Bayesian L-optimal exact design of experiments for biological kinetic models

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Inorganic-Organic Nanocomposite Assembly Using Collagen as a Template and Sodium Tripolyphosphate as a Biomimetic Analog of Matrix Phosphoprotein

Nanocomposites created with polycarboxylic acid alone as a stabilization agent for prenucleation clusters-derived amorphous calcium phosphate exhibit nonperiodic apatite deposition. In the present study, we report the use of inorganic polyphosphate as a biomimetic analog of matrix phosphoprotein for directing poly(acrylic acid)-stabilized amorphous nano-precursor phases to assemble into periodic apatite-collagen nanocomposites. The sorption and desorption characteristics of sodium tripolyphosphate to type I collagen were examined. Periodic nanocomposite assembly with collagen as a template was demonstrated with TEM and SEM using a Portland cement-based resin composite and a phosphate-containing simulated body fluid. Apatite was detected within the collagen at 24 h and became more distinct at 48 h, with prenucleation clusters attaching to the collagen fibril surface during the initial infiltration stage. Apatite-collagen nanocomposites at 72 h were heavily mineralized with periodically arranged intrafibrillar apatite platelets. Defect-containing nanocomposites caused by desorption of TPP from collagen fibrils were observed in regions lacking the inorganic phase.

Monitoring the covariance matrix with the VMAX chart

In this article, we propose a new statistic to control the covariance matrix of bivariate processes. This new statistic is based on the sample vat-lances of the two quality characteristics, shortly VMAX statistic. The points plotted on the chart correspond to the maximum of the values of these two variances. The reasons to consider the VMAX statistic instead of the generalized variance vertical bar S vertical bar are faster detection of process changes and better diagnostic feature, that is, with the VMAX statistic It is easier to identify the out-of-control variable.

Characterization of gallotannins from Astronium species by flow injection analysis-electrospray ionization-ion trap-tandem mass spectrometry and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Structure, ferroelectric/magnetoelectric properties and leakage current density of (Bi0.85Nd0.15)FeO3 thin films

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Controlled Cisplatin Delivery from Ureasil-PEO1900 Hybrid Matrix

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Electronic spectra, ESR and crystal structure of tetrahedral halocuprates(II). The existence of cations (2tbpo·H+) with a very short hydrogen bond

Two compounds [2tbpo·H+)2[CuCl4]= (yellow) and (2tbpo·H+)2[CuBr4]= (dark purple) (tbpo = tribenzylphosphine oxide) have been prepared and investigated by means of crystal structure, electronic, vibrational and ESR spectra. The crystal structure of the (2tbpo·H+)2[CuCl4]= complex was determined by three-dimensional X-ray diffraction. The compound crystallizes in the space group P42/n with unit-cell dimensions a = 19.585(2), c = 9.883(1)Å, V = 3790 (1)Å3, Z = 2, Dm = 1.303 (flotation) Dx = 1.302 Mg m-3. The structure was solved by direct methods and refined by blocked full-matrix least-squares to R = 0.053 for 2583 observed reflections. Cu(II) is coordinated to four chlorides in a tetrahedral arrangement. Tribenzylphosphine oxide molecules, related by a centre of inversion, are connected by a short hydrogen bridge. Chemical analysis, electronic and vibrational spectra showed that the bromide compound is similar to the chloride one and can be formulated as (2tbpo·H+)2[CuBr4]=. The position of the dd transition bands, the charge transfer bands, the ESR and the vibrational spectra of both complexes are discussed. The results are compared with analogous complexes cited in the literature. © 1983.

Two-matrix string model as constrained (2+1)-dimensional integrable system

We show that the 2-matrix string model corresponds to a coupled system of 2 + 1-dimensional KP and modified KP ((m)KP2+1) integrable equations subject to a specific symmetry constraint. The latter together with the Miura-Konopelchenko map for (m)KP2+1 are the continuum incarnation of the matrix string equation. The (m)KP2+1 Miura and Backhand transformations are natural consequences of the underlying lattice structure. The constrained (m)KP2+1 system is equivalent to a 1 + 1-dimensional generalized KP-KdV hierarchy related to graded SL(3,1). We provide an explicit representation of this hierarchy, including the associated W(2,1)-algebra of the second Hamiltonian structure, in terms of free currents.

Constrained KP models as integrable matrix hierarchies

We formulate the constrained KP hierarchy (denoted by cKP K+1,M) as an affine sl(M + K+ 1) matrix integrable hierarchy generalizing the Drinfeld-Sokolov hierarchy. Using an algebraic approach, including the graded structure of the generalized Drinfeld-Sokolov hierarchy, we are able to find several new universal results valid for the cKP hierarchy. In particular, our method yields a closed expression for the second bracket obtained through Dirac reduction of any untwisted affine Kac-Moody current algebra. An explicit example is given for the case sl(M + K + 1), for which a closed expression for the general recursion operator is also obtained. We show how isospectral flows are characterized and grouped according to the semisimple non-regular element E of sl(M + K+ 1) and the content of the center of the kernel of E. © 1997 American Institute of Physics.

Structure of thrombin complexed with selective non-electrophilic inhibitors having cyclohexyl moieties at P1

The crystal structures of five new non-electrophilic β-strand-templated thrombin active-site inhibitors have been determined bound to the enzyme. Four co-crystallize with hirugen and inhibitor isomorphously to produce thrombin-hirugen crystals (monoclinic, space group C2), while one co-crystallizes in the hexagonal system, space group P65. A 1,4-substituted cyclohexyl moiety is conserved at the P1 position of all the inhibitors, along with a fused hetero-bicyclic five- and six-membered ring that occupies the P2 site. Amino, amidino and aminoimidazole groups are attached to the cyclohexyl ring for recognition at the S1 specificity site, while benzylsulfonyl and diphenyl groups enhance the binding at the S3 subsite. The cyclohexyl groups at the P1 positions of three of the inhibitors appear to be in the energetically favored chair conformation, while the imidazole-substituted cyclohexyl rings are in a boat conformation. Somewhat unexpectedly, the two cyclohexyl-aminoimidazole groups bind differently in the specificity site; the unique binding of one is heretofore unreported. The other inhibitors generally mimic arginyl binding at S1. This group of inhibitors combines the nonelectrophilicity and selectivity of DAPA-like compounds and the more optimal binding features of the S1-S3 sites of thrombin for peptidic molecules, which results in highly potent (binding constants 12 nM-16 pM, one being 1.1 μM) and selective (ranging from 140 to 20 000 times more selective compared with trypsin) inhibitors of thrombin. The binding modes of these novel inhibitors are correlated with their binding constants, as is their selectivity, in order to provide further insight for the design of therapeutic antithrombotic agents that inhibit thrombin directly at the active site.

Population structure of the seabob shrimp Xiphopenaeus kroyeri (Heller, 1862) (Crustacea: Penaeoidea) in the littoral of São Paulo, Brazil

The population structure of the penaeidean shrimp Xyphopenacus kroyeri was studied in Ubatuba Bay, Ubatuba, Sd̃ao Paulo, Brazil. The period and site of juvenile recruitment were monitored using a monthly sampling design with eight fixed areas (transects) from September 1995 to August 1996. The population structure was assessed using size frequency distributions (based on carapace length) for each month and sampling area. Females were significantly larger than males, suggesting a differential growth between sexes. The very low occurrence of large adults in the Bay can be related to offshore migration for reproduction. Recruitment occurred throughout the year, with a peak during the summer, when the highest recruitment rates were obtained along inshore transects. The present investigation revealed valuable information on the biology of the species mainly in the study region, which is considered a nursery ground for juveniles of X. kroyeri. The species showed an important variation from the typical life cycle that it is assumed to hold over its entire range and X. kroyeri should be classified as having a life cycle different from that proposed previously in the literature, i.e. the juveniles prefer inshore areas instead of estuaries. Some suggestions for the seabob fishery management are proposed as an alternative for minimising the impact during the harvest period and adjusting the protection schedule.

Kinetics and crystal structure of human purine nucleoside phosphorylase in complex with 7-methyl-6-thio-guanosine

Purine nucleoside phosphorylase (PNP) catalyzes the reversible phosphorolysis of nucleosides and deoxynucleosides, generating ribose 1-phosphate and the purine base, which is an important step of purine catabolism pathway. The lack of such an activity in humans, owing to a genetic disorder, causes T-cell impairment, and drugs that inhibit this enzyme may have the potential of being utilized as modulators of the immunological system to treat leukemia, autoimmune diseases, and rejection in organ transplantation. Here, we describe kinetics and crystal structure of human PNP in complex with 7-methyl-6-thio-guanosine, a synthetic substrate, which is largely used in activity assays. Analysis of the structure identifies different protein conformational changes upon ligand binding, and comparison of kinetic and structural data permits an understanding of the effects of atomic substitution on key positions of the synthetic substrate and their consequences to enzyme binding and catalysis. Such knowledge may be helpful in designing new PNP inhibitors. © 2005 Elsevier Inc. All rights reserved.

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.

cDNA cloning and 1.75 Å crystal structure determination of PPL2, an endochitinase and N-acetylglucosamine-binding hemagglutinin from Parkia platycephala seeds

Parkia platycephala lectin 2 was purified from Parkia platycephala (Leguminosae, Mimosoideae) seeds by affinity chromatography and RP-HPLC. Equilibrium sedimentation and MS showed that Parkia platycephala lectin 2 is a nonglycosylated monomeric protein of molecular mass 29 407 ± 15 Da, which contains six cysteine residues engaged in the formation of three intramolecular disulfide bonds. Parkia platycephala lectin 2 agglutinated rabbit erythrocytes, and this activity was specifically inhibited by N-acetylglucosamine. In addition, Parkia platycephala lectin 2 hydrolyzed β(1-4) glycosidic bonds linking 2-acetoamido-2-deoxy-β-d-glucopyranose units in chitin. The full-length amino acid sequence of Parkia platycephala lectin 2, determined by N-terminal sequencing and cDNA cloning, and its three-dimensional structure, established by X-ray crystallography at 1.75 Å resolution, showed that Parkia platycephala lectin 2 is homologous to endochitinases of the glycosyl hydrolase family 18, which share the (βα) 8 barrel topology harboring the catalytic residues Asp125, Glu127, and Tyr182. © 2006 The Authors.

A unique intraorbital osseous structure in the large fruit-eating bat (Artibeus lituratus)

Objective: To describe the normal bony orbital structure of the large fruit-eating bat (Artibeus lituratus) with emphasis on a unique intraorbital bony structure previously not described in the literature. Procedures: The bony anatomy of the orbital cavity was studied on dissected skulls of large fruit-eating bats. The anatomic description of a unique intraorbital spine was made while studying the bony orbit of macerated skulls. Additional observations were made on dissected formalin-fixed whole heads. Both procedures were performed under a stereo dissecting microscope, using ×2-4-magnification. A histologic analysis of soft tissues surrounding this cylindrical bony structure was performed using cross and longitudinal oblique sections from decalcified whole heads, which had been fixed in formalin. Additionally, biometric measurements and a histomorphometric analysis were performed. Results and conclusions: An intraorbital cylindrical osseous structure measuring 3.96 ± 0.68 mm in length and 155.62 ± 14.03 μm in diameter was observed in the large fruit-eating bat (A. lituratus), creating a unique orbital structural design among mammals. We suggest the name optic spine of the alisphenoid bone. The anatomic, biometric and histologic characterization of this element might contribute to a further understanding of the dynamics of bat vision and the sort of factors that influenced evolution of the visual system of microbats. The authors hope that the documentation of this distinctive anatomic feature will also expand the debate about the phylogenetic analysis of the relationship among bat species in the near future. © 2007 American College of Veterinary Ophthalmologists.