Advances in prodrug design

The background of prodrug design is presented herein as the basis for introducing new and advanced latent systems, taking into account mainly the versatility of polymers and other macromolecules as carriers. PDEPT (Polymer-Directed Enzyme Prodrug Therapy); PELT (Polymer-Enzyme Liposome Therapy); CDS (Chemical Delivery System); ADEPT(Antibody-Directed Enzyme Prodrug Therapy); GDEPT/VDEPT (Gene-Directed Enzyme Prodrug Therapy/Virus-Directed Enzyme Prodrug Therapy); ODDS (Osteotropic Drug Delivery System) and LEAPT (Lectin-directed enzyme-activated prodrug therapy) are briefly described and some examples are given. © 2005 Bentham Science Publishers Ltd.

Optimal linear and nonlinear control design for chaotic systems

In this work, the linear and nonlinear feedback control techniques for chaotic systems were been considered. The optimal nonlinear control design problem has been resolved by using Dynamic Programming that reduced this problem to a solution of the Hamilton-Jacobi-Bellman equation. In present work the linear feedback control problem has been reformulated under optimal control theory viewpoint. The formulated Theorem expresses explicitly the form of minimized functional and gives the sufficient conditions that allow using the linear feedback control for nonlinear system. The numerical simulations for the Rössler system and the Duffing oscillator are provided to show the effectiveness of this method. Copyright © 2005 by ASME.

Usage of enterprise modeling processes and information systems design to forecast demand

Managing the great complexity of enterprise system, due to entities numbers, decision and process varieties involved to be controlled results in a very hard task because deals with the integration of its operations and its information systems. Moreover, the enterprises find themselves in a constant changing process, reacting in a dynamic and competitive environment where their business processes are constantly altered. The transformation of business processes into models allows to analyze and redefine them. Through computing tools usage it is possible to minimize the cost and risks of an enterprise integration design. This article claims for the necessity of modeling the processes in order to define more precisely the enterprise business requirements and the adequate usage of the modeling methodologies. Following these patterns, the paper concerns the process modeling relative to the domain of demand forecasting as a practical example. The domain of demand forecasting was built based on a theoretical review. The resulting models considered as reference model are transformed into information systems and have the aim to introduce a generic solution and be start point of better practical forecasting. The proposal is to promote the adequacy of the information system to the real needs of an enterprise in order to enable it to obtain and accompany better results, minimizing design errors, time, money and effort. The enterprise processes modeling are obtained with the usage of CIMOSA language and to the support information system it was used the UML language.

Design of SPR systems with dynamic compensators and output variable structure control

This paper presents necessary and sufficient conditions for the following problem: given a linear time invariant plant G(s) = N(s)D(s)-1 = C(sI - A]-1B, with m inputs, p outputs, p > m, rank(C) = p, rank(B) = rank(CB) = m, £nd a tandem dynamic controller Gc(s) = D c(s)-1Nc(s) = Cc(sI - A c)-1Bc + Dc, with p inputs and m outputs and a constant output feedback matrix Ko ε ℝm×p such that the feedback system is Strictly Positive Real (SPR). It is shown that this problem has solution if and only if all transmission zeros of the plant have negative real parts. When there exists solution, the proposed method firstly obtains Gc(s) in order to all transmission zeros of Gc(s)G(s) present negative real parts and then Ko is found as the solution of some Linear Matrix Inequalities (LMIs). Then, taking into account this result, a new LMI based design for output Variable Structure Control (VSC) of uncertain dynamic plants is presented. The method can consider the following design specifications: matched disturbances or nonlinearities of the plant, output constraints, decay rate and matched and nonmatched plant uncertainties. © 2006 IEEE.

Molecular hybridization: A useful tool in the design of new drug prototypes

Molecular hybridization is a new concept in drug design and development based on the combination of pharmacophoric moieties of different bioactive substances to produce a new hyrid compound with improved affinity and efficacy, when compared to the parent drugs. Additionally, this strategy can results in compounds presenting modified selectivity profile, different and/or dual modes of action and reduced undesired side effects. So, in this described several example of different strategies for drug design, discovery and pharmacomodulation focused on new innovative hybrid compounds presenting analgesic, anti-inflammatory, platelet anti-aggregating, anti-infections, anticancer, cardio- and neuroactive properties.

Biometria e qualidade fisiológica de sementes de diferentes matrizes de Tabebuia chrysotricha (Mart. Ex A. DC.) Stand I.

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Design and validity of a questionnaire to assess sexuality in pregnant women

Background. A review of validated methods for assessing female sexual dysfunction and a review of male and female sexual dysfunction did not refer to any specific questionnaire for evaluating sexuality during pregnancy. A study was performed at the Obstetrics and Gynecology Department of Botucatu Medical School, São Paulo State University, Brazil to design and validate a pregnancy sexuality questionnaire, the Pregnancy Sexual Response Inventory (PSRI). Methods. Women with a singleton pregnancy between 10 and 35 weeks of gestation were randomly recruited. There were five phases in the development of the PSRI: (1) item selection; (2) item development; (3) determination of internal consistency, reliability and convergence; (4) content validity; and (5) determination of inter-interviewer reliability. Internal consistency and reliability were evaluated using Cronbach's alpha. Inter-interviewer reliability was assessed by evaluating the responses of 18 academics at various institutions, using Kappa Index and Student t test. Results. Good internal consistency and reliability were obtained (Cronbach's alpha coefficient = 0.79). Among the 18 academics, 13 totally agreed (K = 1.0), three partially agreed (K = 0.67) and two disagreed (K = 0.33) with the proposed questions. Comparisons of the mean PSRI domain scores made between the primary investigators and the other interviewers showed no significant differences in all domains (p > 0.05). Conclusion. PSRI is a new validated instrument for evaluating sexuality and sexual activity and related health concerns during pregnancy. © 2009 Rudge et al; licensee BioMed Central Ltd.

Digital system design process automation using place/transition petri nets

The constant increase in digital systems complexity definitely demands the automation of the corresponding synthesis process. This paper presents a computational environment designed to produce both software and hardware implementations of a system. The tool for code generation has been named ACG8051. As for the hardware synthesis there has been produced a larger environment consisting of four programs, namely: PIPE2TAB, AGPS, TABELA, and TAB2VHDL. ACG8051 and PIPE2TAB use place/transition net descriptions from PIPE as inputs. ACG8051 is aimed at generating assembly code for the 8051 micro-controller. PIPE2TAB produces a tabular version of a Mealy type finite state machine of the system, its output is fed into AGPS that is used for state allocation. The resulting digital system is then input to TABELA, which minimizes control functions and outputs of the digital system. Finally, the output generated by TABELA is fed to TAB2VHDL that produces a VHDL description of the system at the register transfer level. Thus, we present here a set of tools designed to take a high-level description of a digital system, represented by a place/transition net, and produces as output both an assembly code that can be immediately run on an 8051 micro-controller, and a VHDL description that can be used to directly implement the hardware parts either on an FPGA or as an ASIC.

Cyclodextrin glycosyltransferase production by the Bacillus sp., subgroup alcalophilus using a central composite design

Cyclodextrin glycosyltransferase (CGTase) activity was produced by the Bacillus sp., subgroup alcalophilus in a culture medium containing cassava starch. A central composite design and response surface methodology were used to study the influence of carbon source (cassava starch), nitrogen sources (yeast extract and tryptone) and sodium carbonate in the production medium. Assays were performed in 300 mL Erlenmeyer flasks containing 100 mL of production medium maintained in a shaker at 150 rpm at 35±1°C for 72 h of fermentation. The independent variables [0.75% cassava starch, nitrogen sources (0.375% yeast extract and 0.375% tryptone) and 1% Na2CO3] produced an enzyme activity of 96.07 U mL-1.© Academic Journals Inc.

Design of a state observer using decay rate LMI constraints for fault detection in mechanical systems

Nowadays, one of the most important concerns for many companies is to maintain the operation of their systems without sudden equipment break down. Because of this, new techniques for fault detection and location in mechanical systems subject to dynamic loads have been developed. This paper studies of the influence of the decay rate in the design of state observers using LMI for fault detection in mechanical systems. This influence is analyzed by the performance index proposed by Huh and Stein for the condition of a state observer. An example is presented to illustrate the methodology discussed.

Digestibilidade e tempo de trânsito gastrintestinal de dietas contendo níveis crescentes de fibra bruta para pacu

This work aimed to evaluate the effect of increasing dietary fiber levels on the digestibility and gastrointestinal transit time (GTT) for pacu. The digestibility trial used 288 pacu in a completely randomized design, fed in aquaria and transferred to a modified Guelf-type feces collector, using the partial sampling method. The inert marker on the diets was chromic oxide (1%) to establish the diet digestibility. In the GTT assay, 288 pacu were distributed in 24 aquaria in a completely randomized design. Fish were fed with two colored diets - green and white - and feces color was determined after abdominal pressure. The white and green diets used 1% of titanium and chromic oxides, respectively. Total GTT was determined when all fish showed green feces. The apparent digestibility coefficients and GTT of diets decreased as dietary fiber levels increased. These results indicated that 9% dietary fiber can be used in pacu diets without negative effects on energy, protein, crude fiber and ether extract digestibility and GTT.

Two-level network design with intermediate facilities: An application to electrical distribution systems

We consider the two-level network design problem with intermediate facilities. This problem consists of designing a minimum cost network respecting some requirements, usually described in terms of the network topology or in terms of a desired flow of commodities between source and destination vertices. Each selected link must receive one of two types of edge facilities and the connection of different edge facilities requires a costly and capacitated vertex facility. We propose a hybrid decomposition approach which heuristically obtains tentative solutions for the vertex facilities number and location and use these solutions to limit the computational burden of a branch-and-cut algorithm. We test our method on instances of the power system secondary distribution network design problem. The results show that the method is efficient both in terms of solution quality and computational times. © 2010 Elsevier Ltd.

Comparison of β-1,3-glucanase production by Botryosphaeria rhodina MAMB-05 and Trichoderma harzianum Rifai and its optimization using a statistical mixture-design

Botryosphaeria rhodina MAMB-05 produced β-1,3-glucanases and botryosphaeran when grown on glucose, while Trichoderma harzianum Rifai only produced the enzyme. A comparison of long-term cultivation (300h) by B. rhodina demonstrated a correlation between the formation of botryosphaeran (48h) and its consumption (after 108h), and de-repression of β-1,3-glucanase synthesis when glucose was depleted from the nutrient medium, whereas for T. harzianum enzyme production commenced during exponential growth. Growth profiles and levels of β-1,3-glucanases produced by both fungi on botryosphaeran also differed, as well as the production of β-1,3-glucanases and β-1,6-glucanases on glucose, lactose, laminarin, botryosphaeran, lasiodiplodan, curdlan, Brewer's yeast powder and lyophilized fungal mycelium, which were dependent upon the carbon source used. A statistical mixture-design used to optimize β-1,3-glucanase production by both fungi evaluated botryosphaeran, glucose and lactose concentrations as variables. For B. rhodina, glucose and lactose promoted enzyme production at the same levels (2.30UmL -1), whereas botryosphaeran added to these substrates exerted a synergic effect favorable for β-glucanase production by T. harzianum (4.25UmL -1). © 2010 Elsevier B.V.

On a control design to an AFM microcantilever beam, operating in a tapping-mode, with irregular behavior

In last decades, control of nonlinear dynamic systems became an important and interesting problem studied by many authors, what results the appearance of lots of works about this subject in the scientific literature. In this paper, an Atomic Force Microscope micro cantilever operating in tapping mode was modeled, and its behavior was studied using bifurcation diagrams, phase portraits, time history, Poincare maps and Lyapunov exponents. Chaos was detected in an interval of time; those phenomena undermine the achievement of accurate images by the sample surface. In the mathematical model, periodic and chaotic motion was obtained by changing parameters. To control the chaotic behavior of the system were implemented two control techniques. The SDRE control (State Dependent Riccati Equation) and Time-delayed feedback control. Simulation results show the feasibility of the bothmethods, for chaos control of an AFM system. Copyright © 2011 by ASME.

Design and implementation of a dc-dc converter based on variable structure control of switched systems

This paper presents a control method for a class of continuous-time switched systems, using state feedback variable structure controllers. The method is applied to the control of a non-trivial dc-dc power converter and a simple and inexpensive control circuit design, that was simulated using the software PSpice, is proposed. The design is based on Lyapunov-Metzler-SPR systems and the performance of the resulting control system is superior to that afforded by a recently proposed alternative sliding-mode control technique. © 2011 IFAC.