A rational protocol for the successful crystallization of l-amino-acid oxidase from Bothrops atrox

Despite the valuable contributions of robotics and high-throughput approaches to protein crystallization, the role of an experienced crystallographer in the evaluation and rationalization of a crystallization process is still crucial to obtaining crystals suitable for X-ray diffraction measurements. In this work, the difficult task of crystallizing the flavoenzyme l-amino-acid oxidase purified from Bothrops atrox snake venom was overcome by the development of a protocol that first required the identification of a non-amorphous precipitate as a promising crystallization condition followed by the implementation of a methodology that combined crystallization in the presence of oil and seeding techniques. Crystals were obtained and a complete data set was collected to 2.3 A resolution. The crystals belonged to space group P2(1), with unit-cell parameters a = 73.64, b = 123.92, c = 105.08 A, beta = 96.03 degrees. There were four protein subunits in the asymmetric unit, which gave a Matthews coefficient V (M) of 2.12 A3 Da-1, corresponding to 42% solvent content. The structure has been solved by molecular-replacement techniques.

STRESS-STRAIN CURVES FOR STEEL FIBER-REINFORCED CONCRETE IN COMPRESSION

This paper presents a study on the compressive behavior of steel fiber-reinforced concrete. In this study, an analytical model for stress-strain curve for steel fiber-reinforced concrete is derived for concretes with strengths of 40 MPa and 60 MPa at the age of 28 days. Those concretes were reinforced with steel fibers with hooked ends 35 mm long and with aspect ratio of 65. The analytical model was compared with some experimental stress-strain curves and with some models reported in technical literature. Also, the accuracy of the proposed stress-strain curve was evaluated by comparison of the area under stress-strain curve. The results showed good agreement between analytical and experimental data and the benefits of the using of fibers in the compressive behavior of concrete.

A family of implementation-friendly BN elliptic curves

For the last decade, elliptic curve cryptography has gained increasing interest in industry and in the academic community. This is especially due to the high level of security it provides with relatively small keys and to its ability to create very efficient and multifunctional cryptographic schemes by means of bilinear pairings. Pairings require pairing-friendly elliptic curves and among the possible choices, Barreto-Naehrig (BN) curves arguably constitute one of the most versatile families. In this paper, we further expand the potential of the BN curve family. We describe BN curves that are not only computationally very simple to generate, but also specially suitable for efficient implementation on a very broad range of scenarios. We also present implementation results of the optimal ate pairing using such a curve defined over a 254-bit prime field. (C) 2001 Elsevier Inc. All rights reserved.

Thermal analysis of vitamin PP Niacin and niacinamide

Vitamin PP includes two vitamers, niacin and niacinamide which are essential for energy production. Vitamins are sensitive and losses can occur during shelf life and heating processes. Thermal analysis can provide information about thermal behavior of each vitamer relating them with time and/or temperature exposure. The vitamers thermal behavior were studied by TG/DTG and DSC under air and nitrogen atmosphere and the results showed that niacin is more stable than the niacinamide and the decomposition happens by volatilization at 238 A degrees C while niacinamide melts at 129 A degrees C and volatilize at 254 A degrees C when there is the total mass loss in the TG/DTG curves.

Rational Design and 3D-Pharmacophore Mapping of 5 `-Thiourea-Substituted alpha-Thymidine Analogues as Mycobacterial TMPK Inhibitors

Thymidine monophosphate kinase (TMPK) has emerged as an attractive target for developing inhibitors of Mycobacterium tuberculosis growth. In this study the receptor-independent (RI) 4D-QSAR formalism has been used to develop QSAR models and corresponding 3D-pharmacophores for a set of 5`-thiourea-substituted alpha-thymidine inhibitors. Models were developed for the entire training set and for a subset of the training set consisting of the most potent inhibitors. The optimized (RI) 4D-QSAR models are statistically significant (r(2) = 0.90, q(2) = 0.83 entire set, r(2) = 0.86, q(2) = 0.80 high potency subset) and also possess good predictivity based on test set predictions. The most and least potent inhibitors, in their respective postulated active conformations derived from the models, were docked in the active site of the TMPK crystallographic structure. There is a solid consistency between the 3D-pharmacophore sites defined by the QSAR models and interactions with binding site residues. This model identifies new regions of the inhibitors that contain pharmacophore sites, such as the sugar-pyrimidine ring structure and the region of the 5`-arylthiourea moiety. These new regions of the ligands can be further explored and possibly exploited to identify new, novel, and, perhaps, better antituberculosis inhibitors of TMPKmt. Furthermore, the 3D-pharmacophores defined by these models can be used as a starting point for future receptor-dependent antituberculosis drug design as well as to elucidate candidate sites for substituent addition to optimize ADMET properties of analog inhibitors.

The rational reconstruction of the research program on classic rationalism: Locke and the empiricist approach

This article intends to rationally reconstruct Locke`s theory of knowledge as incorporated in a research program concerning the nature and structure of the theories and models of rationality. In previous articles we argued that the rationalist program can be subdivided into the classical rationalistic subprogram, which includes the knowledge theories of Descartes, Locke, Hume and Kant, the neoclassical subprogram, which includes the approaches of Duhem, Poincare and Mach, and the critical subprogram of Popper. The subdivision results from the different views of rationality proposed by each one of these subprograms, as well as from the tools made available by each one of them, containing theoretical instruments used to arrange, organize and develop the discussion on rationality, the main one of which is the structure of solution of problems. In this essay we intend to reconstruct the assumptions of Locke`s theory of knowledge, which in our view belongs to the classical rationalistic subprogram because it shares with it the thesis of the identity of (scientific) knowledge and certain knowledge.

Zipping up transcription factors: Rational design of anti-Jun and anti-Fos peptides

Various members of the bZip and bHLH-Zip families of eukaryotic transcription factors, including Jun, Fos, and Myc, have been identified as oncoproteins; mutation or deregulated expression of these proteins leads to certain types of cancer. These proteins can only bind to their cognate DNA enhancer sites following homodimerization, or heterodimerization with another family member, via their leucine zipper domain. Thus, a novel anticancer strategy would be to inhibit dimerization of these proteins, thereby blocking their DNA binding and transactivation functions. In this paper we show that it is possible to rationally design leucine zipper peptides that bind with high affinity to the leucine zipper dimerization domains of c-Jun and c-Fos, thus preventing the formation of functional c-Jun homodimers and c-Jun:c-Fos heterodimers; we refer to such peptides as superzippers (SZs). In vivo, c-Jun:SZ and c-Fos:SZ heterodimers should be nonfunctional as they lack one of the two basic domains that are essential for DNA binding. While the transport of a peptidic agent into cells often poses a severe obstacle to its therapeutic use, we show that a 46-residue leucine zipper peptide can be transported into HeLa cells by coupling it to a 17-residue carrier peptide from the Antennapedia homeodomain, thus paving the way for detailed studies of the therapeutic potential of superzipper peptides.

Rational combinatorial chemistry-based selection, synthesis and evaluation of an affinity adsorbent for recombinant human clotting factor VII

The selection, synthesis and chromatographic evaluation of a synthetic affinity adsorbent for human recombinant factor VIIa is described. The requirement for a metal ion-dependent immunoadsorbent step in the purification of the recombinant human clotting factor, FVIIa, has been obviated by using the X-ray crystallographic structure of the complex of tissue factor (TF) and Factor VIIa and has directed our combinatorial approach to select, synthesise and evaluate a rationally-selected affinity adsorbent from a limited library of putative ligands. The selected and optimised ligand comprises a triazine scaffold bis-substituted with 3-aminobenzoic acid and has been shown to bind selectively to FVIIa in a Ca2+-dependent manner. The adsorbent purifies FVIIa to almost identical purity (>99%), yield (99%), activation/degradation profile and impurity content (∼1000 ppm) as the current immunoadsorption process, while displaying a 10-fold higher static capacity and substantially higher reusability and durability. © 2002 Elsevier Science B.V. All rights reserved.

The Limits of Rational Choice: New Institutionalism in the Test Bed of Central Banking Politics in Australia

This paper tests the explanatory capacities of different versions of new institutionalism by examining the Australian case of a general transition in central banking practice and monetary politics: namely, the increased emphasis on low inflation and central bank independence. Standard versions of rational choice institutionalism largely dominate the literature on the politics of central banking, but this approach (here termed RC1) fails to account for Australian empirics. RC1 has a tendency to establish actor preferences exogenously to the analysis; actors' motives are also assumed a priori; actor's preferences are depicted in relatively static, ahistorical terms. And there is the tendency, even a methodological requirement, to assume relatively simple motives and preference sets among actors, in part because of the game theoretic nature of RC1 reasoning. It is possible to build a more accurate rational choice model by re-specifying and essentially updating the context, incentives and choice sets that have driven rational choice in this case. Enter RC2. However, this move subtly introduces methodological shifts and new theoretical challenges. By contrast, historical institutionalism uses an inductive methodology. Compared with deduction, it is arguably better able to deal with complexity and nuance. It also utilises a dynamic, historical approach, and specifies (dynamically) endogenous preference formation by interpretive actors. Historical institutionalism is also able to more easily incorporate a wider set of key explanatory variables and incorporate wider social aggregates. Hence, it is argued that historical institutionalism is the preferred explanatory theory and methodology in this case.

Combining the rational and relational perspectives of electronic trading

Many organisations make extensive use of electronic linkages to facilitate their trading exchanges with partners such as suppliers, distributors and customers. This research explores how the use of inter-organisational systems (IOS) both affects, and is affected by, the relationships between trading partners. In doing this, it brings together two existing but distinct perspectives and literatures; the rational view informed by IOS research, and the behavioural or relationship perspective embodied in inter-organisational relationships (IOR) literature. The research was undertaken in the European paper industry by means of six dyadic case studies. The dyads studied covered both traditional electronic data interchange systems and newer e-marketplace environments. A framework was derived from existing literature that integrates the two perspectives of interest. The framework was used to analyse the case studies undertaken and enabled the inter-relationship between IOS use and IOR to be explained.

Harvesting dynamic aspects from a real rational map : the bulb of period 5

This journal provides immediate open access to its content on the principle that making research freely available to the public supports a greater global exchange of knowledge.

Mapping stability : real rational maps of degree zero

In memory of our beloved Professor José Rodrigues Santos de Sousa Ramos (1948-2007), who João Cabral, one of the authors of this paper, had the honor of being his student between 2000 and 2006, we wrote this paper following the research by experimentation, using the new technologies to capture a new insight about a problem, as him so much love to do it. His passion was to create new relations between different fields of mathematics. He was a builder of bridges of knowledge, encouraging the birth of new ways to understand this science. One of the areas that Sousa Ramos researched was the iteration of maps and the description of its behavior, using the symbolic dynamics. So, in this issue of this journal, honoring his memory, we use experimental results to find some stable regions of a specific family of real rational maps, the ones that he worked with João Cabral. In this paper we describe a parameter space (a,b) to the real rational maps fa,b(x) = (x2 −a)/(x2 −b), using some tools of dynamical systems, as the study of the critical point orbit and Lyapunov exponents. We give some results regarding the stability of these family of maps when we iterate it, specially the ones connected to the order 3 of iteration. We hope that our results would help to understand better the behavior of these maps, preparing the ground to a more efficient use of the Kneading Theory on these family of maps, using symbolic dynamics.

Towards the rational biosynthesis of substituted phenazines and phenoxazinones by laccases

Laccases are multi-copper oxidases that oxidise a wide range of substrates including phenol and aniline derivatives, which could be further involved in coupling reactions leading to the formation of dimeric and trimeric structures. This paper describes the enzyme-mediated dimerisation of several ortho and meta, para-disubstituted aromatic amines into phenazine ("head-to-tail" dimers) and phenoxazinone chromophores. The redox properties of substituted aromatic amines were studied by cyclic voltammetry and the kinetic constants of CotA and Trametes versicolor laccases were measured for selected aromatic amines. The structure of novel enzymatically synthesised phenazine and phenoxazinone dyes using CotA laccase was assessed by NMR and MS. Overall our data show that this enzymatic green process is an efficient alternative to the classic chemical oxidation of aromatic amines and phenols, with an impact on the broad field of applications of these heterocyclic compounds.