294 research outputs found

    Experimental analysis of direct thermal methane cracking

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    The analysis of the viability of Hydrogen production without CO2 emissions is one of the most challenging activities that have been initiated for a sustainable energy supply. As one of the tracks to fulfil such objective, direct methane cracking has been analysed experimentally to assess the scientific viability and reaction characterization in a broad temperature range, from 875 to 1700 ?C. The effect of temperature, sweeping/carrier gas fraction proposed in some concepts, methane flow rate, residence time, and tube material and porosity has been analysed. The aggregation of carbon black particles to the reaction tube is the main technological show-stopper that has been identified

    <i>In vivo</i> gene silencing following non-invasive siRNA delivery into the skin using a novel topical formulation

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    AbstractTherapeutics based on short interfering RNAs (siRNAs), which act by inhibiting the expression of target transcripts, represent a novel class of potent and highly specific next-generation treatments for human skin diseases. Unfortunately, the intrinsic barrier properties of the skin combined with the large size and negative charge of siRNAs make epidermal delivery of these macromolecules quite challenging. To help evaluate the in vivo activity of these therapeutics and refine delivery strategies we generated an innovative reporter mouse model that predominantly expresses firefly luciferase (luc2p) in the paw epidermis — the region of murine epidermis that most closely models the tissue architecture of human skin. Combining this animal model with state-of-the-art live animal imaging techniques, we have developed a real-time in vivo analysis work-flow that has allowed us to compare and contrast the efficacies of a wide range nucleic acid-based gene silencing reagents in the skin of live animals. While inhibition was achieved with all of the reagents tested, only the commercially available “self-delivery” modified Accell-siRNAs (Dharmacon) produced potent and sustained in vivo gene silencing. Together, these findings highlight just how informative reliable reporter mouse models can be when assessing novel therapeutics in vivo. Using this work-flow, we developed a novel clinically-relevant topical formulation that facilitates non-invasive epidermal delivery of unmodified and “self-delivery” siRNAs. Remarkably, a sustained >40% luc2p inhibition was observed after two 1-hour treatments with Accell-siRNAs in our topical formulation. Importantly, our ability to successfully deliver siRNA molecules topically brings these novel RNAi-based therapeutics one-step closer to clinical use

    Are motor inhibition and cognitive flexibility dead ends in ADHD?

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    Contains fulltext : 53518.pdf (publisher's version ) (Closed access)Executive dysfunction has been postulated as the core deficit in ADHD, although many deficits in lower order cognitive processes have also been identified. By obtaining an appropriate baseline of lower order cognitive functioning light may be shed on as to whether executive deficits result from problems in lower order and/or higher order cognitive processes. We examined motor inhibition and cognitive flexibility in relation to a baseline measure in 816 children from ADHD and control families. Multiple children in a family were tested in order to examine the familiality of the measures. No evidence was found for deficits in motor inhibition or cognitive flexibility in children with ADHD or their nonaffected siblings: Compared to their baseline speed and accuracy of responding, children with ADHD and their (non)affected siblings were not disproportionally slower or inaccurate when demands for motor inhibition or cognitive flexibility were added to the task. However, children with ADHD and their (non)affected siblings were overall less accurate than controls, which could not be attributed to differences in response speed. This suggests that inaccuracy of responding is characteristic of children having (a familial risk for) ADHD. Motor inhibition and cognitive flexibility as operationalized with mean reaction time were found to be familial. It is concluded that poorer performance on executive tasks in children with ADHD and their (non)affected siblings may result from deficiencies in lower order cognitive processes and not (only) from higher order cognitive processes/executive functions

    Assessment of penetration of Ascorbyl Tetraisopalmitate into biological membranes by molecular dynamics

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    The present work, involves the simulation of the transport of a vitamin C derivative, Ascorbyl Tetraisopalmitate (ATI), through human skin by molecular dynamics. Percutaneous absorption of the ATI molecule through the infundibulum, an important route of absorption into the hair follicle of the human skin, has been modeled and compared with the stratum corneum membrane. The comparative study was done, using molecular dynamics with Martini force field. In infundibulum, a single ATI molecule require more time to penetrate, and the data obtained suggested that a high concentration of ATI molecule accelerated the process of penetration. In conclusion, the ATI molecule was found to have more affinity towards the stratum corneum as compared towards the infundibulum and it followed a straight pathway to penetrate (until 600 ns of simulation). In infundibulum, it showed less affinity, more mobility and followed a lateral pathway. Thus, this work contributes to a better understanding of the different molecular interactions during percutaneous absorption of active molecules in these two different types of biological membranes.The authors acknowledge financial support from the Brazilian agencies CAPES, Finep and Fapesp (Project FINEP 01.10.0661-00, FAPESP 2011/13250-0, FAPESP 2013/17247-9, FAPESP 2014/05975-2, CAPES 88887068264/2014-00), of Institute of Research and Development, University of Vale Paraíba

    Parental rating of sleep in children with attention deficit/hyperactivity disorder

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    Objective: Sleep problems have often been associated with attention deficit/hyperactivity disorder (ADHD). Parents of those with ADHD and children with ADHD report sleep difficulties more frequently than healthy children and their parents. The primary objective of this paper is to describe sleep patterns and problems of 5 to 11-year-old children suffering from ADHD as described by parental reports and sleep questionnaires. Method: The study included 321 children aged 5–11 years (average age 8.4 years); 45 were diagnosed with ADHD, 64 had other psychiatric diagnoses, and 212 were healthy. One hundred and ninety-six of the test subjects were boys and 125 were girls. A semi-structured interview (Kiddie-SADS-PL) was used to DSM-IV diagnose ADHD and comorbidity in the clinical group. Sleep difficulties were rated using a structured sleep questionnaire (Children Sleep Behaviour Scale). Results: Children diagnosed with ADHD had a significantly increased occurrence of sleep problems. Difficulties relating to bedtime and unsettled sleep were significantly more frequent in the ADHD group than in the other groups. Children with ADHD showed prolonged sleep onset latency, but no difference was shown regarding numbers of awakenings per night and total sleep time per night. Comorbid oppositional defiant disorder appeared not to have an added effect on problematic behaviour around bedtime. Conclusion: Parents of children with ADHD report that their children do not sleep properly more often than other parents. The ADHD group report problems with bedtime resistance, problems with sleep onset latency, unsettled sleep and nightmares more often than the control groups. It may therefore be relevant for clinicians to initiate a closer examination of those cases reporting sleep difficulties

    Biosynthesis of Vitamin C by Yeast Leads to Increased Stress Resistance

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    during respiration, or indirectly-caused by other stressing factors. Vitamin C or L-ascorbic acid acts as a scavenger of ROS, thereby potentially protecting cells from harmful oxidative products. While most eukaryotes synthesize ascorbic acid, yeast cells produce erythro-ascorbic acid instead. The actual importance of this antioxidant substance for the yeast is still a subject of scientific debate. is increased, but also the tolerance to low pH and weak organic acids at low pH is increased. cells endogenously producing vitamin C as a cellular model to study the genesis/protection of ROS as well as genotoxicity

    Phospholipids and sports performance

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    Phospholipids are essential components of all biological membranes. Phosphatidylcholine (PC) and Phosphatidylserine (PS) are Phosphatidyl-phospholipids that are required for normal cellular structure and function. The participation in physical activity often challenges a variety of physiological systems; consequently, the ability to maintain normal cellular function during activity can determine sporting performance. The participation in prolonged intense exercise has been shown to reduce circulatory choline concentrations in some individuals. As choline is a pre-cursor to the neurotransmitter Acetylcholine, this finding has encouraged researchers to investigate the hypothesis that supplementation with PC (or choline salts) could enhance sporting performance. Although the available data that evaluates the effects of PC supplementation on performance are equivocal, acute oral supplementation with PC (~0.2 g PC per kg body mass) has been demonstrated to improve performance in a variety of sporting activities where exercise has depleted circulatory choline concentrations. Short term oral supplementation with soy-derived PS (S-PS) has been reported to attenuate circulating cortisol concentrations, improve perceived well-being, and reduce perceived muscle soreness after exercise. More recently, short term oral supplementation (750 mg per day of S-PS for 10 days) has been demonstrated to improve exercise capacity during high intensity cycling and tended to increase performance during intermittent running. Although more research is warranted to determine minimum dietary Phospholipid requirements for optimal sporting performance, these findings suggest that some participants might benefit from dietary interventions that increase the intakes of PC and PS
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