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•HIV broadly neutralizing antibodies were conjugated to cholesterol.•A high membrane affinity was achieved for cholesterol-tagged antibodies.•High antiviral activity correlates with a ...strong membrane affinity.
The HIV broadly neutralizing antibody 2F5 targets the transiently exposed epitope in the membrane proximal external region (MPER) of HIV-1 gp41, by a two-step mechanism involving the viral membrane and this viral glycoprotein. It was recently shown that 2F5 conjugation with a cholesterol moiety outside of the antibody paratope substantially increases its antiviral activity. Additionally, the antiviral activity of D5, a human antibody that binds to the N-terminal heptad repeat (NHR) of gp41 and lacks membrane binding, was boosted by the same cholesterol conjugation. In this work, we evaluated the membrane affinity of both antibodies towards membranes of different compositions, using surface plasmon resonance. A correlation was found between membrane affinity and antiviral activity against HIV-1. We propose that the conjugation of cholesterol to 2F5 or D5 allows a higher degree of antibody pre-concentration at the viral membrane. This way, the antibodies become more available to bind efficiently to the gp41 epitope, blocking viral fusion faster than the unconjugated antibody. These results set up a relevant strategy to improve the rational design of therapeutic antibodies against HIV.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Microstructures of a single layer AISI M4 high speed steel deposited on a AISI D2 tool steel substrate using the L‑DED process with two levels of global energy density were characterized and ...compared.
A five-axes PRECO-SL 8600 CNC machine was used to deposit the M4 powder feedstock with a continuous wave laser source, near-infrared wavelength laser beam, 2.0 mm spot size, and coaxial continuous feed nozzle. The M4 powder had particle sizes between 60 and 210 μm and a volumetric mean diameter of 119 µm. The quenched and tempered D2 substrate had a thickness of 15 mm and a hardness of with 755 HV. Two
laser power/scan speed
sets were used:
700
W/800
mm/min
and
1100
W/500
mm/min
, that is GED = 26.3 J/mm
2
and GED = 66 J/mm
2
, respectively.
The microstructures were characterized through optical micrography, SEM and EDS, and WDS microanalyses. Five different zones could be distinguished, according to their microstructure features, and differences related to the energy density were analyzed.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The purpose of this study was to evaluate the effect of build direction on the mechanical properties of AISI 316L stainless steel using the Laser Directed Energy Deposition (L-DED) process, in the ...as-built and heat-treated conditions. The test specimens were manufactured in vertical and horizontal directions for tensile and impact tests. In addition, analysis test specimens cube-shaped were manufactured for microstructural and microhardness evaluation. The microstructure in the as-built condition showed a combination of cellular, equiaxial dendritic, cellular dendritic and columnar dendritic, while the microstructure in the heat-treated condition showed a homogeneous characteristic, composed by differently sized grains. The microhardness evaluation in the heat-treated condition presented a reduction of 26.52% compared to the as-build condition. The ultimate tensile strength of horizontal test specimens in the as-built condition was 4.86% higher than the heat-treated condition, whereas the ultimate tensile strength of vertical test specimens in the as-built condition was 5.55% higher than the heat-treated condition. The impact resistance of horizontal test specimens in the heat-treated condition was 12.36% higher than the as-built condition, whereas the impact resistance of vertical test specimens in the heat-treated condition was 18.92% higher than the as-built condition. Briefly, the build direction directly affects the mechanical properties of components manufactured through the L-DED process, and it is possible to improve certain mechanical properties, such as ductility and toughness, through heat treatment.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
ABSTRACT Objectives: The development of antibodies (inhibitors) against exogenous factors is the main complication in the treatment of hemophilia. Both genetic and non-genetic factors are related to ...inhibitor development. Among the genetic factors, the type of mutation that caused the disease is one of the most important. The objectives of the present study were to establish the prevalence of inversions in introns 1 and 22 of the factor VIII gene in patients with severe hemophilia A, correlating these with inhibitor development, and to compare the results with data from the literature. Method: Unrelated severe hemophilia A patients were analyzed for the presence of inversions in intron 1 (n = 77) and intron 22 (n = 39) by polymerase chain reaction (PCR). Detection of the inhibitor was performed by the mixing test and its quantification was performed by the Bethesda method. Results: The prevalence of inversions in introns 1 and 22 was 2.6% and 41%, respectively. No patient with inversions in intron 1 had inhibitors, whereas 26.3% of patients with inversions in intron 22 developed inhibitors. Conclusion: Due to the small number of patients with inversions in intron 1, it was not possible to perform a statistical test for the correlation with risk of inhibitor development. Inversions in intron 22 of the factor VIII gene were not associated with an increased risk of inhibitor development in the analyzed samples (p = 1).
The aim of this work was to evaluate the effect of different heat treatment routes on the microstructure and sliding wear resistance of Inconel 718 alloy deposited by laser cladding on an AISI 316 L ...stainless steel substrate. Three heat treatment conditions were tested: double aged, solubilized and double aged, and homogenized, solubilized and double aged. These conditions were compared between each other and the as built samples. Both as built and double aged conditions presented a dendritic microstructure. The solubilized and double aged samples exhibited a recrystallized characteristic, however still containing a dendritic structure. While the homogenized, solubilized and double aged samples reveled equiaxial grains with the total replacement of the dendrites. Regarding the top and cross-section hardness, the heat-treated claddings were superior (about 65% higher) when compared to the as built condition. The friction coefficient for all conditions were statistically equal, however the solubilized and double aged and homogenized, solubilized and double aged conditions showed better results of wear loss (about 25% lower) when compared to the as built condition, whereas the double aged condition displayed statistically equal results in relation to the others. The wear mechanisms were predominantly adhesive for the as built conditions, adhesive and abrasive for the double aged and mostly abrasive for the solubilized and double aged and homogenized, solubilized and double aged samples. The results presented confirmed the need for heat treatment to improve the hardness of the coating and, in addition, it can be concluded that the different heat treatment routes did not have significant impacts on wear resistance. Therefore, from the conditions tested in this study it is possible to assume that the double aged route is the most suitable, for the point of view of wear resistance.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Economic, political, and technological uncertainties require organizations to prepare adequately for new events that occur each day. Economic crisis, changes in the policies of each country and ...technological developments are classic examples of these changes in organizations. Seasonality is one of the economic phenomena that occur, and different forms of management are required. The seasonality that is described as a systematic and temporal imbalance of the tourist phenomenon that does not need to be regular, caused by the climate or by the vacation periods, and is based on the consumer behavior that can be expressed in terms of the number of visitors, traffic, highways, jobs, and tickets at attractions. Therefore, through a careful analysis of seasonality, it is possible that the losses are predicted, and the negative impact is not so grotesque on the company. For this, it is good that the manager uses the cost assessment methods to assume the seasonality of sales and thus be able to guard against the negative effects of the same. The objective of this research is to understand how owners of micro and small businesses in coastal cities consider themselves entrepreneurs or not and how they deal with obstacles such as seasonality through cost management. The methodology used was based on an exploratory and bibliographic research with a qualitative approach, seeking to analyze the triad: Entrepreneurship, Seasonality and Cost Management. The field research was applied through a semi-structured questionnaire to the sample of 100 Microentrepreneurs in the trade of goods and services in Caraguatatuba and São Sebastião, central cities of the North Coast of São Paulo. The main results show that most of the interviewed entrepreneurs perceive a certain impact caused by seasonality, understand the use of Cost Management to improve their processes and are adapted to one of the main costing methods highlighted by the bibliography.
The present work aimed to assess the combination of the use of an empirical-statistical model and design of experiments (DoE) to minimally validate the geometrical characteristics (dilution, coating ...height, waviness and porosity) of a laser-induced Inconel 625 coating on AISI 316L substrate. Employing the estimated laser processing parameters, a verification coating was deposited to assess its microstructure, microhardness and bending resistance. The statistical model showed to be an efficient computational tool for the planning of the design of experiments (DoE), resulting in errors less than 15% for all geometrical characteristics evaluated. The presence of some pores along the verification Inconel 625 coating was observed. Additionally, the verification coating showed good dilution and low waviness. Regarding the microstructure and microhardness, the verification coating showed a columnar dendritic microstructure, and its microhardness was about 110% higher than that observed for the AISI 316L substrate. Its resistance to bending was 30% higher when compared to that of the uncoated samples. By considering the experimental conditions explored within this work, one can state that the laser-cladded Inconel 625 coatings performed well on AISI 316L stainless steel substrate.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Resumo: O presente trabalho teve como objetivo determinar parâmetros de processamento a laser para deposição de revestimentos de Stellite 6 livres de descontinuidades e com geometria adequada sobre ...aço inoxidável austenítico. Revestimentos foram depositados com uma fonte de laser de diodo, equipada com um cabeçote coaxial contínuo, utilizando diferentes potências do feixe e velocidades de varredura. A geometria (largura, altura, ondulação e diluição) dos revestimentos foi medida por meio de análise da secção transversal. Esses dados obtidos foram utilizados para a modelagem do processo (superfície de resposta) e para estimar parâmetros otimizados (função desejabilidade), que foram posteriormente verificados experimentalmente. A microestrutura dos revestimentos depositados com os parâmetros otimizados foi caracterizada por microscopia óptica e eletrônica de varredura. A seleção adequada dos parâmetros resultou em revestimentos com bom acabamento, livre de descontinuidades superficiais e baixa diluição. Os resultados mostram que a potência do laser teve efeito significativo sobre a diluição, enquanto a velocidade influenciou na altura da camada depositada. A microestrutura resultante do revestimento é composta por dendritas ricas em cobalto e a região interdendrítica com carbonetos de cromo. Os resultados de dureza estão de acordo com o previsto na literatura.
Abstract: The present work aimed to determine laser processing parameters for deposition of defect-free Stellite 6 coatings and with suitable geometry on austenitic stainless steel. Coatings were deposited with a diode laser source, equipped with a continuous coaxial head, using different beam powers and scanning speeds. The geometry (width, height, undulation and dilution) of the coatings was measured by analyzing the cross section. These obtained data were used to model the process (response surface) and to estimate optimized parameters (function desirability), which were later verified experimentally. The microstructure of the coatings deposited with the optimized parameters was characterized by optical and scanning electron microscopy. The proper selection of parameters resulted in coatings with good surface finish, free of superficial defects and low dilution. The results show that the laser power had a significant effect on the dilution, while the speed influenced the height of the deposited layer. The microstructure resulting from the coating is composed of dendrites rich in cobalt and interdendritic region with chromium carbides. The hardness results are in line with the predicted in the literature.
Inflation forecasting is an important but difficult task. Here, we explore advances in machine learning (ML) methods and the availability of new datasets to forecast U.S. inflation. Despite the ...skepticism in the previous literature, we show that ML models with a large number of covariates are systematically more accurate than the benchmarks. The ML method that deserves more attention is the random forest model, which dominates all other models. Its good performance is due not only to its specific method of variable selection but also the potential nonlinearities between past key macroeconomic variables and inflation.
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