A new SOS-DFPT approximation for NMR shielding calculations : the Loc.3 correction applied to the catalytic mechanism of Serine Proteases

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

A new SOS-DFPT approximation for NMR shielding calculations : the Loc.3 correction applied to the catalytic mechanism of Serine Proteases

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

Disability Discrimination: Obesity and the Court of Justice of the European Union’s decision in Karsten Kaltoft v Billund Kommune Case C-354/13 ECJ

Walker and Karsten are two important decisions in disability discrimination law – not solely on the basis of their legal and practical repercussions for the United Kingdom (UK) and European Union (EU), respectively, but because they capture the very ideological spirit of domestic and European anti-discrimination legislation. The former directly relates to disability discrimination in the UK and the entire EU is feeling the brunt of the Court of Justice of the European Union’s decision in the latter. This article explores the impact of both these decisions and to what extent the obese or those suffering from a functional overlay are now protected from being discriminated against by the Framework Directive 2000/78 and the United Kingdom’s Equality Act 2010.

First-Principles Calculations of the Electronic and Structural Properties of GaSb

In this paper, we carried out first-principles calculations in order to investigate the structural and electronic properties of the binary compound gallium antimonide (GaSb). This theoretical study was carried out using the Density Functional Theory within the plane-wave pseudopotential method. The effects ofexchange and correlation (XC) were treated using the functional Local Density Approximation (LDA), generalized gradient approximation (GGA): Perdew–Burke–Ernzerhof (PBE), Perdew-Burke-Ernzerhof revised for solids (PBEsol), Perdew-Wang91 (PW91), revised Perdew–Burke–Ernzerhof (rPBE), Armiento–Mattson 2005 (AM05) and meta-generalized gradient approximation (meta-GGA): Tao–Perdew– Staroverov–Scuseria (TPSS) and revised Tao–Perdew–Staroverov–Scuseria (RTPSS) and modified Becke-Johnson (MBJ). We calculated the densities of state (DOS) and band structure with different XC potentials identified and compared them with the theoretical and experimental results reported in the literature. It was discovered that functional: LDA, PBEsol, AM05 and RTPSS provide the best results to calculate the lattice parameters (a) and bulk modulus (B0); while for the cohesive energy (Ecoh), functional: AM05, RTPSS and PW91 are closer to the values obtained experimentally. The MBJ, Rtpss and AM05 values found for the band gap energy is slightly underestimated with those values reported experimentally.

The Applicability Of Ordered Mesoporous Sba-15 And Its Hydrophobic Glutaraldehyde-bridge Derivative To Improve Ibuprofen-loading In Releasing System.

The mesoporous SBA-15 silica with uniform hexagonal pore, narrow pore size distribution and tuneable pore diameter was organofunctionalized with glutaraldehyde-bridged silylating agent. The precursor and its derivative silicas were ibuprofen-loaded for controlled delivery in simulated biological fluids. The synthesized silicas were characterized by elemental analysis, infrared spectroscopy, (13)C and (29)Si solid state NMR spectroscopy, nitrogen adsorption, X-ray diffractometry, thermogravimetry and scanning electron microscopy. Surface functionalization with amine containing bridged hydrophobic structure resulted in significantly decreased surface area from 802.4 to 63.0 m(2) g(-1) and pore diameter 8.0-6.0 nm, which ultimately increased the drug-loading capacity from 18.0% up to 28.3% and a very slow release rate of ibuprofen over the period of 72.5h. The in vitro drug release demonstrated that SBA-15 presented the fastest release from 25% to 27% and SBA-15GA gave near 10% of drug release in all fluids during 72.5 h. The Korsmeyer-Peppas model better fits the release data with the Fickian diffusion mechanism and zero order kinetics for synthesized mesoporous silicas. Both pore sizes and hydrophobicity influenced the rate of the release process, indicating that the chemically modified silica can be suggested to design formulation of slow and constant release over a defined period, to avoid repeated administration.

A New Platinum Complex With Tryptophan: Synthesis, Structural Characterization, Dft Studies And Biological Assays In Vitro Over Human Tumorigenic Cells.

A new platinum(II) complex with the amino acid L-tryptophan (trp), named Pt-trp, was synthesized and characterized. Elemental, thermogravimetric and ESI-QTOF mass spectrometric analyses led to the composition [Pt(C11H11N2O2)2]⋅6H2O. Infrared spectroscopic data indicate the coordination of trp to Pt(II) through the oxygen of the carboxylate group and also through the nitrogen atom of the amino group. The (13)C CP/MAS NMR spectroscopic data confirm coordination through the oxygen atom of the carboxylate group, while the (15)N CP/MAS NMR data confirm coordination of the nitrogen of the NH2 group to the metal. Density functional theory (DFT) studies were applied to evaluate the cis and trans coordination modes of trp to platinum(II). The trans isomer was shown to be energetically more stable than the cis one. The Pt-trp complex was evaluated as a cytotoxic agent against SK-Mel 103 (human melanoma) and Panc-1 (human pancreatic carcinoma) cell lines. The complex was shown to be cytotoxic over the considered cells.

Bp-13 Pla2: Purification And Neuromuscular Activity Of A New Asp49 Toxin Isolated From Bothrops Pauloensis Snake Venom.

A new PLA2 (Bp-13) was purified from Bothrops pauloensis snake venom after a single chromatographic step of RP-HPLC on μ-Bondapak C-18. Amino acid analysis showed a high content of hydrophobic and basic amino acids and 14 half-cysteine residues. The N-terminal sequence showed a high degree of homology with basic Asp49 PLA2 myotoxins from other Bothrops venoms. Bp-13 showed allosteric enzymatic behavior and maximal activity at pH 8.1, 36°-45°C. Full Bp-13 PLA2 activity required Ca(2+); its PLA2 activity was inhibited by Mg(2+), Mn(2+), Sr(2+), and Cd(2+) in the presence and absence of 1 mM Ca(2+). In the mouse phrenic nerve-diaphragm (PND) preparation, the time for 50% paralysis was concentration-dependent (P < 0.05). Both the replacement of Ca(2+) by Sr(2+) and temperature lowering (24°C) inhibited the Bp-13 PLA2-induced twitch-tension blockade. Bp-13 PLA2 inhibited the contractile response to direct electrical stimulation in curarized mouse PND preparation corroborating its contracture effect. In biventer cervicis preparations, Bp-13 induced irreversible twitch-tension blockade and the KCl evoked contracture was partially, but significantly, inhibited (P > 0.05). The main effect of this new Asp49 PLA2 of Bothrops pauloensis venom is on muscle fiber sarcolemma, with avian preparation being less responsive than rodent preparation. The study enhances biochemical and pharmacological characterization of B. pauloensis venom.

Estudo teórico da interação existente entre a artemisinina e o heme

The purpose of this work is to study theoretically stereoelectronic aspects of the interaction between heme and artemisinin in the transitional heme-artemisinin complex. Through semi-empirical calculations using the PM3 method, the potential energy barrier of artemisinin rotation relative to heme in the heme-artemisinin complex was studied in vacuum and in the partially solvated state. The minimum heat of formation obtained for the complex with and without water molecules is -702.39 and -100.86 kcal mol-1, respectively, which corresponds to the dihedral angle C-Fe-O1-O2 of 43.93º and 51.90º around the iron-oxygen O1 bond, respectively. The water molecules bind to heme via 13 hydrogen bonds and O-H O and 6 C-H O interactions, which accounts for -67.23 kcal mol-1. It is observed that the inclusion of water molecules does not affect significantly the stability of the heme-artemisinin complex.

O uso da mitomicina C em cirurgia combinada

Purpose: To analyze the efficacy and safety of intraope-rative mitomycin C (MMC) in combined procedures (extra-capsular cataract extraction + trabeculectomy). Methods: Twenty-four patients were randomized to either MMC (0.5 mg/ml) (n = 14) or saline solution (n = 10) for 3 minutes during the combined procedure. Results: Twelve months after surgery, mean IOP in the MMC group (13.2 ± 2.9 mmHg) was significantly lower than in the control group (16.3 ± 3.9 mmHg) (p = 0.02). The mean number of medications used during the 12-month follow-up in the control group (1.33 ± 0.5) was significantly higher than in the MMC-treated group (0.5 ± 0.5) (p = 0.005). Life table analysis showed a significantly higher probability of IOP control in the MMC group than in the control group (p < 0.01). Conclusions: Intraoperative MMC is safe and effective in pro-moting a better IOP control and reducing the need for postoperative antiglaucoma medications. We suggest intraope-rative MMC to be routinely employed in combined procedures.

Teste de banco com carga continua para analise do volume de oxigenio (VO2) predito e analisado por tempo de esforço em pessoas treinadas (TRD), ativas (ATV) e destreinadas (DTR) a partir dos 13 anos : proposta de validação

Universidade Estadual de Campinas . Faculdade de Educação Física

Impacto da proteína-C reativa no risco cardiovascular de adolescentes

FUNDAMENTO: Vários estudos sugerem que a proteína-C reativa (PCR) se correlaciona com doença arterial coronariana em adultos. Entretanto, essa associação ainda é pouco explorada em adolescentes. OBJETIVO: Avaliar a associação entre a PCR e os fatores de risco cardiovascular em adolescentes obesos. MÉTODOS: Oitenta e quatro adolescentes (12,6 ± 1,3 anos), ambos os sexos, foram distribuídos nos grupos Eutrófico (n = 28), Sobrepeso (n = 28) e Obeso (n = 28), segundo o índice de massa corpórea (IMC). A concentração de PCR (ELISA ultrassensível), o perfil lipídico e o conteúdo de anticorpos anti-LDLox (ELISA) foram determinados após jejum de 12h. RESULTADOS: Os grupos foram semelhantes quanto a idade (p = 0,13) e sexo (p = 0,83). Colesterol total, HDL-C, CT/HDL-C e LDL-C/HDL-C apresentaram diferenças significativas entre os grupos Eutrófico e Obeso. Não houve variação significativa no conteúdo de anticorpos anti-LDLox. Os valores de PCR foram diferentes entre os três grupos (p < 0,01). PCR apresentou associação significativa com IMC (β = 2,533), CB (β = 2,645) e CC (β = 2,945), CT (β = 0,006), LDL-C (β = 0,006) e anticorpos anti-LDLox (β = 0,383) e negativa entre HDL-C (β = -0,017). CONCLUSÃO: Os resultados indicam que a PCR se associa significativamente com marcadores de risco cardiovascular em adolescentes.

Impacto da Proteína-C reativa no risco cardiovascular de adolescentes

Vários estudos sugerem que a proteína-C reativa (PCR) se correlaciona com doença arterial coronariana em adultos. Entretanto, essa associação ainda é pouco explorada em adolescentes. Avaliar a associação entre a PCR e os fatores de risco cardiovascular em adolescentes obesos. Oitenta e quatro adolescentes (12,6 ± 1,3 anos), ambos os sexos, foram distribuídos nos grupos Eutrófico (n = 28), Sobrepeso (n = 28) e Obeso (n = 28), segundo o índice de massa corpórea (IMC). A concentração de PCR (ELISA ultrassensível), o perfil lipídico e o conteúdo de anticorpos anti-LDLox (ELISA) foram determinados após jejum de 12h. Os grupos foram semelhantes quanto a idade (p = 0,13) e sexo (p = 0,83). Colesterol total, HDL-C, CT/HDL-C e LDL-C/HDL-C apresentaram diferenças significativas entre os grupos Eutrófico e Obeso. Não houve variação significativa no conteúdo de anticorpos anti-LDLox. Os valores de PCR foram diferentes entre os três grupos (p < 0,01). PCR apresentou associação significativa com IMC (β = 2,533), CB (β = 2,645) e CC (β = 2,945), CT (β = 0,006), LDL-C (β = 0,006) e anticorpos anti-LDLox (β = 0,383) e negativa entre HDL-C (β = -0,017). Os resultados indicam que a PCR se associa significativamente com marcadores de risco cardiovascular em adolescentes

Distribution of hepatitis c virus (hcv) genotypes in patients with chronic infection from Rondonia, Brazil

Background: Hepatitis C virus (HCV) is an important human pathogen affecting around 3% of the human population. In Brazil, it is estimated that there are approximately 2 to 3 million HCV chronic carriers. There are few reports of HCV prevalence in Rondonia State (RO), but it was estimated in 9.7% from 1999 to 2005. The aim of this study was to characterize HCV genotypes in 58 chronic HCV infected patients from Porto Velho, Rondonia (RO), Brazil. Methods: A fragment of 380 bp of NS5B region was amplified by nested PCR for genotyping analysis. Viral sequences were characterized by phylogenetic analysis using reference sequences obtained from the GenBank (n = 173). Sequences were aligned using Muscle software and edited in the SE-AL software. Phylogenetic analyses were conducted using Bayesian Markov chain Monte Carlo simulation (MCMC) to obtain the MCC tree using BEAST v. 1.5.3. Results: From 58 anti-HCV positive samples, 22 were positive to the NS5B fragment and successfully sequenced. Genotype 1b was the most prevalent in this population (50%), followed by 1a (27.2%), 2b (13.6%) and 3a (9.0%). Conclusions: This study is the first report of HCV genotypes from Rondonia State and subtype 1b was found to be the most prevalent. This subtype is mostly found among people who have a previous history of blood transfusion but more detailed studies with a larger number of patients are necessary to understand the HCV dynamics in the population of Rondonia State, Brazil.

Transiting exoplanets from the CoRoT space mission X. CoRoT-10b: a giant planet in a 13.24 day eccentric orbit

Context. The space telescope CoRoT searches for transiting extrasolar planets by continuously monitoring the optical flux of thousands of stars in several fields of view. Aims. We report the discovery of CoRoT-10b, a giant planet on a highly eccentric orbit (e = 0.53 +/- 0.04) revolving in 13.24 days around a faint (V = 15.22) metal-rich K1V star. Methods. We used CoRoT photometry, radial velocity observations taken with the HARPS spectrograph, and UVES spectra of the parent star to derive the orbital, stellar, and planetary parameters. Results. We derive a radius of the planet of 0.97 +/- 0.07 R(Jup) and a mass of 2.75 +/- 0.16 M(Jup). The bulk density,rho(p) = 3.70 +/- 0.83 g cm(-3), is similar to 2.8 that of Jupiter. The core of CoRoT-10b could contain up to 240 M(circle plus) of heavy elements. Moving along its eccentric orbit, the planet experiences a 10.6-fold variation in insolation. Owing to the long circularisation time, tau(circ) > 7 Gyr, a resonant perturber is not required to excite and maintain the high eccentricity of CoRoT-10b.