Program for establishing long-time flight service performance of composite materials in the center wing structure of C-130 aircraft. Phase 3: Fabrication

The manufacturing plan for three C-130 aircraft center wing box test articles, selectively reinforced with boron-epoxy composites, is outlined for the following tasks: (1) tooling; (2) metal parts fabrication: (3) reinforcing laminate fabrication; (4) laminate-to-metal parts bonding; and (5) wing box assembly. The criteria used for reliability and quality assurance are discussed, and several solutions to specific manufacturing problems encountered during fabrication are given. For Vol. 1, see N73-13011; for Vol. 2, see N73-22929

Development of the technology for the fabrication of reliable laminar from control panels

Materials were assessed and fabrication techniques were developed for use in the manufacture of wing surface materials compatible with the application of both aluminum alloys and nonmetallic composites. The concepts investigated included perforations and slots in the metallic test panels and microporosity and perforations in the composite test panels. Perforations were produced in the metallic test panels by the electron beam process and slots were developed by controlled gaps between the metal sheets. Microporosity was produced in the composite test panels by the resin bleed process, and perforations were produced by the fugitive fiber technique. Each of these concepts was fabricated into test panels, and air flow tests were conducted on the panels

Mudanças nos compostos bioativos e atividade antioxidante de pimentas da região amazônica.

A Embrapa Amazônia Oriental possui um Banco Ativo de Pimenteira com diferentes genótipos do gênero Capsicum, os quais ainda não foram analisados, quanto às suas características funcionais e capacidade antioxidante. Este estudo objetivou determinar os teores de ácido ascórbico, compostos fenólicos, carotenoides totais e a atividade antioxidante total, em frutos imaturos e maduros de genótipos de pimentas Capsicum spp. As concentrações de vitamina C (100,76-361,65 mg 100 g-1 nos frutos imaturos e 36,70-157,76 mg 100 g-1 nos maduros) decresceram com a maturação dos frutos. Carotenoides totais não foram detectados nos frutos imaturos, porém, nos frutos maduros, observaram-se valores de 73,80-1349,97 mg g-1, em função do genótipo. Os teores de compostos fenólicos aumentaram nos frutos maduros (147,40-718,64 mg GAE 100 g-1), para oito dos nove genótipos avaliados. Os frutos de pimenteira apresentaram significativa atividade antioxidante (55,02-92,03 mM trolox g-1 nos frutos imaturos e 39,60-113,08 mM trolox g- 1 nos maduros). Concluiu-se que o grau de maturação dos frutos influenciou nos teores de compostos bioativos dos genótipos estudados. Destacaram-se, como genótipos promissores com potencial para serem utilizados em programas de melhoramento genético, IAN-186301 e IAN-186324, pelos altos teores de carotenoides totais; IAN-186301, IAN-186311, IAN-186312 e IAN-186313, com relação às altas concentrações de ácido ascórbico; IAN-186304 e IAN-186311, pelos altos teores de compostos fenólicos; e IAN-186311, para atividade antioxidante

Efficacious and Safe Tissue-Selective Controlled Gene Therapy Approaches for the Cornea

Untargeted and uncontrolled gene delivery is a major cause of gene therapy failure. This study aimed to define efficient and safe tissue-selective targeted gene therapy approaches for delivering genes into keratocytes of the cornea in vivo using a normal or diseased rabbit model. New Zealand White rabbits, adeno-associated virus serotype 5 (AAV5), and a minimally invasive hair-dryer based vector-delivery technique were used. Fifty microliters of AAV5 titer (6.5×1012 vg/ml) expressing green fluorescent protein gene (GFP) was topically applied onto normal or diseased (fibrotic or neovascularized) rabbit corneas for 2-minutes with a custom vector-delivery technique. Corneal fibrosis and neovascularization in rabbit eyes were induced with photorefractive keratectomy using excimer laser and VEGF (630 ng) using micropocket assay, respectively. Slit-lamp biomicroscopy and immunocytochemistry were used to confirm fibrosis and neovascularization in rabbit corneas. The levels, location and duration of delivered-GFP gene expression in the rabbit stroma were measured with immunocytochemistry and/or western blotting. Slot-blot measured delivered-GFP gene copy number. Confocal microscopy performed in whole-mounts of cornea and thick corneal sections determined geometric and spatial localization of delivered-GFP in three-dimensional arrangement. AAV5 toxicity and safety were evaluated with clinical eye exam, stereomicroscopy, slit-lamp biomicroscopy, and H&E staining. A single 2-minute AAV5 topical application via custom delivery-technique efficiently and selectively transduced keratocytes in the anterior stroma of normal and diseased rabbit corneas as evident from immunocytochemistry and confocal microscopy. Transgene expression was first detected at day 3, peaked at day 7, and was maintained up to 16 weeks (longest tested time point). Clinical and slit-lamp eye examination in live rabbits and H&E staining did not reveal any significant changes between AAV5-treated and untreated control corneas. These findings suggest that defined gene therapy approaches are safe for delivering genes into keratocytes in vivo and has potential for treating corneal disorders in human patients

Decreased surfactant phosphatidylcholine synthesis in neonates with congenital diaphragmatic hernia during extracorporeal membrane oxygenation

Purpose: Congenital diaphragmatic hernia (CDH) may result in severe respiratory insufficiency with a high morbidity. The role of a disturbed surfactant metabolism in the pathogenesis of CDH is unclear. We therefore studied endogenous surfactant metabolism in the most severe CDH patients who required extracorporeal membrane oxygenation (ECMO). Methods: Eleven neonates with CDH who required ECMO and ten ventilated neonates without significant lung disease received a 24-h infusion of the stable isotope [U-13C] glucose. The13C-incorporation into palmitic acid in surfactant phosphatidylcholine (PC) isolated from serial tracheal aspirates was measured. Mean PC concentration in epithelial lining fluid (ELF) was measured during the first 4 days of the study. Results: Fractional surfactant PC synthesis was decreased in CDH-ECMO patients compared to controls (2.4 ± 0.33 vs. 8.0 ± 2.4%/day, p = 0.04). The control group had a higher maximal enrichment (0.18 ± 0.03 vs. 0.09 ± 0.02 APE, p = 0.04) and reached this maximal enrichment earlier (46.7 ± 3.0 vs. 69.4 ± 6.6 h, p = 0.004) compared to the CDH-ECMO group, which reflects higher and faster precursor incorporation in the control group. Surfactant PC concentration in ELF was similar in both groups. Conclusion: These results show that CDH patients who require ECMO have a decreased surfactant PC synthesis, which may be part of the pathogenesis of severe pulmonary insufficiency and has a negative impact on weaning from ECMO

Decreased surfactant phosphatidylcholine synthesis in neonates with congenital diaphragmatic hernia during extracorporeal membrane oxygenation

Purpose: Congenital diaphragmatic hernia (CDH) may result in severe respiratory insufficiency with a high morbidity. The role of a disturbed surfactant metabolism in the pathogenesis of CDH is unclear. We therefore studied endogenous surfactant metabolism in the most severe CDH patients who required extracorporeal membrane oxygenation (ECMO). Methods: Eleven neonates with CDH who required ECMO and ten ventilated neonates without significant lung disease received a 24-h infusion of the stable isotope [U-13C] glucose. The13C-incorporation into palmitic acid in surfactant phosphatidylcholine (PC) isolated from serial tracheal aspirates was measured. Mean PC concentration in epithelial lining fluid (ELF) was measured during the first 4 days of the study. Results: Fractional surfactant PC synthesis was decreased in CDH-ECMO patients compared to controls (2.4 ± 0.33 vs. 8.0 ± 2.4%/day, p = 0.04). The control group had a higher maximal enrichment (0.18 ± 0.03 vs. 0.09 ± 0.02 APE, p = 0.04) and reached this maximal enrichment earlier (46.7 ± 3.0 vs. 69.4 ± 6.6 h, p = 0.004) compared to the CDH-ECMO group, which reflects higher and faster precursor incorporation in the control group. Surfactant PC concentration in ELF was similar in both groups. Conclusion: These results show that CDH patients who require ECMO have a decreased surfactant PC synthesis, which may be part of the pathogenesis of severe pulmonary insufficiency and has a negative impact on weaning from ECMO

Integrating data types to estimate spatial patterns of avian migration across the Western Hemisphere

For many avian species, spatial migration patterns remain largely undescribed, especially across hemispheric extents. Recent advancements in tracking technologies and high-resolution species distribution models (i.e., eBird Status and Trends products) provide new insights into migratory bird movements and offer a promising opportunity for integrating independent data sources to describe avian migration. Here, we present a three-stage modeling framework for estimating spatial patterns of avian migration. First, we integrate tracking and band re-encounter data to quantify migratory connectivity, defined as the relative proportions of individuals migrating between breeding and nonbreeding regions. Next, we use estimated connectivity proportions along with eBird occurrence probabilities to produce probabilistic least-cost path (LCP) indices. In a final step, we use generalized additive mixed models (GAMMs) both to evaluate the ability of LCP indices to accurately predict (i.e., as a covariate) observed locations derived from tracking and band re-encounter data sets versus pseudo-absence locations during migratory periods and to create a fully integrated (i.e., eBird occurrence, LCP, and tracking/band re-encounter data) spatial prediction index for mapping species-specific seasonal migrations. To illustrate this approach, we apply this framework to describe seasonal migrations of 12 bird species across the Western Hemisphere during pre- and postbreeding migratory periods (i.e., spring and fall, respectively). We found that including LCP indices with eBird occurrence in GAMMs generally improved the ability to accurately predict observed migratory locations compared to models with eBird occurrence alone. Using three performance metrics, the eBird + LCP model demonstrated equivalent or superior fit relative to the eBird-only model for 22 of 24 species–season GAMMs. In particular, the integrated index filled in spatial gaps for species with over-water movements and those that migrated over land where there were few eBird sightings and, thus, low predictive ability of eBird occurrence probabilities (e.g., Amazonian rainforest in South America). This methodology of combining individual-based seasonal movement data with temporally dynamic species distribution models provides a comprehensive approach to integrating multiple data types to describe broad-scale spatial patterns of animal movement. Further development and customization of this approach will continue to advance knowledge about the full annual cycle and conservation of migratory birds

Biological Earth observation with animal sensors.

Space-based tracking technology using low-cost miniature tags is now delivering data on fine-scale animal movement at near-global scale. Linked with remotely sensed environmental data, this offers a biological lens on habitat integrity and connectivity for conservation and human health; a global network of animal sentinels of environmen-tal change

Female-Biased Dispersal and Gene Flow in a Behaviorally Monogamous Mammal, the Large Treeshrew (Tupaia tana)

Background: Female-biased dispersal (FBD) is predicted to occur in monogamous species due to local resource competition among females, but evidence for this association in mammals is scarce. The predicted relationship between FBD and monogamy may also be too simplistic, given that many pair-living mammals exhibit substantial extra-pair paternity. Methodology/Principal Findings: I examined whether dispersal and gene flow are female-biased in the large treeshrew (Tupaia tana) in Borneo, a behaviorally monogamous species with a genetic mating system characterized by high rates (50%) of extra-pair paternity. Genetic analyses provided evidence of FBD in this species. As predicted for FBD, I found lower mean values for the corrected assignment index for adult females than for males using seven microsatellite loci, indicating that female individuals were more likely to be immigrants. Adult female pairs were also less related than adult male pairs. Furthermore, comparison of Bayesian coalescent-based estimates of migration rates using maternally and bi-parentally inherited genetic markers suggested that gene flow is female-biased in T. tana. The effective number of migrants between populations estimated from mitochondrial DNA sequence was three times higher than the number estimated using autosomal microsatellites. Conclusions/Significance: These results provide the first evidence of FBD in a behaviorally monogamous species without mating fidelity. I argue that competition among females for feeding territories creates a sexual asymmetry in the costs an