13 research outputs found
A preliminary investigation of finite-element modeling for composite rotor blades
The results from an initial phase of an in-house study aimed at improving the dynamic and aerodynamic characteristics of composite rotor blades through the use of elastic couplings are presented. Large degree of freedom shell finite element models of an extension twist coupled composite tube were developed and analyzed using MSC/NASTRAN. An analysis employing a simplified beam finite element representation of the specimen with the equivalent engineering stiffness was additionally performed. Results from the shell finite element normal modes and frequency analysis were compared to those obtained experimentally, showing an agreement within 13 percent. There was appreciable degradation in the frequency prediction for the torsional mode, which is elastically coupled. This was due to the absence of off-diagonal coupling terms in the formulation of the equivalent engineering stiffness. Parametric studies of frequency variation due to small changes in ply orientation angle and ply thickness were also performed. Results showed linear frequency variations less than 2 percent per 1 degree variation in the ply orientation angle, and 1 percent per 0.0001 inch variation in the ply thickness
Experimental and analytical investigation of dynamic characteristics of extension-twist-coupled composite tubular spars
The results from a study aimed at improving the dynamic and aerodynamic characteristics of composite rotor blades through the use of extension-twist coupling are presented. A set of extension-twist-coupled composite spars was manufactured with four plies of graphite-epoxy cloth prepreg. These spars were noncircular in cross-section design and were therefore subject to warping deformations. Three different cross-sectional geometries were developed: D-shape, square, and flattened ellipse. Three spars of each type were fabricated to assess the degree of repeatability in the manufacturing process of extension-twist-coupled structures. Results from free-free vibration tests of the spars were compared with results from normal modes and frequency analyses of companion shell-finite-element models. Five global modes were identified within the frequency range from 0 to 2000 Hz for each spar. The experimental results for only one D-shape spar could be determined, however, and agreed within 13.8 percent of the analytical results. Frequencies corresponding to the five global modes for the three square spars agreed within 9.5, 11.6, and 8.5 percent of the respective analytical results and for the three elliptical spars agreed within 4.9, 7.7, and 9.6 percent of the respective analytical results
Evaluation of a Head-Worn Display with Ambient Vision Cues for Unusual Attitude Recovery
A Commercial Aviation Safety Team (CAST) study of 18 loss-of-control events determined that a lack of external visual references was a contributing factor in 17 of these events. CAST recommended that manufacturers should develop and implement virtual day-VMC display systems, such as synthetic vision (SV) or equivalent systems (CAST Safety Enhancement, SE-200). In support of this recommended action, CAST has requested studies to define minimum requirements for virtual day-visual meteorological conditions (VMC) displays to improve flight crew awareness of airplane attitude. NASAs research in Virtual day-VMC displays, known as synthetic vision systems, are intended to support intuitive flight crew attitude awareness similar to a day-VMC-like environment, especially if they could be designed to create visual dominance. A study was conducted to evaluate the utility of ambient vision (AV) cues paired with virtual Head-Up Display (HUD) symbology on a prototype head-worn display (HWD) during recovery from unusual attitudes in a simulated environment. The virtual-HUD component meets the requirement that the HWD may be used as an equivalent display to the HUD. The presence of AV cueing leverages the potential that a HWD has over the HUD for spatial disorientation prevention. The simulation study was conducted as a single-pilot operation, under realistic flight scenarios, with off-nominal events occurring that were capable of inducing unusual attitudes. Independent variables of the experiment included: 1) AV capability (on vs off) 2) AV display opaqueness (transparent vs opaque) and display location (HWD vs traditional head- down displays); AV cues were only present when the HWD was being worn by the subject pilot
African-Caribbean cancer consortium for the study of viral, genetic and environmental cancer risk factors
This is a short summary of a meeting of the "African-Caribbean Cancer Consortium", jointly organized by the University of Pittsburgh, Department of Epidemiology and the University of Pittsburgh Cancer Institute, held in Montego Bay, Jamaica as a satellite meeting at the Caribbean Health Research Council, 52nd Annual Council and Scientific meeting on May 4, 2007
Comparative cellular analysis of motor cortex in human, marmoset and mouse
The primary motor cortex (M1) is essential for voluntary fine-motor control and is functionally conserved across mammals1. Here, using high-throughput transcriptomic and epigenomic profiling of more than 450,000 single nuclei in humans, marmoset monkeys and mice, we demonstrate a broadly conserved cellular makeup of this region, with similarities that mirror evolutionary distance and are consistent between the transcriptome and epigenome. The core conserved molecular identities of neuronal and non-neuronal cell types allow us to generate a cross-species consensus classification of cell types, and to infer conserved properties of cell types across species. Despite the overall conservation, however, many species-dependent specializations are apparent, including differences in cell-type proportions, gene expression, DNA methylation and chromatin state. Few cell-type marker genes are conserved across species, revealing a short list of candidate genes and regulatory mechanisms that are responsible for conserved features of homologous cell types, such as the GABAergic chandelier cells. This consensus transcriptomic classification allows us to use patch-seq (a combination of whole-cell patch-clamp recordings, RNA sequencing and morphological characterization) to identify corticospinal Betz cells from layer 5 in non-human primates and humans, and to characterize their highly specialized physiology and anatomy. These findings highlight the robust molecular underpinnings of cell-type diversity in M1 across mammals, and point to the genes and regulatory pathways responsible for the functional identity of cell types and their species-specific adaptations
31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two
Background
The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd.
Methods
We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background.
Results
First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001).
Conclusions
In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival
Aeroservoelastic and Structural Dynamics Research on Smart Structures Conducted at NASA Langley Research Center
An overview of smart structures research currently underway at the NASA Langley Research Center in the areas of aeroservoelasticity and structural dynamics is presented. Analytical and experimental results, plans, potential technology pay-offs, and challenges are discussed. The goal of this research is to develop the enabling technologies to actively and passively control aircraft and rotorcraft vibration and loads using smart devices. These enabling technologies and related research efforts include developing experimentally-validated finite element and aeroservoelastic modeling techniques; conducting bench experimental tests to assess feasibility and understand system trade-offs; and conducting large-scale wind tunnel tests to demonstrate system performance. The key aeroservoelastic applications of this research include: active twist control of rotor blades using interdigitated electrode piezoelectric composites and active control of flutter, and gust and buffeting responses using discrete piezoelectric patches. In addition, NASA Langley is an active participant in the DARPA/Air Force Research Laboratory/NASA/Northrop Grumman Smart Wing program which is assessing aerodynamic performance benefits using smart materials
Handbook of curriculum development. 'Manual de desarrollo curricular'
Incluye Ãndice temático. Resumen basado en el de la publicaciónEl desarrollo de un curriculum es una especie de planificación sistemática de lo que se enseña y se aprende en las escuelas tal y como se refleja en los cursos de estudio y en los programas escolares. Un curriculum se centra en lo que se va a enseñar y cuándo, dejando a los profesionales de la enseñanza decisiones sobre cómo deberÃa realizarse esta enseñanza. Repartidos en veinte capÃtulos, se tratan, entre otros, los siguientes temas: La aplicación de la estrategia del Aprendizaje Basado en Problemas o Problem Based Learning (PBL); El desarrollo de un modelo de situación formativa para enseñar ciencia y tecnologÃa, que pretende ser tomado como base a las decisiones de los profesores para lograr la calidad en la enseñanza; La discusión de cinco modelos de desarrollo curricular basados en diferentes conceptos de experiencia de aprendizaje; Las habilidades para realizar presentaciones orales; El estudio de cómo los maestros de Primaria aprenden a participar en el diseño de materiales curriculares para ciencia; Las razones para desarrollar un curriculum centrado en el aprendizaje en la enseñanza superior; La mejora del conocimiento académico de los estudiantes y el incremento de su competencia social; El efecto del uso de estructuras de texto expositivas como estrategia en la habilidad de resumir; El desarrollo curricular en ambientes online; La evaluación de la reforma curricular en la Educación Secundaria turca; La importancia del desarrollo social y emocional en el éxito; entre otros.SCBiblioteca de Educación del Ministerio de Educación, Cultura y Deporte; Calle San AgustÃn 5 -3 Planta; 28014 Madrid; Tel. +34917748000; [email protected]
Mathematical Model of the Firefly Luciferase Complementation Assay Reveals a Non-Linear Relationship between the Detected Luminescence and the Affinity of the Protein Pair Being Analyzed
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Comparative cellular analysis of motor cortex in human, marmoset and mouse.
The primary motor cortex (M1) is essential for voluntary fine-motor control and is functionally conserved across mammals1. Here, using high-throughput transcriptomic and epigenomic profiling of more than 450,000 single nuclei in humans, marmoset monkeys and mice, we demonstrate a broadly conserved cellular makeup of this region, with similarities that mirror evolutionary distance and are consistent between the transcriptome and epigenome. The core conserved molecular identities of neuronal and non-neuronal cell types allow us to generate a cross-species consensus classification of cell types, and to infer conserved properties of cell types across species. Despite the overall conservation, however, many species-dependent specializations are apparent, including differences in cell-type proportions, gene expression, DNA methylation and chromatin state. Few cell-type marker genes are conserved across species, revealing a short list of candidate genes and regulatory mechanisms that are responsible for conserved features of homologous cell types, such as the GABAergic chandelier cells. This consensus transcriptomic classification allows us to use patch-seq (a combination of whole-cell patch-clamp recordings, RNA sequencing and morphological characterization) to identify corticospinal Betz cells from layer 5 in non-human primates and humans, and to characterize their highly specialized physiology and anatomy. These findings highlight the robust molecular underpinnings of cell-type diversity in M1 across mammals, and point to the genes and regulatory pathways responsible for the functional identity of cell types and their species-specific adaptations