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.

Room-temperature photoluminescence in amorphous SrTiO3-The influence of acceptor-type dopants

Room-temperature photoluminescence (PL) was observed in undoped and 2 mol% Cr-, Al- and Y-doped amorphous SrTiO3 thin films. Doping increased the PL, and in the case of Cr significantly reduced the associated PL wavelength. The optical bandgaps, calculated by means of UV-vis absorption spectra, increased with crystallinity and decreased with the doping level. It was considered that yttrium and aluminum substituted Sr2+, whereas chromium replaced Ti4+. It is believed that luminescence centers are oxygen-deficient BO6 complexes, or the same centers with some other defects, such as oxygen or strontium vacancies, or BO6 complexes with some other defects placed in their neighborhood. The character of excitation and the competition for negatively charged non-bridging oxygen (NBO) among numerous types of BO6 defect complexes in doped SrTiO3 results in various broadband luminescence peak positions. The results herein reported are an indicative that amorphous titanates are sensitive to doping, which is important for the control of the electro-optic properties of these materials. The probable incorporation of Cr into the Ti site suggests that the existence of a double network former can lead to materials displaying a more intense photoluminescence.

Free diet selection by broilers as influenced by dietary macronutrient ratio and corticosterone supplementation. 1. Diet selection, organ weights, and plasma metabolites

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Magnetic properties of spinel-type oxides NiMn2-xMexO4

New materials, based on the well-known spinel compound NiMn 2O4, have been synthesized and characterized from the magnetic point of view. The manganese cation was partially substituted in the general formula NiMn2-xMexO4, by nonmagnetic and magnetic elements, such as Me = Ga, Zn, Ni and Cr (0 × 1). Prior to the determination of their magnetic properties, the non-substituted spinel NiMn2O4 was carefully characterized and studied as a function of the oxygen stoichiometry, based on the influence of the annealing atmosphere and quenching rate. The ferrimagnetic character was observed in all samples, with a paramagnetic-to-ferromagnetic transition temperature T c stabilized at 110 K, and well defined long-range antiferromagnetic interactions at lower temperatures, which depend on the applied field and the substitute concentration. © 2006 Sociedad Chilena de Química.

Some considerations about a new procedure to derive transmission line parameters concerning three-phase lines

The paper shows an alternative methodology to calculate transmission line parameters per unit length and to apply it in a three-phase line with a vertical symmetry plane. This procedure is derived from a general procedure where the modal transformation matrix of the line is required. In this paper, the unknown modal transformation matrix requested by general procedure is substituted by Clarke's matrix. With the substitution that is shown in the paper, the transmission line parameters can be obtained starting from impedances measured in one terminal of the line. First, the article shows the classical methodology to calculate frequency dependent transmission line parameters by using Carson and Pollaczeck's equations for representing the ground effect and Bessel's functions to represent the skin effect. After that, a new procedure is shown to calculate frequency dependent transmission line parameters directly from currents and voltages of an existing line. Then, this procedure is applied in a non-transposed three-phase transmission line whose parameters have been previously calculated by using the classical methodology. Finally, the results obtained by using the new procedure and by using the classical methodology are compared. The article shows simulation results for typical frequency spectra of switching transients (10 Hz to 10 kHz). Results have shown that procedure has © 2006 IEEE.

Structural control of photoluminescence of four poly(urethane-urea-co-1,3,5-triazine)s: Synthesis and characterization

A series of segmented poly(urethane-urea)s containing 1,3,5 triazine in the hard block and hexamethylene spacers in the soft block was prepared. The hard to soft segment ratio was varied systematically, to afford a series of polymers in which the chromophore concentration varied from 4.2% to 18.1%. Although triazine emission is located in the UV region, the films with higher content of the chromophore emitted a visible blue light (425 nm) when excited at the very red-edge of the absorption band. The photophysical properties of the materials were strongly dependent on the relative amount of triazine moieties along the main chain. Isolated moieties emit in copolymers with small amount of triazine groups, indicating that even though in solid state, these moieties tend to be apart. Two photophysical consequences were observed when the amount of triazine increases: there is some energy transfer process involving isolated moieties with consequent decrease of the lifetime and an additional red-edge emission attributed to aggregated lumophores. The mono-exponential decay observed for the isolated form is substituted by a bi-exponential decay of the aggregated species. The materials were not strong emitters, but since the N-containing triazine moieties are good electron transport groups, the polymers have potential application as electron transport enhancers in various applications. © 2006 Elsevier B.V. All rights reserved.

Optimal contract pricing of distributed generation under a competitive framework

A bilevel programming approach for the optimal contract pricing of distributed generation (DG) in distribution networks is presented. The outer optimization problem corresponds to the owner of the DG who must decide the contract price that would maximize his profits. The inner optimization problem corresponds to the distribution company (DisCo), which procures the minimization of the payments incurred in attending the expected demand while satisfying network constraints. The meet the expected demand the DisCo can purchase energy either form the transmission network through the substations or form the DG units within its network. The inner optimization problem is substituted by its Karush- Kuhn-Tucker optimality conditions, turning the bilevel programming problem into an equivalent single-level nonlinear programming problem which is solved using commercially available software. © 2010 IEEE.

Filtering for discrete-time Markov jump systems with network transmitted mode

This paper is concerned with ℋ 2 and ℋ ∞ filter design for discrete-time Markov jump systems. The usual assumption of mode-dependent design, where the current Markov mode is available to the filter at every instant of time is substituted by the case where that availability is subject to another Markov chain. In other words, the mode is transmitted to the filter through a network with given transmission failure probabilities. The problem is solved by modeling a system with N modes as another with 2N modes and cluster availability. We also treat the case where the transition probabilities are not exactly known and demonstrate our conditions for calculating an ℋ ∞ norm bound are less conservative than the available results in the current literature. Numerical examples show the applicability of the proposed results. ©2010 IEEE.

Plasma suíno e ovo inteiro em rações de leitões sobre desempenho na fase inicial e efeito residual até a terminação

Were used 64 weaned pigs, distributed in eight treatments: ration with skim milk (SM), three rations with crescent levels of swine plasma (SP), three rations with whole egg (WE) and a ration with high inclusion of soybean meal (SB). Daily weight gain (DWG), daily feed intake (DFI) and feed conversion (FC) were evaluated. The animals that consumed ration SB have the mean of DWG higher that other treatments, and inferior FC, from 35 to 48 days of age. The crescent levels of SP promoted linear reduction in DWG, from 21 to 35, and from 35 to 48 days of age, in DFI from 48 to 138 days of age and linear increased in FC from 21 to 35 of age. Considering the weaned phase until finishing, initial rations can be formulated with SP and WE substituted partially the CP of skim milk in 25 and 45%, respectively.

Geoinformação na gestão dos recursos hídricos em sub-bacia hidrográfica

By remote sensing, geodatabase digital processing, information and expeditions to Capivara's sub-basin, was possible to identify the changes in the landscape mainly the expansion of eucalyptus, sugar-cane, and orange trees, being the last two, mainly on the Periferic Depression of Basaltic Cuesta. A significant portion of the soil on this geological area is formed from sandstones, providing high permeability to them, making them important places to groundwater recharge areas as sensible to contamination by pesticides. Throughout last decade was observed that the native vegetation fragments stabilization, keeping a reason of 26.5% on the land used between 2000 and 2010. The pasture decrease being substituted by eucalyptus, sugar-cane and orange trees call attention for the changes in the agribusiness model demanded by the current economic and social necessity. Pasture decrease followed by erosions decrease on sub-basin is evidence that these two aspects are strongly related.

Alface americana fertirrigada com diferentes doses de ácido fosfórico e hidróxido de potássio

Fertirrigation with phosphoric acid has been considered as an option to avoid drips from clogging. In some cases, this acid cause soil acidification and it can be substituted bypotassium hydroxide. This study had the objective of evaluating the effects of different phosphoric acid and potassium hydroxide doses, applied via fertirrigation, on soil fertility, plant nutrition and lettuce yield, compared to the conventional fertilization system. The experiment was carried out in greenhouse, in the College of Agricultural Sciences, FCA/UNESP, Botucatu-SP-Brazil. The experimental design was the completely randomized block, with 6 treatments and 4 replications. Treatments consisted of the combinations of doses (25% and 50% of the recommended complete dose for the lettuce) and application ofcomplete dose (100%) of phosphorus (P) and potassium (K) applied via fertirrigation, and a control (conventional fertilization system). The results showed that P and K availability in soil and nutrient concentration in plants were affected by treatments. Low phosphorus and potassium doses, applied via fertirrigation, were not efficient for the appropriate development of lettuce plants. The results showed that agronomic characteristics and commercial lettuce were affected by doses and application systems, especially the treatment with application of P and K full dose fertirrigation.

Uso de sig e fotografias aéreas na determinação de conflitos na rede de drenagem na bacia experimental do Rio Pardo

This study aimed to detect and evaluate potential conflicts in the land use along the Rio Pardo's tributaries and sub-tributaries from its source which is in Pardinho, SP to the water capture system by the Basic Sanitation Company located in Botucatu, SP. It was used 2005 colored aerial photos, taking as a tool for assessing the Geographical Information System - IDRISI Andes. The results showed that the riparian forests were substituted predominantly by pastures, which is called conflict. In other words, the 1590.82ha of environmental preservation areas (PPA's) that should be protected by riparian forests and meadows (41.51%) in 2005, were used as pastures, being in conflict with the legislation. The aerial pictures associated to SIG-Idrisi proved to be efficient tools in mapping the area and monitoring the environmental impacts.

Genotoxicity of the medicinal plant Maytenus robusta in mammalian cells in vivo.

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

Synthesis, characterization and antifungal activity of quaternary derivatives of chitosan on Aspergillus flavus

Two series of new chitosan derivatives were synthesized by reaction of deacetylated chitosan (CH) with propyl (CH-Propyl) and pentyl (CH-Pentyl) trimethylammonium bromides to obtain derivatives with increasing degrees of substitution (DS). The derivatives were characterized by 1H NMR and potentiometric titration techniques and their antifungal activities on the mycelial growth of Aspergillus flavus were investigated in vitro. The antifungal activities increase with DS and the more substituted derivatives of both series, CH-Propyl and CH-Pentyl, exhibited antifungal activities respectively three and six times higher than those obtained with commercial and deacetylated chitosan. The minimum inhibitory concentrations (MIC) were evaluated at 24, 48 and 72h by varying the polymer concentration from 0.5 to 16g/L and the results showed that the quaternary derivatives inhibited the fungus growth at polymer concentrations four times lower than that obtained with deacetylated chitosan (CH). The chitosans modified with pentyltrimethylammonium bromide exhibited higher activity and results are discussed taking into account the degree of substitution (DS). © 2012 Elsevier GmbH.

Piezoresponse force microscopy characterization of rare-earth doped BiFeO3 thin films grown by the soft chemical method

The multiferroic behavior with ion modification using rare-earth cations on crystal structures, along with the insulating properties of BiFeO3 (BFO) thin films was investigated using piezoresponse force microscopy. Rare-earth-substituted BFO films with chemical compositions of (Bi 1.00-xRExFe1.00O3 (x=0; 0.15), RE=La and Nd were fabricated on Pt (111)/Ti/SiO2/Si substrates using a chemical solution deposition technique. A crystalline phase of tetragonal BFO was obtained by heat treatment in ambient atmosphere at 500 °C for 2 h. Ion modification using La3+ and Nd3+ cations lowered the leakage current density of the BFO films at room temperature from approximately 10-6 down to 10-8 A/cm2. The observed improved magnetism of the Nd3+ substituted BFO thin films can be related to the plate-like morphology in a nanometer scale. We observed that various types of domain behavior such as 71° and 180° domain switching, and pinned domain formation occurred. The maximum magnetoelectric coefficient in the longitudinal direction was close to 12 V/cm Oe. © 2012 Elsevier Ltd and Techna Group S.r.l.