Chiral HPLC analysis of venlafaxine metabolites in rat liver microsomal preparations after LPME extraction and application to an in vitro biotransformation study

A three-phase LPME (liquid-phase microextraction) method for the enantioselective analysis of venlafaxine (VF) metabolites (O-desmethylvenlafaxine (ODV) and N-desmethylvenlafaxine (NDV) in microsomal preparations is described for the first time. The assay involves the chiral HPLC separation of drug and metabolites using a Chiralpak AD column under normal-phase mode of elution and detection at 230 nm. The LPME procedure was optimized using multifactorial experiments and the following optimal condition was established: sample agitation at 1,750 rpm, 20 min of extraction, acetic acid 0.1 mol/L as acceptor phase, 1-octanol as organic phase and donor phase pH adjustment to 10.0. Under these conditions, the mean recoveries were 41% and 42% for (-)-(R)-ODV and (+)-(S)-ODV, respectively, and 47% and 48% for (-)-( R)-NDV and (+)-( S)-NDV, respectively. The method presented quantification limits of 200 ng/mL and it was linear over the concentration range of 200-5,000 ng/mL for all analytes. The validated method was employed to study the in vitro biotransformation of VF using rat liver microsomal fraction. The results demonstrated the enantioselective biotransformation of VF.

Three-dimensional, fully adaptive simulations of phase-field fluid models

We present an efficient numerical methodology for the 31) computation of incompressible multi-phase flows described by conservative phase-field models We focus here on the case of density matched fluids with different viscosity (Model H) The numerical method employs adaptive mesh refinements (AMR) in concert with an efficient semi-implicit time discretization strategy and a linear, multi-level multigrid to relax high order stability constraints and to capture the flow`s disparate scales at optimal cost. Only five linear solvers are needed per time-step. Moreover, all the adaptive methodology is constructed from scratch to allow a systematic investigation of the key aspects of AMR in a conservative, phase-field setting. We validate the method and demonstrate its capabilities and efficacy with important examples of drop deformation, Kelvin-Helmholtz instability, and flow-induced drop coalescence (C) 2010 Elsevier Inc. All rights reserved

Chemical characterization and oxidative stability of the oils from three morphotypes of Mauritia flexuosa L.f, from the Peruvian Amazon

Three morphotypes of aguaje Mauritia flexuosa were tested, classified by the color of their mesocarpium: ""color"", ""shambo"" and ""amarillo"", collected from different areas near the city of Iquitos, Peru. Also, physical-chemical analyses of the mesocarpium were performed, such as the characterization of fatty acids by gas chromatography, determination of beta- carotene y alpha tocopherol by high efficiency liquid chromatography system in normal and reverse phase and the determination of oxidation induction time in the Rancimat apparatus. Proximate, mineral and fatty acid analyses were done on the seeds. The aguaje mesocarpium is rich in oleic oil (""amarillo"": 75.63% +/- 0.31), (beta-carotene (""amarillo"": 342.42ug/g 0.71) and alpha- tocopherol (""color"": 685.81mg/L +/- 1.04), plus the morphotype ""color"" has a superior oxidation induction time compared to other morphotypes with 6.91 +/- 0.01. The aguaje seed contains significant amounts of (06 (linoleic oil) in ""shambo"" with 36.04 +/- 0.09%. The results indicate that these oils, regardless their classification, contain important chemical compounds that give them a special nutritive value.

Suppression subtractive hybridization profiles of radial growth phase and metastatic melanoma cell lines reveal novel potential targets

Background: Melanoma progression occurs through three major stages: radial growth phase (RGP), confined to the epidermis; vertical growth phase (VGP), when the tumor has invaded into the dermis; and metastasis. In this work, we used suppression subtractive hybridization (SSH) to investigate the molecular signature of melanoma progression, by comparing a group of metastatic cell lines with an RGP-like cell line showing characteristics of early neoplastic lesions including expression of the metastasis suppressor KISS1, lack of alpha v beta 3-integrin and low levels of RHOC. Methods: Two subtracted cDNA collections were obtained, one (RGP library) by subtracting the RGP cell line (WM1552C) cDNA from a cDNA pool from four metastatic cell lines (WM9, WM852, 1205Lu and WM1617), and the other (Met library) by the reverse subtraction. Clones were sequenced and annotated, and expression validation was done by Northern blot and RT-PCR. Gene Ontology annotation and searches in large-scale melanoma expression studies were done for the genes identified. Results: We identified 367 clones from the RGP library and 386 from the Met library, of which 351 and 368, respectively, match human mRNA sequences, representing 288 and 217 annotated genes. We confirmed the differential expression of all genes selected for validation. In the Met library, we found an enrichment of genes in the growth factors/receptor, adhesion and motility categories whereas in the RGP library, enriched categories were nucleotide biosynthesis, DNA packing/repair, and macromolecular/vesicular trafficking. Interestingly, 19% of the genes from the RGP library map to chromosome 1 against 4% of the ones from Met library. Conclusion: This study identifies two populations of genes differentially expressed between melanoma cell lines from two tumor stages and suggests that these sets of genes represent profiles of less aggressive versus metastatic melanomas. A search for expression profiles of melanoma in available expression study databases allowed us to point to a great potential of involvement in tumor progression for several of the genes identified here. A few sequences obtained here may also contribute to extend annotated mRNAs or to the identification of novel transcripts.

Dynamic transitions in a three dimensional associating lattice gas model

The aggregation of interacting Brownian particles in sheared concentrated suspensions is an important issue in colloid and soft matter science per se. Also, it serves as a model to understand biochemical reactions occurring in vivo where both crowding and shear play an important role. We present an effective medium approach within the Smoluchowski equation with shear which allows one to calculate the encounter kinetics through a potential barrier under shear at arbitrary colloid concentrations. Experiments on a model colloidal system in simple shear flow support the validity of the model in the concentration range considered. By generalizing Kramers' rate theory to the presence of shear and collective hydrodynamics, our model explains the significant increase in the shear-induced reaction-limited aggregation kinetics upon increasing the colloid concentration.

Dynamical breaking of gauge symmetry in supersymmetric quantum electrodynamics in three-dimensional spacetime

The dynamical breaking of gauge symmetry in the supersymmetric quantum electrodynamics in three-dimensional spacetime is studied at two-loop approximation. At this level, the effective superpotential is evaluated in a supersymmetric phase. At one-loop order, we observe a generation of the Chern-Simons term due to a parity violating term present in the classical action. At two-loop order, the scalar background superfield acquires a nonvanishing vacuum expectation value, generating a mass term A(alpha)A(alpha) through the Coleman-Weinberg mechanism. It is observed that the mass of gauge superfield is predominantly an effect of the topological Chern-Simons term.

Isotropic and anisotropic spin-spin interactions and a quantum phase transition in a dinuclear Cu(II) compound

We report electron-paramagnetic resonance (EPR) studies at similar to 9.5 GHz (X band) and similar to 34 GHz (Q band) of powder and single-crystal samples of the compound Cu(2)[TzTs](4) [N-thiazol-2-yl-toluenesulfonamidatecopper(II)], C(40)H(36)Cu(2)N(8)O(8)S(8), having copper(II) ions in dinuclear units. Our data allow determining an antiferromagnetic interaction J(0)=(-113 +/- 1) cm(-1) (H(ex)=-J(0)S(1)center dot S(2)) between Cu(II) ions in the dinuclear unit and the anisotropic contributions to the spin-spin coupling matrix D (H(ani)=S(1)center dot D center dot S(2)), a traceless symmetric matrix with principal values D/4=(0.198 +/- 0.003) cm(-1) and E/4=(0.001 +/- 0.003) cm(-1) arising from magnetic dipole-dipole and anisotropic exchange couplings within the units. In addition, the single-crystal EPR measurements allow detecting and estimating very weak exchange couplings between neighbor dinuclear units, with an estimated magnitude parallel to J(')parallel to=(0.060 +/- 0.015) cm(-1). The interactions between a dinuclear unit and the ""environment"" of similar units in the structure of the compound produce a spin dynamics that averages out the intradinuclear dipolar interactions. This coupling with the environment leads to decoherence, a quantum phase transition that collapses the dipolar interaction when the isotropic exchange coupling with neighbor dinuclear units equals the magnitude of the intradinuclear dipolar coupling. Our EPR experiments provide a new procedure to follow the classical exchange-narrowing process as a shift and collapse of the line structure (not only as a change of the resonance width), which is described with general (but otherwise simple) theories of magnetic resonance. Using complementary procedures, our EPR measurements in powder and single-crystal samples allow measuring simultaneously three types of interactions differing by more than three orders of magnitude (between 113 cm(-1) and 0.060 cm(-1)).

Low dimensional behavior in three-dimensional coupled map lattices

The analysis of one-, two-, and three-dimensional coupled map lattices is here developed under a statistical and dynamical perspective. We show that the three-dimensional CML exhibits low dimensional behavior with long range correlation and the power spectrum follows 1/f noise. This approach leads to an integrated understanding of the most important properties of these universal models of spatiotemporal chaos. We perform a complete time series analysis of the model and investigate the dependence of the signal properties by change of dimension. (c) 2008 Elsevier Ltd. All rights reserved.

Comparison of three-dimensional lower extremity running kinematics of young adult and elderly runners

The objective of this study was to compare the three-dimensional lower extremity running kinematics of young adult runners and elderly runners. Seventeen elderly adults (age 67-73 years) and 17 young adults (age 26-36 years) ran at 3.1ms-1 on a treadmill while the movements of the lower extremity during the stance phase were recorded at 120Hz using three-dimensional video. The three-dimensional kinematics of the lower limb segments and of the ankle and knee joints were determined, and selected variables were calculated to describe the movement. Our results suggest that elderly runners have a different movement pattern of the lower extremity from that of young adults during the stance phase of running. Compared with the young adults, the elderly runners had a substantial decrease in stride length (1.97 vs. 2.23m; P=0.01), an increase in stride frequency (1.58 vs. 1.37Hz; P=0.002), less knee flexion/extension range of motion (26 vs. 33; P=0.002), less tibial internal/external rotation range of motion (9 vs. 12; P0.001), larger external rotation angle of the foot segment (toe-out angle) at the heel strike (-5.8 vs. -1.0; P=0.009), and greater asynchronies between the ankle and knee movements during running. These results may help to explain why elderly individuals could be more susceptible to running-related injuries.

Rapid solidification and phase stability evaluation of Ti-Si-B alloys

Ti-rich Ti-Si-B alloys can be considered for structural applications at high temperatures (max. 700 degrees C), however, phase equilibria data is reported only for T = 1250 degrees C. Thus, in this work the phase stability of this system has been evaluated at 700 degrees C. In order to attain equilibrium conditions in shorter time, rapid solidified samples have been prepared and carefully characterized. The microstructural characterization of the produced materials were based on X-ray diffraction (XRD), scanning electron microscopy (SEM-BSE), high resolution transmission electron microscopy (HRTEM), High Temperature X-ray diffraction with Synchrotron radiation (XRDSR) and Differential Scanning Calorimetry (DSC). Amorphous and amorphous with embedded nanocrystals have been observed after rapid solidification from specific alloy compositions. The values of the crystallization temperature (Tx) of the alloys were in the 509-647 degrees C temperature range. After Differential Scanning Calorimetry and High Temperature X-ray Diffraction with Synchrotron radiation, the alloys showed crystalline and basically formed by two or three of the following phases: alpha Ti, Ti(6)Si(2)B; Ti(5)Si(3); Ti(3)Si and TiB. It has been shown the stability of the Ti(3)Si and Ti(6)Si(2)B phases at 700 degrees C and the proposition of an isothermal section at this temperature. (C) 2011 Elsevier B.V. All rights reserved.

Aerodynamic study of three-dimensional larynx models using finite element methods

The airflow velocities and pressures are calculated from a three-dimensional model of the human larynx by using the finite element method. The laryngeal airflow is assumed to be incompressible, isothermal, steady, and created by fixed pressure drops. The influence of different laryngeal profiles (convergent, parallel, and divergent), glottal area, and dimensions of false vocal folds in the airflow are investigated. The results indicate that vertical and horizontal phase differences in the laryngeal tissue movements are influenced by the nonlinear pressure distribution across the glottal channel, and the glottal entrance shape influences the air pressure distribution inside the glottis. Additionally, the false vocal folds increase the glottal duct pressure drop by creating a new constricted channel in the larynx, and alter the airflow vortexes formed after the true vocal folds. (C) 2007 Elsevier Ltd. All rights reserved.

Performance evaluation of packing materials in the removal of hydrogen sulphide in gas-phase biofilters: Polyurethane foam, sugarcane bagasse, and coconut fibre

The main objective of this work was to investigate three packing materials (polyurethane foam, sugar-cane bagasse, and coconut fibre) for biofiltration of a gaseous mixture containing hydrogen sulphide (H(2)S). Mixed cultures were obtained from two sources, aerated submerged biofilters and activated sludge, and were utilised as inoculums. Biofilters reached 100% removal efficiency after two clays of operation. The empty bed residence time was 495 for each of the biofilters. The reactors were operated simultaneously, and the inlet concentrations of H(2)S varied between 184 and 644 ppmv during the long-term continuous operation of the biofilters (100 clays). Average removal efficiencies remained above 99.3%, taking into consideration the entire period of operation. Average elimination capacities reached by the biofilters packed with polyurethane foam, coconut fibre, and sugarcane bagasse were in the range of 17.8-66.6; 18.9-68.8, and 18.7-72.9g m(-3) h(-1), respectively. Finally, we concluded that the packing materials tested in this work are appropriate for the long-term biofiltration of hydrogen sulphide. (C) 2010 Elsevier B.V. All rights reserved.

Network of phase-locking oscillators and a possible model for neural synchronization

In order to model the synchronization of brain signals, a three-node fully-connected network is presented. The nodes are considered to be voltage control oscillator neurons (VCON) allowing to conjecture about how the whole process depends on synaptic gains, free-running frequencies and delays. The VCON, represented by phase-locked loops (PLL), are fully-connected and, as a consequence, an asymptotically stable synchronous state appears. Here, an expression for the synchronous state frequency is derived and the parameter dependence of its stability is discussed. Numerical simulations are performed providing conditions for the use of the derived formulae. Model differential equations are hard to be analytically treated, but some simplifying assumptions combined with simulations provide an alternative formulation for the long-term behavior of the fully-connected VCON network. Regarding this kind of network as models for brain frequency signal processing, with each PLL representing a neuron (VCON), conditions for their synchronization are proposed, considering the different bands of brain activity signals and relating them to synaptic gains, delays and free-running frequencies. For the delta waves, the synchronous state depends strongly on the delays. However, for alpha, beta and theta waves, the free-running individual frequencies determine the synchronous state. (C) 2011 Elsevier B.V. All rights reserved.

Continuous extraction of alpha-toxin from a fermented broth of Clostridium perfringens Type A in perforated rotating disc contactor using aqueous two-phase PEG-phosphate system

A 2(3-1) factorial experimental design was used to evaluate the performance of a perforated rotating disc contactor to extract alpha-toxin from the fermented broth of Clostridium perfringens Type A by aqueous two-phase system of polyethylene glycol-phosphate salts. The influence of three independent variables, specifically the dispersed phase flowrate, the continuous phase flowrate and the disc rotational speed, was investigated on the hold up, the mass transfer coefficient, the separation efficiency and the purification factor, taken as the response variables. The optimum dispersed phase flowrate was 3.0 mL/min for all these responses. Besides, maximum values of hold up (0.80), separation efficiency (0. 10) and purification factor (2.4) were obtained at this flowrate using the lowest disc rotational speed (35 rpm), while the optimum mass transfer coefficient (0. 165 h(-1)) was achieved at the highest agitation level (140 rpm). The results of this study demonstrated that the dispersed phase flowrate strongly influenced the performance of PRDC, in that both the mass transfer coefficient and hold up increased with this parameter. (c) 2007 Elsevier B. V. All rights reserved.

Liquid-liquid extraction of proteases from fermented broth by PEG/citrate aqueous two-phase system

This work deals with the use of an aqueous two-phase system (ATPS) of PEG/citrate to remove proteases from a Clostridium perfringens fermentation broth. To plan the experimental tests and evaluate the corresponding results, three successive experimental designs were employed, for which the PEG molar mass (M-PEG) and concentration (C-PEG), the citrate concentration (C-C) and the pH were selected as independent variables, while the purification factor (PF), the partition coefficient (K), the activity yield (Y) and the selectivity (S) were selected as responses. PF of proteases in the top phase was shown to increase with increasing MPEG and decreasing Cc, whereas a completely opposite trend was observed for K. On the other hand, Y was favored by simultaneous decreases in both these variables, while S decreased with increasing Cc. Therefore, selecting a simultaneous increase in PF and Y as the most desirable result, the best performance of the system was obtained using M-PEG = 10-000 g/mol C-PEG = 22% (w/w) and C-c = 8.0% (w/w) at pH 8.5. Under these conditions, the activity yield was very high (131 %) but the purification factor (4.2) and the selectivity (4.3) were lower than those ensured by more selective purification methods. According to these results, the ATPS seems to be an interesting alternative primary concentration/decontamination step for vaccine preparation from C. perfringens fermented broth. (C) 2007 Elsevier B.V. All rights reserved.