere growth experiments by midsummer and conduct experiments for at least 4 months. These requirements make it difficult for many university students to plan, undertake and complete long-term cashmere nutrition experiments without considerable management support. It is not possible for experiments to disprove the Null hypothesis regarding the effects of nutrition on cashmere production as they can only report a failure to detect treatment effects. Researchers and journals need to be more rigorous in providing statistical information including: degrees of freedom for error terms, treatment variances, standard error of differences or similar to enable readers to compare treatment effects. Publications that do not provide sufficient statistical information should be disregarded from future discussions. Claims that an experiment shows no responses to nutrition should be subject to rigorous examination using the issues identified in this review.