Search results for: Ednaldo C. Rêgo.
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 16

Search results for: Ednaldo C. Rêgo.

16 The Residual Efficacy of Etofenprox WP on Different Surfaces for Malaria Control in the Brazilian Legal Amazon

Authors: Ana Paula S. A. Correa, Allan K. R. Galardo, Luana A. Lima, Talita F. Sobral, Josiane N. Muller, Jessica F. S. Barroso, Nercy V. R. Furtado, Ednaldo C. Rêgo., Jose B. P. Lima

Abstract:

Malaria is a public health problem in the Brazilian Legal Amazon. Among the integrated approaches for anopheline control, the Indoor Residual Spraying (IRS) remains one of the main tools in the basic strategy applied in the Amazonian States, where the National Malaria Control Program currently uses one of the insecticides from the pyrethroid class, the Etofenprox WP. Understanding the residual efficacy of insecticides on different surfaces is essential to determine the spray cycles, in order to maintain a rational use and to avoid product waste. The aim of this study was to evaluate the residual efficacy of Etofenprox - VECTRON ® 20 WP on surfaces of Unplastered Cement (UC) and Unpainted Wood (UW) on panels, in field, and in semi-field evaluation of Brazil’s Amapa State. The evaluation criteria used was the cone bioassay test, following the World Health Organization (WHO) recommended method, using plastic cones and female mosquitos of Anopheles sp. The tests were carried out in laboratory panels, semi-field evaluation in a “test house” built in the Macapa municipality, and in the field in 20 houses, being ten houses per surface type (UC and UW), in an endemic malaria area in Mazagão’s municipality. The residual efficacy was measured from March to September 2017, starting one day after the spraying, repeated monthly for a period of six months. The UW surface presented higher residual efficacy than the UC. In fact, the UW presented a residual efficacy of the insecticide throughout the period of this study with a mortality rate above 80% in the panels (= 95%), in the "test house" (= 86%) and in field houses ( = 87%). On the UC surface it was observed a mortality decreased in all the tests performed, with a mortality rate of 45, 47 and 29% on panels, semi-field and in field, respectively; however, the residual efficacy ≥ 80% only occurred in the first evaluation after the 24-hour spraying bioassay in the "test house". Thus, only the UW surface meets the specifications of the World Health Organization Pesticide Evaluation Scheme (WHOPES) regarding the duration of effective action (three to six months). To sum up, the insecticide residual efficacy presented variability on the different surfaces where it was sprayed. Although the IRS with Etofenprox WP was efficient on UW surfaces, and it can be used in spraying cycles at 4-month intervals, it is important to consider the diversity of houses in the Brazilian Legal Amazon, in order to implement alternatives for vector control, including the evaluation of new products or different formulations types for insecticides.

Keywords: Anopheles, vector control, insecticide, bioassay

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15 Sustainable Tourism and Tourism Product Development Conference - Praga

Authors: Ana Rita Conde, Pilar Mota, Tânia Botelho, Carlos Rodrigues, Osvaldo Silva, Áurea Sousa, Suzana Caldeira, Isabel Rego, Jéssica Pacheco

Abstract:

Families with children with ASD are interested in traveling but end up not traveling due to the obstacles they face and not finding inclusive traveling offers. This study will identify the needs of families with children with ASD, to develop the products targeted to their tourist needs. 137 families from different countries answered a questionnaire about their travel experiences, needs and preferences. Based on the results, guidelines are presented for the development of products specially aimed for this market niche.

Keywords: inclusive tourism, sustainability, autism spectrum disorder, children, families

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14 Implementation and Validation of Therapeutic Tourism Products for Families With Children With Autism Spectrum Disorder in Azores Islands: “Azores All in Blue” Project

Authors: Ana Rita Conde, Pilar Mota, Tânia Botelho, Suzana Caldeira, Isabel Rego, Jessica Pacheco, Osvaldo Silva, Áurea Sousa

Abstract:

Tourism promotes well-being and health to children with ASD and their families. Literature indicates the need to provide tourist activities that integrate the therapeutic component, to promote the development and well-being of children with ASD. The study aims to implement tourist offers in Azores that integrate the therapeutic feature, assess their suitability and impact on the well-being and health of the child and caregivers. Using a mixed methodology, the study integrates families that experience and evaluate the impact of tourism products developed specifically for them.

Keywords: austism spectrum disorder, children, therapeutic tourism activities, well-being, health, inclusive tourism

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13 Life Cycle Assessment in Road Pavements: A Literature Review and the Potential Use in Brazil

Authors: B. V. Santos, M. T. M. Carvalho, J. H. S. Rêgo

Abstract:

The article presents a literature review on recent advances related to studies of the environmental impact of road pavements, with reference to the concepts of Life Cycle Assessment (LCA). An introduction with the main motivations for the development of the research is presented, with a current overview of the Brazilian transport infrastructure and the projections for the road mode for the coming years, and the possibility of using the referred methodology by the road sector in Brazil. The article explores the origin of LCA in road pavements and the details linked to its implementation from the perspective of the four main phases of the study (goal and scope definition, inventory analysis, impact assessment, and interpretation). Finally, the main advances and deficiencies observed in the selected studies are gathered, with the proposition of research fields that can be explored in future national or international studies of LCA of road pavements.

Keywords: Brazil, life cycle assessment, road pavements, sustainable

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12 Determination of the Optimal Content of Commercial Superplasticizer Additives in Cements with Calcined Clay

Authors: Amanda R. Teixeira, João H. S. Rego, Gabriel F. S. Brito, Fabricio M. Silva

Abstract:

The use of superplasticizer additives has provided several advances for the civil construction industry, enabling gains in the rheological behavior and mechanical properties of cementitious matrices. These compounds act at the solid-liquid interface of colloidal suspensions of cement pastes, preventing agglomeration of the particles. Although the use in the concrete industry is wide, the mechanisms of dispersion of concrete admixtures composed of polycarboxylate in cement with supplementary cementitious materials have ample opportunity to be investigated, providing the attainment of increasingly compatible and efficient cement-addition-additive systems. The cements used in the research are Portland Cement CPV and two cements Portland Cement Composite (CPIV) with calcined clay contents of 20% and 28% and three commercial additives based on polycarboxylate. The performance of the additives and obtaining the optimal content was determined by the Marsh Cone test and spread by Mini-Slump.

Keywords: calcined clay, composite cements, superplasticizer additives, polycarboxylate

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11 A Numerical Study of the Interaction between Residual Stress Profiles Induced by Quasi-Static Plastification

Authors: Guilherme F. Guimaraes, Alfredo R. De Faria, Ronnie R. Rego, Andre L. R. D'Oliveira

Abstract:

The development of methods for predicting manufacturing phenomena steadily grows due to their high potential to contribute to the component’s performance and durability. One of the most relevant phenomena in manufacturing is the residual stress state development through the manufacturing chain. In most cases, the residual stresses have their origin due to heterogenous plastifications produced by the processes. Although a few manufacturing processes have been successfully approached by numerical modeling, there is still a lack of understanding on how these processes' interactions will affect the final stress state. The objective of this work is to analyze the influence of previous stresses on the residual stress state induced by plastic deformation of a quasi-static indentation. The model consists of a simplified approach of shot peening, modeling four cases with variations in indenter size and force. This model was validated through topography, measured by optical 3D focus-variation, and residual stress, measured with the X-ray diffraction technique. The validated model was then exposed to several initial stress states, and the effect on the final residual stress was analyzed.

Keywords: plasticity, residual stress, finite element method, manufacturing

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10 Preliminary Design of an Aerodynamic Protection for the Scramjet Engine Inlet of the Brazilian Technological Demonstrator Scramjet 14-X S

Authors: Gustavo J. Costa, Felipe J. Costa, Bruno L. Coelho, Ronaldo L. Cardoso, Rafael O. Santos, Israel S. Rêgo, Marco A. S. Minucci, Antonio C. Oliveira, Paulo G. P. Toro

Abstract:

The Prof. Henry T. Nagamatsu Aerothermodynamics and Hipersonics Laboratory, of the Institute for Advanced Studies (IEAv) conducts research and development (R&D) of the Technological Demonstrator scramjet 14-X S, aiming atmospheric flight at 30 km altitude with the speed correspondent to Mach number 7, using scramjet technology providing hypersonic propulsion system based on supersonic combustion. Hypersonic aerospace vehicles with air-breathing supersonic propulsion system face extremal environments for super/hypersonic flights in terms of thermal and aerodynamic loads. Thus, it is necessary to use aerodynamic protection at the scramjet engine inlet to face the thermal and aerodynamic loads without compromising the efficiency of scramjet engine, taking into account: i) inlet design (boundary layer, oblique shockwave and reflected oblique shockwave); ii) wall temperature of the cowl and of the compression ramp; iii) supersonic flow into the combustion chamber. The aerodynamic protection of the scramjet engine inlet will act to prevent the engine unstart and match the predictions made by theoretical-analytical, numerical analysis and experimental research, during the atmospheric flight of the Technological Demonstrator scramjet 14-X S.

Keywords: 14-X, hypersonic, scramjet, supersonic combustion

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9 Stem Covers of Leibniz n-Algebras

Authors: Natália Maria Rego

Abstract:

ALeibnizn-algebraGis aK-vector space endowed whit a n-linearbracket operation [-,…-] : GG … G→ Gsatisfying the fundamental identity, which can be expressed saying that the right multiplication map Ry2, …, ᵧₙ: Gn→ G, Rᵧ₂, …, ᵧₙn(ˣ¹, …, ₓₙ) = [[ˣ¹, …, ₓₙ], ᵧ₂, …, ᵧₙ], is a derivation. This structure, together with its skew-symmetric version, named as Lie n-algebra or Filippov algebra, arose in the setting of Nambumechanics, an n-ary generalization of the Hamiltonian mechanics. Thefirst goal of this work is to provide a characterization of various classes of central extensions of Leibniz n-algebras in terms of homological properties. Namely, Commutator extension, Quasi-commutator extension, Stem extension, and Stem cover. These kind of central extensions are characterized by means of the character of the map *(E): nHL1(G) → M provided by the five-term exact sequence in homology with trivial coefficients of Leibniz n-algebras associated to an extension E : 0 → M → K → G → 0. For a free presentation 0 →R→ F →G→ 0of a Leibniz n-algebra G,the term M(G) = (R[F,…n.., F])/[R, F,..n-1..,F] is called the Schur multiplier of G, which is a Baer invariant, i.e., it does not depend on the chosen free presentation, and it is isomorphic to the first Leibniz n-algebras homology with trivial coefficients of G. A central extension of Leibniz n-algebras is a short exact sequenceE : 0 →M→K→G→ 0such that [M, K,.. ⁿ⁻¹.., K]=0. It is said to be a stem extension if M⊆[G, .. n.., G]. Additionally, if the induced map M(K) → M(G) is the zero map, then the stem extension Eis said to be a stem cover. The second aim of this work is to analyze the interplay between stem covers of Leibniz n-algebras and the Schur multiplier. Concretely, in the case of finite-dimensional Leibniz n-algebras, we show the existence of coverings, and we prove that all stem covers with finite-dimensional Schur multiplier are isoclinic. Additionally, we characterize stem covers of perfect Leibniz n-algebras.

Keywords: leibniz n-algebras, central extensions, Schur multiplier, stem cover

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8 Preliminary Conceptions of 3D Prototyping Model to Experimental Investigation in Hypersonic Shock Tunnels

Authors: Thiago Victor Cordeiro Marcos, Joao Felipe de Araujo Martos, Ronaldo de Lima Cardoso, David Romanelli Pinto, Paulo Gilberto de Paula Toro, Israel da Silveira Rego, Antonio Carlos de Oliveira

Abstract:

Currently, the use of 3D rapid prototyping, also known as 3D printing, has been investigated by some universities around the world as an innovative technique, fast, flexible and cheap for a direct plastic models manufacturing that are lighter and with complex geometries to be tested for hypersonic shock tunnel. Initially, the purpose is integrated prototyped parts with metal models that actually are manufactured through of the conventional machining and hereafter replace them with completely prototyped models. The mechanical design models to be tested in hypersonic shock tunnel are based on conventional manufacturing processes, therefore are limited forms and standard geometries. The use of 3D rapid prototyping offers a range of options that enables geometries innovation and ways to be used for the design new models. The conception and project of a prototyped model for hypersonic shock tunnel should be rethought and adapted when comparing the conventional manufacturing processes, in order to fully exploit the creativity and flexibility that are allowed by the 3D prototyping process. The objective of this paper is to compare the conception and project of a 3D rapid prototyping model and a conventional machining model, while showing the advantages and disadvantages of each process and the benefits that 3D prototyping can bring to the manufacture of models to be tested in hypersonic shock tunnel.

Keywords: 3D printing, 3D prototyping, experimental research, hypersonic shock tunnel

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7 Influences of Separation of the Boundary Layer in the Reservoir Pressure in the Shock Tube

Authors: Bruno Coelho Lima, Joao F.A. Martos, Paulo G. P. Toro, Israel S. Rego

Abstract:

The shock tube is a ground-facility widely used in aerospace and aeronautics science and technology for studies on gas dynamic and chemical-physical processes in gases at high-temperature, explosions and dynamic calibration of pressure sensors. A shock tube in its simplest form is comprised of two separate tubes of equal cross-section by a diaphragm. The diaphragm function is to separate the two reservoirs at different pressures. The reservoir containing high pressure is called the Driver, the low pressure reservoir is called Driven. When the diaphragm is broken by pressure difference, a normal shock wave and non-stationary (named Incident Shock Wave) will be formed in the same place of diaphragm and will get around toward the closed end of Driven. When this shock wave reaches the closer end of the Driven section will be completely reflected. Now, the shock wave will interact with the boundary layer that was created by the induced flow by incident shock wave passage. The interaction between boundary layer and shock wave force the separation of the boundary layer. The aim of this paper is to make an analysis of influences of separation of the boundary layer in the reservoir pressure in the shock tube. A comparison among CDF (Computational Fluids Dynamics), experiments test and analytical analysis were performed. For the analytical analysis, some routines in Python was created, in the numerical simulations (Computational Fluids Dynamics) was used the Ansys Fluent, and the experimental tests were used T1 shock tube located in IEAv (Institute of Advanced Studies).

Keywords: boundary layer separation, moving shock wave, shock tube, transient simulation

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6 On Lie-Central Derivations and Almost Inner Lie-Derivations of Leibniz Algebras

Authors: Natalia Pacheco Rego

Abstract:

The Liezation functor is a map from the category of Leibniz algebras to the category of Lie algebras, which assigns a Leibniz algebra to the Lie algebra given by the quotient of the Leibniz algebra by the ideal spanned by the square elements of the Leibniz algebra. This functor is left adjoint to the inclusion functor that considers a Lie algebra as a Leibniz algebra. This environment fits in the framework of central extensions and commutators in semi-abelian categories with respect to a Birkhoff subcategory, where classical or absolute notions are relative to the abelianization functor. Classical properties of Leibniz algebras (properties relative to the abelianization functor) were adapted to the relative setting (with respect to the Liezation functor); in general, absolute properties have the corresponding relative ones, but not all absolute properties immediately hold in the relative case, so new requirements are needed. Following this line of research, it was conducted an analysis of central derivations of Leibniz algebras relative to the Liezation functor, called as Lie-derivations, and a characterization of Lie-stem Leibniz algebras by their Lie-central derivations was obtained. In this paper, we present an overview of these results, and we analyze some new properties concerning Lie-central derivations and almost inner Lie-derivations. Namely, a Leibniz algebra is a vector space equipped with a bilinear bracket operation satisfying the Leibniz identity. We define the Lie-bracket by [x, y]lie = [x, y] + [y, x] , for all x, y . The Lie-center of a Leibniz algebra is the two-sided ideal of elements that annihilate all the elements in the Leibniz algebra through the Lie-bracket. A Lie-derivation is a linear map which acts as a derivative with respect to the Lie-bracket. Obviously, usual derivations are Lie-derivations, but the converse is not true in general. A Lie-derivation is called a Lie-central derivation if its image is contained in the Lie-center. A Lie-derivation is called an almost inner Lie-derivation if the image of an element x is contained in the Lie-commutator of x and the Leibniz algebra. The main results we present in this talk refer to the conditions under which Lie-central derivation and almost inner Lie-derivations coincide.

Keywords: almost inner Lie-derivation, Lie-center, Lie-central derivation, Lie-derivation

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5 Experimental Analysis for the Inlet of the Brazilian Aerospace Vehicle 14-X B

Authors: João F. A. Martos, Felipe J. Costa, Sergio N. P. Laiton, Bruno C. Lima, Israel S. Rêgo, Paulo P. G. Toro

Abstract:

Nowadays, the scramjet is a topic that has attracted the attention of several scientific communities (USA, Australia, Germany, France, Japan, India, China, Russia), that are investing in this in this type of propulsion system due its interest to facilitate access to space and reach hypersonic speed, who have invested in this type of propulsion due to the interest in facilitating access to space. The Brazilian hypersonic scramjet aerospace vehicle 14-X B is a technological demonstrator of a hypersonic airbreathing propulsion system based on the supersonic combustion (scramjet) intended to be tested in flight into the Earth's atmosphere at 30 km altitude and Mach number 7. The 14-X B has been designed at the Prof. Henry T. Nagamatsu Laboratory of Aerothermodynamics and Hypersonics of the Institute for Advanced Studies (IEAv) in Brazil. The IEAv Hypersonic Shock Tunnel, named T3, is a ground-test facility able to reproduce the flight conditions as the Mach number as well as pressure and temperature in the test section close to those encountered during the test flight of the vehicle 14-X B into design conditions. A 1-m long stainless steel 14-X B model was experimentally investigated at T3 Hypersonic Shock Tunnel, for freestream Mach number 7. Static pressure measurements along the lower surface of the 14-X B model, along with high-speed schlieren photographs taken from the 5.5° leading edge and the 14.5° deflection compression ramp, provided experimental data that were compared to the analytical-theoretical solutions and the computational fluid dynamics (CFD) simulations. The results show a good qualitative agreement, and in consequence demonstrating the importance of these methods in the project of the 14-X B hypersonic aerospace vehicle.

Keywords: 14-X, CFD, hypersonic, hypersonic shock tunnel, scramjet

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4 Investigation of the Technological Demonstrator 14x B in Different Angle of Attack in Hypersonic Velocity

Authors: Victor Alves Barros Galvão, Israel Da Silveira Rego, Antonio Carlos Oliveira, Paulo Gilberto De Paula Toro

Abstract:

The Brazilian hypersonic aerospace vehicle 14-X B, VHA 14-X B, is a vehicle integrated with the hypersonic airbreathing propulsion system based on supersonic combustion (scramjet), developing in Aerothermodynamics and hypersonic Prof. Henry T. Nagamatsu Laboratory, to conduct demonstration in atmospheric flight at the speed corresponding to Mach number 7 at an altitude of 30km. In the experimental procedure the hypersonic shock tunnel T3 was used, installed in that laboratory. This device simulates the flow over a model is fixed in the test section and can also simulate different atmospheric conditions. The scramjet technology offers substantial advantages to improve aerospace vehicle performance which flies at a hypersonic speed through the Earth's atmosphere by reducing fuel consumption on board. Basically, the scramjet is an aspirated aircraft engine fully integrated that uses oblique/conic shock waves generated during hypersonic flight, to promote the deceleration and compression of atmospheric air in scramjet inlet. During the hypersonic flight, the vehicle VHA 14-X will suffer atmospheric influences, promoting changes in the vehicle's angles of attack (angle that the mean line of vehicle makes with respect to the direction of the flow). Based on this information, a study is conducted to analyze the influences of changes in the vehicle's angle of attack during the atmospheric flight. Analytical theoretical analysis, simulation computational fluid dynamics and experimental investigation are the methodologies used to design a technological demonstrator prior to the flight in the atmosphere. This paper considers analysis of the thermodynamic properties (pressure, temperature, density, sound velocity) in lower surface of the VHA 14-X B. Also, it considers air as an ideal gas and chemical equilibrium, with and without boundary layer, considering changes in the vehicle's angle of attack (positive and negative in relation to the flow) and bi-dimensional expansion wave theory at the expansion section (Theory of Prandtl-Meyer).

Keywords: angle of attack, experimental hypersonic, hypersonic airbreathing propulsion, Scramjet

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3 Aerothermal Analysis of the Brazilian 14-X Hypersonic Aerospace Vehicle at Mach Number 7

Authors: Felipe J. Costa, João F. A. Martos, Ronaldo L. Cardoso, Israel S. Rêgo, Marco A. S. Minucci, Antonio C. Oliveira, Paulo G. P. Toro

Abstract:

The Prof. Henry T. Nagamatsu Laboratory of Aerothermodynamics and Hypersonics, at the Institute for Advanced Studies designed the Brazilian 14-X Hypersonic Aerospace Vehicle, which is a technological demonstrator endowed with two innovative technologies: waverider technology, to obtain lift from conical shockwave during the hypersonic flight; and uses hypersonic airbreathing propulsion system called scramjet that is based on supersonic combustion, to perform flights on Earth's atmosphere at 30 km altitude at Mach numbers 7 and 10. The scramjet is an aeronautical engine without moving parts that promote compression and deceleration of freestream atmospheric air at the inlet through the conical/oblique shockwaves generated during the hypersonic flight. During high speed flight, the shock waves and the viscous forces yield the phenomenon called aerodynamic heating, where this physical meaning is the friction between the fluid filaments and the body or compression at the stagnation regions of the leading edge that converts the kinetic energy into heat within a thin layer of air which blankets the body. The temperature of this layer increases with the square of the speed. This high temperature is concentrated in the boundary-layer, where heat will flow readily from the boundary-layer to the hypersonic aerospace vehicle structure. Fay and Riddell and Eckert methods are applied to the stagnation point and to the flat plate segments in order to calculate the aerodynamic heating. On the understanding of the aerodynamic heating it is important to analyze the heat conduction transfer to the 14-X waverider internal structure. ANSYS Workbench software provides the Thermal Numerical Analysis, using Finite Element Method of the 14-X waverider unpowered scramjet at 30 km altitude at Mach number 7 and 10 in terms of temperature and heat flux. Finally, it is possible to verify if the internal temperature complies with the requirements for embedded systems, and, if is necessary to do modifications on the structure in terms of wall thickness and materials.

Keywords: aerodynamic heating, hypersonic, scramjet, thermal analysis

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2 Effectiveness Assessment of a Brazilian Larvicide on Aedes Control

Authors: Josiane N. Muller, Allan K. R. Galardo, Tatiane A. Barbosa, Evan P. Ferro, Wellington M. Dos Santos, Ana Paula S. A. Correa, Edinaldo C. Rego, Jose B. P. Lima

Abstract:

The susceptibility status of an insect population to any larvicide depends on several factors such includes genetic constitution, environmental conditions and others. The mosquito Aedes aegypti is the primary vector of three important viral diseases, Zika, Dengue, and Chikungunya. The frequent outbreaks of those diseases in different parts of Brazil demonstrate the importance of testing the susceptibility of vectors in different environments. Since the control of this mosquito leads to the control of disease, alternatives for vector control that value the different Brazilian environmental conditions are needed for effective actions. The aim of this study was to evaluate a new commercial formulation of Bacillus thuringiensis israelenses (DengueTech: Brazilian innovative technology) in the Brazilian Legal Amazon considering the climate conditions. Semi-field tests were conducted in the Institute of Scientific and Technological Research of the State of Amapa in two different environments, one in a shaded area and the other exposed to sunlight. The mosquito larvae were exposed to larvicide concentration and a control; each group was tested in three containers of 40 liters each. To assess persistence 50 third instar larvae of Aedes aegypti laboratory lineages (Rockefeller) and 50 larvae of Aedes aegypti collected in the municipality of Macapa, Brazil’s Amapa state, were added weekly and after 24 hours the mortality was assessed. In total 16 tests were performed, where 12 were done with replacement of water (1/5 of the volume, three times per week). The effectiveness of the product was determined through mortality of ≥ 80%, as recommend by the World Health Organization. The results demonstrated that high-water temperatures (26-35 °C) on the containers influenced the residual time of the product, where the maximum effect achieved was 21 days in the shaded area; and no effectiveness of 60 days was found in any of the tests, as expected according to the larvicide company. The test with and without water replacement did not present significant differences in the mortality rate. Considering the different environments and climate, these results stimulate the need to test larvicide and its effectiveness in specific environmental settings in order to identify the parameters required for better results. Thus, we see the importance of semi-field researches considering the local climate conditions for a successful control of Aedes aegypti.

Keywords: Aedes aegypti, bioassay, larvicida, vector control

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1 The Regulation of the Cancer Epigenetic Landscape Lies in the Realm of the Long Non-coding RNAs

Authors: Ricardo Alberto Chiong Zevallos, Eduardo Moraes Rego Reis

Abstract:

Pancreatic adenocarcinoma (PDAC) patients have a less than 10% 5-year survival rate. PDAC has no defined diagnostic and prognostic biomarkers. Gemcitabine is the first-line drug in PDAC and several other cancers. Long non-coding RNAs (lncRNAs) contribute to the tumorigenesis and are potential biomarkers for PDAC. Although lncRNAs aren’t translated into proteins, they have important functions. LncRNAs can decoy or recruit proteins from the epigenetic machinery, act as microRNA sponges, participate in protein translocation through different cellular compartments, and even promote chemoresistance. The chromatin remodeling enzyme EZH2 is a histone methyltransferase that catalyzes the methylation of histone 3 at lysine 27, silencing local expression. EZH2 is ambivalent, it can also activate gene expression independently of its histone methyltransferase activity. EZH2 is overexpressed in several cancers and interacts with lncRNAs, being recruited to a specific locus. EZH2 can be recruited to activate an oncogene or silence a tumor suppressor. The lncRNAs misregulation in cancer can result in the differential recruitment of EZH2 and in a distinct epigenetic landscape, promoting chemoresistance. The relevance of the EZH2-lncRNAs interaction to chemoresistant PDAC was assessed by Real Time quantitative PCR (RT-qPCR) and RNA Immunoprecipitation (RIP) experiments with naïve and gemcitabine-resistant PDAC cells. The expression of several lncRNAs and EZH2 gene targets was evaluated contrasting naïve and resistant cells. Selection of candidate genes was made by bioinformatic analysis and literature curation. Indeed, the resistant cell line showed higher expression of chemoresistant-associated lncRNAs and protein coding genes. RIP detected lncRNAs interacting with EZH2 with varying intensity levels in the cell lines. During RIP, the nuclear fraction of the cells was incubated with an antibody for EZH2 and with magnetic beads. The RNA precipitated with the beads-antibody-EZH2 complex was isolated and reverse transcribed. The presence of candidate lncRNAs was detected by RT-qPCR, and the enrichment was calculated relative to INPUT (total lysate control sample collected before RIP). The enrichment levels varied across the several lncRNAs and cell lines. The EZH2-lncRNA interaction might be responsible for the regulation of chemoresistance-associated genes in multiple cancers. The relevance of the lncRNA-EZH2 interaction to PDAC was assessed by siRNA knockdown of a lncRNA, followed by the analysis of the EZH2 target expression by RT-qPCR. The chromatin immunoprecipitation (ChIP) of EZH2 and H3K27me3 followed by RT-qPCR with primers for EZH2 targets also assess the specificity of the EZH2 recruitment by the lncRNA. This is the first report of the interaction of EZH2 and lncRNAs HOTTIP and PVT1 in chemoresistant PDAC. HOTTIP and PVT1 were described as promoting chemoresistance in several cancers, but the role of EZH2 is not clarified. For the first time, the lncRNA LINC01133 was detected in a chemoresistant cancer. The interaction of EZH2 with LINC02577, LINC00920, LINC00941, and LINC01559 have never been reported in any context. The novel lncRNAs-EZH2 interactions regulate chemoresistant-associated genes in PDAC and might be relevant to other cancers. Therapies targeting EZH2 alone weren’t successful, and a combinatorial approach also targeting the lncRNAs interacting with it might be key to overcome chemoresistance in several cancers.

Keywords: epigenetics, chemoresistance, long non-coding RNAs, pancreatic cancer, histone modification

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