Advanced Technology Composite Fuselage-Structural Performance

Boeing is studying the technologies associated with the application of composite materials to commercial transport fuselage structure under the NASA-sponsored contracts for Advanced Technology Composite Aircraft Structures (ATCAS) and Materials Development Omnibus Contract (MDOC). This report addresses the program activities related to structural performance of the selected concepts, including both the design development and subsequent detailed evaluation. Design criteria were developed to ensure compliance with regulatory requirements and typical company objectives. Accurate analysis methods were selected and/or developed where practical, and conservative approaches were used where significant approximations were necessary. Design sizing activities supported subsequent development by providing representative design configurations for structural evaluation and by identifying the critical performance issues. Significant program efforts were directed towards assessing structural performance predictive capability. The structural database collected to perform this assessment was intimately linked to the manufacturing scale-up activities to ensure inclusion of manufacturing-induced performance traits. Mechanical tests were conducted to support the development and critical evaluation of analysis methods addressing internal loads, stability, ultimate strength, attachment and splice strength, and damage tolerance. Unresolved aspects of these performance issues were identified as part of the assessments, providing direction for future development

Overturning established chemoselectivities : selective reduction of arenes over malonates and cyanoacetates by photoactivated organic electron donors

The prevalence of metal-based reducing reagents, including metals, metal complexes, and metal salts, has produced an empirical order of reactivity that governs our approach to chemical synthesis. However, this reactivity may be influenced by stabilization of transition states, intermediates, and products through substrate-metal bonding. This article reports that in the absence of such stabilizing interactions, established chemoselectivities can be overthrown. Thus, photoactivation of the recently developed neutral organic superelectron donor 5 selectively reduces alkyl-substituted benzene rings in the presence of activated esters and nitriles, in direct contrast to metal-based reductions, opening a new perspective on reactivity. The altered outcomes arising from the organic electron donors are attributed to selective interactions between the neutral organic donors and the arene rings of the substrates

A rapidly-reversible absorptive and emissive vapochromic Pt(II) pincer based chemical sensor

Selective, robust and cost-effective chemical sensors for detecting small volatile-organic compounds (VOCs) have widespread applications in industry, healthcare and environmental monitoring. Here we design a Pt(II) pincer-type material with selective absorptive and emissive responses to methanol and water. The yellow anhydrous form converts reversibly on a subsecond timescale to a red hydrate in the presence of parts-per-thousand levels of atmospheric water vapour. Exposure to methanol induces a similarly-rapid and reversible colour change to a blue methanol solvate. Stable smart coatings on glass demonstrate robust switching over 104 cycles, and flexible microporous polymer membranes incorporating microcrystals of the complex show identical vapochromic behaviour. The rapid vapochromic response can be rationalized from the crystal structure, and in combination with quantum-chemical modelling we provide a complete microscopic picture of the switching mechanism. We discuss how this multiscale design approach can be used to obtain new compounds with tailored VOC selectivity and spectral responses

Analysis of Microplastics in Food Samples

This chapter presents a compilation of the analytical techniques used to detect and analyze microplastics in food. A detailed description of microplastics found in different samples is provided as well as an estimate of the annual intake of these particles. A total of 22–37 milligrams of microplastics per year was found. The factors that can influence the presence of particles in food, especially table salt, are discussed, showing that a background presence of microplastics in the environment can explain a large amount of experimental data.Support for this work was provided by the CTQ2016-76608-R project from the Ministry of Economy, Industry and Competitiveness (Spain) and by the University of Alicante under the project UAUSTI18-06

Photochemical fingerprinting Is a sensitive probe for the detection of synthetic cannabinoid receptor agonists; toward robust point-of-care detection

With synthetic cannabinoid receptor agonist (SCRA) use still prevalent across Europe and structurally advanced generations emerging, it is imperative that drug detection methods advance in parallel. SCRAs are a chemically diverse and evolving group, which makes rapid detection challenging. We have previously shown that fluorescence spectral fingerprinting (FSF) has the potential to provide rapid assessment of SCRA presence directly from street material with minimal processing and in saliva. Enhancing the sensitivity and discriminatory ability of this approach has high potential to accelerate the delivery of a point-of-care technology that can be used confidently by a range of stakeholders, from medical to prison staff. We demonstrate that a range of structurally distinct SCRAs are photochemically active and give rise to distinct FSFs after irradiation. To explore this in detail, we have synthesized a model series of compounds which mimic specific structural features of AM-694. Our data show that FSFs are sensitive to chemically conservative changes, with evidence that this relates to shifts in the electronic structure and cross-conjugation. Crucially, we find that the photochemical degradation rate is sensitive to individual structures and gives rise to a specific major product, the mechanism and identification of which we elucidate through density-functional theory (DFT) and time-dependent DFT. We test the potential of our hybrid “photochemical fingerprinting” approach to discriminate SCRAs by demonstrating SCRA detection from a simulated smoking apparatus in saliva. Our study shows the potential of tracking photochemical reactivity via FSFs for enhanced discrimination of SCRAs, with successful integration into a portable device

Applications of CRISPR–Cas systems in neuroscience

Genome-editing tools, and in particular those based on CRISPR-Cas (clustered regularly interspaced short palindromic repeat (CRISPR)-CRISPR-associated protein) systems, are accelerating the pace of biological research and enabling targeted genetic interrogation in almost any organism and cell type. These tools have opened the door to the development of new model systems for studying the complexity of the nervous system, including animal models and stem cell-derived in vitro models. Precise and efficient gene editing using CRISPR-Cas systems has the potential to advance both basic and translational neuroscience research.National Institute of Mental Health (U.S.) (Grant 5DP1-MH100706)National Institute of Mental Health (U.S.) (Grant 1R01-MH110049)National Institute of Diabetes and Digestive and Kidney Diseases (U.S.) (Grant 5R01DK097768-03

p53 Gene Repair with Zinc Finger Nucleases Optimised by Yeast 1-Hybrid and Validated by Solexa Sequencing

The tumor suppressor gene p53 is mutated or deleted in over 50% of human tumors. As functional p53 plays a pivotal role in protecting against cancer development, several strategies for restoring wild-type (wt) p53 function have been investigated. In this study, we applied an approach using gene repair with zinc finger nucleases (ZFNs). We adapted a commercially-available yeast one-hybrid (Y1H) selection kit to allow rapid building and optimization of 4-finger constructs from randomized PCR libraries. We thus generated novel functional zinc finger nucleases against two DNA sites in the human p53 gene, near cancer mutation ‘hotspots’. The ZFNs were first validated using in vitro cleavage assays and in vivo episomal gene repair assays in HEK293T cells. Subsequently, the ZFNs were used to restore wt-p53 status in the SF268 human cancer cell line, via ZFN-induced homologous recombination. The frequency of gene repair and mutation by non-homologous end-joining was then ascertained in several cancer cell lines, using a deep sequencing strategy. Our Y1H system facilitates the generation and optimisation of novel, sequence-specific four- to six-finger peptides, and the p53-specific ZFN described here can be used to mutate or repair p53 in genomic loci

Understanding How Microplastics Affect Marine Biota on the Cellular Level Is Important for Assessing Ecosystem Function: A Review

Plastic has become indispensable for human life. When plastic debris is discarded into waterways, these items can interact with organisms. Of particular concern are microscopic plastic particles (microplastics) which are subject to ingestion by several taxa. This review summarizes the results of cutting-edge research about the interactions between a range of aquatic species and microplastics, including effects on biota physiology and secondary ingestion. Uptake pathways via digestive or ventilatory systems are discussed, including (1) the physical penetration of microplastic particles into cellular structures, (2) leaching of chemical additives or adsorbed persistent organic pollutants (POPs), and (3) consequences of bacterial or viral microbiota contamination associated with microplastic ingestion. Following uptake, a number of individual-level effects have been observed, including reduction of feeding activities, reduced growth and reproduction through cellular modifications, and oxidative stress. Microplastic-associated effects on marine biota have become increasingly investigated with growing concerns regarding human health through trophic transfer. We argue that research on the cellular interactions with microplastics provide an understanding of their impact to the organisms’ fitness and, therefore, its ability to sustain their functional role in the ecosystem. The review summarizes information from 236 scientific publications. Of those, only 4.6% extrapolate their research of microplastic intake on individual species to the impact on ecosystem functioning. We emphasize the need for risk evaluation from organismal effects to an ecosystem level to effectively evaluate the effect of microplastic pollution on marine environments. Further studies are encouraged to investigate sublethal effects in the context of environmentally relevant microplastic pollution conditions

Environmental sensing and response genes in cnidaria : the chemical defensome in the sea anemone Nematostella vectensis

Author Posting. © The Author(s), 2008. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Cell Biology and Toxicology 24 (2008): 483-502, doi:10.1007/s10565-008-9107-5.The starlet sea anemone Nematostella vectensis has been recently established as a new model system for the study of the evolution of developmental processes, as cnidaria occupy a key evolutionary position at the base of the bilateria. Cnidaria play important roles in estuarine and reef communities, but are exposed to many environmental stressors. Here I describe the genetic components of a ‘chemical defensome’ in the genome of N. vectensis, and review cnidarian molecular toxicology. Gene families that defend against chemical stressors and the transcription factors that regulate these genes have been termed a ‘chemical defensome,’ and include the cytochromes P450 and other oxidases, various conjugating enyzymes, the ATP-dependent efflux transporters, oxidative detoxification proteins, as well as various transcription factors. These genes account for about 1% (266/27200) of the predicted genes in the sea anemone genome, similar to the proportion observed in tunicates and humans, but lower than that observed in sea urchins. While there are comparable numbers of stress-response genes, the stress sensor genes appear to be reduced in N. vectensis relative to many model protostomes and deuterostomes. Cnidarian toxicology is understudied, especially given the important ecological roles of many cnidarian species. New genomic resources should stimulate the study of chemical stress sensing and response mechanisms in cnidaria, and allow us to further illuminate the evolution of chemical defense gene networks.WHOI Ocean Life Institute and NIH R01-ES01591

Videogame-based group therapy to improve self-awareness and social skills after traumatic brain injury

[EN] Background: This study determines the feasibility of different approaches to integrative videogame-based group therapy for improving self-awareness, social skills, and behaviors among traumatic brain injury (TBI) victims and retrieves participant feedback. Methods: Forty-two adult TBI survivors were included in a longitudinal study with a pre- and post-assessments. The experimental intervention involved weekly one-hour sessions conducted over six months. Participants were assessed using the Self-Awareness Deficits Interview (SADI), Patient Competency Rating Scale (PCRS), the Social Skills Scale (SSS), the Frontal Systems Behavior Scale (FrSBe), the System Usability Scale (SUS). Pearson's chi-squared test (χ 2 ) was applied to determine the percentage of participants who had changed their clinical classification in these tests. Feedback of the intervention was collected through the Intrinsic Motivation Inventory (IMI). Results: SADI results showed an improvement in participant perceptions of deficits (χ 2 = 5.25, p < 0.05), of their implications (χ 2 = 4.71, p < 0.05), and of long-term planning (χ 2 = 7.86, p < 0.01). PCRS results confirm these findings (χ 2 = 5.79, p < 0.05). SSS results were also positive with respect to social skills outcomes (χ 2 = 17.52, p < 0.01), and FrSBe results showed behavioral improvements (χ 2 = 34.12, p < 0.01). Participants deemed the system accessible (80.43 ± 8.01 out of 100) and regarded the intervention as interesting and useful (5.74 ± 0.69 out of 7). Conclusions: Integrative videogame-based group therapy can improve self-awareness, social skills, and behaviors among individuals with chronic TBI, and the approach is considered effective and motivating.This study was funded in part by Ministerio de Economia y Competitividad of Spain (Project TEREHA, IDI-20110844; and NeuroVR, TIN2013-44741-R), by Ministerio de Educacion y Ciencia of Spain (Projects Consolider-C, SEJ2006-14301/PSIC; and "CIBER of Physiopathology of Obesity and Nutrition, an initiative of ISCIII"), and by the Excellence Research Program PROMETEO (Generalitat Valenciana. Conselleria de Educacion, 2008-157).Llorens Rodríguez, R.; Noé Sebastián, E.; Ferri, J.; Alcañiz Raya, ML. (2015). Videogame-based group therapy to improve self-awareness and social skills after traumatic brain injury. Journal of NeuroEngineering and Rehabilitation. 12(37):1-9. https://doi.org/10.1186/s12984-015-0029-1S191237Sherer M, Bergloff P, Levin E, High Jr WM, Oden KE, Nick TG. 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