A Rational Design of a Selective Inhibitor for Kv1.1 Channels Prevalent in Demyelinated Nerves That Improves Their Impaired Axonal Conduction

K+ channels containing Kv1.1 α subunits, which become prevalent at internodes in demyelinated axons, may underlie their dysfunctional conduction akin to muscle weakness in multiple sclerosis. Small inhibitors were sought with selectivity for the culpable hyper-polarizing K+ currents. Modeling of interactions with the extracellular pore in a Kv1.1-deduced structure identified diaryldi(2-pyrrolyl)methane as a suitable scaffold with optimized alkyl ammonium side chains. The resultant synthesized candidate [2,2′-((5,5′(di-p-topyldiaryldi(2-pyrrolyl)methane)bis(2,2′carbonyl)bis(azanediyl)) diethaneamine·2HCl] (8) selectively blocked Kv1.1 channels (IC50 ≈ 15 μM) recombinantly expressed in mammalian cells, induced a positive shift in the voltage dependency of K+ current activation, and slowed its kinetics. It preferentially inhibited channels containing two or more Kv1.1 subunits regardless of their positioning in concatenated tetramers. In slices of corpus callosum from mice subjected to a demyelination protocol, this novel inhibitor improved neuronal conduction, highlighting its potential for alleviating symptoms in multiple sclerosis

Keeping Data Science Broad: Negotiating the Digital and Data Divide Among Higher Education Institutions

The goal of the “Keeping Data Science Broad” series of webinars and workshops was to garner community input into pathways for keeping data science education broadly inclusive across sectors, institutions, and populations. Input was collected from data science programs across the nation, either traditional or alternative, and from a range of institution types including community colleges, minority-led and minority-serving institutions, liberal arts colleges, tribal colleges, universities, and industry partners. The series consisted of two webinars (August 2017 and September 2017) leading up to a workshop (November 2017) exploring the future of data science education and workforce at institutions of higher learning that are primarily teaching-focused. A third follow-up webinar was held after the workshop (January 2018) to report on outcomes and next steps. Program committee members were chosen to represent a broad spectrum of communities with a diversity of geography (West, Northeast, Midwest, and South), discipline (Computer Science, Math, Statistics, and Domains), as well as institution type (Historically Black Colleges and Universities (HBCU’s), Hispanic-Serving Institutions (HSI’s), other Minority-Serving Institutions (MSI\u27s), Community College\u27s (CC’s), 4-year colleges, Tribal Colleges, R1 Universities, Government and Industry Partners)

Keeping Data Science Broad: Negotiating the Digital and Data Divide Among Higher Education Institutions

The goal of the “Keeping Data Science Broad” series of webinars and workshops was to garner community input into pathways for keeping data science education broadly inclusive across sectors, institutions, and populations. Input was collected from data science programs across the nation, either traditional or alternative, and from a range of institution types including community colleges, minority-led and minority-serving institutions, liberal arts colleges, tribal colleges, universities, and industry partners. The series consisted of two webinars (August 2017 and September 2017) leading up to a workshop (November 2017) exploring the future of data science education and workforce at institutions of higher learning that are primarily teaching-focused. A third follow-up webinar was held after the workshop (January 2018) to report on outcomes and next steps. Program committee members were chosen to represent a broad spectrum of communities with a diversity of geography (West, Northeast, Midwest, and South), discipline (Computer Science, Math, Statistics, and Domains), as well as institution type (Historically Black Colleges and Universities (HBCU’s), Hispanic-Serving Institutions (HSI’s), other Minority-Serving Institutions (MSI\u27s), Community College\u27s (CC’s), 4-year colleges, Tribal Colleges, R1 Universities, Government and Industry Partners)

Оцінка оновлення основних засобів за рахунок позикових коштів

Оновлення основних засобів є актуальною проблемою сьогодення. Для багатьох підприємств кредити банків є чи не єдиним джерелом коштів на модернізацію виробничих потужностей. В даній статті нами були розглянуті можливості і перспективи приватних фірм для використання з цією метою позикових засобів, оцінений ступінь прозорості банківських установ, річні ставки за інвестиційними кредитами та інші умови їхнього надання.Modernizing of the basic assets is a topical problem of the present. For many business firms bank loans are may be the only source of funds for renewal of production facilities. In the article we have considered the opportunities and prospects for use of borrowed funds by private firms for this purpose, rated the degree of transparency of banking institutions, the annual rates of investment credits and other conditions of their granting

Citizen science in schools: Engaging students in research on urban habitat for pollinators

Citizen science can play an important role in school science education. Citizen science is particularly relevant to addressing current societal environmental sustainability challenges, as it engages the students directly with environmental science and gives students an understanding of the scientific process. In addition, it allows students to observe local representations of global challenges. Here, we report a citizen science programme designed to engage school-age children in real-world scientific research. The programme used standardized methods deployed across multiple schools through scientist–school partnerships to engage students with an important conservation problem: habitat for pollinator insects in urban environments. Citizen science programmes such as the programme presented here can be used to enhance scientific literacy and skills. Provided key challenges to maintain data quality are met, this approach is a powerful way to contribute valuable citizen science data for understudied, but ecologically important study systems, particularly in urban environments across broad geographical areas

Influences on gum feeding in primates

This chapter reviews the factors that may affect patterns of gum feeding by primates. These are then examined for mixed-species troops of saddleback (S. fuscicollis) and mustached (S. mystax) tamarins. An important distinction is made between gums produced by tree trunks and branches as a result of damage and those produced by seed pods as part of a dispersal strategy as these may be expected to differ in their biochemistry. Feeding on fruit and Parkia seed pod exudates was more prevalent in the morning whereas other exudates were eaten in the afternoon. This itinerary may represent a deliberate strategy to retain trunk gums in the gut overnight, thus maximising the potential for microbial fermentation of their β-linked oligosaccharides. Both types of exudates were eaten more in the dry than the wet season. Consumption was linked to seasonal changes in resource availability and not the tamarins’ reproductive status pro-viding no support for the suggestion that gums are eaten as a pri-mary calcium source in the later stages of gestation and lactation. The role of availability in determining patterns of consumption is further supported by the finding that dietary overlap for the trunk gums eaten was greater between species within mixed-species troops within years than it was within species between years. These data and those for pygmy marmosets (Cebuella pygmaea) suggest that patterns of primate gummivory may reflect the interaction of prefer-ence and availability for both those able to stimulate gum production and those not

Anti-cancer effects and mechanism of actions of aspirin analogues in the treatment of glioma cancer

INTRODUCTION: In the past 25 years only modest advancements in glioma treatment have been made, with patient prognosis and median survival time following diagnosis only increasing from 3 to 7 months. A substantial body of clinical and preclinical evidence has suggested a role for aspirin in the treatment of cancer with multiple mechanisms of action proposed including COX 2 inhibition, down regulation of EGFR expression, and NF-κB signaling affecting Bcl-2 expression. However, with serious side effects such as stroke and gastrointestinal bleeding, aspirin analogues with improved potency and side effect profiles are being developed. METHOD: Effects on cell viability following 24 hr incubation of four aspirin derivatives (PN508, 517, 526 and 529) were compared to cisplatin, aspirin and di-aspirin in four glioma cell lines (U87 MG, SVG P12, GOS – 3, and 1321N1), using the PrestoBlue assay, establishing IC50 and examining the time course of drug effects. RESULTS: All compounds were found to decrease cell viability in a concentration and time dependant manner. Significantly, the analogue PN517 (IC50 2mM) showed approximately a twofold increase in potency when compared to aspirin (3.7mM) and cisplatin (4.3mM) in U87 cells, with similar increased potency in SVG P12 cells. Other analogues demonstrated similar potency to aspirin and cisplatin. CONCLUSION: These results support the further development and characterization of novel NSAID derivatives for the treatment of glioma

DyNeuMo Mk-1: Design and pilot validation of an investigational motion-adaptive neurostimulator with integrated chronotherapy.

There is growing interest in using adaptive neuromodulation to provide a more personalized therapy experience that might improve patient outcomes. Current implant technology, however, can be limited in its adaptive algorithm capability. To enable exploration of adaptive algorithms with chronic implants, we designed and validated the 'Picostim DyNeuMo Mk-1' (DyNeuMo Mk-1 for short), a fully-implantable, adaptive research stimulator that titrates stimulation based on circadian rhythms (e.g. sleep, wake) and the patient's movement state (e.g. posture, activity, shock, free-fall). The design leverages off-the-shelf consumer technology that provides inertial sensing with low-power, high reliability, and relatively modest cost. The DyNeuMo Mk-1 system was designed, manufactured and verified using ISO 13485 design controls, including ISO 14971 risk management techniques to ensure patient safety, while enabling novel algorithms. The system was validated for an intended use case in movement disorders under an emergency-device authorization from the Medicines and Healthcare Products Regulatory Agency (MHRA). The algorithm configurability and expanded stimulation parameter space allows for a number of applications to be explored in both central and peripheral applications. Intended applications include adaptive stimulation for movement disorders, synchronizing stimulation with circadian patterns, and reacting to transient inertial events such as posture changes, general activity, and walking. With appropriate design controls in place, first-in-human research trials are now being prepared to explore the utility of automated motion-adaptive algorithms

Green and lean sustainable development path in China: Guanxi, practices and performance

Globalisation has created both drivers and pressure for Chinese organisations to enhance their business performance as well as environmental performance. Green and lean practice is emerging as a critical approach for Chinese organisations to achieve sustainable development and improve organisational performance. By conducting empirical studies from 172 respondents on green and lean practice in different Chinese organisations, this research shows how green and lean practice affects organisational performance and how this association is affected by guanxi. The findings explain that guanxi between organisational partners improves the positive effect of green and lean practice on organisational performance. The results of this paper offer helpful insights into how managers should enhance their guanxi initiatives, in order to improve environmental and business performance over their supply chains. The paper also suggests the limitations of this research, as well as directions for future research

An integrated study of geochemistry and mineralogy of the Upper Tukau Formation, Borneo Island (East Malaysia): Sediment provenance, depositional setting and tectonic implications

An integrated study using bulk chemical composition, mineralogy and mineral chemistry of sedimentary rocks from the Tukau Formation of Borneo Island (Sarawak, Malaysia) is presented in order to understand the depositional and tectonic settings during the Neogene. Sedimentary rocks are chemically classified as shale, wacke, arkose, litharenite and quartz arenite and consist of quartz, illite, feldspar, rutile and anatase, zircon, tourmaline, chromite and monazite. All of them are highly matured and were derived from a moderate to intensively weathered source. Bulk and mineral chemistries suggest that these rocks were recycled from sedimentary to metasedimentary source regions with some input from granitoids and mafic-ultramafic rocks. The chondrite normalized REE signature indicates the presence of felsic rocks in the source region. Zircon geochronology shows that the samples were of Cretaceous and Triassic age. Comparable ages of zircon from the Tukau Formation sedimentary rocks, granitoids of the Schwaner Mountains (southern Borneo) and Tin Belt of the Malaysia Peninsular suggest that the principal provenance for the Rajang Group were further uplifted and eroded during the Neogene. Additionally, presence of chromian spinels and their chemistry indicate a minor influence of mafic and ultramafic rocks present in the Rajang Group. From a tectonic standpoint, the Tukau Formation sedimentary rocks were deposited in a passive margin with passive collisional and rift settings. Our key geochemical observation on tectonic setting is comparable to the regional geological setting of northwestern Borneo as described in the literature