Baseline Susceptibility of Primary HIV-2 to Entry Inhibitors

BACKGROUND: The baseline susceptibility of primary HIV-2 to maraviroc (MVC) and other entry inhibitors is currently unknown. METHODS: The susceptibility of 19 HIV-2 isolates obtained from asymptomatic and AIDS patients and seven HIV-1 clinical isolates to the fusion inhibitors enfuvirtide (ENF) and T-1249, and to the coreceptor antagonists AMD3100, TAK-779 and MVC, was measured using a TZM-bl cell-based assay. The 50% inhibitory concentration (IC(50)), 90% inhibitory concentration (IC(90)) and dose-response curve slopes were determined for each drug. RESULTS: ENF and T-1249 were significantly less active on HIV-2 than on HIV-1 (211- and 2-fold, respectively). AMD3100 and TAK-779 inhibited HIV-2 and HIV-1 CXCR4 tropic (X4) and CCR5 tropic (R5) variants with similar IC(50) and IC(90) values. MVC, however, inhibited the replication of R5 HIV-2 variants with significantly higher IC(90) values (42.7 versus 9.7 nM; P<0.0001) and lower slope values (0.7 versus 1.3; P<0.0001) than HIV-1. HIV-2 R5 variants derived from AIDS patients were significantly less sensitive to MVC than variants from asymptomatic patients, this being inversely correlated with the absolute number of CD4(+) T-cells. CONCLUSIONS: T-1249 is a potent inhibitor of HIV-2 replication indicating that new fusion inhibitors might be useful to treat HIV-2 infection. Coreceptor antagonists TAK-779 and AMD3100 are also potent inhibitors of HIV-2 replication. The reduced sensitivity of R5 variants to MVC, especially in severely immunodeficient patients, indicates that the treatment of HIV-2-infected patients with MVC might require higher dosages than those used in HIV-1 patients, and should be adjusted to the disease stage.

Patterns in financial markets: Dynamic time warping

A Work Project, presented as part of the requirements for the Award of a Masters Degree in Finance from the NOVA – School of Business and Economics

Influenza A(H1N1)pdm09 Resistance and Cross-Decreased Susceptibility to Oseltamivir and Zanamivir Antiviral Drugs

Neuraminidase inhibitors (NAIs) oseltamivir and zanamivir are currently the only effective antiviral drugs available worldwide for the management of influenza. The potential development of resistance is continually threatening their use, rationalizing and highlighting the need for a close and sustained evaluation of virus susceptibility. This study aimed to analyze and characterize the phenotypic and genotypic NAIs susceptibility profiles of A(H1N1)pdm09 viruses circulating in Portugal from 2009 to 2010/2011. A total of 144 cases of A(H1N1)pdm09 virus infection from community and hospitalized patients were studied, including three suspected cases of clinical resistance to oseltamivir. Oseltamivir resistance was confirmed for two of the suspected cases. Neuraminidase (NA) H275Y resistant marker was found in viruses from both cases but for one it was only present in 26.2% of virus population, raising questions about the minimal percentage of resistant virus that should be considered relevant. Cross-decreased susceptibility to oseltamivir and zanamivir (2-4 IC50 fold-change) was detected on viruses from two potentially linked community patients from 2009. Both viruses harbored the NA I223V mutation. NA Y155H mutation was found in 18 statistical non-outlier viruses from 2009, having no impact on virus susceptibility. The mutations at NA N369K and V241I may have contributed to the significantly higher baseline IC50 value obtained to oseltamivir for 2010/2011 viruses, compared to viruses from the pandemic period. These results may contribute to a better understanding of the relationship between phenotype and genotype, which is currently challenging, and to the global assessment of A(H1N1)pdm09 virus susceptibility profile and baseline level to NAIs.

Long-term behaviour of railway transitions under dynamic loading application to soft soil sites

Dissertação para obtenção do Grau de Doutor em Engenharia Civil

The fitting of the German yield curve: A dynamic approach using latent, macroeconomic and stock market variables

A Work Project, presented as part of the requirements for the Award of a Masters Degree in Finance from the NOVA – School of Business and Economics

Enterococcus faecalis V583 prophages: Dynamic interactions and contribution to bacterial pathogenic traits

Dissertation presented to obtain the Ph.D degree in Biology.

Trypanosoma cruzi: susceptibility to chemotherapy with benznidazole of clones isolated from the highly resistant Colombian strain

The present investigation was performed to evaluate the susceptibility of seven clones isolated from the highly resistant Colombian strains, prototype of Biodeme Type III. Seven clones previously obtained, showed a phenotypic homogeneity and high similarity with the parental strain. Eight groups of 30 mice were inoculated with one of seven clones or the parental strain; 20 were treated with benznidazole (100mg/kg/day) and 10 were untreated controls. Cure evaluations were done by parasitological and serological tests and PCR. Cure rates varied from 0% (null) to 16.7%. Correlation between positivity of parasitological and serological tests with positive PCR reached 37%. The results demonstrated the high resistance of the clones, suggesting the predominance of a highly resistant principal clone in this strain. The findings apparently indicate that the possibility of cure is minimal for patients infected with this biodeme; a fact that could affect the control of Chagas' disease through treatment of chronically infected people.

Dynamic adaptation of interaction models for stateful web services

Dissertação para obtenção do Grau de Mestre em Engenharia Informática

Carbon prices. Dynamic analysis of European and Californian markets

Dissertação para obtenção do Grau de Doutor em Alterações Climáticas e Políticas de Desenvolvimento Sustentável

Susceptibility of Aedes aegypti (L) to the insect growth regulators diflubenzuron and methoprene in Uberlândia, State of Minas Gerais

Aedes aegypti (L) (Diptera: Culicidae) was reared in several concentrations of diflubenzuron and methoprene under laboratory conditions in Uberlândia, State of Minas Gerais, southeastern Brazil. Characteristics such as LC50 and LC95, the susceptibility of immature stages of different ages to these insect growth regulators and their residual effects were studied. The LC50 and LC95 of diflubenzuron and methoprene were 5.19 and 12.24 ppb; 19.95 and 72.08 ppb, respectively. While diflubenzuron caused great mortality in all larval instars, methoprene was more effective when the mosquito was exposed from the start of the fourth larval instar onwards. Commercial concentrations of these two insect growth regulators close to LC95 presented greater residual activity than did their respective technical formulations. The parameters were compared with those obtained elsewhere. The characteristics investigated here indicate that these insect growth regulators are effective alternatives for controlling the dengue vector in the Uberlândia region.

Application of NMR RDC’s, relaxation and self-diffusion for the study of dynamic processes of small molecules in solution

Spin-lattice Relaxation, self-Diffusion coefficients and Residual Dipolar Couplings (RDC’s) are the basis of well established Nuclear Magnetic Resonance techniques for the physicochemical study of small molecules (typically organic compounds and natural products with MW < 1000 Da), as they proved to be a powerful and complementary source of information about structural dynamic processes in solution. The work developed in this thesis consists in the application of the earlier-mentioned NMR techniques to explore, analyze and systematize patterns of the molecular dynamic behavior of selected small molecules in particular experimental conditions. Two systems were chosen to investigate molecular dynamic behavior by these techniques: the dynamics of ion-pair formation and ion interaction in ionic liquids (IL) and the dynamics of molecular reorientation when molecules are placed in oriented phases (alignment media). The application of NMR spin-lattice relaxation and self-diffusion measurements was applied to study the rotational and translational molecular dynamics of the IL: 1-butyl-3-methylimidazolium tetrafluoroborate [BMIM][BF4]. The study of the cation-anion dynamics in neat and IL-water mixtures was systematically investigated by a combination of multinuclear NMR relaxation techniques with diffusion data (using by H1, C13 and F19 NMR spectroscopy). Spin-lattice relaxation time (T1), self-diffusion coefficients and nuclear Overhauser effect experiments were combined to determine the conditions that favor the formation of long lived [BMIM][BF4] ion-pairs in water. For this purpose and using the self-diffusion coefficients of cation and anion as a probe, different IL-water compositions were screened (from neat IL to infinite dilution) to find the conditions where both cation and anion present equal diffusion coefficients (8% water fraction at 25 ºC). This condition as well as the neat IL and the infinite dilution were then further studied by 13C NMR relaxation in order to determine correlation times (c) for the molecular reorientational motion using a mathematical iterative procedure and experimental data obtained in a temperature range between 273 and 353 K. The behavior of self-diffusion and relaxation data obtained in our experiments point at the combining parameters of molar fraction 8 % and temperature 298 K as the most favorable condition for the formation of long lived ion-pairs. When molecules are subjected to soft anisotropic motion by being placed in some special media, Residual Dipolar Couplings (RDCs), can be measured, because of the partial alignment induced by this media. RDCs are emerging as a powerful routine tool employed in conformational analysis, as it complements and even outperforms the approaches based on the classical NMR NOE or J3 couplings. In this work, three different alignment media have been characterized and evaluated in terms of integrity using 2H and 1H 1D-NMR spectroscopy, namely the stretched and compressed gel PMMA, and the lyotropic liquid crystals CpCl/n-hexanol/brine and cromolyn/water. The influence that different media and degrees of alignment have on the dynamic properties of several molecules was explored. Different sized sugars were used and their self-diffusion was determined as well as conformation features using RDCs. The results obtained indicate that no influence is felt by the small molecules diffusion and conformational features studied within the alignment degree range studied, which was the 3, 5 and 6 % CpCl/n-hexanol/brine for diffusion, and 5 and 7.5 % CpCl/n-hexanol/brine for conformation. It was also possible to determine that the small molecules diffusion verified in the alignment media presented close values to the ones observed in water, reinforcing the idea of no conditioning of molecular properties in such media.

Dynamic stiffness of the piled foundation of a onshore wind turbine

One of today's biggest concerns is the increase of energetic needs, especially in the developed countries. Among various clean energies, wind energy is one of the technologies that assume greater importance on the sustainable development of humanity. Despite wind turbines had been developed and studied over the years, there are phenomena that haven't been yet fully understood. This work studies the soil-structure interaction that occurs on a wind turbine's foundation composed by a group of piles that is under dynamic loads caused by wind. This problem assumes special importance when the foundation is implemented on locations where safety criteria are very demanding, like the case of a foundation mounted on a dike. To the phenomenon of interaction between two piles and the soil between them it's given the name of pile-soil-pile interaction. It is known that such behavior is frequency dependent, and therefore, on this work evaluation of relevant frequencies for the intended analysis is held. During the development of this thesis, two methods were selected in order to assess pile-soil-pile interaction, being one of analytical nature and the other of numerical origin. The analytical solution was recently developed and its called Generalized pile-soil-pile theory, while for the numerical method the commercial nite element software PLAXIS 3D was used. A study of applicability of the numerical method is also done comparing the given solution by the nite element methods with a rigorous solution widely accepted by the majority of the authors.

Characterization tests for insulation boards made from corn cob and natural glues

In recent years there has been a growing interest in developing news solutions for more ecologic and efficient construction, including natural, renewable and local materials, thus contributing in the search for more efficient, economic and environmentally friendly construction. Several authors have assessed the possibility of using various agricultural sub products or wastes, as part of the effort of the scientific community to find alternative and more ecologic construction materials. Corn cob is an agricultural waste from a very important worldwide crop. Natural glues are made from natural materials, non-mineral, that can be used as such or after some modifications to achieve the behaviour and performance required. Two examples of these natural glues are casein and wheat flour-based glues that were used in the present study. Boards with different compositions were manufactured, having as variables the type of glue, the dimension of the corn cob particles and the features of the pressing process. The tests boards were characterized with physical and mechanical tests, such as thermal conductivity (λ) with a ISOMET 2104 and 60 mm diameter contact probe, density (ρ) based on EN 1602:2013, surface hardness (SH) with a PCE Shore A durometer, surface resistance (SR) with a PROCEQ PT pendular sclerometer, bending behaviour (σ) based on EN 12089:2013, compression behaviour (σ10) based on EN 826:2013 and resilience (R) based on EN 1094-1:2008, with a Zwick Rowell bending equipment with 2 kN and 50 kN load cells (Fig. 1), dynamic modulus of elasticity (Ed) with a Zeus Resonance Meter equipment (Fig. 5) based on NP EN 14146:2006 and water vapour permeability (δ) based on EN 12086:2013. The various boards produced were characterized according to the tests and the ones with the best results were C8_c8 (casein glue, grain size 2,38-4,76 mm, cold pressing for 8 hours), C8_c4 (casein glue, grain size 2,38-4,76 mm, cold pressing for 4 hours), F8_h0.5 (wheat flour glue, grain size 2,38-4,76 mm, hot pressing for 0,5 hours), FEV8_h0.5 (wheat flour, egg white and vinegar glue, grain size 2,38-4,76 mm, hot pressing for 0,5 hours) and FEVH68_c4 (wheat flour, egg white, vinegar and 6 g of sodium hydroxide glue, grain size 2,38-4,76 mm, cold pressing for 4 hours). Taking into account the various boards produced and respective test results the type of glue and the pressure and pressing time are very important factors which strongly influence the final product. The results obtained confirmed the initial hypotheses that these boards have potential as a thermal and, eventually, acoustic insulation material, to use as coating or intermediate layer on walls, floors or false ceilings. This type of board has a high mechanical resistance when compared with traditional insulating materials.The integrity of these boards seems to be maintained even in higher humidity environments. However, due to biological susceptibility and sensitivity to water, they would be more adequate for application in dry interior conditions.

Study of the electromyographic signal dynamic behavior in Amyotrophic Lateral Sclerosis (ALS)

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease characterized by motor neurons degeneration, which reduces muscular force, being very difficult to diagnose. Mathematical methods are used in order to analyze the surface electromiographic signal’s dynamic behavior (Fractal Dimension (FD) and Multiscale Entropy (MSE)), evaluate different muscle group’s synchronization (Coherence and Phase Locking Factor (PLF)) and to evaluate the signal’s complexity (Lempel-Ziv (LZ) techniques and Detrended Fluctuation Analysis (DFA)). Surface electromiographic signal acquisitions were performed in upper limb muscles, being the analysis executed for instants of contraction for ipsilateral acquisitions for patients and control groups. Results from LZ, DFA and MSE analysis present capability to distinguish between the patient group and the control group, whereas coherence, PLF and FD algorithms present results very similar for both groups. LZ, DFA and MSE algorithms appear then to be a good measure of corticospinal pathways integrity. A classification algorithm was applied to the results in combination with extracted features from the surface electromiographic signal, with an accuracy percentage higher than 70% for 118 combinations for at least one classifier. The classification results demonstrate capability to distinguish members between patients and control groups. These results can demonstrate a major importance in the disease diagnose, once surface electromyography (sEMG) may be used as an auxiliary diagnose method.

Sporothrix schenckii associated with armadillo hunting in Southern Brazil: epidemiological and antifungal susceptibility profiles

INTRODUCTION: Sporotrichosis is the most common subcutaneous mycosis observed in Brazil and it is generally consequent to a little trauma caused by vegetal particles or spines which inoculate the fungi in the subcutaneous area. Although sporotrichosis had been frequently mentioned with armadillo hunting this form has not been widely reported in Brazil until now. In this study we report ten cases of sporotrichosis evolving the armadillo's hunting diagnosed in some towns located in the central and west regions of Rio Grande do Sul State. METHODS: The cases were established based on clinical and classic mycological laboratorial techniques. The susceptibility tests were conducted by microdilution technique according to M38-A2 CLSI documents. RESULTS: Ten cases of sporotrichosis associated with armadillo hunting detected in the State of Rio Grande do Sul were diagnosed by mycological methods. The susceptibility tests of Sporothrix schenckii isolates to antifungal agents itraconazole, ketoconazole and terbinafine showed that all the isolates were susceptible. CONCLUSIONS: The paper discusses some cultural aspects related to hunting of this wild animal as well as possible causes of this unexpected occurrence in southern Brazil.