460 research outputs found

    Monitoring maturation of neural stem cell grafts within a host microenvironment

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    Neural stem cells (NSC) act as a versatile tool for neuronal cell replacement strategies to treat neurodegenerative disorders in which functional neurorestorative mechanisms are limited. While the beneficial effects of such cell-based therapy have already been documented in terms of neurodegeneration of various origins, a neurophysiological basis for improvement in the recovery of neurological function is still not completely understood. This overview briefly describes the cumulative evidence from electrophysiological studies of NSC-derived neurons, aimed at establishing the maturation of differentiated neurons within a host microenvironment, and their integration into the host circuits, with a particular focus on the neurogenesis of NSC grafts within the post-ischemic milieu. Overwhelming evidence demonstrates that the host microenvironment largely regulates the lineage of NSC grafts. This regulatory role, as yet underestimated, raises possibilities for the favoured maturation of a subset of neural phenotypes in order to gain timely remodelling of the impaired brain tissue and amplify the therapeutic effects of NSC-based therapy for recovery of neurological function

    Spinal AMPA receptors: Amenable players in central sensitization for chronic pain therapy?

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    The activity-dependent trafficking of AMPA receptors (AMPAR) mediates synaptic strength and plasticity, while the perturbed trafficking of the receptors of different subunit compositions has been linked to memory impairment and to causing neuropathology. In the spinal cord, nociceptive-induced changes in AMPAR trafficking determine the central sensitization of the dorsal horn (DH): changes in AMPAR subunit composition compromise the balance between synaptic excitation and inhibition, rendering interneurons hyperexcitable to afferent inputs, and promoting Ca2+ influx into the DH neurons, thereby amplifying neuronal hyperexcitability. The DH circuits become over-excitable and carry out aberrant sensory processing; this causes an increase in pain sensation in central sensory pathways, giving rise to chronic pain syndrome. Current knowledge of the contribution of spinal AMPAR to the cellular mechanisms relating to chronic pain provides opportunities for developing target-based therapies for chronic pain intervention

    Modeling of the NIST Intelligent Building Agents Labratory

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    The Intelligent Building Agents Laboratory (IBAL) at the National Institute of Standards and Technology (NIST) will be used to experimentally study control strategies within the realm of commercial building air-conditioning systems. A simulation software (Klein, 2020) model of the IBAL has been created to help guide the experiments in the IBAL and to provide a software-based method of evaluating control strategies implemented in this facility. This simulation model is composed of the various components comprising the IBAL HVAC system such as heating coils, cooling coils, fans and dampers that can accurately simulate the actual component behavior under transient and off-design conditions. Additionally, pressure and airflow throughout the system are simulated to support associated controls for modulating damper positions and fan speeds. The resulting system simulation is flexible; it is possible to study the expected IBAL system response to forcing functions such as weather and loads under the influence of different control strategies. The initial controller included in the IBAL simulation model replicates the controls used in most commercial buildings. The resulting tool will be validated in the IBAL and allow NIST to test alternate, advanced control strategies quickly, providing guidance for the experimental work

    Zinc oxide-nickel cermet selective coatings obtained by sequential electrodeposition

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    The investigation of pulse electrodepositing modes influence on crystal structure, morphology and optical properties of ZnO has revealed the conditions in which quasi-one-dimensional (1D) ZnO nanorod arrays are formed as separate nanorods. Due to a sufficiently high resistance of zinc oxide, the electrodeposition of nickel on the fluorine doped tin oxide (FTO)/ZnO surfaces carried out in space between the ZnO nanorods. An incomplete filling of the gaps between nanorods by the nickel nanoparticles through subsequent Ni electrodeposition ensured the creation of ZnO–Ni graded cermets. The cermets, in which electrochemical filling of the spaces between ZnO nanorods by Ni, was performed in the pulse mode. It provided higher absorption of visible and near IR light. It was shown that the manufactured ZnO–Ni graded cermets have high light absorption combined with comparatively low thermal losses, so these cermets are promising cheap and affordable selective coatings for solar heat collectors

    Optical monitoring of glutamate release at multiple synapses in situ detects changes following LTP induction

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    Information processing and memory formation in the brain relies on release of the main excitatory neurotransmitter glutamate from presynaptic axonal specialisations. The classical Hebbian paradigm of synaptic memory, long-term potentiation (LTP) of transmission, has been widely associated with an increase in the postsynaptic receptor current. Whether and to what degree LTP induction also enhances presynaptic glutamate release has been the subject of debate. Here, we took advantage of the recently developed genetically encoded optical sensors of glutamate (iGluSnFR) to monitor its release at CA3-CA1 synapses in acute hippocampal slices, before and after the induction of LTP. We attempted to trace release events at multiple synapses simultaneously, by using two-photon excitation imaging in fast frame-scanning mode. We thus detected a significant increase in the average iGluSnFR signal during potentiation, which lasted for up to 90 min. This increase may reflect an increased amount of released glutamate or, alternatively, reduced glutamate binding to high-affinity glutamate transporters that compete with iGluSnFR

    Аналіз інструментів розвитку людського капіталу в страхових компаніях

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    Introduction. The urgent task of modern corporate governance is to use innovative tools to develop the knowledge economy, where the primary source of wealth is human capital. A critical factor in the development of human capital in the new pandemic environment is to ensure the efficiency of staff to achieve commercial goals under any conditions of a sharp change in quarantine restrictions. The search for new tools for human capital development in insurance companies is an urgent and objective need. It will strengthen the competitive advantages of insurance companies in the face of such global challenges and threats as a pandemic. Aim and tasks. The article aims to determine the role and importance of tools for human capital development, to find new ways to improve them, taking into account the trends of pandemic waves. The following main tasks are 1) to explore the essence of existing tools for human capital development; 2) to establish the relationship between the use of appropriate tools for human capital development in the context of the spread of the COVID-19 pandemic; 3) propose approaches to the use of human capital development tools to qualitatively and quantitatively increase the competitiveness of insurance companies. Results. The article examines the essence of existing tools for human capital development at the macro and micro levels. The essence of outsourcing, outstaffing, personnel leasing, crowdsourcing, coworking, freelancing is analyzed. The relationship between the use of appropriate tools for human capital development in the context of the spread of new waves of the COVID-19 pandemic and the effectiveness of insurance companies is established. Approaches to using human capital development tools to qualitatively and quantitatively increase insurance companies' competitiveness are proposed. Conclusions. The paper defines the role and importance of such tools for human capital development as outsourcing, outstaffing, staff leasing, crowdsourcing, coworking, freelancing. Ways to improve them, taking into account the trends of pandemic waves, are proposed. A direct relationship between applying the tools of human capital development in the new waves of the COVID-19 pandemic and the effectiveness of insurance companies is established. It is proposed to use the analyzed tools to qualitatively and quantitatively increase the competitiveness of insurance companies.Вступ. Актуальним завданням сучасного управління компаніями є використання інноваційних інструментів розвитку економіки знань, де головним джерелом багатства є людський капітал. Ключовим фактором розвитку людського капіталу в нових пандемічних умовах є забезпечення ефективності роботи персоналу з метою досягнення поставлених комерційних цілей за будь-яких умов різкої зміни карантинних обмежень. Пошук нових інструментів розвитку людського капіталу в страхових компаніях є актуальною та об‘єктивною потребою. Це дозволить зміцнити конкурентні переваги страхових компаній в умовах існування таких глобальних викликів та загроз як пандемія. Мета і завдання. Метою статті є визначення ролі та значення інструментів розвитку людського капіталу, пошук нових способів їх вдосконалення з урахуванням тенденцій поширення хвиль пандемії. Для досягнення цієї мети слід вирішити наступні основні завдання: 1) дослідити суть існуючих інструментів розвитку людського капіталу; 2) встановити взаємозв’язок між застосування відповідних інструментів для розвитку людського капіталу в умовах поширення пандемії COVID-19; 3) запропонувати підходи щодо використання інструментів розвитку людського капіталу для якісного та кількісного підвищення конкурентоспроможності страхових компаній. Результати. У статті досліджено суть існуючих інструментів розвитку людського капіталу на макро- та мікрорівнях. Проаналізовано сутність понять аутсорсинг, аутстафінг, лізинг персоналу, краудсорсинг, коворкінг, фрілансинг. Встановлено взаємозв’язок між застосування відповідних інструментів для розвитку людського капіталу в умовах поширення нових хвиль пандемії COVID-19 та результативністю страхових компаній. Запропоновано підходи щодо використання інструментів розвитку людського капіталу для якісного та кількісного підвищення конкурентоспроможності страхових компаній. Висновки. У роботі визначено визначення ролі та значення таких інструментів розвитку людського капіталу як аутсорсинг, аутстафінг, лізинг персоналу, краудсорсинг, коворкінг, фрілансинг. Запропоновано шляхи їх вдосконалення з урахуванням тенденцій поширення хвиль пандемії. Встановлено, що між застосування досліджуваних інструментів розвитку людського капіталу в умовах поширення нових хвиль пандемії COVID-19 та результативністю страхових компаній існує безпосередній взаємозв’язок, запропоновано використовувати проаналізовані інструменти для якісного та кількісного підвищення конкурентоспроможності страхових компаній

    The Fabry disease-associated lipid Lyso-Gb3 enhances voltage-gated calcium currents in sensory neurons and causes pain

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    Fabry disease is an X-linked lysosomal storage disorder characterised by accumulation of glycosphingolipids, and accompanied by clinical manifestations, such as cardiac disorders, renal failure, pain and peripheral neuropathy. Globotriaosylsphingosine (lyso-Gb3), a deacylated form of globotriaosylceramide (Gb3), has emerged as a marker of Fabry disease. We investigated the link between Gb3, lyso-Gb3 and pain. Plantar administration of lyso-Gb3 or Gb3 caused mechanical allodynia in healthy mice. In vitro application of 100nM lyso-Gb3 caused uptake of extracellular calcium in 10% of sensory neurons expressing nociceptor markers, rising to 40% of neurons at 1μM, a concentration that may occur in Fabry disease patients. Peak current densities of voltage-dependent Ca(2+) channels were substantially enhanced by application of 1μM lyso-Gb3. These studies suggest a direct role for lyso-Gb3 in the sensitisation of peripheral nociceptive neurons that may provide an opportunity for therapeutic intervention in the treatment of Fabry disease-associated pain
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