Sample records for cns development plasticity

  1. CNS development: an overview (United States)

    Nowakowski, R. S.; Hayes, N. L.


    The basic principles of the development of the central nervous system (CNS) are reviewed, and their implications for both normal and abnormal development of the brain are discussed. The goals of this review are (a) to provide a set of concepts to aid in understanding the variety of complex processes that occur during CNS development, (b) to illustrate how these concepts contribute to our knowledge of the normal anatomy of the adult brain, and (c) to provide a basis for understanding how modifications of normal developmental processes by traumatic injury, by environmental or experiential influences, or by genetic variations may lead to modifications in the resultant structure and function of the adult CNS.

  2. Basic Concepts of CNS Development. (United States)

    Nowakowski, R. S.


    The goals of this review are to: (1) provide a set of concepts to aid in the understanding of complex processes which occur during central nervous system (CNS) development; (2) illustrate how they contribute to our knowlege of adult brain anatomy; and (3) delineate how modifications of normal developmental processes may affect the structure and…

  3. Tuning up the developing auditory CNS. (United States)

    Sanes, Dan H; Bao, Shaowen


    Although the auditory system has limited information processing resources, the acoustic environment is infinitely variable. To properly encode the natural environment, the developing central auditory system becomes somewhat specialized through experience-dependent adaptive mechanisms that operate during a sensitive time window. Recent studies have demonstrated that cellular and synaptic plasticity occurs throughout the central auditory pathway. Acoustic-rearing experiments can lead to an over-representation of the exposed sound frequency, and this is associated with specific changes in frequency discrimination. These forms of cellular plasticity are manifest in brain regions, such as midbrain and cortex, which interact through feed-forward and feedback pathways. Hearing loss leads to a profound re-weighting of excitatory and inhibitory synaptic gain throughout the auditory CNS, and this is associated with an over-excitability that is observed in vivo. Further behavioral and computational analyses may provide insights into how theses cellular and systems plasticity effects underlie the development of cognitive functions such as speech perception.

  4. Complement emerges as a masterful regulator of CNS homeostasis, neural synaptic plasticity and cognitive function. (United States)

    Mastellos, Dimitrios C


    Growing evidence points to a previously elusive role of complement-modulated pathways in CNS development, neurogenesis and synaptic plasticity. Distinct complement effectors appear to play a multifaceted role in brain homeostasis by regulating synaptic pruning in the retinogeniculate system and sculpting functional neural circuits both in the developing and adult mammalian brain. A recent study by Perez-Alcazar et al. (2014) provides novel insights into this intricate interplay between complement and the dynamically regulated brain synaptic circuitry, by reporting that mice deficient in C3 exhibit enhanced hippocampus-dependent spatial learning and cognitive performance. This behavioral pattern is associated with an impact of C3 on the functional capacity of glutamatergic synapses, supporting a crucial role for complement in excitatory synapse elimination in the hippocampus. These findings add a fresh twist to this rapidly evolving research field, suggesting that discrete complement components may differentially modulate synaptic connectivity by wiring up with diverse neural effectors in different regions of the brain. The emerging role of complement in synaptogenesis and neural network plasticity opens new conceptual avenues for considering complement interception as a potential therapeutic modality for ameliorating progressive cognitive impairment in age-related, debilitating brain diseases with a prominent inflammatory signature.

  5. CNS Anticancer Drug Discovery and Development Conference White Paper. (United States)

    Levin, Victor A; Tonge, Peter J; Gallo, James M; Birtwistle, Marc R; Dar, Arvin C; Iavarone, Antonio; Paddison, Patrick J; Heffron, Timothy P; Elmquist, William F; Lachowicz, Jean E; Johnson, Ted W; White, Forest M; Sul, Joohee; Smith, Quentin R; Shen, Wang; Sarkaria, Jann N; Samala, Ramakrishna; Wen, Patrick Y; Berry, Donald A; Petter, Russell C


    Following the first CNS Anticancer Drug Discovery and Development Conference, the speakers from the first 4 sessions and organizers of the conference created this White Paper hoping to stimulate more and better CNS anticancer drug discovery and development. The first part of the White Paper reviews, comments, and, in some cases, expands on the 4 session areas critical to new drug development: pharmacological challenges, recent drug approaches, drug targets and discovery, and clinical paths. Following this concise review of the science and clinical aspects of new CNS anticancer drug discovery and development, we discuss, under the rubric "Accelerating Drug Discovery and Development for Brain Tumors," further reasons why the pharmaceutical industry and academia have failed to develop new anticancer drugs for CNS malignancies and what it will take to change the current status quo and develop the drugs so desperately needed by our patients with malignant CNS tumors. While this White Paper is not a formal roadmap to that end, it should be an educational guide to clinicians and scientists to help move a stagnant field forward. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail:

  6. Development of plastic surgery

    Directory of Open Access Journals (Sweden)

    Pećanac Marija Đ.


    Full Text Available Introduction. Plastic surgery is a medical specialty dealing with corrections of defects, improvements in appearance and restoration of lost function. Ancient Times. The first recorded account of reconstructive plastic surgery was found in ancient Indian Sanskrit texts, which described reconstructive surgeries of the nose and ears. In ancient Greece and Rome, many medicine men performed simple plastic cosmetic surgeries to repair damaged parts of the body caused by war mutilation, punishment or humiliation. In the Middle Ages, the development of all medical braches, including plastic surgery was hindered. New age. The interest in surgical reconstruction of mutilated body parts was renewed in the XVIII century by a great number of enthusiastic and charismatic surgeons, who mastered surgical disciplines and became true artists that created new forms. Modern Era. In the XX century, plastic surgery developed as a modern branch in medicine including many types of reconstructive surgery, hand, head and neck surgery, microsurgery and replantation, treatment of burns and their sequelae, and esthetic surgery. Contemporary and future plastic surgery will continue to evolve and improve with regenerative medicine and tissue engineering resulting in a lot of benefits to be gained by patients in reconstruction after body trauma, oncology amputation, and for congenital disfigurement and dysfunction.

  7. Prospects for the development of epigenetic drugs for CNS conditions. (United States)

    Szyf, Moshe


    Advances in our understanding of the epigenetic mechanisms that control gene expression in the central nervous system (CNS) and their role in neuropsychiatric disorders are paving the way for a potential new therapeutic approach that is focused on reversing the epigenetic underpinnings of neuropsychiatric conditions. In this article, the complexity of epigenetic processes and the current level of proof for their involvement in CNS disorders are discussed. The preclinical evidence for efficacy of pharmacological approaches that target epigenetics in the CNS and the particular challenges of this approach are also examined. Finally, strategies to address these challenges through the development of improved evidence-based epigenetic therapeutics and through combining pharmacological and behavioural approaches are presented.

  8. Vertebrate Neural Stem Cells: Development, Plasticity, and Regeneration. (United States)

    Shimazaki, Takuya


    Natural recovery from disease and damage in the adult mammalian central nervous system (CNS) is limited compared with that in lower vertebrate species, including fish and salamanders. Species-specific differences in the plasticity of the CNS reflect these differences in regenerative capacity. Despite numerous extensive studies in the field of CNS regeneration, our understanding of the molecular mechanisms determining the regenerative capacity of the CNS is still relatively poor. The discovery of adult neural stem cells (aNSCs) in mammals, including humans, in the early 1990s has opened up new possibilities for the treatment of CNS disorders via self-regeneration through the mobilization of these cells. However, we now know that aNSCs in mammals are not plastic enough to induce significant regeneration. In contrast, aNSCs in some regenerative species have been found to be as highly plastic as early embryonic neural stem cells (NSCs). We must expand our knowledge of NSCs and of regenerative processes in lower vertebrates in an effort to develop effective regenerative treatments for damaged CNS in humans.

  9. Programmed cell death in developing human fetal CNS

    Institute of Scientific and Technical Information of China (English)


    The spatial and temporal distributions of programmed cell death (PCD) in developing central nervous system (CNS) of human fetuses ranging from 12 to 39 weeks of gestation were investigated using techniques of flow cytometry and terminal transferase-mediated nick end labeling (TUNEL). The results showed that PCD did occur in every representative brain region of all fetuses examined in different stages. It was found that there were two peaks of PCD appearing at the 12th and 39th weeks respectively, which suggested that the first peak of apoptosis may be involved in the selective elimination of neurons overproduced during the early development and the second may play an important role in establishing the correct neuronal circuitry.

  10. Glucocorticoid treatment of MCMV infected newborn mice attenuates CNS inflammation and limits deficits in cerebellar development.

    Directory of Open Access Journals (Sweden)

    Kate Kosmac


    Full Text Available Infection of the developing fetus with human cytomegalovirus (HCMV is a major cause of central nervous system disease in infants and children; however, mechanism(s of disease associated with this intrauterine infection remain poorly understood. Utilizing a mouse model of HCMV infection of the developing CNS, we have shown that peripheral inoculation of newborn mice with murine CMV (MCMV results in CNS infection and developmental abnormalities that recapitulate key features of the human infection. In this model, animals exhibit decreased granule neuron precursor cell (GNPC proliferation and altered morphogenesis of the cerebellar cortex. Deficits in cerebellar cortical development are symmetric and global even though infection of the CNS results in a non-necrotizing encephalitis characterized by widely scattered foci of virus-infected cells with mononuclear cell infiltrates. These findings suggested that inflammation induced by MCMV infection could underlie deficits in CNS development. We investigated the contribution of host inflammatory responses to abnormal cerebellar development by modulating inflammatory responses in infected mice with glucocorticoids. Treatment of infected animals with glucocorticoids decreased activation of CNS mononuclear cells and expression of inflammatory cytokines (TNF-α, IFN-β and IFNγ in the CNS while minimally impacting CNS virus replication. Glucocorticoid treatment also limited morphogenic abnormalities and normalized the expression of developmentally regulated genes within the cerebellum. Importantly, GNPC proliferation deficits were normalized in MCMV infected mice following glucocorticoid treatment. Our findings argue that host inflammatory responses to MCMV infection contribute to deficits in CNS development in MCMV infected mice and suggest that similar mechanisms of disease could be responsible for the abnormal CNS development in human infants infected in-utero with HCMV.

  11. DNA methylation functions as a critical regulator of Kir4.1 expression during CNS development. (United States)

    Nwaobi, Sinifunanya E; Lin, Erica; Peramsetty, Sasank R; Olsen, Michelle L


    Kir4.1, a glial-specific K+ channel, is critical for normal CNS development. Studies using both global and glial-specific knockout of Kir4.1 reveal abnormal CNS development with the loss of the channel. Specifically, Kir4.1 knockout animals are characterized by ataxia, severe hypomyelination, and early postnatal death. Additionally, Kir4.1 has emerged as a key player in several CNS diseases. Notably, decreased Kir4.1 protein expression occurs in several human CNS pathologies including CNS ischemic injury, spinal cord injury, epilepsy, ALS, and Alzheimer's disease. Despite the emerging significance of Kir4.1 in normal and pathological conditions, its mechanisms of regulation are unknown. Here, we report the first epigenetic regulation of a K+ channel in the CNS. Robust developmental upregulation of Kir4.1 expression in rats is coincident with reductions in DNA methylation of the Kir4.1 gene, KCNJ10. Chromatin immunoprecipitation reveals a dynamic interaction between KCNJ10 and DNA methyltransferase 1 during development. Finally, demethylation of the KCNJ10 promoter is necessary for transcription. These findings indicate DNA methylation is a key regulator of Kir4.1 transcription. Given the essential role of Kir4.1 in normal CNS development, understanding the regulation of this K+ channel is critical to understanding normal glial biology.

  12. Bassoon-disruption slows vesicle replenishment and induces homeostatic plasticity at a CNS synapse. (United States)

    Mendoza Schulz, Alejandro; Jing, Zhizi; Sánchez Caro, Juan María; Wetzel, Friederike; Dresbach, Thomas; Strenzke, Nicola; Wichmann, Carolin; Moser, Tobias


    Endbulb of Held terminals of auditory nerve fibers (ANF) transmit auditory information at hundreds per second to bushy cells (BCs) in the anteroventral cochlear nucleus (AVCN). Here, we studied the structure and function of endbulb synapses in mice that lack the presynaptic scaffold bassoon and exhibit reduced ANF input into the AVCN. Endbulb terminals and active zones were normal in number and vesicle complement. Postsynaptic densities, quantal size and vesicular release probability were increased while vesicle replenishment and the standing pool of readily releasable vesicles were reduced. These opposing effects canceled each other out for the first evoked EPSC, which showed unaltered amplitude. We propose that ANF activity deprivation drives homeostatic plasticity in the AVCN involving synaptic upscaling and increased intrinsic BC excitability. In vivo recordings from individual mutant BCs demonstrated a slightly improved response at sound onset compared to ANF, likely reflecting the combined effects of ANF convergence and homeostatic plasticity. Further, we conclude that bassoon promotes vesicular replenishment and, consequently, a large standing pool of readily releasable synaptic vesicles at the endbulb synapse.

  13. Simulation and mockup tests for developing TRR-II CNS (United States)

    Lee, C. H.; Kawai, T.; Chan, Y. K.; Hong, W. T.; Lee, D. J.; Guung, T. C.; Lan, K. C.


    The Taiwan Research Reactor improvement and the utilization promotion project (TRR-II) with Cold Neutron Source (CNS) was carried out at Institute of Nuclear Energy Research. The CNS with a two-phase thermosiphon loop consists of an annular cylindrical moderator cell, a single moderator transfer tube, and a condenser. The self-regulating characteristics of a two-phase thermosiphon loop are investigated against variations of heat load. The experiments on the thermal-hydraulic characteristics have been performed using a full-scale mockup loop and a Freon-11 was used as a working fluid. Two cases were evaluated by the simulation and experiments. One case is an ORPHEE-type moderator cell in which an inner shell is open at the bottom, the other case is one with an inner cavity with no hole at the bottom but a vapor inlet opening at the uppermost part of the cavity. The flooding limitations, liquid level and void fraction in the moderator cell as a function of the initial Freon-11 inventory and the heat load are also reported.

  14. Use of functional imaging across clinical phases in CNS drug development


    Borsook, D.; Becerra, L; Fava, M


    The use of novel brain biomarkers using nuclear magnetic resonance imaging holds potential of making central nervous system (CNS) drug development more efficient. By evaluating changes in brain function in the disease state or drug effects on brain function, the technology opens up the possibility of obtaining objective data on drug effects in the living awake brain. By providing objective data, imaging may improve the probability of success of identifying useful drugs to treat CNS diseases a...

  15. Innovation Promotes Development of Plastic Assistant

    Institute of Scientific and Technical Information of China (English)


    @@ Driven by the rapid growth of China's plastic product sector, the development of the plastic sector has been accelerated and assistant products are now becoming more multi-function, high performance, high in molecular weight and environmentfriendly.

  16. Development of technetium-99m-based CNS receptor ligands: have there been any advances?

    Energy Technology Data Exchange (ETDEWEB)

    Johannsen, B. [Forschungszentrum Rossendorf e.V. (FZR), Dresden (Germany); Pietzsch, H.-J. [Forschungszentrum Rossendorf, Institut fuerr Bioanorganische und Radiopharmazeutische Chemie, Dresden (Germany)


    By virtue of its ideal nuclear physical characteristics for routine nuclear medicine diagnostics and its ready availability, technetium-99m is of outstanding interest in the development of novel radiopharmaceuticals. The potential for the development of {sup 99m}Tc-based radioligands for the study the receptor function in the central nervous system (CNS) is also well recognised despite the difficulties to be overcome. A fundamental challenge is the pharmacologically acceptable integration of the transition metal technetium, with its specific coordination chemistry, into the molecular entity of CNS receptor ligands. Conceptually, the ligand molecule can be assembled by three building blocks: a small neutral chelate unit, an organic linker that may also serve as a pharmacological modifier and a receptor-binding region derived from selective receptor antagonists. The recent introduction of novel technetium chelate units, particularly mixed-ligand complexes and low-valency organometallic compounds of technetium, provides an impetus for the further development of CNS receptor ligands. Moreover, progress in receptor pharmacology and the experience gained with positron emission tomography radiotracers have facilitated the design of numerous {sup 99m}Tc-based CNS receptor ligands. The formidable challenge of developing {sup 99m}Tc probes as single-photon emission tomography imaging agents targeting CNS receptors can be viewed with optimism given the successful development of [{sup 99m}Tc]TRODAT-1 as a {sup 99m}Tc complex for imaging dopamine transporters in the brain, although there are a number of receptor-specific imaging agents that have so far resisted all efforts to develop them. This review presents recent advances and discusses the remaining hurdles in the design of {sup 99m}Tc-based CNS receptor imaging agents. (orig.)

  17. PIKE is essential for oligodendroglia development and CNS myelination. (United States)

    Chan, Chi Bun; Liu, Xia; Zhao, Lixia; Liu, Guanglu; Lee, Chi Wai; Feng, Yue; Ye, Keiqang


    Oligodendrocyte (OL) differentiation and myelin development are complex events regulated by numerous signal transduction factors. Here, we report that phosphoinositide-3 kinase enhancer L (PIKE-L) is required for OL development and myelination. PIKE-L expression is up-regulated when oligodendrocyte progenitor cells commit to differentiation. Conversely, depleting phosphoinositide-3 kinase enhancer (PIKE) expression by shRNA prevents oligodendrocyte progenitor cell differentiation. In both conventional PIKE knockout (PIKE(-/-)) and OL-specific PIKE knockout mice, the number of OLs is reduced in the corpus callosum. PIKE(-/-) OLs also display defects when forming myelin sheath on neuronal axons during neonatal development, which is partially rescued when PTEN is ablated. In addition, Akt/mTOR signaling is impaired in OL-enriched tissues of the PIKE(-/-) mutant, leading to reduced expression of critical proteins for myelin development and hypomyelination. Moreover, myelin repair of lysolecithin-induced lesions is delayed in PIKE(-/-) brain. Thus, PIKE plays pivotal roles to advance OL development and myelinogenesis through Akt/mTOR activation.

  18. Studying neuronal biomechanics and its role in CNS development (United States)

    Franze, Kristian; Svoboda, Hanno; da F. Costa, Luciano; Guck, Jochen; Holt, Christine


    During the development of the nervous system, neurons migrate and grow over great distances. Currently, our understanding of nervous tissue development is, in large part, based on studies of biochemical signaling. Despite the fact that forces are involved in any kind of cell motion, mechanical aspects have so far rarely been considered. Here we used deformable cell culture substrates, traction force microscopy and calcium imaging to investigate how neurons probe and respond to their mechanical environment. While the growth rate of retinal ganglion cell axons was increased on stiffer substrates, their tendency to grow in bundles, which they show in vivo, was significantly enhanced on more compliant substrates. Moreover, if grown on substrates incorporating linear stiffness gradients, neuronal axons were repelled by stiff substrates. Mechanosensing involved the application of forces driven by the interaction of actin and myosin II, and the activation of stretch-activated ion channels leading to calcium influxes into the cells. Applying a modified atomic force microscopy techniquein vivo, we found mechanical gradients in developing brain tissue along which neurons grow. The application of chondroitin sulfate, which is a major extracellular matrix component in the developing brain, changed tissue mechanics and disrupted axonal pathfinding. Hence, our data suggest that neuronal growth is not only guided by chemical signals - as it is currently assumed - but also by the nervous tissue's mechanical properties.

  19. Pluripotent stem cells for the study of CNS development

    Directory of Open Access Journals (Sweden)

    Timothy J. Petros


    Full Text Available The mammalian central nervous system is a complex neuronal meshwork consisting of a diverse array of cellular subtypes generated in a precise spatial and temporal pattern throughout development. Achieving a greater understanding of the molecular and genetic mechanisms that direct a relatively uniform population of neuroepithelial progenitors into the diverse neuronal subtypes remains a significant challenge. A firmer knowledge of the fundamental aspects of developmental neuroscience will allow us to better study the vast array of neurodevelopmental diseases. The advent of stem cell technologies has expedited our ability to generate and isolate populations of distinct interneuron subtypes. To date, researchers have successfully developed protocols to derive many types of neural cells from pluripotent stem cells, with varying degrees of efficiencies and reproducibility. The stem cell field is devoted to the potential of stem cell-derived neurons for the treatment of disease, highlighted by the ability to create patient specific induced pluripotent stem cells. However, another application that is often overlooked is the use of stem cell technology for studying normal neural development. This is especially important for human neurodevelopment, since obtaining embryonic tissue presents numerous technical and ethical challenges. In this review, we will explore the use of pluripotent stem cells for the study of neural development. We will review the different classes of pluripotent stem cells and focus on the types of neurodevelopmental questions that stem cell technologies can help address. In addition to covering the different neural cells derived from stem cells to date, we will detail the derivation and characterization of three of the more thoroughly studied cell groups. We hope that this review encourages researchers to develop innovative strategies for using pluripotent stem cells for the study of mammalian, and specifically human

  20. Chronic stress and brain plasticity: mechanisms underlying adaptive and maladaptive changes and implications for stress-related CNS disorders (United States)

    Radley, Jason; Morilak, David; Viau, Victor; Campeau, Serge


    Stress responses entail neuroendocrine, autonomic, and behavioral changes to promote effective coping with real or perceived threats to one’s safety. While these responses are critical for the survival of the individual, adverse effects of repeated exposure to stress are widely known to have deleterious effects on health. Thus, a considerable effort in the search for treatments to stress-related CNS disorders necessitates unraveling the brain mechanisms responsible for adaptation under acute conditions and their perturbations following chronic stress exposure. This paper is based upon a symposium from the 2014 International Behavioral Neuroscience Meeting, summarizing some recent advances in understanding the effects of stress on adaptive and maladaptive responses subserved by limbic forebrain networks. An important theme highlighted in this review is that the same networks mediating neuroendocrine, autonomic, and behavioral processes during adaptive coping also comprise targets of the effects of repeated stress exposure in the development of maladaptive states. Where possible, reference is made to the similarity of neurobiological substrates and effects observed following repeated exposure to stress in laboratory animals and the clinical features of stress-related disorders in humans. PMID:26116544

  1. MAP’ing CNS Development and Cognition: An ERKsome Process


    Samuels, Ivy S.; Saitta, Sulagna C.; Landreth, Gary E.


    The ERK MAP kinase signaling cascade plays critical roles in brain development, learning, memory, and cognition. It has recently been appreciated that mutation or deletion of elements within this signaling pathway leads to developmental syndromes in humans that are associated with impaired cognitive function and autism. Here, we review recent studies that provide insight into the biological roles of the ERKs in the brain that may underlie the cognitive deficits seen in these syndromes.

  2. Maternal stress, nutrition and physical activity: Impact on immune function, CNS development and psychopathology. (United States)

    Marques, Andrea Horvath; Bjørke-Monsen, Anne-Lise; Teixeira, Antônio L; Silverman, Marni N


    Evidence suggests that maternal and fetal immune dysfunction may impact fetal brain development and could play a role in neurodevelopmental disorders, although the definitive pathophysiological mechanisms are still not completely understood. Stress, malnutrition and physical inactivity are three maternal behavioral lifestyle factors that can influence immune and central nervous system (CNS) functions in both the mother and fetus, and may therefore, increase risk for neurodevelopmental/psychiatric disorders. First, we will briefly review some aspects of maternal-fetal immune system interactions and development of immune tolerance. Second, we will discuss the bidirectional communication between the immune system and CNS and the pathways by which immune dysfunction could contribute to neurodevelopmental disorders. Third, we will discuss the effects of prenatal stress and malnutrition (over and undernutrition) on perinatal programming of the CNS and immune system, and how this might influence neurodevelopment. Finally, we will discuss the beneficial impact of physical fitness during pregnancy on the maternal-fetal unit and infant and how regular physical activity and exercise can be an effective buffer against stress- and inflammatory-related disorders. Although regular physical activity has been shown to promote neuroplasticity and an anti-inflammatory state in the adult, there is a paucity of studies evaluating its impact on CNS and immune function during pregnancy. Implementing stress reduction, proper nutrition and ample physical activity during pregnancy and the childbearing period may be an efficient strategy to counteract the impact of maternal stress and malnutrition/obesity on the developing fetus. Such behavioral interventions could have an impact on early development of the CNS and immune system and contribute to the prevention of neurodevelopmental and psychiatric disorders. Further research is needed to elucidate this relationship and the underlying

  3. Developments in Plasticity Approach to Shear

    DEFF Research Database (Denmark)

    Hoang, Cao Linh; Nielsen, Mogens Peter


    The paper deals with plastic methods applied to shear design of reinforced concrete beams. Emphasis is put on the recently developed crack sliding model applicable to non-shear reinforced and lightly shear reinforced beams and slabs. The model, which is an upper bound plasticity approach, takes...

  4. Perinatal asphyxia: CNS development and deficits with delayed onset

    Directory of Open Access Journals (Sweden)

    Mario eHerrera-Marschitz


    Full Text Available Perinatal asphyxia constitutes a prototype of obstetric complications occurring when pulmonary oxygenation is delayed or interrupted. The primary insult relates to the duration of the period lacking oxygenation, leading to death if not re-established. Re-oxygenation leads to a secondary insult, related to a cascade of biochemical events required for restoring proper function. Perinatal asphyxia interferes with neonatal development, resulting in long-term deficits associated to mental and neurological diseases with delayed clinical onset, by mechanisms not yet clarified.In the experimental scenario, the effects observed long after perinatal asphyxia have been explained by over expression of sentinel proteins, such as poly(ADP-ribose polymerase-1 (PARP-1, competing for NAD+ during re-oxygenation, leading to the idea that sentinel protein inhibition constitutes a suitable therapeutic strategy. Asphyxia induces transcriptional activation of pro-inflammatory factors, in tandem with PARP-1 overactivation, and pharmacologically induced PARP-1 inhibition also down-regulates the expression of proinflammatory cytokines. Nicotinamide has been proposed as a suitable PARP-1 inhibitor. Its effect has been studied in an experimental model of global hypoxia in rats. In that model, the insult is induced by immersing rat foetuses into a water bath for various periods of time. Following asphyxia, the pups are delivered, treated, and nursed by surrogate dams, pending further experiments. Nicotinamide rapidly distributes into the brain following systemic administration, reaching steady state concentrations sufficient to inhibit PARP-1 activity for several hours, preventing several of the long-term consequences of perinatal asphyxia, supporting the idea that it constitutes a lead for exploring compounds with similar or better pharmacological profiles.



    Bukhovets, B. O.; Romanchuk, A. P.


    The article represents therapy of Bobath such as one of the most effective author method which use in correction psychomotor development of children with disorders of musculoskeletal system. Bobath method is not new in the correction of movement disorders since last century and still supplementing and improving. In this work highlight topic of the effective use Bobath therapy in correction of psychomotor development in children age 3 – 6 years with organic involvement CNS. the experi...

  6. Presynaptic active zone density during development and synaptic plasticity.

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    Gwenaëlle L Clarke


    Full Text Available Neural circuits transmit information through synapses, and the efficiency of synaptic transmission is closely related to the density of presynaptic active zones, where synaptic vesicles are released. The goal of this review is to highlight recent insights into the molecular mechanisms that control the number of active zones per presynaptic terminal (active zone density during developmental and stimulus-dependent changes in synaptic efficacy. At the neuromuscular junctions (NMJs, the active zone density is preserved across species, remains constant during development, and is the same between synapses with different activities. However, the NMJ active zones are not always stable, as exemplified by the change in active zone density during acute experimental manipulation or as a result of aging. Therefore, a mechanism must exist to maintain its density. In the central nervous system (CNS, active zones have restricted maximal size, exist in multiple numbers in larger presynaptic terminals, and maintain a constant density during development. These findings suggest that active zone density in the CNS is also controlled. However, in contrast to the NMJ, active zone density in the CNS can also be increased, as observed in hippocampal synapses in response to synaptic plasticity. Although the numbers of known active zone proteins and protein interactions have increased, less is known about the mechanism that controls the number or spacing of active zones. The following molecules are known to control active zone density and will be discussed herein: extracellular matrix laminins and voltage-dependent calcium channels, amyloid precursor proteins, the small GTPase Rab3, an endocytosis mechanism including synaptojanin, cytoskeleton protein spectrins and β-adducin, and a presynaptic web including spectrins. The molecular mechanisms that organize the active zone density are just beginning to be elucidated.

  7. Developing highER-throughput zebrafish screens for in-vivo CNS drug discovery


    Adam Michael Stewart; Robert eGerlai; Kalueff, Allan V.


    The high prevalence of brain disorders and the lack of their efficient treatments necessitate improved in-vivo pre-clinical models and tests. The zebrafish (Danio rerio), a vertebrate species with high genetic and physiological homology to humans, is an excellent organism for innovative central nervous system (CNS) drug discovery and small molecule screening. Here, we outline new strategies for developing higher-throughput zebrafish screens to test neuroactive drugs and predict their pharmaco...

  8. Strategies for Utilizing Neuroimaging Biomarkers in CNS Drug Discovery and Development: CINP/JSNP Working Group Report. (United States)

    Suhara, Tetsuya; Chaki, Shigeyuki; Kimura, Haruhide; Furusawa, Makoto; Matsumoto, Mitsuyuki; Ogura, Hiroo; Negishi, Takaaki; Saijo, Takeaki; Higuchi, Makoto; Omura, Tomohiro; Watanabe, Rira; Miyoshi, Sosuke; Nakatani, Noriaki; Yamamoto, Noboru; Liou, Shyh-Yuh; Takado, Yuhei; Maeda, Jun; Okamoto, Yasumasa; Okubo, Yoshiaki; Yamada, Makiko; Ito, Hiroshi; Walton, Noah M; Yamawaki, Shigeto


    Despite large unmet medical needs in the field for several decades, CNS drug discovery and development has been largely unsuccessful. Biomarkers, particularly those utilizing neuroimaging, have played important roles in aiding CNS drug development, including dosing determination of investigational new drugs (INDs). A recent working group was organized jointly by CINP and Japanese Society of Neuropsychopharmacology (JSNP) to discuss the utility of biomarkers as tools to overcome issues of CNS drug development.The consensus statement from the working group aimed at creating more nuanced criteria for employing biomarkers as tools to overcome issues surrounding CNS drug development. To accomplish this, a reverse engineering approach was adopted, in which criteria for the utilization of biomarkers were created in response to current challenges in the processes of drug discovery and development for CNS disorders. Based on this analysis, we propose a new paradigm containing 5 distinct tiers to further clarify the use of biomarkers and establish new strategies for decision-making in the context of CNS drug development. Specifically, we discuss more rational ways to incorporate biomarker data to determine optimal dosing for INDs with novel mechanisms and targets, and propose additional categorization criteria to further the use of biomarkers in patient stratification and clinical efficacy prediction. Finally, we propose validation and development of new neuroimaging biomarkers through public-private partnerships to further facilitate drug discovery and development for CNS disorders. © The Author 2016. Published by Oxford University Press on behalf of CINP.

  9. Cug2 is essential for normal mitotic control and CNS development in zebrafish

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    Kim Nam-Soon


    Full Text Available Abstract Background We recently identified a novel oncogene, Cancer-upregulated gene 2 (CUG2, which is essential for kinetochore formation and promotes tumorigenesis in mammalian cells. However, the in vivo function of CUG2 has not been studied in animal models. Results To study the function of CUG2 in vivo, we isolated a zebrafish homologue that is expressed specifically in the proliferating cells of the central nervous system (CNS. Morpholino-mediated knockdown of cug2 resulted in apoptosis throughout the CNS and the development of neurodegenerative phenotypes. In addition, cug2-deficient embryos contained mitotically arrested cells displaying abnormal spindle formation and chromosome misalignment in the neural plate. Conclusions Therefore, our findings suggest that Cug2 is required for normal mitosis during early neurogenesis and has functions in neuronal cell maintenance, thus demonstrating that the cug2 deficient embryos may provide a model system for human neurodegenerative disorders.

  10. CNS-derived glia ensheath peripheral nerves and mediate motor root development. (United States)

    Kucenas, Sarah; Takada, Norio; Park, Hae-Chul; Woodruff, Elvin; Broadie, Kendal; Appel, Bruce


    Motor function requires that motor axons extend from the spinal cord at regular intervals and that they are myelinated by Schwann cells. Little attention has been given to another cellular structure, the perineurium, which ensheaths the motor nerve, forming a flexible, protective barrier. Consequently, the origin of perineurial cells and their roles in motor nerve formation are poorly understood. Using time-lapse imaging in zebrafish, we show that perineurial cells are born in the CNS, arising as ventral spinal-cord glia before migrating into the periphery. In embryos lacking perineurial glia, motor neurons inappropriately migrated outside of the spinal cord and had aberrant axonal projections, indicating that perineurial glia carry out barrier and guidance functions at motor axon exit points. Additionally, reciprocal signaling between perineurial glia and Schwann cells was necessary for motor nerve ensheathment by both cell types. These insights reveal a new class of CNS-born glia that critically contributes to motor nerve development.

  11. The DOCK protein sponge binds to ELMO and functions in Drosophila embryonic CNS development.

    Directory of Open Access Journals (Sweden)

    Bridget Biersmith

    Full Text Available Cell morphogenesis, which requires rearrangement of the actin cytoskeleton, is essential to coordinate the development of tissues such as the musculature and nervous system during normal embryonic development. One class of signaling proteins that regulate actin cytoskeletal rearrangement is the evolutionarily conserved CDM (C. elegansCed-5, human DOCK180, DrosophilaMyoblast city, or Mbc family of proteins, which function as unconventional guanine nucleotide exchange factors for the small GTPase Rac. This CDM-Rac protein complex is sufficient for Rac activation, but is enhanced upon the association of CDM proteins with the ELMO/Ced-12 family of proteins. We identified and characterized the role of Drosophila Sponge (Spg, the vertebrate DOCK3/DOCK4 counterpart as an ELMO-interacting protein. Our analysis shows Spg mRNA and protein is expressed in the visceral musculature and developing nervous system, suggesting a role for Spg in later embryogenesis. As maternal null mutants of spg die early in development, we utilized genetic interaction analysis to uncover the role of Spg in central nervous system (CNS development. Consistent with its role in ELMO-dependent pathways, we found genetic interactions with spg and elmo mutants exhibited aberrant axonal defects. In addition, our data suggests Ncad may be responsible for recruiting Spg to the membrane, possibly in CNS development. Our findings not only characterize the role of a new DOCK family member, but help to further understand the role of signaling downstream of N-cadherin in neuronal development.

  12. Expression of planar cell polarity genes during development of the mouse CNS. (United States)

    Tissir, Fadel; Goffinet, André M


    Atypical cadherin (Celsr3) and the receptor Frizzled3 (Fzd3) are crucial for the development of axonal tracts in the mouse CNS. Celsr3 and Fzd3 are orthologues of the Drosophila'planar cell polarity' (PCP) genes flamingo/starry night (fmi/stan) and frizzled, respectively. Reasoning that Celsr3 and Fzd3 might interact with PCP orthologues in mammals like they do in flies, we used mRNA in situ hybridization to compare the expression of Celsr3 and Fzd3 with that of dishevelled 1, 2 and 3 (Dvl1-3), van gogh-like 1 and 2 (Vangl1, 2), and prickle-like 1 and 2 (Prickle1, 2), during mouse CNS development, from embryonic day 10.5 to postnatal day 21. With the relative exception of Vangl1, all genes were expressed in the developing CNS. Although Celsr3- and Fzd3-deficient mice have similar phenotypes, Fzd3 expression was more widespread than that of Celsr3. Vangl2 and Dvl2 were preferentially expressed in ventricular zones, in keeping with their role during neural tube closure, where they could be partners of Celsr1. Dvl1 had a broad expression, reminiscent of that of Celsr2, and may be involved in neural maintenance. A large overlap in the expression territories of Dvl genes suggested redundancy. Vangl1 and Prickle1 had expression canvases different from each other and from other candidates, indicating unrelated function. Like Celsr3, Dvl3 and Prickle2 were expressed more strongly in postmitotic neurons than in precursors. Thus, the analogy between the PCP and Celsr3-Fzd3 genetic networks is limited, but may include Dvl3 and/or Prickle2.

  13. Polymers from plants to develop biodegradable plastics. (United States)

    Conrad, Udo


    Katrin Neumann et al. have recently shown that transgenic tobacco and potato plants can accumulate high levels of cyanophycin, a possible source for poly-aspartate. This work opens the way to the future production of biodegradable plastics using a plant-based production system. Several problems need to be overcome first, such as growth retardation as a result of cyanophycin accumulating in the cytosol, and a co-production system needs to be developed for economical reasons.

  14. Sugar-dependent modulation of neuronal development, regeneration, and plasticity by chondroitin sulfate proteoglycans. (United States)

    Miller, Gregory M; Hsieh-Wilson, Linda C


    Chondroitin sulfate proteoglycans (CSPGs) play important roles in the developing and mature nervous system, where they guide axons, maintain stable connections, restrict synaptic plasticity, and prevent axon regeneration following CNS injury. The chondroitin sulfate glycosaminoglycan (CS GAG) chains that decorate CSPGs are essential for their functions. Through these sugar chains, CSPGs are able to bind and regulate the activity of a diverse range of proteins. CSPGs have been found both to promote and inhibit neuronal growth. They can promote neurite outgrowth by binding to various growth factors such as midkine (MK), pleiotrophin (PTN), brain-derived neurotrophic factor (BDNF) and other neurotrophin family members. CSPGs can also inhibit neuronal growth and limit plasticity by interacting with transmembrane receptors such as protein tyrosine phosphatase σ (PTPσ), leukocyte common antigen-related (LAR) receptor protein tyrosine phosphatase, and the Nogo receptors 1 and 3 (NgR1 and NgR3). These CS-protein interactions depend on specific sulfation patterns within the CS GAG chains, and accordingly, particular CS sulfation motifs are upregulated during development, in the mature nervous system, and in response to CNS injury. Thus, spatiotemporal regulation of CS GAG biosynthesis may provide an important mechanism to control the functions of CSPGs and to modulate intracellular signaling pathways. Here, we will discuss these sulfation-dependent processes and highlight how the CS sugars on CSPGs contribute to neuronal growth, axon guidance, and plasticity in the nervous system. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. 3. Impact of altered gravity on CNS development and behavior in male and female rats (United States)

    Sajdel-Sulkowska, E. M.; Nguon, K.; Ladd, B.; Sulkowski, V. A.; Sulkowski, Z. L.; Baxter, M. G.

    The present study examined the effect of altered gravity on CNS development. Specifically, we compared neurodevelopment, behavior, cerebellar structure and protein expression in rat neonates exposed perinatally to hypergravity. Pregnant Sprague-Dawley rats were exposed to 1.5G-1.75G hypergravity on a 24-ft centrifuge starting on gestational day (G) 10, through giving birth on G22/G23, and nursing their offspring through postnatal day (P) 21. Cerebellar mass on P6 was decreased in 1.75G-exposed male pups by 27.5 percent; in 1.75G-exposed female pups it was decreased by 22.5 percent. The observed cerebellar changes were associated with alterations in neurodevelopment and motor behavior. Exposure to hypergravity impaired performance on the following neurocognitive tests: (1) righting time on P3 was more than doubled in 1.75G-exposed rats and the effect appeared more pronounced in female pups, (2) startle response on P10 was delayed in both male and female HG pups; HG pups were one-fifth as likely to respond to a clapping noise as SC pups, and (3) performance on a rotorod on P21 was decreased in HG pups; the duration of the stay on rotorod recorded for HG pups of both sexes was one tenth of the SC pups. Furthermore, Western blot analysis of selected cerebellar proteins suggested gender-specific changes in glial and neuronal proteins. On P6, GFAP expression was decreased by 59.2 percent in HG males, while no significant decrease was observed in female cerebella. Synaptophysin expression was decreased in HG male neonates by 29.9 percent and in HG female neonates by 20.7 percent as compared to its expression in SC cerebella. The results of this experiment suggest that perinatal exposure to hypergravity affects cerebellar development and behavior differently in male and female neonates. If one accepts that hypergravity is a good paradigm to study the effect of microgravity on the CNS, and since males and females were shown to respond differently to hypergravity, it can be

  16. Microglia across the lifespan: from origin to function in brain development, plasticity and cognition. (United States)

    Tay, Tuan Leng; Savage, Julie C; Hui, Chin Wai; Bisht, Kanchan; Tremblay, Marie-Ève


    Microglia are the only immune cells that permanently reside in the central nervous system (CNS) alongside neurons and other types of glial cells. The past decade has witnessed a revolution in our understanding of their roles during normal physiological conditions. Cutting-edge techniques revealed that these resident immune cells are critical for proper brain development, actively maintain health in the mature brain, and rapidly adapt their function to physiological or pathophysiological needs. In this review, we highlight recent studies on microglial origin (from the embryonic yolk sac) and the factors regulating their differentiation and homeostasis upon brain invasion. Elegant experiments tracking microglia in the CNS allowed studies of their unique roles compared with other types of resident macrophages. Here we review the emerging roles of microglia in brain development, plasticity and cognition, and discuss the implications of the depletion or dysfunction of microglia for our understanding of disease pathogenesis. Immune activation, inflammation and various other conditions resulting in undesirable microglial activity at different stages of life could severely impair learning, memory and other essential cognitive functions. The diversity of microglial phenotypes across the lifespan, between compartments of the CNS, and sexes, as well as their crosstalk with the body and external environment, is also emphasised. Understanding what defines particular microglial phenotypes is of major importance for future development of innovative therapies controlling their effector functions, with consequences for cognition across chronic stress, ageing, neuropsychiatric and neurological diseases.

  17. Sleep-wake mechanisms and drug discovery: sleep EEG as a tool for the development of CNS-acting drugs


    Staner, Luc


    Sleep laboratory investigations constitute a unique noninvasive tool to analyze brain functioning, Polysomnographic recordings, even in the very early phase of development in humans, are mandatory in a developmental plan of a new sleep-acting compound. Sleep is also an interesting tool for the development of other drugs acting on the central nervous system (CNS), Indeed, changes in sleep electroencephalographic (EEG) characteristics are a very sensitive indication of the objective central eff...

  18. Redox Abnormalities as a Vulnerability Phenotype for Autism and Related Alternations in CNS Development (United States)


    examined in parallel with our own experiments led to surprising insights into the possible importance of micronutrient deficiencies as contributory...factors to CNS changes that occur in the brains of children with autism. Moreover, the interplay between this micronutrient deficiency (which is

  19. Comparison of Cashew Nut Shell Liquid (CNS Resin with Polyester Resin in Composite Development

    Directory of Open Access Journals (Sweden)

    C. C. Ugoamadi


    Full Text Available Natural resins can compete effectively with the synthetic ones in composite development. In this research, cashew nuts were picked and processed for the extraction of the resin content. The resin (natural resin so obtained was mixed with cobalt amine (accelerator, methyl ethyl ketone peroxide (catalyst to develop two sets of composite specimens – specimens without fibres and specimens reinforced with glass fibres. This method of sample specimen development was repeated with polyester (synthetic resin. Compressive and tensile strength tests conducted proved that composites developed with cashew nut shell liquid (CNSL resin were comparable to those developed with polyester resin. In the results, CNSL has an ultimate compressive strength of 55MPa compared to that of polyester resin with an ultimate strength of 68MPa. The result of tensile strength proved cashew nut shell liquid resin (with ultimate strength of 44MPa to be better than polyester resin with 39MPa as ultimate tensile strength. This means that natural resins could be a better substitute for the synthetic ones when the required quantities of fibers (reinforcements and fillers are used in the fibre-reinforced plastic composite developments.

  20. Role of the cellular prion protein in oligodendrocyte precursor cell proliferation and differentiation in the developing and adult mouse CNS.

    Directory of Open Access Journals (Sweden)

    Ana Bribián

    Full Text Available There are numerous studies describing the signaling mechanisms that mediate oligodendrocyte precursor cell (OPC proliferation and differentiation, although the contribution of the cellular prion protein (PrP(c to this process remains unclear. PrP(c is a glycosyl-phosphatidylinositol (GPI-anchored glycoprotein involved in diverse cellular processes during the development and maturation of the mammalian central nervous system (CNS. Here we describe how PrP(c influences oligodendrocyte proliferation in the developing and adult CNS. OPCs that lack PrP(c proliferate more vigorously at the expense of a delay in differentiation, which correlates with changes in the expression of oligodendrocyte lineage markers. In addition, numerous NG2-positive cells were observed in cortical regions of adult PrP(c knockout mice, although no significant changes in myelination can be seen, probably due to the death of surplus cells.

  1. Human synaptic plasticity gene expression profile and dendritic spine density changes in HIV-infected human CNS cells: role in HIV-associated neurocognitive disorders (HAND.

    Directory of Open Access Journals (Sweden)

    Venkata Subba Rao Atluri

    Full Text Available HIV-associated neurocognitive disorders (HAND is characterized by development of cognitive, behavioral and motor abnormalities, and occur in approximately 50% of HIV infected individuals. Our current understanding of HAND emanates mainly from HIV-1 subtype B (clade B, which is prevalent in USA and Western countries. However very little information is available on neuropathogenesis of HIV-1 subtype C (clade C that exists in Sub-Saharan Africa and Asia. Therefore, studies to identify specific neuropathogenic mechanisms associated with HAND are worth pursuing to dissect the mechanisms underlying this modulation and to prevent HAND particularly in clade B infection. In this study, we have investigated 84 key human synaptic plasticity genes differential expression profile in clade B and clade C infected primary human astrocytes by using RT(2 Profile PCR Array human Synaptic Plasticity kit. Among these, 31 and 21 synaptic genes were significantly (≥3 fold down-regulated and 5 genes were significantly (≥3 fold up-regulated in clade B and clade C infected cells, respectively compared to the uninfected control astrocytes. In flow-cytometry analysis, down-regulation of postsynaptic density and dendrite spine morphology regulatory proteins (ARC, NMDAR1 and GRM1 was confirmed in both clade B and C infected primary human astrocytes and SK-N-MC neuroblastoma cells. Further, spine density and dendrite morphology changes by confocal microscopic analysis indicates significantly decreased spine density, loss of spines and decreased dendrite diameter, total dendrite and spine area in clade B infected SK-N-MC neuroblastoma cells compared to uninfected and clade C infected cells. We have also observed that, in clade B infected astrocytes, induction of apoptosis was significantly higher than in the clade C infected astrocytes. In conclusion, this study suggests that down-regulation of synaptic plasticity genes, decreased dendritic spine density and induction of

  2. Neurotrophic regulation of synapse development and plasticity

    Institute of Scientific and Technical Information of China (English)


    Neurotrophic factors are traditionally thought to be secretory proteins that regulate long-tern survival and differe, ntiation of neurons. Recent studies have revealed a previously unexpected role for these factors in synaptie de velopment ami plasticity in diverse neuronal populations. Here we review experimeuts carried oul in our own laboratory in the last few years.. We have made two important discoveries.First,we were among the first to report that brain-derived. neurotrophie faclor (BDNF) facilitates hippocampal hmg-term potentiation (LTP), a form of synaptic plaslicity believed to be involved in learning and memory. BDNF modulates LTP al CAI synapses by enhaneing synaptic responses to high frequency, tetanic slimulalion. This is achieved primafily by facilitating synaptie vesicle doeking, possibly due to an in crease in the levels of the vesicle prolein synaptobrevin and synaptoplysin in the nerve terminals. Gene knockout study demonstrates thai the effects of BDNF are primarily mediated through presynaptic mechanisms. Second, we demonstrated a form of long-term, neurotrophin-mediated synaptic regulation. We showed that long-term treatment of the neuromuscu lar synapses with neurotrophin-3 (NT3) resulted in an enhancement of both spontaneous and evoked synaptic currcuts, as well as profound changes in thc number of synaptic varicosities and syuaptic vesicle proteins in motoneurons, all of which are indicative of more mature synapses. Our current work addresses the following issues:(i) activity-dependent trafficking of neurotrophin receptors, and its role in synapse-specific modulation; (ii) signal transduction mechanisms medialing the acute enhancement of synaplic transmission by neurotrophins; (iii) acute and long-tenn synaptie actions of the GDNF family; (iv) role of BDNF in late-phase LTP and in the development of hippocampal circuit.

  3. Plasticity in the Developing Brain: Implications for Rehabilitation (United States)

    Johnston, Michael V.


    Neuronal plasticity allows the central nervous system to learn skills and remember information, to reorganize neuronal networks in response to environmental stimulation, and to recover from brain and spinal cord injuries. Neuronal plasticity is enhanced in the developing brain and it is usually adaptive and beneficial but can also be maladaptive…

  4. Plasticity in the Developing Brain: Implications for Rehabilitation (United States)

    Johnston, Michael V.


    Neuronal plasticity allows the central nervous system to learn skills and remember information, to reorganize neuronal networks in response to environmental stimulation, and to recover from brain and spinal cord injuries. Neuronal plasticity is enhanced in the developing brain and it is usually adaptive and beneficial but can also be maladaptive…

  5. Microglia in neuronal plasticity: Influence of stress. (United States)

    Delpech, Jean-Christophe; Madore, Charlotte; Nadjar, Agnes; Joffre, Corinne; Wohleb, Eric S; Layé, Sophie


    The central nervous system (CNS) has previously been regarded as an immune-privileged site with the absence of immune cell responses but this dogma was not entirely true. Microglia are the brain innate immune cells and recent findings indicate that they participate both in CNS disease and infection as well as facilitate normal CNS function. Microglia are highly plastic and play integral roles in sculpting the structure of the CNS, refining neuronal circuitry and connectivity, and contribute actively to neuronal plasticity in the healthy brain. Interestingly, psychological stress can perturb the function of microglia in association with an impaired neuronal plasticity and the development of emotional behavior alterations. As a result it seemed important to describe in this review some findings indicating that the stress-induced microglia dysfunction may underlie neuroplasticity deficits associated to many mood disorders. This article is part of a Special Issue entitled 'Neuroimmunology and Synaptic Function'.

  6. New Opportunities in Developing Engineering Plastics

    Institute of Scientific and Technical Information of China (English)

    Yang Weicai


    @@ Owing to their excellent mechanical property, electric behavior, chemical resistance, heat resistance, abrasion resistance, size stability, weather resistance, lighter weight than metal materials and small energy consumption in molding, engineering plastics are extensively used in the sectors-electronic/electric, automobile, construction and office equipment.

  7. Development trends and market analysis of China's plastics industry

    Institute of Scientific and Technical Information of China (English)

    LIAO Zheng-Pin


    @@ China's plastics industry has witnessed the leap-forward development with the stable and sound growth of national economy,having increased its economic and technical indicators stably and greatly for consecutive ten years.

  8. Development of a Prototype Automated Sorting System for Plastic Recycling

    Directory of Open Access Journals (Sweden)

    D. A. Wahab


    Full Text Available Automated sorting for plastic recyclables has been seen as the way forward in the plastic recycling industry. Automated sorting provides significant improvements in terms of efficiency and consistency in the sorting process. In the case of macro sorting, which is the most common type of automated sorting, efficiency is determined by the mechanical details of the material handling system as well as the detection system. This paper provides a review on the state of-the-art technologies that have been deployed by some of the recycling facilities abroad. The design and development of a cost effective prototype automated system for sorting plastic recyclables is proposed and discussed.

  9. Research on plastic fender development and key technologies

    Institute of Scientific and Technical Information of China (English)

    Yang Hao; Li Li; Liu Qiang; Yang Anzhi; Ma Fangwu; Zhao Fuquan; Guo Yihui; Song Leifeng


    Automotive lightweight and safety performance come into play as key technologies to promote competiveness, and average applied amount of automotive plastics has become a significant sign for automotive industrial development level of a country. Various performances of a vehicle with plastic automotive fenders are analyzed in the paper. The re- search is emphasized on sinking-resistance and pedestrian protection performance of the plastic fenders by studying plas- tics characteristics and simulation analysis. It offers references for engineering design in which both automotive light- weight and safety performance are achieved and well balanced.

  10. Phenotypic plasticity in development and evolution: facts and concepts (United States)

    Fusco, Giuseppe; Minelli, Alessandro


    This theme issue pursues an exploration of the potential of taking into account the environmental sensitivity of development to explaining the evolution of metazoan life cycles, with special focus on complex life cycles and the role of developmental plasticity. The evolution of switches between alternative phenotypes as a response to different environmental cues and the evolution of the control of the temporal expression of alternative phenotypes within an organism's life cycle are here treated together as different dimensions of the complex relationships between genotype and phenotype, fostering the emergence of a more general and comprehensive picture of phenotypic evolution through a quite diverse sample of case studies. This introductory article reviews fundamental facts and concepts about phenotypic plasticity, adopting the most authoritative terminology in use in the current literature. The main topics are types and components of phenotypic variation, the evolution of organismal traits through plasticity, the origin and evolution of phenotypic plasticity and its adaptive value. PMID:20083631

  11. Hormone signaling and phenotypic plasticity in nematode development and evolution. (United States)

    Sommer, Ralf J; Ogawa, Akira


    Phenotypic plasticity refers to the ability of an organism to adopt different phenotypes depending on environmental conditions. In animals and plants, the progression of juvenile development and the formation of dormant stages are often associated with phenotypic plasticity, indicating the importance of phenotypic plasticity for life-history theory. Phenotypic plasticity has long been emphasized as a crucial principle in ecology and as facilitator of phenotypic evolution. In nematodes, several examples of phenotypic plasticity have been studied at the genetic and developmental level. In addition, the influence of different environmental factors has been investigated under laboratory conditions. These studies have provided detailed insight into the molecular basis of phenotypic plasticity and its ecological and evolutionary implications. Here, we review recent studies on the formation of dauer larvae in Caenorhabditis elegans, the evolution of nematode parasitism and the generation of a novel feeding trait in Pristionchus pacificus. These examples reveal a conserved and co-opted role of an endocrine signaling module involving the steroid hormone dafachronic acid. We will discuss how hormone signaling might facilitate life-history and morphological evolution.

  12. CNS Tumors in Neurofibromatosis. (United States)

    Campian, Jian; Gutmann, David H


    Neurofibromatosis (NF) encompasses a group of distinct genetic disorders in which affected children and adults are prone to the development of benign and malignant tumors of the nervous system. The purpose of this review is to discuss the spectrum of CNS tumors arising in individuals with NF type 1 (NF1) and NF type 2 (NF2), their pathogenic etiologies, and the rational treatment options for people with these neoplasms. This article is a review of preclinical and clinical data focused on the treatment of the most common CNS tumors encountered in children and adults with NF1 and NF2. Although children with NF1 are at risk for developing low-grade gliomas of the optic pathway and brainstem, individuals with NF2 typically manifest low-grade tumors affecting the cranial nerves (vestibular schwannomas), meninges (meningiomas), and spinal cord (ependymomas). With the identification of the NF1 and NF2 genes, molecularly targeted therapies are beginning to emerge, as a result of a deeper understanding of the mechanisms underlying NF1 and NF2 protein function. As we enter into an era of precision oncology, a more comprehensive awareness of the factors that increase the risk of developing CNS cancers in affected individuals, coupled with a greater appreciation of the cellular and molecular determinants that maintain tumor growth, will undoubtedly yield more effective therapies for these cancer predisposition syndromes.

  13. Adult myelination:wrapping up neuronal plasticity

    Institute of Scientific and Technical Information of China (English)

    Megan ORourke; Robert Gasperini; Kaylene M.Young


    In this review, we outline the major neural plasticity mechanisms that have been identiifed in the adult central nervous system (CNS), and offer a perspective on how they regulate CNS function. In particular we examine how myelin plasticity can operate alongside neurogenesis and synaptic plasticity to inlfuence information processing and transfer in the mature CNS.

  14. Development Trend of China's Plastics Industry

    Institute of Scientific and Technical Information of China (English)

    YANG Hui-di


    @@ China's economy is at an important turning point. After more than 20 years of high-speed development, to maintain a high growth rate continuously is more difficult ,as shown by international experience.

  15. Microglia: Dynamic Mediators of Synapse Development and Plasticity. (United States)

    Wu, Yuwen; Dissing-Olesen, Lasse; MacVicar, Brian A; Stevens, Beth


    Neuronal communication underlies all brain activity and the genesis of complex behavior. Emerging research has revealed an unexpected role for immune molecules in the development and plasticity of neuronal synapses. Moreover microglia, the resident immune cells of the brain, express and secrete immune-related signaling molecules that alter synaptic transmission and plasticity in the absence of inflammation. When inflammation does occur, microglia modify synaptic connections and synaptic plasticity required for learning and memory. Here we review recent findings demonstrating how the dynamic interactions between neurons and microglia shape the circuitry of the nervous system in the healthy brain and how altered neuron-microglia signaling could contribute to disease. Copyright © 2015. Published by Elsevier Ltd.

  16. Axonal plasticity elicits long-term changes in oligodendroglia and myelinated fibers

    DEFF Research Database (Denmark)

    Drøjdahl, Nina; Nielsen, Helle Hvilsted; Gardi, Jonathan E


    Axons are linked to induction of myelination during development and to the maintenance of myelin and myelinated tracts in the adult CNS. Currently, it is unknown whether and how axonal plasticity in adult CNS impacts the myelinating cells and their precursors. In this article, we report that newly...

  17. Development and growth in synanthropic species: plasticity and constraints (United States)

    Kralj-Fišer, Simona; Čelik, Tatjana; Lokovšek, Tjaša; Šuen, Klavdija; Šiling, Rebeka; Kuntner, Matjaž


    Urbanization poses serious extinction risks, yet some species thrive in urban environments. This may be due to a pronounced developmental plasticity in these taxa, since phenotypically, plastic organisms may better adjust to unpredictable urban food resources. We studied phenotypic plasticity in Nuctenea umbratica, a common European forest and urban vegetation spider. We subjected spiderlings to low (LF), medium (MF) and high (HF) food treatments and documented their growth and developmental trajectories into adulthood. Spiders from the three treatments had comparable numbers of instars and growth ratios, but differed in developmental periods. Longest developing LF spiders (♀ = 390, ♂ = 320 days) had the smallest adults, but MF (♀ = 300, ♂ = 240 days) and HF (♀ = 240, ♂ = 210 days) spiders reached comparable adult sizes through shorter development. While males and females had comparable instar numbers, females had longer development, higher growth ratios, adult sizes and mass; and while males adjusted their moulting to food availability, female moulting depended on specific mass, not food treatment. We discussed the patterns of Nuctenea sex-specific development and compared our results with published data on two other Holarctic urban colonizers ( Larinioides sclopetarius, Zygiella x- notata) exhibiting high plasticity and fast generation turn-over. We conclude that despite relatively unconstrained developmental time in the laboratory enabling Nuctenea to achieve maximal mass and size—main female fitness proxies—their relatively fixed growth ratio and long generation turn-over may explain their lower success in urban environments.

  18. Genetic pharmacotherapy as an early CNS drug development strategy: testing glutaminase inhibition for schizophrenia treatment in adult mice

    Directory of Open Access Journals (Sweden)

    Susana eMingote


    Full Text Available Genetic pharmacotherapy is an early drug development strategy for the identification of novel CNS targets in mouse models prior to the development of specific ligands. Here for the first time, we have implemented this strategy to address the potential therapeutic value of a glutamate-based pharmacotherapy for schizophrenia involving inhibition of the glutamate recycling enzyme phosphate-activated glutaminase. Mice constitutively heterozygous for GLS1, the gene encoding glutaminase, manifest a schizophrenia resilience phenotype, a key dimension of which is an attenuated locomotor response to propsychotic amphetamine challenge. If resilience is due to glutaminase deficiency in adulthood, then glutaminase inhibitors should have therapeutic potential. However, this has been difficult to test given the dearth of neuroactive glutaminase inhibitors. So, we used genetic pharmacotherapy to test the therapeutic potential of glutaminase inhibition. We specifically asked whether adult induction of GLS1 heterozygosity would attenuate amphetamine responsiveness. We generated conditional floxGLS1 mice and crossed them with global CAG ERT2 cre/+ mice to produce GLS1 iHET mice, susceptible to tamoxifen induction of GLS1 heterozygosity. One month after tamoxifen treatment of adult GLS1 iHET mice, we found a 50% reduction in GLS1 allelic abundance and glutaminase mRNA levels in the brain. While GLS1 iHET mice showed some recombination prior to tamoxifen, there was no impact on mRNA levels. We then asked whether induction of GLS heterozygosity would attenuate the locomotor response to propsychotic amphetamine challenge. Before tamoxifen, control and GLS1 iHET mice did not differ in their response to amphetamine. One month after tamoxifen treatment, amphetamine-induced hyperlocomotion was blocked in GLS1 iHET mice. The block was largely maintained after 5 months. Thus, a genetically induced glutaminase reduction — mimicking pharmacological inhibition — strongly

  19. Neuron-specific expression of p48 Ebp1 during murine brain development and its contribution to CNS axon regeneration. (United States)

    Ko, Hyo Rim; Hwang, Inwoo; Ahn, So Yoon; Chang, Yun Sil; Park, Won Soon; Ahn, Jee-Yin


    P48 Ebp1 is expressed in rapidly proliferating cells such as cancer cells and accelerates cell growth and survival. However, its expression pattern and role in central nervous system development have not been studied. Here, we demonstrated the spatiotemporal expression pattern of p48 Ebp1 during embryonic development and the postnatal period. During embryonic development, p48 Ebp1 was highly expressed in the brain. Expression gradually decreased after birth but was still more abundant than p42 expression after birth. Strikingly, we found that p48 Ebp1 was expressed in a cell type specific manner in neurons but not astrocytes. Moreover, p48 Ebp1 physically interacted with beta tubulin but not alpha tubulin. This fits with its accumulation in distal microtubule growth cone regions. Furthermore, in injured hippocampal slices, p48 Ebp1 introduction promoted axon regeneration. Thus, we speculate that p48 Ebp1 might contribute to microtubule dynamics acting as an MAP and promotes CNS axon regeneration. [BMB Reports 2017; 50(3): 126-131].

  20. The plasticity of intellectual development: insights from preventive intervention. (United States)

    Ramey, C T; Yeates, K O; Short, E J


    Debates regarding the plasticity of intelligence are often fired by a confusion between 2 distinct realms of development, that is, between developmental functions (e.g., a group's average IQ over time) and individual differences (e.g., the relative rank ordering of individual IQs within a group). Questions concerning the stability of these 2 realms are statistically independent. Thus there are 2 kinds of intellectual plasticity, and there may be no developmental convergences between them. In the present study, data from an early intervention program were used to investigate the 2 kinds of plasticity separately and to examine certain possible convergences between them. The program involved children at risk for developmental retardation who were randomly assigned at birth to 2 rearing conditions (i.e., educational daycare vs. no educational intervention) and whose intellectual development was then studied longitudinally to 4 years of age. Our findings indicate that developmental functions are moderately alterable through systemic early education, particularly after infancy, whereas individual differences are moderately stable, again particularly after infancy. They also indicate that the 2 kinds of plasticity are independent; the alteration of developmental functions through daycare affects neither the stability nor the determinants of individual differences. We discuss the implications that these findings have for current models of mental development, for the nature-nurture debate, and for arguments concerning the efficacy of early intervention programs.


    Institute of Scientific and Technical Information of China (English)


    An effect of unequal deformation in development of advanced plastic processing technologies is researched by studying an in-plane bending process of strip metal under unequal compressing. The research results show the following: If appropriately controlled, unequal plastic deformation can play an important role not only in the improvement of quality of parts obtained by plastic processing technologies, but also in the development of new processes for advanced plastic working technologies. A coordinated growth of unequal plastic deformation can develop the deformation potentiality of material to the full. The degree of unequal plastic deformation can be used as bases for optimization design of processes and dies of plastic forming.

  2. Polarity Determinants in Dendritic Spine Development and Plasticity. (United States)

    Zhang, Huaye


    The asymmetric distribution of various proteins and RNAs is essential for all stages of animal development, and establishment and maintenance of this cellular polarity are regulated by a group of conserved polarity determinants. Studies over the last 10 years highlight important functions for polarity proteins, including apical-basal polarity and planar cell polarity regulators, in dendritic spine development and plasticity. Remarkably, many of the conserved polarity machineries function in similar manners in the context of spine development as they do in epithelial morphogenesis. Interestingly, some polarity proteins also utilize neuronal-specific mechanisms. Although many questions remain unanswered in our understanding of how polarity proteins regulate spine development and plasticity, current and future research will undoubtedly shed more light on how this conserved group of proteins orchestrates different pathways to shape the neuronal circuitry.

  3. Polarity Determinants in Dendritic Spine Development and Plasticity

    Directory of Open Access Journals (Sweden)

    Huaye Zhang


    Full Text Available The asymmetric distribution of various proteins and RNAs is essential for all stages of animal development, and establishment and maintenance of this cellular polarity are regulated by a group of conserved polarity determinants. Studies over the last 10 years highlight important functions for polarity proteins, including apical-basal polarity and planar cell polarity regulators, in dendritic spine development and plasticity. Remarkably, many of the conserved polarity machineries function in similar manners in the context of spine development as they do in epithelial morphogenesis. Interestingly, some polarity proteins also utilize neuronal-specific mechanisms. Although many questions remain unanswered in our understanding of how polarity proteins regulate spine development and plasticity, current and future research will undoubtedly shed more light on how this conserved group of proteins orchestrates different pathways to shape the neuronal circuitry.

  4. Embryonic expression of Drosophila IMP in the developing CNS and PNS

    DEFF Research Database (Denmark)

    Adolph, Sidsel Kramshøj; Delotto, Robert; Nielsen, Finn Cilius;


    Drosophila IMP (dIMP) is related to the vertebrate RNA-binding proteins IMP1-3, ZBP1, Vg1RBP and CRD-BP, which are involved in RNA regulatory processes such as translational repression, localization and stabilization. The proteins are expressed in many fetal tissues, including the developing nerv...

  5. CNS drug development in Europe--past progress and future challenges. (United States)

    Nutt, David J; Attridge, Jim


    Despite enormous progress in defining, diagnosing and treating mental disorders, EU health systems face a mounting challenge in responding to 'unmet need'. Mental illnesses produce a societal burden that exceeds that for either cancers or cardiovascular conditions. Leveraging advances in science and medicine to make available new innovative medicines is a key component in responding to this challenge. The dominant paradigm has been, is and will continue to be, one of incremental progress. Better medicines for depression, anxiety and psychoses in the working age population would add great value to patients and improve labour productivity. But psychotropic medicines face exceptional challenges in demonstrating their added value, due to uncertainty in patient diagnosis, selecting treatments and ensuring adherence. Also, there are major difficulties in estimating costs. Advances in understanding brain processes, identifying biomarkers and neuro-imaging techniques promise far more effective 'diagnostic-therapeutic' treatments and improved patient outcomes in the future. Currently there are valuable incremental innovations in late development, which may well fail to recover their R&D costs, because of very low reimbursed prices. This will send a signal to innovators not to persist with product development in this area. Recently several leading companies have withdrawn from R&D in these mental disorders. This is a worrying development since building the capabilities to succeed in any disease sector takes many years and, once dismantled, they cannot easily be re-established. Three policy interventions could improve innovation incentives: Further 'push' incentives under i) and streamlining under ii) alone will not reverse the decline in investment incentives. An EU consensus, based upon an innovation model which encompasses the Research, Development and Market phases as a single cyclical process, which addresses the weak 'market pull incentives' under iii) is needed. There

  6. Effect of cadmium on CNS function and development in rat offspring: effect of vitamin E

    Directory of Open Access Journals (Sweden)

    H. M. Jasem


    Full Text Available The work was designed to study the effect of vitamin E ( 500 mg /kg diet on the central nervous system function and landmarks development in offspring of rats whoser mothers treated with cadmium (50mg/L of drinking water during lactation. Cadmium chloride caused a significant increase in righting reflex , olfactory discrimination tests in pups (aged one week and in the onset of movement test in weaned pups. The results indicated a significant reduction in motor activity in the open field, cliff avoidance, click response and weight in weaned pups. Cadmium chloride caused a significant increased in negative geotaxic in weaned pups. Cadmium chloride did not affect significantly on landmarks development ( opening of eyes and ears , appearance of teeth and hair with the exception of a significant increase in descending time of testis and a significant decrease in appearance time of vaginal opening . Administration of vitamin E caused a significant increase in motor activity in the open field. and significant reduction in the onset of movement test, negative geotaxic and weight of weaned pups and in descending time of testis . It is concluded from this study that vitamin E caused positive effects on central nervous system and some landmarks development in pups whose their mothers treated with cadmium chloride.

  7. Loss of methylation at the IFNG promoter and CNS-1 is associated with the development of functional IFN-γ memory in human CD4(+) T lymphocytes. (United States)

    Dong, Jun; Chang, Hyun-Dong; Ivascu, Claudia; Qian, Yu; Rezai, Soheila; Okhrimenko, Anna; Cosmi, Lorenzo; Maggi, Laura; Eckhardt, Florian; Wu, Peihua; Sieper, Joachim; Alexander, Tobias; Annunziato, Francesco; Gossen, Manfred; Li, Jun; Radbruch, Andreas; Thiel, Andreas


    Cytokine memory for IFN-γ production by effector/memory Th1 cells plays a key role in both protective and pathological immune responses. To understand the epigenetic mechanism determining the ontogeny of effector/memory Th1 cells characterized by stable effector functions, we identified a T-cell-specific methylation pattern at the IFNG promoter and CNS-1 in ex vivo effector/memory Th1 cells, and investigated methylation dynamics of these regions during the development of effector/memory Th1 cells. During Th1 differentiation, demethylation occurred at both the promoter and CNS-1 regions of IFNG as early as 16 h, and this process was independent of cell proliferation and DNA synthesis. Using an IFN-γ capture assay, we found early IFN-γ-producing cells from 2-day differentiating cultures acquired "permissive" levels of demethylation and developed into effector/memory Th1 cells undergoing progressive demethylation at the IFNG promoter and CNS-1 when induced by IL-12. Methylation levels of these regions in effector/memory Th1 cells of peripheral blood from rheumatoid arthritis patients correlated inversely with reduced frequencies of IFN-γ-producers, coincident with recruitment of effector/memory Th1 cells to the site of inflammation. Thus, after termination of TCR stimulation, IL-12 signaling potentiates the stable functional IFN-γ memory in effector/memory Th1 cells characterized by hypomethylation at the IFNG promoter and CNS-1.

  8. Development and Plasticity of Intra- and Intersensory Information Processing (United States)

    Polley, Daniel B.; Hillock, Andrea R.; Spankovich, Christopher; Popescu, Maria V.; Royal, David W.; Wallace, Mark T.


    The functional architecture of sensory brain regions reflects an ingenious biological solution to the competing demands of a continually changing sensory environment. While they are malleable, they have the constancy necessary to support a stable sensory percept. How does the functional organization of sensory brain regions contend with these antithetical demands? Here we describe the functional organization of auditory and multisensory (i.e., auditory-visual) information processing in three sensory brain structures: (1) a low-level unisensory cortical region, the primary auditory cortex (A1); (2) a higher-order multisensory cortical region, the anterior ectosylvian sulcus (AES); and (3) a multisensory subcortical structure, the superior colliculus (SC), We then present a body of work that characterizes the ontogenic expression of experience-dependent influences on the operations performed by the functional circuits contained within these regions. We will present data to support the hypothesis that the competing demands for plasticity and stability are addressed through a developmental transition in operational properties of functional circuits from an initially labile mode in the early stages of postnatal development to a more stable mode in the mature brain that retains the capacity for plasticity under specific experiential conditions. Finally, we discuss parallels between the central tenets of functional organization and plasticity of sensory brain structures drawn from animal studies and a growing literature on human brain plasticity and the potential applicability of these principles to the audiology clinic. PMID:19358458

  9. CNS development of health maintenance programs: quality improvement and cost reduction. (United States)

    Mullin, M H; Opperwall, B C; White, S L


    Several outpatient health maintenance programs were developed by CNSs that resulted in quality improvement and cost savings. Common implementation strategies, barriers to implementation, marketing issues and techniques, and revenue generation issues were found. An outpatient consultation model was used to expand enterostomal therapy and diabetic teaching services. Education and support programs include a cardiac support group and community education classes on aging. Preadmission programs include physical therapy consultation for patients scheduled for elective orthopedic surgery. Outpatient programs facilitate continuity of care in a managed care format, promote cost savings, and provide unique services that encourage patients to return to our hospital, thereby increasing market share. Key barriers encountered include inconsistent or ambiguous administrative support, budgetary constraints, lack of collaboration, communication problems, facility limitations, funding considerations, resource allocation, and territoriality. The programs are consistent with the change in focus of health care from treatment to prevention.

  10. Plasticity of lung development in the amphibian, Xenopus laevis

    Directory of Open Access Journals (Sweden)

    Christopher S. Rose


    Contrary to previous studies, we found that Xenopus laevis tadpoles raised in normoxic water without access to air can routinely complete metamorphosis with lungs that are either severely stunted and uninflated or absent altogether. This is the first demonstration that lung development in a tetrapod can be inhibited by environmental factors and that a tetrapod that relies significantly on lung respiration under unstressed conditions can be raised to forego this function without adverse effects. This study compared lung development in untreated, air-deprived (AD and air-restored (AR tadpoles and frogs using whole mounts, histology, BrdU labeling of cell division and antibody staining of smooth muscle actin. We also examined the relationship of swimming and breathing behaviors to lung recovery in AR animals. Inhibition and recovery of lung development occurred at the stage of lung inflation. Lung recovery in AR tadpoles occurred at a predictable and rapid rate and correlated with changes in swimming and breathing behavior. It thus presents a new experimental model for investigating the role of mechanical forces in lung development. Lung recovery in AR frogs was unpredictable and did not correlate with behavioral changes. Its low frequency of occurrence could be attributed to developmental, physical and behavioral changes, the effects of which increase with size and age. Plasticity of lung inflation at tadpole stages and loss of plasticity at postmetamorphic stages offer new insights into the role of developmental plasticity in amphibian lung loss and life history evolution.

  11. Ecrg4 expression and its product augurin in the choroid plexus: impact on fetal brain development, cerebrospinal fluid homeostasis and neuroprogenitor cell response to CNS injury

    Directory of Open Access Journals (Sweden)

    Gonzalez Ana


    Full Text Available Abstract Background The content and composition of cerebrospinal fluid (CSF is determined in large part by the choroid plexus (CP and specifically, a specialized epithelial cell (CPe layer that responds to, synthesizes, and transports peptide hormones into and out of CSF. Together with ventricular ependymal cells, these CPe relay homeostatic signals throughout the central nervous system (CNS and regulate CSF hydrodynamics. One new candidate signal is augurin, a newly recognized 14 kDa protein that is encoded by esophageal cancer related gene-4 (Ecrg4, a putative tumor suppressor gene whose presence and function in normal tissues remains unexplored and enigmatic. The aim of this study was to explore whether Ecrg4 and its product augurin, can be implicated in CNS development and the response to CNS injury. Methods Ecrg4 gene expression in CNS and peripheral tissues was studied by in situ hybridization and quantitative RT-PCR. Augurin, the protein encoded by Ecrg4, was detected by immunoblotting, immunohistochemistry and ELISA. The biological consequence of augurin over-expression was studied in a cortical stab model of rat CNS injury by intra-cerebro-ventricular injection of an adenovirus vector containing the Ecrg4 cDNA. The biological consequences of reduced augurin expression were evaluated by characterizing the CNS phenotype caused by Ecrg4 gene knockdown in developing zebrafish embryos. Results Gene expression and immunohistochemical analyses revealed that, the CP is a major source of Ecrg4 in the CNS and that Ecrg4 mRNA is predominantly localized to choroid plexus epithelial (CPe, ventricular and central canal cells of the spinal cord. After a stab injury into the brain however, both augurin staining and Ecrg4 gene expression decreased precipitously. If the loss of augurin was circumvented by over-expressing Ecrg4 in vivo, BrdU incorporation by cells in the subependymal zone decreased. Inversely, gene knockdown of Ecrg4 in developing

  12. Test Plan Development for Plastic Ammunition Containers. Volume 1 (United States)


    122 xii TEST PLAN DEVELOPMENT FOR PLASTIC AM4MINITION CONTAINERS - VOLUME I 1.0 INTRODUCTION The purpose of this project...11 LA 00 Li C:0 z CP -0 133 0( LIE r r ’ D2 U)~ E C IP a g 0- L) LaLn 4’ MOIAIV3H-Q3.~f-trCYin, 20o Tabla 6-D Performance Prediction Model 155ram

  13. Spindle Activity Orchestrates Plasticity during Development and Sleep

    Directory of Open Access Journals (Sweden)

    Christoph Lindemann


    Full Text Available Spindle oscillations have been described during early brain development and in the adult brain. Besides similarities in temporal patterns and involved brain areas, neonatal spindle bursts (NSBs and adult sleep spindles (ASSs show differences in their occurrence, spatial distribution, and underlying mechanisms. While NSBs have been proposed to coordinate the refinement of the maturating neuronal network, ASSs are associated with the implementation of acquired information within existing networks. Along with these functional differences, separate synaptic plasticity mechanisms seem to be recruited. Here, we review the generation of spindle oscillations in the developing and adult brain and discuss possible implications of their differences for synaptic plasticity. The first part of the review is dedicated to the generation and function of ASSs with a particular focus on their role in healthy and impaired neuronal networks. The second part overviews the present knowledge of spindle activity during development and the ability of NSBs to organize immature circuits. Studies linking abnormal maturation of brain wiring with neurological and neuropsychiatric disorders highlight the importance to better elucidate neonatal plasticity rules in future research.

  14. Emotion Processing by ERP Combined with Development and Plasticity

    Directory of Open Access Journals (Sweden)

    Rui Ding


    Full Text Available Emotions important for survival and social interaction have received wide and deep investigations. The application of the fMRI technique into emotion processing has obtained overwhelming achievements with respect to the localization of emotion processes. The ERP method, which possesses highly temporal resolution compared to fMRI, can be employed to investigate the time course of emotion processing. The emotional modulation of the ERP component has been verified across numerous researches. Emotions, described as dynamically developing along with the growing age, have the possibility to be enhanced through learning (or training or to be damaged due to disturbances in growth, which is underlain by the neural plasticity of emotion-relevant nervous systems. And mood disorders with typical symptoms of emotion discordance probably have been caused by the dysfunctional neural plasticity.

  15. Development and test of a plastic deep-well pump (United States)

    Zhang, Q. H.; Gao, X. F.; Xu, Y.; Shi, W. D.; Lu, W. G.; Liu, W.


    To develop a plastic deep-well pump, three methods are proposed on structural and forming technique. First, the major hydraulic components are constructed by plastics, and the connection component is constructed by steel. Thus the pump structure is more concise and slim, greatly reducing its weight and easing its transportation, installation, and maintenance. Second, the impeller is designed by maximum diameter method. Using same pump casing, the stage head is greatly increased. Third, a sealing is formed by impeller front end face and steel end face, and two slots are designed on the impeller front end face, thus when the two end faces approach, a lubricating pair is formed, leading to an effective sealing. With above methods, the pump's axial length is greatly reduced, and its stage head is larger and more efficient. Especially, the pump's axial force is effectively balanced. To examine the above proposals, a prototype pump is constructed, and its testing results show that the pump efficiency exceeds the national standard by 6%, and the stage head is improved by 41%, meanwhile, its structure is more concise and ease of transportation. Development of this pump would provide useful experiences for further popularity of plastic deep-well pumps.

  16. Mockup tests for developing the CARR-CNS with a two-phase thermo-siphon loop

    Institute of Scientific and Technical Information of China (English)

    DU She-Jiao; BI Qin-Cheng; CHEN Ting-Kuan; FENG Quan-Ke; LI Xiao-Ming


    The cold neutron source (CNS) is a facility to increase cold neutrons by scattering thermal neutrons in liquid hydrogen or deuterium around 20 K. For extracting a stable cold neutron flux fiom the CNS, the liquid quantity in the moderator cell should be maintained stably against disturbance of nuclear heating. The China Institute of Atomic Energy (CIAE) is now constructing the China Advanced Research Reactor (CARR: 60 MW), and designing the CARR-CNS with a two-phase thermo-siphon loop consisting of a condenser, two moderator transfer tubes and an annular cylindrical moderator cell. The mock-up tests were carried out using a full-scale loop with Freon-113, for validating the self-regulating characteristics of the loop, the void fraction less than 20% in the liquid hydrogen of the moderator cell, and the requirements for establishing the condition under which the inner shell has only vapor. The density ratio of liquid to vapor and the volumetric evaporation rate due to heat load are kept the same as those in normal operation of the CARR-CNS. The results show that the loop has the self-regulating characteristics and the inner shell contains only vapor, while the outer shell liquid. The local void fraction in the liquid increases with increasing of the loop pressure.

  17. Development of transdermal therapeutic formulation of CNS5161, a novel NMDA receptor antagonist, by utilizing pressure-sensitive adhesives II: improved transdermal absorption and evaluation of efficacy and safety. (United States)

    Naruse, Mamoru; Ogawara, Ken-ichi; Kimura, Toshikiro; Konishi, Ryoji; Higaki, Kazutaka


    The aim of this study was to prepare a transdermal therapeutic formulation of CNS5161, an NMDA receptor antagonist developed as a drug for neuropathic pain. Since a silicone pressure-sensitive adhesive (PSA) was found to be the best PSA for CNS5161 among six different PSAs examined in our previous study, the effects of the loading concentration of CNS5161 on release and rat skin permeability were investigated using silicone PSAs. The release of CNS5161 was elevated with an increase in the drug concentration from 1% to 14%. The transdermal flux at the steady state reached a plateau at 8% and over, while crystallization of CNS5161 was not observed for any formulation even at high drug concentrations. The drug concentration in rat skin at the steady state was also saturated at 8% and over, which correlated well with the transdermal flux at the steady state. Therefore, skin permeation clearance defined to the skin concentration at the steady state was almost constant at 0.21/h from 2% to 14% of CNS5161, which suggests that drug concentrations in the skin would be a driving force for transport of the drug to the receptor side. Since increasing the concentration of CNS5161 in the PSA patch was not able to elevate the transdermal flux, 12 formulations containing several permeation enhancers were examined to improve the transdermal transport of CNS5161. Among them, the formulation containing propylene glycol, diisopropyl adipate, and polyvinylpyrrolidone significantly increased the transdermal flux by approximately 1.8-fold by improving the diffusivity of CNS5161 in the skin, and also significantly enhanced the analgesic effect of CNS5161. This formulation caused only slight skin irritation, which indicated that it would be a promising transdermal therapeutic system for CNS5161.

  18. MicroRNA networks direct neuronal development and plasticity. (United States)

    Olde Loohuis, N F M; Kos, A; Martens, G J M; Van Bokhoven, H; Nadif Kasri, N; Aschrafi, A


    MicroRNAs (miRNAs) constitute a class of small, non-coding RNAs that act as post-transcriptional regulators of gene expression. In neurons, the functions of individual miRNAs are just beginning to emerge, and recent studies have elucidated roles for neural miRNAs at various stages of neuronal development and maturation, including neurite outgrowth, dendritogenesis, and spine formation. Notably, miRNAs regulate mRNA translation locally in the axosomal and synaptodendritic compartments, and thereby contribute to the dynamic spatial organization of axonal and dendritic structures and their function. Given the critical role for miRNAs in regulating early brain development and in mediating synaptic plasticity later in life, it is tempting to speculate that the pathology of neurological disorders is affected by altered expression or functioning of miRNAs. Here we provide an overview of recently identified mechanisms of neuronal development and plasticity involving miRNAs, and the consequences of miRNA dysregulation.

  19. The Role of Plastic Surgeons in Advancing Development Global. (United States)

    Broer, P Niclas; Jenny, Hillary E; Ng-Kamstra, Joshua S; Juran, Sabrina


    In September 2015, the international community came together to agree on the 2030 Agenda for Sustainable Development, a plan of action for people, the planet, and prosperity. Ambitious and far-reaching as they are, they are built on three keystones: the elimination of extreme poverty, fighting climate change, and a commitment to fighting injustice and inequality. Critical to the achievement of the Agenda is the global realization of access to safe, affordable surgical and anesthesia care when needed. The landmark report by the Lancet Commission on Global Surgery estimated that between 28 and 32 percent of the global burden of disease is amenable to surgical treatment. However, as many as five billion people lack access to safe, timely, and affordable surgical care, a burden felt most severely in low- and middle-income countries (LMICs). Surgery, and specifically plastic surgery, should be incorporated into the international development and humanitarian agenda. As a community of care providers dedicated to the restoration of the form and function of the human body, plastics surgeons have a collective opportunity to contribute to global development, making the world more equitable and helping to reduce extreme poverty. As surgical disease comprises a significant burden of disease and surgery can be delivered in a cost-effective manner, surgery must be considered a public health priority.

  20. Mitochondrial dynamics in neuronal injury, development and plasticity. (United States)

    Flippo, Kyle H; Strack, Stefan


    Mitochondria fulfill numerous cellular functions including ATP production, Ca(2+) buffering, neurotransmitter synthesis and degradation, ROS production and sequestration, apoptosis and intermediate metabolism. Mitochondrial dynamics, a collective term for the processes of mitochondrial fission, fusion and transport, governs mitochondrial function and localization within the cell. Correct balance of mitochondrial dynamics is especially important in neurons as mutations in fission and fusion enzymes cause peripheral neuropathies and impaired development of the nervous system in humans. Regulation of mitochondrial dynamics is partly accomplished through post-translational modification of mitochondrial fission and fusion enzymes, in turn influencing mitochondrial bioenergetics and transport. The importance of post-translational regulation is highlighted by numerous neurodegenerative disorders associated with post-translational modification of the mitochondrial fission enzyme Drp1. Not surprisingly, mitochondrial dynamics also play an important physiological role in the development of the nervous system and synaptic plasticity. Here, we highlight recent findings underlying the mechanisms and regulation of mitochondrial dynamics in relation to neurological disease, as well as the development and plasticity of the nervous system. © 2017. Published by The Company of Biologists Ltd.

  1. Development of recycled plastic composites for structural applications from CEA plastics (United States)

    Bhalla, Agrim

    Plastic waste from consumer electronic appliances (CEAs) such as computer and printer parts including Polystyrene (PS), Acrylonitrile Butadiene Styrene (ABS), Polystyrene (PS) and PC/ABS were collected using handheld FTIR Spectrophotometer. The blends of these plastics with High Density Polyethylene (HDPE) are manufactured under special processing conditions in a single screw compounding injection molding machine. The blends are thermoplastics have high stiffness and strength, which may enhance the mechanical properties of HDPE like tensile modulus, ultimate tensile strength, tensile break and tensile yield. These composites have a potential to be used for the future application of recycled plastic lumber, thus replacing the traditional wood lumber.

  2. Neural stem cells and neuro/gliogenesis in the central nervous system: understanding the structural and functional plasticity of the developing, mature, and diseased brain. (United States)

    Yamaguchi, Masahiro; Seki, Tatsunori; Imayoshi, Itaru; Tamamaki, Nobuaki; Hayashi, Yoshitaka; Tatebayashi, Yoshitaka; Hitoshi, Seiji


    Neurons and glia in the central nervous system (CNS) originate from neural stem cells (NSCs). Knowledge of the mechanisms of neuro/gliogenesis from NSCs is fundamental to our understanding of how complex brain architecture and function develop. NSCs are present not only in the developing brain but also in the mature brain in adults. Adult neurogenesis likely provides remarkable plasticity to the mature brain. In addition, recent progress in basic research in mental disorders suggests an etiological link with impaired neuro/gliogenesis in particular brain regions. Here, we review the recent progress and discuss future directions in stem cell and neuro/gliogenesis biology by introducing several topics presented at a joint meeting of the Japanese Association of Anatomists and the Physiological Society of Japan in 2015. Collectively, these topics indicated that neuro/gliogenesis from NSCs is a common event occurring in many brain regions at various ages in animals. Given that significant structural and functional changes in cells and neural networks are accompanied by neuro/gliogenesis from NSCs and the integration of newly generated cells into the network, stem cell and neuro/gliogenesis biology provides a good platform from which to develop an integrated understanding of the structural and functional plasticity that underlies the development of the CNS, its remodeling in adulthood, and the recovery from diseases that affect it.

  3. Texture developed during deformation of Transformation Induced Plasticity (TRIP) steels (United States)

    Bhargava, M.; Shanta, C.; Asim, T.; Sushil, M.


    Automotive industry is currently focusing on using advanced high strength steels (AHSS) due to its high strength and formability for closure applications. Transformation Induced Plasticity (TRIP) steel is promising material for this application among other AHSS. The present work is focused on the microstructure development during deformation of TRIP steel sheets. To mimic complex strain path condition during forming of automotive body, Limit Dome Height (LDH) tests were conducted and samples were deformed in servo hydraulic press to find the different strain path. FEM Simulations were done to predict different strain path diagrams and compared with experimental results. There is a significant difference between experimental and simulation results as the existing material models are not applicable for TRIP steels. Micro texture studies were performed on the samples using EBSD and X-RD techniques. It was observed that austenite is transformed to martensite and texture developed during deformation had strong impact on limit strain and strain path.

  4. Recent developments in plastic optical fiber components for automotive applications (United States)

    Cirillo, James R.; Jennings, Kurt L.; Lynn, Mark A.; Steele, Robert E.


    The majority of production applications using plastic optical fiber (POF) have been for illumination applications. These applications continue to be refined and new illumination applications continue to be introduced. Point-to-point data communication applications of POF are beginning to appear in production vehicles. New developments in connection systems and networking components are occurring rapidly. This paper discusses recently developed components for illumination and data communications. The illumination components were designed for three different applications: lamp monitoring, keyhole illumination, and PRNDL indication (gear shift). Components for data communications include two connection systems and two passive stars designed for networking. The two connections systems are a 16 electrical/1 optical system for point-to-point links and a 5 electrical/2 optical for two-way optical communications. The two stars are a 16 node star and 7 node star. Performance characteristics and design advantages are described for all components.

  5. Development of Biodegradable Plastic as Mango Fruit Bag

    Directory of Open Access Journals (Sweden)

    Andres M Tuates jr


    Full Text Available Plastics have achieved a dominant position in agriculture because of their transparency, lightness in weight, impermeability to water and their resistance to microbial attack. It is use as food and fruits packaging, fruit bag, food container, seedling bag, mulching film, protective for greenhouse, dryer shed and among others. However, this generates higher quantity of wastes that are difficult to dispose by farmers. The plastic residues remain on the soil for some years as large pieces and they are impediment to plant growth and also a potential hazard to animals if the land is subsequently put down to grass. To address these problems, the project aim to develop and evaluate the biodegradable film for mango fruit bag during development. Cassava starch and polybutylene succinate (PBS was used in the development biodegradable film. The PBS and starch was melt-blended in a twin-screw extruder and then blown into film extrusion machine. The physic-chemical-mechanical properties of biodegradable fruit bag were done following standard methods of test. Field testing of fruit bag was also conducted to evaluate its durability and efficiency field condition.  The PHilMech-FiC fruit bag is made of biodegradable material measuring 6 x 8 inches with a thickness of 150 microns. The tensile strength is within the range of LDPE while the elongation is within the range of HDPE. However, it has higher density, thickness swelling and absorbed more water. It is projected that after thirty six (36 weeks, the film will be totally degraded. Results of field testing shows that the quality of harvested fruits using PHilMech-FiC biodegradable fruit bag in terms of percent marketable, non-marketable and export, peel color at ripe stage, flesh color, TSS, oBrix, percent edible portion is comparable with the existing bagging materials such as Chinese brown paper bag  and old newspaper.  

  6. CNS infections in Greenland

    DEFF Research Database (Denmark)

    Nordholm, Anne Christine; Søborg, Bolette; Andersson, Mikael


    BACKGROUND: Indigenous Arctic people suffer from high rates of infectious diseases. However, the burden of central nervous system (CNS) infections is poorly documented. This study aimed to estimate incidence rates and mortality of CNS infections among Inuits and non-Inuits in Greenland...... and in Denmark. METHODS: We conducted a nationwide cohort study using the populations of Greenland and Denmark 1990-2012. Information on CNS infection hospitalizations and pathogens was retrieved from national registries and laboratories. Incidence rates were estimated as cases per 100,000 person......-years. Incidence rate ratios were calculated using log-linear Poisson-regression. Mortality was estimated using Kaplan-Meier curves and Log Rank test. RESULTS: The incidence rate of CNS infections was twice as high in Greenland (35.6 per 100,000 person years) as in Denmark (17.7 per 100,000 person years...

  7. The Role of Neurogenic Inflammation in Blood-Brain Barrier Disruption and Development of Cerebral Oedema Following Acute Central Nervous System (CNS) Injury. (United States)

    Sorby-Adams, Annabel J; Marcoionni, Amanda M; Dempsey, Eden R; Woenig, Joshua A; Turner, Renée J


    Acute central nervous system (CNS) injury, encompassing traumatic brain injury (TBI) and stroke, accounts for a significant burden of morbidity and mortality worldwide, largely attributable to the development of cerebral oedema and elevated intracranial pressure (ICP). Despite this, clinical treatments are limited and new therapies are urgently required to improve patient outcomes and survival. Originally characterised in peripheral tissues, such as the skin and lungs as a neurally-elicited inflammatory process that contributes to increased microvascular permeability and tissue swelling, neurogenic inflammation has now been described in acute injury to the brain where it may play a key role in the secondary injury cascades that evolve following both TBI and stroke. In particular, release of the neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP) appear to be critically involved. In particular, increased SP expression is observed in perivascular tissue following acute CNS injury, with the magnitude of SP release being related to both the frequency and degree of the insult. SP release is associated with profound blood-brain barrier disruption and the subsequent development of vasogenic oedema, as well as neuronal injury and poor functional outcomes. Inhibition of SP through use of a neurokinin 1 (NK1) antagonist is highly beneficial following both TBI and ischaemic stroke in pre-clinical models. The role of CGRP is more unclear, especially with respect to TBI, with both elevations and reductions in CGRP levels reported following trauma. However, a beneficial role has been delineated in stroke, given its potent vasodilatory effects. Thus, modulating neuropeptides represents a novel therapeutic target in the treatment of cerebral oedema following acute CNS injury.

  8. Abbreviated exposure to hypoxia is sufficient to induce CNS dysmyelination, modulate spinal motor neuron composition, and impair motor development in neonatal mice. (United States)

    Watzlawik, Jens O; Kahoud, Robert J; O'Toole, Ryan J; White, Katherine A M; Ogden, Alyssa R; Painter, Meghan M; Wootla, Bharath; Papke, Louisa M; Denic, Aleksandar; Weimer, Jill M; Carey, William A; Rodriguez, Moses


    Neonatal white matter injury (nWMI) is an increasingly common cause of cerebral palsy that results predominantly from hypoxic injury to progenitor cells including those of the oligodendrocyte lineage. Existing mouse models of nWMI utilize prolonged periods of hypoxia during the neonatal period, require complex cross-fostering and exhibit poor growth and high mortality rates. Abnormal CNS myelin composition serves as the major explanation for persistent neuro-motor deficits. Here we developed a simplified model of nWMI with low mortality rates and improved growth without cross-fostering. Neonatal mice are exposed to low oxygen from postnatal day (P) 3 to P7, which roughly corresponds to the period of human brain development between gestational weeks 32 and 36. CNS hypomyelination is detectable for 2-3 weeks post injury and strongly correlates with levels of body and brain weight loss. Immediately following hypoxia treatment, cell death was evident in multiple brain regions, most notably in superficial and deep cortical layers as well as the subventricular zone progenitor compartment. PDGFαR, Nkx2.2, and Olig2 positive oligodendrocyte progenitor cell were significantly reduced until postnatal day 27. In addition to CNS dysmyelination we identified a novel pathological marker for adult hypoxic animals that strongly correlates with life-long neuro-motor deficits. Mice reared under hypoxia reveal an abnormal spinal neuron composition with increased small and medium diameter axons and decreased large diameter axons in thoracic lateral and anterior funiculi. Differences were particularly pronounced in white matter motor tracts left and right of the anterior median fissure. Our findings suggest that 4 days of exposure to hypoxia are sufficient to induce experimental nWMI in CD1 mice, thus providing a model to test new therapeutics. Pathological hallmarks of this model include early cell death, decreased OPCs and hypomyelination in early postnatal life, followed by

  9. Present and future development in plastics from biomass

    NARCIS (Netherlands)

    Shen, L.; Worrell, E.; Patel, M.K.


    Biobased plastics have experienced fast growth in the past decade thanks to the public concerns over the environment, climate change and the depletion of fossil fuels. This perspective provides an overview of the current global market of biobased plastics, their material properties, technical substi

  10. Present and future development in plastics from biomass

    NARCIS (Netherlands)

    Shen, L.; Worrell, E.; Patel, M.K.


    Biobased plastics have experienced fast growth in the past decade thanks to the public concerns over the environment, climate change and the depletion of fossil fuels. This perspective provides an overview of the current global market of biobased plastics, their material properties, technical

  11. Regulatory gene networks that shape the development of adaptive phenotypic plasticity in a cichlid fish. (United States)

    Schneider, Ralf F; Li, Yuanhao; Meyer, Axel; Gunter, Helen M


    Phenotypic plasticity is the ability of organisms with a given genotype to develop different phenotypes according to environmental stimuli, resulting in individuals that are better adapted to local conditions. In spite of their ecological importance, the developmental regulatory networks underlying plastic phenotypes often remain uncharacterized. We examined the regulatory basis of diet-induced plasticity in the lower pharyngeal jaw (LPJ) of the cichlid fish Astatoreochromis alluaudi, a model species in the study of adaptive plasticity. Through raising juvenile A. alluaudi on either a hard or soft diet (hard-shelled or pulverized snails) for between 1 and 8 months, we gained insight into the temporal regulation of 19 previously identified candidate genes during the early stages of plasticity development. Plasticity in LPJ morphology was first detected between 3 and 5 months of diet treatment. The candidate genes, belonging to various functional categories, displayed dynamic expression patterns that consistently preceded the onset of morphological divergence and putatively contribute to the initiation of the plastic phenotypes. Within functional categories, we observed striking co-expression, and transcription factor binding site analysis was used to examine the prospective basis of their coregulation. We propose a regulatory network of LPJ plasticity in cichlids, presenting evidence for regulatory crosstalk between bone and muscle tissues, which putatively facilitates the development of this highly integrated trait. Through incorporating a developmental time-course into a phenotypic plasticity study, we have identified an interconnected, environmentally responsive regulatory network that shapes the development of plasticity in a key innovation of East African cichlids.

  12. Development of Improved Chemicals and Plastics from Oilseeds

    Energy Technology Data Exchange (ETDEWEB)

    Nugent, Patricia A.; Lysenko, Zenon


    The overall objective of this program was to develop technology that can be applied to the production of various chemicals and plastics from seed oils. This research and development program included activities in all four key barrier areas identified in the US DOE Technology Roadmap for Plant/Crop-Based Renewable Resources, namely Plant Science, Production, Processing, and Utilization. Participants in the project included The Dow Chemical Company, Castor Oil, Inc., and the USDA Western Regional Research Center (WRRC). The objective of this production task was to evaluate and develop metathesis catalyst technology as a means of utilizing seed oils as feedstocks for the chemical industry. Specifically, ethenolysis of fatty acid methyl esters, FAME’s, leads to functionalized derivatives. These serve as valuable starting points for materials which cascade into a variety of applications, many of which have a current market presence. The relatively recent discovery and commercial availability of a family of metathesis catalysts which are tolerant of polar functional groups and the acquisition and implementation of high throughput synthesis and screening infrastructure led to a prime opportunity to investigate this project area.





    Development of small injection moulding machine for forming small plastic articles in small-scale industries was studied. This work which entailed design, construction and test small injection moulding machine that was capable of forming small plastic articles by injecting molten resins into a closed, cooled mould, where it solidifies to give the desired products was developed. The machine was designed and constructed to work as a prototype for producing very small plastic components. Design ...

  14. Knowledge-Based, Central Nervous System (CNS) Lead Selection and Lead Optimization for CNS Drug Discovery. (United States)

    Ghose, Arup K; Herbertz, Torsten; Hudkins, Robert L; Dorsey, Bruce D; Mallamo, John P


    The central nervous system (CNS) is the major area that is affected by aging. Alzheimer's disease (AD), Parkinson's disease (PD), brain cancer, and stroke are the CNS diseases that will cost trillions of dollars for their treatment. Achievement of appropriate blood-brain barrier (BBB) penetration is often considered a significant hurdle in the CNS drug discovery process. On the other hand, BBB penetration may be a liability for many of the non-CNS drug targets, and a clear understanding of the physicochemical and structural differences between CNS and non-CNS drugs may assist both research areas. Because of the numerous and challenging issues in CNS drug discovery and the low success rates, pharmaceutical companies are beginning to deprioritize their drug discovery efforts in the CNS arena. Prompted by these challenges and to aid in the design of high-quality, efficacious CNS compounds, we analyzed the physicochemical property and the chemical structural profiles of 317 CNS and 626 non-CNS oral drugs. The conclusions derived provide an ideal property profile for lead selection and the property modification strategy during the lead optimization process. A list of substructural units that may be useful for CNS drug design was also provided here. A classification tree was also developed to differentiate between CNS drugs and non-CNS oral drugs. The combined analysis provided the following guidelines for designing high-quality CNS drugs: (i) topological molecular polar surface area of <76 Å(2) (25-60 Å(2)), (ii) at least one (one or two, including one aliphatic amine) nitrogen, (iii) fewer than seven (two to four) linear chains outside of rings, (iv) fewer than three (zero or one) polar hydrogen atoms, (v) volume of 740-970 Å(3), (vi) solvent accessible surface area of 460-580 Å(2), and (vii) positive QikProp parameter CNS. The ranges within parentheses may be used during lead optimization. One violation to this proposed profile may be acceptable. The

  15. Crack development through plastic shrinkage in fresh concretes and mortars

    Directory of Open Access Journals (Sweden)

    Aguanell García, M.


    Full Text Available The rate of water evaporation in the exposed surfaces plays an important part in the development of cracks in fresh concretes and mortars before hardening is completed. This rate of evaporation depends on the drying power of the wind sweeping such surfaces as a function of the relative humidity, temperature and speed of the air. After many studies and research work on the subject of plastic cracking, the following axiom has been established: "Plastic shrinkage and cracking of concrete surfaces take place when water evaporates from the surface quicker than it can be replaced through exudation". Once the value of weather parameters are known, the extent of the risk of crack development can be known and preventive steps taken to overcome such risk. Obviously, such steps are all oriented to reducing or stopping evaporation and go from covering surfaces with wet sackcloth or plastic foil, through sprinkling water mists or lowering the concrete temperature, to using film-forming curing products. Another additional measure can be the addition of polypropelene fibers to the concrete while in the mixer, at the rate of 0.9 kg fiber to 1 m3 of concrete.

    En la formación de grietas en morteros y hormigones frescos, antes de finalizar el fraguado, tiene una primordial importancia la velocidad de evaporación del agua de las superficies expuestas al exterior, velocidad que depende del poder desecante de los vientos que barren estas superficies y que está en función de la humedad relativa del aire, de su temperatura y de su velocidad. Después de los múltiples estudios e investigaciones sobre este tema de la formación de las grietas plásticas, se ha llegado a establecer el siguiente axioma: "La retracción plástica y las grietas se producen, en las superficies del hormigón, cuando el agua se evapora de ellas más rápidamente que la que puede ser reemplazada por exudación." Conociendo el valor de los parámetros meteorol

  16. Plastic surgery-myths and realities in developing countries: experience from eastern Nepal. (United States)

    Mishra, Brijesh; Koirala, Robin; Tripathi, Nalini; Shrestha, Kajan Raj; Adhikary, Buddhinath; Shah, Surendra


    B.P. Koirala Institute of Health Sciences, Dharan, Nepal, is the only tertiary care referral centre in the eastern region of Nepal. This paper discusses the author's experience of starting a plastic surgery unit in eastern Nepal regarding need and present status of plastic surgery care in Nepal. Methods. We analyzed the data of patients treated in Plastic surgery unit from July 2007 to February 2009. We did evaluation regarding type of patients, procedures, and their outcome. We also evaluated the limitations and their possible solutions to overcome the barriers to establish effective plastic surgical centers in developing countries. Results. Plastic surgery services were started as a unit in general surgery by single plastic surgeon and one general surgery resident on rotation. Total 848 patients were treated for different plastic-surgery-related conditions, which included 307 acute burn patients 541 general plastic surgery patients. Trauma constituted the major bulk 22%, followed by tumors 20%, while aesthetic surgery operations were only 10.1%. Conclusions. In developing countries, aesthetic procedures constitute very small part of plastic surgery interventions and plastic surgery units are primarily required for reconstructive needs for optimum management of patients.

  17. optimization of the development of a plastic recycling machine

    African Journals Online (AJOL)

    machine and shows that at a speed of 268 rpm the machine functions effectively ... Keywords: recycling machine, plastics-recycling, recyclability/efficiency, throughput/capacity, ...... cycling such as the sorting and cleaning should be efficient so ...

  18. Ionotropic glutamate receptors & CNS disorders. (United States)

    Bowie, Derek


    Disorders of the central nervous system (CNS) are complex disease states that represent a major challenge for modern medicine. Although aetilogy is often unknown, it is established that multiple factors such as defects in genetics and/or epigenetics, the environment as well as imbalance in neurotransmitter receptor systems are all at play in determining an individual's susceptibility to disease. Gene therapy is currently not available and therefore, most conditions are treated with pharmacological agents that modify neurotransmitter receptor signaling. Here, I provide a review of ionotropic glutamate receptors (iGluRs) and the roles they fulfill in numerous CNS disorders. Specifically, I argue that our understanding of iGluRs has reached a critical turning point to permit, for the first time, a comprehensive re-evaluation of their role in the cause of disease. I illustrate this by highlighting how defects in AMPA receptor (AMPAR) trafficking are important to fragile X mental retardation and ectopic expression of kainate receptor (KAR) synapses contributes to the pathology of temporal lobe epilepsy. Finally, I discuss how parallel advances in studies of other neurotransmitter systems may allow pharmacologists to work towards a cure for many CNS disorders rather than developing drugs to treat their symptoms.

  19. Flavonoids and the CNS

    DEFF Research Database (Denmark)

    Jäger, Anna Katharina; Saaby, Lasse


    , sulphatation or glucuronidation. Both the aglycones and the conjugates can pass the blood-brain barrier. In the CNS several flavones bind to the benzodiazepine site on the GABA(A)-receptor resulting in sedation, anxiolytic or anti-convulsive effects. Flavonoids of several classes are inhibitors of monoamine...

  20. Prominin-1 (CD133 defines both stem and non-stem cell populations in CNS development and gliomas.

    Directory of Open Access Journals (Sweden)

    Karl Holmberg Olausson

    Full Text Available Prominin-1 (CD133 is a commonly used cancer stem cell marker in central nervous system (CNS tumors including glioblastoma (GBM. Expression of Prom1 in cancer is thought to parallel expression and function in normal stem cells. Using RNA in situ hybridization and antibody tools capable of detecting multiple isoforms of Prom1, we find evidence for two distinct Prom1 cell populations in mouse brain. Prom1 RNA is first expressed in stem/progenitor cells of the ventricular zone in embryonic brain. Conversely, in adult mouse brain Prom1 RNA is low in SVZ/SGZ stem cell zones but high in a rare but widely distributed cell population (Prom1(hi. Lineage marker analysis reveals Prom1(hi cells are Olig2+Sox2+ glia but Olig1/2 knockout mice lacking oligodendroglia retain Prom1(hi cells. Bromodeoxyuridine labeling identifies Prom1(hi as slow-dividing distributed progenitors distinct from NG2+Olig2+ oligodendrocyte progenitors. In adult human brain, PROM1 cells are rarely positive for OLIG2, but express astroglial markers GFAP and SOX2. Variability of PROM1 expression levels in human GBM and patient-derived xenografts (PDX - from no expression to strong, uniform expression--highlights that PROM1 may not always be associated with or restricted to cancer stem cells. TCGA and PDX data show that high expression of PROM1 correlates with poor overall survival. Within proneural subclass tumors, high PROM1 expression correlates inversely with IDH1 (R132H mutation. These findings support PROM1 as a tumor cell-intrinsic marker related to GBM survival, independent of its stem cell properties, and highlight potentially divergent roles for this protein in normal mouse and human glia.

  1. A 2D analytical multiple slip model for continuum texture development and plastic spin

    NARCIS (Netherlands)

    Giessen, E. van der; Houtte, P. van


    A two-dimensional continuum slip model is presented which accounts in an approximate way for texture development in polycrystalline metals during large strain plastic deformations. The basic kinematic model is that of a rigid-plastic laminated material deforming predominantly by slip along its conta

  2. MyD88 is crucial for the development of a protective CNS immune response to Toxoplasma gondii infection

    Directory of Open Access Journals (Sweden)

    Torres Marbel


    establish a role for MyD88 in T cell-mediated control of T. gondii in the central nervous system (CNS.

  3. We Need 2C but Not 2B: Developing Serotonin 2C (5-HT2C) Receptor Agonists for the Treatment of CNS Disorders. (United States)

    Cheng, Jianjun; Kozikowski, Alan P


    The serotonin 2C (5-HT2C ) receptor has been identified as a potential drug target for the treatment of a variety of central nervous system (CNS) disorders, such as obesity, substance abuse, and schizophrenia. In this Viewpoint article, recent progress in developing selective 5-HT2C agonists for use in treating these disorders is summarized, including the work of our group. Challenges in this field and the possible future directions are described. Homology modeling as a method to predict the binding modes of 5-HT2C ligands to the receptor is also discussed. Compared to known ligands, the improved pharmacological profiles of the 2-phenylcyclopropylmethylamine-based 5-HT2C agonists make them preferred candidates for further studies. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Development of Plastic Scintillator Detector Array Based on SPMT

    Institute of Scientific and Technical Information of China (English)

    SU; Dan; ZHANG; Guo-guang; ZHAO; Xiao; FENG; Shu-qiang; ZHANG; Shuai


    Silicon photoelectric multiplier tuber(SPMT)is made of silicon chip,which can collect weak optical signal(Fig.1).When visible light irradiates SPMT,SPMT can change optical signal to electrical signal.The electrical signal size can be obtained through detecting optical signal size.When putting plastic scintillator before

  5. Interneuron progenitor transplantation to treat CNS dysfunction

    Directory of Open Access Journals (Sweden)

    Muhammad O Chohan


    Full Text Available Due to the inadequacy of endogenous repair mechanisms diseases of the nervous system remain a major challenge to scientists and clinicians. Stem cell based therapy is an exciting and viable strategy that has been shown to ameliorate or even reverse symptoms of CNS dysfunction in preclinical animal models. Of particular importance has been the use of GABAergic interneuron progenitors as a therapeutic strategy. Born in the neurogenic niches of the ventral telencephalon, interneuron progenitors retain their unique capacity to disperse, integrate and induce plasticity in adult host circuitries following transplantation. Here we discuss the potential of interneuron based transplantation strategies as it relates to CNS disease therapeutics. We also discuss mechanisms underlying their therapeutic efficacy and some of the challenges that face the field.

  6. Influence of Shrinkage-Reducing Admixtures on the Development of Plastic Shrinkage Cracks

    DEFF Research Database (Denmark)

    Lura, Pietro; Pease, Bradley Justin; Mazzotta, Guy;


    settlement of the concrete and tensile stress development in the surface of the concrete, which increase the potential for development of plastic shrinkage cracks. Specifically, this paper studies the development of plastic shrinkage cracks in mortars containing a commercially available shrinkage......-reducing admixture (SRA). Mortars containing SRA show fewer and narrower plastic shrinkage cracks than plain mortars when exposed to the same environmental conditions. It is proposed that the lower surface tension of the pore fluid in the mortars containing SRA results in less evaporation, reduced settlement......, reduced capillary tension, and lower crack-inducing stresses at the topmost layer of the mortar....

  7. Neuronal cytoskeleton in synaptic plasticity and regeneration. (United States)

    Gordon-Weeks, Phillip R; Fournier, Alyson E


    During development, dynamic changes in the axonal growth cone and dendrite are necessary for exploratory movements underlying initial axo-dendritic contact and ultimately the formation of a functional synapse. In the adult central nervous system, an impressive degree of plasticity is retained through morphological and molecular rearrangements in the pre- and post-synaptic compartments that underlie the strengthening or weakening of synaptic pathways. Plasticity is regulated by the interplay of permissive and inhibitory extracellular cues, which signal through receptors at the synapse to regulate the closure of critical periods of developmental plasticity as well as by acute changes in plasticity in response to experience and activity in the adult. The molecular underpinnings of synaptic plasticity are actively studied and it is clear that the cytoskeleton is a key substrate for many cues that affect plasticity. Many of the cues that restrict synaptic plasticity exhibit residual activity in the injured adult CNS and restrict regenerative growth by targeting the cytoskeleton. Here, we review some of the latest insights into how cytoskeletal remodeling affects neuronal plasticity and discuss how the cytoskeleton is being targeted in an effort to promote plasticity and repair following traumatic injury in the central nervous system. © 2013 International Society for Neurochemistry.

  8. Development and Properties of Glass Fiber Reinforced Plastics Geogrid

    Institute of Scientific and Technical Information of China (English)

    WANG Qingbiao; ZHANG Cong; WEN Xiaokang; L Rongshan; LIANG Xunmei; LU Shide


    Glassfi ber reinforced plastics geogrid has a wide application in thefi eld of soil reinforcement because of its high strength, good toughness, and resistance to environmental stress, creep resistance and strong stability. In order to get high-powered glassfi ber reinforced plastics geogrid and its mechanical characteristics, the properties and physical mechanical index of geogrid have been got through the study of its raw material, production process and important quality index. The analysis and study have been made to the geogrid’s mechanical properties with loading speed, three-axial compression, temperature tensile test and FLAC3D numerical simulation, thus obtain the mechanical parameters of its displacement time curve, breaking strength and elongation at break. Some conclusions can be drawn as follows: (a) Using glassfi ber materials, knurling and coated projection process, the fracture strength and corrosion resistance of geogrid are greatly improved and the interlocking bite capability of soil is enhanced. (b) The fracture strength of geogrid is related to temperature and loading rate. When the surrounding rock pressure is fixed, the strength and anti-deformation ability of reinforced soil are significantly enhanced with increasing reinforced layers. (c) The pullout test shows the positive correlation between geogrid displacement and action time. (d) As a new reinforced material, the glass fi ber reinforced plastics geogrid is not mature enough in theoretical research and practical experience, so it has become an urgent problem both in theoretical study and practical innovation.

  9. Establishing sustainable design and development for plastic mold under product service system

    National Research Council Canada - National Science Library

    Huang, Yu-Chen; Tu, Jui-Che; Kuo, Kuo-Pin


    Face the energy recovery and environmental concerns and policy, the plastic molds design and develop have to focus on the issues of the lead-free, non-toxic, recyclable, re-manufactured, and integrate...

  10. Plastic Pollution at a Sea Turtle Conservation Area in NE Brazil: Contrasting Developed and Undeveloped Beaches.


    Ivar do Sul, Juliana Assunção; Santos, Isaac Rodrigues dos; Friedrich, Ana Cláudia; Matthiensen, Alexandre; Fillmann, Gilberto


    Sea turtles are highly susceptible to plastic ingestion and entanglement. Beach debris were surveyed along the most important sea turtle nesting beaches in Brazil (Costa dos Coqueiros, Bahia State). No significant differences among developed and undeveloped beaches were observed in terms of total number of items. Local sources (tourism activities) represented 70% of debris on developed beaches, where cigarette butts, straws, paper fragments, soft plastic fragments, and food packaging...

  11. An invertebrate model for CNS drug discovery

    DEFF Research Database (Denmark)

    Al-Qadi, Sonia; Schiøtt, Morten; Hansen, Steen Honoré


    BACKGROUND: ABC efflux transporters at the blood brain barrier (BBB), namely the P-glycoprotein (P-gp), restrain the development of central nervous system (CNS) drugs. Consequently, early screening of CNS drug candidates is pivotal to identify those affected by efflux activity. Therefore, simple,...... barriers. CONCLUSION: Findings suggest a conserved mechanism of brain efflux activity between insects and vertebrates, confirming that this model holds promise for inexpensive and high-throughput screening relative to in vivo models, for CNS drug discovery......., high-throughput and predictive screening models are required. The grasshopper (locust) has been developed as an invertebrate in situ model for BBB permeability assessment, as it has shown similarities to vertebrate models. METHODS: Transcriptome profiling of ABC efflux transporters in the locust brain......BACKGROUND: ABC efflux transporters at the blood brain barrier (BBB), namely the P-glycoprotein (P-gp), restrain the development of central nervous system (CNS) drugs. Consequently, early screening of CNS drug candidates is pivotal to identify those affected by efflux activity. Therefore, simple...

  12. Immune cell trafficking from the brain maintains CNS immune tolerance. (United States)

    Mohammad, Mohammad G; Tsai, Vicky W W; Ruitenberg, Marc J; Hassanpour, Masoud; Li, Hui; Hart, Prue H; Breit, Samuel N; Sawchenko, Paul E; Brown, David A


    In the CNS, no pathway dedicated to immune surveillance has been characterized for preventing the anti-CNS immune responses that develop in autoimmune neuroinflammatory disease. Here, we identified a pathway for immune cells to traffic from the brain that is associated with the rostral migratory stream (RMS), which is a forebrain source of newly generated neurons. Evaluation of fluorescently labeled leukocyte migration in mice revealed that DCs travel via the RMS from the CNS to the cervical LNs (CxLNs), where they present antigen to T cells. Pharmacologic interruption of immune cell traffic with the mononuclear cell-sequestering drug fingolimod influenced anti-CNS T cell responses in the CxLNs and modulated experimental autoimmune encephalomyelitis (EAE) severity in a mouse model of multiple sclerosis (MS). Fingolimod treatment also induced EAE in a disease-resistant transgenic mouse strain by altering DC-mediated Treg functions in CxLNs and disrupting CNS immune tolerance. These data describe an immune cell pathway that originates in the CNS and is capable of dampening anti-CNS immune responses in the periphery. Furthermore, these data provide insight into how fingolimod treatment might exacerbate CNS neuroinflammation in some cases and suggest that focal therapeutic interventions, outside the CNS have the potential to selectively modify anti-CNS immunity.

  13. Blood-brain barrier models and their relevance for a successful development of CNS drug delivery systems: a review. (United States)

    Bicker, Joana; Alves, Gilberto; Fortuna, Ana; Falcão, Amílcar


    During the research and development of new drugs directed at the central nervous system, there is a considerable attrition rate caused by their hampered access to the brain by the blood-brain barrier. Throughout the years, several in vitro models have been developed in an attempt to mimic critical functionalities of the blood-brain barrier and reliably predict the permeability of drug candidates. However, the current challenge lies in developing a model that retains fundamental blood-brain barrier characteristics and simultaneously remains compatible with the high throughput demands of pharmaceutical industries. This review firstly describes the roles of all elements of the neurovascular unit and their influence on drug brain penetration. In vitro models, including non-cell based and cell-based models, and in vivo models are herein presented, with a particular emphasis on their methodological aspects. Lastly, their contribution to the improvement of brain drug delivery strategies and drug transport across the blood-brain barrier is also discussed.

  14. Requirements for an Integrated UAS CNS Architecture (United States)

    Templin, Fred; Jain, Raj; Sheffield, Greg; Taboso, Pedro; Ponchak, Denise


    The National Aeronautics and Space Administration (NASA) Glenn Research Center (GRC) is investigating revolutionary and advanced universal, reliable, always available, cyber secure and affordable Communication, Navigation, Surveillance (CNS) options for all altitudes of UAS operations. In Spring 2015, NASA issued a Call for Proposals under NASA Research Announcements (NRA) NNH15ZEA001N, Amendment 7 Subtopic 2.4. Boeing was selected to conduct a study with the objective to determine the most promising candidate technologies for Unmanned Air Systems (UAS) air-to-air and air-to-ground data exchange and analyze their suitability in a post-NextGen NAS environment. The overall objectives are to develop UAS CNS requirements and then develop architectures that satisfy the requirements for UAS in both controlled and uncontrolled air space. This contract is funded under NASAs Aeronautics Research Mission Directorates (ARMD) Aviation Operations and Safety Program (AOSP) Safe Autonomous Systems Operations (SASO) project and proposes technologies for the Unmanned Air Systems Traffic Management (UTM) service. Communications, Navigation and Surveillance (CNS) requirements must be developed in order to establish a CNS architecture supporting Unmanned Air Systems integration in the National Air Space (UAS in the NAS). These requirements must address cybersecurity, future communications, satellite-based navigation APNT, and scalable surveillance and situational awareness. CNS integration, consolidation and miniaturization requirements are also important to support the explosive growth in small UAS deployment. Air Traffic Management (ATM) must also be accommodated to support critical Command and Control (C2) for Air Traffic Controllers (ATC). This document therefore presents UAS CNS requirements that will guide the architecture.

  15. Convulsant bicuculline modifies CNS muscarinic receptor affinity

    Directory of Open Access Journals (Sweden)

    Rodríguez de Lores Arnaiz Georgina


    Full Text Available Abstract Background Previous work from this laboratory has shown that the administration of the convulsant drug 3-mercaptopropionic acid (MP, a GAD inhibitor, modifies not only GABA synthesis but also binding of the antagonist [3H]-quinuclidinyl benzilate ([3H]-QNB to central muscarinic receptors, an effect due to an increase in affinity without modifications in binding site number. The cholinergic system has been implicated in several experimental epilepsy models and the ability of acetylcholine to regulate neuronal excitability in the neocortex is well known. To study the potential relationship between GABAergic and cholinergic systems with seizure activity, we analyzed the muscarinic receptor after inducing seizure by bicuculline (BIC, known to antagonize the GABA-A postsynaptic receptor subtype. Results We analyzed binding of muscarinic antagonist [3H]-QNB to rat CNS membranes after i.p. administration of BIC at subconvulsant (1.0 mg/kg and convulsant (7.5 mg/kg doses. Subconvulsant BIC dose failed to develop seizures but produced binding alteration in the cerebellum and hippocampus with roughly 40% increase and 10% decrease, respectively. After convulsant BIC dose, which invariably led to generalized tonic-clonic seizures, binding increased 36% and 15% to cerebellar and striatal membranes respectively, but decreased 12% to hippocampal membranes. Kd value was accordingly modified: with the subconvulsant dose it decreased 27% in cerebellum whereas it increased 61% in hippocampus; with the convulsant dose, Kd value decreased 33% in cerebellum but increased 85% in hippocampus. No change in receptor number site was found, and Hill number was invariably close to unity. Conclusion Results indicate dissimilar central nervous system area susceptibility of muscarinic receptor to BIC. Ligand binding was modified not only by a convulsant BIC dose but also by a subconvulsant dose, indicating that changes are not attributable to the seizure process


    Wainford, Richard D; Carmichael, Casey Y; Pascale, Crissey L; Kuwabara, Jill T


    Excess dietary salt-intake is an established cause of hypertension. At present our understanding of the neuro-pathophysiology of salt-sensitive hypertension is limited by a lack of identification of the central nervous system mechanisms that modulate sympathetic outflow and blood pressure in response to dietary salt-intake. We hypothesized that impairment of brain Gαi2 protein-gated signal transduction pathways would result in increased sympathetically mediated renal sodium retention, thus promoting the development of salt-sensitive hypertension. To test this hypothesis, naïve or renal denervated Dahl salt-resistant and Dahl salt-sensitive rats were assigned to receive a continuous intracerebroventricular control scrambled or a targeted Gαi2 oligodeoxynucleotide infusion, and naïve Brown Norway and 8-congenic Dahl salt-sensitive rats, were fed a 21-day normal or high-salt diet. High salt-intake did not alter blood pressure, suppressed plasma norepinephrine, and evoked a site-specific increase in hypothalamic paraventricular nucleus Gαi2 protein levels in naïve Brown-Norway, Dahl salt-resistant and scrambled oligodeoxynucleotide-infused Dahl salt-resistant, but not Dahl salt-sensitive rats. In Dahl salt-resistant rats Gαi2 down-regulation evoked rapid renal nerve-dependent hypertension, sodium retention and sympathoexcitation. In Dahl salt-sensitive rats, Gαi2 down-regulation exacerbated salt-sensitive hypertension via a renal nerve-dependent mechanism. Congenic-8 Dahl salt-sensitive rats exhibited sodium-evoked paraventricular nucleus specific Gαi2 protein up-regulation and attenuated hypertension, sodium retention and global sympathoexcitation compared to Dahl salt-sensitive rats. These data demonstrate that paraventricular nucleus Gαi2 protein-gated pathways represent a conserved central molecular pathway mediating sympathoinhibitory renal-nerve dependent responses evoked to maintain sodium homeostasis and a salt-resistant phenotype. Impairment of this

  17. CNS regulation of appetite. (United States)

    Harrold, Joanne A; Dovey, Terry M; Blundell, John E; Halford, Jason C G


    This article reviews the regulation of appetite from a biopsychological perspective. It considers psychological experiences and peripheral nutritional systems (both episodic and tonic) and addresses their relationship with the CNS networks that process and integrate their input. Whilst such regulatory aspects of obesity focus on homeostatic control mechanisms, in the modern environment hedonic aspects of appetite are also critical. Enhanced knowledge of the complexity of appetite regulation and the mechanisms that sustain obesity indicate the challenge presented by management of the obesity epidemic. Nonetheless, effective control of appetite expression remains a critical therapeutic target for weight management. Currently, strategies which utilise a combination of agents to target both homeostatic and hedonic control mechanisms represent the most promising approaches. This article is part of a Special Issue entitled 'Central Control of Food Intake'. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. Development of Wood-Plastic Composite at Dedan Kimathi University of Technology, Kenya

    Directory of Open Access Journals (Sweden)

    Madaraka F. Mwema


    Full Text Available Disposal of plastics and other solid wastes has been a major problem in Kenya. Most of these wastes can be recycled through various ways and methods to produce new products. Plastics can be combined with sawdust to develop composite materials for applications such as in building. In this project, a wood-plastic composite (WPC was developed from sawdust and plastic solid wastes. The composite bore the advantages of both wood and plastics which can be applied in various sectors including interior design work and in automotive among others, thereby curbing the problem of garbage accumulation in the environment. The project provides eco-friendly solutions by making best use of the available resources (wood and plastic resins thus, finding sustainable solutions to the problem of limited waste dumping sites and deforestation in the country. The composites were made from PP and HDPE thermoplastics and mahogany sawdust obtained from our wood workshop in Dedan Kimathi University. From the tests carried out and results obtained, it was found that, the composite has more advantages than the individual constituent materials. Water absorption test revealed that all the samples took up water though not as much pronounced as for plain sawdust. Additionally, the rate of water reduction was found to be excellent. They took less time to release the absorbed water to the environment meaning that they can be applied in humid or wet environ. The composite samples were easy to machine since they were easily shaped using a handsaw.

  19. Expression of the EGF receptor family members ErbB2, ErbB3, and ErbB4 in germinal zones of the developing brain and in neurosphere cultures containing CNS stem cells. (United States)

    Kornblum, H I; Yanni, D S; Easterday, M C; Seroogy, K B


    The epidermal growth factor receptor family consists of four related tyrosine kinases: the epidermal growth factor receptor (EGF-R or ErbB), ErbB2, ErbB3, and ErbB4. These receptors are capable of extensive cross-activation upon the binding of their ligands - the EGF family of peptides for EGF-R and the neuregulins for ErbB3 and ErbB4. Since EGF-R is expressed by proliferating cells in the central nervous system (CNS), including multipotent CNS stem cells, we examined the expression of ErbB2, ErbB3 and ErbB4 in the germinal epithelia of the developing rat brain using in situ hybridization. ErbB2 and ErbB4 mRNAs were widely distributed within the germinal zones as early as E12. However, as development proceeded, ErbB2 mRNA was mainly present within the layers of cells immediately adjacent to the ventricular surface - the ventricular zone, while ErbB4 mRNA was predominantly expressed by subventricular zone cells, in the regions where these specialized germinal epithelia were present. ErbB3 mRNA distribution within germinal epithelia was more restricted, primarily confined to the diencephalon and rostral midbrain. Cultured neurospheres, which contain CNS stem cells, expressed ErbB2, ErbB4 and, to a lesser extent, ErbB3 protein as demonstrated by Western blot analysis. This expression declined during following differentiation. Heregulin-beta1, a neuregulin, had no effect on the proliferative capacity of neurospheres. Overall, our results indicate that ErbB2, ErbB3 and ErbB4 may play important and distinct roles in the genesis of the CNS. However, our in vitro data do not support a role for neuregulins in proliferation, per se, of CNS stem cells.

  20. Innate Interferons Regulate CNS Inflammation

    DEFF Research Database (Denmark)

    Dieu, Ruthe; Khorooshi, Reza M. H.; Mariboe, Anne

    Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) whose pathology is characterised by demyelination and axonal damage. This results from interplay between CNS-resident glia, infiltrating leukocytes and a plethora of cytokines and chemokines. Currently, ...

  1. A Stability Formula for Plastic-Tipped Bullets Part 1: Motivation and Development of New Formula

    CERN Document Server

    Courtney, Michael W


    Part 1 of this paper describes a modification of the original Miller twist rule for computing gyroscopic bullet stability that is better suited to plastic-tipped bullets. The original Miller twist rule assumes a bullet of constant density, but it also works well for conventional copper (or gilding metal) jacketed lead bullets because the density of copper and lead are sufficiently close. However, the original Miller twist rule significantly underestimates the gyroscopic stability of plastic-tipped bullets, because the density of plastic is much lower than the density of copper and lead. Here, a new amended formula is developed for the gyroscopic stability of plastic-tipped bullets by substituting the length of just the metal portion for the total length in the $(1 + L^2)$ term of the original Miller twist rule. Part 2 describes experimental testing of this new formula on three plastic-tipped bullets. The new formula is relatively accurate for plastic-tipped bullets whose metal portion has nearly uniform densi...

  2. New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs. (United States)

    Sturm, Dominik; Orr, Brent A; Toprak, Umut H; Hovestadt, Volker; Jones, David T W; Capper, David; Sill, Martin; Buchhalter, Ivo; Northcott, Paul A; Leis, Irina; Ryzhova, Marina; Koelsche, Christian; Pfaff, Elke; Allen, Sariah J; Balasubramanian, Gnanaprakash; Worst, Barbara C; Pajtler, Kristian W; Brabetz, Sebastian; Johann, Pascal D; Sahm, Felix; Reimand, Jüri; Mackay, Alan; Carvalho, Diana M; Remke, Marc; Phillips, Joanna J; Perry, Arie; Cowdrey, Cynthia; Drissi, Rachid; Fouladi, Maryam; Giangaspero, Felice; Łastowska, Maria; Grajkowska, Wiesława; Scheurlen, Wolfram; Pietsch, Torsten; Hagel, Christian; Gojo, Johannes; Lötsch, Daniela; Berger, Walter; Slavc, Irene; Haberler, Christine; Jouvet, Anne; Holm, Stefan; Hofer, Silvia; Prinz, Marco; Keohane, Catherine; Fried, Iris; Mawrin, Christian; Scheie, David; Mobley, Bret C; Schniederjan, Matthew J; Santi, Mariarita; Buccoliero, Anna M; Dahiya, Sonika; Kramm, Christof M; von Bueren, André O; von Hoff, Katja; Rutkowski, Stefan; Herold-Mende, Christel; Frühwald, Michael C; Milde, Till; Hasselblatt, Martin; Wesseling, Pieter; Rößler, Jochen; Schüller, Ulrich; Ebinger, Martin; Schittenhelm, Jens; Frank, Stephan; Grobholz, Rainer; Vajtai, Istvan; Hans, Volkmar; Schneppenheim, Reinhard; Zitterbart, Karel; Collins, V Peter; Aronica, Eleonora; Varlet, Pascale; Puget, Stephanie; Dufour, Christelle; Grill, Jacques; Figarella-Branger, Dominique; Wolter, Marietta; Schuhmann, Martin U; Shalaby, Tarek; Grotzer, Michael; van Meter, Timothy; Monoranu, Camelia-Maria; Felsberg, Jörg; Reifenberger, Guido; Snuderl, Matija; Forrester, Lynn Ann; Koster, Jan; Versteeg, Rogier; Volckmann, Richard; van Sluis, Peter; Wolf, Stephan; Mikkelsen, Tom; Gajjar, Amar; Aldape, Kenneth; Moore, Andrew S; Taylor, Michael D; Jones, Chris; Jabado, Nada; Karajannis, Matthias A; Eils, Roland; Schlesner, Matthias; Lichter, Peter; von Deimling, Andreas; Pfister, Stefan M; Ellison, David W; Korshunov, Andrey; Kool, Marcel


    Primitive neuroectodermal tumors of the central nervous system (CNS-PNETs) are highly aggressive, poorly differentiated embryonal tumors occurring predominantly in young children but also affecting adolescents and adults. Herein, we demonstrate that a significant proportion of institutionally diagnosed CNS-PNETs display molecular profiles indistinguishable from those of various other well-defined CNS tumor entities, facilitating diagnosis and appropriate therapy for patients with these tumors. From the remaining fraction of CNS-PNETs, we identify four new CNS tumor entities, each associated with a recurrent genetic alteration and distinct histopathological and clinical features. These new molecular entities, designated "CNS neuroblastoma with FOXR2 activation (CNS NB-FOXR2)," "CNS Ewing sarcoma family tumor with CIC alteration (CNS EFT-CIC)," "CNS high-grade neuroepithelial tumor with MN1 alteration (CNS HGNET-MN1)," and "CNS high-grade neuroepithelial tumor with BCOR alteration (CNS HGNET-BCOR)," will enable meaningful clinical trials and the development of therapeutic strategies for patients affected by poorly differentiated CNS tumors.

  3. Flavonoids and the CNS

    Directory of Open Access Journals (Sweden)

    Anna K. Jäger


    Full Text Available Flavonoids are present in almost all terrestrial plants, where they provide UV-protection and colour. Flavonoids have a fused ring system consisting of an aromatic ring and a benzopyran ring with a phenyl substituent. The flavonoids can be divided into several classes depending on their structure. Flavonoids are present in food and medicinal plants and are thus consumed by humans. They are found in plants as glycosides. Before oral absorption, flavonoids undergo deglycosylation either by lactase phloridzin hydrolase or cytosolic β-glucocidase. The absorbed aglycone is then conjugated by methylation, sulphatation or glucuronidation. Both the aglycones and the conjugates can pass the blood-brain barrier. In the CNS several flavones bind to the benzodiazepine site on the GABAA-receptor resulting in sedation, anxiolytic or anti-convulsive effects. Flavonoids of several classes are inhibitors of monoamine oxidase A or B, thereby working as anti-depressants or to improve the conditions of Parkinson’s patients. Flavanols, flavanones and anthocyanidins have protective effects preventing inflammatory processes leading to nerve injury. Flavonoids seem capable of influencing health and mood.

  4. Development of methods for predicting large crack growth in elastic-plastic work-hardening materials in fully plastic conditions (United States)

    Ford, Hugh; Turner, C. E.; Fenner, R. T.; Curr, R. M.; Ivankovic, A.


    The objects of the first, exploratory, stage of the project were listed as: (1) to make a detailed and critical review of the Boundary Element method as already published and with regard to elastic-plastic fracture mechanics, to assess its potential for handling present concepts in two-dimensional and three-dimensional cases. To this was subsequently added the Finite Volume method and certain aspects of the Finite Element method for comparative purposes; (2) to assess the further steps needed to apply the methods so far developed to the general field, covering a practical range of geometries, work hardening materials, and composites: to consider their application under higher temperature conditions; (3) to re-assess the present stage of development of the energy dissipation rate, crack tip opening angle and J-integral models in relation to the possibilities of producing a unified technology with the previous two items; and (4) to report on the feasibility and promise of this combined approach and, if appropriate, make recommendations for the second stage aimed at developing a generalized crack growth technology for its application to real-life problems.

  5. Development of a highly transparent superamphiphobic plastic sheet by nanoparticle and chemical coating. (United States)

    Wong, Ten It; Wang, Hao; Wang, Fuke; Sin, Sau Leng; Quan, Cheng Gen; Wang, Shi Jie; Zhou, Xiaodong


    A highly transparent superamphiphobic plastic sheet was developed. The plastic sheet polymethyl methacrylate (PMMA) was spin-coated on a glass substrate. Synthesized silica nanoparticles were sprayed on PMMA, followed by fluorosilane drop-coating. The results of contact angle measurements show that the developed PMMA sheet has superamphiphobic properties with high advancing contact angles for water (154°), toluene (139°), and silicone oil (132.9°). The amphiphobicity of the plastic sheet can be tuned by the surface coverage of the silica nanoparticles distributed on the PMMA surface. The surface coverage of the nanoparticles on our PMMA sheet is about 20%, and it agrees with our contact angle calculations for the sheet with and without nanoparticles.


    Energy Technology Data Exchange (ETDEWEB)

    Hitesh Patadia


    The report presents a comprehensive summary of the project status related to the development of a permanent mechanical repair fitting intended to be installed on damaged PE mains under blowing gas conditions. Specifically, the product definition has been developed taking into account relevant codes and standards and industry input. A conceptual design for the mechanical repair sleeve has been developed which meets the product definition.

  7. The Gut-Brain Axis, BDNF, NMDA and CNS Disorders. (United States)

    Maqsood, Raeesah; Stone, Trevor W


    Gastro-intestinal (GI) microbiota and the 'gut-brain axis' are proving to be increasingly relevant to early brain development and the emergence of psychiatric disorders. This review focuses on the influence of the GI tract on Brain-Derived Neurotrophic Factor (BDNF) and its relationship with receptors for N-methyl-D-aspartate (NMDAR), as these are believed to be involved in synaptic plasticity and cognitive function. NMDAR may be associated with the development of schizophrenia and a range of other psychopathologies including neurodegenerative disorders, depression and dementias. An analysis of the routes and mechanisms by which the GI microbiota contribute to the pathophysiology of BDNF-induced NMDAR dysfunction could yield new insights relevant to developing novel therapeutics for schizophrenia and related disorders. In the absence of GI microbes, central BDNF levels are reduced and this inhibits the maintenance of NMDAR production. A reduction of NMDAR input onto GABA inhibitory interneurons causes disinhibition of glutamatergic output which disrupts the central signal-to-noise ratio and leads to aberrant synaptic behaviour and cognitive deficits. Gut microbiota can modulate BDNF function in the CNS, via changes in neurotransmitter function by affecting modulatory mechanisms such as the kynurenine pathway, or by changes in the availability and actions of short chain fatty acids (SCFAs) in the brain. Interrupting these cycles by inducing changes in the gut microbiota using probiotics, prebiotics or antimicrobial drugs has been found promising as a preventative or therapeutic measure to counteract behavioural deficits and these may be useful to supplement the actions of drugs in the treatment of CNS disorders.

  8. A dramatic increase of C1q protein in the CNS during normal aging. (United States)

    Stephan, Alexander H; Madison, Daniel V; Mateos, José María; Fraser, Deborah A; Lovelett, Emilie A; Coutellier, Laurence; Kim, Leo; Tsai, Hui-Hsin; Huang, Eric J; Rowitch, David H; Berns, Dominic S; Tenner, Andrea J; Shamloo, Mehrdad; Barres, Ben A


    The decline of cognitive function has emerged as one of the greatest health threats of old age. Age-related cognitive decline is caused by an impacted neuronal circuitry, yet the molecular mechanisms responsible are unknown. C1q, the initiating protein of the classical complement cascade and powerful effector of the peripheral immune response, mediates synapse elimination in the developing CNS. Here we show that C1q protein levels dramatically increase in the normal aging mouse and human brain, by as much as 300-fold. This increase was predominantly localized in close proximity to synapses and occurred earliest and most dramatically in certain regions of the brain, including some but not all regions known to be selectively vulnerable in neurodegenerative diseases, i.e., the hippocampus, substantia nigra, and piriform cortex. C1q-deficient mice exhibited enhanced synaptic plasticity in the adult and reorganization of the circuitry in the aging hippocampal dentate gyrus. Moreover, aged C1q-deficient mice exhibited significantly less cognitive and memory decline in certain hippocampus-dependent behavior tests compared with their wild-type littermates. Unlike in the developing CNS, the complement cascade effector C3 was only present at very low levels in the adult and aging brain. In addition, the aging-dependent effect of C1q on the hippocampal circuitry was independent of C3 and unaccompanied by detectable synapse loss, providing evidence for a novel, complement- and synapse elimination-independent role for C1q in CNS aging.

  9. Development of flexible plasmonic plastic sensor using nanograting textured laminating film (United States)

    Kumari, Sudha; Mohapatra, Saswat; Moirangthem, Rakesh S.


    The work presented in this paper describes the development of a cost-effective, flexible plasmonic plastic sensor using gold-coated nanograting nanoimprinted on a laminating plastic. The fabrication of plasmonic plastic sensor involved the transfer of nanograting pattern from polydimethylsiloxane (PDMS) polymer stamp to laminating plastic via thermal nanoimprint lithography, and subsequent gold film deposition. Gold-coated nanograting sample acted as a plasmonic chip, which exhibited surface plasmon resonance (SPR) mode in reflectance spectra under the white light illumination. The theoretical calculation was performed to study and analyze the excited SPR mode on the plasmonic chip. Further, the bulk refractive index sensitivity was demonstrated with respect to changing surrounding dielectric medium giving a value about 800  ±  27 nm/RIU (refractive index unit). In addition, the surface binding sensitivity upon adsorption of bovine serum albumin protein on the sensor surface was approximately 4.605 nm/(ng/mm2).We believe that our proposed low-cost plastic based plasmonic sensing device could be a potential candidate for the label-free and high-throughput screening of biological molecules.

  10. Migration of plasticizers from PVC medical devices: Development of an infusion model. (United States)

    Bernard, L; Cueff, R; Chagnon, Mc; Abdoulouhab, F; Décaudin, B; Breysse, C; Kauffmann, S; Cosserant, B; Souweine, B; Sautou, V


    Alternatives to DEHP plasticizers are used in various PVC medical devices (MD) for infusion. As they are able to migrate from these MDs into infused solutions, they may come into contact with patient. Different and specific clinical parameters influence their migration in at-risk situations such as infusion. In contrast to the regulations for Food Contact Materials (MCDA), there is currently no acceptable migration limits for the use of these plasticizers in clinical situations. In order to assess their migration, and thus control the risks linked to these MDs, we developed a migration model for the plasticizers in MDs. To this end, we applied a cross-disciplinary methodological process similar to that used in the food-processing industry, taking into account the MDs' conditions of use in clinical practice. The simulation model is simple and includes the following conditions: MD should be tested with a dynamic method that respects our established clinical assumption (2 L of infused solutions via 13 dm(2) of plasticized PVC), at a temperature of 25 °C and during 24 h of contact, using a 50/50 (v/v) ethanol/water simulant. This model could be proposed as a tool for the safety evaluation of the patients' exposure risk to plasticizers from PVC medical devices for infusions.

  11. Development of high plasticity Al-Si alloy and its casting process

    Institute of Scientific and Technical Information of China (English)

    郭国文; 李元元; 陈维平; 张大童; 龙雁


    Aiming to meet the challenge of the shape complexity and high plasticity demanded for the upper connective plate(UCP) in motorcycle, a high plasticity Al-Si alloy named HGZL-02 was developed by optimizing the chemical composition and casting process. Premium UCP castings were obtained by using optimized casting process. Results show that fine and dense microstructure are obtained in the UCP castings. An average of 224MPa in ultimate tensile strength, 149MPa in yield strength and 13.2% in elongation are achieved for T6 heat-treated UPS castings.

  12. Development of a Plastic Melt Waste Compactor for Space Missions Experiments and Prototype Design (United States)

    Pace, Gregory; Wignarajah, Kanapathipillai; Pisharody, Suresh; Fisher, John


    This paper describes development at NASA Ames Research Center of a heat melt compactor that can be used on both near term and far term missions. Experiments have been performed to characterize the behavior of composite wastes that are representative of the types of wastes produced on current and previous space missions such as International Space Station, Space Shuttle, MIR and Skylab. Experiments were conducted to characterize the volume reduction, bonding, encapsulation and biological stability of the waste composite and also to investigate other key design issues such as plastic extrusion, noxious off-gassing and removal of the of the plastic waste product from the processor. The experiments provided the data needed to design a prototype plastic melt waste processor, a description of which is included in the paper.


    DEFF Research Database (Denmark)

    Carmignato, Simone; De Chiffre, Leonardo; Fisker, Rune


    and plastic parts. A first prototype of the novel measuring system has been developed, using laser triangulation. The system, besides ensuring the automatic reconstruction of complete surface models, has been designed to guarantee user-friendliness, versatility, reliability and speed. The paper focuses mainly...... dimensional measurements with adequate accuracy for most industrial requirements....

  14. Plasticity in the Developing Brain: Intellectual, Language and Academic Functions in Children with Ischaemic Perinatal Stroke (United States)

    Ballantyne, Angela O.; Spilkin, Amy M.; Hesselink, John; Trauner, Doris A.


    The developing brain has the capacity for a great deal of plasticity. A number of investigators have demonstrated that intellectual and language skills may be in the normal range in children following unilateral perinatal stroke. Questions have been raised, however, about whether these skills can be maintained at the same level as the brain…

  15. Development of Integrated Simulation System for Plastic Injection Molding

    Institute of Scientific and Technical Information of China (English)

    CHENGXue-wen; LIDe-qun; ZHOUHua-min


    Numerical simulation of injection molding have had success in predicting the behavior of polymer melt in extremely complicated geometries. Most of the current numerical solutions are based on finite-element/finite-difference/boundary-element/volume-control methods and the surface model. This paper discusses the development of an integrated CAE system for injection molding in detail, and presents the mathematics for numerical simulation of filling, packing,cooling, stress and warpage in injection molding. The developed system named as HsCAE3D is introduced at the end.

  16. Environmental Causes of CNS Maldevelopment

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap


    Full Text Available Developmental processes and the effects of toxic agents in the environment that alter CNS growth and maturation are reviewed by a researcher in the Department of OB/GYN, University of Rochester Medical Center, Rochester, NY.

  17. Actuarial risk of isolated CNS involvement in Ewing's sarcoma following prophylactic cranial irradiation and intrathecal methotrexate

    Energy Technology Data Exchange (ETDEWEB)

    Trigg, M.E.; Makuch, R.; Glaubiger, D.


    Records of 154 patients with Ewing's sarcoma treated at the National Cancer Institute were reviewed to assess the incidence and risk of developing isolated central nervous system (CNS) Ewing's sarcoma. Sixty-two of the 154 patients had received CNS irradiation and intrathecal (i.t.) methotrexate as part of their initial therapy to prevent the occurrence of isolated CNS Ewing's sarcoma. The risk of developing isolate CNS Ewing's sarcoma was greatest within the first two years after diagnosis and was approximately 10%. The overall risk of CNS recurrence in the group of patients receiving DNS treatment was similar to the group receiving no therapy directed to the CNS. The occurrence of isolated CNS involvement was not prevented by the use of CNS irradiation and i.t. methotrexate. Because of a lack of efficacy to the CNS irradiation regimen, current treatment regimens do not include therapy directed to CNS.

  18. Design and development of a laminated glass-plastic Fresnel lens for point focus photovoltaic systems

    Energy Technology Data Exchange (ETDEWEB)

    Matalon, L. A.


    The design and development of a laminated glass-plastic Fresnel lens for point focus photovoltaic systems use is described. The objective of this development was to examine the feasibility of producing lenses with a cost effectiveness superior to that of lenses made by casting of acrylic. The procedure used in executing this development, the method used in cost effectiveness evaluation, results obtained and recommendations for further work are presented.

  19. Cellular Plasticity within the Pancreas— Lessons Learned from Development (United States)

    Puri, Sapna; Hebrok, Matthias


    The pancreas has been the subject of intense research due to the debilitating diseases that result from its dysfunction. In this review, we summarize current understanding of the critical tissue interactions and intracellular regulatory events that take place during formation of the pancreas from a small cluster of cells in the foregut domain of the mouse embryo. Importantly, an understanding of principles that govern the development of this organ has equipped us with the means to manipulate both embryonic and differentiated adult cells in the context of regenerative medicine. The emerging area of lineage modulation within the adult pancreas is of particular interest, and this review summarizes recent findings that exemplify how lessons learned from development are being applied to reveal the potential of fully differentiated cells to change fate. PMID:20230744

  20. Cellular plasticity within the pancreas--lessons learned from development. (United States)

    Puri, Sapna; Hebrok, Matthias


    The pancreas has been the subject of intense research due to the debilitating diseases that result from its dysfunction. In this review, we summarize current understanding of the critical tissue interactions and intracellular regulatory events that take place during formation of the pancreas from a small cluster of cells in the foregut domain of the mouse embryo. Importantly, an understanding of principles that govern the development of this organ has equipped us with the means to manipulate both embryonic and differentiated adult cells in the context of regenerative medicine. The emerging area of lineage modulation within the adult pancreas is of particular interest, and this review summarizes recent findings that exemplify how lessons learned from development are being applied to reveal the potential of fully differentiated cells to change fate.

  1. Selective processes in development: implications for the costs and benefits of phenotypic plasticity. (United States)

    Snell-Rood, Emilie C


    Adaptive phenotypic plasticity, the ability of a genotype to develop a phenotype appropriate to the local environment, allows organisms to cope with environmental variation and has implications for predicting how organisms will respond to rapid, human-induced environmental change. This review focuses on the importance of developmental selection, broadly defined as a developmental process that involves the sampling of a range of phenotypes and feedback from the environment reinforcing high-performing phenotypes. I hypothesize that understanding the degree to which developmental selection underlies plasticity is key to predicting the costs, benefits, and consequences of plasticity. First, I review examples that illustrate that elements of developmental selection are common across the development of many different traits, from physiology and immunity to circulation and behavior. Second, I argue that developmental selection, relative to a fixed strategy or determinate (switch) mechanisms of plasticity, increases the probability that an individual will develop a phenotype best matched to the local environment. However, the exploration and environmental feedback associated with developmental selection is costly in terms of time, energy, and predation risk, resulting in major changes in life history such as increased duration of development and greater investment in individual offspring. Third, I discuss implications of developmental selection as a mechanism of plasticity, from predicting adaptive responses to novel environments to understanding conditions under which genetic assimilation may fuel diversification. Finally, I outline exciting areas of future research, in particular exploring costs of selective processes in the development of traits outside of behavior and modeling developmental selection and evolution in novel environments.

  2. Plastics Technology. (United States)

    Barker, Tommy G.

    This curriculum guide is designed to assist junior high schools industrial arts teachers in planning new courses and revising existing courses in plastics technology. Addressed in the individual units of the guide are the following topics: introduction to production technology; history and development of plastics; safety; youth leadership,…

  3. Plasticity during childhood and adolescence: innovative approaches to investigating neurocognitive development. (United States)

    Cohen Kadosh, Kathrin; Linden, David E J; Lau, Jennifer Y F


    Adolescence is a period of profound change, which holds substantial developmental milestones, but also unique challenges to the individual. In this opinion paper, we highlight the potential of combining two recently developed behavioural and neural training techniques (cognitive bias modification and functional magnetic neuroimaging-based neurofeedback) into a research approach that could help make the most of increased levels of plasticity during childhood and adolescence. We discuss how this powerful combination could be used to explore changing brain-behaviour relationships throughout development in the context of emotion processing, a cognitive domain that exhibits continuous development throughout the second decade of life. By targeting both behaviour and brain response, we would also be in an excellent position to define sensible time windows for enhancing plasticity, thereby allowing for targeted intervention approaches that can help improve emotion processing in both typically and atypically developing populations.

  4. Considerations for an Integrated UAS CNS Architecture (United States)

    Templin, Fred L.; Jain, Raj; Sheffield, Greg; Taboso-Bellesteros, Pedro; Ponchak, Denise


    The National Aeronautics and Space Administration (NASA) Glenn Research Center (GRC) is investigating revolutionary and advanced universal, reliable, always available, cyber secure and affordable Communication, Navigation, Surveillance (CNS) options for all altitudes of UAS operations. In Spring 2015, NASA issued a Call for Proposals under NASA Research Announcements (NRA) NNH15ZEA001N, Amendment 7 Subtopic 2.4. Boeing was selected to conduct a study with the objective to determine the most promising candidate technologies for Unmanned Air Systems (UAS) air-to-air and air-to-ground data exchange and analyze their suitability in a post-NextGen NAS environment. The overall objectives are to develop UAS CNS requirements and then develop architectures that satisfy the requirements for UAS in both controlled and uncontrolled air space. This contract is funded under NASAs Aeronautics Research Mission Directorates (ARMD) Aviation Operations and Safety Program (AOSP) Safe Autonomous Systems Operations (SASO) project and proposes technologies for the Unmanned Air Systems Traffic Management (UTM) service.There is a need for accommodating large-scale populations of Unmanned Air Systems (UAS) in the national air space. Scale obviously impacts capacity planning for Communication, Navigation, and Surveillance (CNS) technologies. For example, can wireless communications data links provide the necessary capacity for accommodating millions of small UASs (sUAS) nationwide? Does the communications network provide sufficient Internet Protocol (IP) address space to allow air traffic control to securely address both UAS teams as a whole as well as individual UAS within each team? Can navigation and surveillance approaches assure safe route planning and safe separation of vehicles even in crowded skies?Our objective is to identify revolutionary and advanced CNS alternatives supporting UASs operating at all altitudes and in all airspace while accurately navigating in the absence of

  5. Development of plastic heat exchangers for ocean thermal energy conversion. Final report, August 1976--December 1978

    Energy Technology Data Exchange (ETDEWEB)

    Hart, G.K.; Lee, C.O.; Latour, S.R.


    Materials and processes have been selected and design information obtained for plastic ocean thermal energy conversion (OTEC) heat exchangers as the result of a program comprising five types of laboratory experiments. Tests to evaluate the chemical resistance of seven commercially available thermoplastics to sea water and several possible working fluids were conducted with emphasis placed on compatibility with ammonia. Environmental rupture tests involving exposure of stressed specimens to sea water or liquid ammonia indicated that the high density polyethylene (HDPE) is the best suited candidate and produced an extrapolated 100,000 hour failure stress of 1060 psi for HDPE. Long term durability tests of extruded HDPE plate-tube panel confirmed that plastic heat transfer surface is mechanically reliable in an OTEC environment. Thermal conductivity measurements of acetylene black filled HDPE indicated that conductivity may be increased by 50% with a 35% by weight filler loading. The permeability coefficient measured for liquid ammonia through HDPE was higher than previous estimates. Test showed that the rate can be significantly reduced by sulfonation of HDPE. A review of biofouling mechanisms revealed that the permeable nature of the plastic heat exchanger surface may be used to control primary biofouling form formation by allowing incorporation of non-toxic organic repellents into the plastic. A preliminary design and fabrication development program suggests that construction of an ammonia condenser test unit is feasible using currently available materials and manufacturing techniques.

  6. Effects of plasticization and shear stress on phase structure development and properties of soy protein blends. (United States)

    Chen, Feng; Zhang, Jinwen


    In this study, soy protein concentrate (SPC) was used as a plastic component to blend with poly(butylene adipate-co-terephthalate) (PBAT). Effects of SPC plasticization and blend composition on its deformation during mixing were studied in detail. Influence of using water as the major plasticizer and glycerol as the co-plasticizer on the deformation of the SPC phase during mixing was explored. The effect of shear stress, as affected by SPC loading level, on the phase structure of SPC in the blends was also investigated. Quantitative analysis of the aspect ratio of SPC particles was conducted by using ImageJ software, and an empirical model predicting the formation of percolated structure was applied. The experimental results and the model prediction showed a fairly good agreement. The experimental results and statistic analysis suggest that both SPC loading level and its water content prior to compounding had significant influences on development of the SPC phase structure and were correlated in determining the morphological structures of the resulting blends. Consequently, physical and mechanical properties of the blends greatly depended on the phase morphology and PBAT/SPC ratio of the blends.

  7. A rare case of CNS tuberculosis with pregnancy

    Directory of Open Access Journals (Sweden)

    Sanjay Singh


    Full Text Available Whereas pelvic tuberculosis leading to infertility is quite common in female population of developing countries, Central Nervous System (CNS tuberculosis (TB with pregnancy is a rare entity. Most of the information on this subject is based on sporadic case reports only. Most of the earlier reports suggest very high adverse outcome of CNS Tuberculosis in pregnancy. We are presenting a case of CNS Tuberculosis which was diagnosed timely and managed appropriately in our institute with a favourable outcome, thus highlighting the importance of early diagnosis and treatment. [Int J Reprod Contracept Obstet Gynecol 2015; 4(3.000: 911-914

  8. Chondroitin sulfate proteogly can and the plasticity of central nervous system%硫酸软骨素蛋白多糖与中枢神经系统可塑性

    Institute of Scientific and Technical Information of China (English)

    陈歆然; 余剑


    硫酸软骨素蛋白多糖(chondroitin sulfate proteoglycan,CSPG)是在发育和成熟的中枢神经系统(central nervous syste,CNS)中广泛表达的一组细胞外基质分子,在胚胎CNS发育和成年期CNS可塑性中发挥着重要作用.CSPG作为一种主要的细胞外抑制性成分,可影响CNS损伤后轴突再生和神经功能恢复.%Chondroitin sulfate proteoglycan (CSPG) is a group of extracellular matrix molecules expressed widely in the developing and mature central nervous system (CNS).They play an important role during embryonic CNS development and adult CNS plasticity.As a major extracellular inhibitory compound,CSPG can affect the axon regeneration and neurological recovery after CNS injury.

  9. VIIP: Central Nervous System (CNS) Modeling (United States)

    Vera, Jerry; Mulugeta, Lealem; Nelson, Emily; Raykin, Julia; Feola, Andrew; Gleason, Rudy; Samuels, Brian; Ethier, C. Ross; Myers, Jerry


    Current long-duration missions to the International Space Station and future exploration-class missions beyond low-Earth orbit expose astronauts to increased risk of Visual Impairment and Intracranial Pressure (VIIP) syndrome. It has been hypothesized that the headward shift of cerebrospinal fluid (CSF) and blood in microgravity may cause significant elevation of intracranial pressure (ICP), which in turn may then induce VIIP syndrome through interaction with various biomechanical pathways. However, there is insufficient evidence to confirm this hypothesis. In this light, we are developing lumped-parameter models of fluid transport in the central nervous system (CNS) as a means to simulate the influence of microgravity on ICP. The CNS models will also be used in concert with the lumped parameter and finite element models of the eye described in the related IWS works submitted by Nelson et al., Feola et al. and Ethier et al.

  10. microRNAs in CNS disorders

    DEFF Research Database (Denmark)

    Kocerha, Jannet; Kauppinen, Sakari; Wahlestedt, Claes


    In recent years, there has been a shift in the conventional paradigms for transcriptional and translational regulation as extensive sequencing efforts have yielded new insights into the landscape of the human genome and transcriptome. Hundreds of non-coding regulatory RNA molecules called microRNAs...... (miRNAs) have been identified in the mammalian central nervous system (CNS) and are reported to mediate pivotal roles in many aspects of neuronal functions. Disruption of miRNA-based post-transcriptional regulation has been implicated in a range of CNS disorders as one miRNA is predicted to impact...... the expression of numerous downstream mRNA targets. The intricate molecular networks mediated by an miRNA form a robust mechanism for rapid and potent responses to cellular events throughout the development of the human brain. Recent studies have identified a molecular and ultimately pathogenic role for a subset...

  11. Evolution and plasticity of anuran larval development in response to desiccation. A comparative analysis. (United States)

    Richter-Boix, Alex; Tejedo, Miguel; Rezende, Enrico L


    Anurans breed in a variety of aquatic habitats with contrasting levels of desiccation risk, which may result in selection for faster development during larval stages. Previous studies suggest that species in ephemeral ponds reduce their developmental times to minimize desiccation risks, although it is not clear how variation in desiccation risk affects developmental strategies in different species. Employing a comparative phylogenetic approach including data from published and unpublished studies encompassing 62 observations across 30 species, we tested if species breeding in ephemeral ponds (High risk) develop faster than those from permanent ponds (Low risk) and/or show increased developmental plasticity in response to drying conditions. Our analyses support shorter developmental times in High risk, primarily by decreasing body mass at metamorphosis. Plasticity in developmental times was small and did not differ between groups. However, accelerated development in High risk species generally resulted in reduced sizes at metamorphosis, while some Low risk species were able compensate this effect by increasing mean growth rates. Taken together, our results suggest that plastic responses in species breeding in ephemeral ponds are constrained by a general trade-off between development and growth rates.

  12. Ovarian actinomycosis developed during the use of a plastic intrauterine contraceptive device. (United States)

    Csapó, Z; Csömör, S; Zámbó, Z; Fedák, L; Vilics, G; Németh, F


    The case of a primary ovarian actinomycosis developed during the use of a Szontágh--Szereday type plastic IUD is presented. After a radical operation the patient was discharged in a good condition but 40 days later had to be readmitted because of a pelvic and abdominal wall abscess. After local surgery and massive penicillin treatment she is free of complaints. It is assumed that the IUD had a pathomechanical role.

  13. Endocannabinoids and synaptic function in the CNS. (United States)

    Hashimotodani, Yuki; Ohno-Shosaku, Takako; Kano, Masanobu


    Marijuana affects neural functions through the binding of its active component (Delta(9)-THC) to cannabinoid receptors in the CNS. Recent studies have elucidated that endogenous ligands for cannabinoid receptors, endocannabinoids, serve as retrograde messengers at central synapses. Endocannabinoids are produced on demand in activity-dependent manners and released from postsynaptic neurons. The released endocannabinoids travel backward across the synapse, activate presynaptic CB1 cannabinoid receptors, and modulate presynaptic functions. Retrograde endocannabinoid signaling is crucial for certain forms of short-term and long-term synaptic plasticity at excitatory or inhibitory synapses in many brain regions, and thereby contributes to various aspects of brain function including learning and memory. Molecular identities of the CB1 receptor and enzymes involved in production and degradation of endocannabinoids have been elucidated. Anatomical studies have demonstrated unique distributions of these molecules around synapses, which provide morphological bases for the roles of endocannabinoids as retrograde messengers. CB1-knockout mice exhibit various behavioral abnormalities and multiple defects in synaptic plasticity, supporting the notion that endocannabinoid signaling is involved in various aspects of neural function. In this review article, the authors describe molecular mechanisms of the endocannabinoid-mediated synaptic modulation and its possible physiological significance.

  14. Theoretical Development of an Orthotropic Elasto-Plastic Generalized Composite Material Model (United States)

    Goldberg, Robert K.; Carney, Kelly S.; DuBois, Paul; Hoffarth, Canio; Harrington, Joseph; Subramanian, Rajan; Blankenhorn, Gunther


    The need for accurate material models to simulate the deformation, damage and failure of polymer matrix composites is becoming critical as these materials are gaining increased usage in the aerospace and automotive industries. While there are several composite material models currently available within LS-DYNA (Registered), there are several features that have been identified that could improve the predictive capability of a composite model. To address these needs, a combined plasticity and damage model suitable for use with both solid and shell elements is being developed and is being implemented into LS-DYNA as MAT_213. A key feature of the improved material model is the use of tabulated stress-strain data in a variety of coordinate directions to fully define the stress-strain response of the material. To date, the model development efforts have focused on creating the plasticity portion of the model. The Tsai-Wu composite failure model has been generalized and extended to a strain-hardening based orthotropic material model with a non-associative flow rule. The coefficients of the yield function, and the stresses to be used in both the yield function and the flow rule, are computed based on the input stress-strain curves using the effective plastic strain as the tracking variable. The coefficients in the flow rule are computed based on the obtained stress-strain data. The developed material model is suitable for implementation within LS-DYNA for use in analyzing the nonlinear response of polymer composites.

  15. The development of strain anisotropy during plastic deformation of an aluminium polycrystal

    Energy Technology Data Exchange (ETDEWEB)

    Korsunsky, A.M. [Oxford Univ. (United Kingdom). Dept. of Engineering Science; Daymond, M.R. [ISIS Facility, Rutherford Appleton Lab., Chilton, Oxon (United Kingdom); Wells, K.E. [Dept. of Mechanical, Materials and Mfg. Engineering, Univ. of Newcastle (United Kingdom)


    To measure internal strains in an Al MMC, time-of-flight (TOF) neutron diffraction was used on the ENGIN instrument at ISIS, RAL, in Oxfordshire, and a monochromated X-ray beam was employed on the BM16 beamline at the ESRF in Grenoble. The development of intergranular stresses between groups of grains possessing certain crystallographic orientations was studied using diffraction of penetrating radiation. Due to aluminium's highly isotropic elastic modulus, the variation of measured strains in the alloy matrix with orientation can be attributed to the anisotropy of the crystal yield surface and plastic flow parameters. A simple illustrative model is presented which explains the observed correlation between the amount of plastic strain (PS) and the measured anisotropy strain (AS) values. In particular, the model explains why a linear relationship is observed between AS and PS for low strain values, and how saturation of AS sets in at higher imposed PS levels. (orig.)

  16. Metabolic plasticity during mammalian development is directionally dependent on early nutritional status. (United States)

    Gluckman, Peter D; Lillycrop, Karen A; Vickers, Mark H; Pleasants, Anthony B; Phillips, Emma S; Beedle, Alan S; Burdge, Graham C; Hanson, Mark A


    Developmental plasticity in response to environmental cues can take the form of polyphenism, as for the discrete morphs of some insects, or of an apparently continuous spectrum of phenotype, as for most mammalian traits. The metabolic phenotype of adult rats, including the propensity to obesity, hyperinsulinemia, and hyperphagia, shows plasticity in response to prenatal nutrition and to neonatal administration of the adipokine leptin. Here, we report that the effects of neonatal leptin on hepatic gene expression and epigenetic status in adulthood are directionally dependent on the animal's nutritional status in utero. These results demonstrate that, during mammalian development, the direction of the response to one cue can be determined by previous exposure to another, suggesting the potential for a discontinuous distribution of environmentally induced phenotypes, analogous to the phenomenon of polyphenism.

  17. Modeling texture development during cold rolling of IF steel by crystal plasticity finite element method

    Institute of Scientific and Technical Information of China (English)


    With the consideration of slip deformation mechanism and various slip systems of body centered cubic (BCC) metals,Taylor-type and finite element polycrystai models were embedded into the commercial finite element code ABAQUS to realize crystal plasticity finte element modeling,based on the rate dependent crystal constitutive equations.Initial orientations measured by electron backscatter diffraction (EBSD) were directly input into the crystal plasticity finite element model to simulate the development of rolling texture of interstitial-flee steel (IF steel) at various reductions.The modeled results show a good agreement with the experimental results.With increasing reduction,the predicted and experimental rolling textures tend to sharper,and the results simulated by the Taylor-type model are stronger than those simulated by finite element model.Conclusions are obtained that rolling textures calculated with 48 {110}+{ 112}+{123} slip systems are more approximate to EBSD results.


    Directory of Open Access Journals (Sweden)



    Full Text Available Development of small injection moulding machine for forming small plastic articles in small-scale industries was studied. This work which entailed design, construction and test small injection moulding machine that was capable of forming small plastic articles by injecting molten resins into a closed, cooled mould, where it solidifies to give the desired products was developed. The machine was designed and constructed to work as a prototype for producing very small plastic components. Design concept, operation, and assembly of components parts were made. Also, working drawings and materials selection were made based on calculations of the diameter of injection plunger, number of teeth required for the plunger rack and spur gear, the angular velocity, number of revolution, torque and power obtained from the electric motor selected and the leverage on the handle of the machine. The machine parts/components were then assembled in line with the designed made, thereafter the constructed machine was tested using high density polyethylene and master batch. The results obtained from the test were satisfactory.

  19. Genetic models for CNS inflammation

    DEFF Research Database (Denmark)

    Owens, T; Wekerle, H; Antel, J


    The use of transgenic technology to over-express or prevent expression of genes encoding molecules related to inflammation has allowed direct examination of their role in experimental disease. This article reviews transgenic and knockout models of CNS demyelinating disease, focusing primarily on ...

  20. Implementation of Lumped Plasticity Models and Developments in an Object Oriented Nonlinear Finite Element Code (United States)

    Segura, Christopher L.

    Numerical simulation tools capable of modeling nonlinear material and geometric behavior are important to structural engineers concerned with approximating the strength and deformation capacity of a structure. While structures are typically designed to behave linear elastic when subjected to building code design loads, exceedance of the linear elastic range is often an important consideration, especially with regards to structural response during hazard level events (i.e. earthquakes, hurricanes, floods), where collapse prevention is the primary goal. This thesis addresses developments made to Mercury, a nonlinear finite element program developed in MATLAB for numerical simulation and in C++ for real time hybrid simulation. Developments include the addition of three new constitutive models to extend Mercury's lumped plasticity modeling capabilities, a constitutive driver tool for testing and implementing Mercury constitutive models, and Mercury pre and post-processing tools. Mercury has been developed as a tool for transient analysis of distributed plasticity models, offering accurate nonlinear results on the material level, element level, and structural level. When only structural level response is desired (collapse prevention), obtaining material level results leads to unnecessarily lengthy computational time. To address this issue in Mercury, lumped plasticity capabilities are developed by implementing two lumped plasticity flexural response constitutive models and a column shear failure constitutive model. The models are chosen for implementation to address two critical issues evident in structural testing: column shear failure and strength and stiffness degradation under reverse cyclic loading. These tools make it possible to model post-peak behavior, capture strength and stiffness degradation, and predict global collapse. During the implementation process, a need was identified to create a simple program, separate from Mercury, to simplify the process of

  1. Simultaneous imaging of structural plasticity and calcium dynamics in developing dendrites and axons. (United States)

    Siegel, Friederike; Lohmann, Christian


    During nervous system development, the formation of synapses between pre- and postsynaptic neurons is a remarkably specific process. Both structural and functional plasticity are critical for the selection of synaptic partners and for the establishment and maturation of synapses. To unravel the respective contributions of structural and functional mechanisms as well as their interactions during synaptogenesis, it is important to directly observe structural changes and functional signaling simultaneously. Here, we present an imaging approach to simultaneously follow changes in structure and function. Differential labeling of individual cells and the neuronal network with distinct dyes allows the study of structural plasticity and changes in calcium signaling associated with neural activity at the same time and with high resolution. This is achieved by bulk loading of neuronal populations with a calcium-sensitive indicator in combination with electroporation of individual cells with a calcium indicator and an additional noncalcium-sensitive dye with a different excitation spectrum. Recordings of the two differently labeled structures can be acquired simultaneously using confocal microscopy. Thus, structural plasticity and calcium dynamics of the individually labeled neuron and the surrounding network can be related to each other. This combined imaging approach can be applied to virtually all systems of neuronal networks to study structure and function. We provide a comprehensive description of the labeling procedure, the imaging parameters, and the important aspects of analysis for simultaneous recordings of structure and function in individual neurons.

  2. Mapping plastic greenhouse with medium spatial resolution satellite data: Development of a new spectral index (United States)

    Yang, Dedi; Chen, Jin; Zhou, Yuan; Chen, Xiang; Chen, Xuehong; Cao, Xin


    Plastic greenhouses (PGs) are an important agriculture development technique to protect and control the growing environment for food crops. The extensive use of PGs can change the agriculture landscape and affects the local environment. Accurately mapping and estimating the coverage of PGs is a necessity to the strategic planning of modern agriculture. Unfortunately, PG mapping over large areas is methodologically challenging, as the medium spatial resolution satellite imagery (such as Landsat data) used for analysis lacks spatial details and spectral variations. To fill the gap, the paper proposes a new plastic greenhouse index (PGI) based on the spectral, sensitivity, and separability analysis of PGs using medium spatial resolution images. In the context of the Landsat Enhanced Thematic Mapper Plus (ETM+) imagery, the paper examines the effectiveness and capability of the proposed PGI. The results indicate that PGs in Landsat ETM+ image can be successfully detected by the PGI if the PG fraction is greater than 12% in a mixed pixel. A kappa coefficient of 0.83 and overall accuracy of 91.2% were achieved when applying the proposed PGI in the case of Weifang District, Shandong, China. These results show that the proposed index can be applied to identifying transparent PGs in atmospheric corrected Landsat image and has the potential for the digital mapping of plastic greenhouse coverage over a large area.

  3. Emerging Roles of BAI Adhesion-GPCRs in Synapse Development and Plasticity

    Directory of Open Access Journals (Sweden)

    Joseph G. Duman


    Full Text Available Synapses mediate communication between neurons and enable the brain to change in response to experience, which is essential for learning and memory. The sites of most excitatory synapses in the brain, dendritic spines, undergo rapid remodeling that is important for neural circuit formation and synaptic plasticity. Abnormalities in synapse and spine formation and plasticity are associated with a broad range of brain disorders, including intellectual disabilities, autism spectrum disorders (ASD, and schizophrenia. Thus, elucidating the mechanisms that regulate these neuronal processes is critical for understanding brain function and disease. The brain-specific angiogenesis inhibitor (BAI subfamily of adhesion G-protein-coupled receptors (adhesion-GPCRs has recently emerged as central regulators of synapse development and plasticity. In this review, we will summarize the current knowledge regarding the roles of BAIs at synapses, highlighting their regulation, downstream signaling, and physiological functions, while noting the roles of other adhesion-GPCRs at synapses. We will also discuss the relevance of BAIs in various neurological and psychiatric disorders and consider their potential importance as pharmacological targets in the treatment of these diseases.

  4. Insights into the Physiological Role of CNS Regeneration Inhibitors

    Directory of Open Access Journals (Sweden)

    Katherine Therese Baldwin


    Full Text Available The growth inhibitory nature of injured adult mammalian central nervous system (CNS tissue constitutes a major barrier to robust axonal outgrowth and functional recovery following trauma or disease. Prototypic CNS regeneration inhibitors are broadly expressed in the healthy and injured brain and spinal cord and include myelin-associated glycoprotein (MAG, the reticulon family member NogoA, oligodendrocyte myelin glycoprotein (OMgp, and chondroitin sulfate proteoglycans (CSPGs. These structurally diverse molecules strongly inhibit neurite outgrowth in vitro, and have been most extensively studied in the context of nervous system injury in vivo. The physiological role of CNS regeneration inhibitors in the naïve, or uninjured, CNS remains less well understood, but has received growing attention in recent years and is the focus of this review. CNS regeneration inhibitors regulate myelin development and axon stability, consolidate neuronal structure shaped by experience, and limit activity-dependent modification of synaptic strength. Altered function of CNS regeneration inhibitors is associated with neuropsychiatric disorders, suggesting crucial roles in brain development and health.

  5. The role of inflammation in CNS injury and disease. (United States)

    Lucas, Sian-Marie; Rothwell, Nancy J; Gibson, Rosemary M


    For many years, the central nervous system (CNS) was considered to be 'immune privileged', neither susceptible to nor contributing to inflammation. It is now appreciated that the CNS does exhibit features of inflammation, and in response to injury, infection or disease, resident CNS cells generate inflammatory mediators, including proinflammatory cytokines, prostaglandins, free radicals and complement, which in turn induce chemokines and adhesion molecules, recruit immune cells, and activate glial cells. Much of the key evidence demonstrating that inflammation and inflammatory mediators contribute to acute, chronic and psychiatric CNS disorders is summarised in this review. However, inflammatory mediators may have dual roles, with detrimental acute effects but beneficial effects in long-term repair and recovery, leading to complications in their application as novel therapies. These may be avoided in acute diseases in which treatment administration might be relatively short-term. Targeting interleukin (IL)-1 is a promising novel therapy for stroke and traumatic brain injury, the naturally occurring antagonist (IL-1ra) being well tolerated by rheumatoid arthritis patients. Chronic disorders represent a greater therapeutic challenge, a problem highlighted in Alzheimer's disease (AD); significant data suggested that anti-inflammatory agents might reduce the probability of developing AD, or slow its progression, but prospective clinical trials of nonsteroidal anti-inflammatory drugs or cyclooxygenase inhibitors have been disappointing. The complex interplay between inflammatory mediators, ageing, genetic background, and environmental factors may ultimately regulate the outcome of acute CNS injury and progression of chronic neurodegeneration, and be critical for development of effective therapies for CNS diseases.

  6. [Modern neuroimaging of brain plasticity]. (United States)

    Kasprian, G; Seidel, S


    Modern neuroimaging methods offer new insights into the plasticity of the human brain. As the techniques of functional MRI and diffusion tensor imaging are increasingly being applied in a clinical setting, the examiner is now frequently confronted with the interpretation of imaging findings related to regenerative processes in response to lesions of the central and also of the peripheral nervous system. In this article individual results of modern neuroimaging studies are discussed in the context of structural and functional plasticity of the CNS.

  7. Sexually dimorphic body size and development time plasticity in Aedes mosquitoes (Diptera: Culicidae). (United States)

    Wormington, Jillian D; Juliano, Steven A

    Sexual size dimorphism (SSD) in insects often accompanies a sexual difference in development time, sexual bimaturism (SBM). To determine whether three Aedes mosquito species have similar plasticity in SSD, attain sexual dimorphism through similar strategies, and whether SSD and SBM are associated. Aedes albopictus, Aedes aegypti, and Aedes triseriatus (Diptera: Culicidae). In four different food availability environments, we quantified plastic responses of relative growth rate (RGR), development time, and adult body size in individually reared males and females. Food availability affected RGR differently for the sexes for all three species. The RGR of males and females differed significantly in the 0.1 g/L food treatment. This difference did not account for observed SSD. Food levels over which the largest changes in RGR were observed differed among the species. Male and female adult mass and development time were jointly affected by food availability in a pattern that differed among the three species, so that degree of SSD and SBM changed differentially with food availability for all three species. Development time was generally less sexually dimorphic than mass, particularly in A. albopictus. At lower food levels, A. aegypti and A. triseriatus had accentuated dimorphism in development time. These results, combined with our knowledge of mosquito life history, suggest that a direct benefit of SBM is improbable for mosquitoes and that the observed intersexual differences in development time are more likely byproducts of selection for SSD.

  8. General Information about Primary CNS Lymphoma (United States)

    ... Research Primary CNS Lymphoma Treatment (PDQ®)–Patient Version General Information About Primary CNS Lymphoma Go to Health ... start in the eye (called ocular lymphoma). Enlarge Anatomy of the lymph system, showing the lymph vessels ...

  9. Surveillance as an innovative tool for furthering technological development as applied to the plastic packaging sector

    Directory of Open Access Journals (Sweden)

    Freddy Abel Vargas


    Full Text Available The demand for production process efficiency and quality has made it necessary to resort to new tools for development and technological innovation. Surveillance of the enviroment has thus bee identified as beign a priority, paying special attention to technology which (by its changing nature is a key factor in competitiveness. Surveillance is a routine activity in developed countries ' organisations; however, few suitable studies have been carried out in Colombia and few instruments produced for applying it to existing sectors of the economy. The present article attempts to define a methodology for technological awareness (based on transforming the information contained in databases by means of constructing technological maps contributing useful knowledge to production processes. This methodology has been applied to the flexible plastic packaging sector. The main trends in this industry's technological development were identified allowing strategies to be proposed for incorporating these advances and tendencies in national companies and research groups involved in flexible plastic packaging technological development and innovation. Technological mappiong's possibilities as an important instrument for producing technological development in a given sector are the analysed as are their possibilities for being used in other production processes.

  10. Neuronal stathmins: a family of phosphoproteins cooperating for neuronal development, plasticity and regeneration. (United States)

    Chauvin, Stéphanie; Sobel, André


    Nervous system development, plasticity and regeneration require numerous, coordinated and finely tuned subcellular mechanisms. Phosphoproteins of the stathmin family, originally identified as intracellular signal relay proteins, are mostly or exclusively expressed in the nervous system with a high level of expression during brain development. Vertebrate stathmins 1-4 all possess a C-terminal "stathmin-like domain" that binds or releases tubulin in a phosphorylation dependent way, and hence participates in the control of microtubule dynamics, an essential process for neuronal differentiation. Contrary to stathmin 1, stathmins 2-4 possess an N-terminal extension whose reversible palmitoylation specifically targets them to the Golgi and intracellular membranes. Regulation of stathmins 2-4 palmitoylation is therefore an important regulatory mechanism that controls their shuttling to various neuronal compartments where they can then act locally. Expression of stathmins is upregulated during neuronal differentiation and plasticity, and altered in numerous neurodegenerative diseases. Experimental perturbation of stathmins expression in Drosophila or in neurons in culture revealed their importance in neuronal growth and differentiation, each stathmin fulfilling at least partially distinct and likely complementary roles. On the other hand, knock-out of stathmins in mice, with the exception of stathmin 2, resulted in mostly mild or no detected phenotype, revealing likely compensations among stathmins. Altogether, through their combinatorial expression and regulation by phosphorylation and by palmitoylation, and through their interactions with tubulin and other neuronal protein targets, the various stathmins appear as essential regulators of neuronal differentiation at the various stages during development and plasticity of the nervous system. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Plasticity of hatching and the duration of planktonic development in marine invertebrates. (United States)

    Oyarzun, Fernanda X; Strathmann, Richard R


    Plasticity in hatching potentially adjusts risks of benthic and planktonic development for benthic marine invertebrates. The proportionate effect of hatching plasticity on duration of larval swimming is greatest for animals that can potentially brood or encapsulate offspring until hatching near metamorphic competence. As an example, early hatching of the nudibranch mollusk Phestilla sibogae is stimulated by scattering of encapsulated offspring, as by a predator feeding on the gelatinous egg ribbon. When egg ribbons are undisturbed, hatching is at or near metamorphic competence. Disturbance of an unguarded benthic egg mass can insert 4 or more days of obligate larval dispersal into the life history. As another example, the spionid annelid Boccardia proboscidea broods capsules, each with both cannibalistic and developmentally arrested planktivorous siblings plus nurse eggs. Early hatching produces mainly planktivorous larvae with a planktonic duration of 15 days. Late hatching produces mainly adelphophages who have eaten their planktivorous siblings and metamorphose with little or no period of swimming. Mothers actively hatch their offspring by tearing the capsules, and appeared to time hatching in response to their environment and not to the stage of development of their offspring. Higher temperature increased the variance of brooding time. Females appeared to hatch capsules at an earlier developmental stage at lower temperatures. Species that release gametes or zygotes directly into the plankton have less scope for plasticity in stage at hatching. Their embryos develop singly with little protection and hatch at early stages, often as blastulae or gastrulae. Time of hatching cannot be greatly advanced, and sensory capabilities of blastulae may be limited.

  12. Development of Standardized Clinical Assessment and Management Plans (SCAMPs) in Plastic and Reconstructive Surgery. (United States)

    Caterson, Stephanie A; Singh, Mansher; Orgill, Dennis; Ghazinouri, Roya; Han, Elizabeth; Ciociolo, George; Laskowski, Karl; Greenberg, Jeffery O


    With rising cost of healthcare, there is an urgent need for developing effective and economical streamlined care. In clinical situations with limited data or conflicting evidence-based data, there is significant institutional and individual practice variation. Quality improvement with the use of Standardized Clinical Assessment and Management Plans (SCAMPs) might be beneficial in such scenarios. The SCAMPs method has never before been reported to be utilized in plastic surgery. The topic of immediate breast reconstruction was identified as a possible SCAMPs project. The initial stages of SCAMPs development, including planning and implementation, were entered. The SCAMP Champion, along with the SCAMPs support team, developed targeted data statements. The SCAMP was then written and a decision-tree algorithm was built. Buy-in was obtained from the Division of Plastic Surgery and a SCAMPs data form was generated to collect data. Decisions pertaining to "immediate implant-based breast reconstruction" were approved as an acceptable topic for SCAMPs development. Nine targeted data statements were made based on the clinical decision points within the SCAMP. The SCAMP algorithm, and the SDF, required multiple revisions. Ultimately, the SCAMP was effectively implemented with multiple iterations in data collection. Full execution of the SCAMP may allow better-defined selection criteria for this complex patient population. Deviations from the SCAMP may allow for improvement of the SCAMP and facilitate consensus within the Division. Iterative and adaptive quality improvement utilizing SCAMPs creates an opportunity to reduce cost by improving knowledge about best practice.

  13. Molecular mechanism linking BDNF/TrkB signaling with the NMDA receptor in memory: the role of Girdin in the CNS. (United States)

    Itoh, Norimichi; Enomoto, Atsushi; Nagai, Taku; Takahashi, Masahide; Yamada, Kiyofumi


    It is well known that synaptic plasticity is the cellular mechanism underlying learning and memory. Activity-dependent synaptic changes in electrical properties and morphology, including synaptogenesis, lead to alterations of synaptic strength, which is associated with long-term potentiation (LTP). Brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase B (TrkB) signaling is involved in learning and memory formation by regulating synaptic plasticity. The phosphatidylinositol 3-kinase (PI3-K)/Akt pathway is one of the key signaling cascades downstream BDNF/TrkB and is believed to modulate N-methyl-d-aspartate (NMDA) receptor-mediated synaptic plasticity. However, the molecular mechanism underlying the connection between these two key players in synaptic plasticity remains largely unknown. Girders of actin filament (Girdin), an Akt substrate that directly binds to actin filaments, has been shown to play a role in neuronal migration and neuronal development. Recently, we identified Girdin as a key molecule involved in regulating long-term memory. It was demonstrated that phosphorylation of Girdin by Akt contributed to the maintenance of LTP by linking the BDNF/TrkB signaling pathway with NMDA receptor activity. These findings indicate that Girdin plays a pivotal role in a variety of processes in the CNS. Here, we review recent advances in our understanding about the roles of Girdin in the CNS and focus particularly on neuronal migration and memory.

  14. Obstructive hydrocephalus due to CNS toxocariasis. (United States)

    Choi, Jae-Hwan; Cho, Jae-Wook; Lee, Jae-Hyeok; Lee, Sang Weon; Kim, Hak-Jin; Choi, Kwang-Dong


    A 46-year-old man developed intermittent headache, diplopia, and visual obscuration for two months. Funduscopic examination showed optic disk swelling in both eyes. Brain MRI exhibited hydrocephalus and leptomeningeal enhancement at the prepontine cistern, left cerebellopontine angle cistern and bilateral cerebral hemisphere, and hemosiderin deposition along the cerebellar folia. CSF analysis revealed an elevated opening pressure with xanthochromic appearance and small amount of red blood cells. Antibody titer against Toxocariasis using ELISA was elevated both in blood and CSF. Obstructive hydrocephalus and hemosiderin deposition in this case may result from the active inflammatory process due to CNS toxocariasis within the subarachnoid space.

  15. Synaptogenesis in the CNS: an odyssey from wiring together to firing together. (United States)

    Munno, David W; Syed, Naweed I


    To acquire a better comprehension of nervous system function, it is imperative to understand how synapses are assembled during development and subsequently altered throughout life. Despite recent advances in the fields of neurodevelopment and synaptic plasticity, relatively little is known about the mechanisms that guide synapse formation in the central nervous system (CNS). Although many structural components of the synaptic machinery are pre-assembled prior to the arrival of growth cones at the site of their potential targets, innumerable changes, central to the proper wiring of the brain, must subsequently take place through contact-mediated cell-cell communications. Identification of such signalling molecules and a characterization of various events underlying synaptogenesis are pivotal to our understanding of how a brain cell completes its odyssey from "wiring together to firing together". Here we attempt to provide a comprehensive overview that pertains directly to the cellular and molecular mechanisms of selection, formation and refinement of synapses during the development of the CNS in both vertebrates and invertebrates.

  16. Phantom limb pain: a case of maladaptive CNS plasticity?

    DEFF Research Database (Denmark)

    Flor, Herta; Nikolajsen, Lone; Jensen, Troels Staehelin


    Phantom pain refers to pain in a body part that has been amputated or deafferented. It has often been viewed as a type of mental disorder or has been assumed to stem from pathological alterations in the region of the amputation stump. In the past decade, evidence has accumulated that phantom pain...... studies and derive suggestions for innovative interventions aimed at alleviating phantom pain....

  17. JTEC monograph on biodegradable polymers and plastics in Japan: Research, development, and applications (United States)

    Lenz, Robert W.


    A fact-finding team of American scientists and engineers visited Japan to assess the status of research and development and applications in biodegradable polymers. The visit was sponsored by the National Science Foundation and industry. In Japan, the team met with representatives of 31 universities, government ministries and institutes, companies, and associations. Japan's national program on biodegradable polymers and plastics evaluates new technologies, testing methods, and potential markets for biodegradables. The program is coordinated by the Biodegradable Plastics Society of Japan, which seeks to achieve world leadership in biodegradable polymer technology and identify commercial opportunities for exploiting this technology. The team saw no major new technology breakthroughs. Japanese scientists and engineers are focusing on natural polymers from renewable resources, synthetic polymers, and bacterially-produced polymers such as polyhydroxyalkanoates, poly(amino acids), and polysaccharides. The major polymers receiving attention are the Zeneca PHBV copolymers, Biopol(registered trademark), poly(lactic acid) from several sources, polycaprolactone, and the new synthetic polyester, Bionolle(registered trademark), from Showa High Polymer. In their present state of development, these polymers all have major deficiencies that inhibit their acceptance for large-scale applications.

  18. Overcoming maladaptive plasticity through plastic compensation

    Directory of Open Access Journals (Sweden)

    Matthew R.J. MORRIS, Sean M. ROGERS


    Full Text Available Most species evolve within fluctuating environments, and have developed adaptations to meet the challenges posed by environmental heterogeneity. One such adaptation is phenotypic plasticity, or the ability of a single genotype to produce multiple environmentally-induced phenotypes. Yet, not all plasticity is adaptive. Despite the renewed interest in adaptive phenotypic plasticity and its consequences for evolution, much less is known about maladaptive plasticity. However, maladaptive plasticity is likely an important driver of phenotypic similarity among populations living in different environments. This paper traces four strategies for overcoming maladaptive plasticity that result in phenotypic similarity, two of which involve genetic changes (standing genetic variation, genetic compensation and two of which do not (standing epigenetic variation, plastic compensation. Plastic compensation is defined as adaptive plasticity overcoming maladaptive plasticity. In particular, plastic compensation may increase the likelihood of genetic compensation by facilitating population persistence. We provide key terms to disentangle these aspects of phenotypic plasticity and introduce examples to reinforce the potential importance of plastic compensation for understanding evolutionary change [Current Zoology 59 (4: 526–536, 2013].

  19. Overcoming maladaptive plasticity through plastic compensation

    Institute of Scientific and Technical Information of China (English)

    Matthew R.J.MORRIS; Sean M.ROGERS


    Most species evolve within fluctuating environments,and have developed adaptations to meet the challenges posed by environmental heterogeneity.One such adaptation is phenotypic plasticity,or the ability of a single genotype to produce multiple environmentally-induced phenotypes.Yet,not all plasticity is adaptive.Despite the renewed interest in adaptive phenotypic plasticity and its consequences for evolution,much less is known about maladaptive plasticity.However,maladaptive plasticity is likely an important driver of phenotypic similarity among populations living in different environments.This paper traces four strategies for overcoming maladaptive plasticity that result in phenotypic similarity,two of which involve genetic changes (standing genetic variation,genetic compensation) and two of which do not (standing epigenetic variation,plastic compensation).Plastic compensation is defined as adaptive plasticity overcoming maladaptive plasticity.In particular,plastic compensation may increase the likelihood of genetic compensation by facilitating population persistence.We provide key terms to disentangle these aspects of phenotypic plasticity and introduce examples to reinforce the potential importance of plastic compensation for understanding evolutionary change.

  20. New advances in the rehabilitation of CNS diseases applying rTMS. (United States)

    Málly, Judit; Stone, Trevor W


    Transcranial magnetic stimulation (TMS) can directly stimulate the CNS, modifying the brain's plasticity to enhance the behavior of the paretic extremities. Studies with low-frequency repetitive TMS (rTMS) on the intact hemisphere and those with high frequencies on the affected hemisphere could increase the speed of movement in the hand affected by CNS injury. Stimulation of the motor pathway may contribute to faster improvement in patients with spinal cord injury. Symptoms of Parkinson's disease (such as cognition and working memory, neglect syndrome and global aphasia) can be influenced by rTMS. However, the site of stimulation and the parameters of rTMS are different. Processes that contribute to the behavior of rTMS include the modification of brain plasticity, induction of neurogenesis, growth of new fibers in the spinal cord or all of these together. According to previous research, rTMS may be suitable as an add-on therapy to rehabilitation in CNS diseases.

  1. Plastic Bronchitis. (United States)

    Rubin, Bruce K


    Plastic bronchitis is an uncommon and probably underrecognized disorder, diagnosed by the expectoration or bronchoscopic removal of firm, cohesive, branching casts. It should not be confused with purulent mucous plugging of the airway as seen in patients with cystic fibrosis or bronchiectasis. Few medications have been shown to be effective and some are now recognized as potentially harmful. Current research directions in plastic bronchitis research include understanding the genetics of lymphatic development and maldevelopment, determining how abnormal lymphatic malformations contribute to cast formation, and developing new treatments. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Radiation therapy of CNS lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Imai, Yutaka; Wako, Tadashi (Shinshu Univ., Matsumoto, Nagano (Japan). Faculty of Medicine)


    Six cases of the CNS malignant lymphoma occurring among 165 cases seen between 1975 -- 1981 were reviewed. Two cases had primary brain mass lesions and one case had a secondary brain mass in the systemic remission period. Two cases had primary extradural spinal mass lesions and one case had a secondary extradural spinal mass in the systemic relapse period. All patients were treated with radiotherapy. Irradiation fields, doses and those effects were discussed. Whole brain irradiation more than 40 Gy was recommended for brain lesion. Prognosis of the secondary case without systemic remission was poor.

  3. Activity- and age-dependent GABAergic synaptic plasticity in the developing rat hippocampus. (United States)

    Gubellini, P; Ben-Ari, Y; Gaïarsa, J L


    Activity-dependent plasticity of GABAergic synaptic transmission was investigated in rat hippocampal slices obtained between postnatal day (P) 0-15 using the whole-cell patch-clamp recording technique. Spontaneous GABA(A) receptor-mediated postsynaptic currents (sGABA(A)-PSCs) were isolated in the presence of ionotropic glutamate receptor antagonists. A conditioning protocol relevant to the physiological condition, consisting of repetitive depolarizing pulses (DPs) at 0.1 Hz, was able to induce long-lasting changes in both frequency and amplitude of sGABA(A)-PSCs between P0 and P8. Starting from P12, DPs were unable to induce any form of synaptic plasticity. The effects of DPs were tightly keyed to the frequency at which they were delivered. When delivered at a lower (0.05 Hz) or higher (1 Hz) frequency, DPs failed to induce any long-lasting change in the frequency or amplitude of sGABA(A)-PSCs. In two cases, DPs were able to activate sGABA(A)-PSCs in previously synaptically silent cells at P0-1. These results show that long-term changes in GABAergic synaptic activity can be induced during a restricted period of development by a conditioning protocol relevant to the physiological condition. It is suggested that such activity-induced modifications may represent a physiological mechanism for the functional maturation of GABAergic synaptic transmission.

  4. Development of a plastic injection molding training system using Petri nets and virtual reality

    Institute of Scientific and Technical Information of China (English)


    In this study, Virtual Reality (VR)-based plastic injection molding training system (VPIMTS), which can be modeled as an integrated system with a task planning module, an intelligent instruction module, a simulation module, and virtual environment (VE) module, was developed. Presented in this paper are an architecture of VPIMTS, a practical knowledge modelling approach for modelling the training scenarios of the system by using Petri nets formalism and key techniques (FEM, injection molding procedure modelling) which have been developed independently. The utilization of the Petri net model realized the environment where the trainee can behave freely, and also made it possible to equip the system with the function of showing the next action of the trainee whenever he wants. The overall system is a powerful approach for highly improving the trainee's comprehension and injection molding study-efficiency by building digital, intelligent, knowledgeable, and visual aids.

  5. A period of structural plasticity at the axon initial segment in developing visual cortex

    Directory of Open Access Journals (Sweden)

    Annika eGutzmann


    Full Text Available Cortical networks are shaped by sensory experience and are most susceptible to modifications during critical periods characterized by enhanced plasticity at the structural and functional level. A system particularly well-studied in this context is the mammalian visual system. Plasticity has been documented for the somatodendritic compartment of neurons in detail. A neuronal microdomain not yet studied in this context is the axon initial segment (AIS located at the proximal axon segment. It is a specific electrogenic axonal domain and the site of action potential generation. Recent studies showed that structure and function of the AIS can be dynamically regulated. Here we hypothesize that the AIS shows a dynamic regulation during maturation of the visual cortex. We therefore analyzed AIS length development from embryonic day (E 12.5 to adulthood in mice. A tri-phasic time course of AIS length remodeling during development was observed. AIS first appeared at E14.5 and increased in length throughout the postnatal period to a peak between postnatal day (P 10 to P15 (eyes open P13-14. Then, AIS length was reduced significantly around the beginning of the critical period for ocular dominance plasticity (CP, P21. Shortest AIS were observed at the peak of the CP (P28, followed by a moderate elongation towards the end of the CP (P35. To test if the dynamic maturation of the AIS is influenced by eye opening (onset of activity, animals were deprived of visual input before and during the CP. Deprivation for 1 week prior to eye opening did not affect AIS length development. However, deprivation from P0-P28 and P14-P28 resulted in AIS length distribution similar to the peak at P15. In other words, deprivation from birth prevents the transient shortening of the AIS and maintains an immature AIS length. These results are the first to suggest a dynamic maturation of the AIS in cortical neurons and point to novel mechanisms in the development of neuronal

  6. Plastic Surgery (United States)

    ... Surgery? A Week of Healthy Breakfasts Shyness Plastic Surgery KidsHealth > For Teens > Plastic Surgery Print A A ... forehead lightened with a laser? What Is Plastic Surgery? Just because the name includes the word "plastic" ...

  7. A 3D elasto-plastic FEM program developed for reservoir Geomechanics simulations: Introduction and case studies

    Directory of Open Access Journals (Sweden)

    Amin Chamani


    Full Text Available The development of yielded or failure zone due to an engineering construction is a subject of study in different disciplines. In Petroleum engineering, depletion from and injection of gas into a porous rock can cause development of a yield zone around the reservoir. Studying this phenomenon requires elasto-plastic analysis of geomaterial, in this case the porous rocks. In this study, which is a continuation of a previous study investigating the elastic behaviour of geomaterial, the elasto-plastic responses of geomaterial were studied. A 3D finite element code (FEM was developed, which can consider different constitutive models. The code features were explained and some case studies were presented to validate the output results of the code. The numerical model was, then, applied to study the development of the plastic zone around a horizontal porous formation subjected to the injection of gas. The model is described in detail and the results are presented. It was observed that by reducing the cohesion of rocks the extension of the plastic zone increased. Comparing to the elastic model, the ability to estimate the extension of the yield and failure zone is the main advantage of an elasto-plastic model.

  8. Detection of transgenerational spermatogenic inheritance of adult male acquired CNS gene expression characteristics using a Drosophila systems model.

    Directory of Open Access Journals (Sweden)

    Abhay Sharma

    Full Text Available Available instances of inheritance of epigenetic transgenerational phenotype are limited to environmental exposures during embryonic and adult gonadal development. Adult exposures can also affect gametogenesis and thereby potentially result in reprogramming of the germline. Although examples of epigenetic effects on gametogenesis exist, it is notable that transgenerational inheritance of environment-induced adult phenotype has not yet been reported. Epigenetic codes are considered to be critical in neural plasticity. A Drosophila systems model of pentylenetetrazole (PTZ induced long-term brain plasticity has recently been described. In this model, chronic PTZ treatment of adult males causes alterations in CNS transcriptome. Here, we describe our search for transgenerational spermatogenic inheritance of PTZ induced gene expression phenotype acquired by adult Drosophila males. We generated CNS transcriptomic profiles of F(1 adults after treating F(0 adult males with PTZ and of F(2 adults resulting from a cross between F(1 males and normal females. Surprisingly, microarray clustering showed F(1 male profile as closest to F(1 female and F(0 male profile closest to F(2 male. Differentially expressed genes in F(1 males, F(1 females and F(2 males showed significant overlap with those caused by PTZ. Interestingly, microarray evidence also led to the identification of upregulated rRNA in F(2 males. Next, we generated microarray expression profiles of adult testis from F(0 and F(1 males. Further surprising, clustering of CNS and testis profiles and matching of differentially expressed genes in them provided evidence of a spermatogenic mechanism in the transgenerational effect observed. To our knowledge, we report for the first time detection of transgenerational spermatogenic inheritance of adult acquired somatic gene expression characteristic. The Drosophila systems model offers an excellent opportunity to understand the epigenetic mechanisms underlying

  9. Development of a fast plastic scintillation detector with time resolution of less than 10 ps

    CERN Document Server

    Zhao, J W; Tanihata, I; Terashima, S; Zhu, L H; Enomoto, A; Nagae, D; Nishimura, T; Omika, S; Ozawa, A; Takeuchi, Y; Yamaguchi, T


    Timing-pick up detectors with excellent timing resolutions are essential in many modern nuclear physics experiments. Aiming to develop a Time-Of-Flight system with precision down to about 10 ps, we have made a systematic study of the timing characteristic of TOF detectors, which consist of several combinations of plastic scintillators and photomultiplier tubes. With the conventional electronics, the best timing resolution of about 5.1 ps ({\\sigma}) has been achieved for detectors with an area size of 3x1 cm2. It is found that for data digitalization a combination of TAC and ADC can achieve a better time resolution than currently available TDC. Simultaneously measurements of both time and pulse height are very valuable for correction of time-walk effect.

  10. First performance test of newly developed plastic scintillator for radiation detection

    Energy Technology Data Exchange (ETDEWEB)

    Watanabe, M., E-mail: [Graduate School of Science and Technology, Niigata University, Niigata 950-2181 (Japan); Katsumata, M. [Faculty of Science, Physics Department, Niigata University, Niigata 950-2181 (Japan); Ono, H. [Nippon Dental University, School of Life Dentistry at Niigata, Niigata 951-8580 (Japan); Suzuki, T. [Graduate School of Science and Technology, Niigata University, Niigata 950-2181 (Japan); Miyata, H. [Faculty of Science, Physics Department, Niigata University, Niigata 950-2181 (Japan); Itoh, Y.; Ishida, K. [Graduate School of Science and Technology, Niigata University, Niigata 950-2181 (Japan); Tamura, M.; Yamaguchi, Y. [Carlit Holdings Co., Ltd., Chiyoda, Tokyo 101-0024 (Japan)


    We present a plastic scintillator, developed in collaboration with Carlit Holdings Co., Ltd., that is fabricated using a liquid parent material cured at room temperature by adding a hardener. The new scintillator can incorporate heat-labile functional materials such as gadolinium to enhance neutron sensitivity. The characteristics of the new scintillator, in particular the light yield and attenuation length, were evaluated using a {sup 90}Sr β-ray source. The light yield was measured 7% Anthracene on the basis of a comparison with commercially available scintillator (BC-408) at a distance of 18 cm from the photodetector surface. This light yield is dependent on the distance between the luminous point and the photodetector because of light attenuation. The attenuation length of the Gd-doped scintillator was about 50 cm.

  11. Development of high-flexible triboelectric generators using plastic metal as electrodes (United States)

    Yang, Sen-Yeu; Shih, Jian-Fu; Chang, Chih-Chieh; Yang, Chii-Rong


    A triboelectric generator is a device that harvests energy through the conversion of mechanical energy into electrical energy. In this work, two polymer materials (PDMS and PET) were selected as triboelectric layers in conjunction with plastic metal (PM) films as conductive layers to produce an electrode with high flexibility. The PDMS film was fabricated with a microstructural array to enhance friction. The proposed PM material was prepared by mixing gallium-indium liquid metal and a glaze powder with excellent coating ability, extensibility, and conductivity. Results demonstrate the superior characteristics of the PM flexible electrodes, including large bending angle (≥180°), small curvature radius (≤1 mm), and stable conductivity. This PM-based triboelectric generator can achieve average output voltage of 80 V and current of 37.2 μA. The proposed flexible electrode with a PM conductive layer could be expected to make a notable contribution to the development of wearable devices.

  12. Spatial and temporal plasticity of chromatin during programmed DNA-reorganization in Stylonychia macronuclear development

    Directory of Open Access Journals (Sweden)

    Postberg Jan


    Full Text Available Abstract Background: In this study we exploit the unique genome organization of ciliates to characterize the biological function of histone modification patterns and chromatin plasticity for the processing of specific DNA sequences during a nuclear differentiation process. Ciliates are single-cell eukaryotes containing two morphologically and functionally specialized types of nuclei, the somatic macronucleus and the germline micronucleus. In the course of sexual reproduction a new macronucleus develops from a micronuclear derivative. During this process specific DNA sequences are eliminated from the genome, while sequences that will be transcribed in the mature macronucleus are retained. Results: We show by immunofluorescence microscopy, Western analyses and chromatin immunoprecipitation (ChIP experiments that each nuclear type establishes its specific histone modification signature. Our analyses reveal that the early macronuclear anlage adopts a permissive chromatin state immediately after the fusion of two heterochromatic germline micronuclei. As macronuclear development progresses, repressive histone modifications that specify sequences to be eliminated are introduced de novo. ChIP analyses demonstrate that permissive histone modifications are associated with sequences that will be retained in the new macronucleus. Furthermore, our data support the hypothesis that a PIWI-family protein is involved in a transnuclear cross-talk and in the RNAi-dependent control of developmental chromatin reorganization. Conclusion: Based on these data we present a comprehensive analysis of the spatial and temporal pattern of histone modifications during this nuclear differentiation process. Results obtained in this study may also be relevant for our understanding of chromatin plasticity during metazoan embryogenesis.

  13. Aberrant development and plasticity of excitatory visual cortical networks in the absence of cpg15. (United States)

    Picard, Nathalie; Leslie, Jennifer H; Trowbridge, Sara K; Subramanian, Jaichandar; Nedivi, Elly; Fagiolini, Michela


    During development, experience plays a crucial role in sculpting neuronal connections. Patterned neural activity guides formation of functional neural circuits through the selective stabilization of some synapses and the pruning of others. Activity-regulated factors are fundamental to this process, but their roles in synapse stabilization and maturation is still poorly understood. CPG15, encoded by the activity-regulated gene candidate plasticity gene 15, is a small, glycosylphosphatidylinositol (GPI)-linked, extracellular protein that promotes synapse stabilization. Here we show that global knock-out of cpg15 results in abnormal postnatal development of the excitatory network in visual cortex and an associated disruption in development of visual receptive field properties. In addition, whereas repeated stimulation induced potentiation and depression in wild-type mice, the depression was slower in cpg15 knock-out mice, suggesting impairment in short-term depression-like mechanisms. These findings establish the requirement for cpg15 in activity-dependent development of the visual system and demonstrate the importance of timely excitatory network development for normal visual function.

  14. Pericytes Stimulate Oligodendrocyte Progenitor Cell Differentiation during CNS Remyelination

    Directory of Open Access Journals (Sweden)

    Alerie Guzman De La Fuente


    Full Text Available The role of the neurovascular niche in CNS myelin regeneration is incompletely understood. Here, we show that, upon demyelination, CNS-resident pericytes (PCs proliferate, and parenchymal non-vessel-associated PC-like cells (PLCs rapidly develop. During remyelination, mature oligodendrocytes were found in close proximity to PCs. In Pdgfbret/ret mice, which have reduced PC numbers, oligodendrocyte progenitor cell (OPC differentiation was delayed, although remyelination proceeded to completion. PC-conditioned medium accelerated and enhanced OPC differentiation in vitro and increased the rate of remyelination in an ex vivo cerebellar slice model of demyelination. We identified Lama2 as a PC-derived factor that promotes OPC differentiation. Thus, the functional role of PCs is not restricted to vascular homeostasis but includes the modulation of adult CNS progenitor cells involved in regeneration.

  15. Evolution, development, and plasticity of the human brain: from molecules to bones

    Directory of Open Access Journals (Sweden)

    Branka eHrvoj-Mihic


    Full Text Available Neuroanatomical, molecular, and paleontological evidence is examined in light of human brain evolution. The brain of extant humans differs from the brains of other primates in its overall size and organization, and differences in size and organization of specific cortical areas and subcortical structures implicated into complex cognition and social and emotional processing. The human brain is also characterized by functional lateralizations, reflecting specializations of the cerebral hemispheres in humans for different types of processing, facilitating fast and reliable communication between neural cells in an enlarged brain. The features observed in the adult brain reflect human-specific patterns of brain development. Compared to the brains of other primates, the human brain takes longer to mature, promoting an extended period for establishing cortical microcircuitry and its modifications. Together, these features may underlie the prolonged period of learning and acquisition of technical and social skills necessary for survival, creating a unique cognitive and behavioral niche typical of our species.The neuroanatomical findings are in concordance with molecular analyses, which suggest a trend toward heterochrony in the expression of genes implicated in different functions. These include synaptogenesis, neuronal maturation and plasticity in humans, mutations in genes implicated in neurite outgrowth and plasticity, and an increased role of regulatory mechanisms, potentially promoting fast modification of neuronal morphologies in response to new computational demands. At the same time, endocranial casts of fossil hominins provide an insight into the timing of the emergence of uniquely human features in the course of evolution. We conclude by proposing several ways of combining comparative neuroanatomy, molecular biology and insights gained from fossil endocasts in future research.

  16. Differential neuronal plasticity in mouse hippocampus associated with various periods of enriched environment during postnatal development. (United States)

    Hosseiny, Salma; Pietri, Mariel; Petit-Paitel, Agnès; Zarif, Hadi; Heurteaux, Catherine; Chabry, Joëlle; Guyon, Alice


    Enriched environment (EE) is characterized by improved conditions for enhanced exploration, cognitive activity, social interaction and physical exercise. It has been shown that EE positively regulates the remodeling of neural circuits, memory consolidation, long-term changes in synaptic strength and neurogenesis. However, the fine mechanisms by which environment shapes the brain at different postnatal developmental stages and the duration required to induce such changes are still a matter of debate. In EE, large groups of mice were housed in bigger cages and were given toys, nesting materials and other equipment that promote physical activity to provide a stimulating environment. Weaned mice were housed in EE for 4, 6 or 8 weeks and compared with matched control mice that were raised in a standard environment. To investigate the differential effects of EE on immature and mature brains, we also housed young adult mice (8 weeks old) for 4 weeks in EE. We studied the influence of onset and duration of EE housing on the structure and function of hippocampal neurons. We found that: (1) EE enhances neurogenesis in juvenile, but not young adult mice; (2) EE increases the number of synaptic contacts at every stage; (3) long-term potentiation (LTP) and spontaneous and miniature activity at the glutamatergic synapses are affected differently by EE depending on its onset and duration. Our study provides an integrative view of the role of EE during postnatal development in various mechanisms of plasticity in the hippocampus including neurogenesis, synaptic morphology and electrophysiological parameters of synaptic connectivity. This work provides an explanation for discrepancies found in the literature about the effects of EE on LTP and emphasizes the importance of environment on hippocampal plasticity.

  17. Evolution, development, and plasticity of the human brain: from molecules to bones. (United States)

    Hrvoj-Mihic, Branka; Bienvenu, Thibault; Stefanacci, Lisa; Muotri, Alysson R; Semendeferi, Katerina


    Neuroanatomical, molecular, and paleontological evidence is examined in light of human brain evolution. The brain of extant humans differs from the brains of other primates in its overall size and organization, and differences in size and organization of specific cortical areas and subcortical structures implicated into complex cognition and social and emotional processing. The human brain is also characterized by functional lateralizations, reflecting specializations of the cerebral hemispheres in humans for different types of processing, facilitating fast and reliable communication between neural cells in an enlarged brain. The features observed in the adult brain reflect human-specific patterns of brain development. Compared to the brains of other primates, the human brain takes longer to mature, promoting an extended period for establishing cortical microcircuitry and its modifications. Together, these features may underlie the prolonged period of learning and acquisition of technical and social skills necessary for survival, creating a unique cognitive and behavioral niche typical of our species. The neuroanatomical findings are in concordance with molecular analyses, which suggest a trend toward heterochrony in the expression of genes implicated in different functions. These include synaptogenesis, neuronal maturation, and plasticity in humans, mutations in genes implicated in neurite outgrowth and plasticity, and an increased role of regulatory mechanisms, potentially promoting fast modification of neuronal morphologies in response to new computational demands. At the same time, endocranial casts of fossil hominins provide an insight into the timing of the emergence of uniquely human features in the course of evolution. We conclude by proposing several ways of combining comparative neuroanatomy, molecular biology and insights gained from fossil endocasts in future research.

  18. Epigenetics of drought-induced trans-generational plasticity: consequences for range limit development. (United States)

    Alsdurf, Jacob; Anderson, Cynthia; Siemens, David H


    Genetic variation gives plants the potential to adapt to stressful environments that often exist beyond their geographic range limits. However, various genetic, physiological or developmental constraints might prevent the process of adaptation. Alternatively, environmentally induced epigenetic changes might sustain populations for several generations in stressful areas across range boundaries, but previous work on Boechera stricta, an upland mustard closely related to Arabidopsis, documented a drought-induced trans-generational plastic trade-off that could contribute to range limit development. Offspring of parents who were drought treated had higher drought tolerance, but lower levels of glucosinolate toxins. Both drought tolerance and defence are thought to be needed to expand the range to lower elevations. Here, we used methylation-sensitive amplified fragment length polymorphisms to determine whether environmentally induced DNA methylation and thus epigenetics could be a mechanism involved in the observed trans-generational plastic trade-off. We compared 110 offspring from the same self-fertilizing lineages whose parents were exposed to experimental drought stress treatments in the laboratory. Using three primer combinations, 643 polymorphic epi-loci were detected. Discriminant function analysis (DFA) on the amount of methylation detected resulted in significant combinations of epi-loci that distinguished the parent drought treatments in the offspring. Principal component (PC) and univariate association analyses also detected the significant differences, even after controlling for lineage, planting flat, developmental differences and multiple testing. Univariate tests also indicated significant associations between the amount of methylation and drought tolerance or glucosinolate toxin concentration. One epi-locus that was implicated in DFA, PC and univariate association analysis may be directly involved in the trade-off because increased methylation at this

  19. Development and Plasticity of Cognitive Flexibility in Early and Middle Childhood. (United States)

    Buttelmann, Frances; Karbach, Julia


    Cognitive flexibility, the ability to flexibly switch between tasks, is a core dimension of executive functions (EFs) allowing to control actions and to adapt flexibly to changing environments. It supports the management of multiple tasks, the development of novel, adaptive behavior and is associated with various life outcomes. Cognitive flexibility develops rapidly in preschool and continuously increases well into adolescence, mirroring the growth of neural networks involving the prefrontal cortex. Over the past decade, there has been increasing interest in interventions designed to improve cognitive flexibility in children in order to support the many developmental outcomes associated with cognitive flexibility. This article provides a brief review of the development and plasticity of cognitive flexibility across early and middle childhood (i.e., from preschool to elementary school age). Focusing on interventions designed to improve cognitive flexibility in typically developing children, we report evidence for significant training and transfer effects while acknowledging that current findings on transfer are heterogeneous. Finally, we introduce metacognitive training as a promising new approach to promote cognitive flexibility and to support transfer of training.

  20. Research and Development of a New Waste Collection Bin to Facilitate Education in Plastic Recycling (United States)

    Chow, Cheuk-fai; So, Wing-Mui Winnie; Cheung, Tsz-Yan


    Plastic recycling has been an alternative method for solid waste management apart from landfill and incineration. However, recycling quality is affected when all plastics are discarded into a single recycling bin that increases cross contaminations and operation cost to the recycling industry. Following the engineering design process, a new…

  1. Protein-kinase C : its role in activity-dependent Purkinje cell dendritic development and plasticity

    NARCIS (Netherlands)

    Metzger, F; Kapfhammer, JP


    The cerebellum is a central organ in the control of motor learning and performance. In this respect, the cellular plasticity model systems of multiple climbing fiber elimination and long-term depression have been intensively studied. The signalling pathways involved in these plastic changes are now

  2. Research and Development of a New Waste Collection Bin to Facilitate Education in Plastic Recycling (United States)

    Chow, Cheuk-fai; So, Wing-Mui Winnie; Cheung, Tsz-Yan


    Plastic recycling has been an alternative method for solid waste management apart from landfill and incineration. However, recycling quality is affected when all plastics are discarded into a single recycling bin that increases cross contaminations and operation cost to the recycling industry. Following the engineering design process, a new…

  3. Myeloid leukemia with transdifferentiation plasticity developing from T-cell progenitors

    NARCIS (Netherlands)

    Riemke, P. (Pia); Czeh, M. (Melinda); Fischer, J. (Josephine); Walter, C. (Carolin); Ghani, S. (Saeed); Zepper, M. (Matthias); Agelopoulos, K. (Konstantin); Lettermann, S. (Stephanie); Gebhardt, M.L. (Marie L); Mah, N. (Nancy); Weilemann, A. (Andre); Grau, M. (Michael); Gröning, V. (Verena); T. Haferlach (Torsten); D. Lenze (Dido); H.R. Delwel (Ruud); M. Prinz (Marco); Andrade-Navarro, M.A. (Miguel A); Lenz, G. (Georg); Dugas, M. (Martin); C. Müller-Tidow (Carsten); Rosenbauer, F. (Frank)


    textabstractUnfavorable patient survival coincides with lineage plasticity observed in human acute leukemias. These cases are assumed to arise from hematopoietic stem cells, which have stable multipotent differentiation potential. However, here we report that plasticity in leukemia can result from

  4. Development of TOF-PET using Compton scattering by plastic scintillators (United States)

    Kuramoto, M.; Nakamori, T.; Kimura, S.; Gunji, S.; Takakura, M.; Kataoka, J.


    We propose a time-of-flight (TOF) technique using plastic scintillators which have fast decay time of a few ns for positron emission tomography (PET). While the photoelectric absorption probability of the plastic for 511 keV gamma rays are extremely low due to its small density and effective atomic number, the cross section of Compton scattering is comparable to that of absorption by conventional inorganic scintillators. We thus propose TOF-PET using Compton scattering with plastic scintillators (Compton-PET), and performed fundamental experiments towards exploration of the Compton-PET capability. We demonstrated that the plastic scintillators achieved the better time resolution in comparison to LYSO(Ce) and GAGG(Ce) scintillators. In addition we evaluated the depth-of-interaction resolving capability with the plastic scintillators.

  5. Plastic condoms. (United States)


    Only simple equipment, simple technology and low initial capital investment are needed in their manufacture. The condoms can be made by people who were previously unskilled or only semi-skilled workers. Plastic condoms differ from those made of latex rubber in that the nature of the plastic film allows unlimited shelf-life. Also, the plastic has a higher degree of lubricity than latex rubber; if there is a demand for extra lubrication in a particular market, this can be provided. Because the plastic is inert, these condoms need not be packaged in hermetically sealed containers. All these attributes make it possible to put these condoms on the distributors' shelves in developing countries competitively with rubber condoms. The shape of the plastic condom is based on that of the lamb caecum, which has long been used as luxury-type condom. The plastic condom is made from plastic film (ethylene ethyl acrilate) of 0.001 inch (0.0254 mm.) thickness. In addition, a rubber ring is provided and sealed into the base of the condom for retention during coitus. The advantage of the plastic condom design and the equipment on which it is made is that production can be carried out either in labour-intensive economy or with varying degrees of mechanization and automation. The uniform, finished condom if made using previously untrained workers. Training of workers can be done in a matter of hours on the two machines which are needed to produce and test the condoms. The plastic film is provided on a double wound roll, and condom blanks are prepared by means of a heat-sealing die on the stamping machine. The rubber rings are united to the condom blanks on an assembly machine, which consists of a mandrel and heat-sealing equipment to seal the rubber ring to the base of the condom. Built into the assembly machine is a simple air-testing apparatus that can detect the smallest pinhole flaw in a condom. The manufacturing process is completed by unravelling the condom from the assembly

  6. Plastic deformation of high-purity a-titanium: model development and validation using the Taylor cylinder impact test (United States)

    Chandola, Nitin; Revil-Baudard, Benoit; Cazacu, Oana


    Results of an experimental study on the quasi-static and high-rate plastic deformation due to impact of a high-purity, polycrystalline, a-titanium material are presented. To quantify the plastic anisotropy and tension-compression asymmetry of the material, first monotonic uniaxial compression and tension tests were carried out at room temperature under quasi-static conditions. It was found that the material is transversely isotropic and displays strong strength differential effects. To characterize the material's strain rate sensitivity, Split Hopkinson Pressure Bar tests in tension and compression were also conducted. Taylor impact tests were performed for impact velocity of 196 m/s. Plastic deformation extended to 64% of the length of the deformed specimen, with little radial spreading. To model simultaneously the observed anisotropy, strain-rate sensitivity, and tension-compression asymmetry of the material, a three-dimensional constitutive model was developed. Key in the formulation is a macroscopic yield function [1] that incorporates the specificities of the plastic flow, namely the combined effects of anisotropy and tension-compression asymmetry. Comparison between model predictions and data show the capabilities of the model to describe with accuracy the plastic behavior of the a-Ti material for both quasi-static and dynamic loadings, in particular, a very good agreement was obtained between the simulated and experimental post-test Taylor specimen geometries.

  7. Metallothionein expression and roles in the CNS

    DEFF Research Database (Denmark)

    Penkowa, Milena


    -I+II) are regulated and expressed coordinately and are currently the best characterized MT isoforms. This review will focus on the expression and roles of MT-I+II in the CNS. MT-I+II are implicated in diverse physiological and pathophysiological functions, such as metal ion metabolism, regulation of the CNS...

  8. Exclusion of integrins from CNS axons is regulated by Arf6 activation and the AIS

    NARCIS (Netherlands)

    Franssen, Elske H P; Zhao, Rong-Rong; Koseki, Hiroaki; Kanamarlapudi, Venkateswarlu; Hoogenraad, Casper C; Eva, Richard; Fawcett, James W


    Integrins are adhesion and survival molecules involved in axon growth during CNS development, as well as axon regeneration after injury in the peripheral nervous system (PNS). Adult CNS axons do not regenerate after injury, partly due to a low intrinsic growth capacity. We have previously studied

  9. Are Supramodality and Cross-Modal Plasticity the Yin and Yang of Brain Development? From Blindness to Rehabilitation

    DEFF Research Database (Denmark)

    Cecchetti, Luca; Kupers, Ron; Ptito, Maurice


    Research in blind individuals has primarily focused for a long time on the brain plastic reorganization that occurs in early visual areas. Only more recently, scientists have developed innovative strategies to understand to what extent vision is truly a mandatory prerequisite for the brain’s fine...

  10. Emerging Roles of Filopodia and Dendritic Spines in Motoneuron Plasticity during Development and Disease

    Directory of Open Access Journals (Sweden)

    Refik Kanjhan


    Full Text Available Motoneurons develop extensive dendritic trees for receiving excitatory and inhibitory synaptic inputs to perform a variety of complex motor tasks. At birth, the somatodendritic domains of mouse hypoglossal and lumbar motoneurons have dense filopodia and spines. Consistent with Vaughn’s synaptotropic hypothesis, we propose a developmental unified-hybrid model implicating filopodia in motoneuron spinogenesis/synaptogenesis and dendritic growth and branching critical for circuit formation and synaptic plasticity at embryonic/prenatal/neonatal period. Filopodia density decreases and spine density initially increases until postnatal day 15 (P15 and then decreases by P30. Spine distribution shifts towards the distal dendrites, and spines become shorter (stubby, coinciding with decreases in frequency and increases in amplitude of excitatory postsynaptic currents with maturation. In transgenic mice, either overexpressing the mutated human Cu/Zn-superoxide dismutase (hSOD1G93A gene or deficient in GABAergic/glycinergic synaptic transmission (gephyrin, GAD-67, or VGAT gene knockout, hypoglossal motoneurons develop excitatory glutamatergic synaptic hyperactivity. Functional synaptic hyperactivity is associated with increased dendritic growth, branching, and increased spine and filopodia density, involving actin-based cytoskeletal and structural remodelling. Energy-dependent ionic pumps that maintain intracellular sodium/calcium homeostasis are chronically challenged by activity and selectively overwhelmed by hyperactivity which eventually causes sustained membrane depolarization leading to excitotoxicity, activating microglia to phagocytose degenerating neurons under neuropathological conditions.

  11. [The diversity of ontogeny in animals with asexual reproduction and plasticity of early development]. (United States)

    Isaeva, V V


    Diversity of blastogenesis and embryogenesis in animals with different reproductive strategy and different variants of the isolation of germ lineage cells, defined in the literature as preformation, epigenesis, and somatic embryogenesis, is discussed. In the course of somatic embryogenesis (or, more precisely, blastogenesis), the oozooid that has developed from the egg is naturally cloned and forms numerous genetically and morphologically identical clonal individuals or modular units of a colony. This cloning results in amplification of the parent genotype; the subsequent sexual reproduction provides for genetic recombination, and the emergence of a huge number of larvae with dispersal function provides for reproductive success. In invertebrates that reproduce asexually, no isolation of the germ cell lineage takes place; the population of stem cell capable of realizing the complete developmental program, which includes gametogenesis and blastogenesis, is represented by a diaspora of cells dispersed in the organism and possessing evolutionarily conservative features of morphofunctional organization typical to cells of the germ lineage. The plasticity of early animal embryogenesis is revealed in experiments with embryonic cells cultivated in vitro. Asexual reproduction emerged repeatedly in the course of metazoan evolution; blastogenesis in animals of different taxa is more variable and less conservative than embryogenesis, but the installation of blastogenesis into the process of early embryogenesis undermines the conservatism of embryonic development.

  12. Plasticity of Streptomyces coelicolor membrane composition under different growth conditions and during development

    Directory of Open Access Journals (Sweden)

    Mario eSandoval-Calderón


    Full Text Available Streptomyces coelicolor is a model actinomycete that is well known for the diversity of its secondary metabolism and its complex life cycle. As a soil inhabitant, it is exposed to heterogeneous and frequently changing environmental circumstances. In the present work, we studied the effect of diverse growth conditions and phosphate depletion on its lipid profile and the relationship between membrane lipid composition and development in S. coelicolor. The lipid profile from cultures grown on solid media, which is closer to the natural habitat of this microorganism, does not resemble the previously reported lipid composition from liquid grown cultures of S. coelicolor. Wide variations were also observed across different media, growth phases, and developmental stages indicating active membrane remodeling. Ornithine lipids (OL are phosphorus-free polar lipids that were accumulated mainly during sporulation stages, but were also major components of the membrane under phosphorus limitation. In contrast, phosphatidylethanolamine, which had been reported as one of the major polar lipids in the genus Streptomyces, is almost absent under these conditions. We identified one of the genes responsible for the synthesis of OL (SCO0921 and found that its inactivation causes the absence of OL, precocious morphological development and actinorhodin production. Our observations indicate a remarkable plasticity of the membrane composition in this bacterial species, reveal a higher metabolic complexity than expected, and suggest a relationship between cytoplasmic membrane components and the differentiation programs in S. coelicolor.

  13. Alterations of CNS structure & function by charged particle radiation & resultant oxidative stress (United States)

    Nelson, Gregory; Chang, Polly; Favre, Cecile; Fike, John; Komarova, Natalia; Limoli, Charles; Mao, Xiao-Wen; Obenaus, Andre; Raber, Jacob; Spigelman, Igor; Soltesz, Ivan; Song, Sheng-Kwei; Stampanoni, Marco; Vlkolinsky, Roman; Wodarz, Dominik

    were complex and suggested continuous remodeling of the brain for up to 6 months. Thus we demonstrated a suite of CNS structural and functional changes after proton and iron ion exposure in the low dose regime. Based on these findings we will now test whether oxidative stress mediates the reactions of CNS to radiation exposure and what role radiation quality and dose rate play in the responses. We will use cultured neural precursor cells (mouse human) to detect changes in oxidative status and differentiation as functions of charged particle charge and velocity. These results will inform the selection of particles for many in vivo measurements that will compare wild type mice to a transgenic strain that over-expresses a human catalase gene (which inactivates hydrogen peroxide) in the mitochondrial compartment. This will explicitly test the role of reactive oxygen species in mediating the mechanisms underlying the CNS endpoints that we will measure. We will extend the electrophysiological measurements on individual nerves in hippocampal slices to characterize both inhibitory and excitatory synapses. Further, multi-electrode arrays will be used to follow correlated electrical activity in different hippocampal regions in order to understand network-level function as well as synaptic efficacy and plasticity. Controlled oxidative stress on irradiated samples will explore whether response mechanisms are shared. To link alterations in neurogenesis to performance we will explore behavioral changes mediated by the hippocampus simultaneously with measures of expression of the Arc gene in newly-born neurons. This will test whether decrements in performance correlate with loss of new cells and whether behavior properly stimulates functional integration of the new cells; the behavioral paradigm will be contextual fear conditioning. We will develop mathematical frameworks for CNS responses to radiation in order to inform risk estimates. Finally, we will couple a high

  14. Subsequent neoplasms of the CNS among survivors of childhood cancer: a systematic review. (United States)

    Bowers, Daniel C; Nathan, Paul C; Constine, Louis; Woodman, Catherine; Bhatia, Smita; Keller, Karen; Bashore, Lisa


    Childhood cancer survivors are at risk for development of subsequent neoplasms of the CNS. Better understanding of the rates, risk factors, and outcomes of subsequent neoplasms of the CNS among survivors of childhood cancer could lead to more informed screening guidelines. Two investigators independently did a systematic search of Medline and Embase (from January, 1966, through March, 2012) for studies examining subsequent neoplasms of the CNS among survivors of childhood cancer. Articles were selected to answer three questions: what is the risk of CNS tumours after radiation to the cranium for a paediatric cancer, compared with the risk in the general population; what are the outcomes in children with subsequent neoplasms of the CNS who received CNS-directed radiation for a paediatric cancer; and, are outcomes of subsequent neoplasms different from primary neoplasms of the same histology? Our search identified 72 reports, of which 18 were included in this Review. These studies reported that childhood cancer survivors have an 8·1-52·3-times higher incidence of subsequent CNS neoplasms compared with the general population. Nearly all cancer survivors who developed a CNS neoplasm had been exposed to cranial radiation, and some studies showed a correlation between radiation dose and risk of subsequent CNS tumours. 5-year survival ranged from 0-19·5% for subsequent high-grade gliomas and 57·3-100% for meningiomas, which are similar rates to those observed in patients with primary gliomas or meningiomas. The quality of evidence was limited by variation in study design, heterogeneity of details regarding treatment and outcomes, limited follow-up, and small sample sizes. We conclude that survivors of childhood cancer who received cranial radiation therapy have an increased risk for subsequent CNS neoplasms. The current literature is insufficient to comment about the potential harms and benefits of routine screening for subsequent CNS neoplasms.

  15. The wiring of developing sensory circuits - from patterned spontaneous activity to mechanisms of synaptic plasticity

    Directory of Open Access Journals (Sweden)

    Alexandra Helen Leighton


    Full Text Available In order to accurately process incoming sensory stimuli, neurons must be organized into functional networks, with both genetic and environmental factors influencing the precise arrangement of connections between cells. Teasing apart the relative contributions of molecular guidance cues, spontaneous activity and visual experience during this maturation is on-going. During development of the sensory system, the first, rough organization of connections is created by molecular factors. These connections are then modulated by the intrinsically generated activity of neurons, even before the senses have become operational. Spontaneous waves of depolarisations sweep across the nervous system, placing them in a prime position to strengthen correct connections and weaken others, shaping synapses into a useful network. A large body of work now supports the idea that, rather than being a mere side-effect of the system, spontaneous activity actually contains information which readies the nervous system so that, as soon as the senses become active, sensory information can be utilized by the animal. An example is the neonatal mouse. As soon as the eyelids first open, neurons in the cortex respond to visual information without the animal having previously encountered structured sensory input (Cang et al., 2005a; Ko et al., 2013; Rochefort et al., 2011; Zhang et al., 2012. In vivo imaging techniques have advanced considerably, allowing observation of the natural activity in the brain of living animals down to the level of the individual synapse. New (optogenetic methods make it possible to subtly modulate the spatio-temporal properties of activity, aiding our understanding of how these characteristics relate to the function of spontaneous activity. Such experiments have had a huge impact on our knowledge by permitting direct testing of ideas about the plasticity mechanisms at play in the intact system, opening up a provocative range of fresh questions. Here, we

  16. Detection of CNS and PrPSc in meat products. (United States)

    Lücker, Ernst; Hardt, Michael; Groschup, Martin H


    Several methods for the detection of tissues of the central nervous system (CNS) in meat products have been developed and partly validated for use in official food control as pertaining to human BSE-exposure risk. So far, however, methods for the detection of abnormal prion protein (PrPSc) were not evaluated for their potential applicability to the matrix of heat treated meat products. We developed a micro technological procedure for the preparation of meat products suitable for high security laboratories as masses were 6 to 8 orders of magnitude lower than in conventional meat technology. Thus it was possible to produce standard micro sausages containing defined amounts of bovine BSE-positive brain. This material showed all characteristics of normal meat products and a homogeneous distribution of brain as indicated by NSE and GFAP western immunoblotting and GFAP immunometric analyses. Using a commercially available and certified immunometric assay for detection of PrPSc in untreated brain it was possible to detect BSE-positive CNS down to a content of 0.25% in heat treated meat products. We found a high correlation between PrPSc OD-values and CNS content and linearity up to 10% CNS. In 30 samples of retail meat products no sample transgressed the official cut off value for untreated bovine brain. Further studies are needed to show whether an increase of sensitivity in PrPSc detection from the meat product matrix is possible, in particular by optimisation of the extraction procedure.

  17. Macrophage and microglial plasticity in the injured spinal cord. (United States)

    David, S; Greenhalgh, A D; Kroner, A


    Macrophages in the injured spinal cord arise from resident microglia and from infiltrating peripheral myeloid cells. Microglia respond within minutes after central nervous system (CNS) injury and along with other CNS cells signal the influx of their peripheral counterpart. Although some of the functions they carry out are similar, they appear to be specialized to perform particular roles after CNS injury. Microglia and macrophages are very plastic cells that can change their phenotype drastically in response to in vitro and in vivo conditions. They can change from pro-inflammatory, cytotoxic cells to anti-inflammatory, pro-repair phenotypes. The microenvironment of the injured CNS importantly influences macrophage plasticity. This review discusses the phagocytosis and cytokine-mediated effects on macrophage plasticity in the context of spinal cord injury.

  18. Development of suitable plastic standards for X-ray fluorescence analysis (United States)

    Mans, Christian; Hanning, Stephanie; Simons, Christoph; Wegner, Anne; Janβen, Anton; Kreyenschmidt, Martin


    For the adoption of the EU directive "Restriction on use of certain Hazardous Substances" and "Waste Electrical and Electronic Equipment" using X-ray fluorescence analysis suitable standard materials are required. Plastic standards based on acrylonitrile-butadiene-styrene terpolymer, containing the regulated elements Br, Cd, Cr, Hg and Pb were developed and produced as granulates and solid bodies. The calibration materials were not generated as a dilution from one master batch but rather the element concentrations were distributed over nine independent calibration samples. This was necessary to enable inter-elemental corrections and empirical constant mass absorption coefficients. The produced standard materials are characterized by a homogenous element distribution, which is more than sufficient for X-ray fluorescence analysis. Concentrations for all elements except for Br could be determined by Inductively Coupled Plasma Atomic Emission Spectroscopy after microwave assisted digestion. The concentration of Br was determined by use of Neutron Activation Analysis at Hahn-Meitner-Institute in Berlin, Germany. The correlation of the X-ray fluorescence analysis measurements with the values determined using Inductively Coupled Plasma Atomic Emission Spectroscopy and Neutron Activation Analysis showed a very good linearity.

  19. Editing the Neuronal Genome: a CRISPR View of Chromatin Regulation in Neuronal Development, Function, and Plasticity (United States)

    Yang, Marty G.; West, Anne E.


    The dynamic orchestration of gene expression is crucial for the proper differentiation, function, and adaptation of cells. In the brain, transcriptional regulation underlies the incredible diversity of neuronal cell types and contributes to the ability of neurons to adapt their function to the environment. Recently, novel methods for genome and epigenome editing have begun to revolutionize our understanding of gene regulatory mechanisms. In particular, the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system has proven to be a particularly accessible and adaptable technique for genome engineering. Here, we review the use of CRISPR/Cas9 in neurobiology and discuss how these studies have advanced understanding of nervous system development and plasticity. We cover four especially salient applications of CRISPR/Cas9: testing the consequences of enhancer mutations, tagging genes and gene products for visualization in live cells, directly activating or repressing enhancers in vivo, and manipulating the epigenome. In each case, we summarize findings from recent studies and discuss evolving adaptations of the method. PMID:28018138

  20. Development of Non-Quenched Prehardened Steel for Large Section Plastic Mould

    Institute of Scientific and Technical Information of China (English)

    LUO Yi; WU Xiao-chun; MIN Yong-an; ZHU Zhu; WANG Hong-bin


    In order to meet the demand of prehardened steel for large section plastic mould and save energy, a non-quenched prehardened (NQP) steel is developed. The temperature field of a large block is researched by finite ele-ment method simulation and 9 test steels are designed in the laboratory. Their microstructures and hardness are in-vestigated when they are air cooled and control cooled at cooling rate similar to the simulation. The result shows that the hardness uniformity through section is closely correlated to bainitic hardenability for the NQP steel, and the hardness of one test steel (0.27C-1.95Mn-1.04Cr-0. 45Mo-0.1V) fluctuates between HRC 40 and 43 under both cooling conditions. The test steel has better machinability compared with C45 steel, and the NQP steel is produced successfully in the factory based on the laboratory results. Its microstructure is bainite, and it is distributed uniformly through the size of 460 mm×800 mm×3 200 mm.

  1. Plasticity in the development of handedness: evidence from normal development and early asymmetric brain injury. (United States)

    Corbetta, Daniela; Williams, Joshua; Snapp-Childs, Winona


    Previous research revealed that shifting patterns of hand preference in the first year of life are linked to infants' sensory-motor experiences as they learn to sit, creep, and walk. In this report, we examine whether new and different forms of locomotion and sensory-motor experiences similarly contribute to alter patterns of hand preference in early development. We examined the cases of three infants with unique developmental histories. Two infants adopted distinctive forms of locomotion in lieu of typical hands-and-knees crawling. One infant scooted using both hands and legs in a coupled fashion, while the other infant performed an asymmetrical, left-biased belly-crawl using only one arm to drag his body. The third infant suffered damage to his left-brain hemisphere shortly after birth and received intense physical therapy to his right arm as a result of it. We followed all three infants on a weekly basis and tracked changes in their reaching behavior, mode of locomotion, and postural achievements. The two infants with unique locomotor patterns displayed changes in hand preference that reciprocated the arm patterns that they used during locomotion. The infant who coupled his body for scooting began to reach bimanually, while the infant who adopted the left-biased belly-crawl developed a strong unimanual, right-hand, preference. The infant with left-hemisphere damage initially displayed a right-hand preference, then a temporary decline in preferred hand use as he began to cruise and walk, and ultimately resumed a right-hand preference in the 2nd year of life. This data is consistent with previous work showing that the development of hand preference in the 1st year of life is highly malleable and sensitive to a variety of new sensory-motor experiences.

  2. Mechanism of plasticity Development for Ceramic Dough (Part 2). Investigation on Plasticity by Particle Packing Structure; Seramiku nendo no kasakusei hatsugen mekanizumu 2. Nendo juten kozo to kasakusei

    Energy Technology Data Exchange (ETDEWEB)

    Kawai, Shuji. [Wet Forming of Ceramics Technology Research Association, Aichi (Japan); Ichikawa, Yukari.; Ishida, Hideki. [INAX Corporation, Aichi (Japan); Shibasaki, Yasuo.; Oda, Kiichi. [National Industrial Research Institute of Nagoya, Aichi (Japan)


    Plasticity and packing structure of clay and alumina dough, and of alumina mixed with water-soluble and non-water-soluble plasticizers were investigated. It was found that both plastic clay dough and alumina dough with plasticizers showed a two-peak pore population. When the larger-sized pores increased in volume, the fluidity of the dough was improved. On the otherhand, when the smaller-sized pores decreased in volume, a high rigidity was showed. An aggregate structure was observed in the clay and the dough mixed with water-soluble plasticizer like methyl cellulose. Plasticity was generated when the aggregates were deformed by using the larger-sized pores among each aggregate. The non-water-soluble curdlan did not dissolve in the dough and remained in gel. The larger-sized pores were formed by the gel, whose deformation produced plasticity. It was understood that plasticity is fenerated when either the aggregates or the gel act as a buffer in the dough and enhance deformation of the dough. (author)

  3. Plastic value chains

    DEFF Research Database (Denmark)

    Baxter, John; Wahlstrom, Margareta; Zu Castell-Rüdenhausen, Malin


    Optimizing plastic value chains is regarded as an important measure in order to increase recycling of plastics in an efficient way. This can also lead to improved awareness of the hazardous substances contained in plastic waste, and how to avoid that these substances are recycled. As an example......, plastics from WEEE is chosen as a Nordic case study. The project aims to propose a number of improvements for this value chain together with representatives from Nordic stakeholders. Based on the experiences made, a guide for other plastic value chains shall be developed....

  4. School achievement and school adaptation in children in relation to CNS development as assessed by a complex reaction time measured on school entry--a follow-up. (United States)

    Frisk, M


    Schoolchildren aged seven years underwent a complex reaction time (CRT) measurement and were followed up regarding language achievements and performance in gymnastics during the nine years of compulsory school. An analysis was made of the correlation between school results and CRT findings. In grade 3, there were large differences in psychomotor development between children with fast and slow CRT in both sexes. Only minor differences in school achievement were seen between girls in different CRT groups. Among the boys, however, many with a slow CRT were considered handicapped in language development, with dyslexia as the most important problem in addition to poor motoricity. They left compulsory school with poor results in Swedish, their native language, and gymnastics, and with a certificate that may reduce their changes of future studies and employment. The boys in general were inferior to the girls. The slow CRT boys, who were mainly considered to be developmentally delayed, also carried a risk of social maladjustment. It would appear to be important that psychophysical maturity receives attention at school, in addition to emotional and social factors. The school health services have an important responsibility in this respect.

  5. A philosophy for CNS radiotracer design. (United States)

    Van de Bittner, Genevieve C; Ricq, Emily L; Hooker, Jacob M


    Decades after its discovery, positron emission tomography (PET) remains the premier tool for imaging neurochemistry in living humans. Technological improvements in radiolabeling methods, camera design, and image analysis have kept PET in the forefront. In addition, the use of PET imaging has expanded because researchers have developed new radiotracers that visualize receptors, transporters, enzymes, and other molecular targets within the human brain. However, of the thousands of proteins in the central nervous system (CNS), researchers have successfully imaged fewer than 40 human proteins. To address the critical need for new radiotracers, this Account expounds on the decisions, strategies, and pitfalls of CNS radiotracer development based on our current experience in this area. We discuss the five key components of radiotracer development for human imaging: choosing a biomedical question, selection of a biological target, design of the radiotracer chemical structure, evaluation of candidate radiotracers, and analysis of preclinical imaging. It is particularly important to analyze the market of scientists or companies who might use a new radiotracer and carefully select a relevant biomedical question(s) for that audience. In the selection of a specific biological target, we emphasize how target localization and identity can constrain this process and discuss the optimal target density and affinity ratios needed for binding-based radiotracers. In addition, we discuss various PET test-retest variability requirements for monitoring changes in density, occupancy, or functionality for new radiotracers. In the synthesis of new radiotracer structures, high-throughput, modular syntheses have proved valuable, and these processes provide compounds with sites for late-stage radioisotope installation. As a result, researchers can manage the time constraints associated with the limited half-lives of isotopes. In order to evaluate brain uptake, a number of methods are available

  6. Cross-modal plasticity in sensory deprived animal models: From the thalamocortical development point of view. (United States)

    Mezzera, Cecilia; López-Bendito, Guillermina


    Over recent decades, our understanding of the plasticity of the central nervous system has expanded enormously. Accordingly, it is now widely accepted that the brain can adapt to changes by reorganizing its circuitry, both in response to external stimuli and experience, as well as through intrinsic mechanisms. A clear example of this is the activation of a deprived sensory area and the expansion of spared sensory cortical regions in individuals who suffered peripheral sensory loss. Despite the efforts to understand these neuroplastic changes, the mechanisms underlying such adaptive remodeling remains poorly understood. Progress in understanding these events may be hindered by the highly varied data obtained from the distinct experimental paradigms analyzed, which include different animal models and neuronal systems, as well as studies into the onset of sensory loss. Here, we will establish the current state-of-the-art describing the principal observations made according to the time of sensory deprivation with respect to the development of the thalamocortical connectivity. We will review the experimental data obtained from animal models where sensory deprivation has been induced either before or after thalamocortical axons reach and invade their target cortical areas. The anatomical and functional effects of sensory loss on the primary sensory areas of the cortex will be presented. Indeed, we consider that the comparative approach of this review is a necessary step in order to help deciphering the processes that underlie sensory neuroplasticity, for which studies in animal models have been indispensable. Understanding these mechanisms will then help to develop restorative strategies and prostheses that will overcome the functional loss.

  7. Overlapping expression patterns of the multiligand endocytic receptors cubilin and megalin in the CNS, sensory organs and developing epithelia of the rodent embryo. (United States)

    Assémat, Emeline; Châtelet, François; Chandellier, Jacqueline; Commo, Frédéric; Cases, Olivier; Verroust, Pierre; Kozyraki, Renata


    Cubilin and megalin are multiligand epithelial endocytic receptors well characterized in the adult kidney and ileum where they form a complex essential for protein, lipid and vitamin uptake. Although inactivation of the megalin gene leads to holoprosencephaly and administration of anti-cubilin antibodies induces fetal resorptions or cranio-facial malformations their function in the developing embryo remains unclear. We recently showed that both proteins are strongly expressed by the maternal-fetal interfaces and the neuroepithelium of the early rodent embryo where they co-localize and form a complex important for nutrient uptake. The aim of the present study was the further investigation of cubilin expression at later developmental stages of the rodent embryo and its correlation to that of megalin. Immunohistochemical and in situ hybridization analysis showed striking similarities in the spatial and temporal expression patterns of cubilin and megalin. The electrophoretic mobility of both proteins was identical to that of the adult as revealed by Western blot analysis. Cubilin and megalin were strongly expressed in the sensory organs, the central nervous system, the respiratory and urogenital tracts as well as in the thymus, parathyroids and thyroid. In each site, the expression mainly concerned epithelial structures and correlated with the onset of epithelial induction. Depending on the site, a decreased or restricted expression was observed by the end of the gestation for both proteins.

  8. Clinical features, outcomes, and cerebrospinal fluid findings in adult patients with central nervous system (CNS) infections caused by varicella-zoster virus: comparison with enterovirus CNS infections. (United States)

    Hong, Hyo-Lim; Lee, Eun Mi; Sung, Heungsup; Kang, Joong Koo; Lee, Sang-Ahm; Choi, Sang-Ho


    Varicella-zoster virus (VZV) is known to be associated with central nervous system (CNS) infections in adults. However, the clinical characteristics of VZV CNS infections are not well characterized. The aim of this study was to compare the clinical manifestations, outcomes, and cerebrospinal fluid (CSF) findings in patients with VZV CNS infections with those in patients with enterovirus (EV) CNS infections. This retrospective cohort study was performed at a 2,700-bed tertiary care hospital. Using a clinical microbiology computerized database, all adults with CSF PCR results positive for VZV or EV that were treated between January 1999 and February 2013 were identified. Thirty-eight patients with VZV CNS infection and 68 patients with EV CNS infection were included in the study. Compared with the EV group, the median age in the VZV group was higher (VZV, 35 years vs. EV, 31 years; P = 0.02), and showed a bimodal age distribution with peaks in the third and seventh decade. Encephalitis was more commonly encountered in the VZV group (VZV, 23.7% vs. EV, 4.4%; P = 0.01). The median lymphocyte percentage in the CSF (VZV, 81% vs. EV, 36%; P < 0.001) and the CSF protein level (VZV, 100 mg/dl vs. EV, 46 mg/dl; P < 0.001) were higher in the VZV group. Compared with patients with EV CNS infection, patients with VZV CNS infection developed encephalitis more often and exhibited more intense inflammatory reaction. Nevertheless, both VZV and EV CNS infections were associated with excellent long-term prognosis. © 2014 Wiley Periodicals, Inc.

  9. Are Supramodality and Cross-Modal Plasticity the Yin and Yang of Brain Development? From Blindness to Rehabilitation. (United States)

    Cecchetti, Luca; Kupers, Ron; Ptito, Maurice; Pietrini, Pietro; Ricciardi, Emiliano


    Research in blind individuals has primarily focused for a long time on the brain plastic reorganization that occurs in early visual areas. Only more recently, scientists have developed innovative strategies to understand to what extent vision is truly a mandatory prerequisite for the brain's fine morphological architecture to develop and function. As a whole, the studies conducted to date in sighted and congenitally blind individuals have provided ample evidence that several "visual" cortical areas develop independently from visual experience and do process information content regardless of the sensory modality through which a particular stimulus is conveyed: a property named supramodality. At the same time, lack of vision leads to a structural and functional reorganization within "visual" brain areas, a phenomenon known as cross-modal plasticity. Cross-modal recruitment of the occipital cortex in visually deprived individuals represents an adaptative compensatory mechanism that mediates processing of non-visual inputs. Supramodality and cross-modal plasticity appears to be the "yin and yang" of brain development: supramodal is what takes place despite the lack of vision, whereas cross-modal is what happens because of lack of vision. Here we provide a critical overview of the research in this field and discuss the implications that these novel findings have for the development of educative/rehabilitation approaches and sensory substitution devices (SSDs) in sensory-impaired individuals.

  10. Are supramodality and cross-modal plasticity the yin and yang of brain development? From blindness to rehabilitation.

    Directory of Open Access Journals (Sweden)

    Luca Cecchetti


    Full Text Available Research in blind individuals has primarily focused for a long time on the brain plastic reorganization that occurs in early visual areas. Only more recently, scientists have developed innovative strategies to understand to what extent vision is truly a mandatory prerequisite for the brain’s fine morphological architecture to develop and function. As a whole, the studies conducted to date in sighted and congenitally blind individuals have provided ample evidence that several ‘visual’ cortical areas develop independently from visual experience and do process information content regardless of the sensory modality through which a particular stimulus is conveyed: a property named supramodality. At the same time, lack of vision leads to a structural and functional reorganization within 'visual' brain areas, a phenomenon known as cross-modal plasticity. Cross-modal recruitment of the occipital cortex in visually deprived individuals represents an adaptative compensatory mechanism that mediates processing of non-visual inputs. Supramodality and cross-modal plasticity appear to be the 'yin and yang' of brain development: supramodal is what takes place despite the lack of vision, whereas cross-modal is what happens because of lack of vision. Here we provide a critical overview of the research in this field and discuss the implications that these novel findings have for the development of educative/rehabilitation approaches and sensory substitution devices in sensory-impaired individuals.

  11. INS/CNS/GNSS integrated navigation technology

    CERN Document Server

    Quan, Wei; Gong, Xiaolin; Fang, Jiancheng


    This book not only introduces the principles of INS, CNS and GNSS, the related filters and semi-physical simulation, but also systematically discusses the key technologies needed for integrated navigations of INS/GNSS, INS/CNS, and INS/CNS/GNSS, respectively. INS/CNS/GNSS integrated navigation technology has established itself as an effective tool for precise positioning navigation, which can make full use of the complementary characteristics of different navigation sub-systems and greatly improve the accuracy and reliability of the integrated navigation system. The book offers a valuable reference guide for graduate students, engineers and researchers in the fields of navigation and its control. Dr. Wei Quan, Dr. Jianli Li, Dr. Xiaolin Gong and Dr. Jiancheng Fang are all researchers at the Beijing University of Aeronautics and Astronautics.

  12. Development of a unified viscoplasticity constitutive model based on classical plasticity theory

    Institute of Scientific and Technical Information of China (English)

    GUAN Ping; LIU ChangChun; L(U) HeXiang


    The traditional unified viscoplasticity constitutive model can be only applied to metal materials. The study of the unified constitutive theory for metal materials has discovered the correlation between the classical plasticity theory and the unified viscoplasticity constitutive model, thus leading to the con-cepts of the classic plastic potential and yield surface in the unified constitutive model. Moreover, this research has given the continuous expression of the classical plastic multiplier and presented the corresponding constructive method, which extends its physical significance and lays down a good foundation for the application of the unified constitutive theory to the material analysis in more fields.This paper also introduces the unified constitutive model for metal materials and geo-materials. The numerical simulation indicates that the construction should be both reasonable and practical.

  13. Development of a unified viscoplasticity constitutive model based on classical plasticity theory

    Institute of Scientific and Technical Information of China (English)


    The traditional unified viscoplasticity constitutive model can be only applied to metal materials.The study of the unified constitutive theory for metal materials has discovered the correlation between the classical plasticity theory and the unified viscoplasticity constitutive model,thus leading to the con-cepts of the classic plastic potential and yield surface in the unified constitutive model.Moreover,this research has given the continuous expression of the classical plastic multiplier and presented the corresponding constructive method,which extends its physical significance and lays down a good foundation for the application of the unified constitutive theory to the material analysis in more fields.This paper also introduces the unified constitutive model for metal materials and geo-materials.The numerical simulation indicates that the construction should be both reasonable and practical.

  14. The spectrum of post-vaccination inflammatory CNS demyelinating syndromes. (United States)

    Karussis, Dimitrios; Petrou, Panayiota


    A wide variety of inflammatory diseases temporally associated with the administration of various vaccines, has been reported in the literature. A PubMed search from 1979 to 2013 revealed seventy one (71) documented cases. The most commonly reported vaccinations that were associated with CNS demyelinating diseases included influenza (21 cases), human papilloma virus (HPV) (9 cases), hepatitis A or B (8 cases), rabies (5 cases), measles (5 cases), rubella (5 cases), yellow fever (3 cases), anthrax (2 cases),meningococcus (2 cases) and tetanus (2 cases). The vast majority of post-vaccination CNS demyelinating syndromes, are related to influenza vaccination and this could be attributed to the high percentage of the population that received the vaccine during the HI1N1 epidemia from 2009 to 2012. Usually the symptoms of the CNS demyelinating syndrome appear few days following the immunization (mean: 14.2 days) but there are cases where the clinical presentation was delayed (more than 3 weeks or even up to 5 months post-vaccination) (approximately a third of all the reported cases). In terms of the clinical presentation and the affected CNS areas, there is a great diversity among the reported cases of post-vaccination acute demyelinating syndromes. Optic neuritis was the prominent clinical presentation in 38 cases, multifocal disseminated demyelination in 30, myelitis in 24 and encephalitis in 17. Interestingly in a rather high proportion of the patients (and especially following influenza and human papiloma virus vaccination-HPV) the dominant localizations of demyelination were the optic nerves and the myelon, presenting as optic neuritis and myelitis (with or without additional manifestations of ADEM), reminiscent to neuromyelitic optica (or, more generally, the NMO-spectrum of diseases). Seven patients suffered an NMO-like disease following HPV and we had two similar cases in our Center. One patient with post-vaccination ADEM, subsequently developed NMO. Overall, the

  15. HIV-1 target cells in the CNS


    Joseph, Sarah B.; Arrildt, Kathryn T.; Sturdevant, Christa B.; Swanstrom, Ronald


    HIV-1 replication in the central nervous system (CNS) is typically limited by the availability of target cells. HIV-1 variants that are transmitted and dominate the early stages of infection almost exclusively use the CCR5 coreceptor and are well adapted to entering, and thus infecting, cells expressing high CD4 densities similar to those found on CD4+ T cells. While the “immune privileged” CNS is largely devoid of CD4+ T cells, macrophage and microglia are abundant throughout ...

  16. CNS toxoplasmosis in an immunocompetent individual



    Toxoplasmosis is a serious and life-threatening disease in humans with a high prevalence in immunocompromised persons. The disease has a wide spectrum, depending on the immune status of the person. A CNS manifestation of toxoplasmosis in an immunocompetent person is very rare and often undetected. Our case of CNS toxoplasmosis in an immunocompetent person emphasizes the radiological diagnosis, which was further confirmed by advanced microbiology technique.

  17. CNS toxoplasmosis in an immunocompetent individual

    Directory of Open Access Journals (Sweden)

    Rajoo Ramachandran, MBBS, MD


    Full Text Available Toxoplasmosis is a serious and life-threatening disease in humans with a high prevalence in immunocompromised persons. The disease has a wide spectrum, depending on the immune status of the person. A CNS manifestation of toxoplasmosis in an immunocompetent person is very rare and often undetected. Our case of CNS toxoplasmosis in an immunocompetent person emphasizes the radiological diagnosis, which was further confirmed by advanced microbiology technique.

  18. Plasticity theory

    CERN Document Server

    Lubliner, Jacob


    The aim of Plasticity Theory is to provide a comprehensive introduction to the contemporary state of knowledge in basic plasticity theory and to its applications. It treats several areas not commonly found between the covers of a single book: the physics of plasticity, constitutive theory, dynamic plasticity, large-deformation plasticity, and numerical methods, in addition to a representative survey of problems treated by classical methods, such as elastic-plastic problems, plane plastic flow, and limit analysis; the problem discussed come from areas of interest to mechanical, structural, and

  19. IQGAP1: A microtubule-microfilament scaffolding protein with multiple roles in nerve cell development and synaptic plasticity. (United States)

    Jausoro, Ignacio; Mestres, Iván; Remedi, Mónica; Sanchez, Mónica; Cáceres, Alfredo


    In this article, we review our current understanding of the biology of IQ domain-containing GTPase-Activating Protein 1, IQGAP1, a scaffolding protein with multiple binding partners, which is widely expressed among different cell types, including neurons, and capable of linking Rho-GTPase signaling with cytosleletal elements and environmental cues. Interestingly, a series of recent studies suggest that IQGAP family members have an important role in neuronal development, synaptic plasticity and nervous system disorders involving alterations in spine density.

  20. Development of PPR Copper-Plastic Pipe Fitting%PPR铜塑管件的开发

    Institute of Scientific and Technical Information of China (English)

    袁飞; 王聚中


    Injection molding method was used to produce PPR copper-plastic pipe fitting. The effect of process conditions, such as copper surface treatment, copper groove depth, injection pressure, injection pressure holding time on PPR copper-plastic pipe fitting quality were discussed. The results show that when the copper surface is plated with chrome, copper groove depth is 2. 0 mm, injection pressure is 60 Mpa, plasticizing temperature is 200 ℃ , injection holding time is 20 s, the Dn63 PPR copper-plastic pipe fitting quality is good.%采用注靼法生产出无规共聚聚丙烯(PPR)铜塑管件.讨论了铜件表面处理、铜件沟槽深度、注射压力、注射保压时间等工艺条件对PPR铜塑管件质量的影响.结果表明,当铜件表面经镀铬处理、铜件沟槽深度2.0 mm、注射压力60 MPa、塑化温度200℃、注射保压时间20 s时,Dn63规格的PPR铜塑管件质量较理想.

  1. Development of a prototype sensor to detect plastic contamination in seed cotton at the gin (United States)

    US cotton is considered to have some of the lowest levels of contamination in the world. That reputation is expected by foreign and domestic mills. Despite this reputation, U.S. spinners have recently experienced some serious contamination issues with US cotton. Of particular concern are plastic con...

  2. Green building blocks for biobased plastics: biobased processes and market development

    NARCIS (Netherlands)

    Harmsen, P.F.H.; Hackmann, M.M.


    From a chemical perspective, nearly all building blocks for plastics can be made using renewable raw materials. However, not every process is commercially feasible. Processes often remain inefficient, products have insufficient purity or the raw materials are simply too expensive. This publication p

  3. Dr. J. F. S. Esser and his influence on the development of plastic and reconstructive surgery

    NARCIS (Netherlands)

    B. Haeseker (Barend)


    textabstractJan F.S. Esser (1877-1946) was a remarkable and gifled Dutch surgeon whose contributions to plastic and reconstructive surgery, made long befare this specialty was recognised as a branch of surgery, are part of our surgical heritage. His interest in the bloodsupply of skin flaps was the


    Energy Technology Data Exchange (ETDEWEB)

    Michael V. Glazoff; Jeong-Whan Yoon


    In this report (prepared in collaboration with Prof. Jeong Whan Yoon, Deakin University, Melbourne, Australia) a research effort was made to develop a non associated flow rule for zirconium. Since Zr is a hexagonally close packed (hcp) material, it is impossible to describe its plastic response under arbitrary loading conditions with any associated flow rule (e.g. von Mises). As a result of strong tension compression asymmetry of the yield stress and anisotropy, zirconium displays plastic behavior that requires a more sophisticated approach. Consequently, a new general asymmetric yield function has been developed which accommodates mathematically the four directional anisotropies along 0 degrees, 45 degrees, 90 degrees, and biaxial, under tension and compression. Stress anisotropy has been completely decoupled from the r value by using non associated flow plasticity, where yield function and plastic potential have been treated separately to take care of stress and r value directionalities, respectively. This theoretical development has been verified using Zr alloys at room temperature as an example as these materials have very strong SD (Strength Differential) effect. The proposed yield function reasonably well models the evolution of yield surfaces for a zirconium clock rolled plate during in plane and through thickness compression. It has been found that this function can predict both tension and compression asymmetry mathematically without any numerical tolerance and shows the significant improvement compared to any reported functions. Finally, in the end of the report, a program of further research is outlined aimed at constructing tensorial relationships for the temperature and fluence dependent creep surfaces for Zr, Zircaloy 2, and Zircaloy 4.

  5. Positron emission tomography in CNS drug discovery and drug monitoring. (United States)

    Piel, Markus; Vernaleken, Ingo; Rösch, Frank


    Molecular imaging methods such as positron emission tomography (PET) are increasingly involved in the development of new drugs. Using radioactive tracers as imaging probes, PET allows the determination of the pharmacokinetic and pharmacodynamic properties of a drug candidate, via recording target engagement, the pattern of distribution, and metabolism. Because of the noninvasive nature and quantitative end point obtainable by molecular imaging, it seems inherently suited for the examination of a pharmaceutical's behavior in the brain. Molecular imaging, most especially PET, can therefore be a valuable tool in CNS drug research. In this Perspective, we present the basic principles of PET, the importance of appropriate tracer selection, the impact of improved radiopharmaceutical chemistry in radiotracer development, and the different roles that PET can fulfill in CNS drug research.

  6. The shifting landscape of metastatic breast cancer to the CNS. (United States)

    Quigley, Matthew R; Fukui, Olivia; Chew, Brandon; Bhatia, Sanjay; Karlovits, Steven


    The improved survival following the diagnosis of breast cancer has potentially altered the characteristics and course of patients presenting with CNS involvement. We therefore sought to define our current cohort of breast cancer patients with metastatic disease to the CNS in regard to modern biomarkers and clinical outcome. Review of clinical and radiographic records of women presenting to a tertiary medical center with the new diagnosis of CNS metastatic disease from breast cancer. This was a retrospective review from patients identities obtained from two prospective databases. There were 88 women analyzed who were treated over the period of January 2003 to February 2010, average age 56.9 years. At the time of initial presentation of CNS disease, 68 % of patients had multiple brain metastases, 17 % had a solitary metastasis, and 15 % had only leptomeningeal disease (LMD). The median survival for all patients from the time of diagnosis of breast disease was 50.0 months, and 9.7 months from diagnosis of CNS involvement. The only factor related to overall survival was estrogen receptor-positive pathology (57.6 v. 38.2 months, p = .02 log-rank); those related to survival post CNS diagnosis were presentation with LMD (p = .004, HR = 3.1, Cox regression) and triple-negative hormonal/HER2 status (p = .02, HR = 2.3, Cox regression). Patients with either had a median survival of 3.1 months (no patients in common). Of the 75 patients who initially presented with metastatic brain lesions, 20 (26 %) subsequently developed LMD in the course of their disease (median 10.4 months), following which survival was grim (1.8 months median). Symptoms of LMD were most commonly lower extremity weakness (14/33), followed by cranial nerve deficits (11/33). The recently described Graded Prognostic Assessment (GPA) tumor index stratified median survival at 2.5, 5.9, 13.1, and 21.7 months, respectively, for indices of 1-4 (p = .004, log-rank), which

  7. Monitoring the CNS pathology in aspartylglucosaminuria mice. (United States)

    Tenhunen, K; Uusitalo, A; Autti, T; Joensuu, R; Kettunen, M; Kauppinen, R A; Ikonen, S; LaMarca, M E; Haltia, M; Ginns, E I; Jalanko, A; Peltonen, L


    Aspartylglucosaminuria (AGU) is a recessively inherited lysosomal storage disorder caused by the deficiency of the aspartylglucosaminidase (AGA) enzyme. The hallmark of AGU is slowly progressing mental retardation but the progression of brain pathology has remained uncharacterized in humans. Here we describe the long-term follow-up of mice carrying a targeted AGU-mutation in both alleles. Immunohistochemistry, histology, electron microscopy, quantitative magnetic resonance imaging (MRI) and behavioral studies were carried out to evaluate the CNS affection of the disease during development. The lysosomal storage vacuoles of the AGA -/- mice were most evident in central brain regions where MRI also revealed signs of brain atrophy similar to that seen in the older human patients. By immunohistochemistry and MRI examinations, a subtle delay of myelination was observed in AGA -/- mice. The life span of the AGA -/- mice was not shortened. Similar to the slow clinical course observed in human patients, the AGA -/- mice have behavioral symptoms that emerge at older age. Thus, the AGU knock-out mice represent an accurate model for AGU, both histopathologically and phenotypically.

  8. Environmental cues from CNS, PNS, and ENS cells regulate CNS progenitor differentiation

    DEFF Research Database (Denmark)

    Brännvall, Karin; Corell, Mikael; Forsberg-Nilsson, Karin;


    Cellular origin and environmental cues regulate stem cell fate determination. Neuroepithelial stem cells form the central nervous system (CNS), whereas neural crest stem cells generate the peripheral (PNS) and enteric nervous system (ENS). CNS neural stem/progenitor cell (NSPC) fate determination...

  9. [Peculiarities of brain mechanisms of compensation of oxygen-dependent energy deficit, organization of emotions and cognitive activity at delayed consequences of perinatal lesion of CNS of the hypoxic-ischemic genesis in children of 3-6 years with delay of psychic development]. (United States)

    Ilyukhina, V A; Matveev, Yu K; Ivanova, T B; Koshulko, M A; Nurok, M Yu


    There are summarized results of studies on peculiarities of formation of compensatory-adaptive mechanisms of brain circulation and respiration at oxygen-dependent energy deficit in the 3-6-year old children with delayed consequences of perinatal CNS lesion of the hypoxic-ischemic genesis and delay of psychic development (DPD) with use of the systemic-integrative approach and of parameters of superslow information-control systems of brain and of organism. In the examined contingent of children, differences have been revealed in development of emotional sphere and the higher psychic functions depending on character of disorganization of regulatory CNS functions and of the type of formed compensatory-adaptive mechanisms of autoregulation of cerebral circulation and of the system of external respiration.

  10. Laser Sensor Development for Fluorescence Detection of Plastics and other Anthropogenic Compounds Dissolved in Seawater (United States)


    in situ AUV-mounted instrument designed to locate and identify plastic and rubber-coated objects, such as mines, in the water column and buried...particulate (phytoplankton) fluorescence for remote sensing, plume tracking, and pollution applications. The multi-channel UV laser-induced fluorescence...deformulation and chemical analyses of commercial marine epoxy systems (Chemir/Polytech, Inc.). Results of the chemical analyses indicate that the water



    Kool, Marcel; Sturm, Dominik; Northcott, Paul A.; Jones, David T. W.; Korshunov, Andrey; Lichter, Peter; Pfister, Stefan


    BACKGROUND: According to the current WHO classification of CNS tumors, childhood CNS primitive neuro-ectodermal tumors (CNS-PNETs; WHO °IV) are poorly differentiated embryonal tumors with early onset and aggressive clinical behavior. Histological diagnosis can be complicated by morphological heterogeneity and divergent differentiation. Recent studies suggest the existence of molecular subgroups of CNS-PNETs sharing biological characteristics with other childhood CNS tumors. Here, we aimed at ...

  12. Armies of pestilence: CNS infections as potential weapons of mass destruction. (United States)

    Hart, B L; Ketai, L


    Infectious agents have been investigated, developed, and used by both governments and terrorist groups as weapons of mass destruction. CNS infections, though traditionally considered less often than respiratory diseases in this scenario, may be very important. Viruses responsible for encephalitides can be highly infectious in aerosol form. CNS involvement in anthrax is ominous but should change treatment. Brucellosis, plague, Q fever, and other bacteria can uncommonly manifest with meningoencephalitis and other findings. Emerging diseases may also pose threats. We review infectious agents of particular concern for purposes of biowarfare with respect to CNS manifestations and imaging features. © 2015 by American Journal of Neuroradiology.

  13. Cell state switching factors and dynamical patterning modules: complementary mediators of plasticity in development and evolution

    Indian Academy of Sciences (India)

    Stuart A Newman; Ramray Bhat; Nadejda V Mezentseva


    Ancient metazoan organisms arose from unicellular eukaryotes that had billions of years of genetic evolution behind them. The transcription factor networks present in single-celled ancestors at the origin of the Metazoa (multicellular animals) were already capable of mediating the switching of the unicellular phenotype among alternative states of gene activity in response to environmental conditions. Cell differentiation, therefore, had its roots in phenotypic plasticity, with the ancient regulatory proteins acquiring new targets over time and evolving into the ``developmental transcription factors” (DTFs) of the ``developmental-genetic toolkit.” In contrast, the emergence of pattern formation and morphogenesis in the Metazoa had a different trajectory. Aggregation of unicellular metazoan ancestors changed the organisms’ spatial scale, leading to the first ``dynamical patterning module” (DPM): cell-cell adhesion. Following this, other DPMs (defined as physical forces and processes pertinent to the scale of the aggregates mobilized by a set of toolkit gene products distinct from the DTFs), transformed simple cell aggregates into hollow, multilayered, segmented, differentiated and additional complex structures, with minimal evolution of constituent genes. Like cell differentiation, therefore, metazoan morphologies also originated from plastic responses of cells and tissues. Here we describe examples of DTFs and most of the important DPMs, discussing their complementary roles in the evolution of developmental mechanisms. We also provide recently characterized examples of DTFs in cell type switching and DPMs in morphogenesis of avian limb bud mesenchyme, an embryo-derived tissue that retains a high degree of developmental plasticity.

  14. 汽车用改性塑料的发展概况%Automotive Modified Plastics Development Overview

    Institute of Scientific and Technical Information of China (English)



    在汽车工业中,“以轻代重”“以塑代钢”已经逐渐成为了该行业未来发展的主流方向,特别是聚苯醚(PPO)、尼龙(PA)、聚丙烯(PP)、聚碳酸酯(PC)和聚甲醛(POM)这5类材料改性塑料的应用。简要探讨了与这些材料有关的最新研究成果和其在汽车零部件上的最新应用情况,并分析了改性塑料行业的技术发展趋势和行业应用趋势。%In the automotive industry, the“light generation heavy”“plastic steel”has gradually become the mainstream of the industry’s future development, especially polyphenylene oxide(PPO), nylon(PA), polypropylene(PP), polycarbonate(PC)and POM(POM)plastic material modification of these five categories of applications. Brief discussion of the latest research results and its latest applications with these materials related to the automotive components and analyzes technology trends and industry trends modified plastics industry applications.

  15. Use of a relational database program for quantification of the CNS role. (United States)

    Picella, D V


    In the current state of flux and economic retrenchment in the healthcare system, clinical nurse specialists (CNSs) are challenged to clearly define their contribution to high quality patient care services. Systems for documenting and reporting on CNS activities that are flexible, easy to use, and do not require extensive time commitments to use are needed. A systematic approach for developing a tool to collect data about the CNS role is presented. This tool can be used with an adaptation of computerized relational database technology that can handle the inputting, managing, and reporting of data collected about the CNS roles and associated activities. A relational database computer software application can run on a personal computer or laptop. When applied to structural evaluation of the CNS role, this system has potential for quickly and effectively performing periodic evaluations that clearly document how CNS time is spent. An accurate and usable database of CNS activities is a critical step toward demonstrating whether or not the CNS is performing appropriate functions and establishes a foundation of critical information for further evaluation of process and outcome data. Further exploration of this technology through experience in its applied use is needed.

  16. Plastic Jellyfish. (United States)

    Moseley, Christine


    Presents an environmental science activity designed to enhance students' awareness of the hazards of plastic waste for wildlife in aquatic environments. Discusses how students can take steps to reduce the effects of plastic waste. (WRM)

  17. Mechanisms of Plastic and Fracture Instabilities for Alloy Development of Fusion Materials. Final Project Report for period July 15, 1998 - July 14, 2003

    Energy Technology Data Exchange (ETDEWEB)

    Ghoniem, N. M.


    The main objective of this research was to develop new computational tools for the simulation and analysis of plasticity and fracture mechanisms of fusion materials, and to assist in planning and assessment of corresponding radiation experiments.

  18. Development of Craze and Impact Resistance in Glazing Plastics by Multiaxial Stretching (United States)

    Kline, G M; Wolock, I; Axilrod, B M; Sherman, M A; George, D A; Cohen, V


    The loss of strength of cast polymethyl methacrylate plastic as a result of crazing is of considerable importance to the aircraft industry. Because of the critical need for basic information on the nature of crazing and the effects of various treatments and environmental conditions on its incidence and magnitude, an investigation of this phenomenon was undertaken. The following factors were examined: (1) the effect of stress-solvent crazing on tensile strength of polymethyl methacrylate; (2) the critical stress and strain for onset of crazing at various temperatures; (3) the effect of molecular weight on crazing; and (4) the effect of multiaxial stretching on crazing of polymethyl methacrylate and other acrylic glazing materials.

  19. Drug induced increases in CNS dopamine alter monocyte, macrophage and T cell functions: implications for HAND (United States)

    Gaskill, Peter J.; Calderon, Tina M.; Coley, Jacqueline S.; Berman, Joan W.


    Central nervous system (CNS) complications resulting from HIV infection remain a major public health problem as individuals live longer due to the success of combined antiretroviral therapy (cART). As many as 70% of HIV infected people have HIV associated neurocognitive disorders (HAND). Many HIV infected individuals abuse drugs, such as cocaine, heroin or methamphetamine, that may be important cofactors in the development of HIV CNS disease. Despite different mechanisms of action, all drugs of abuse increase extracellular dopamine in the CNS. The effects of dopamine on HIV neuropathogenesis are not well understood, and drug induced increases in CNS dopamine may be a common mechanism by which different types of drugs of abuse impact the development of HAND. Monocytes and macrophages are central to HIV infection of the CNS and to HAND. While T cells have not been shown to be a major factor in HIV-associated neuropathogenesis, studies indicate that T cells may play a larger role in the development of HAND in HIV infected drug abusers. Drug induced increases in CNS dopamine may dysregulate functions of, or increase HIV infection in, monocytes, macrophages and T cells in the brain. Thus, characterizing the effects of dopamine on these cells is important for understanding the mechanisms that mediate the development of HAND in drug abusers. PMID:23456305

  20. Myelin Damage and Repair in Pathologic CNS: Challenges and Prospects

    Directory of Open Access Journals (Sweden)

    Arsalan eAlizadeh


    Full Text Available Injury to the central nervous system (CNS results in oligodendrocyte cell death and progressive demyelination. Demyelinated axons undergo considerable physiological changes and molecular reorganizations that collectively result in axonal dysfunction, degeneration and loss of sensory and motor functions. Endogenous adult oligodendrocyte precursor cells (OPCs and neural stem/progenitor cells (NPCs contribute to the replacement of oligodendrocytes, however, the extent and quality of endogenous remyelination is suboptimal. Emerging evidence indicates that optimal remyelination is restricted by multiple factors including (i low levels of factors that promote oligodendrogenesis; (ii cell death among newly generated oligodendrocytes, (iii inhibitory factors in the post-injury milieu that impede remyelination, and (iv deficient expression of key growth factors essential for proper re-construction of a highly organized myelin sheath. Considering these challenges, over the past several years, a number of cell-based strategies have been developed to optimize remyelination therapeutically. Outcomes of these basic and preclinical discoveries are promising and signify the importance of remyelination as a mechanism for improving functions in CNS injuries. In this review, we provide an overview on: 1 the precise organization of myelinated axons and the reciprocal axo-myelin interactions that warrant properly balanced physiological activities within the CNS; 2 underlying cause of demyelination and the structural and functional consequences of demyelination in axons following injury and disease; 3 the endogenous mechanisms of oligodendrocyte replacement; 4 the modulatory role of reactive astrocytes and inflammatory cells in remyelination; and 5 the current status of cell-based therapies for promoting remyelination. Careful elucidation of the cellular and molecular mechanisms of demyelination in the pathologic CNS is a key to better understanding the impact of

  1. Origin, fate and dynamics of macrophages at CNS interfaces (United States)

    Goldmann, Tobias; Jordão, Marta Joana Costa; Wieghofer, Peter; Prutek, Fabiola; Hagemeyer, Nora; Frenzel, Kathrin; Staszewski, Ori; Kierdorf, Katrin; Amann, Lukas; Krueger, Martin; Locatelli, Giuseppe; Hochgarner, Hannah; Zeiser, Robert; Epelman, Slava; Geissmann, Frederic; Priller, Josef; Rossi, Fabio; Bechmann, Ingo; Kerschensteiner, Martin; Linnarsson, Sten; Jung, Steffen; Prinz, Marco


    Perivascular, meningeal and choroid plexus macrophages are non-parenchymal macrophages that mediate immune responses at brain boundaries. Although the origin of parenchymal microglia has recently been elucidated, much less is known about the precursors, the underlying transcriptional program and the dynamics of the other macrophages in the central nervous system (CNS). It has been assumed that they have a high turnover with blood-borne monocytes. However, large scale single-cell RNA-sequencing reveals a striking molecular overlap between perivascular macrophages and microglia but not monocytes. Using several fate mapping approaches and parabiosis we demonstrate that CNS macrophages arise from yolk sac precursors during embryonic development and remain a stable population. Notably, the generation of CNS macrophages relies on the transcription factor Pu.1 whereas myb, Batf3 and Nr4a1 are not required. Upon autoimmune inflammation, macrophages undergo extensive self-renewal by local proliferation. Our data provide challenging new insights into brains innate immune system. PMID:27135602

  2. Role of Academic Drug Discovery in the Quest for New CNS Therapeutics. (United States)

    Yokley, Brian H; Hartman, Matthew; Slusher, Barbara S


    There was a greater than 50% decline in central nervous system (CNS) drug discovery and development programs by major pharmaceutical companies from 2009 to 2014. This decline was paralleled by a rise in the number of university led drug discovery centers, many in the CNS area, and a growth in the number of public-private drug discovery partnerships. Diverse operating models have emerged as the academic drug discovery centers adapt to this changing ecosystem.

  3. Recycling of plastic wastes from electric and electronic sector new developments; Reciclado de residuos plasticos del sector electrico y electronico. Nuevos desarrollos

    Energy Technology Data Exchange (ETDEWEB)

    Miguel, R.; Larrauri, E.; Cacho, I.


    Automated technologies for the identification and sorting of plastic wastes have been developed to get an adequate and cost-effective recycling. When dealing with plastics from end-of-live electric and electronic equipment not only the polymeric matrix but also fillers and/or flame retardant additives and/or pigments, need to be taken in account. At present, several specific projects are being carried out by GAIKER in order to solve the technological challenge of recycling plastics from the electric and electronic sector. (Author)

  4. Analysis, design and development of a carbon fibre reinforced plastic knee-ankle-foot orthosis prototype for myopathic patients. (United States)

    Granata, C; De Lollis, A; Campo, G; Piancastelli, L; Merlini, L


    A traditional knee-ankle-foot orthosis (KAFO) for myopathic patients has been studied for the assessment of loads and fatigue resistance. Starting from this basis a thermoplastic matrix carbon fibre reinforced plastic composite (CFRP) KAFO has been developed in order to reduce the weight. A finite-element simulation programme for deformation analysis was used to compare the behaviour of conventional and CFRP orthosis. There were no breakages either of the prototype or of its parts. The CFRP orthosis allows a weight reduction of more than 40 per cent.

  5. Development of a Plastic-Based Microfluidic Immunosensor Chip for Detection of H1N1 Influenza

    Directory of Open Access Journals (Sweden)

    Tae Jung Park


    Full Text Available Lab-on-a-chip can provide convenient and accurate diagnosis tools. In this paper, a plastic-based microfluidic immunosensor chip for the diagnosis of swine flu (H1N1 was developed by immobilizing hemagglutinin antigen on a gold surface using a genetically engineered polypeptide. A fluorescent dye-labeled antibody (Ab was used for quantifying the concentration of Ab in the immunosensor chip using a fluorescent technique. For increasing the detection efficiency and reducing the errors, three chambers and three microchannels were designed in one microfluidic chip. This protocol could be applied to the diagnosis of other infectious diseases in a microfluidic device.

  6. Distinctive response of CNS glial cells in oro-facial pain associated with injury, infection and inflammation

    Directory of Open Access Journals (Sweden)

    Ribeiro-da-Silva Alfredo


    contrast, CFA injection led to minor microglial morphological changes and an induction of IκB-α mRNA in the CVO regions; a significant increase in IL-1β and IL-6 mRNA started only at 48 hours post-injection, when the induced pain-related behavior started to resolve. Our detailed analysis of CNS glial response clearly revealed that both nerve injury and oro-facial infection/inflammation induced CNS glial activation, but in a completely different pattern, which suggests a remarkable plasticity of glial cells in response to dynamic changes in their microenvironment and different potential involvement of this non-neuronal cell population in pathological pain development.

  7. Development of Bake Hardening Effect by Plastic Deformation and Annealing Conditions

    Directory of Open Access Journals (Sweden)

    Kvačkaj, T.


    Full Text Available The paper deals with the classification of steel sheets for automotives industry on the basis of strength and structural characteristics. Experimental works were aimed to obtain the best possible strengthening parameters as well as work hardening and solid solution ferrite hardening, which are the result of thermal activation of interstitial carbon atoms during paint-baking of auto body. Hardening process coming from interstitial atoms is realized as two-step process. The first step is BH (bake hardening effect achieved by interaction of interstitial atoms with dislocations. The Cottrels atmosphere is obtained. The second step of BH effect is to produced the hardening from precipitation of the carbon atoms in e-carbides, or formation of Fe32C4 carbides. WH (work hardening effect is obtained as dislocation hardening from plastic deformations during sheet deep drawing. Experimental works were aimed at as to achieve such plastic material properties after cold rolling, annealing and skin-pass rolling, which would be able to classify the material ZStE220BH into the drawing categories at the level of DQ – DDQ. As resulting from the experimental results, the optimal treatment conditions for the maximal sum (WH+BH = 86 MPa are as follows: total cold rolling deformation ecold = 65 %, annealing temperature Tanneal. = 700 °C.

  8. Delusional Disorder Arising From a CNS Neoplasm. (United States)

    Stupinski, John; Kim, Jihye; Francois, Dimitry


    Erotomania arising from a central nervous system (CNS) neoplasm has not been previously described. Here, we present the first known case, to our knowledge, of erotomania with associated persecutory delusions arising following diagnosis and treatment of a left frontal lobe brain tumor.

  9. Immune regulation and CNS autoimmune disease

    DEFF Research Database (Denmark)

    Antel, J P; Owens, T


    The central nervous system is a demonstrated target of both clinical and experimental immune mediated disorders. Immune regulatory mechanisms operative at the levels of the systemic immune system, the blood brain barrier, and within the CNS parenchyma are important determinants of the intensity a...

  10. Coordinated Noninvasive Studies (CNS) Project (United States)


    indicated for each. Identification of the molecules represented by each of the peaks here is difficult, even in the invasive dog experiments described by...defined dysfunctions, Such as autism and dementia, and to obtain detailed Information regarding brain function even In subjects who cannot Ann NY Acad Sc 508: 1-537. Courchesne E (In press) Cerebellar changes In autism . In J Swann and A Messer (Eds) Disorders of the developing

  11. Developments in plastic wire chambers operated in the limited streamer mode (LSM detectors) (United States)

    Laakso, Mikko; Kurvinen, Kari; Orava, Risto


    We have calculated the photon detection efficiency of a wire chamber constructed with conductive nylon-66 plastic as cathode material in the photon energy range of 100 keV-1 MeV. The calculated results are compared with the results obtained with a Monte Carlo simulation using the FLUKA [1] transport code and with experimental results. We have also calculated the efficiency for copper and compared these two cathode materials. The comparison shows that wire chambers with nylon and copper cathodes are equally efficient in detecting the 100 keV-1 MeV photons. Furthermore, we have studied the different physical processes contributing to photon detection as well as the detection efficiency as a function of cathode thickness. Finally, we report some results from the first LSM detector operational tests performed with our new wire chamber testing device.

  12. Effects of the kainate receptor agonist ATPA on glutamatergic synaptic transmission and plasticity during early postnatal development. (United States)

    Sallert, Marko; Malkki, Hemi; Segerstråle, Mikael; Taira, Tomi; Lauri, Sari E


    Kainate type of glutamate receptors (KARs) modulate synaptic transmission in a developmentally regulated manner at several synapses in the brain. Previous studies have shown that KARs depress glutamatergic transmission at CA3-CA1 synapses in the hippocampus and these receptors are tonically active during early postnatal development. Here we use the GluR5 subunit specific agonist ATPA to further characterize the role of KARs in the modulation of synaptic transmission and plasticity in area CA1 during the first two weeks of life. We find that the depressant effect of ATPA on evoked fEPSPs/EPSCs is smaller in the neonate (P3-P6) than in the juvenile (P14-P18) rat CA1, due to endogenous activity of KAR in the neonate. Further, in the neonate but not juvenile CA1, ATPA downregulates action-potential independent transmission (mEPSCs) and its effects are dependent on protein kinase C activity. ATPA-induced depression of fEPSPs in the neonate occludes the presynaptic component of long-term depression (LTD). In contrast, at P14-P18, ATPA prevents LTD indirectly via GABAergic mechanisms. These data show that GluR5 signaling mechanisms are developmentally regulated and suggest distinct functional role for KARs in the modulation of synaptic transmission and plasticity at different stages of development.

  13. 3D standard brain of the red flour beetle Tribolium castaneum: a tool to study metamorphic development and adult plasticity

    Directory of Open Access Journals (Sweden)

    David Dreyer


    Full Text Available The red flour beetle Tribolium castaneum is emerging as a further standard insect model beside Drosophila. Its genome is fully sequenced and it is susceptible for genetic manipulations including RNA-interference. We use this beetle to study adult brain development and plasticity primarily with respect to the olfactory system. In the current study, we provide 3D standard brain atlases of freshly eclosed adult female and male beetles (A0. The atlases include eight paired and three unpaired neuropils including antennal lobes, optic lobe neuropils, mushroom body calyces and pedunculi, and central complex. For each of the two standard brains, we averaged brain areas of 20 individual brains. Additionally, we characterized eight selected olfactory glomeruli from 10 A0 female and male beetles respectively, which we could unequivocally recognize from individual to individual owing to their size and typical position in the antennal lobes. In summary, comparison of the averaged neuropil volumes revealed no sexual dimorphism in any of the reconstructed neuropils in A0 Tribolium brains. Both, the female and male 3D standard brain are also used for interspecies comparisons, and, very importantly, will serve as future volumetric references after genetical manipulation especially regarding metamorphic development and adult plasticity.

  14. Anti-homeostatic synaptic plasticity of glycine receptor function after chronic strychnine in developing cultured mouse spinal neurons. (United States)

    Carrasco, M A; Castro, P A; Sepulveda, F J; Cuevas, M; Tapia, J C; Izaurieta, P; van Zundert, B; Aguayo, L G


    In this study, we describe a novel form of anti-homeostatic plasticity produced after culturing spinal neurons with strychnine, but not bicuculline or 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Strychnine caused a large increase in network excitability, detected as spontaneous synaptic currents and calcium transients. The calcium transients were associated with action potential firing and activation of gamma-aminobutyric acid (GABA(A)) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors as they were blocked by tetrodotoxin (TTX), bicuculline, and CNQX. After chronic blockade of glycine receptors (GlyRs), the frequency of synaptic transmission showed a significant enhancement demonstrating the phenomenon of anti-homeostatic plasticity. Spontaneous inhibitory glycinergic currents in treated cells showed a fourfold increase in frequency (from 0.55 to 2.4 Hz) and a 184% increase in average peak amplitude compared with control. Furthermore, the augmentation in excitability accelerated the decay time constant of miniature inhibitory post-synaptic currents. Strychnine caused an increase in GlyR current density, without changes in the apparent affinity. These findings support the idea of a post-synaptic action that partly explains the increase in synaptic transmission. This phenomenon of synaptic plasticity was blocked by TTX, an antibody against brain-derived neurotrophic factor (BDNF) and K252a suggesting the involvement of the neuronal activity-dependent BDNF-TrkB signaling pathway. These results show that the properties of GlyRs are regulated by the degree of neuronal activity in the developing network.

  15. MAG, myelin and overcoming growth inhibition in the CNS

    National Research Council Canada - National Science Library

    McKerracher, Lisa; Rosen, Kenneth M


    While neurons in the central nervous system (CNS) have the capacity to regenerate their axons after injury, they fail to do so, in part because regeneration is limited by growth inhibitory proteins present in CNS myelin...

  16. The New Trends of the Research and Development in the Biodegradeble Plastics%可降解塑料开发的动向

    Institute of Scientific and Technical Information of China (English)

    柳明珠; 刘锴


      本文概述了国内外可降解性材料的研究、开发现状与市场前景。并重点考察了发达国家有关生物降解、可控光、生双降解塑料的实际应用和使用降解塑料(包括农膜、包装材料等)的研究。%  It is increasingly being realized that the use of long-lasting for short-lived applications is not entirely justified especially when increased concern exists about the preservation of living systems. The elimination of the waste plastics is therefor of interest in surgery, hygiene, and catering, packing, agriculture, fishing, environmental protection and other potential applications. Most of today’s plastics and synthetic polymers are produced from petrochemicals. As conventional plastics are persistent in the environment, improperly disposed plastics materials are a significant source of environmental pollution, potentially harming wildlife. The production of biodegradable plastics can be viewed within the wider context of the “greening of industry”. Considering of the new development in the field of the biodegradable polymers, this paper discusses current status and new developments of research and technology of the biodegradable plastics in the foreign countries and also in China.

  17. 塑料水杯盖注塑模具设计%Development of Injection Mold for Plastic Cup Cover

    Institute of Scientific and Technical Information of China (English)

    李润娟; 张艳霞


    The 3D shape of the plastic cup cover is generated by the software UG.Based on the analysis of the structure process of the plastic parts, The gate location and the mould joint are selected,the core and cavity of the mould structure are designed.A large number of computer aided design is used in the course of design, which shorts the development cycle and reduces production cost.%利用UG软件对塑料水杯盖进行了产品的三维造型,在对塑件结构工艺性分析的基础上,进行了浇口位置和分型面的选择,型芯、型腔、模具等结构的设计,设计过程中采用了大量计算机辅助模具设计,缩短了开发周期,降低了生产成本。

  18. Development of plastic elongation in nanocrystalline and amorphous Ni–W dual phase alloys by brushing technique

    Energy Technology Data Exchange (ETDEWEB)

    Nakayama, S., E-mail:; Adachi, H., E-mail:; Yamasaki, T., E-mail:


    Highlights: • A novel agitation technique called the brushing technique is proposed. • A homogeneous material can be obtained with the brushing technique. • The brushed material exhibits large plastic elongation with work hardening. - Abstract: A novel agitation technique, referred to as the “brushing technique” is proposed to treat the surface of a Ni–W alloy film during electrodeposition. This technique was developed to directly remove hydrogen bubbles on the film surface and to apply Ni ions to the interfacial layer with the substrate. The intrinsic mechanical properties of the Ni–W electrodeposits are then evaluated with respect to application. High resolution transmission electron microscopy observations revealed that both treated and untreated films have nanocrystallites of approximately 5 nm in diameter and an amorphous phase. There was a compositional difference of about. 1.4 at% W between the face side and the reverse side of the film that was not subjected to the brushing technique, whereas this difference was absent in the film subjected to the brushing technique. In addition, the brushing technique reduced the surface roughness of the film and decreased the number of defects. As a result, a large plastic strain of about. 2.9% was observed with work hardening under tensile testing.

  19. Consequences of brain-derived neurotrophic factor withdrawal in CNS neurons and implications in disease. (United States)

    Mariga, Abigail; Mitre, Mariela; Chao, Moses V


    Growth factor withdrawal has been studied across different species and has been shown to have dramatic consequences on cell survival. In the nervous system, withdrawal of nerve growth factor (NGF) from sympathetic and sensory neurons results in substantial neuronal cell death, signifying a requirement for NGF for the survival of neurons in the peripheral nervous system (PNS). In contrast to the PNS, withdrawal of central nervous system (CNS) enriched brain-derived neurotrophic factor (BDNF) has little effect on cell survival but is indispensible for synaptic plasticity. Given that most early events in neuropsychiatric disorders are marked by a loss of synapses, lack of BDNF may thus be an important part of a cascade of events that leads to neuronal degeneration. Here we review reports on the effects of BDNF withdrawal on CNS neurons and discuss the relevance of the loss in disease.

  20. The plasticizer bisphenol A affects somatic and sexual development, but differently in pipid, hylid and bufonid anurans. (United States)

    Tamschick, Stephanie; Rozenblut-Kościsty, Beata; Ogielska, Maria; Kekenj, David; Gajewski, Franz; Krüger, Angela; Kloas, Werner; Stöck, Matthias


    Due to their terrestrial habitats and aquatic reproduction, many amphibians are both very vulnerable and highly suitable bioindicators. The plasticizer bisphenol A (BPA) is one of the most produced chemical substances worldwide, and knowledge on its impacts on humans and animals is mounting. BPA is used for the industrial production of polycarbonate plastics and epoxy resins and found in a multitude of consumer products. Studies on BPA have involved mammals, fish and the fully aquatic anuran model Xenopus laevis. However, our knowledge about the sexual development of non-model, often semi-terrestrial anuran amphibians remains poor. Using a recently developed experimental design, we simultaneously applied BPA to two non-model species (Hyla arborea, Hylidae; Bufo viridis, Bufonidae) and the model X. laevis (Pipidae), compared their genetic and phenotypic sex for detection of sex reversals, and studied sexual development, focusing on anatomical and histological features of gonads. We compared three concentrations of BPA (0.023, 2.28 and 228 μg/L) to control groups in a high-standard flow-through-system, and tested whether conclusions, drawn from the model species, can be extrapolated to non-model anurans. In contrast to previous studies on fish and Xenopus, often involving dosages much higher than most environmental pollution data, we show that BPA causes neither the development of mixed sex nor of sex-reversed individuals (few, seemingly BPA-independent sex reversals) in all focal species. However, environmentally relevant concentrations, as low as 0.023 μg/L, were sufficient to provoke species-specific anatomically and histologically detectable impairments of gonads, and affected morphological traits of metamorphs. As the intensity of these effects differed between the three species, our data imply that BPA diversely affects amphibians with different evolutionary history, sex determination systems and larval ecologies. These results highlight the role of

  1. Equal perimeter yield criterion and its specific plastic work rate: Development, validation and application

    Institute of Scientific and Technical Information of China (English)

    章顺虎; 赵德文; 陈晓东


    In order to overcome the nonlinearity of Mises criterion, a new linear yield criterion with a dodecagon shape of the same perimeter as Mises criterion was derived by means of geometrical analysis. Its specific plastic work rate expressed as a linear function of the yield stress, the maximum and minimum strains was also deduced and compared with that of Mises criterion. The physical meaning of the proposed yield criterion is that yielding of materials begins when the shear yield stress τs reaches the magnitude of 0.594σs. By introducing the Lode parameter, validation of evolution expressions of the proposed yield criterion with those based on Tresca, Mises and TSS criteria as well as available classical yield experimental results of various metals shows that the present results intersect with Mises results and coincide well with experimental data. Moreover, further application to the limit analysis of circle plate as an example is performed to demonstrate the effectiveness of the proposed yield criterion, and the subsequent comparison of limit loads with the Tresca analytical solutions and Mises numerical results shows that the present results are higher than the Tresca analytical results, and are in good agreement with the Mises numerical results.

  2. Achieving Control of Lesion Growth in CNS with Minimal Damage

    CERN Document Server

    Raja, Mathankumar


    Lesions in central nervous system (CNS) and their growth leads to debilitating diseases like Multiple Sclerosis (MS), Alzheimer's etc. We developed a model earlier which shows how the lesion growth can be arrested through a beneficial auto-immune mechanism. The success of the approach depends on a set of control parameters and their phase space was shown to have a smooth manifold separating the uncontrolled lesion growth region from the controlled. Here we show that an optimal set of parameter values exist which minimizes system damage while achieving control of lesion growth.

  3. Plasticity of Myeloid Cells during Oral Barrier Wound Healing and the Development of Bisphosphonate-related Osteonecrosis of the Jaw. (United States)

    Sun, Yujie; Kaur, Kawaljit; Kanayama, Keiichi; Morinaga, Kenzo; Park, Sil; Hokugo, Akishige; Kozlowska, Anna; McBride, William H; Li, Jun; Jewett, Anahid; Nishimura, Ichiro


    Injury to the barrier tissue initiates a rapid distribution of myeloid immune cells from bone marrow, which guide sound wound healing. Bisphosphonates, a widely used anti-bone resorptive drug with minimal systemic side effects, have been linked to an abnormal wound healing in the oral barrier tissue leading to, in some cases, osteonecrosis of the jaw (ONJ). Here we report that the development of ONJ may involve abnormal phenotypic plasticity of Ly6G+/Gr1+ myeloid cells in the oral barrier tissue undergoing tooth extraction wound healing. A bolus intravenous zoledronate (ZOL) injection to female C57Bl/6 mice followed by maxillary first molar extraction resulted in the development of ONJ-like lesion during the second week of wound healing. The multiplex assay of dissociated oral barrier cells exhibited the secretion of cytokines and chemokines, which was significantly modulated in ZOL mice. Tooth extraction-induced distribution of Ly6G+/Gr1+ cells in the oral barrier tissue increased in ZOL mice at week 2. ONJ-like lesion in ZOL mice contained Ly6G+/Gr1+ cells with abnormal size and morphology as well as different flow cytometric staining intensity. When anti-Ly6G (Gr1) antibody was intraperitoneally injected for 5 days during the second week of tooth extraction, CD11b+GR1(hi) cells in bone marrow and Ly6G+ cells in the oral barrier tissue were depleted, and the development of ONJ-like lesion was significantly attenuated. This study suggests that local modulation of myeloid cell plasticity in the oral barrier tissue may provide the basis for pathogenesis and thus therapeutic as well as preventive strategy of ONJ.

  4. SINS/CNS Nonlinear Integrated Navigation Algorithm for Hypersonic Vehicle

    Directory of Open Access Journals (Sweden)

    Yong-jun Yu


    Full Text Available Celestial Navigation System (CNS has characteristics of accurate orientation and strong autonomy and has been widely used in Hypersonic Vehicle. Since the CNS location and orientation mainly depend upon the inertial reference that contains errors caused by gyro drifts and other error factors, traditional Strap-down Inertial Navigation System (SINS/CNS positioning algorithm setting the position error between SINS and CNS as measurement is not effective. The model of altitude azimuth, platform error angles, and horizontal position is designed, and the SINS/CNS tightly integrated algorithm is designed, in which CNS altitude azimuth is set as measurement information. GPF (Gaussian particle filter is introduced to solve the problem of nonlinear filtering. The results of simulation show that the precision of SINS/CNS algorithm which reaches 130 m using three stars is improved effectively.

  5. An Example of Learning about Plastics and Their Evaluation as a Contribution to Education for Sustainable Development in Secondary School Chemistry Teaching (United States)

    Burmeister, Mareike; Eilks, Ingo


    This paper describes the development and evaluation of a secondary school lesson plan for chemistry education on the topic Education for Sustainable Development (ESD). The lessons focus both on the chemistry of plastics and on learning about the societal evaluation of competing, chemistry-based industrial products. A specific teaching method was…

  6. Potential environmental benefits of improving recycling of polyolefines – LCA of Magnetic density separation (MDS) developed in the EU FP7 funded project W2Plastic

    DEFF Research Database (Denmark)

    Olsen, Stig Irving; Bonou, Alexandra


    The core of the EU FP7 funded project W2Plastic is development of a magnetic density separation (MDS) of polyolefines in order to improve the sorting efficiency of these polymer types in different waste fractions. As part of the project a life cycle assessment is performed in order to firstly...... identify eco-design criteria for the development and secondly to document the potential environmental improvement of polyolefin recycling using the MDS technology. A preliminary study focusing solely on the carbon footprint benefits of recycling plastic waste compared to virgin production of polymers...

  7. Natural host genetic resistance to lentiviral CNS disease: a neuroprotective MHC class I allele in SIV-infected macaques.

    Directory of Open Access Journals (Sweden)

    Joseph L Mankowski

    Full Text Available Human immunodeficiency virus (HIV infection frequently causes neurologic disease even with anti-retroviral treatment. Although associations between MHC class I alleles and acquired immunodeficiency syndrome (AIDS have been reported, the role MHC class I alleles play in restricting development of HIV-induced organ-specific diseases, including neurologic disease, has not been characterized. This study examined the relationship between expression of the MHC class I allele Mane-A*10 and development of lentiviral-induced central nervous system (CNS disease using a well-characterized simian immunodeficiency (SIV/pigtailed macaque model. The risk of developing CNS disease (SIV encephalitis was 2.5 times higher for animals that did not express the MHC class I allele Mane-A*10 (P = 0.002; RR = 2.5. Animals expressing the Mane-A*10 allele had significantly lower amounts of activated macrophages, SIV RNA, and neuronal dysfunction in the CNS than Mane-A*10 negative animals (P<0.001. Mane-A*10 positive animals with the highest CNS viral burdens contained SIV gag escape mutants at the Mane-A*10-restricted KP9 epitope in the CNS whereas wild type KP9 sequences dominated in the brain of Mane-A*10 negative animals with comparable CNS viral burdens. These concordant findings demonstrate that particular MHC class I alleles play major neuroprotective roles in lentiviral-induced CNS disease.

  8. Plastic bronchitis

    National Research Council Canada - National Science Library

    Singhi, Anil Kumar; Vinoth, Bharathi; Kuruvilla, Sarah; Sivakumar, Kothandam


    Plastic bronchitis, a rare but serious clinical condition, commonly seen after Fontan surgeries in children, may be a manifestation of suboptimal adaptation to the cavopulmonary circulation with unfavorable hemodynamics...

  9. Cerebellar Development and Plasticity: Perspectives for Motor Coordination Strategies, for Motor Skills, and for Therapy

    Directory of Open Access Journals (Sweden)

    J. D. Swinny


    Full Text Available The role of the mammalian cerebellum ranges from motor coordination, sensory-motor integration, motor learning, and timing to nonmotor functions such as cognition. In terms of motor function, the development of the cerebellum is of particular interest because animal studies show that the development of the cerebellar cortical circuitry closely parallels motor coordination. Ultrastructural analysis of the morphological development of the cerebellar circuitry, coupled with the temporal and spatial identification of the neurochemical substrates expressed during development, will help to elucidate their roles in the establishment of the cerebellar circuitry and hence motor activity. Furthermore, the convenience of a number of naturally occurring mouse mutations has allowed a functional dissection of the various cellular elements that make up the cerebellar circuitry. This understanding will also help in the approach to possible therapies of pathologies arising during development because tile cerebellum is especially prone to such perturbation because of its late development.

  10. Drug Delivery Systems, CNS Protection, and the Blood Brain Barrier

    Directory of Open Access Journals (Sweden)

    Ravi Kant Upadhyay


    Full Text Available Present review highlights various drug delivery systems used for delivery of pharmaceutical agents mainly antibiotics, antineoplastic agents, neuropeptides, and other therapeutic substances through the endothelial capillaries (BBB for CNS therapeutics. In addition, the use of ultrasound in delivery of therapeutic agents/biomolecules such as proline rich peptides, prodrugs, radiopharmaceuticals, proteins, immunoglobulins, and chimeric peptides to the target sites in deep tissue locations inside tumor sites of brain has been explained. In addition, therapeutic applications of various types of nanoparticles such as chitosan based nanomers, dendrimers, carbon nanotubes, niosomes, beta cyclodextrin carriers, cholesterol mediated cationic solid lipid nanoparticles, colloidal drug carriers, liposomes, and micelles have been discussed with their recent advancements. Emphasis has been given on the need of physiological and therapeutic optimization of existing drug delivery methods and their carriers to deliver therapeutic amount of drug into the brain for treatment of various neurological diseases and disorders. Further, strong recommendations are being made to develop nanosized drug carriers/vehicles and noninvasive therapeutic alternatives of conventional methods for better therapeutics of CNS related diseases. Hence, there is an urgent need to design nontoxic biocompatible drugs and develop noninvasive delivery methods to check posttreatment clinical fatalities in neuropatients which occur due to existing highly toxic invasive drugs and treatment methods.

  11. Cerebellar Development and Plasticity: Perspectives for Motor Coordination Strategies, for Motor Skills, and for Therapy


    Swinny, J. D; van der Want, J.J.L.; Gramsbergen, A.


    The role of the mammalian cerebellum ranges from motor coordination, sensory-motor integration, motor learning, and timing to nonmotor functions such as cognition. In terms of motor function, the development of the cerebellum is of particular interest because animal studies show that the development of the cerebellar cortical circuitry closely parallels motor coordination. Ultrastructural analysis of the morphological development of the cerebellar circuitry, coupled with the temporal and spat...

  12. China Plastics Industry (2011) China Plastics Processing Industry Association

    Institute of Scientific and Technical Information of China (English)

    Li Ying


    General situation of China plastics industry in 2011 was reviewed, including the output and export/import of plastics products, synthetic resins,and plastics processing machinery, as well as major economic data, such as the total industrial values, sales and profits of plastics products, etc. Analysis of the market of plastics products in 2011 was made, and the developing trend of China plastics industry in 2012 was proposed.

  13. Plastic Fishes

    CERN Multimedia

    Trettnak, Wolfgang


    In terms of weight, the plastic pollution in the world’s oceans is estimated to be around 300,000 tonnes. This plastic comes from both land-based and ocean-based sources. A lecture at CERN by chemist Wolfgang Trettnak addressed this issue and highlighted the role of art in raising people’s awareness. The slideshow below gives you a taste of the artworks by Wolfgang Trettnak and Margarita Cimadevila.

  14. Plastic Bridge

    Institute of Scientific and Technical Information of China (English)



    Already ubiquitous in homes and cars, plastic is now appearing inbridges. An academic-industrial consortium based at the University ofCalifornia in San Diego is launching a three-year research program aimed atdeveloping the world’s first plastic highway bridge, a 450-foot span madeentirely from glass-,carbon,and polymer-fiber-reinforced composite mate-rials, the stuff of military aircraft. It will cross Interstate 5 to connect thetwo sides of the school’s campus.

  15. Evaluation of CNS activity of Bramhi Ghrita

    Directory of Open Access Journals (Sweden)

    Achliya G


    Full Text Available OBJECTIVE: To eavaluate the CNS activity of Bramhi Ghrita, a polyherbal formulation containing Bacopa monneri, Evolvulus alsinoids, Acorus calamus, Saussurea lappa and cow′s ghee. MATERIALS AND METHODS: The effect of Bramhi Ghrita on motor coordination, behavior, sleep, convulsions, locomotion and analgesia was evaluated in mice using standard procedures. RESULTS: The formulation exhibited reduced alertness, spontaneous locomotor activity and reactivity. It also antagonized the behavioral effects of d-amphetamine, potentiated the pentobarbitone-induced sleep and increased the pain threshold. Bramhi Ghrita protected mice from maximum electroshock and pentylene tetrazole-induced convulsions.

  16. Positive Allosteric Modulators of Type 5 Metabotropic Glutamate Receptors (mGluR5 and Their Therapeutic Potential for the Treatment of CNS Disorders

    Directory of Open Access Journals (Sweden)

    Richard M. Cleva


    Full Text Available Studies utilizing selective pharmacological antagonists or targeted gene deletion have demonstrated thattype 5 metabotropic glutamate receptors (mGluR5 are critical mediators and potential therapeutic targets for the treatment of numerous disorders of the central nervous system (CNS, including depression, anxiety, drug addiction, chronic pain, Fragile X syndrome, Parkinson’s disease, and gastroesophageal reflux disease. However, in recent years, the development of positive allosteric modulators (PAMs of the mGluR5 receptor have revealed that allosteric activation of this receptor may also be of potential therapeutic benefit for the treatment of other CNS disorders, including schizophrenia, cognitive deficits associated with chronic drug use, and deficits in extinction learning. Here we summarize the discovery and characterization of various mGluR5 PAMs, with an emphasis on those that are systemically active. We will also review animal studies showing that these molecules have potential efficacy as novel antipsychotic agents. Finally, we will summarize findings that suggest that mGluR5 PAMs have pro-cognitive effects such as the ability toenhance synaptic plasticity, improve performance in various learning and memory tasks, including extinction of drug-seeking behavior, and reverse cognitive deficits produced by chronic drug use.

  17. Marine microplastics - Method development for detection of plastic particles from sea water down to 10 μm

    DEFF Research Database (Denmark)

    Lenz, Robin; Enders, Kristina


    ingesting seabirds are perceived easily by the broad public through emotionally charged photographs and personal experiences on beaches all around the globe. Monitoring programs, beach clean-ups, source elimination, and societal changes such as local bans of single-use plastic bags or outphasing......During the past few years and especially in 2014, plastic pollution has gained a lot of media attention and public awareness is rising. Management plans and policies start to adopt strategies for mitigating effects and reducing entry of marine litter and beached plastic. Strangled seals or plastic...... on the bottom of the food web, whose existence and importance we are rarely aware of. There are chances for severe impacts in plastic accumulating ocean gyres which are of oligotrophic nature and consequently low food availability. So far the concentrations, biological impact and the fate of disintegrating...

  18. Are capecitabine and the active metabolite 5-Fu CNS penetrable to treat breast cancer brain metastasis? (United States)

    Zhang, Jinqiang; Zhang, Lingli; Yan, Yumei; Li, Shaorong; Xie, Liang; Zhong, Wei; Lv, Jing; Zhang, Xiuhua; Bai, Yu; Cheng, Ziqiang


    Brain metastasis (BM) is increasingly diagnosed in Her2 positive breast cancer (BC) patients. Lack of effective treatment to breast cancer brain metastases (BCBMs) is probably due to inability of the current therapeutic agents to cross the blood-brain barrier. The central nervous system (CNS) response rate in BCBM patients was reported to improve from 2.6%-6% (lapatinib) to 20%-65% (lapatinib in combination with capecitabine). Lapatinib is a poor brain penetrant. In this study, we evaluated the CNS penetration of capecitabine and hoped to interpret the mechanism of the improved CNS response from the pharmacokinetic (PK) perspective. Capecitabine does not have antiproliferative activity and 5-fluorouracil (5-FU) is the active metabolite. Capecitabine was orally administered to mouse returning an unbound brain-to-blood ratio (Kp,uu,brain) at 0.13 and cerebrospinal fluid (CSF)-to-unbound blood ratio (Kp,uu,CSF) at 0.29 for 5-FU. Neither free brain nor CSF concentration of 5-FU can achieve antiproliferative concentration for 50% of maximal inhibition of cell proliferation of 4.57 µM. BCBM mice were treated with capecitabine monotherapy or in combination with lapatinib. The Kp,uu,brain value of 5-FU increased to 0.17 in the brain tumor in the presence of lapatinib, which is still far below unity. The calculated free concentration of 5-FU and lapatinib in the brain tumor did not reach the antiproliferative potency and neither treatment showed antitumor activity in the BCBM mice. The CNS penetration of 5-FU in human was predicted based on the penetration in preclinical brain tumor, CSF, and human PK and the predicted free CNS concentration was below the antiproliferative potency. These results suggest that CNS penetration of 5-FU and lapatinib are not desirable and development of a true CNS penetrable therapeutic agent will further improve the response rate for BCBM.

  19. Degradation of Oxo-Biodegradable Plastic by Pleurotus ostreatus


    José Maria Rodrigues da Luz; Sirlaine Albino Paes; Mateus Dias Nunes; Marliane de Cássia Soares da Silva; Maria Catarina Megumi Kasuya


    Growing concerns regarding the impact of the accumulation of plastic waste over several decades on the environmental have led to the development of biodegradable plastic. These plastics can be degraded by microorganisms and absorbed by the environment and are therefore gaining public support as a possible alternative to petroleum-derived plastics. Among the developed biodegradable plastics, oxo-biodegradable polymers have been used to produce plastic bags. Exposure of this waste plastic to ul...

  20. Degradation of Oxo-Biodegradable Plastic by Pleurotus ostreatus


    José Maria Rodrigues da Luz; Sirlaine Albino Paes; Mateus Dias Nunes; Marliane de Cássia Soares da Silva; Maria Catarina Megumi Kasuya


    Growing concerns regarding the impact of the accumulation of plastic waste over several decades on the environmental have led to the development of biodegradable plastic. These plastics can be degraded by microorganisms and absorbed by the environment and are therefore gaining public support as a possible alternative to petroleum-derived plastics. Among the developed biodegradable plastics, oxo-biodegradable polymers have been used to produce plastic bags. Exposure of this waste plastic to ul...

  1. Insulin-like growth factor binding protein-2 as a regulator of IGF actions in CNS : Implications in multiple sclerosis

    NARCIS (Netherlands)

    Chesik, Daniel; De Keyser, Jacques; Wilczak, Nadine


    Insulin-like growth factors (IGFs) are indispensable peptide hormones for proper development of the central nervous system (CNS). Because IGF-1 exhibits neuroprotective and myelinogenetic effects, it possesses therapeutic potential in treating neurodegenerative demyelinating diseases such as


    Ryzhkova, M V; Lopatina, E B


    The goal of this study was to examine the plasticity of the thermal reaction norms for development in the European Peacock butterfly Inachis io under the effect of different photoperiodic conditions and group versus individual maintenance. The overwintered imagoes were collected in Old Peterhof (near Saint-Petersburg) in May, 2010 and 2012-2013. 12 experimental regimens were used: 4 temperatures (16, 18, 20 and 22 degrees C) and 3 photoperiods (12, 18 and 22 h of light a day). It was found that under short-day conditions (12 h) the caterpillars developed a little faster than under long-day ones (22 h). The developmental temperature thresholds in these two cases did not differ. A linear regression coefficient characterizing thermal sensitivity of development was significantly higher only in males with their development affected by short-day photoperiod stronger than in females. At 18-h day length, the caterpillar development was less temperature-sensitive and characterized by a lower threshold than in shorter and longer days. The influence of short-day photoperiod on the caterpillar development manifested itself most distinctly in the emerging pupae' weight changes: in all the temperature regimens the pupae were lighter at short than at long days. The pupal weight increased as the temperature rose. The found dependence does not agree with the "temperature-size rule". Individual rearing led to a longer duration and lower thermal sensitivity of caterpillar and pupal development as well as to a reduced weight of the pupae. Individual rearing had a stronger impact on the mineral of females than males.



    Mr. Pankaj Kumar*, Sonia


    This paper gives a brief idea about a new type of plastic called as bio-plastic or green plastic. Plastic is used as a packaging material for various products, but this plastic is made up of non renewable raw materials. There are various disadvantages of using conventional plastic like littering, CO2 production, non-degradable in nature etc. To overcome these problems a new type of plastic is discovered called bio-plastic or green plastic. Bio-plastic is made from renewable resources and also...

  4. Evolution of phenotypic plasticity in colonizing species. (United States)

    Lande, Russell


    I elaborate an hypothesis to explain inconsistent empirical findings comparing phenotypic plasticity in colonizing populations or species with plasticity from their native or ancestral range. Quantitative genetic theory on the evolution of plasticity reveals that colonization of a novel environment can cause a transient increase in plasticity: a rapid initial increase in plasticity accelerates evolution of a new optimal phenotype, followed by slow genetic assimilation of the new phenotype and reduction of plasticity. An association of colonization with increased plasticity depends on the difference in the optimal phenotype between ancestral and colonized environments, the difference in mean, variance and predictability of the environment, the cost of plasticity, and the time elapsed since colonization. The relative importance of these parameters depends on whether a phenotypic character develops by one-shot plasticity to a constant adult phenotype or by labile plasticity involving continuous and reversible development throughout adult life. © 2014 John Wiley & Sons Ltd.

  5. The Role of Rho GTPase Proteins in CNS Neuronal Migration (United States)

    Govek, Eve-Ellen; Hatten, Mary E.; Van Aelst, Linda


    The architectonics of the mammalian brain arise from a remarkable range of directed cell migrations, which orchestrate the emergence of cortical neuronal layers and pattern brain circuitry. At different stages of cortical histogenesis, specific modes of cell motility are essential to the stepwise formation of cortical architecture. These movements range from interkinetic nuclear movements at the ventricular zone (VZ), to migrations of early-born, postmitotic polymorphic cells into the preplate, to the radial migration of precursors of cortical output neurons across the thickening cortical wall, and the vast, tangential migrations of interneurons from the basal forebrain into the emerging cortical layers. In all cases, acto-myosin motors act in concert with cell adhesion receptor systems to provide the force and traction needed for forward movement. As key regulators of actin and microtubule cytoskeletons, cell polarity, and adhesion, the Rho GTPases play a critical role in CNS neuronal migration. This review will focus on the different types of migration in the developing neocortex and cerebellar cortex, and the role of the Rho GTPases, their regulators and effectors in these CNS migrations, with particular emphasis on their involvement in radial migration. PMID:21557504

  6. Development of plastic deformations in 12Kh18N10T steel under cyclic symmetrical bending of specimens of various length

    Energy Technology Data Exchange (ETDEWEB)

    Pisarenko, G.S.; Leonets, V.A.; Bega, N.D. (AN Ukrainskoj SSR, Kiev. Inst. Problem Prochnosti)


    Effect of specimen length on intensity of plastic deformation development and cyclic strength is studied for annealed 12Kh18N10T steel under cyclic symmetrical bending. The intensity of microplastic deformations and cyclic strength of annealed 12Kh18N10T steel in the considered case is due to self-heating.




  8. Microstructural Development during Welding of Silicon- and Aluminum-Based Transformation-Induced Plasticity Steels—Inclusion and Elemental Partitioning Analysis

    NARCIS (Netherlands)

    Amirthalingam, M.; Hermans, M.; Richardson, I.


    Microstructural development in gas tungsten arc (GTA) welded silicon- and aluminum-based transformation-induced plasticity (TRIP) steels was studied by optical and electron microscopy. The fusion zone (FZ) of both welds contained complex inclusions. Energy-dispersive spectroscopic (EDS) analysis on

  9. Potential environmental benefits of improving recycling of polyolefines – LCA of Magnetic density separation (MDS) developed in the EU FP7 funded project W2Plastic

    DEFF Research Database (Denmark)

    Olsen, Stig Irving; Bonou, Alexandra


    The core of the EU FP7 funded project W2Plastic is development of a magnetic density separation (MDS) of polyolefines in order to improve the sorting efficiency of these polymer types in different waste fractions. As part of the project a life cycle assessment is performed in order to firstly...

  10. Xenopus laevis neuronal cell adhesion molecule (nrcam): plasticity of a CAM in the developing nervous system. (United States)

    Lokapally, Ashwin; Metikala, Sanjeeva; Hollemann, Thomas


    Neuron-glial-related cell adhesion molecule (NRCAM) is a neuronal cell adhesion molecule of the L1 immunoglobulin superfamily, which plays diverse roles during nervous system development including axon growth and guidance, synapse formation, and formation of the myelinated nerve. Perturbations in NRCAM function cause a wide variety of disorders, which can affect wiring and targeting of neurons, or cause psychiatric disorders as well as cancers through abnormal modulation of signaling events. In the present study, we characterize the Xenopus laevis homolog of nrcam. Expression of Xenopus nrcam is most abundant along the dorsal midline throughout the developing brain and in the outer nuclear layer of the retina.

  11. Identification of Intrinsic Axon Growth Modulators for Intact CNS Neurons after Injury

    Directory of Open Access Journals (Sweden)

    Kathren L. Fink


    Full Text Available Functional deficits persist after spinal cord injury (SCI because axons in the adult mammalian central nervous system (CNS fail to regenerate. However, modest levels of spontaneous functional recovery are typically observed after trauma and are thought to be mediated by the plasticity of intact circuitry. The mechanisms underlying intact circuit plasticity are not delineated. Here, we characterize the in vivo transcriptome of sprouting intact neurons from Ngr1 null mice after partial SCI. We identify the lysophosphatidic acid signaling modulators LPPR1 and LPAR1 as intrinsic axon growth modulators for intact corticospinal motor neurons after adjacent injury. Furthermore, in vivo LPAR1 inhibition or LPPR1 overexpression enhances sprouting of intact corticospinal tract axons and yields greater functional recovery after unilateral brainstem lesion in wild-type mice. Thus, the transcriptional profile of injury-induced sprouting of intact neurons reveals targets for therapeutic enhancement of axon growth initiation and new synapse formation.

  12. Can Functional Magnetic Resonance Imaging Improve Success Rates in CNS Drug Discovery? (United States)

    Borsook, David; Hargreaves, Richard; Becerra, Lino


    Introduction The bar for developing new treatments for CNS disease is getting progressively higher and fewer novel mechanisms are being discovered, validated and developed. The high costs of drug discovery necessitate early decisions to ensure the best molecules and hypotheses are tested in expensive late stage clinical trials. The discovery of brain imaging biomarkers that can bridge preclinical to clinical CNS drug discovery and provide a ‘language of translation’ affords the opportunity to improve the objectivity of decision-making. Areas Covered This review discusses the benefits, challenges and potential issues of using a science based biomarker strategy to change the paradigm of CNS drug development and increase success rates in the discovery of new medicines. The authors have summarized PubMed and Google Scholar based publication searches to identify recent advances in functional, structural and chemical brain imaging and have discussed how these techniques may be useful in defining CNS disease state and drug effects during drug development. Expert opinion The use of novel brain imaging biomarkers holds the bold promise of making neuroscience drug discovery smarter by increasing the objectivity of decision making thereby improving the probability of success of identifying useful drugs to treat CNS diseases. Functional imaging holds the promise to: (1) define pharmacodynamic markers as an index of target engagement (2) improve translational medicine paradigms to predict efficacy; (3) evaluate CNS efficacy and safety based on brain activation; (4) determine brain activity drug dose-response relationships and (5) provide an objective evaluation of symptom response and disease modification. PMID:21765857

  13. Cortical Development, Plasticity and Re-Organization in Children with Cochlear Implants (United States)

    Sharma, Anu; Nash, Amy A.; Dorman, Michael


    A basic tenet of developmental neurobiology is that certain areas of the cortex will re-organize, if appropriate stimulation is withheld for long periods. Stimulation must be delivered to a sensory system within a narrow window of time (a sensitive period) if that system is to develop normally. In this article, we will describe age cut-offs for a…

  14. Development time plasticity of the pine processionary moth (Thaumetopoea pityocampa populations under laboratory conditions

    Directory of Open Access Journals (Sweden)

    L. Berardi


    Full Text Available The pine processionary moth Thaumetopoea pityocampa (Lepidoptera, Notodontidae is a univoltine defoliator that is active over a wide range of latitudes and elevations, being largely influenced by temperature variations, especially during larval development across the winter. This work compares field development time with that observed in the laboratory rearing under controlled conditions, in four Th. pityocampa populations characterized by different life history phenology: two populations from the Italian Alps characterized by early and late adult emergence, and two populations from Portugal, the first characterized by winter feeding and late adult emergence, the second by a switch of the larval feeding from winter to summer. The rearing started from the egg stage and was maintained in the laboratory at 20-25°C under natural light in transparent boxes. In spite of the different geographic origins and asynchrony of the period of larval development, all populations maintained an annual life cycle under laboratory conditions, as well as a phenology similar to that of the field populations. Such an outcome was possible due to a trade-off in the duration of the larval and pupal stages, the latter being identified as the phase of development when an efficient regulatory mechanism is acting to maintain the univoltine life cycle.

  15. Plasticity during Childhood and Adolescence: Innovative Approaches to Investigating Neurocognitive Development (United States)

    Cohen Kadosh, Kathrin; Linden, David E. J.; Lau, Jennifer Y. F.


    Adolescence is a period of profound change, which holds substantial developmental milestones, but also unique challenges to the individual. In this opinion paper, we highlight the potential of combining two recently developed behavioural and neural training techniques (cognitive bias modification and functional magnetic neuroimaging-based…

  16. Kv3.1b is a novel component of CNS nodes. (United States)

    Devaux, Jérôme; Alcaraz, Gisèle; Grinspan, Judith; Bennett, Vann; Joho, Rolf; Crest, Marcel; Scherer, Steven S


    We herein demonstrate that Kv3.1b subunits are present at nodes of Ranvier in the CNS of both rats and mice. Kv3.1b colocalizes with voltage-gated Na+ channels in a subset of nodes in the spinal cord, particularly those of large myelinated axons. Kv3.1b is abundantly expressed in the gray matter of the spinal cord, but does not colocalize with Na+ channels in initial segments. In the PNS, few nodes are Kv3.1b-positive. During the development of the CNS, Kv3.1b clustering at nodes occurs later than that of Na+ channels, but precedes the juxtaparanodal clustering of Kv1.2. Moreover, in myelin-deficient rats, which have severe CNS dysmyelination, node-like clusters of Kv3.1b and Na+ channels are observed even in regions devoid of oligodendrocytes. Ankyrin G coimmunoprecipitates Kv3.1b in vivo, indicating that these two proteins may interact in the CNS at nodes. 4-Aminopyridine, a K+ channel blocker, broadened the compound action potential recorded from adult rat optic nerve and spinal cord, but not from the sciatic nerve. These effects were also observed in Kv3.1-deficient mice. In conclusion, Kv3.1b is the first K+ channel subunit to be identified in CNS nodes; but Kv3.1b does not account for the effects of 4-aminopyridine on central myelinated tracts.

  17. The rostral migratory stream plays a key role in intranasal delivery of drugs into the CNS.

    Directory of Open Access Journals (Sweden)

    Robert A Scranton

    Full Text Available BACKGROUND: The blood brain barrier (BBB is impermeable to most drugs, impeding the establishment of novel neuroprotective therapies and strategies for many neurological diseases. Intranasal administration offers an alternative path for efficient drug delivery into the CNS. So far, the anatomical structures discussed to be involved in the transport of intranasally administered drugs into the CNS include the trigeminal nerve, olfactory nerve and the rostral migratory stream (RMS, but the relative contributions are debated. METHODS AND FINDINGS: In the present study we demonstrate that surgical transection, and the resulting structural disruption of the RMS, in mice effectively obstructs the uptake of intranasally administered radioligands into the CNS. Furthermore, using a fluorescent cell tracer, we demonstrate that intranasal administration in mice allows agents to be distributed throughout the entire brain, including olfactory bulb, hippocampus, cortex and cerebellum. CONCLUSIONS: This study provides evidence of the vital role the RMS has in the CNS delivery of intranasally administered agents. The identification of the RMS as the major access path for intranasally administered drugs into the CNS may contribute to the development of treatments that are tailored for efficient transport within this structure. Research into the RMS needs to continue to elucidate its limitations, capabilities, mechanisms of transport and potential hazards before we are able to advance this technique into human research.

  18. Matrine protects neuro-axon from CNS inflammation-induced injury. (United States)

    Kan, Quan-Cheng; Lv, Peng; Zhang, Xiao-Jian; Xu, Yu-Ming; Zhang, Guang-Xian; Zhu, Lin


    Neuro-axonal injury in the central nervous system (CNS) is one of the major pathological hallmarks of experimental autoimmune encephalomyelitis (EAE), an experimental model of multiple sclerosis (MS). Matrine (MAT), a quinolizidine alkaloid derived from the herb Radix Sophorae Flave, has recently been shown to effectively suppress EAE through an anti-inflammatory mechanism. However, whether MAT can also protect myelin/axons from damage is not known. In the present study we show that, while untreated rats developed severe clinical disease, CNS inflammatory demyelination, and axonal damage, these clinical and pathological signs were significantly reduced by MAT treatment. Consistently, MAT treatment reduced the concentration of myelin basic protein in serum and downregulated expression of β-amyloid (Aβ) and B-site APP cleaving enzyme 1 (BACE-1) in the CNS. Further, the CNS of MAT-treated rats exhibited increased expression of brain-derived neurotrophic factor (BDNF), an important factor for neuronal survival and axonal growth. Together, these results demonstrate that MAT effectively prevented neuro-axonal injury, which can likely be attributed to inhibiting risk factors such as BACE-1 and upregulating neuroprotective factors such as BDNF. We conclude that this novel natural reagent, MAT, which effectively protects neuro-axons from CNS inflammation-induced damage, could be a potential candidate for the treatment of neurodegenerative diseases such as MS.

  19. Brain-derived neurotrophic factor as a drug target for CNS disorders. (United States)

    Pezet, Sophie; Malcangio, Marzia


    Brain-derived neurotrophic factor (BDNF) belongs to the neurotrophin family of trophic factors. BDNF is widely and abundantly expressed in the CNS and is available to some peripheral nervous system neurons that uptake the neurotrophin produced by peripheral tissues. BDNF promotes survival and differentiation of certain neuronal populations during development. In adulthood, BDNF can modulate neuronal synaptic strength and has been implicated in hippocampal mechanisms of learning and memory and spinal mechanisms for pain. Several CNS disorders are associated with a decrease in trophic support. As BDNF and its high affinity receptor are abundant throughout the whole CNS, and BDNF is a potent neuroprotective agent, this trophic factor is a good candidate for therapeutic treatment of some of CNS disorders. This review aims to correlate the features of some CNS disorders (Parkinson's disease, Alzheimer's disease, depression, epilepsy and chronic pain) to changes in BDNF expression in the brain. The cellular and molecular mechanism by which BDNF might be a therapeutic strategy are critically examined.

  20. The emerging role of in vitro electrophysiological methods in CNS safety pharmacology. (United States)

    Accardi, Michael V; Pugsley, Michael K; Forster, Roy; Troncy, Eric; Huang, Hai; Authier, Simon


    Adverse CNS effects account for a sizeable proportion of all drug attrition cases. These adverse CNS effects are mediated predominately by off-target drug activity on neuronal ion-channels, receptors, transporters and enzymes - altering neuronal function and network communication. In response to these concerns, there is growing support within the pharmaceutical industry for the requirement to perform more comprehensive CNS safety testing prior to first-in-human trials. Accordingly, CNS safety pharmacology commonly integrates several in vitro assay methods for screening neuronal targets in order to properly assess therapeutic safety. One essential assay method is the in vitro electrophysiological technique - the 'gold standard' ion channel assay. The in vitro electrophysiological method is a useful technique, amenable to a variety of different tissues and cell configurations, capable of assessing minute changes in ion channel activity from the level of a single receptor to a complex neuronal network. Recent advances in automated technology have further expanded the usefulness of in vitro electrophysiological methods into the realm of high-throughput, addressing the bottleneck imposed by the manual conduct of the technique. However, despite a large range of applications, manual and automated in vitro electrophysiological techniques have had a slow penetrance into the field of safety pharmacology. Nevertheless, developments in throughput capabilities and in vivo applicability have led to a renewed interest in in vitro electrophysiological techniques that, when complimented by more traditional safety pharmacology methods, often increase the preclinical predictability of potential CNS liabilities.

  1. A multiple-levels-of-analysis perspective on resilience: implications for the developing brain, neural plasticity, and preventive interventions. (United States)

    Cicchetti, Dante; Blender, Jennifer A


    Resilient functioning, the attainment of unexpected competence despite significant adversity, is among the most intriguing and adaptive phenomena of human development. Although growing attention has been paid to discovering the processes through which individuals at high risk do not develop maladaptively, the empirical study of resilience has focused predominantly on detecting the psychosocial determinants of the phenomenon. For the field of resilience to grow in ways that are commensurate with the complexity inherent to the construct, efforts to understand underlying processes will be facilitated by the increased implementation of interdisciplinary research designed within a developmental psychopathology framework. Research of this nature would entail a consideration of psychological, biological, and environmental-contextual processes from which pathways to resilience might eventuate (known as equifinality), as well as those that result in diverse outcomes among individuals who have achieved resilient functioning (know as multifinality). The possible relation between the mechanisms of neural plasticity and resilience and specific suggestions concerning research questions needed to examine this association are discussed. Examples from developmental neuroscience and molecular genetics are provided to illustrate the potential of incorporating biology into the study of resilience. The importance of adopting a multiple-levels-of-analysis perspective for designing and evaluating interventions aimed at fostering resilient outcomes in persons facing significant adversity is emphasized.

  2. The environment and product development: a study of the plastic recycling

    Directory of Open Access Journals (Sweden)

    Leandro José Morilhas


    Full Text Available In this work, it is aimed to identify how the companies have been developing products through the use of recycled materials. It was veriied which challenges the manufacturers face in their productive chain and how the organizations use such products as a strategic tool. The information presented in this article was obtained through a ield research that made use of a questionnaire sent to companies located in the metropolitan area of São Paulo city and through websites of companies of the area. The results of this study show that the process of product development should improve in an accelerated way in order to assist the desires and needs of the market. In this context, it is up to the companies of the area to update themselves by recycling their products, as well as their processes and management.

  3. Final Report: Development of Renewable Microbial Polyesters for Cost Effective and Energy- Efficient Wood-Plastic Composites

    Energy Technology Data Exchange (ETDEWEB)

    Thompson, David N.; Emerick, Robert W.; England, Alfred B.; Flanders, James P.; Loge, Frank J.; Wiedeman, Katherine A.; Wolcott, Michael P.


    In this project, we proposed to produce wood fiber reinforced thermoplastic composites (WFRTCs) using microbial thermoplastic polyesters in place of petroleum-derived plastic. WFRTCs are a rapidly growing product area, averaging a 38% growth rate since 1997. Their production is dependent on substantial quantities of petroleum based thermoplastics, increasing their overall energy costs by over 230% when compared to traditional Engineered Wood Products (EWP). Utilizing bio-based thermoplastics for these materials can reduce our dependence on foreign petroleum. We have demonstrated that biopolymers (polyhydroxyalkanoates, PHA) can be successfully produced from wood pulping waste streams and that viable wood fiber reinforced thermoplastic composite products can be produced from these materials. The results show that microbial polyester (PHB in this study) can be extruded together with wastewater-derived cell mass and wood flour into deck products having performance properties comparable to existing commercial HDPE/WF composite products. This study has thus proven the underlying concept that the microbial polyesters produced from waste effluents can be used to make cost-effective and energy-efficient wood-plastic composites. The cost of purified microbial polyesters is about 5-20 times that of HDPE depending on the cost of crude oil, due to high purification (40%), carbon substrate (40%) and sterilized fermentation (20%) costs for the PHB. Hence, the ability to produce competitive and functional composites with unpurified PHA-biomass mixtures from waste carbon sources in unsterile systems—without cell debris removal—is a significant step forward in producing competitive value-added structural composites from forest products residuals using a biorefinery approach. As demonstrated in the energy and waste analysis for the project, significant energy savings and waste reductions can also be realized using this approach. We recommend that the next step for development of

  4. Development of fast switching photochromic coatings on transparent plastics and glass


    Mennig, Martin; Fries, Kira; Lindenstruth, Marion; Schmidt, Helmut K.


    A new photochromic organic-inorganic nanocomposite (Nanomer(R)) coating system has been developed. It is based on an epoxysilane as network former, an organic bisepoxide as spacer, an organic amine as thermal cross-linker and surface modified SiO2 nanoparticles as fillers. This coating system is compatible with different photochromic dyes, like oxazines and pyrans. Photochromic coatings with blue, yellow, red, green, violet and neutral tints were prepared on flat glass and PMMA substrates by ...

  5. Cell Death, Neuronal Plasticity and Functional Loading in the Development of the Central Nervous System (United States)

    Keefe, J. R.


    Research on the precise timing and regulation of neuron production and maturation in the vestibular and visual systems of Wistar rats and several inbred strains of mice (C57B16 and Pallid mutant) concentrated upon establishing a timing baseline for mitotic development of the neurons of the vestibular nuclei and the peripheral vestibular sensory structures (maculae, cristae). This involved studies of the timing and site of neuronal cell birth and preliminary studies of neuronal cell death in both central and peripheral elements of the mammalian vestibular system. Studies on neuronal generation and maturation in the retina were recently added to provide a mechanism for more properly defining the in utero' developmental age of the individual fetal subject and to closely monitor potential transplacental effects of environmentally stressed maternal systems. Information is given on current efforts concentrating upon the (1) perinatal period of development (E18 thru P14) and (2) the role of cell death in response to variation in the functional loading of the vestibular and proprioreceptive systems in developing mammalian organisms.

  6. Do more intelligent brains retain heightened plasticity for longer in development? A computational investigation

    Directory of Open Access Journals (Sweden)

    Michael S.C. Thomas


    Full Text Available Twin studies indicate that the heritability of general cognitive ability – the genetic contribution to individual differences – increases with age. Brant et al. (2013 reported that this increase in heritability occurs earlier in development for low ability children than high ability children. Allied with structural brain imaging results that indicate faster thickening and thinning of cortex for high ability children (Shaw et al., 2006, Brant and colleagues argued higher cognitive ability represents an extended sensitive period for brain development. However, they admitted no coherent mechanistic account can currently reconcile the key empirical data. Here, computational methods are employed to demonstrate the empirical data can be reconciled without recourse to variations in sensitive periods. These methods utilized population-based artificial neural network models of cognitive development. In the model, ability-related variations stemmed from the timing of the increases in the non-linearity of computational processes, causing dizygotic twins to diverge in their behavior. These occurred in a population where: (a ability was determined by the combined small contributions of many neurocomputational factors, and (b individual differences in ability were largely genetically constrained. The model’s explanation of developmental increases in heritability contrasts with proposals that these increases represent emerging gene-environment correlations (Haworth et al., 2010. The article advocates simulating inherited individual differences within an explicitly developmental framework.

  7. Progress in the development of gas-impregnated lapped plastic film insulation

    Energy Technology Data Exchange (ETDEWEB)

    Forsyth, E B; McNerney, A J; Muller, A C; Rigby, S J


    A flexible superconducting power transmission cable is under development. The electrical insulation consists of lapped polymeric film tapes impregnated with supercritical helium. Ways of satisfying the many constraints on the material were described. Although the cable is intended for low-temperature operation good electrical and mechanical characteristics are needed at room-temperature. Results are given for both small-sample tests and a model cable fabricated commercially. The results are compared with those obtained by other workers and the design of the next test cable is given.

  8. 重视我国眼整形眼眶病专业的发展%Pay attention to development of ophthalmic plastics and orbital diseases in China

    Institute of Scientific and Technical Information of China (English)



    眼整形眼眶病是一门年轻而发展迅猛的眼科学分支专业,包括眼整形、眼美容和眼眶外科.近年来,眼整形眼眶病领域的新技术和新手术不断涌现,技术创新和学科交叉使其对眼睑和眼眶等疾病的治疗力求达到功能重建及形态修复的完美结合.我国眼整形眼眶病专业起步较晚,但立足于创新性研究,积极开展学科交叉、医工合作和国际学术交流,取得了快速发展.针对目前我国眼整形眼眶外科发展中存在的问题,必须规范专业化人才培养、加强国内外多渠道交流、重视基础与临床转化研究,进一步促进眼整形眼眶病专业的发展.%Ophthalmic plastics and orbital diseases have developed rapidly as a young branch of ophthalmology in recent years. The current situation and development of ophthalmic aesthetics,plastics and orbital surgery are discussed in this paper. The functional reconstruction and appearance rehabilitation are both important to the ophthalmic plastic surgery. Although the ophthalmic plastics and orbital surgery started late in China,it developmented rapidly. The development of this branch is based on innovative research,active interdisciplinary,medical-engineering cooperation and academic exchange. However,there are still some problems about ophthalmic plastics and orbital surgery in China. To promote the development of ophthalmic plastic and orbital surgery,we should regulate the training of ophthalmic plastic surgeons,and pay attention to the clinical translational research.

  9. Mechanisms of Long Non-coding RNAs in Mammalian Nervous System Development, Plasticity, Disease, and Evolution. (United States)

    Briggs, James A; Wolvetang, Ernst J; Mattick, John S; Rinn, John L; Barry, Guy


    Only relatively recently has it become clear that mammalian genomes encode tens of thousands of long non-coding RNAs (lncRNAs). A striking 40% of these are expressed specifically in the brain, where they show precisely regulated temporal and spatial expression patterns. This begs the question, what is the functional role of these many lncRNA transcripts in the brain? Here we canvass a growing number of mechanistic studies that have elucidated central roles for lncRNAs in the regulation of nervous system development and function. We also survey studies indicating that neurological and psychiatric disorders may ensue when these mechanisms break down. Finally, we synthesize these insights with evidence from comparative genomics to argue that lncRNAs may have played important roles in brain evolution, by virtue of their abundant sequence innovation in mammals and plausible mechanistic connections to the adaptive processes that occurred recently in the primate and human lineages.

  10. Postnatal development and plasticity of specialized muscle fiber characteristics in the hindlimb. (United States)

    Garry, D J; Bassel-Duby, R S; Richardson, J A; Grayson, J; Neufer, P D; Williams, R S


    Recent progress in defining molecular components of pathways controlling early stages of myogenesis has been substantial, but regulatory factors that govern the striking functional specialization of adult skeletal muscle fibers in vertebrate organisms have not yet been identified. A more detailed understanding of the temporal and spatial patterns by which specialized fiber characteristics arise may provide clues to the identity of the relevant regulatory factors. In this study, we used immunohistochemical, in situ hybridization, and Northern blot analyses to examine the time course and spatial characteristics of expression of myoglobin protein and mRNA during development of the distal hindlimb in the mouse. In adult animals, myoglobin is expressed selectively in oxidative, mitochondria-rich, fatigue-resistant myofibers, and it provides a convenient marker for this particular subset of specialized fibers. We observed only minimal expression of myoglobin in the hindlimb prior to the second day after birth, but a rapid and large (50-fold) induction of this gene in the ensuing neonatal period. Myoglobin expression was limited, however, to fibers located centrally within the limb which coexpress myosin isoforms characteristic of type I, IIA, and IIX fibers. This induction of myoglobin expression within the early postnatal period was accompanied by increased expression of nuclear genes encoding mitochondrial proteins, and exhibited a time course similar to the upregulation of myoglobin and mitochondrial proteins, and exhibited a time course similar to the upregulation of myoglobin and mitochondrial protein expression that can be induced in adult muscle fibers by continuous motor nerve stimulation. This comparison suggests that progressive locomotor activity of neonatal animals may provide signals which trigger the development of the specialized features of oxidative, fatigue-resistant skeletal muscle fibers.

  11. Postnatal lead exposure and the cholinergic system: effects on cholinergically mediated behaviors and cholinergic development and plasticity in the hippocampus

    Energy Technology Data Exchange (ETDEWEB)

    Alfano, D.P.


    A review of previous evidence suggested the possibility of a functional association between the behavioral effect of early lead (Pb) exposure, hippocampal damage and cholinergic deficiency. To further assess this possibility, Long-Evans hooded rat pups were exposed to Pb for the first 25 postnatal days via the maternal milk. Beginning at 65 days of age, animals were tested on behavioral tasks sensitive to both Pb exposure and cholinergic deficiency. Exposure to both levels of Pb impaired passive avoidance acquisition and produced lower rates of spontaneous alternation. The anticholinergic scopolamine (0.4 mg/kg) impaired passive avoidance acquisition, lowered the rate of spontaneous alternation and decreased open field activity scores in control animals. At 30 days of age, the brains of High Pb and control animals were processed for acetylcholinesterase (AChE) histochemistry. Morphometric evaluation of the molecular layer of the hippocampal dentate gyrus indicated no effects of Pb on the development of the cholinergic innervation of this brain region. The results provide strong evidence for the involvement of deficient cholinergic functioning in the behavioral changes observed following postnatal Pb exposure. Further, these findings indicate that a decrease in neuroanatomical plasticity may be a critical brain mechanism underlying the learning deficits observed following exposure to Pb.

  12. Synaptic dysfunction in human immunodeficiency virus type-1-positive subjects: inflammation or impaired neuronal plasticity? (United States)

    Avdoshina, Valeriya; Bachis, Alessia; Mocchetti, Italo


    Many people infected with the human immunodeficiency virus type-1 (HIV) exhibit mild or severe neurological problems, termed HIV-associated neurocognitive disorder (HAND), even when receiving antiretroviral therapy. Thus, novel adjunctive therapies must be developed to overcome the neurotoxic effect of HIV. New therapies require a better understanding of the molecular and cellular mechanisms of HIV-induced neurotoxicity and the risk factors that, besides inflammation and T cell depletion and drugs of abuse, render the central nervous system (CNS) a target of HIV-induced neurotoxicity. HIV appears to impair neuronal plasticity, which refers to the innate ability of the CNS to respond to injury and promote recovery of function. The availability of brain-derived neurotrophic factor (BDNF), a potent neurotrophic factor that is present in abundance in the adult brain, is essential for neuronal plasticity. BDNF acts through a receptor system composed of Trk and p75NTR. Here we present experimental evidence that some of the clinical features of HIV-mediated neurological impairment could result from altered BDNF/TrkB/p75NTR regulation and function. PMID:23600400

  13. TRPV1 in the central nervous system: synaptic plasticity, function, and pharmacological implications. (United States)

    Edwards, Jeffrey G


    The function of TRPV1 in the peripheral nervous system is increasingly being investigated for its anti-inflammatory and antinociceptive properties in an effort to find a novel target to fight pain that is nonaddictive. However, in recent years, it was discovered that TRPV1 is also associated with a wide array of functions and behaviors in the central nervous system, such as fear, anxiety, stress, thermoregulation, pain, and, more recently, synaptic plasticity, the cellular mechanism that allows the brain to adapt to its environment. This suggests a new role for brain TRPV1 in areas such as learning and memory, reward and addiction, and development. This wide array of functional aspects of TRPV1 in the central nervous system (CNS) is in part due to its multimodal form of activation and highlights the potential pharmacological implications of TRPV1 in the brain. As humans also express a TRPV1 homologue, it is likely that animal research will be translational to humans and therefore worthy of exploration. This review outlines the basic expression patterns of TRPV1 in the CNS along with what is known regarding its signaling mechanisms and its role in the aforementioned brain functions. As TRPV1 involvement in synaptic plasticity has never been fully reviewed elsewhere, it will be a focus of this review. The chapter concludes with some of the potential pharmaceutical implications of further TRPV1 research.

  14. Cortical plasticity within and across lifetimes: How can development inform us about phenotypic transformations?

    Directory of Open Access Journals (Sweden)

    James C Dooley


    Full Text Available The neocortex is the part of the mammalian brain that is involved in perception, cognition, and volitional motor control. It is a highly dynamic structure that is dramatically altered within the lifetime of an animal and in different lineages throughout the course of evolution. These alterations account for the remarkable variations in behavior that species exhibit. Of particular interest is how these cortical phenotypes change within the lifetime of the individual and eventually evolve in species over time. Because we cannot study the evolution of the neocortex directly we use comparative analysis to appreciate the types of changes that have been made to the neocortex and the similarities that exist across taxa. Developmental studies inform us about how these phenotypic transitions may arise by alterations in developmental cascades or changes in the physical environment in which the brain develops. Both genes and the sensory environment contribute to aspects of the phenotype and similar features, such as the size of a cortical field, can be altered in a variety of ways. Although both genes and the laws of physics place constraints on the evolution of the neocortex, mammals have evolved a number of mechanisms that allow them to loosen these constraints and often alter the course of their own evolution.

  15. Significance of the plasma membrane for the nerve cell function, development and plasticity. (United States)

    Mourek, Jindrich; Langmeier, Milos; Pokorny, Jaroslav


    Lipoid character of plasma membrane namely the presence of polyenic fatty acids enables to interact with membrane proteins and in certain extent also to modulate their function. During the development, molecules of membrane fatty acids become more and more complex, and the ratio of polyenic fatty acids/saturated fatty acids in the brain rises, while the concentration of monoenic fatty acids remained relatively stable. This phenomenon is apparent also in the ratio of unsaturated fatty acids OMEGA-3 in plasma of newborns which correlates with the birth weight. Plasma membrane reflects local specializations of nerve cells. Its composition varies in functionally specialized regions called domains. Specialized domains of nerve cells determine the function of dendrites, soma, axon, axon hillock ect. Premature weaning of laboratory rats results in structural changes and in the increase of excitability of neuronal circuits in hypothalamus, septum and hippocampus which indicate the possibility of membrane composition changes. In synapses, transport proteins of synaptic vesicles, act together with the specific proteins of the presynaptic membrane. Membrane proteins determine the release of neurotransmitter at different conditions of synaptic activity, and they can contribute to the recovery of neurotransmitter content after the repeated hyperactivity. In the model of experimental kindling, repeated seizures bring about decreases and distribution changes of synaptic vesicles.

  16. Digital media, the developing brain and the interpretive plasticity of neuroplasticity. (United States)

    Choudhury, Suparna; McKinney, Kelly A


    The use and misuse of digital technologies among adolescents has been the focus of fiery debates among parents, educators, policy-makers and in the media. Recently, these debates have become shaped by emerging data from cognitive neuroscience on the development of the adolescent brain and cognition. "Neuroplasticity" has functioned as a powerful metaphor in arguments both for and against the pervasiveness of digital media cultures that increasingly characterize teenage life. In this paper, we propose that the debates concerning adolescents are the meeting point of two major social anxieties both of which are characterized by the threat of "abnormal" (social) behaviour: existing moral panics about adolescent behaviour in general and the growing alarm about intense, addictive, and widespread media consumption in modern societies. Neuroscience supports these fears but the same kinds of evidence are used to challenge these fears and reframe them in positive terms. Here, we analyze discourses about digital media, the Internet, and the adolescent brain in the scientific and lay literature. We argue that while the evidential basis is thin and ambiguous, it has immense social influence. We conclude by suggesting how we might move beyond the poles of neuro-alarmism and neuro-enthusiasm. By analyzing the neurological adolescent in the digital age as a socially extended mind, firstly, in the sense that adolescent cognition is distributed across the brain, body, and digital media tools and secondly, by viewing adolescent cognition as enabled and transformed by the institution of neuroscience, we aim to displace the normative terms of current debates.

  17. Mixed plastics recycling technology

    CERN Document Server

    Hegberg, Bruce


    Presents an overview of mixed plastics recycling technology. In addition, it characterizes mixed plastics wastes and describes collection methods, costs, and markets for reprocessed plastics products.

  18. Plasticity in developing rat uterine sensory nerves: the role of NGF and TrkA. (United States)

    Chalar, C; Richeri, A; Viettro, L; Chávez-Genaro, R; Bianchimano, P; Marmol, N M; Crutcher, K; Burnstock, G; Cowen, T; Brauer, M M


    In the present study we investigated the effects of infantile/prepubertal chronic oestrogen treatment, chemical sympathectomy with guanethidine and combined sympathectomy and chronic oestrogen treatment on developing sensory nerves of the rat uterus. Changes in sensory innervation were assessed quantitatively on uterine cryostat tissue sections stained for calcitonin gene-related peptide (CGRP). Uterine levels of NGF protein, using immunohistochemistry and ELISA, and mRNA, using Northern blots and in situ hybridization, were also measured. Finally, levels of TrkA NGF receptor in sensory neurons of T13 and L1 dorsal root ganglia (DRG), which supply the uterus, were assessed using densitometric immunohistochemistry. These studies showed that: (1) chronic oestrogen treatment led to an 83% reduction in the intercept density of CGRP-immunoreactive nerves; (2) sympathectomy had no effect on the density of uterine sensory nerves or on the pattern of oestrogen-induced changes; (3) NGF mRNA and protein increased following sympathectomy or chronic oestrogen treatment; and (4) oestrogen produced increased intensity of labelling (28%) for TrkA receptors in small-diameter sensory neurons, but decreased labelling (13%) in medium-sized neurons, which represent the large majority of the DRG neurons supplying the upper part of the uterine horn. Contrary to expectations, increased levels of NGF after sympathectomy and oestrogen treatment did not lead to increased sensory innervation of the uterus. The possibility that alterations in neuronal levels of TrkA contribute to the lack of response of uterine sensory nerves to the oestrogen-induced increase in NGF levels is discussed.

  19. Plasticity of the systemic inflammatory response to acute infection during critical illness: development of the riboleukogram.

    Directory of Open Access Journals (Sweden)

    Jonathan E McDunn

    Full Text Available BACKGROUND: Diagnosis of acute infection in the critically ill remains a challenge. We hypothesized that circulating leukocyte transcriptional profiles can be used to monitor the host response to and recovery from infection complicating critical illness. METHODOLOGY/PRINCIPAL FINDINGS: A translational research approach was employed. Fifteen mice underwent intratracheal injections of live P. aeruginosa, P. aeruginosa endotoxin, live S. pneumoniae, or normal saline. At 24 hours after injury, GeneChip microarray analysis of circulating buffy coat RNA identified 219 genes that distinguished between the pulmonary insults and differences in 7-day mortality. Similarly, buffy coat microarray expression profiles were generated from 27 mechanically ventilated patients every two days for up to three weeks. Significant heterogeneity of VAP microarray profiles was observed secondary to patient ethnicity, age, and gender, yet 85 genes were identified with consistent changes in abundance during the seven days bracketing the diagnosis of VAP. Principal components analysis of these 85 genes appeared to differentiate between the responses of subjects who did versus those who did not develop VAP, as defined by a general trajectory (riboleukogram for the onset and resolution of VAP. As patients recovered from critical illness complicated by acute infection, the riboleukograms converged, consistent with an immune attractor. CONCLUSIONS/SIGNIFICANCE: Here we present the culmination of a mouse pneumonia study, demonstrating for the first time that disease trajectories derived from microarray expression profiles can be used to quantitatively track the clinical course of acute disease and identify a state of immune recovery. These data suggest that the onset of an infection-specific transcriptional program may precede the clinical diagnosis of pneumonia in patients. Moreover, riboleukograms may help explain variance in the host response due to differences in ethnic

  20. The gut-brain axis, BDNF, NMDA and CNS disorders


    Maqsood, Raeesah; Stone, Trevor W.


    Gastro-intestinal (GI) microbiota and the ‘gut-brain axis’ are proving to be increasingly relevant to early brain development and the emergence of psychiatric disorders. This review focuses on the influence of the GI tract on Brain-Derived Neurotrophic Factor (BDNF) and its relationship with receptors for N-methyl-d-aspartate (NMDAR), as these are believed to be involved in synaptic plasticity and cognitive function. NMDAR may be associated with the development of schizophrenia and a range of...

  1. Plastic fish

    CERN Multimedia

    Antonella Del Rosso


    In terms of weight, the plastic pollution in the world’s oceans is estimated to be around 300,000 tonnes. This plastic comes from both land-based and ocean-based sources. A lecture at CERN by chemist Wolfgang Trettnak addressed this issue and highlighted the role of art in raising people’s awareness.   Artwork by Wolfgang Trettnak. Packaging materials, consumer goods (shoes, kids’ toys, etc.), leftovers from fishing and aquaculture activities… our oceans and beaches are full of plastic litter. Most of the debris from beaches is plastic bottles. “PET bottles have high durability and stability,” explains Wolfgang Trettnak, a chemist by education and artist from Austria, who gave a lecture on this topic organised by the Staff Association at CERN on 26 May. “PET degrades very slowly and the estimated lifetime of a bottle is 450 years.” In addition to the beach litter accumulated from human use, rivers bring several ki...

  2. Plastic zonnecellen

    NARCIS (Netherlands)

    Roggen, Marjolein


    De zonnecel van de toekomst is in de maak. Onderzoekers van uiteenlopend pluimage werken eendrachtig aan een plastic zonnecel. De basis is technisch gelegd met een optimale, door invallend licht veroorzaakte, vorming van ladingdragers binnen een composiet van polymeren en buckyballs. Nu is het zaak

  3. Evolution of the CNS myelin gene regulatory program. (United States)

    Li, Huiliang; Richardson, William D


    Myelin is a specialized subcellular structure that evolved uniquely in vertebrates. A myelinated axon conducts action potentials many times faster than an unmyelinated axon of the same diameter; for the same conduction speed, the unmyelinated axon would need a much larger diameter and volume than its myelinated counterpart. Hence myelin speeds information transfer and saves space, allowing the evolution of a powerful yet portable brain. Myelination in the central nervous system (CNS) is controlled by a gene regulatory program that features a number of master transcriptional regulators including Olig1, Olig2 and Myrf. Olig family genes evolved from a single ancestral gene in non-chordates. Olig2, which executes multiple functions with regard to oligodendrocyte identity and development in vertebrates, might have evolved functional versatility through post-translational modification, especially phosphorylation, as illustrated by its evolutionarily conserved serine/threonine phospho-acceptor sites and its accumulation of serine residues during more recent stages of vertebrate evolution. Olig1, derived from a duplicated copy of Olig2 in early bony fish, is involved in oligodendrocyte development and is critical to remyelination in bony vertebrates, but is lost in birds. The origin of Myrf orthologs might be the result of DNA integration between an invading phage or bacterium and an early protist, producing a fusion protein capable of self-cleavage and DNA binding. Myrf seems to have adopted new functions in early vertebrates - initiation of the CNS myelination program as well as the maintenance of mature oligodendrocyte identity and myelin structure - by developing new ways to interact with DNA motifs specific to myelin genes. This article is part of a Special Issue entitled SI: Myelin Evolution.

  4. Robust regeneration of CNS axons through a track depleted of CNS glia. (United States)

    Moon, L D; Brecknell, J E; Franklin, R J; Dunnett, S B; Fawcett, J W


    Transected CNS axons do not regenerate spontaneously but may do so if given an appropriate environment through which to grow. Since molecules associated with CNS macroglia are thought to be inhibitory to axon regeneration, we have tested the hypothesis that removing these cell types from an area of brain will leave an environment more permissive for axon regeneration. Adult rats received unilateral knife cuts of the nigrostriatal tract and ethidium bromide (EB) was used to create a lesion devoid of astrocytes, oligodendrocytes, intact myelin sheaths, and NG2 immunoreactive cells from the site of the knife cut to the ipsilateral striatum (a distance of 6 mm). The regenerative response and the EB lesion environment was examined with immunostaining and electron microscopy at different timepoints following surgery. We report that large numbers of dopaminergic nigral axons regenerated for over 4 mm through EB lesions. At 4 days postlesion dopaminergic sprouting was maximal and the axon growth front had reached the striatum, but there was no additional growth into the striatum after 7 days. Regenerating axons did not leave the EB lesion to form terminals in the striatum, there was no recovery of function, and the end of axon growth correlated with increasing glial immunoreactivity around the EB lesion. We conclude that the removal of CNS glia promotes robust axon regeneration but that this becomes limited by the reappearance of nonpermissive CNS glia. These results suggest, first, that control of the glial reaction is likely to be an important feature in brain repair and, second, that reports of axon regeneration must be interpreted with caution since extensive regeneration can occur simply as a result of a major glia-depleting lesion, rather than as the result of some other specific intervention.

  5. Performance Enhancement at the Cost of Potential Brain Plasticity: Neural Ramifications of Nootropic Drugs in the Healthy Developing Brain

    Directory of Open Access Journals (Sweden)

    Kimberly R. Urban


    Full Text Available Cognitive enhancement is perhaps one of the most intriguing and controversial topics in neuroscience today. Currently, the main classes of drugs used as potential cognitive enhancers include psychostimulants (methylphenidate, amphetamine, but wakefulness-promoting agents (modafinil and glutamate activators (ampakine are also frequently used. Pharmacologically, substances that enhance the components of the memory/learning circuits - dopamine, glutamate (neuronal excitation, and/or norepinephrine - stand to improve brain function in healthy individuals beyond their baseline functioning. In particular, non-medical use of prescription stimulants such as methylphenidate and illicit use of psychostimulants for cognitive enhancement have seen a recent rise among teens and young adults in schools and college campuses. However, this enhancement likely comes with a neuronal, as well as ethical, cost. Altering glutamate function via the use of psychostimulants may impair behavioral flexibility, leading to the development and/or potentiation of addictive behaviors. Furthermore, dopamine and norepinephrine do not display linear effects; instead, their modulation of cognitive and neuronal function maps on an inverted-U curve. Healthy individuals run the risk of pushing themselves beyond optimal levels into hyperdopaminergic and hypernoradrenergic states, thus vitiating the very behaviors they are striving to improve. Finally, recent studies have begun to highlight potential damaging effects of stimulant exposure in healthy juveniles. This review explains how the main classes of cognitive enhancing drugs affect the learning and memory circuits, and highlights the potential risks and concerns in healthy individuals, particularly juveniles and adolescents. We emphasize the performance enhancement at the potential cost of brain plasticity that is associated with the neural ramifications of nootropic drugs in the healthy developing brain.

  6. Autoimmune control of lesion growth in CNS with minimal damage (United States)

    Mathankumar, R.; Mohan, T. R. Krishna


    Lesions in central nervous system (CNS) and their growth leads to debilitating diseases like Multiple Sclerosis (MS), Alzheimer's etc. We developed a model earlier [1, 2] which shows how the lesion growth can be arrested through a beneficial auto-immune mechanism. We compared some of the dynamical patterns in the model with different facets of MS. The success of the approach depends on a set of control parameters and their phase space was shown to have a smooth manifold separating the uncontrolled lesion growth region from the controlled. Here we show that an optimal set of parameter values exist in the model which minimizes system damage while, at once, achieving control of lesion growth.

  7. The therapeutic effects of Rho-ROCK inhibitors on CNS disorders

    Directory of Open Access Journals (Sweden)

    Takekazu Kubo


    Full Text Available Takekazu Kubo1, Atsushi Yamaguchi1, Nobuyoshi Iwata2, Toshihide Yamashita1,31Department of Neurobiology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan; 2Information Institute for Medical Research Ltd.; 3Department of Molecular Neuroscience, Graduate School of Medicine, Osaka University 2-2 Yamadaoka, Suita, Osaka 565-0871, JapanAbstract: Rho-kinase (ROCK is a serine/threonine kinase and one of the major downstream effectors of the small GTPase Rho. The Rho-ROCK pathway is involved in many aspects of neuronal functions including neurite outgrowth and retraction. The Rho-ROCK pathway becomes an attractive target for the development of drugs for treating central nervous system (CNS disorders, since it has been recently revealed that this pathway is closely related to the pathogenesis of several CNS disorders such as spinal cord injuries, stroke, and Alzheimer’s disease (AD. In the adult CNS, injured axons regenerate poorly due to the presence of myelin-associated axonal growth inhibitors such as myelin-associated glycoprotein (MAG, Nogo, oligodendrocyte-myelin glycoprotein (OMgp, and the recently identified repulsive guidance molecule (RGM. The effects of these inhibitors are reversed by blockade of the Rho-ROCK pathway in vitro, and the inhibition of this pathway promotes axonal regeneration and functional recovery in the injured CNS in vivo. In addition, the therapeutic effects of the Rho-ROCK inhibitors have been demonstrated in animal models of stroke. In this review, we summarize the involvement of the Rho-ROCK pathway in CNS disorders such as spinal cord injuries, stroke, and AD and also discuss the potential of Rho-ROCK inhibitors in the treatment of human CNS disorders.Keywords: neuron, Rho, Rho-kinase, axonal regeneration, central nervous system disorder

  8. Detection of allergenic compounds using an IL-4/luciferase/CNS-1 transgenic mice model. (United States)

    Bae, Chang Joon; Lee, Jae Won; Bae, Hee Sook; Shim, Sun Bo; Jee, Seung Wan; Lee, Su Hae; Lee, Chang Kyu; Hong, Jin Tae; Hwang, Dae Youn


    The interleukin-4 (IL-4) signaling cascade has been identified as a potentially important pathway in the development of allergies. The principal objective of this study was to produce novel transgenic (Tg) mice harboring the luciferase gene under the control of the human IL-4 promoter and the enhancer of IL-4 (CNS-1), in an effort to evaluate three types of allergens including a respiratory sensitizer, vaccine additives, and crude extracts of natural allergens in vivo. A new lineage of Tg mice was generated by the microinjection of pIL-4/Luc/CNS-1 constructs into a fertilized mice egg. The luciferase activity was successfully regulated by the IL-4 promoter in splenocytes cultured from IL-4/Luc/CNS-1 Tg mice. From the first five founder lines, one (#57) evidencing a profound response to ovalbumin was selected for use in evaluating the allergens. Additionally, the lungs, thymus, and lymph nodes of IL-4/Luc/CNS-1 Tg mice evidenced high luciferase activity in response to allergens such as phthalic anhydride (PA), trimellitic anhydride, ovalbumin, gelatin, Dermatophagoides pteronyssinus extracts, and Japanese cedar pollen, whereas key allergy-related indicators including ear thickness, Immunoglobulin E concentration, and the infiltration of inflammatory leukocytes in response to PA were unaltered in the Tg mice relative to the non-Tg mice. Furthermore, the expression levels of endogenous type 2 helper T cells cytokines and proinflammatory cytokines were similarly increased in these organs of IL-4/Luc/CNS-1 Tg mice in response to allergens. These results indicate that IL-4/Luc/CNS-1 Tg mice may be used as an animal model for the evaluation and prediction of the human body response to a variety of allergens originating from the environment and from certain industrial products.

  9. Shaping development through mechanical strain: the transcriptional basis of diet-induced phenotypic plasticity in a cichlid fish. (United States)

    Gunter, Helen M; Fan, Shaohua; Xiong, Fan; Franchini, Paolo; Fruciano, Carmelo; Meyer, Axel


    Adaptive phenotypic plasticity, the ability of an organism to change its phenotype to match local environments, is increasingly recognized for its contribution to evolution. However, few empirical studies have explored the molecular basis of plastic traits. The East African cichlid fish Astatoreochromis alluaudi displays adaptive phenotypic plasticity in its pharyngeal jaw apparatus, a structure that is widely seen as an evolutionary key innovation that has contributed to the remarkable diversity of cichlid fishes. It has previously been shown that in response to different diets, the pharyngeal jaws change their size, shape and dentition: hard diets induce an adaptive robust molariform tooth phenotype with short jaws and strong internal bone structures, while soft diets induce a gracile papilliform tooth phenotype with elongated jaws and slender internal bone structures. To gain insight into the molecular underpinnings of these adaptations and enable future investigations of the role that phenotypic plasticity plays during the formation of adaptive radiations, the transcriptomes of the two divergent jaw phenotypes were examined. Our study identified a total of 187 genes whose expression differs in response to hard and soft diets, including immediate early genes, extracellular matrix genes and inflammatory factors. Transcriptome results are interpreted in light of expression of candidate genes-markers for tooth size and shape, bone cells and mechanically sensitive pathways. This study opens up new avenues of research at new levels of biological organization into the roles of phenotypic plasticity during speciation and radiation of cichlid fishes.

  10. Dynamic Strength and Accumulated Plastic Strain Development Laws and Models of the Remolded Red Clay under Long-Term Cyclic Loads: Laboratory Test Results

    Directory of Open Access Journals (Sweden)

    Li Jian


    Full Text Available The dynamic strength and accumulated plastic strain are two important parameters for evaluating the dynamic response of soil. As a special clay, the remolded red clay is often used as the high speed railway subgrade filling, but studies on its dynamic characteristics are few. For a thorough analysis of the suitability of the remolded red clay as the subgrade filling, a series of long-term cyclic load triaxial test under different load histories are carried out. Considering the influence of compactness, confining pressure, consolidation ratio, vibration frequency and dynamic load to the remolded red clay dynamic property, the tests obtain the development curves of the dynamic strength and accumulated plastic strain under different test conditions. Then, through curve fitting method, two different hyperbolic models respectively for the dynamic strength and accumulated plastic strain are built, which can match the test datum well. By applying the dynamic strength model, the critical dynamic strength of the remolded red clay are gained. Meanwhile, for providing basic datum and reference for relevant projects, all key parameters for the dynamic strength and accumulated plastic strain of the remolded red clay are given in the paper.

  11. The number of extranodal sites assessed by PET/CT scan is a powerful predictor of CNS relapse for patients with diffuse large B-cell lymphoma

    DEFF Research Database (Denmark)

    El-Galaly, Tarec Christoffer; Villa, Diego; Michaelsen, Thomas Yssing


    Purpose Development of secondary central nervous system involvement (SCNS) in patients with diffuse large B-cell lymphoma is associated with poor outcomes. The CNS International Prognostic Index (CNS-IPI) has been proposed for identifying patients at greatest risk, but the optimal model is unknow...

  12. Mechanism of plasticity development for ceramic dough (5). Influence of the deformability of buffer domain on plasticity; Seramikku nendo no kasakusei hatsugen mekanizumu (5). Kanshoryoiki no henkeino no kasakusei eno eikyo

    Energy Technology Data Exchange (ETDEWEB)

    Kawai, S. [Wet Forming of Ceramics Technology Research Association, Aichi (Japan); Ishida, H. [INAX Corporation, Aichi (Japan). Space Design Research Center; Shibasaki, Y; Oda, K. [National Industrial Research Institute of Nagoya, Aichi (Japan)


    Plasticity of ceramic dough is determined by the deformation of the buffer domain that consists of aggregate or gel. Effect of the deformability of each buffer domain on the plasticity of alumina dough, in presence of various additives, was investigated. Those additives were konjak, agar, curdlan and super-absorbent polymer. Moderately deformable additives such as konjak and agar worked as buffer domains, and plasticity was generated. However, soft and brittle additives such as curdlan and super-absorbent polymer could not improve plasticity because of their lower ability in generating the buffer domains. It was clarified that the deformability of buffer domain directly influences plasticity. (author)

  13. Plastic Surgery Statistics (United States)

    ... PSN PSEN GRAFT Contact Us News Plastic Surgery Statistics Plastic surgery procedural statistics from the American Society of Plastic Surgeons. Statistics by Year Print 2016 Plastic Surgery Statistics 2015 ...

  14. CNS Involvement in the Non-Hodgkin's Lymhoma

    Energy Technology Data Exchange (ETDEWEB)

    Suh, Chang Ok; Kim, Gwi Eon; Park, Chang Yun; Kim, Byung Soo [Yonsei University College of Medicine, Seoul (Korea, Republic of)


    Two cases of primary malignant lymphoma of the brain and six cases of secondary CNS lymphoma seen at Yonsei cancer center, radiotherapy department for recent 4 years are presented. Primary lymphomas revealed single tumor mass on corpus callosum area and secondary lymphoma were intracranial (3 cases) or leptomeningeal type (3 cases). Histology of primary lymphoma were reticulum cell sarcoma and secondary lymphomas were either diffuse histiocytic or diffuse poorly differentiated lymphocytic lymphoma. All patients showed good response to radiation. Two patients with primary CNS lymphoma and two of six secondary CNS lymphoma are alive after radiotherapy (34, 31, 26, 12 months). But the prognosis of secondary CNS lymphoma is grave, because of progressive systemic disease. Incidence, risk factors, diagnosis and therapeutic management of CNS involvement are also discussed.

  15. Phenotypic plasticity with instantaneous but delayed switches

    NARCIS (Netherlands)

    Utz, Margarete; Jeschke, Jonathan M.; Loeschcke, Volker; Gabriel, Wilfried


    Phenotypic plasticity is a widespread phenomenon, allowing organisms to better adapt to changing environments. Most empirical and theoretical studies are restricted to irreversible plasticity where the expression of a specific phenotype is mostly determined during development. However, reversible pl

  16. Plastic bronchitis

    Directory of Open Access Journals (Sweden)

    Anil Kumar Singhi


    Full Text Available Plastic bronchitis, a rare but serious clinical condition, commonly seen after Fontan surgeries in children, may be a manifestation of suboptimal adaptation to the cavopulmonary circulation with unfavorable hemodynamics. They are ominous with poor prognosis. Sometimes, infection or airway reactivity may provoke cast bronchitis as a two-step insult on a vulnerable vascular bed. In such instances, aggressive management leads to longer survival. This report of cast bronchitis discusses its current understanding.

  17. Economical and Ecological Fesasibility of Plastic Recycling


    Hirschpold, Andrew; Juctye, Kristina; Renzhong, Jiang; Debin, LIU; Varona, Hector P.; Kevelaitis, Karolis


    #Group 3 International Nat Bas Economical and Ecological Feasibility of Plastic Recycling Abstract This project is carried out as the final project for the first semester of Bachelor of Science studies. Our project will aim on plastic recycling. Plastic is a manmade material which covers a range of synthetic or semi-synthetic products made thru polymerization. The development of plastic products has accompanied the development of human’s history since it was invented while they ...

  18. Economical and Ecological Fesasibility of Plastic Recycling


    Hirschpold, Andrew; Juctye, Kristina; Renzhong, Jiang; Debin, Liu; Varona, Hector P.; Kevelaitis, Karolis


    #Group 3 International Nat Bas Economical and Ecological Feasibility of Plastic Recycling Abstract This project is carried out as the final project for the first semester of Bachelor of Science studies. Our project will aim on plastic recycling. Plastic is a manmade material which covers a range of synthetic or semi-synthetic products made thru polymerization. The development of plastic products has accompanied the development of human’s history since it was invented while they ...

  19. Lidocaine-induced CNS toxicity--a case report. (United States)

    Chiang, Y Y; Tseng, K F; Lih, Y W; Tsai, T C; Liu, C T; Leung, H K


    Lidocaine is the first local anesthetic of the amide type to be introduced to clinical practice. It is a versatile drug and in anesthesia, is the most commonly used local anesthetic because of its aptness of potency, rapid onset, moderate duration of action and topical activity. It is relatively safe and useful in many other clinical settings. Unfortunately, systemic intoxication and psychotic reaction associated with its use often occur because of its popularity and wider safety margin, for which guide in use is often ignored and overdose becomes commonplace. Moreover, due to its universality in use seldom reports have recently dealt with lidocaine, particularly regarding its toxic reaction. Here, we present a case of lidocaine intoxication occurring during circumcision for a reviewal of the problem. A healthy young male, weighing 65 kg, underwent circumcision for phimosis under penile block with 2% lidocaine which totaled 600 mg. Twenty minutes after injection the patient developed headache, tinnitus, visual and auditory disturbances. Muscle twitching over the mouth angles, trismus and rigidity of extremities were also noted. Later in the course he became restless, agitative, hallucinative, talkative, and verbose with repetitious words. The whole course of the disorder lasted about 5 h. It was believed that lidocaine-induced CNS intoxication, manifested by psychotic reaction broke out. Treatment with thiopental was not very impressive. Also, we took this opportunity to discuss and review the toxic reaction associated with the use of lidocaine, its risk factors, mechanism, treatment and prevention. The complicated associations of lidocaine-induced CNS toxic reaction with central control of behavior and the neurotransmitter systems (adrenergic, dopaminergic and serotonin) were also touched.

  20. Plastic food packaging and health

    Directory of Open Access Journals (Sweden)

    Raika Durusoy


    Full Text Available Plastics have a wide usage in our daily lives. One of their uses is for food packaging and food containers. The aim of this review is to introduce different types of chemicals that can leach from food packaging plastics into foods and cause human exposure and to mention their effects on health. The types of plastics were reviewed under the 13 headings in Turkish Codex Alimentarius and plastics recycling symbols were provided to enable the recognition of the type of plastic when applicable. Chemicals used during the production and that can cause health risks are investigated under the heading of the relevant type of plastic. The most important chemicals from plastic food packaging that can cause toxicity are styrene, 1,3-butadiene, melamine, formaldehyde, acrylamide, di-2-ethylhexyl phthalate, di-2-ethylhexyl adipate, vinyl chloride and bisphenol A. These chemicals have endocrine disrupting, carcinogenic and/or development disrupting effects. These chemicals may leach into foods depending on the chemical properties of the plastic or food, temperature during packaging, processing and storage, exposure to UV and duration of storage. Contact with fatty/oily or acidic foods, heating of the food inside the container, or drinking hot drinks from plastic cups, use of old and scratched plastics and some detergents increase the risk of leaching. The use of plastic containers and packaging for food and beveradges should be avoided whenever possible and when necessary, less harmful types of plastic should be preferred. [TAF Prev Med Bull 2011; 10(1.000: 87-96

  1. Multiscale modeling and synaptic plasticity. (United States)

    Bhalla, Upinder S


    Synaptic plasticity is a major convergence point for theory and computation, and the process of plasticity engages physiology, cell, and molecular biology. In its many manifestations, plasticity is at the hub of basic neuroscience questions about memory and development, as well as more medically themed questions of neural damage and recovery. As an important cellular locus of memory, synaptic plasticity has received a huge amount of experimental and theoretical attention. If computational models have tended to pick specific aspects of plasticity, such as STDP, and reduce them to an equation, some experimental studies are equally guilty of oversimplification each time they identify a new molecule and declare it to be the last word in plasticity and learning. Multiscale modeling begins with the acknowledgment that synaptic function spans many levels of signaling, and these are so tightly coupled that we risk losing essential features of plasticity if we focus exclusively on any one level. Despite the technical challenges and gaps in data for model specification, an increasing number of multiscale modeling studies have taken on key questions in plasticity. These have provided new insights, but importantly, they have opened new avenues for questioning. This review discusses a wide range of multiscale models in plasticity, including their technical landscape and their implications.

  2. The Development of a SPME-GC/MS Method for the Analysis of VOC Emissions from Historic Plastic and Rubber Materials


    Curran, K.; Underhill, M.; Gibson, L. T.; Strlic, M.


    Analytical methods have been developed for the analysis of VOC emissions from historic plastic and rubber materials using SPME-GC/MS. Parameters such as analysis temperature, sampling time and choice of SPME fibre coating were investigated and sampling preparation strategies explored, including headspace sampling in vials and in gas sampling bags. The repeatability of the method was evaluated. It was found that a 7 d accumulation time at room temperature, followed by sampling using a DVB/CAR/...

  3. [The history of plastic surgery in Israel]. (United States)

    Wiser, Itay; Scheflan, Michael; Heller, Lior


    The medical institutions in the country have advanced together with the development of the state of Israel. Plastic surgery, which has progressed significantly during the 20th century, has also grown rapidly in the new state. The arrival of Jewish plastic surgeons from all over the world with the knowledge and experience gained in their countries of origin, as well as the need for reconstructive surgical treatment for many combat injured soldiers, also contributed to the development of plastic surgery. This review tells the story of plastic surgery in Israel, since its foundation until nowadays. This article reviews the work of the founders of plastic surgery in Israel, indicating significant milestones in its development, and clinical and scientific contribution to the international plastic surgery profession. Moreover, the article describes the current condition of the field of plastic surgery in Israel and presents the trends and the future challenges facing the next generation of plastic surgery in Israel.

  4. Integrated microfluidics platforms for investigating injury and regeneration of CNS axons. (United States)

    Kim, Hyung Joon; Park, Jeong Won; Byun, Jae Hwan; Vahidi, Behrad; Rhee, Seog Woo; Jeon, Noo Li


    We describe the development of experimental platforms to quantify the regeneration of injured central nervous system (CNS) neurons by combining engineering technologies and primary neuronal cultures. Although the regeneration of CNS neurons is an important area of research, there are no currently available methods to screen for drugs. Conventional tissue culture based on Petri dish does not provide controlled microenvironment for the neurons and only provide qualitative information. In this review, we introduced the recent advances to generate in vitro model system that is capable of mimicking the niche of CNS injury and regeneration and also of testing candidate drugs. We reconstructed the microenvironment of the regeneration of CNS neurons after injury to provide as in vivo like model system where the soluble and surface bounded inhibitors for regeneration are presented in physiologically relevant manner using microfluidics and surface patterning methods. The ability to control factors and also to monitor them using live cell imaging allowed us to develop quantitative assays that can be used to compare various drug candidates and also to understand the basic mechanism behind nerve regeneration after injury.

  5. Development of hydrophobicity and selective separation of hazardous chlorinated plastics by mild heat treatment after PAC coating and froth flotation. (United States)

    Thanh Truc, Nguyen Thi; Lee, Chi-Hyeon; Lee, Byeong-Kyu; Mallampati, Srinivasa Reddy


    Polyvinyl chloride (PVC) containing chlorine can release highly toxic materials and persistent organic pollutants if improperly disposed of. The combined technique of powder activated carbon (PAC) coating and mild heat treatment has been found to selectively change the surface hydrophobicity of PVC, enhancing its wettability and thereby promoting its separation from heavy plastic mixtures included polycarbonate (PC), polymethyl methacrylate (PMMA), polystyrene (PS) and acrylonitrile butadiene styrene (ABS) by means of froth flotation. The combined treatments helped to rearrange the surface components and make PVC more hydrophobic, while the remaining plastics became more hydrophilic. After the treatments at 150°C for 80s the contact angle of the PVC was greatly increased from 90.5 to 97.9°. The SEM and AFM reveal that the surface morphology and roughness changes on the PVC surface. XPS and FT-IR results further confirmed an increase of hydrophobic functional groups on the PVC surface. At the optimized froth flotation and subsequent mixing at 150rpm, 100% of PVC was recovered from the remaining plastic mixture with 93.8% purity. The combined technique can provide a simple and effective method for the selective separation of PVC from heavy plastics mixtures to facilitate easy industrial recycling.

  6. Continued work to develop a low-cost sensor to detect plastic contamination in seed cotton at the gin (United States)

    Contamination of cotton from plastic trash that collects in cotton fields or introduced at the gin or due to mishandling at the warehouse is one of the most significant threats to US cotton world market share. For U.S. cotton to maintain its status as “contamination-free”, the industry must strive t...

  7. Size effects in crystal plasticity

    DEFF Research Database (Denmark)

    Borg, Ulrik


    Numerical analyses of plasticity size effects have been carried out for different problems using a developed strain gradient crystal plasticiy theory. The theory employs higher order stresses as work conjugates to slip gradients and uses higher order boundary conditions. Problems on localization...... of plastic flow in a single crystal, grain boundary effects in a bicrystal, and grain size effects in a polycrystal are studied. Single crystals containing micro-scale voids have also been analyzed at different loading conditions with focus on the stress and deformation fields around the voids, on void...... growth and interaction between neighboring voids, and on a comparison between the developed strain gradient crystal plasticity theory and a discrete dislocation plasticity theory. Furthermore, voids and rigid inclusions in isotropic materials have been studied using a strain gradient plasticity theory...

  8. LINGO-1 and its role in CNS repair. (United States)

    Mi, Sha; Sandrock, Alfred; Miller, Robert H


    LINGO-1 is selectively expressed in the CNS on both oligodendrocyte precursor cells (OPCs) and neurons. Its expression is developmentally regulated in the normal CNS, as well as up-regulated in human or rat models of neuropathologies. LINGO-1 functions as a negative regulator of oligodendrocyte differentiation and myelination, neuronal survival and axonal regeneration. Across diverse animal CNS disease models, targeted LINGO-1 inhibition was found to promote neuron and oligodendrocyte survival, axon regeneration, oligodendrocyte differentiation, remyelination and improved functional recovery. The targeted inhibition of LINGO-1 therefore presents a novel therapeutic approach for the treatment of neurological diseases.

  9. 3rd ENRI International Workshop on ATM/CNS

    CERN Document Server


    The Electronic Navigation Research Institute (ENRI) held its third International Workshop on ATM / CNS in 2013 with the theme of "Drafting the future sky". There is worldwide activity taking place in the research and development of modern air traffic management (ATM) and its enabling technologies in Communication, Navigation and Surveillance (CNS). Pioneering work is necessary to contribute to the global harmonization of air traffic management and control. At this workshop, leading experts in  research, industry and academia from around the world met to share their ideas and approaches on ATM/CNS related topics.

  10. CNS Vasculitis Associated with Waldenström Macroglobulinemia (United States)

    Riangwiwat, Tanawan; Wu, Chris Y.; Santos-Ocampo, Alberto S.; Liu, Randal J.


    Waldenström macroglobulinemia (WM) is an indolent B cell lymphoproliferative disorder with monoclonal IgM secretion. We present a patient with WM who presented with multifocal acute cortical ischemic strokes and was found to have central nervous system (CNS) vasculitis. Workup was negative for cryoglobulins and hyperviscosity syndrome. Immunosuppression with intravenous steroids and cyclophosphamide stabilized the patient's mental status and neurologic deficits. On followup over 7 years, patient gained independence from walking aids and experienced no recurrences of CNS vasculitis. To our knowledge, CNS vasculitis in a WM patient, in the absence of cryoglobulins, has not been reported. Immunosuppression is the preferred treatment. PMID:27818812

  11. CNS Vasculitis Associated with Waldenström Macroglobulinemia

    Directory of Open Access Journals (Sweden)

    Tanawan Riangwiwat


    Full Text Available Waldenström macroglobulinemia (WM is an indolent B cell lymphoproliferative disorder with monoclonal IgM secretion. We present a patient with WM who presented with multifocal acute cortical ischemic strokes and was found to have central nervous system (CNS vasculitis. Workup was negative for cryoglobulins and hyperviscosity syndrome. Immunosuppression with intravenous steroids and cyclophosphamide stabilized the patient’s mental status and neurologic deficits. On followup over 7 years, patient gained independence from walking aids and experienced no recurrences of CNS vasculitis. To our knowledge, CNS vasculitis in a WM patient, in the absence of cryoglobulins, has not been reported. Immunosuppression is the preferred treatment.

  12. Developing Prospect Analysis of Composite Plastics Construct Framework%浅析复合塑料建筑模板发展前景

    Institute of Scientific and Technical Information of China (English)



    In this paper, the writer analyzes the disadvantage of traditional framework in producing and applying process, summarizes characteristics of building templates market, gives a introduction to the characteristics of composite plastic framework, compares its advantage with wood, steel and bamboo plywood framework, and summarizes the developing prospect of composite plastic framework.%通过对建筑模极市场发展的综述,分析了传统建筑模板在生产和使用过程中存在的弊病,介绍复合塑料模板的特点,比较了相对木模板、钢模板、竹胶模板的优势,总结出复合塑料模板的发展前景.

  13. Evaluation of Lumicyano™ cyanoacrylate fuming process for the development of latent fingermarks on plastic carrier bags by means of a pseudo operational comparative trial. (United States)

    Farrugia, Kevin J; Deacon, Paul; Fraser, Joanna


    There are a number of studies discussing recent developments of a one-step fluorescent cyanoacrylate process. This study is a pseudo operational trial to compare an example of a one-step fluorescent cyanoacrylate product, Lumicyano™, with the two recommended techniques for plastic carrier bags; cyanoacrylate fuming followed by basic yellow 40 (BY40) dyeing and powder suspensions. 100 plastic carrier bags were collected from the place of work and the items were treated as found without any additional fingermark deposition. The bags were split into three and after treatment with the three techniques a comparable number of fingermarks were detected by each technique (average of 300 fingermarks). The items treated with Lumicyano™ were sequentially processed with BY40 and an additional 43 new fingermarks were detected. Lumicyano™ appears to be a suitable technique for the development of fingermarks on plastic carrier bags and it can help save lab space and time as it does not require dyeing or drying procedures. Furthermore, contrary to other one-step cyanoacrylate products, existing cyanoacrylate cabinets do not require any modification for the treatment of articles with Lumicyano™. To date, there is little peer reviewed articles in the literature on trials related to Lumicyano™ and this study aims to contribute to fill this gap.

  14. Loss of Coupling Distinguishes GJB1 Mutations Associated with CNS Manifestations of CMT1X from Those Without CNS Manifestations (United States)

    Abrams, Charles K.; Goman, Mikhail; Wong, Sarah; Scherer, Steven S.; Kleopa, Kleopas A.; Peinado, Alejandro; Freidin, Mona M.


    CMT1X, an X-linked inherited neuropathy, is caused by mutations in GJB1, which codes for Cx32, a gap junction protein expressed by Schwann cells and oligodendrocytes. Many GJB1 mutations cause central nervous system (CNS) abnormality in males, including stable subclinical signs and, less often, short-duration episodes characterized by motor difficulties and altered consciousness. However, some mutations have no apparent CNS effects. What distinguishes mutations with and without CNS manifestations has been unclear. Here we studied a total of 14 Cx32 mutations, 10 of which are associated with florid episodic CNS clinical syndromes in addition to peripheral neuropathy. The other 4 mutations exhibit neuropathy without clinical or subclinical CNS abnormalities. These “PNS-only” mutations (Y151C, V181M, R183C and L239I) form gap junction plaques and produce levels of junctional coupling similar to those for wild-type Cx32. In contrast, mutants with CNS manifestations (F51L, E102del, V139M, R142Q, R142W, R164W T55I, R164Q and C168Y) either form no morphological gap junction plaques or, if they do, produce little or no detectable junctional coupling. Thus, PNS and CNS abnormalities may involve different aspects of connexin function. PMID:28071741

  15. 塑料在灯具中的应用演变及发展浅析%PlasticIn the Lighting Application Evolution And Development Of Elementary Analysis

    Institute of Scientific and Technical Information of China (English)



    Demand for larger lamps in modem life, however, for lack of modem resources, enhance the environmental consciousness of consumers and aesthetic improvement of the manufacturers product processing costs can be reduced to lower the status quo. Based on the plastic has a strong ahernative, low cost, and the diversity of texture and color, a high degree of recycling of thermoplastics, strong shape diversity. Advantage of the many aspects of the plastic, plastic lighting materials of modern applications and future development has a larger space for development, the advantages of following plastic aspects of lighting material.%灯具在现代生活中需求量较大,然而针对现代资源缺乏,消费者环保意识增强及审美性的提高,制造商也要求产品加工成本可以降得更低的现状。基于塑料有很强的替代性,成本的低廉性,肌理和色彩的多样性,热塑性塑料高度的回收性,很强的塑造样性。以上诸多方面的优点,说明了塑料在灯具材料的现代应用和未来发展中都有较大的发展空间,以下就塑料这几方面优点的来进行对灯具材质的探讨。

  16. Plastics. A Handbook for Workplace Educators. (United States)

    Curry, Donna; Smith, Mikki

    This handbook was designed to help adult literacy education teachers to understand the plastics industry, develop a curriculum, and teach basic skills classes in a plastics company. The book contains four main sections. The first section, on the basics of plastics, contains a brief history of the industry, an elementary description of the…

  17. The advent of the restorative plastic surgeon. (United States)

    Carty, Matthew J; Pribaz, Julian J; Talbot, Simon G; Caterson, Edward J; Pomahac, Bohdan


    Plastic surgery is presently typified by the existence of discrete clinical identities, namely that of the cosmetic plastic surgeon and the reconstructive plastic surgeon. The emergence of vascularized composite allotransplantation has been accompanied by the development of a third distinct clinical identity, that of the restorative plastic surgeon. The authors describe the core competencies that characterize this new identity, and discuss the implications of the advent of this new professional paradigm.

  18. Development of design, qualification, screening, and application requirements for plastic encapsulated solid-state devices for space applications (United States)


    Test data were collected on 1035 plastic encapsulated devices and 75 hermetically scaled control group devices that were purchased from each of five different manufacturers in the categories of (1) low power Schottsky TTL (bipolar) digital circuits; (2) CMOS digital circuits; (3) operational amplifier linear circuits; and (4) NPN transistors. These parts were subjected to three different initial screening conditions, then to extended life testing, to determine any possible advantages or trends for any particular screen. Several tests were carried out in the areas of flammability testing, humidity testing, high pressure steam (auroclave) testing, and high temperature storage testing. Test results are presented. Procurement and application considerations for use of plastic encapsulated semiconductors are presented and a statistical analysis program written to study the log normal distributions resulting from life testing is concluded.

  19. Modulation of dendritic spine development and plasticity by BDNF and vesicular trafficking: fundamental roles in neurodevelopmental disorders associated with mental retardation and autism. (United States)

    Chapleau, Christopher A; Larimore, Jennifer L; Theibert, Anne; Pozzo-Miller, Lucas


    The process of axonal and dendritic development establishes the synaptic circuitry of the central nervous system (CNS) and is the result of interactions between intrinsic molecular factors and the external environment. One growth factor that has a compelling function in neuronal development is the neurotrophin brain-derived neurotrophic factor (BDNF). BDNF participates in axonal and dendritic differentiation during embryonic stages of neuronal development, as well as in the formation and maturation of dendritic spines during postnatal development. Recent studies have also implicated vesicular trafficking of BDNF via secretory vesicles, and both secretory and endosomal trafficking of vesicles containing synaptic proteins, such as neurotransmitter and neurotrophin receptors, in the regulation of axonal and dendritic differentiation, and in dendritic spine morphogenesis. Several genes that are either mutated or deregulated in neurodevelopmental disorders associated with mental retardation have now been identified, and several mouse models of these disorders have been generated and characterized. Interestingly, abnormalities in dendritic and synaptic structure are consistently observed in human neurodevelopmental disorders associated with mental retardation, and in mouse models of these disorders as well. Abnormalities in dendritic and synaptic differentiation are thought to underlie altered synaptic function and network connectivity, thus contributing to the clinical outcome. Here, we review the roles of BDNF and vesicular trafficking in axonal and dendritic differentiation in the context of dendritic and axonal morphological impairments commonly observed in neurodevelopmental disorders associated with mental retardation.

  20. Fetal MRI in Prenatal Diagnosis of CNS Abnormalities

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap


    Full Text Available The value of fetal MRI (fMRI compared to ultrasound in the prenatal detection of CNS abnormalities and impact on counseling were determined in 25 pregnant women examined at University of Dusseldorf, Germany.

  1. CNS drug design: balancing physicochemical properties for optimal brain exposure. (United States)

    Rankovic, Zoran


    The human brain is a uniquely complex organ, which has evolved a sophisticated protection system to prevent injury from external insults and toxins. Designing molecules that can overcome this protection system and achieve optimal concentration at the desired therapeutic target in the brain is a specific and major challenge for medicinal chemists working in CNS drug discovery. Analogous to the now widely accepted rule of 5 in the design of oral drugs, the physicochemical properties required for optimal brain exposure have been extensively studied in an attempt to similarly define the attributes of successful CNS drugs and drug candidates. This body of work is systematically reviewed here, with a particular emphasis on the interplay between the most critical physicochemical and pharmacokinetic parameters of CNS drugs as well as their impact on medicinal chemistry strategies toward molecules with optimal brain exposure. A summary of modern CNS pharmacokinetic concepts and methods is also provided.

  2. Pharmacokinetic, Pharmacogenetic, and Other Factors Influencing CNS Penetration of Antiretrovirals

    Directory of Open Access Journals (Sweden)

    Jacinta Nwamaka Nwogu


    Full Text Available Neurological complications associated with the human immunodeficiency virus (HIV are a matter of great concern. While antiretroviral (ARV drugs are the cornerstone of HIV treatment and typically produce neurological benefit, some ARV drugs have limited CNS penetration while others have been associated with neurotoxicity. CNS penetration is a function of several factors including sieving role of blood-brain and blood-CSF barriers and activity of innate drug transporters. Other factors are related to pharmacokinetics and pharmacogenetics of the specific ARV agent or mediated by drug interactions, local inflammation, and blood flow. In this review, we provide an overview of the various factors influencing CNS penetration of ARV drugs with an emphasis on those commonly used in sub-Saharan Africa. We also summarize some key associations between ARV drug penetration, CNS efficacy, and neurotoxicity.

  3. Recombinant human tripeptidyl peptidase-1 infusion to the monkey CNS: Safety, pharmacokinetics, and distribution

    Energy Technology Data Exchange (ETDEWEB)

    Vuillemenot, Brian R., E-mail: [BioMarin Pharmaceutical Inc., Novato, CA (United States); Kennedy, Derek [BioMarin Pharmaceutical Inc., Novato, CA (United States); Reed, Randall P.; Boyd, Robert B. [Northern Biomedical Research, Inc., Muskegon, MI (United States); Butt, Mark T. [Tox Path Specialists, LLC, Hagerstown, MD (United States); Musson, Donald G.; Keve, Steve; Cahayag, Rhea; Tsuruda, Laurie S.; O' Neill, Charles A. [BioMarin Pharmaceutical Inc., Novato, CA (United States)


    CLN2 disease is caused by deficiency in tripeptidyl peptidase-1 (TPP1), leading to neurodegeneration and death. The safety, pharmacokinetics (PK), and CNS distribution of recombinant human TPP1 (rhTPP1) were characterized following a single intracerebroventricular (ICV) or intrathecal-lumbar (IT-L) infusion to cynomolgus monkeys. Animals received 0, 5, 14, or 20 mg rhTPP1, ICV, or 14 mg IT-L, in artificial cerebrospinal fluid (aCSF) vehicle. Plasma and CSF were collected for PK analysis. Necropsies occurred at 3, 7, and 14 days post-infusion. CNS tissues were sampled for rhTPP1 distribution. TPP1 infusion was well tolerated and without effect on clinical observations or ECG. A mild increase in CSF white blood cells (WBCs) was detected transiently after ICV infusion. Isolated histological changes related to catheter placement and infusion were observed in ICV treated animals, including vehicle controls. The CSF and plasma exposure profiles were equivalent between animals that received an ICV or IT-L infusion. TPP1 levels peaked at the end of infusion, at which point the enzyme was present in plasma at 0.3% to 0.5% of CSF levels. TPP1 was detected in brain tissues with half-lives of 3–14 days. CNS distribution between ICV and IT-L administration was similar, although ICV resulted in distribution to deep brain structures including the thalamus, midbrain, and striatum. Direct CNS infusion of rhTPP1 was well tolerated with no drug related safety findings. The favorable nonclinical profile of ICV rhTPP1 supports the treatment of CLN2 by direct administration to the CNS. - Highlights: • TPP1 enzyme replacement therapy to the CNS is in development for CLN2 disease. • Toxicology, pharmacokinetics, and CNS distribution were assessed in monkeys. • TPP1 infusion directly to the brain did not result in any safety concerns. • A positive pharmacokinetic and distribution profile resulted from TPP1 infusion. • This study demonstrates the feasibility of ICV administered

  4. CNS Involvement in AML Patient Treated with 5-Azacytidine

    Directory of Open Access Journals (Sweden)

    Diamantina Vasilatou


    Full Text Available Central nervous system (CNS involvement in acute myeloid leukemia (AML is a rare complication of the disease and is associated with poor prognosis. Sometimes the clinical presentation can be unspecific and the diagnosis can be very challenging. Here we report a case of CNS infiltration in a patient suffering from AML who presented with normal complete blood count and altered mental status.

  5. An instructive case of CNS histoplasmosis in an immunocompetent host. (United States)

    Ramireddy, Sweeya; Wanger, Audrey; Ostrosky, Luis


    Histoplasma capsulatum is a dimorphic endemic fungus which infects both immunocompetent and immunocompromised hosts. Isolated CNS histoplasmosis is a rare presentation with increased risk in individuals with impaired cellular immunity, however not all patients with this condition are immunocompromised. We report a case of isolated CNS histoplasmosis in an otherwise healthy immunocompetent patient who was initially treated with Liposomal Amphotericin B followed by oral Voriconazole and later Itraconazole with significant improvement in clinical status.

  6. Study on Long-term Potentiation in Developing Rat Visual Cortex during the Critical Period of Plasticity

    Institute of Scientific and Technical Information of China (English)

    Pengfen Gao; Zhengqin Yin; Yingbing Liu; Shijun Wang; Huimin Fan


    Purpose: To study the property of LTP in layers Ⅱ~Ⅳof the rats visual cortex at different postnatal days induced by pairing low-frequency stimulation at layer Ⅳ with post synaptic depolarization in order to explore the synaptic and cellular mechanism of experience-dependent plasticity in the visual cortex.Methods: Postsynaptic currents (PSCs) of layers Ⅱ~Ⅳ in visual cortex slices of Wistar rats aged P0-29 d were recorded by patch-clamp whole cell recording method. Long-term potentiation (LTP) was induced by low-frequency stimulation (LFS) at 1Hz for 60~90 s.Each pulse of the LFS paired with depolarization of post-synaptic neurons to -20 mV.100μM APV, a kind of competitive N-methyl-d-aspartate (NMDA) receptor antagonist, was both applied to some slices to test the property of LTP.Results: 1. The LTP incidence was very low before P10d (5/34), and increased rapidly to the top at P15-24 d (17/28), then decreased sharply to 1/5 at P25-29 d, coinciding well with the critical period of plasticity of rat visual cortex. The LTP incidence of P15-29d (after eye opening, 18/33) was significantly higher than that of P0-14 d (before eye opening, 12/43, P < 0.05). 2. Compared with non-APV applied group (30/76), LTP incidence of APV applied group (4/33) was significantly decreased (P < 0.01 ). There were 4 Ⅳ-Ⅳ horizontal synapses. APV application could not block the LTP induction.Conclusions: 1. LTP was a reflection of naturally occurring, experience-dependent plasticity in rat visual cortex. The patterned visual stimuli received after eye opening might be an activation factor of the synaptic plasticity. 2. LTP of visual cortex induced by LFS in layer Ⅳ paired with postsynaptic depolarization was NMDA receptor dependent during the critical period of visual plasticity. However, there were LTP existed in Ⅳ-Ⅳ horizontal synapses which could not be blocked by 100μM APV.

  7. Re-circulating Phagocytes Loaded with CNS Debris: A Potential Marker of Neurodegeneration in Parkinsons Disease?

    Directory of Open Access Journals (Sweden)

    Vanessa J. White


    Full Text Available Diagnosis and monitoring of diseases by measurement of biochemical markers has most commonly been performed on samples of peripheral blood. However, no such markers are available for clinical use in the major diseases of the central nervous system (CNS. In Parkinson's disease circulating biomarkers would find clinical utility in early diagnosis and also monitoring of disease progression. Of particular interest is early diagnosis as this would create .a window of opportunity for treatment with neuroprotective drugs. We have developed a novel strategy for monitoring disease activity in the CNS based on the recognition that tissue injuries incite inflammation and recruitment of phagocytes that engulf debris. We postulated that some of these debris laden phagocytes may return to the peripheral blood and their cargo of CNS proteins could be measured. If CNS antigens can be measured in PBMCs it may be an indicator of active neurodegeneration as the debris engulfed by phagocytes is completely degraded within days. To make this approach more specific to Parkinson's disease we probed PBMC lysates for neuromelanin as a marker of degeneration within the substancia nigra. We performed a proof of principle study in ten subjects with early PD and ten age and sex matched controls. The biomarkers neuromelanin, Tau protein, UCH-L1 and HPCAL-1 were measured in PBMC lysates from these two groups. Neuromelanin and Tau protein mean levels were elevated in PD compared with controls and was extremely statistically significant in both cases. UCH-L1 and HPCAL-1 mean levels were elevated in PD over controls and were not quite significant in both cases. These results suggest that this is a promising new approach for diagnosis and monitoring of PD and potentially other CNS diseases.

  8. Globally Oriented Chinese Plastics Industry

    Institute of Scientific and Technical Information of China (English)

    Liao Zhengpin


    @@ Through continued endeavor and persistent opening to the whole world the Chinese plastics industry has been developed into a comprehensive industrial system that forms the basic material industries side by side with the steel, cement and the timber industry.

  9. Microglia and Spinal Cord Synaptic Plasticity in Persistent Pain

    Directory of Open Access Journals (Sweden)

    Sarah Taves


    Full Text Available Microglia are regarded as macrophages in the central nervous system (CNS and play an important role in neuroinflammation in the CNS. Microglial activation has been strongly implicated in neurodegeneration in the brain. Increasing evidence also suggests an important role of spinal cord microglia in the genesis of persistent pain, by releasing the proinflammatory cytokines tumor necrosis factor-alpha (TNFα, Interleukine-1beta (IL-1β, and brain derived neurotrophic factor (BDNF. In this review, we discuss the recent findings illustrating the importance of microglial mediators in regulating synaptic plasticity of the excitatory and inhibitory pain circuits in the spinal cord, leading to enhanced pain states. Insights into microglial-neuronal interactions in the spinal cord dorsal horn will not only further our understanding of neural plasticity but may also lead to novel therapeutics for chronic pain management.

  10. Effect of Neuroinflammation on Synaptic Organization and Function in the Developing Brain: Implications for Neurodevelopmental and Neurodegenerative Disorders

    DEFF Research Database (Denmark)

    Mottahedin, Amin; Ardalan, Maryam; Chumak, Tetyana


    The brain is a plastic organ where both the intrinsic CNS milieu and extrinsic cues play important roles in shaping and wiring neural connections. The perinatal period constitutes a critical time in central nervous system development with extensive refinement of neural connections, which are highly...... physiology and pathophysiology, including microglia-mediated elimination of synapses. We propose that activation of the immune system dynamically affects synaptic organization and function in the developing brain. We will discuss the role of neuroinflammation in altered synaptic plasticity following...

  11. MidExDB: A database of Drosophila CNS midline cell gene expression

    Directory of Open Access Journals (Sweden)

    Crews Stephen T


    Full Text Available Abstract Background The Drosophila CNS midline cells are an excellent model system to study neuronal and glial development because of their diversity of cell types and the relative ease in identifying and studying the function of midline-expressed genes. In situ hybridization experiments generated a large dataset of midline gene expression patterns. To help synthesize these data and make them available to the scientific community, we developed a web-accessible database. Description MidExDB (Drosophila CNS Midline Gene Expression Database is comprised of images and data from our in situ hybridization experiments that examined midline gene expression. Multiple search tools are available to allow each type of data to be viewed and compared. Descriptions of each midline cell type and their development are included as background information. Conclusion MidExDB integrates large-scale gene expression data with the ability to identify individual cell types providing the foundation for detailed genetic, molecular, and biochemical studies of CNS midline cell neuronal and glial development and function. This information has general relevance for the study of nervous system development in other organisms, and also provides insight into transcriptional regulation.

  12. Corrosion Behavior of Ferritic/Martensitic Steels CNS-I and Modified CNS-II in Supercritical Water

    Institute of Scientific and Technical Information of China (English)

    YANG Ying; YAN Qing-zhi; YANG Ya-feng; ZHANG Le-fu; GE Chang-chun


    The corrosion behaviors of CNS-I and modified CNS-II were evaluated by exposing to superciritical water (SCW) at 550℃ and 25 MPa with a dissolved oxygen concentration of 200× 10 ^-9 for up to 1 000 h. Detailed corrosion results of these two alloys were provided, including the growth rate of the oxide scales, microstructure of the oxide scales, distribution of phases and alloying elements. The mass gains of CNS-I and modified CNS-II were 609.73 mg/dm2 and 459.42 mg/dm2 , respectively, after exposing to SCW for 1 000 h. A duplex oxide scale with an outer porous magnetite layer and an inner relatively dense magnetite/spinel-mixed layer was identified on CNS-I and modified CNS-II after the test. The oxide scales were rather porous at the beginning of the test but the porosity decreased with increase of the exposure duration. It was found that Fe was enriched in the outer oxide layer, Cr was enriched in the inner oxide layer and O existed at a very high concnetration in the whole oxide scale. Other alloying elements such as Mo, W, Mn were depleted from the outer oxide layer and showed slightly enrichment in the inner oxide layer. The distributution of Ni was different from other elements, it was enriched in the interface bewteen the base metal and the oxide scale and depleted in the outer and inner oxide layers.

  13. Finite deformation analysis of continuum structures with time dependent anisotropic elastic plastic material behavior (LWBR/AWBA Development Program)

    Energy Technology Data Exchange (ETDEWEB)

    Hutula, D.N.


    A finite element procedure is presented for finite deformation analysis of continuum structures with time-dependent anisotropic elastic-plastic material behavior. An updated Lagrangian formulation is used to describe the kinematics of deformation. Anisotropic constitutive relations are referred, at each material point, to a set of three mutually orthogonal axes which rotate as a unit with an angular velocity equal to the spin at the point. The time-history of the solution is generated by using a linear incremental procedure with residual force correction, along with an automatic time step control algorithm which chooses time step sizes to control the accuracy and numerical stability of the solution.

  14. Biodegradable plastics from renewable sources. (United States)

    Flieger, M; Kantorová, M; Prell, A; Rezanka, T; Votruba, J


    Plastic waste disposal is a huge ecotechnological problem and one of the approaches to solving this problem is the development of biodegradable plastics. This review summarizes data on their use, biodegradability, commercial reliability and production from renewable resources. Some commercially successful biodegradable plastics are based on chemical synthesis (i.e. polyglycolic acid, polylactic acid, polycaprolactone, and polyvinyl alcohol). Others are products of microbial fermentations (i.e. polyesters and neutral polysaccharides) or are prepared from chemically modified natural products (e.g., starch, cellulose, chitin or soy protein).


    Directory of Open Access Journals (Sweden)

    Tadeusz Mączka


    Full Text Available The article presents the process of obtaining liquid fuels and fuel gas in the process of plasma processing of organic materials, including waste plastics. The concept of plasma pyrolysis of plastics was presented and on its basis a prototype installation was developed. The article describes a general rule of operating the installation and its elements in the process and basic operation parameters determined during its start-up. Initial results of processing plastics and the directions further investigations are also discussed. The effect of the research is to be the design of effective technology of obtaining fuels from gasification/pyrolysis of organic waste and biomass.

  16. Recycling of Plastic

    DEFF Research Database (Denmark)

    Christensen, Thomas Højlund; Fruergaard, Thilde


    Plastic is produced from fossil oil. Plastic is used for many different products. Some plastic products like, for example, wrapping foil, bags and disposable containers for food and beverage have very short lifetimes and thus constitute a major fraction of most waste. Other plastic products like......, good strength and long durability. Recycling of plastic waste from production is well-established, while recycling of postconsumer plastic waste still is in its infancy. This chapter describes briefly how plastic is produced and how waste plastic is recycled in the industry. Quality requirements...

  17. Waste Plastics Recycling and Reuse Technology Situation and Development Trend in China%我国废旧塑料的资源再利用现状与发展趋势

    Institute of Scientific and Technical Information of China (English)

    张雪; 张承龙


    通过对当前我国废旧塑料资源再利用现状的研究,分析和对比了不同废旧塑料资源再利用方法的工艺和特点,并且对废旧塑料处理的发展趋势做出了预测。%Through the study of the current status of waste plastic recycling, the processes and characteristics of different methods of recycling waste plastics are analyzed and compared, and the development trend of waste plastics processing is forecast.

  18. NMDA受体与听觉发育可塑性及学习记忆研究的进展%Development of study on NMDA receptor with auditory plasticity and learning memory

    Institute of Scientific and Technical Information of China (English)

    李建红; 王淑玉; 李晓明


    Neural plasticity is one of the most important research area of developmental neurobiology. NM-DA(N-Methyl-D-aspartale) receptor is one of the glulamate receptors in nervous system, which palys an important role in many biological and pathological changes, such as development of neural network, neural plasticity, learning and memory, degeneration of the neurons and so on. The studies on NMDA receptor with auditory plasticity and learning and memory were reviewed in order to make early intervention for hearing impaired children and provide a theoretical basis.

  19. Development and industry prospect of Straw-Plastic Composites%秸塑复合材料研究及其产业前景

    Institute of Scientific and Technical Information of China (English)

    张文涛; 陈集双


    The history and industrial development of Wood-Plastic Composites (WPC) were analyzed, pointing out the present demands of"straw instead of wood"and"straw instead of plastic". Straw, as a kind of abundant renewable biomass resources, has the potential to be developed as a new environmentally friendly material. The concept of Straw- Plastic Composite (SPC) was creatively proposed in this paper. The characteristics of straw biomass fibers were dissected and the bio-based minerals in the straw may be one of the important factors, led to SPC is superior to WPC. Moreover, the conditions for the development of SPC were elaborated, which pointed out SPC is a typical model for the full-price and high-value industrialization of straw biomass. The feasible solution that pioneered the development of SPC has been put forward under the existing conditions in the country.%通过分析木塑复合材料的发展历程和产业现状,指出了当前"以秸代木"和"以秸代塑"的新需求.秸秆作为一种丰富的可再生生物质资源,具备开发为新型环保材料的潜力.本文创造性地提出了秸塑复合材料(Straw-Plastic Composites,SPC)的概念,剖析了秸秆生物质纤维的特性,秸秆中富含的生物基矿物质可能是秸塑作为新材料形成优于木塑材料的重要因素,同时阐述了秸塑产业发展的条件,指出了SPC是秸秆生物质全价工业化、高值化利用的典范,并提出现有条件下,在我国率先开发SPC的可行方案.

  20. A study of effect of shift work, sex, and smoking on development of ONIHL in plastic weavers

    Directory of Open Access Journals (Sweden)

    Jayesh D Solanki


    Full Text Available Background: Exposure to Occupational noise is the major avoidable cause of permanent hearing loss that is preventable by protective measures. Present study evaluated hearing profile and effects of shift, sex, and smoking on hearing loss in plastic weavers working in textile industry exposed to impact type of noise. Materials and Methods: A cross-sectional study of hearing threshold of various shift workers of plastic weaving industries (18 males, 32 females at various frequencies was done and effect of various factors was tested at low and high frequencies and compared at 4 kHz, 6 kHz, and 8 kHz statistically. Results: Hearing thresholds were significantly higher at high frequencies than speech frequencies, in day shift workers than night shift workers and within day shift workers more with continuous type of shift work than interrupted type. Females showed better hearing than males and for non-smokers than smokers, but the difference observed in both instances proved statistically insignificant. Conclusion: It can be concluded that the use of alternate day and night shift, interrupted day shift may be used to prevent hearing loss and for further confirmation few more studies are warranted. Being female and non smoking also proved an advantage. Comparatively, mild to moderate degree of hearing loss further reinforces the scope of prevention by hearing protective devices and interrupted shift design of work.

  1. CNS fungal meningitis to the "Top of the basilar"

    Institute of Scientific and Technical Information of China (English)

    Logan CS; Kirschner RC; Simonds GR


    Central nervous system(CNS) infections are a rare complication of epidural steroid injections and without strong clinical suspicion, fungal organisms may be overlooked among the long differential of causes of meningitis.Rare sequela of fungal meningitis is the development of stroke.To our knowledge, we present the first case of post epidural steroid injection(ESI) fungal meningitis leading toa basilar artery stroke, otherwise known as“top of the basilar” syndrome.We present a49-year-old female with a history ofESIs who presented to the emergency department with headache, neck stiffness, and abdominal pain.She was discharged after her labs and symptoms were deemed inconsistent with meningitis.She was eventually admitted and twelve days after her originalED visit, she was diagnosed with meningitis and started on anti-fungal treatment.She was discharged88 days later but was readmitted due to left sided weakness and mental status changes.She quickly lost motor and bulbar functions.AnMRA showed diminished distal flow through the basilar artery, suggesting near complete occlusion.Although appropriate long term anti-fungal treatment was started, the patient still succumbed to a rare vascular event.Physicians who are treating patients forESI meningitis should be aware of the potential for vasculitic and encephalitic complications.

  2. Isolated vasculitis of the CNS; Isolierte Vaskulitis des ZNS

    Energy Technology Data Exchange (ETDEWEB)

    Block, F. [RWTH Aachen (Germany). Neurologische Klinik; Reith, W. [Universitaet des Saarlandes, Homburg/Saar (Germany). Radiologische Klinik


    Vasculitis is a rare cause for disease of the CNS. The isolated vasculitis of the CNS is restricted to the CNS whereas other forms of vasculitis affect various organs including the CNS. Headache, encephalopathy, focal deficits and epileptic seizures are the major symptoms suggestive for vasculitis. One major criterion of the isolated vasculitis of the CNS is the lack of evidence for other vasculitis forms or for pathology of other organs. Angiography displays multifocal segmental stenosis of intracranial vessels. MRI demonstrates multiple lesions which in part show enhancement after gadolinium. A definite diagnosis can only be made on the grounds of biopsy from leptomeninges and parenchyma. Therapy consists of corticosteroids and cyclophosphamid. (orig.) [German] Vaskulitiden sind eine seltene Ursache fuer Erkrankungen des ZNS. Die Vaskulitiden lassen sich in primaere und sekundaere einteilen, von denen sich die ueberwiegende Mehrzahl an verschiedenen Organsystemen einschliesslich dem ZNS manifestieren kann. Die isolierte ZNS-Vaskulitis ist auf das ZNS beschraenkt, bei ihr stehen klinisch-neurologisch wie bei den anderen Vaskulitisformen Kopfschmerzen, Enzephalopathie, fokale Defizite und epileptische Anfaelle im Vordergrund. Ein Kriterium der isolierten ZNS-Vaskulitis ist der klinische und laborchemische Ausschluss anderer Vaskulitiden bzw. der Beteiligung anderer Organsysteme. Multiple Kaliberspruenge intrakranieller Arterien in der zerebralen Angiographie und multiple, kleine, z.T. kontrastmittelaufnehmende Laesionen in der MRT des Schaedels sind vaskulitistypische Befunde, die allerdings auch bei anderen Vaskulitiden zu finden sind. Einzig beweisend ist eine Hirnhaut- und Hirnparenchymbiopsie. Besonders vor dem Hintergrund der therapeutischen Option, Immunsuppression mit Kortison und Cyclophosphamid, ist eine moeglichst genaue Diagnose erforderlich. (orig.)

  3. Biodegradable and compostable alternatives to conventional plastics

    National Research Council Canada - National Science Library

    J. H. Song; R. J. Murphy; R. Narayan; G. B. H. Davies


    .... Recently, significant progress has been made in the development of biodegradable plastics, largely from renewable natural resources, to produce biodegradable materials with similar functionality...

  4. A Lesson Plan to Develop Structured Discussion of the Benefits and Disadvantages of Selected Plastics Using the Product-Testing Method (United States)

    Burmeister, Mareike; Eilks, Ingo


    People use many different products made from plastics every day. But conventional plastics such as polyvinyl chloride (PVC) do not always have a good reputation in society at large. Bioplastics such as thermoplastic starch (TPS) promise to be better alternatives but are they really better than conventional plastics? This article presents a new…

  5. Evidence toward an expanded international civil aviation organization (ICAO) concept of a single unified global communication navigation surveillance air traffic management (CNS/ATM) system: A quantitative analysis of ADS-B technology within a CNS/ATM system (United States)

    Gardner, Gregory S.

    This research dissertation summarizes research done on the topic of global air traffic control, to include technology, controlling world organizations and economic considerations. The International Civil Aviation Organization (ICAO) proposed communication, navigation, surveillance, air traffic management system (CNS/ATM) plan is the basis for the development of a single global CNS/ATM system concept as it is discussed within this study. Research will be evaluated on the efficacy of a single technology, Automatic Dependent Surveillance-Broadcast (ADS-B) within the scope of a single global CNS/ATM system concept. ADS-B has been used within the Federal Aviation Administration's (FAA) Capstone program for evaluation since the year 2000. The efficacy of ADS-B was measured solely by using National Transportation Safety Board (NTSB) data relating to accident and incident rates within the Alaskan airspace (AK) and that of the national airspace system (NAS).

  6. Metallothionein induction in human CNS in vitro: neuroprotection from ionizing radiation. (United States)

    Cai, L; Cherian, M G; Iskander, S; Leblanc, M; Hammond, R R


    MT protein and MT-II mRNA can be induced in human CNS cells by ionizing radiation. Furthermore, induction of MT synthesis with Zn and Cd can protect human CNS cells from radiation-induced cytocidal and sublethal injuries. Both findings have implications in the development of strategies to protect human CNS tissue from damage during radiotherapy.

  7. Business Education for Plastic Surgeons: A Systematic Review, Development, and Implementation of a Business Principles Curriculum in a Residency Program. (United States)

    Zarrabi, Bahar; Burce, Karen K; Seal, Stella M; Lifchez, Scott D; Redett, Richard J; Frick, Kevin D; Dorafshar, Amir H; Cooney, Carisa M


    Rising health care costs, decreasing reimbursement rates, and changes in American health care are forcing physicians to become increasingly business-minded. Both academic and private plastic surgeons can benefit from being educated in business principles. The authors conducted a systematic review to identify existing business curricula and integrated a business principles curriculum into residency training. The authors anonymously surveyed their department regarding perceived importance of business principles and performed a systematic literature review from 1993 to 2013 using PubMed and Embase to identify residency training programs that had designed/implemented business curricula. Subsequently, the authors implemented a formal, quarterly business curriculum. Thirty-two of 36 physicians (88.9 percent; 76.6 percent response rate) stated business principles are either "pretty important" or "very important" to being a doctor. Only 36 percent of faculty and 41 percent of trainees had previous business instruction. The authors identified 434 articles in the systematic review: 29 documented formal business curricula. Twelve topics were addressed, with practice management/administration (n = 22) and systems-based practice (n = 6) being the most common. Four articles were from surgical specialties: otolaryngology (n = 1), general surgery (n = 2), and combined general surgery/plastic surgery (n = 1). Teaching formats included lectures and self-directed learning modules; outcomes and participant satisfaction were reported inconsistently. From August of 2013 to June of 2015, the authors held eight business principles sessions. Postsession surveys demonstrated moderately to extremely satisfied responses in 75 percent or more of resident/fellow respondents (n = 13; response rate, 48.1 percent) and faculty (n = 9; response rate, 45.0 percent). Business principles can be integrated into residency training programs. Having speakers familiar with the physician audience and a

  8. 聚酚醚模塑料的研制%Development and Preparation of Poly Phenol Ether Molding Plastics

    Institute of Scientific and Technical Information of China (English)

    唐勇; 李谦; 张志平; 胡卫东


    With poly phenol ether resin as matrix resin, hexamethylenetetramine as cross-linking agent, by adding high temperature binder, quartz powder, glass fiber as filler, blending under certain conditions, poly phenol ether plastics were prepared. The effects of different content of cross-linking agents, high temperature binder on the mechanical properties and high temperature resistance of poly phenol ether molding plastic were studied. Results showed that the properties of the prepared poly phenol ether resin were the best when the amount of hexamethylenetetramine was 4% ~ 12% as that of poly phenol ether, the mass fraction of the filler was 60%~75% , and the mass fraction of high temperature binder was 15%~20%.%以聚酚醚树脂为基体树脂、六次甲基四胺为交联剂,再添加高温黏结剂、石英粉、玻纤等填料,在一定的工艺条件下共混,制得聚酚醚模塑料.研究了不同含量的交联剂、高温黏结剂等成分对聚酚醚模塑料力学性能和耐高温性能的影响.结果表明,六次甲基四胺的用量控制在聚酚醚树脂质量的4%~12%之间,填料的质量分数为60%~75%,其中高温黏结剂的质量分数为15%~20%,所制备的聚酚醚模塑料的各项性能较佳.

  9. Organotypic Cultures as a Model to Study Adult Neurogenesis in CNS Disorders (United States)

    Cavaliere, Fabio; Benito-Muñoz, Monica; Matute, Carlos


    Neural regeneration resides in certain specific regions of adult CNS. Adult neurogenesis occurs throughout life, especially from the subgranular zone of hippocampus and the subventricular zone, and can be modulated in physiological and pathological conditions. Numerous techniques and animal models have been developed to demonstrate and observe neural regeneration but, in order to study the molecular and cellular mechanisms and to characterize multiple types of cell populations involved in the activation of neurogenesis and gliogenesis, investigators have to turn to in vitro models. Organotypic cultures best recapitulate the 3D organization of the CNS and can be explored taking advantage of many techniques. Here, we review the use of organotypic cultures as a reliable and well defined method to study the mechanisms of neurogenesis under normal and pathological conditions. As an example, we will focus on the possibilities these cultures offer to study the pathophysiology of diseases like Alzheimer disease, Parkinson's disease, and cerebral ischemia. PMID:27127518

  10. Organotypic Cultures as a Model to Study Adult Neurogenesis in CNS Disorders

    Directory of Open Access Journals (Sweden)

    Fabio Cavaliere


    Full Text Available Neural regeneration resides in certain specific regions of adult CNS. Adult neurogenesis occurs throughout life, especially from the subgranular zone of hippocampus and the subventricular zone, and can be modulated in physiological and pathological conditions. Numerous techniques and animal models have been developed to demonstrate and observe neural regeneration but, in order to study the molecular and cellular mechanisms and to characterize multiple types of cell populations involved in the activation of neurogenesis and gliogenesis, investigators have to turn to in vitro models. Organotypic cultures best recapitulate the 3D organization of the CNS and can be explored taking advantage of many techniques. Here, we review the use of organotypic cultures as a reliable and well defined method to study the mechanisms of neurogenesis under normal and pathological conditions. As an example, we will focus on the possibilities these cultures offer to study the pathophysiology of diseases like Alzheimer disease, Parkinson’s disease, and cerebral ischemia.

  11. Identification of new therapeutic targets for prevention of CNS inflammation

    DEFF Research Database (Denmark)

    Owens, Trevor


    Multiple sclerosis (MS) is a disease of complex pathologies, which involves infiltration by CD4(+) and CD8(+) T cells of and response within the central nervous system. Expression in the CNS of cytokines, reactive nitrogen species and costimulator molecules have all been described in MS. Notably......, the cytokines IFN-gamma and TNF are strongly expressed. Microglial cells in the CNS express costimulator molecules and it is assumed that they play a role in directing or inducing the T cell response. Transgenic experiments have tested the effects of overexpression of these molecules in mice and have shown...... via the enzyme inducible nitric oxide synthase, which is immunosuppressive, IFN-gamma is predominantly pro-inflammatory. In CNS disease in mice that involves CD8(+) T cells, IFN-gamma blockade is protective. Finally, microglial expression of the costimulator ligand B7.2 induces demyelinating pathology...

  12. Glial connexins and gap junctions in CNS inflammation and disease. (United States)

    Kielian, Tammy


    Gap junctions facilitate direct cytoplasmic communication between neighboring cells, facilitating the transfer of small molecular weight molecules involved in cell signaling and metabolism. Gap junction channels are formed by the joining of two hemichannels from adjacent cells, each composed of six oligomeric protein subunits called connexins. Of paramount importance to CNS homeostasis are astrocyte networks formed by gap junctions, which play a critical role in maintaining the homeostatic regulation of extracellular pH, K+, and glutamate levels. Inflammation is a hallmark of several diseases afflicting the CNS. Within the past several years, the number of publications reporting effects of cytokines and pathogenic stimuli on glial gap junction communication has increased dramatically. The purpose of this review is to discuss recent observations characterizing the consequences of inflammatory stimuli on homocellular gap junction coupling in astrocytes and microglia as well as changes in connexin expression during various CNS inflammatory conditions.

  13. Disruption of microtubule integrity initiates mitosis during CNS repair. (United States)

    Bossing, Torsten; Barros, Claudia S; Fischer, Bettina; Russell, Steven; Shepherd, David


    Mechanisms of CNS repair have vital medical implications. We show that traumatic injury to the ventral midline of the embryonic Drosophila CNS activates cell divisions to replace lost cells. A pilot screen analyzing transcriptomes of single cells during repair pointed to downregulation of the microtubule-stabilizing GTPase mitochondrial Rho (Miro) and upregulation of the Jun transcription factor Jun-related antigen (Jra). Ectopic Miro expression can prevent midline divisions after damage, whereas Miro depletion destabilizes cortical β-tubulin and increases divisions. Disruption of cortical microtubules, either by chemical depolymerization or by overexpression of monomeric tubulin, triggers ectopic mitosis in the midline and induces Jra expression. Conversely, loss of Jra renders midline cells unable to replace damaged siblings. Our data indicate that upon injury, the integrity of the microtubule cytoskeleton controls cell division in the CNS midline, triggering extra mitosis to replace lost cells. The conservation of the identified molecules suggests that similar mechanisms may operate in vertebrates.

  14. Therapeutic immune clearance of rabies virus from the CNS (United States)

    Hooper, D Craig; Roy, Anirban; Kean, Rhonda B; Phares, Timothy W; Barkhouse, Darryll A


    The long-held concept that rabies infection is lethal in humans once the causative rabies virus has reached the CNS has been called into question by the recent survival of a number of patients with clinical rabies. Studies in animal models provide insight into why survival from a rabies virus infection that has spread to the CNS is possible and the immune mechanisms involved. In the CNS, both innate mechanisms capable of inhibiting virus replication and the activity of infiltrating rabies virus-specific T and B cells with the capacity to clear the virus are required. Deficiencies in the induction of either aspect of rabies immunity can lead to lethal consequences but may be overcome by novel approaches to active and passive immunization. PMID:21686076

  15. Development of a constitutive model for the plastic deformation and creep of copper and its use in the estimate of the creep life of the copper canister

    Energy Technology Data Exchange (ETDEWEB)

    Pettersson, Kjell [Matsafe AB, Stockholm (Sweden)


    A previously developed model for the plastic deformation and creep of copper (included as an Appendix to the present report) has been used as the basis for a discussion on the possibility of brittle creep fracture of the copper canister during long term storage of nuclear waste. Reported creep tests on oxygen free (OF) copper have demonstrated that copper can have an extremely low creep ductility. However with the addition of about 50 ppm phosphorus to the copper it appears as if the creep brittleness problem is avoided and that type of copper (OFP) has consequently been chosen as the canister material. It is shown in the report that the experiments performed on OFP copper does not exclude the possibility of creep brittleness of OFP copper in the very long term. The plasticity and creep model has been used to estimate creep life under conditions of intergranular creep cracking according to a model formulated by Cocks and Ashby. The estimated life times widely exceed the design life of the canister. However the observations of creep brittleness in OF copper indicate that the Cocks-Ashby model probably does not apply to the OF copper. Thus additional calculations have been done with the plasticity and creep model in order to estimate stress as a function of time for the probably most severe loading case of the canister with regard to creep failure, an earth quake shear. Despite the fact that the stress in the canister will remain at the 100 MPa level for thousands of years after an earth quake the low temperature, about 50 deg C or less, will make the solid state diffusion process assumed to control the brittle cracking process, too slow to lead to any significant brittle creep cracking in the canister.

  16. Decreased Cognitive/CNS Function in Young Adults at Risk for Hypertension: Effects of Sleep Deprivation

    Directory of Open Access Journals (Sweden)

    James A. McCubbin


    Full Text Available Hypertension has been linked to impaired cognitive/CNS function, and some of these changes may precede development of frank essential hypertension. The stress and fatigue of sleep deprivation may exacerbate these cognitive changes in young adults at risk. We hypothesize that individuals at risk for hypertension will show significant declines in cognitive function during a night of sleep deprivation. Fifty-one young adults were recruited for 28-hour total sleep deprivation studies. Hypertension risk was assessed by mildly elevated resting blood pressure and by family history of hypertension. A series of cognitive memory tasks was given at four test sessions across the sleep deprivation period. Although initially comparable in cognitive performance, persons at risk showed larger declines across the night for several indices of working memory, including code substitution, category, and order recall. These results suggest that cognitive/CNS changes may parallel or precede blood pressure dysregulation in the early stages of hypertension development. The role of CNS changes in the etiology of essential hypertension is discussed.

  17. NFIA haploinsufficiency is associated with a CNS malformation syndrome and urinary tract defects.

    Directory of Open Access Journals (Sweden)

    Weining Lu


    Full Text Available Complex central nervous system (CNS malformations frequently coexist with other developmental abnormalities, but whether the associated defects share a common genetic basis is often unclear. We describe five individuals who share phenotypically related CNS malformations and in some cases urinary tract defects, and also haploinsufficiency for the NFIA transcription factor gene due to chromosomal translocation or deletion. Two individuals have balanced translocations that disrupt NFIA. A third individual and two half-siblings in an unrelated family have interstitial microdeletions that include NFIA. All five individuals exhibit similar CNS malformations consisting of a thin, hypoplastic, or absent corpus callosum, and hydrocephalus or ventriculomegaly. The majority of these individuals also exhibit Chiari type I malformation, tethered spinal cord, and urinary tract defects that include vesicoureteral reflux. Other genes are also broken or deleted in all five individuals, and may contribute to the phenotype. However, the only common genetic defect is NFIA haploinsufficiency. In addition, previous analyses of Nfia(-/- knockout mice indicate that Nfia deficiency also results in hydrocephalus and agenesis of the corpus callosum. Further investigation of the mouse Nfia(+/- and Nfia(-/- phenotypes now reveals that, at reduced penetrance, Nfia is also required in a dosage-sensitive manner for ureteral and renal development. Nfia is expressed in the developing ureter and metanephric mesenchyme, and Nfia(+/- and Nfia(-/- mice exhibit abnormalities of the ureteropelvic and ureterovesical junctions, as well as bifid and megaureter. Collectively, the mouse Nfia mutant phenotype and the common features among these five human cases indicate that NFIA haploinsufficiency contributes to a novel human CNS malformation syndrome that can also include ureteral and renal defects.

  18. Electrical stimulation therapies for CNS disorders and pain are mediated by competition between different neuronal networks in the brain. (United States)

    Faingold, Carl L


    treatment of unanesthetized animals with antagonists (bicuculline or strychnine) of inhibitory neurotransmitter (GABA or glycine) receptors can cause CMR neurons to become consistently responsive to external inputs (e.g., peripheral nerve, sensory, or electrical stimuli in the brain) to which these neurons did not previously respond. Conversely, agents that enhance GABA-mediated inhibition (e.g., barbiturates and benzodiazepines) or antagonize glutamate-mediated excitation (e.g., ketamine) can cause CMR neurons to become unresponsive to inputs to which they responded previously. The responses of CMR neurons exhibit extensive short-term and long-term plasticity, which permits them to participate to a variable degree in many networks. Short-term plasticity subserves termination of disease symptoms, while long-term plasticity in CMR regions subserves symptom prevention. This network interaction hypothesis has value for future research in CNS disease mechanisms and also for identifying therapeutic targets in specific brain networks for more selective stimulation and pharmacological therapies.

  19. Phenotypic plasticity and diversity in insects


    Moczek, Armin P.


    Phenotypic plasticity in general and polyphenic development in particular are thought to play important roles in organismal diversification and evolutionary innovation. Focusing on the evolutionary developmental biology of insects, and specifically that of horned beetles, I explore the avenues by which phenotypic plasticity and polyphenic development have mediated the origins of novelty and diversity. Specifically, I argue that phenotypic plasticity generates novel targets for evolutionary pr...

  20. Identification of Intrinsic Axon Growth Modulators for Intact CNS Neurons after Injury. (United States)

    Fink, Kathren L; López-Giráldez, Francesc; Kim, In-Jung; Strittmatter, Stephen M; Cafferty, William B J


    Functional deficits persist after spinal cord injury (SCI) because axons in the adult mammalian central nervous system (CNS) fail to regenerate. However, modest levels of spontaneous functional recovery are typically observed after trauma and are thought to be mediated by the plasticity of intact circuitry. The mechanisms underlying intact circuit plasticity are not delineated. Here, we characterize the in vivo transcriptome of sprouting intact neurons from Ngr1 null mice after partial SCI. We identify the lysophosphatidic acid signaling modulators LPPR1 and LPAR1 as intrinsic axon growth modulators for intact corticospinal motor neurons after adjacent injury. Furthermore, in vivo LPAR1 inhibition or LPPR1 overexpression enhances sprouting of intact corticospinal tract axons and yields greater functional recovery after unilateral brainstem lesion in wild-type mice. Thus, the transcriptional profile of injury-induced sprouting of intact neurons reveals targets for therapeutic enhancement of axon growth initiation and new synapse formation. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  1. 加强筋地膜加工装置的设计与试验%Development of Reinforced Plastic Processing Device to Strengthen

    Institute of Scientific and Technical Information of China (English)

    蒋建云; 王旭峰; 胡灿; 孟祥营; 陈超


    为了防治地膜受风沙作用破损及提高残膜回收率,研制成功一种加强筋塑料地膜和加工机械。为了提高效率,降低成本,设计了一种加强筋地膜加工装置,与现有棉花覆膜播种机配套使用。同时,对该装置和加强筋地膜加工机械进行加工试验对比分析,结果表明,该装置结构简单、便于维修,有效提高了加强筋加工效率,降低了成本,并能正常进行棉花覆膜播种,且残膜回收率高,达到95.3%。经过棉花种植成本计算分析,加强筋地膜有很好的经济效益,可以大面积推广。%For prevention and control of mulch sand damage and residual film recovery ,our previous successfully devel-oped a kind of reinforced plastic film and processing machinery ,in order to improve efficiency ,reduce cost , this paper de-signed a kind of reinforced plastic processing equipment ,with the existing cotton coated machine supporting the use .And on the device and reinforced plastic processing machinery processing experiment was carried out comparative analysis , the results show that the device has simple structure ,easy maintenance ,effective reinforcement processing efficiency ,reduces the cost, at the same time,it can be carried out as normal and cotton coated seed .After membrane recycling residue test , residual film recovery rate is high ,at 95.3%, after cotton cultivation cost calculation and analysis ,reinforced plastic has good economic benefit ,can large area promotion .

  2. Interaction between vegetable oil based plasticizer molecules and polyvinyl chloride, and their plasticization effect (United States)

    Haryono, Agus; Triwulandari, Evi; Jiang, Pingping


    Plasticizer molecules are low molecular weight compounds that are widely used in polymer industries especially in polyvinyl chloride (PVC) resin. As an additive in PVC resin, the important role of plasticizer molecules is to improve the flexibility and processability of PVC by lowering the glass transition temperature (Tg). However, the commercial plasticizer like di(2-ethylhexyl)phthalate (DEHP) is known to cause liver cancer, at least in laboratory rats. DEHP can leach out from PVC into blood, certain drug solutions and fatty foods, which has been detected in the bloodstream of patients undergoing transfusion. Vegetable oil based plasticizers have some attractive properties such as non-toxic, bio-degradable, good heat and light stability, renewable resources, and environmentally friendly. Here we discussed the main results and development of vegetable oil based plasticizer, and especially palm oil based plasticizer. The interaction between plasticizer and polymer was discussed from the properties of the plasticized polymeric material.

  3. The Future of Plastic Surgery: Surgeon's Perspective. (United States)

    Ozturk, Sinan; Karagoz, Huseyin; Zor, Fatih


    Since the days of Sushruta, innovation has shaped the history of plastic surgery. Plastic surgeons have always been known as innovators or close followers of innovations. With this descriptive international survey study, the authors aimed to evaluate the future of plastic surgeons by analyzing how plastic surgery and plastic surgeons will be affected by new trends in medicine. Aesthetic surgery is the main subclass of plastic surgery thought to be the one that will change the most in the future. Stem cell therapy is considered by plastic surgeons to be the most likely "game changer." Along with changes in surgery, plastic surgeons also expect changes in plastic surgery education. The most approved assumption for the future of plastic surgery is, "The number of cosmetic nonsurgical procedures will increase in the future." If surgeons want to have better outcomes in their practice, they must at least be open minded for innovations if they do not become innovators themselves. Besides the individual effort of each surgeon, international and local plastic surgery associations should develop new strategies to adopt these innovations in surgical practice and education.

  4. Microelectronics plastic molded packaging

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, D.R. [Ktech Corp., Albuquerque, NM (United States); Palmer, D.W.; Peterson, D.W. [Sandia National Lab., Albuquerque, NM (United States)] [and others


    The use of commercial off-the-shelf (COTS) microelectronics for nuclear weapon applications will soon be reality rather than hearsay. The use of COTS for new technologies for uniquely military applications is being driven by the so-called Perry Initiative that requires the U.S. Department of Defense (DoD) to accept and utilize commercial standards for procurement of military systems. Based on this philosophy, coupled with several practical considerations, new weapons systems as well as future upgrades will contain plastic encapsulated microelectronics. However, a conservative Department of Energy (DOE) approach requires lifetime predictive models. Thus, the focus of the current project is on accelerated testing to advance current aging models as well as on the development of the methodology to be used during WR qualification of plastic encapsulated microelectronics. An additional focal point involves achieving awareness of commercial capabilities, materials, and processes. One of the major outcomes of the project has been the definition of proper techniques for handling and evaluation of modern surface mount parts which might be used in future systems. This program is also raising the familiarity level of plastic within the weapons complex, allowing subsystem design rules accommodating COTS to evolve. A two year program plan is presented along with test results and commercial interactions during this first year.

  5. A development and biological safety evaluation of novel PVC medical devices with surface structures modified by UV irradiation to suppress plasticizer migration. (United States)

    Haishima, Yuji; Isama, Kazuo; Hasegawa, Chie; Yuba, Toshiyasu; Matsuoka, Atsuko


    This study examines the chemical, physicochemical, and biological properties of PVC sheets treated with UV irradiation on their surfaces to suppress the elution of a plasticizer, di-(2-ethylhexyl) phthalate (DEHP), for developing novel polyvinyl chloride (PVC) medical devices. The PVC sheets irradiated under conditions 1 (52.5 μW/cm(2), 136 J/cm(2)) and 2 (0.45 mW/cm(2), 972 J/cm(2)) exhibited considerable toxicity in cytotoxicity tests and chromosome aberration tests due to the generation of DEHP oxidants, but no toxicity was detected in the PVC sheet irradiated under condition 3 (8.3 mW/cm(2), 134 J/cm(2)). The release of DEHP from the surface irradiated under condition 3 was significantly suppressed, and mono-(2-ethylhexyl) phthalate (MEHP) converted from a portion of DEHP could be easily removed from the surface by washing with methanol. The physicochemical properties of the surface regarding the suppression of DEHP elution remained stable through all sterilizations tested, but MEHP elution was partially recrudesced by the sterilizations except for gamma irradiation. These results indicated that UV irradiation using a strong UV-source over a short time (condition 3) followed by methanol washing and gamma sterilization may be useful for preparing novel PVC products that did not elute plasticizers and do not exhibit toxicity originating from UV irradiation.

  6. 木塑复合材料托盘的研究%Study on Development Prospect of the Wood-Plastic-Composite Pallet

    Institute of Scientific and Technical Information of China (English)

    赵磊; 肖生苓


    在对目前国内外托盘材料和产品研究技术综述的基础上,比较木塑复合材料托盘与实木托盘、塑料托盘及钢制托盘的使用性能及特点,论述木塑复合材料托盘的研制工艺和技术难点并指出,以废弃塑料作为基体材料,以木质剩余物纤维作为增强材料,利用挤出方法制作的新型复合材料托盘将成为托盘家族的主力军.%The paper compares the performance and characteristics of the wood-plastic- composite pallet with that of the solid wood, plastic and steel pallets, introduces the processes and technological difficulties in the development of such pallet and points out that this innovated composite material pallet will be the future's most popular type.

  7. The risk of CNS involvement in aggressive lymphomas in the rituximab era. (United States)

    Benevolo, Giulia; Chiappella, Annalisa; Vitolo, Umberto


    The risk of CNS dissemination and CNS prophylaxis strategies in aggressive non-Hodgkin lymphoma (NHL) is still debated. CNS dissemination is a rare but fatal event. A CNS prophylaxis is common for Burkitt and B-cell lymphoblastic lymphoma; however, in other NHLs, prophylactic treatments are not systematically warranted. Current risk models showed low sensitivity in predicting CNS involvement, implying overtreatment in roughly 70% of high-risk patients. Risk models in the rituximab era were modulated for the detection of occult CNS disease at diagnosis using flow cytometry. The optimal regimen for CNS prophylaxis in aggressive lymphoma patients has not been established thus far and should be modulated at different levels of 'intensity' such as standard intrathecal chemotherapy, 'active' intrathecal chemotherapy with liposomal cytarabine or more aggressive systemic treatment with high doses of drugs having good CNS bioavailability reserved for patients who are truly at high risk of CNS dissemination.

  8. Research cooperation project on the development of easy injection molding control technology for engineering plastics; Engineering plastic no seikei joken kan`i settei gijutsu ni kansuru kenkyu kyoryoku jigyo seika hokokusho

    Energy Technology Data Exchange (ETDEWEB)



    In order to enhance the industries which supply assembly parts to Japan`s assembly industries in Thailand, research cooperation project on the plastic parts production technology has started. For the research cooperation, the mold design is effectively conducted using simulation technique of CAE (computer aided engineering), and an international easy injection molding control system is made using the molding support software for injection molding machines. In FY 1996, actual situations of plastic parts and assembly industries in Thailand have been investigated through the cooperation with the counterpart of Thailand. Demand and supply of engineering plastics, receive and inspection of parts, and current circumstances of molding processing makers in Thailand have been grasped. Based on the results of this investigation, proposal of basic plan, time schedule, and delivery plan of molding machines and testing equipment have been discussed, to make the basic plan. 18 refs., 4 figs., 23 tabs.

  9. 14-3-3 adaptor protein-protein interactions as therapeutic targets for CNS diseases. (United States)

    Kaplan, Andrew; Ottmann, Christian; Fournier, Alyson E


    14-3-3s are a family of ubiquitously expressed adaptor proteins that regulate hundreds of functionally diverse 'client proteins.' In humans, there are seven isoforms with conserved structure and function. 14-3-3s typically bind to client proteins at phosphorylated serine/threonine motifs via a linear binding groove. Binding can have a variety of effects on the stability, activity and/or localization of the client protein. 14-3-3s are generating significant interest as potential drug targets for their involvement in cellular homeostasis and disease. They are especially abundant in the central nervous system (CNS) and are implicated in numerous CNS diseases, often through specific interactions with disease-relevant client proteins. Several tool compounds that can modulate 14-3-3 interactions with client proteins to elicit therapeutic effects have recently been described. Here we offer a perspective on the functions of 14-3-3s in neurons and the potential development of drugs to therapeutically target 14-3-3 PPIs for CNS diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Nucleoside reverse transcriptase inhibitors (NRTIs) induce proinflammatory cytokines in the CNS via Wnt5a signaling. (United States)

    Wu, Ting; Zhang, Juan; Geng, Mingxing; Tang, Shao-Jun; Zhang, Wenping; Shu, Jianhong


    HAART is very effective in suppressing HIV-1 replication in patients. However, patients staying on long-term HAART still develop various HIV-associated neurological disorders, even when the viral load is low. The underlying pathogenic mechanisms are largely unknown. Emerging evidence implicated that persistent neuroinflammation plays an important role in NeuroAIDS. Although residual virus or viral proteins are commonly thought as the causal factors, we are interested in the alternative possibility that HAART critically contributes to the neuroinflammation in the central nervous system (CNS). To test this hypothesis, we have determined the effect of NRTIs on the expression of proinflammatory cytokines in the various CNS regions. Mice (C57Bl/6) were administered with AZT (Zidovudine 100 mg/kg/day), 3TC (Lamivudine 50 mg/kg/day) or D4T (Stavudine 10 mg/kg/day) for 5 days, and cortices, hippocampi and spinal cords were collected for immunoblotting. Our results showed that NRTI administration up-regulated cytokines, including IL-1β, TNF-α and IL-6 in various CNS regions. In addition, we found that NRTIs also up-regulated Wnt5a protein. Importantly, BOX5 attenuated NRTI-induced cytokine up-regulation. These results together suggest that NRTIs up-regulate proinflammatory cytokines via a Wnt5a signaling-dependent mechanism. Our findings may help understand the potential pathogenic mechanisms of HAART-associated NeuroAIDS and design effective adjuvants.

  11. The development of thermal nanoprobe methods as a means of characterizing and mapping plasticizer incorporation into ethylcellulose films. (United States)

    Meng, Jin; Levina, Marina; Rajabi-Siahboomi, Ali R; Round, Andrew N; Reading, Mike; Craig, Duncan Q M


    The phase composition and distribution of ethylcellulose (EC) films containing varying amounts of the plasticizer fractionated coconut oil (FCO) were studied using a novel combination of thermal and mapping approaches. The thermal and thermomechanical properties of films containing up to 30% FCO were characterized using modulated temperature differential scanning calorimetry (MTDSC) and dynamic mechanical analysis (DMA). Film surfaces were mapped using atomic force microscopy (AFM; topographic and pulsed force modes) and the composition of specific regions identified using nanothermal probes. Clear evidence of distinct conjugate phases was obtained for the 20-30% FCO/EC film systems. We suggest a model whereby the composition of the distinct phases may be estimated via consideration of the glass transition temperatures observed using DSC and DMA. By combining pulsed force AFM and nano-thermal analysis we demonstrate that it is possible to map the two separated phases. In particular, the use of thermal probes allowed identification of the distinct regions via localized thermomechanical analysis, whereby nanoscale probe penetration is measured as a function of temperature. The study has indicated that by using thermal and imaging techniques in conjunction it is possible to both identify and map distinct regions in binary films.

  12. Degradation of oxo-biodegradable plastic by Pleurotus ostreatus.

    Directory of Open Access Journals (Sweden)

    José Maria Rodrigues da Luz

    Full Text Available Growing concerns regarding the impact of the accumulation of plastic waste over several decades on the environmental have led to the development of biodegradable plastic. These plastics can be degraded by microorganisms and absorbed by the environment and are therefore gaining public support as a possible alternative to petroleum-derived plastics. Among the developed biodegradable plastics, oxo-biodegradable polymers have been used to produce plastic bags. Exposure of this waste plastic to ultraviolet light (UV or heat can lead to breakage of the polymer chains in the plastic, and the resulting compounds are easily degraded by microorganisms. However, few studies have characterized the microbial degradation of oxo-biodegradable plastics. In this study, we tested the capability of Pleurotus ostreatus to degrade oxo-biodegradable (D2W plastic without prior physical treatment, such as exposure to UV or thermal heating. After 45 d of incubation in substrate-containing plastic bags, the oxo-biodegradable plastic, which is commonly used in supermarkets, developed cracks and small holes in the plastic surface as a result of the formation of hydroxyl groups and carbon-oxygen bonds. These alterations may be due to laccase activity. Furthermore, we observed the degradation of the dye found in these bags as well as mushroom formation. Thus, P. ostreatus degrades oxo-biodegradable plastics and produces mushrooms using this plastic as substrate.

  13. Degradation of oxo-biodegradable plastic by Pleurotus ostreatus. (United States)

    da Luz, José Maria Rodrigues; Paes, Sirlaine Albino; Nunes, Mateus Dias; da Silva, Marliane de Cássia Soares; Kasuya, Maria Catarina Megumi


    Growing concerns regarding the impact of the accumulation of plastic waste over several decades on the environmental have led to the development of biodegradable plastic. These plastics can be degraded by microorganisms and absorbed by the environment and are therefore gaining public support as a possible alternative to petroleum-derived plastics. Among the developed biodegradable plastics, oxo-biodegradable polymers have been used to produce plastic bags. Exposure of this waste plastic to ultraviolet light (UV) or heat can lead to breakage of the polymer chains in the plastic, and the resulting compounds are easily degraded by microorganisms. However, few studies have characterized the microbial degradation of oxo-biodegradable plastics. In this study, we tested the capability of Pleurotus ostreatus to degrade oxo-biodegradable (D2W) plastic without prior physical treatment, such as exposure to UV or thermal heating. After 45 d of incubation in substrate-containing plastic bags, the oxo-biodegradable plastic, which is commonly used in supermarkets, developed cracks and small holes in the plastic surface as a result of the formation of hydroxyl groups and carbon-oxygen bonds. These alterations may be due to laccase activity. Furthermore, we observed the degradation of the dye found in these bags as well as mushroom formation. Thus, P. ostreatus degrades oxo-biodegradable plastics and produces mushrooms using this plastic as substrate.

  14. Degradation of Oxo-Biodegradable Plastic by Pleurotus ostreatus (United States)

    da Luz, José Maria Rodrigues; Paes, Sirlaine Albino; Nunes, Mateus Dias; da Silva, Marliane de Cássia Soares; Kasuya, Maria Catarina Megumi


    Growing concerns regarding the impact of the accumulation of plastic waste over several decades on the environmental have led to the development of biodegradable plastic. These plastics can be degraded by microorganisms and absorbed by the environment and are therefore gaining public support as a possible alternative to petroleum-derived plastics. Among the developed biodegradable plastics, oxo-biodegradable polymers have been used to produce plastic bags. Exposure of this waste plastic to ultraviolet light (UV) or heat can lead to breakage of the polymer chains in the plastic, and the resulting compounds are easily degraded by microorganisms. However, few studies have characterized the microbial degradation of oxo-biodegradable plastics. In this study, we tested the capability of Pleurotus ostreatus to degrade oxo-biodegradable (D2W) plastic without prior physical treatment, such as exposure to UV or thermal heating. After 45 d of incubation in substrate-containing plastic bags, the oxo-biodegradable plastic, which is commonly used in supermarkets, developed cracks and small holes in the plastic surface as a result of the formation of hydroxyl groups and carbon-oxygen bonds. These alterations may be due to laccase activity. Furthermore, we observed the degradation of the dye found in these bags as well as mushroom formation. Thus, P. ostreatus degrades oxo-biodegradable plastics and produces mushrooms using this plastic as substrate. PMID:23967057

  15. Advances in brain barriers and brain fluid research and news from Fluids and Barriers of the CNS. (United States)

    Drewes, Lester R; Jones, Hazel C; Keep, Richard F


    Research into brain barriers and brain fluids has been advancing rapidly in recent years. This editorial aims to highlight some of the advances that have improved our understanding of this complex subject. It also brings you news of developments for Fluids and Barriers of the CNS including a new affiliation between the journal and the International Society for Hydrocephalus and CSF disorders.

  16. HIV-associated opportunistic CNS infections: pathophysiology, diagnosis and treatment. (United States)

    Bowen, Lauren N; Smith, Bryan; Reich, Daniel; Quezado, Martha; Nath, Avindra


    Nearly 30 years after the advent of antiretroviral therapy (ART), CNS opportunistic infections remain a major cause of morbidity and mortality in HIV-positive individuals. Unknown HIV-positive disease status, antiretroviral drug resistance, poor drug compliance, and recreational drug abuse are factors that continue to influence the morbidity and mortality of infections. The clinical and radiographic pattern of CNS opportunistic infections is unique in the setting of HIV infection: opportunistic infections in HIV-positive patients often have characteristic clinical and radiological presentations that can differ from the presentation of opportunistic infections in immunocompetent patients and are often sufficient to establish the diagnosis. ART in the setting of these opportunistic infections can lead to a paradoxical worsening caused by an immune reconstitution inflammatory syndrome (IRIS). In this Review, we discuss several of the most common CNS opportunistic infections: cerebral toxoplasmosis, progressive multifocal leukoencephalopathy (PML), tuberculous meningitis, cryptococcal meningitis and cytomegalovirus infection, with an emphasis on clinical pearls, pathological findings, MRI findings and treatment. Moreover, we discuss the risk factors, pathophysiology and management of IRIS. We also summarize the challenges that remain in management of CNS opportunistic infections, which includes the lack of phase II and III clinical trials, absence of antimicrobials for infections such as PML, and controversy regarding the use of corticosteroids for treatment of IRIS.

  17. Diagnostic and therapeutic challenges in superficial CNS siderosis

    DEFF Research Database (Denmark)

    Kondziella, Daniel; Lindelof, M.; Haziri, Donika


    that neurodegeneration due to haemosiderin-associated iron toxicity becomes irreversible with time. CONCLUSION: Surgical therapy in superficial CNS siderosis is rarely achieved. We suggest that prospective, large-scale multicentre studies are needed to search for non-surgical therapies that reverse (or prevent) ongoing...... neurotoxicity due to accumulating iron toxicity. FUNDING: not relevant. TRIAL REGISTRATION: not relevant....


    Nanometer size particles carry free radical activity on their surface and can create oxidative stress (OS)-mediated inflammatory changes upon impact. The oxidative burst signals the activation of phage-lineage cells such as peripheral macrophages, Kupffer cells and CNS microgl...

  19. Causes of CNS inflammation and potential targets for anticonvulsants. (United States)

    Falip, Mercé; Salas-Puig, Xavier; Cara, Carlos


    Inflammation is one of the most important endogenous defence mechanisms in an organism. It has been suggested that inflammation plays an important role in the pathophysiology of a number of human epilepsies and convulsive disorders, and there is clinical and experimental evidence to suggest that inflammatory processes within the CNS may either contribute to or be a consequence of epileptogenesis. This review discusses evidence from human studies on the role of inflammation in epilepsy and highlights potential new targets in the inflammatory cascade for antiepileptic drugs. A number of mechanisms have been shown to be involved in CNS inflammatory reactions. These include an inflammatory response at the level of the blood-brain barrier (BBB), immune-mediated damage to the CNS, stress-induced release of inflammatory mediators and direct neuronal dysfunction or damage as a result of inflammatory reactions. Mediators of inflammation in the CNS include interleukin (IL)-1β, tumour necrosis factor-α, nuclear factor-κB and toll-like receptor-4 (TLR4). IL-1β, BBB and high-mobility group box-1-TLR4 signalling appear to be the most promising targets for anticonvulsant agents directed at inflammation. Such agents may provide effective therapy for drug-resistant epilepsies in the future.

  20. Commentary on Special Issue : CNS Diseases and the Immune System

    NARCIS (Netherlands)

    't Hart, Bert A.; den Dunnen, Wilfred F.


    In an increasing number of central nervous system (CNS) diseases a pathogenic contribution of the immune system is proposed. However, the exact underlying mechanisms are often poorly understood. The collection of articles in this special issue presents a state-of-the-art review of adaptive and innat

  1. Activity-Driven CNS Changes in Learning and Development (United States)


    NY. 9. HICKEY, T. L. & R. W. GuiI.LERY. 1974. J. Comp. Neurol. 156: 239- 254. 10. SANDERSON , K. J. 1971. J. Cotmp. Neurol. 143: 101-118. I1. HUBEL. D...Neurocytol. 6: 211-230, 82 APpi M-oA ri. M. D., D. S. KLRR & P. W. L ND:III I1). 1987. Brain Res. 401: 401-400 83. BRANDON . J. G. & R. G. Coss. 1982

  2. Recycling of Plastic

    DEFF Research Database (Denmark)

    Christensen, Thomas Højlund; Fruergaard, Thilde


    Plastic is produced from fossil oil. Plastic is used for many different products. Some plastic products like, for example, wrapping foil, bags and disposable containers for food and beverage have very short lifetimes and thus constitute a major fraction of most waste. Other plastic products like......, for example, gutters, window frames, car parts and transportation boxes have long lifetimes and thus appear as waste only many years after they have been introduced on the market. Plastic is constantly being used for new products because of its attractive material properties: relatively cheap, easy to form......, good strength and long durability. Recycling of plastic waste from production is well-established, while recycling of postconsumer plastic waste still is in its infancy. This chapter describes briefly how plastic is produced and how waste plastic is recycled in the industry. Quality requirements...

  3. Extruded plastic scintillator for MINERvA

    Energy Technology Data Exchange (ETDEWEB)

    Pla-Dalmau, Anna; Bross, Alan D.; /Fermilab; Rykalin, Victor V.; Wood, Brian M.; /NICADD, DeKalb


    An extrusion line has recently been installed at Fermilab in collaboration with NICADD (Northern Illinois Center for Accelerator and Detector Development). This new facility will serve to further develop and improve extruded plastic scintillator. Since polystyrene is widely used in the consumer industry, the logical path was to investigate the extrusion of commercial-grade polystyrene pellets with dopants to yield high quality plastic scintillator. The D0 and MINOS experiments are already using extruded scintillator strips in their detectors. A new experiment at Fermilab is pursuing the use of extruded plastic scintillator. A new plastic scintillator strip is being tested and its properties characterized. The initial results are presented here.

  4. Communicating the financial worth of the CNS through the use of fiscal reports. (United States)

    Ferraro-McDuffie, A; Chan, J S; Jerome, A M


    To maintain the clinical nurse specialist's (CNS's) leading role within hospital nursing services, routine communication to hospital administration of the impact of the CNS role on the hospital's budget is imperative. The CNS group at Children's Hospital of The King's Daughters implemented a quarterly Fiscal Report to clarify the financial worth of CNS practice. The Fiscal Report presents cost savings and revenue generating activities utilizing the role components of the CNS. During fiscal year 1991, the CNS group reported a total impact of $1,600,000. This article describes in detail the use of the Fiscal Report.

  5. PEG minocycline-liposomes ameliorate CNS autoimmune disease.

    Directory of Open Access Journals (Sweden)

    Wei Hu

    Full Text Available BACKGROUND: Minocycline is an oral tetracycline derivative with good bioavailability in the central nervous system (CNS. Minocycline, a potent inhibitor of matrix metalloproteinase (MMP-9, attenuates disease activity in experimental autoimmune encephalomyelitis (EAE, an animal model of multiple sclerosis (MS. Potential adverse effects associated with long-term daily minocycline therapy in human patients are concerning. Here, we investigated whether less frequent treatment with long-circulating polyethylene glycol (PEG minocycline liposomes are effective in treating EAE. FINDINGS: Performing in vitro time kinetic studies of PEG minocycline-liposomes in human peripheral blood mononuclear cells (PBMCs, we determined that PEG minocycline-liposome preparations stabilized with CaCl(2 are effective in diminishing MMP-9 activity. Intravenous injections of PEG minocycline-liposomes every five days were as effective in ameliorating clinical EAE as daily intraperitoneal injections of minocycline. Treatment of animals with PEG minocycline-liposomes significantly reduced the number of CNS-infiltrating leukocytes, and the overall expression of MMP-9 in the CNS. There was also a significant suppression of MMP-9 expression and proteolytic activity in splenocytes of treated animals, but not in CNS-infiltrating leukocytes. Thus, leukocytes gaining access to the brain and spinal cord require the same absolute amount of MMP-9 in all treatment groups, but minocycline decreases the absolute cell number. CONCLUSIONS: Our data indicate that less frequent injections of PEG minocycline-liposomes are an effective alternative pharmacotherapy to daily minocycline injections for the treatment of CNS autoimmune diseases. Also, inhibition of MMP-9 remains a promising treatment target in EAE and patients with MS.

  6. Fabrication of plastic biochips

    Energy Technology Data Exchange (ETDEWEB)

    Saaem, Ishtiaq; Ma, Kuo-Sheng; Alam, S. Munir; Tian Jingdong [Department of Biomedical Engineering and Institute for Genome Sciences and Policy, Duke University, Durham, North Carolina 27708 (United States); Department of Medicine and Human Vaccine Institute, Duke University, Durham, North Carolina 27708 (United States); Department of Biomedical Engineering and Institute for Genome Sciences and Policy, Duke University, Durham, North Carolina 27708 (United States)


    A versatile surface functionalization procedure based on rf magnetron sputtering of silica was performed on poly(methylmethacrylate), polycarbonate, polypropylene, and cyclic olefin copolymers (Topas 6015). The hybrid thermoplastic surfaces were characterized by x-ray photoelectron spectrometer analysis and contact angle measurements. The authors then used these hybrid materials to perform a sandwich assay targeting an HIV-1 antibody using fluorescent detection and biotinylated peptides immobilized using the bioaffinity of biotin-neutravidin. They found a limit of detection similar to arrays on glass surfaces and believed that this plastic biochip platform may be used for the development of disposable immunosensing and diagnostic applications.

  7. 77 FR 54930 - Carlyle Plastics and Resins, Formerly Known as Fortis Plastics, A Subsidiary of Plastics... (United States)


    ... Employment and Training Administration Carlyle Plastics and Resins, Formerly Known as Fortis Plastics, A... plastic parts. New information shows that Fortis Plastics is now called Carlyle Plastics and Resins. In... of Carlyle Plastics and Resins, formerly known as Fortis Plastics, a subsidiary of...

  8. A review of plastic waste biodegradation. (United States)

    Zheng, Ying; Yanful, Ernest K; Bassi, Amarjeet S


    With more and more plastics being employed in human lives and increasing pressure being placed on capacities available for plastic waste disposal, the need for biodegradable plastics and biodegradation of plastic wastes has assumed increasing importance in the last few years. This review looks at the technological advancement made in the development of more easily biodegradable plastics and the biodegradation of conventional plastics by microorganisms. Additives, such as pro-oxidants and starch, are applied in synthetic materials to modify and make plastics biodegradable. Recent research has shown that thermoplastics derived from polyolefins, traditionally considered resistant to biodegradation in ambient environment, are biodegraded following photo-degradation and chemical degradation. Thermoset plastics, such as aliphatic polyester and polyester polyurethane, are easily attacked by microorganisms directly because of the potential hydrolytic cleavage of ester or urethane bonds in their structures. Some microorganisms have been isolated to utilize polyurethane as a sole source of carbon and nitrogen source. Aliphatic-aromatic copolyesters have active commercial applications because of their good mechanical properties and biodegradability. Reviewing published and ongoing studies on plastic biodegradation, this paper attempts to make conclusions on potentially viable methods to reduce impacts of plastic waste on the environment.

  9. Steroid hormones and CNS sexual dimorphisms modulate symptom expression in Tourette's syndrome. (United States)

    Peterson, B S; Leckman, J F; Scahill, L; Naftolin, F; Keefe, D; Charest, N J; Cohen, D J


    We present our hypothesis that various steroid hormones play an important role in the symptom expression of Gilles de la Tourette's syndrome (TS) and that androgenic hormones, in particular, are likely to exacerbate symptoms of the disorder. We review the clinical evidence supporting our hypothesis. Sex steroids establish brain sexual dimorphisms early in CNS development, and we suggest mechanisms whereby androgenic and other hormonal changes later in human development might act at dimorphic brain regions to influence the natural history of TS. Finally, we discuss the various ways in which neuroendocrine studies might assist in genetic and neurobiologic research programs in TS.

  10. Auditory system physiology (CNS) : behavioral studies psychoacoustics

    CERN Document Server

    Neff, William


    nerve; subsequently, however, they concluded that the recordings had been from aberrant cells of the cochlear nucleus lying central to the glial margin of the VIII nerve (GALAMBOS and DAVIS, 1948). The first successful recordmgs from fibres of the cochlear nerve were made by TASAKI (1954) in the guinea pig. These classical but necessarily limited results were greatly extended by ROSE, GALAMBOS, and HUGHES (1959) in the cat cochlear nucleus and by KATSUKI and co-workers (KATSUKI et at. , 1958, 1961, 1962) in the cat and monkey cochlear nerve. Perhaps the most significant developments have been the introduction of techniques for precise control of the acoustic stimulus and the quantitative analysis of neuronal response patterns, notably by the laboratories of KIANG (e. g. GERSTEIN and KIANG, 1960; KIANG et at. , 1962b, 1965a, 1967) and ROSE (e. g. ROSE et at. , 1967; HIND et at. , 1967). These developments have made possible a large number of quanti­ tative investigations of the behaviour of representative num...

  11. The role of the immune system in central nervous system plasticity after acute injury. (United States)

    Peruzzotti-Jametti, L; Donegá, M; Giusto, E; Mallucci, G; Marchetti, B; Pluchino, S


    Acute brain injuries cause rapid cell death that activates bidirectional crosstalk between the injured brain and the immune system. In the acute phase, the damaged CNS activates resident and circulating immune cells via the local and systemic release of soluble mediators. This early immune activation is necessary to confine the injured tissue and foster the clearance of cellular debris, thus bringing the inflammatory reaction to a close. In the chronic phase, a sustained immune activation has been described in many CNS disorders, and the degree of this prolonged response has variable effects on spontaneous brain regenerative processes. The challenge for treating acute CNS damage is to understand how to optimally engage and modify these immune responses, thus providing new strategies that will compensate for tissue lost to injury. Herein we have reviewed the available information regarding the role and function of the innate and adaptive immune responses in influencing CNS plasticity during the acute and chronic phases of after injury. We have examined how CNS damage evolves along the activation of main cellular and molecular pathways that are associated with intrinsic repair, neuronal functional plasticity and facilitation of tissue reorganization.

  12. Our plastic age

    National Research Council Canada - National Science Library

    Richard C. Thompson; Shanna H. Swan; Charles J. Moore; Frederick S. vom Saal


    Within the last few decades, plastics have revolutionized our daily lives. Globally we use in excess of 260 million tonnes of plastic per annum, accounting for approximately 8 per cent of world oil production...

  13. Weinig plastic in vissenmaag

    NARCIS (Netherlands)

    Foekema, E.M.


    Waar de magen van sommige zeevogels vol plastic zitten, lijken vissen in de Noordzee nauwelijks last te hebben van kunststofafval. Onderzoekers die plastic resten zochten in vissenmagen vonden ze in elk geval nauwelijks.

  14. Ear Plastic Surgery (United States)

    ... ENTCareers Marketplace Find an ENT Doctor Near You Ear Plastic Surgery Ear Plastic Surgery Patient Health Information ... they may improve appearance and self-confidence. Can Ear Deformities Be Corrected? Formation of the ear during ...

  15. Neuro-oncology of CNS tumors

    Energy Technology Data Exchange (ETDEWEB)

    Tonn, J.C. [Klinikum Grosshadern, Muenchen (Germany). Dept. of Neurosurgery; Westphal, M. [Universitaetskrankenhaus Eppendorf, Hamburg (Germany). Neurochirurgische Klinik; Rutka, J.T. [Toronto Univ. Hospital for Sick Children, ON (Canada). Div. of Neurosurgery; Grossmann, S.A. (eds.) [Johns Hopkins Oncology Center Neuro-Oncology, Baltimore, MD (United States)


    Diagnosis and treatment modalities for neuro-oncologic diseases have made considerable advances in recent years. There is hardly a segment of the field of solid tumours that is experiencing such dynamic development with regard to basic scientific findings and clinical results. In the present book the world's leading experts have compiled the current practice-relevant knowledge of neuro-oncologic diseases. The book's clear structure and the uniform presentation of all chapters make this volume a valuable reference, especially for practice-oriented activities, allowing swift access to information about current treatment standards. Hence it will be of great value to both clinicians and researchers. (orig.)

  16. Blockade of CD47 ameliorates autoimmune inflammation in CNS by suppressing IL-1-triggered infiltration of pathogenic Th17 cells. (United States)

    Gao, Qiangguo; Zhang, Yi; Han, Chaofeng; Hu, Xiang; Zhang, Hua; Xu, Xiongfei; Tian, Jun; Liu, Yiqi; Ding, Yuanyuan; Liu, Juan; Wang, Chunmei; Guo, Zhenhong; Yang, Yongguang; Cao, Xuetao


    The migration of Th17 cells into central nervous system (CNS) tissue is the key pathogenic step in experimental autoimmune encephalomyelitis (EAE) model. However, the mechanism underlying the pathogenic Th17 cell migration remains elusive. Here we report that blockade of CD47 with CD47-Fc fusion protein is effective in preventing and curing EAE by impairing infiltration of Th17 cells into CNS. However, CD47 deficiency does not directly impair the migration of Th17 cells. Mechanistic studies showed that CD47 deficiency inhibited degradation of inducible nitric oxide synthase (iNOS) in proteasome of macrophages by Src activation and led to the increased nitric oxide (NO) production. Then NO suppressed inflammasome activation-induced IL-1β production. This lower IL-1β reduces the expression of IL-1R1 and migration-related chemokine receptors on CD47(-/-) Th17 cells, inhibiting the ability of Th17 cells to infiltrate into the CNS of CD47(-/-) mice and therefore suppressing EAE development. In vivo administration of exogenous IL-1β indeed promoted the infiltration CD47(-/-) Th17 cells into CNS and antagonized the protective role of CD47 deficiency in EAE pathogenesis. Our results demonstrate a potential preventive and therapeutic application of CD47 blockade in controlling EAE development.

  17. Biodegradability of Plastics


    Yutaka Tokiwa; Calabia, Buenaventurada P.; Charles U. Ugwu; Seiichi Aiba


    Plastic is a broad name given to different polymers with high molecular weight, which can be degraded by various processes. However, considering their abundance in the environment and their specificity in attacking plastics, biodegradation of plastics by microorganisms and enzymes seems to be the most effective process. When plastics are used as substrates for microorganisms, evaluation of their biodegradability should not only be based on their chemical structure, but also on their physical ...

  18. The role of zinc in the pathogenesis and treatment of central nervous system (CNS) diseases. Implications of zinc homeostasis for proper CNS function. (United States)

    Tyszka-Czochara, Małgorzata; Grzywacz, Agata; Gdula-Argasińska, Joanna; Librowski, Tadeusz; Wiliński, Bogdan; Opoka, Włodzimierz


    Zinc, the essential trace element, is known to play multiple biological functions in human organism. This metal is a component of many structural as well as regulatory and catalytic proteins. The precise regulation of zinc homeostasis is essential for central nervous system and for the whole organism. Zinc plays a significant role in the brain development and in the proper brain function at every stage of life. This article is a review of knowledge about the role of zinc in central nervous system (CNS) function. The influence of this biometal on etiopathogenesis, prevention and treatment of selected brain diseases and disorders was discussed. Zinc imbalance can result not only from insufficient dietary intake, but also from impaired activity of zinc transport proteins and zinc dependent regulation of metabolic pathways. It is known that some neurodegenerative processes are connected with zinc dyshomeostasis and it may influence the state of Alzheimer's disease, depression and ageing-connected loss of cognitive function. The exact role of zinc and zinc-binding proteins in CNS pathogenesis processes is being under intensive investigation. The appropriate zinc supplementation in brain diseases may help in the prevention as well as in the proper treatment of several brain dysfunctions.

  19. Restoring axonal localization and transport of transmembrane receptors to promote repair within the injured CNS: a critical step in CNS regeneration

    Directory of Open Access Journals (Sweden)

    Lindsey H Forbes


    Full Text Available Each neuronal subtype is distinct in how it develops, responds to environmental cues, and whether it is capable of mounting a regenerative response following injury. Although the adult central nervous system (CNS does not regenerate, several experimental interventions have been trialled with successful albeit limited instances of axonal repair. We highlight here some of these approaches including extracellular matrix (ECM modification, cellular grafting, gene therapy-induced replacement of proteins, as well as application of biomaterials. We also review the recent report demonstrating the failure of axonal localization and transport of growth-promoting receptors within certain classes of mature neurons. More specifically, we discuss an inability of integrin receptors to localize within the axonal compartment of mature motor neurons such as in the corticospinal and rubrospinal tracts, whereas in immature neurons of those pathways and in mature sensory tracts such as in the optic nerve and dorsal column pathways these receptors readily localize within axons. Furthermore we assert that this failure of axonal localization contributes to the intrinsic inability of axonal regeneration. We conclude by highlighting the necessity for both combined therapies as well as a targeted approach specific to both age and neuronal subtype will be required to induce substantial CNS repair.

  20. Chemical Recycle of Plastics

    Directory of Open Access Journals (Sweden)

    Sara Fatima


    Full Text Available Various chemical processes currently prevalent in the chemical industry for plastics recycling have been discussed. Possible future scenarios in chemical recycling have also been discussed. Also analyzed are the effects on the environment, the risks, costs and benefits of PVC recycling. Also listed are the various types of plastics and which plastics are safe to use and which not after rcycle

  1. Plastic value chains

    DEFF Research Database (Denmark)

    Baxter, John; Wahlstrom, Margareta; Zu Castell-Rüdenhausen, Malin


    Optimizing plastic value chains is regarded as an important measure in order to increase recycling of plastics in an efficient way. This can also lead to improved awareness of the hazardous substances contained in plastic waste, and how to avoid that these substances are recycled. As an example...

  2. CNS-specific regulatory elements in brain-derived HIV-1 strains affect responses to latency-reversing agents with implications for cure strategies (United States)

    Gray, L R; Cowley, D; Welsh, C; Lu, H K; Brew, B J; Lewin, S R; Wesselingh, S L; Gorry, P R; Churchill, M J


    Latency-reversing agents (LRAs), including histone deacetylase inhibitors (HDACi), are being investigated as a strategy to eliminate latency in HIV-infected patients on suppressive antiretroviral therapy. The effectiveness of LRAs in activating latent infection in HIV strains derived from the central nervous system (CNS) is unknown. Here we show that CNS-derived HIV-1 strains possess polymorphisms within and surrounding the Sp transcription factor motifs in the long terminal repeat (LTR). These polymorphisms result in decreased ability of the transcription factor specificity protein 1 to bind CNS-derived LTRs, reducing the transcriptional activity of CNS-derived viruses. These mutations result in CNS-derived viruses being less responsive to activation by the HDACi panobinostat and romidepsin compared with lymphoid-derived viruses from the same subjects. Our findings suggest that HIV-1 strains residing in the CNS have unique transcriptional regulatory mechanisms, which impact the regulation of latency, the consideration of which is essential for the development of HIV-1 eradication strategies. PMID:26303660

  3. CNS metastasis from malignant uveal melanoma: a clinical and histopathological characterisation

    DEFF Research Database (Denmark)

    Holfort, S K; Lindegaard, J; Isager, P;


    to the CNS were identified. For each patient, clinical and histopathological data were gathered. RESULTS: Sixteen patients with CNS metastasis were identified. The median age was 58 years. The majority of CNS metastases were located in the frontal and parietal lobes. Eleven patients had widespread metastases...

  4. Pulsar/CNS integrated navigation based on federated UKF

    Institute of Scientific and Technical Information of China (English)

    Jin Liu; Jie Ma; Jinwen Tian


    In order to improve the autonomous navigation capability of satellite,a pulsar/CNS(celestial navigation system)integrated navigation method based on federated unscented Kalman filter(UKF)is proposed.The celestial navigation is a mature and stable navigation method.However,its position determination performance is not satisfied due to the low accuracy of horizon sensor.Single pulsar navigation is a new navigation method,which can provide highly accurate range measurements.The major drawback of single pulsar navigation is that the system is completely unobservabie.As two methods are complementary to each other,the federated UKF is used here for fusing the navigation data from single pulsar navigation and CNS.Compared to the traditional celestial navigation method and single pulsar navigation,the integrated navigation method can provide better navigation performance.The simulation results demonstrate the feasibility and effectiveness of the navigation method.

  5. Autoradiographic visualization of CNS receptors for vasoactive intestinal peptide

    Energy Technology Data Exchange (ETDEWEB)

    Shaffer, M.M.; Moody, T.W.


    Receptors for VIP were characterized in the rat CNS. /sup 125/I-VIP bound with high affinity to rat brain slices. Binding was time dependent and specific. Pharmacology studies indicated that specific /sup 125/I-VIP binding was inhibited with high affinity by VIP and low affinity by secretin and PHI. Using in vitro autoradiographic techniques high grain densities were present in the dentate gyrus, pineal gland, supraoptic and suprachiasmatic nuclei, superficial gray layer of the superior colliculus and the area postrema. Moderate grain densities were present in the olfactory bulb and tubercle, cerebral cortex, nucleus accumbens, caudate putamen, interstitial nucleus of the stria terminalis, paraventricular thalamic nucleus, medial amygdaloid nucleus, subiculum and the medial geniculate nucleus. Grains were absent in the corpus callosum and controls treated with 1 microM unlabeled VIP. The discrete regional distribution of VIP receptors suggest that it may function as an important modulator of neural activity in the CNS.

  6. Development of a new approach based on midwave infrared spectroscopy for post-consumer black plastic waste sorting in the recycling industry. (United States)

    Rozenstein, Offer; Puckrin, Eldon; Adamowski, Jan


    Waste sorting is key to the process of waste recycling. Exact identification of plastic resin and wood products using Near Infrared (NIR, 1-1.7µm) sensing is currently in use. Yet, dark targets characterized by low reflectance, such as black plastics, are hard to identify by this method. Following the recent success of Midwave Infrared (MWIR, 3-12µm) measurements to identify coloured plastic polymers, the aim of this study was to assess whether this technique is applicable to sorting black plastic polymers and wood products. We performed infrared reflectance contact measurements of 234 plastic samples and 29 samples of wood and paper products. Plastic samples included black, coloured and transparent Polyethylene Terephthalate (PET), Polyethylene (PE), Polyvinyl Chloride (PVC), Polypropylene (PP), Polylactic acid (PLA) and Polystyrene (PS). The spectral signatures of the black and coloured plastic samples were compared with clear plastic samples and signatures documented in the literature to identify the polymer spectral features in the presence of coloured material. This information was used to determine the spectral bands that best suit the sorting of black plastic polymers. The main NIR-MWIR absorption features of wood, cardboard and paper were identified as well according to the spectral measurements. Good agreement was found between our measurements and the absorption features documented in the literature. The new approach using MWIR spectral features appears to be useful for black plastics as it overcomes some of the limitations in the NIR region to identify them. The main limitation of this technique for industrial applications is the trade-off between the signal-to-noise ratio of the sensor operating in standoff mode and the speed at which waste is moved under the sensor. This limitation can be resolved by reducing the system's spectral resolution to 16cm(-1), which allows for faster spectra acquisition while maintaining a reasonable signal-to-noise ratio

  7. The pharmacology of neuroplasticity induced by non-invasive brain stimulation: building models for the clinical use of CNS active drugs. (United States)

    Nitsche, Michael A; Müller-Dahlhaus, Florian; Paulus, Walter; Ziemann, Ulf


    The term neuroplasticity encompasses structural and functional modifications of neuronal connectivity. Abnormal neuroplasticity is involved in various neuropsychiatric diseases, such as dystonia, epilepsy, migraine, Alzheimer's disease, fronto-temporal degeneration, schizophrenia, and post cerebral stroke. Drugs affecting neuroplasticity are increasingly used as therapeutics in these conditions. Neuroplasticity was first discovered and explored in animal experimentation. However, non-invasive brain stimulation (NIBS) has enabled researchers recently to induce and study similar processes in the intact human brain. Plasticity induced by NIBS can be modulated by pharmacological interventions, targeting ion channels, or neurotransmitters. Importantly, abnormalities of plasticity as studied by NIBS are directly related to clinical symptoms in neuropsychiatric diseases. Therefore, a core theme of this review is the hypothesis that NIBS-induced plasticity can explore and potentially predict the therapeutic efficacy of CNS-acting drugs in neuropsychiatric diseases. We will (a) review the basics of neuroplasticity, as explored in animal experimentation, and relate these to our knowledge about neuroplasticity induced in humans by NIBS techniques. We will then (b) discuss pharmacological modulation of plasticity in animals and humans. Finally, we will (c) review abnormalities of plasticity in neuropsychiatric diseases, and discuss how the combination of NIBS with pharmacological intervention may improve our understanding of the pathophysiology of abnormal plasticity in these diseases and their purposeful pharmacological treatment.


    Directory of Open Access Journals (Sweden)

    F. Jadali


    Full Text Available AbstractObjectiveTumors of the central nervous system constitute the largest group of solid neoplasms in children and are second only to leukemia in their overall frequency during childhood. The main purpose of the present study is to determine the incidence, age, sex, location and histological diagnosis of CNS tumors in children, less than 15 years of age, in the Mofid Children's Hospital, in the past 10 years. Materials and MethodsIn this descriptive retrospective study we reviewed the medical records of 143 children with diagnosis of CNS tumors admitted during the past 10 years in neurology and surgery departments of Mofid Children's Hospital between the years 1996 and 2006.ResultsDuring the 10 year study period, CNS tumor was diagnosed in 143 patients; of these tumors, 119 were intracranial and 58 were intraspinal; 51.3% of brain tumors were located in the supratentorial and 48.7% in the infratentorial regions. The most common intracranial neoplasms were astrocytic tumors (36.8%, embryonal tumors (31.1% and ependymal tumors (13.4%. Of the intraspinal neoplasms the most frequently noted were embryonal tumors(37.5%, mesenchymal meningothelial tumors (20.8%, followed by astrocytic tumors (16.7%. The median age at diagnosis was 8.9 ± 4.1 years with a male to female ratio of 1.4:1 (P Conclusion Brain tumors in children constitute a diverse group in terms of incidence,distribution and histopathological diagnosis.Keywords: CNS tumors, Histopathology, Children.

  9. C.N.S. tumors in eastern Saudi Arabia. (United States)

    Ibrahim, A W


    In Saudi Arabia, there were no attempts previously to describe a population based frequency or incidence, particularly so the age adjusted incidence of various CNS tumors. This paper presents the primary CNS tumors from a population based tumor registry over two years period, from January 1987 till December 1988. There was a total of 85 cases representing 5.4% of the total captured cases (1,568 cases of malignant tumors at all sites). The population of the Eastern Province is estimated to be 1.37 million, the Saudis forming 80% of the total population. Out of the 85 cases captured over two years, there were 64 cases diagnosed in indigenous Saudi population forming 75%. The remaining occurred in non-Saudi residents. The male/female ratio in Saudis was 1:1.1 with a slight predominance of the female, while the reverse is true in the non-Saudis (2:1). The total captured cases per annum is 43, making the incidence of primary CNS neoplasms in the Eastern Province of Saudi Arabia 3.1/100,000 of all the population and 2.9/100,000 in Saudi nationals. Comparing this incidence to the international figure, it was clear that it is far less than the incidence reported from North America and Europe, particularly in the Caucasian population, but similar to incidences reported in the Chinese, black Americans, Romanians and Yugoslavians, but certainly less than the Ashkenazi or Safari Jews, and slightly higher than the incidence reported in Japan and Southeast Asia. Malignant brain tumors of various types dominated the primary CNS neoplasms reported over these two years forming 69% of the cases and 52% of the primary brain tumors.

  10. 4th ENRI International Workshop on ATM/CNS

    CERN Document Server


    This book is a compilation of selected papers from the 4th ENRI International Workshop on ATM/CNS (EIWAC2015). The work focuses on novel techniques for aviation infrastructure in air traffic management (ATM) and communications, navigation, surveillance, and informatics (CNSI) domains. The contents make valuable contributions to academic researchers, engineers in the industry, and regulators of aviation authorities. As well, readers will encounter new ideas for realizing a more efficient and safer aviation system. .

  11. Virally mediated gene manipulation in the adult CNS

    Directory of Open Access Journals (Sweden)

    Efrat eEdry


    Full Text Available Understanding how the CNS functions poses one of the greatest challenges in modern life science and medicine. Studying the brain is especially challenging because of its complexity, the heterogeneity of its cellular composition, and the substantial changes it undergoes throughout its life-span. The complexity of adult-brain neural networks results also from the diversity of properties and functions of neuronal cells, governed, inter alia, by temporally and spatially differential expression of proteins in mammalian brain cell populations. Hence, research into the biology of CNS activity and its implications to human and animal behavior must use novel scientific tools. One source of such tools is the field of molecular genetics – recently utilized more and more frequently in neuroscience research. Transgenic approaches in general, and gene targeting in rodents have become fundamental tools for elucidating gene function in the CNS. Although spectacular progress has been achieved over recent decades by using these approaches, it is important to note that they face a number of restrictions. One of the main challenges is presented by the temporal and spatial regulation of introduced genetic manipulations. Viral vectors provide an alternative approach to temporally regulated, localized delivery of genetic modifications into neurons. In this review we describe available technologies for gene transfer into the adult mammalian CNS that use both viral and non-viral tools. We discuss viral vectors frequently used in neuroscience, with emphasis on lentiviral vector (LV systems. We consider adverse effects of LVs, and the use of LVs for temporally and spatially controllable manipulations. Especially, we highlight the significance of viral vector-mediated genetic manipulations in studying learning and memory processes, and how they may be effectively used to separate out the various phases of learning: acquisition, consolidation, retrieval, and maintenance.

  12. Target Identification for CNS Diseases by Transcriptional Profiling


    Altar, C. Anthony; Vawter, Marquis P.; Ginsberg, Stephen D.


    Gene expression changes in neuropsychiatric and neurodegenerative disorders, and gene responses to therapeutic drugs, provide new ways to identify central nervous system (CNS) targets for drug discovery. This review summarizes gene and pathway targets replicated in expression profiling of human postmortem brain, animal models, and cell culture studies. Analysis of isolated human neurons implicates targets for Alzheimer’s disease and the cognitive decline associated with normal aging and mild ...

  13. Leptin and the CNS Control of Glucose Metabolism (United States)

    Morton, Gregory J.; Schwartz, Michael W.


    The regulation of body fat stores and blood glucose levels is critical for survival. This review highlights growing evidence that leptin action in the central nervous system (CNS) plays a key role in both processes. Investigation into underlying mechanisms has begun to clarify the physiological role of leptin in the control of glucose metabolism and raises interesting new possibilities for the treatment of diabetes and related disorders. PMID:21527729

  14. Rickettsioses as causes of CNS infection in southeast Asia


    Carole Eldin; Philippe Parola


    International audience; In The Lancet Global Health, Sabine Dittrich and colleagues 1 report that scrub typhus caused by Orientia tsutsugamushi, murine typhus caused by Rickettsia typhi, and leptospirosis caused by various Leptospira species account for more than a third of CNS infections diagnosed over 8 years in Vientiane Hospital in Laos. The study is one more great contribution from this team in their investigation of undocumented syndromes, as well as in the public health challenge of ri...

  15. Blood-CNS Barrier Impairment in ALS Patients versus an Animal Model

    Directory of Open Access Journals (Sweden)

    Svitlana eGarbuzova-Davis


    Full Text Available Amyotrophic lateral sclerosis (ALS is a severe neurodegenerative disease with a compli-cated and poorly understood pathogenesis. Recently, alterations in the blood-Central Nervous System barrier (B-CNS-B have been recognized as a key factor possibly aggravating motor neuron damage. The majority of findings on ALS microvascular pathology have been deter-mined in mutant SOD1 rodent models, identifying barrier damage during disease develop-ment which might similarly occur in familial ALS patients carrying the SOD1 mutation. However, our knowledge of B-CNS-B competence in sporadic ALS (SALS has been limited. We recently showed structural and functional impairment in postmortem gray and white mat-ter microvessels of medulla and spinal cord tissue from SALS patients, suggesting pervasive barrier damage. Although numerous signs of barrier impairment (endothelial cell degenera-tion, capillary leakage, perivascular edema, downregulation of tight junction proteins, and microhemorrhages are indicated in both mutant SOD1 animal models of ALS and SALS pa-tients, other pathogenic barrier alterations have as yet only been identified in SALS patients. Pericyte degeneration, perivascular collagen IV expansion, and white matter capillary abnor-malities in SALS patients are significant barrier related pathologies yet to be noted in ALS SOD1 animal models. In the current review, these important differences in blood-CNS barrier damage between ALS patients and animal models, which may signify altered barrier transport mechanisms, are discussed. Understanding discrepancies in barrier condition between ALS patients and animal models may be crucial for developing effective therapies.

  16. Biodegradability of plastics. (United States)

    Tokiwa, Yutaka; Calabia, Buenaventurada P; Ugwu, Charles U; Aiba, Seiichi


    Plastic is a broad name given to different polymers with high molecular weight, which can be degraded by various processes. However, considering their abundance in the environment and their specificity in attacking plastics, biodegradation of plastics by microorganisms and enzymes seems to be the most effective process. When plastics are used as substrates for microorganisms, evaluation of their biodegradability should not only be based on their chemical structure, but also on their physical properties (melting point, glass transition temperature, crystallinity, storage modulus etc.). In this review, microbial and enzymatic biodegradation of plastics and some factors that affect their biodegradability are discussed.

  17. Biodegradability of Plastics

    Directory of Open Access Journals (Sweden)

    Yutaka Tokiwa


    Full Text Available Plastic is a broad name given to different polymers with high molecular weight, which can be degraded by various processes. However, considering their abundance in the environment and their specificity in attacking plastics, biodegradation of plastics by microorganisms and enzymes seems to be the most effective process. When plastics are used as substrates for microorganisms, evaluation of their biodegradability should not only be based on their chemical structure, but also on their physical properties (melting point, glass transition temperature, crystallinity, storage modulus etc.. In this review, microbial and enzymatic biodegradation of plastics and some factors that affect their biodegradability are discussed.

  18. Journal of CHINA PLASTICS

    Institute of Scientific and Technical Information of China (English)


    Journal of CHINA PLASTICS was authorized and approved by The State Committee of Science and Technology of China and The Bureau of News Press of China, and published by The China Plastics Processing Industry Association,Beijing Technology and Business University and The Institute of Plastics Processing and Application of Light Industry, distributed worldwide. Since its birth in 1987, CHINA PLASTICS has become a leading magazine in plastics industry in China, a national Chinese core journal and journal of Chinese scientific and technological article statistics. It is covered by CA.


    The ultimate goal of this research was to develop technology to convert recycled wood fiber and plastics into durable products that are recyclable and otherwise environmentally friendly. Two processing technologies were used to prepare wood-plastic composites: air-laying and melt...

  20. Advances in Drug Design Based on the Amino Acid Approach: Taurine Analogues for the Treatment of CNS Diseases

    Directory of Open Access Journals (Sweden)

    Paulo Renato Yamasaki


    Full Text Available Amino acids are well known to be an important class of compounds for the maintenance of body homeostasis and their deficit, even for the polar neuroactive aminoacids, can be controlled by supplementation. However, for the amino acid taurine (2-aminoethanesulfonic acid this is not true. Due its special physicochemical properties, taurine is unable to cross the blood-brain barrier. In addition of injured taurine transport systems under pathological conditions, CNS supplementation of taurine is almost null. Taurine is a potent antioxidant and anti-inflammatory semi-essential amino acid extensively involved in neurological activities, acting as neurotrophic factor, binding to GABA A/glycine receptors and blocking the excitotoxicity glutamate-induced pathway leading to be a neuroprotective effect and neuromodulation. Taurine deficits have been implicated in several CNS diseases, such as Alzheimer’s, Parkinson’s, epilepsy and in the damage of retinal neurons. This review describes the  CNS physiological functions of taurine and the development of new derivatives based on its structure useful in CNS disease treatment.

  1. Transplantation of autologous bone marrow stromal cells (BMSC for CNS disorders – Strategy and tactics for clinical application

    Directory of Open Access Journals (Sweden)

    Satoshi Kuroda


    Full Text Available Background – There is increasing evidence that the transplanted bone marrow stromal cells (BMSC significantly promote functional recovery after central nervous system (CNS damage in the animal models of various kinds of CNS disorders, including cerebral infarct, brain contusion and spinal cord injury. However, there are several shortages of information when considering clinical application of BMSC transplantation for patients with neurological disorders. In this paper, therefore, we discuss what we should clarify to establish cell transplantation therapy in clinical situation and describe our recent works for this purpose.Methods and Results – The BMSC have the ability to alter their gene expression profile and phenotype in response to the surrounding circumstances and to protect the neurons by producing some neurotrophic factors. They also promote neurite extension and rebuild the neural circuits in the injured CNS. Using optical imaging and MRI techniques, the transplanted BMSC can non-invasively be tracked in the living animals for at least 8 weeks after transplantation. Functional imaging such as PET scan may have the potential to assess the beneficial effects of BMSC transplantation. The BMSC can be expanded using the animal protein-free culture medium, which would maintain their potential of proliferation, migration, and neural differentiation.Conclusion – It is urgent issues to develop clinical imaging technique to track the transplanted cells in the CNS and evaluate the therapeutic significance of BMSC transplantation in order to establish it as a definite therapeutic strategy in clinical situation in the future

  2. Mechanisms of CNS invasion and damage by parasites. (United States)

    Kristensson, Krister; Masocha, Willias; Bentivoglio, Marina


    Invasion of the central nervous system (CNS) is a most devastating complication of a parasitic infection. Several physical and immunological barriers provide obstacles to such an invasion. In this broad overview focus is given to the physical barriers to neuroinvasion of parasites provided at the portal of entry of the parasites, i.e., the skin and epithelial cells of the gastrointestinal tract, and between the blood and the brain parenchyma, i.e., the blood-brain barrier (BBB). A description is given on how human pathogenic parasites can reach the CNS via the bloodstream either as free-living or extracellular parasites, by embolization of eggs, or within red or white blood cells when adapted to intracellular life. Molecular mechanisms are discussed by which parasites can interact with or pass across the BBB. The possible targeting of the circumventricular organs by parasites, as well as the parasites' direct entry to the brain from the nasal cavity through the olfactory nerve pathway, is also highlighted. Finally, examples are given which illustrate different mechanisms by which parasites can cause dysfunction or damage in the CNS related to toxic effects of parasite-derived molecules or to immune responses to the infection.

  3. PPAR agonists as therapeutics for CNS trauma and neurological diseases (United States)

    Mandrekar-Colucci, Shweta; Sauerbeck, Andrew; Popovich, Phillip G.; McTigue, Dana M.


    Traumatic injury or disease of the spinal cord and brain elicits multiple cellular and biochemical reactions that together cause or are associated with neuropathology. Specifically, injury or disease elicits acute infiltration and activation of immune cells, death of neurons and glia, mitochondrial dysfunction, and the secretion of substrates that inhibit axon regeneration. In some diseases, inflammation is chronic or non-resolving. Ligands that target PPARs (peroxisome proliferator-activated receptors), a group of ligand-activated transcription factors, are promising therapeutics for neurologic disease and CNS injury because their activation affects many, if not all, of these interrelated pathologic mechanisms. PPAR activation can simultaneously weaken or reprogram the immune response, stimulate metabolic and mitochondrial function, promote axon growth and induce progenitor cells to differentiate into myelinating oligodendrocytes. PPAR activation has beneficial effects in many pre-clinical models of neurodegenerative diseases and CNS injury; however, the mechanisms through which PPARs exert these effects have yet to be fully elucidated. In this review we discuss current literature supporting the role of PPAR activation as a therapeutic target for treating traumatic injury and degenerative diseases of the CNS. PMID:24215544

  4. Neonatal Treatment with a Pegylated Leptin Antagonist Induces Sexually Dimorphic Effects on Neurones and Glial Cells, and on Markers of Synaptic Plasticity in the Developing Rat Hippocampal Formation. (United States)

    López-Gallardo, M; Antón-Fernández, A; Llorente, R; Mela, V; Llorente-Berzal, A; Prada, C; Viveros, M P


    The present study aimed to better understand the role of the neonatal leptin surge, which peaks on postnatal day (PND)9-10, on the development of the hippocampal formation. Accordingly, male and female rats were administered with a pegylated leptin antagonist on PND9 and the expression of neurones, glial cells and diverse markers of synaptic plasticity was then analysed by immunohistochemistry in the hippocampal formation. Antagonism of the actions of leptin at this specific postnatal stage altered the number of glial fibrillary acidic protein positive cells, and also affected type 1 cannabinoid receptors, synaptophysin and brain-derived neurotrophic factor (BDNF), with the latter effect being sexually dimorphic. The results indicate that the physiological leptin surge occurring around PND 9-10 is critical for hippocampal formation development and that the dynamics of leptin activity might be different in males and females. The data obtained also suggest that some but not all the previously reported effects of maternal deprivation on hippocampal formation development (which markedly reduces leptin levels at PND 9-10) might be mediated by leptin deficiency in these animals.

  5. Development of a Direct Carbon Fuel Cell for Power and Fuels Cogeneration Directly from Plastic Trash Project (United States)

    National Aeronautics and Space Administration — This small business innovation research is intended to develop a simple processing concept based-on an advanced direct carbon fuel cell (DCFC) technology enabling...

  6. Mechanisms of GABAergic Homeostatic Plasticity

    Directory of Open Access Journals (Sweden)

    Peter Wenner


    Full Text Available Homeostatic plasticity ensures that appropriate levels of activity are maintained through compensatory adjustments in synaptic strength and cellular excitability. For instance, excitatory glutamatergic synapses are strengthened following activity blockade and weakened following increases in spiking activity. This form of plasticity has been described in a wide array of networks at several different stages of development, but most work and reviews have focussed on the excitatory inputs of excitatory neurons. Here we review homeostatic plasticity of GABAergic neurons and their synaptic connections. We propose a simplistic model for homeostatic plasticity of GABAergic components of the circuitry (GABAergic synapses onto excitatory neurons, excitatory connections onto GABAergic neurons, cellular excitability of GABAergic neurons: following chronic activity blockade there is a weakening of GABAergic inhibition, and following chronic increases in network activity there is a strengthening of GABAergic inhibition. Previous work on GABAergic homeostatic plasticity supports certain aspects of the model, but it is clear that the model cannot fully account for some results which do not appear to fit any simplistic rule. We consider potential reasons for these discrepancies.

  7. Challenges in plastics recycling

    DEFF Research Database (Denmark)

    Pivnenko, Kostyantyn; Jakobsen, L. G.; Eriksen, Marie Kampmann


    Recycling of waste plastics still remains a challenging area in the waste management sector. The current and potential goals proposed on EU or regional levels are difficult to achieve, and even to partially fullfil them the improvements in collection and sorting should be considerable. A study...... was undertaken to investigate the factors affecting quality in plastics recycling. The preliminary results showed factors primarily influencing quality of plastics recycling to be polymer cross contamination, presence of additives, non-polymer impurities, and polymer degradation. Deprivation of plastics quality......, with respect to recycling, has been shown to happen throughout the plastics value chain, but steps where improvements may happen have been preliminary identified. Example of Cr in plastic samples analysed showed potential spreading and accumulation of chemicals ending up in the waste plastics. In order...

  8. Glassy metallic plastics

    Institute of Scientific and Technical Information of China (English)


    This paper reports a class of bulk metallic glass including Ce-, LaCe-, CaLi-, Yb-, and Sr-based metallic glasses, which are regarded as glassy metallic plastics because they combine some unique properties of both plastics and metallic alloys. These glassy metallic plastics have very low glass transition temperature (Tg~25oC to 150oC) and low Young’s modulus (~20 GPa to 35 GPa). Similar to glassy plastics, these metallic plastics show excellent plastic-like deformability on macro-, micro- and even nano-scale in their supercooled liquid range and can be processed, such as elongated, compressed, bent, and imprinted at low temperatures, in hot water for instance. Under ambient conditions, they display such metallic properties as high thermal and electric conductivities and excellent mechanical properties and other unique properties. The metallic plastics have potential applications and are also a model system for studying issues in glass physics.

  9. An in vitro clonogenic assay to assess radiation damage in rat CNS glial progenitor cells

    Energy Technology Data Exchange (ETDEWEB)

    Maazen, R.W.M. van der; Verhagen, I.; Kogel, A.J. van der (Katholieke Univ., Nijmegen (Netherlands). Inst. of Radiotherapy)


    Normal glial progenitor cells can be isolated from the rat central nervous system (CNS) and cultured in vitro on a monolayer of type-1 astrocytes. These monolayers are able to support and stimulate explanted glial progenitor cells to proliferate. Employing these in vitro interactions of specific glial cell types, an in vivo-in vitro clonogenic assay has been developed. This method offers the possibility to study the intrinsic radiosensitivity, repair and regeneration of glial progenitor cells after in vitro or in vivo irradiation. (author).

  10. Dual DNA methylation patterns in the CNS reveal developmentally poised chromatin and monoallelic expression of critical genes. (United States)

    Wang, Jinhui; Valo, Zuzana; Bowers, Chauncey W; Smith, David D; Liu, Zheng; Singer-Sam, Judith


    As a first step towards discovery of genes expressed from only one allele in the CNS, we used a tiling array assay for DNA sequences that are both methylated and unmethylated (the MAUD assay). We analyzed regulatory regions of the entire mouse brain transcriptome, and found that approximately 10% of the genes assayed showed dual DNA methylation patterns. They include a large subset of genes that display marks of both active and silent, i.e., poised, chromatin during development, consistent with a link between differential DNA methylation and lineage-specific differentiation within the CNS. Sixty-five of the MAUD hits and 57 other genes whose function is of relevance to CNS development and/or disorders were tested for allele-specific expression in F(1) hybrid clonal neural stem cell (NSC) lines. Eight MAUD hits and one additional gene showed such expression. They include Lgi1, which causes a subtype of inherited epilepsy that displays autosomal dominance with incomplete penetrance; Gfra2, a receptor for glial cell line-derived neurotrophic factor GDNF that has been linked to kindling epilepsy; Unc5a, a netrin-1 receptor important in neurodevelopment; and Cspg4, a membrane chondroitin sulfate proteoglycan associated with malignant melanoma and astrocytoma in human. Three of the genes, Camk2a, Kcnc4, and Unc5a, show preferential expression of the same allele in all clonal NSC lines tested. The other six genes show a stochastic pattern of monoallelic expression in some NSC lines and bi-allelic expression in others. These results support the estimate that 1-2% of genes expressed in the CNS may be subject to allelic exclusion, and demonstrate that the group includes genes implicated in major disorders of the CNS as well as neurodevelopment.

  11. Dual DNA methylation patterns in the CNS reveal developmentally poised chromatin and monoallelic expression of critical genes.

    Directory of Open Access Journals (Sweden)

    Jinhui Wang

    Full Text Available As a first step towards discovery of genes expressed from only one allele in the CNS, we used a tiling array assay for DNA sequences that are both methylated and unmethylated (the MAUD assay. We analyzed regulatory regions of the entire mouse brain transcriptome, and found that approximately 10% of the genes assayed showed dual DNA methylation patterns. They include a large subset of genes that display marks of both active and silent, i.e., poised, chromatin during development, consistent with a link between differential DNA methylation and lineage-specific differentiation within the CNS. Sixty-five of the MAUD hits and 57 other genes whose function is of relevance to CNS development and/or disorders were tested for allele-specific expression in F(1 hybrid clonal neural stem cell (NSC lines. Eight MAUD hits and one additional gene showed such expression. They include Lgi1, which causes a subtype of inherited epilepsy that displays autosomal dominance with incomplete penetrance; Gfra2, a receptor for glial cell line-derived neurotrophic factor GDNF that has been linked to kindling epilepsy; Unc5a, a netrin-1 receptor important in neurodevelopment; and Cspg4, a membrane chondroitin sulfate proteoglycan associated with malignant melanoma and astrocytoma in human. Three of the genes, Camk2a, Kcnc4, and Unc5a, show preferential expression of the same allele in all clonal NSC lines tested. The other six genes show a stochastic pattern of monoallelic expression in some NSC lines and bi-allelic expression in others. These results support the estimate that 1-2% of genes expressed in the CNS may be subject to allelic exclusion, and demonstrate that the group includes genes implicated in major disorders of the CNS as well as neurodevelopment.

  12. Phenotypic plasticity: molecular mechanisms and adaptive significance. (United States)

    Kelly, Scott A; Panhuis, Tami M; Stoehr, Andrew M


    Phenotypic plasticity can be broadly defined as the ability of one genotype to produce more than one phenotype when exposed to different environments, as the modification of developmental events by the environment, or as the ability of an individual organism to alter its phenotype in response to changes in environmental conditions. Not surprisingly, the study of phenotypic plasticity is innately interdisciplinary and encompasses aspects of behavior, development, ecology, evolution, genetics, genomics, and multiple physiological systems at various levels of biological organization. From an ecological and evolutionary perspective, phenotypic plasticity may be a powerful means of adaptation and dramatic examples of phenotypic plasticity include predator avoidance, insect wing polymorphisms, the timing of metamorphosis in amphibians, osmoregulation in fishes, and alternative reproductive tactics in male vertebrates. From a human health perspective, documented examples of plasticity most commonly include the results of exercise, training, and/or dieting on human morphology and physiology. Regardless of the discipline, phenotypic plasticity has increasingly become the target of a plethora of investigations with the methodological approaches utilized ranging from the molecular to whole organsimal. In this article, we provide a brief historical outlook on phenotypic plasticity; examine its potential adaptive significance; emphasize recent molecular approaches that provide novel insight into underlying mechanisms, and highlight examples in fishes and insects. Finally, we highlight examples of phenotypic plasticity from a human health perspective and underscore the use of mouse models as a powerful tool in understanding the genetic architecture of phenotypic plasticity.

  13. Impaired novelty acquisition and synaptic plasticity in congenital hyperammonemia caused by hepatic glutamine synthetase deficiency (United States)

    Chepkova, Aisa N.; Sergeeva, Olga A.; Görg, Boris; Haas, Helmut L.; Klöcker, Nikolaj; Häussinger, Dieter


    Genetic defects in ammonia metabolism can produce irreversible damage of the developing CNS causing an impairment of cognitive and motor functions. We investigated alterations in behavior, synaptic plasticity and gene expression in the hippocampus and dorsal striatum of transgenic mice with systemic hyperammonemia resulting from conditional knockout of hepatic glutamine synthetase (LGS-ko). These mice showed reduced exploratory activity and delayed habituation to a novel environment. Field potential recordings from LGS-ko brain slices revealed significantly reduced magnitude of electrically-induced long-term potentiation (LTP) in both CA3-CA1 hippocampal and corticostriatal synaptic transmission. Corticostriatal but not hippocampal slices from LGS-ko brains demonstrated also significant alterations in long-lasting effects evoked by pharmacological activation of glutamate receptors. Real-time RT-PCR revealed distinct patterns of dysregulated gene expression in the hippocampus and striatum of LGS-ko mice: LGS-ko hippocampus showed significantly modified expression of mRNAs for mGluR1, GluN2B subunit of NMDAR, and A1 adenosine receptors while altered expression of mRNAs for D1 dopamine receptors, the M1 cholinoreceptor and the acetylcholine-synthetizing enzyme choline-acetyltransferase was observed in LGS-ko striatum. Thus, inborn systemic hyperammonemia resulted in significant deficits in novelty acquisition and disturbed synaptic plasticity in corticostriatal and hippocampal pathways involved in learning and goal-directed behavior. PMID:28067279

  14. Acquired changes in stomatal characteristics in response to ozone during plant growth and leaf development of bush beans (Phaseolus vulgaris L.) indicate phenotypic plasticity

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    Elagoez, Vahram [Plant Biology Graduate Program, University of Massachusetts, Amherst, MA 01003 (United States)]. E-mail:; Han, Susan S. [Department of Plant, Soil and Insect Sciences, University of Massachusetts, Amherst, MA 01003 (United States); Manning, William J. [Department of Plant, Soil and Insect Sciences, University of Massachusetts, Amherst, MA 01003 (United States)


    Bush bean (Phaseolus vulgaris L.) lines 'S156' (O{sub 3}-sensitive)/'R123' (O{sub 3}-tolerant) and cultivars 'BBL 290' (O{sub 3}-sensitive)/'BBL 274' (O{sub 3}-tolerant) were used to study the effects of O{sub 3} on stomatal conductance (g {sub s}), density, and aperture size on leaf and pod surfaces with the objective of establishing links between the degree of plant sensitivity to O{sub 3} and plasticity of stomatal properties in response to O{sub 3}. Studies in open-top chambers (OTCs) and in continuously stirred tank reactors (CSTRs) established a clear relationship between plant developmental stages, degrees of O{sub 3} sensitivity and g {sub s}: while 'S156' had higher g {sub s} rates than 'R123' earlier in development, similar differences between 'BBL 290' and 'BBL 274' were observed at later stages. G {sub s} rates on the abaxial leaf surfaces of 'S156' and 'BBL 290', accompanied by low leaf temperatures, were significantly higher than their O{sub 3}-tolerant counterparts. Exposure to O{sub 3} in CSTRs had greater and more consistent impacts on both stomatal densities and aperture sizes of O{sub 3}-sensitive cultivars. Stomatal densities were highest on the abaxial leaf surfaces of 'S156' and 'BBL 290' at higher O{sub 3} concentrations (60 ppb), but the largest aperture sizes were recorded on the adaxial leaf surfaces at moderate O{sub 3} concentrations (30 ppb). Exposure to O{sub 3} eliminated aperture size differences on the adaxial leaf surfaces between sensitive and tolerant cultivars. Regardless of sensitivity to O{sub 3} and treatment regimes, the smallest aperture sizes and highest stomatal densities were found on the abaxial leaf surface. Our studies showed that O{sub 3} has the potential to affect stomatal plasticity and confirmed the presence of different control mechanisms for stomatal development on each leaf surface. This

  15. Plasticity Theory of Fillet Welds

    DEFF Research Database (Denmark)

    Hansen, Thomas


    This paper deals with simple methods for calculation of fillet welds based on the theory of plasticity. In developing the solutions the lower-bound theorem is used. The welding material and parts of the base material are subdivided into triangular regions with homogeneous stress fields; thereby...

  16. Immune Privilege as an Intrinsic CNS Property: Astrocytes Protect the CNS against T-Cell-Mediated Neuroinflammation

    Directory of Open Access Journals (Sweden)

    Ulrike Gimsa


    Full Text Available Astrocytes have many functions in the central nervous system (CNS. They support differentiation and homeostasis of neurons and influence synaptic activity. They are responsible for formation of the blood-brain barrier (BBB and make up the glia limitans. Here, we review their contribution to neuroimmune interactions and in particular to those induced by the invasion of activated T cells. We discuss the mechanisms by which astrocytes regulate pro- and anti-inflammatory aspects of T-cell responses within the CNS. Depending on the microenvironment, they may become potent antigen-presenting cells for T cells and they may contribute to inflammatory processes. They are also able to abrogate or reprogram T-cell responses by inducing apoptosis or secreting inhibitory mediators. We consider apparently contradictory functions of astrocytes in health and disease, particularly in their interaction with lymphocytes, which may either aggravate or suppress neuroinflammation.

  17. TNF signaling inhibition in the CNS: implications for normal brain function and neurodegenerative disease

    Directory of Open Access Journals (Sweden)

    Tansey Malú G


    Full Text Available Abstract The role of tumor necrosis factor (TNF as an immune mediator has long been appreciated but its function in the brain is still unclear. TNF receptor 1 (TNFR1 is expressed in most cell types, and can be activated by binding of either soluble TNF (solTNF or transmembrane TNF (tmTNF, with a preference for solTNF; whereas TNFR2 is expressed primarily by microglia and endothelial cells and is preferentially activated by tmTNF. Elevation of solTNF is a hallmark of acute and chronic neuroinflammation as well as a number of neurodegenerative conditions including ischemic stroke, Alzheimer's (AD, Parkinson's (PD, amyotrophic lateral sclerosis (ALS, and multiple sclerosis (MS. The presence of this potent inflammatory factor at sites of injury implicates it as a mediator of neuronal damage and disease pathogenesis, making TNF an attractive target for therapeutic development to treat acute and chronic neurodegenerative conditions. However, new and old observations from animal models and clinical trials reviewed here suggest solTNF and tmTNF exert different functions under normal and pathological conditions in the CNS. A potential role for TNF in synaptic scaling and hippocampal neurogenesis demonstrated by recent studies suggest additional in-depth mechanistic studies are warranted to delineate the distinct functions of the two TNF ligands in different parts of the brain prior to large-scale development of anti-TNF therapies in the CNS. If inactivation of TNF-dependent inflammation in the brain is warranted by additional pre-clinical studies, selective targeting of TNFR1-mediated signaling while sparing TNFR2 activation may lessen adverse effects of anti-TNF therapies in the CNS.

  18. AVN-101: A Multi-Target Drug Candidate for the Treatment of CNS Disorders (United States)

    Ivachtchenko, Alexandre V.; Lavrovsky, Yan; Okun, Ilya


    Lack of efficacy of many new highly selective and specific drug candidates in treating diseases with poorly understood or complex etiology, as are many of central nervous system (CNS) diseases, encouraged an idea of developing multi-modal (multi-targeted) drugs. In this manuscript, we describe molecular pharmacology, in vitro ADME, pharmacokinetics in animals and humans (part of the Phase I clinical studies), bio-distribution, bioavailability, in vivo efficacy, and safety profile of the multimodal drug candidate, AVN-101. We have carried out development of a next generation drug candidate with a multi-targeted mechanism of action, to treat CNS disorders. AVN-101 is a very potent 5-HT7 receptor antagonist (Ki = 153 pM), with slightly lesser potency toward 5-HT6, 5-HT2A, and 5HT-2C receptors (Ki = 1.2–2.0 nM). AVN-101 also exhibits a rather high affinity toward histamine H1 (Ki = 0.58 nM) and adrenergic α2A, α2B, and α2C (Ki = 0.41–3.6 nM) receptors. AVN-101 shows a good oral bioavailability and facilitated brain-blood barrier permeability, low toxicity, and reasonable efficacy in animal models of CNS diseases. The Phase I clinical study indicates the AVN-101 to be well tolerated when taken orally at doses of up to 20 mg daily. It does not dramatically influence plasma and urine biochemistry, nor does it prolong QT ECG interval, thus indicating low safety concerns. The primary therapeutic area for AVN-101 to be tested in clinical trials would be Alzheimer’s disease. However, due to its anxiolytic and anti-depressive activities, there is a strong rational for it to also be studied in such diseases as general anxiety disorders, depression, schizophrenia, and multiple sclerosis. PMID:27232215

  19. System xc⁻ cystine/glutamate antiporter: an update on molecular pharmacology and roles within the CNS. (United States)

    Bridges, Richard J; Natale, Nicholas R; Patel, Sarjubhai A


    System x(c)(-) is an amino acid antiporter that typically mediates the exchange of extracellular l-cystine and intracellular L-glutamate across the cellular plasma membrane. Studied in a variety of cell types, the import of L-cystine through this transporter is critical to glutathione production and oxidative protection. The exchange-mediated export of L-glutamate takes on added significance within the CNS, as it represents a non-vesicular route of release through which this excitatory neurotransmitter can participate in either neuronal signalling or excitotoxic pathology. When both the import of L-cystine and the export of L-glutamate are taken into consideration, system x(c)(-) has now been linked to a wide range of CNS functions, including oxidative protection, the operation of the blood-brain barrier, neurotransmitter release, synaptic organization, viral pathology, drug addiction, chemosensitivity and chemoresistance, and brain tumour growth. The ability to selectively manipulate system x(c)(-), delineate its function, probe its structure and evaluate it as a therapeutic target is closely linked to understanding its pharmacology and the subsequent development of selective inhibitors and substrates. Towards that goal, this review will examine the current status of our understanding of system x(c)(-) pharmacology and the structure-activity relationships that have guided the development of an initial pharmacophore model, including the presence of lipophilic domains adjacent to the substrate binding site. A special emphasis is placed on the roles of system x(c)(-) within the CNS, as it is these actions that are among the most exciting as potential long-range therapeutic targets.

  20. Fiscal 1999 achievement report on regional consortium research and development project. Regional consortium research and development in its 1st year (Development of plastic/metal compositing technology utilizing biogradable natural macromolecules); 1999 nendo seibunkaisei tennen kobunshi wo katsuyoshita plastic to kinzoku no fukugoka gijutsu no kaihatsu seika hokokusho. 1

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    Research and development is conducted to composite plastic and metal into an electromagnetic shield, for which the metal adsorbing function of chitin and chitosan which are biomass to be obtained from crab and lobster shells is utilized. In the research and development of a method for manufacturing chitosan with its molecular weight decreased, it is found that the molecular weight of the substance is effectively lowered by the use of amorphous chitin as the matrix, lysozyme, chitinase, and chitosanase. In the research on the application of biogradable materials to an electromagnetic shield, studies are conducted about the melting and dispersion of biogradable materials into the primer used for pre-coating treatment. In the evaluation of the physical properties and functions of a novel electromagnetic shield system, coatings prepared by use of various chitosan derivatives are tested, and then it is found that a 2,4-dihydroxybenzaldehyde derivative achieves excellent adhesion. Studies are conducted as to how to decompose such a shield system, when experiments are performed for a chitosan derivative film etc. (NEDO)