Femtosecond laser writing of embedded waveguides in polymers

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How should our pedagogy keep up with rapidly changing technology?

The place and potential of e-learning technology in education is in a state of constant development. Previously 'cutting edge' articles and books for teachers are quickly obsolete, as these resources, written for the age of Myspace and desktops, did not prepare educators for the arrival and popularity of tablets, smart-phones, and social media applications. This literature review explores six different articles on this subject addressing a range of perspectives in this area. They were found searching academic databases with the terms 'e-learning', 'pedagogy' and 'technology'. To keep the articles relatively current- to reflect the development of web 2.0 and 3.0 and other recent trends- the search parameters were restricted to 2011 onwards. The overwhelming position in the literature is that pedagogy must guide our e-learning. While some articles focussed on applying this in a classroom, others preferred to construct a framework to guide educators in their e-learning design

Rating and selecting CRM systems for trade enterprises management

Статья посвящена исследованию современного состояния торговой отрасли Украины, рейтинговой оценке и выбору CRM-систем для управления торговыми предприятиями. Проанализирована динамика структуры экономики Украины за 2010-2017 годы и определено, что за этот период оптовая и розничная торговля была ведущей отраслью экономики Украины, сохраняя в структуре экономики первое место по объему реализованной продукции. Экспертным методом проверено степень согласованности мнений экспертов относительно рейтинга 4-х CRM-систем: bpm online sales, Bitrix24, AmoCRM, Мегаплан. Рассчитан коэффициент конкордации Кендалла, значение χ2-критерия Пирсона свидетельствует о значимости коэффициента конкордации и сильной связи между признаками. Определена наиболее оптимальная CRM-система для управления торговыми предприятиями Украины и предложены пути популяризации использования CRM-систем в торговой отрасли Украины.The article is devoted to the current state study of the Ukrainian trade industry, rating and selecting CRM systems for trade enterprise management. The process of the trade enterprises management determines the need to use information systems and technologies because they can increase the efficiency of enterprises and processes management. This leads to increased sales and profits. However, CRM systems and technologies are not sufficiently used in the Ukrainian trade industry because only 6 percent of enterprises actively used systems for customer relationship management. That’s why the current state analysis of the Ukrainian trade industry, the rating and the selecting CRM systems for the trade enterprises management are relevant and has a great practical importance. The dynamics of Ukraine’s national economy structure for 2010-2017 has been analyzed. It is shown that the relations between the Ukrainian economy sectors change over time and will change in the future. Despite this fact, the wholesale and retail trade ranked first in the structure of the national economy in terms of sales. As the result, the trade industry was a leading branch of the Ukrainian economy during this period. The ratings of CRM systems compiled by authors are very different. Therefore, it is proposed to use an expert method and different sources of information to determine the degree of consistency of expert opinions on this issue. In this study, only those CRM systems that are recognized as major players in Ukraine are used. Thus, a comparative analysis of four CRM systems such as bpm online sales, Bitrix24, AmoCRM, Megaplan was carried out. Kendall concordance coefficient has been calculated. Its value indicates a strong consistency of expert opinions. Then, Pearson's chi-squared test is used to assess the relationship between considered signs. Pearson criterion value indicates the importance of the coefficient of concordance and the strong correlation between the signs. Provided analysis in the article allowed us to determine the most optimal CRM-system for Ukraine’s trade enterprises management. Ways to popularize the use of CRM-systems in the Ukrainian trade industry are proposed

Molecular dissection of the mechanism by which EWS/FLI expression compromises actin cytoskeletal integrity and cell adhesion in Ewing sarcoma.

Ewing sarcoma is the second-most-common bone cancer in children. Driven by an oncogenic chromosomal translocation that results in the expression of an aberrant transcription factor, EWS/FLI, the disease is typically aggressive and micrometastatic upon presentation. Silencing of EWS/FLI in patient-derived tumor cells results in the altered expression of hundreds to thousands of genes and is accompanied by dramatic morphological changes in cytoarchitecture and adhesion. Genes encoding focal adhesion, extracellular matrix, and actin regulatory proteins are dominant targets of EWS/FLI-mediated transcriptional repression. Reexpression of genes encoding just two of these proteins, zyxin and α5 integrin, is sufficient to restore cell adhesion and actin cytoskeletal integrity comparable to what is observed when the EWS/FLI oncogene expression is compromised. Using an orthotopic xenograft model, we show that EWS/FLI-induced repression of α5 integrin and zyxin expression promotes tumor progression by supporting anchorage-independent cell growth. This selective advantage is paired with a tradeoff in which metastatic lung colonization is compromised

Time-resolved FRET reports FGFR1 dimerization and formation of a complex with its effector PLCγ1.

In vitro and in vivo imaging of protein tyrosine kinase activity requires minimally invasive, molecularly precise optical probes to provide spatiotemporal mechanistic information of dimerization and complex formation with downstream effectors. We present here a construct with genetically encoded, site-specifically incorporated, bioorthogonal reporter that can be selectively labelled with exogenous fluorogenic probes to monitor the structure and function of fibroblast growth factor receptor (FGFR). GyrB.FGFR1KD.TC contains a coumermycin-induced artificial dimerizer (GyrB), FGFR1 kinase domain (KD) and a tetracysteine (TC) motif that enables fluorescent labelling with biarsenical dyes FlAsH-EDT2 and ReAsH-EDT2. We generated bimolecular system for time-resolved FRET (TR-FRET) studies, which pairs FlAsH-tagged GyrB.FGFR1KD.TC and N-terminal Src homology 2 (nSH2) domain of phospholipase Cγ (PLCγ), a downstream effector of FGFR1, fused to mTurquoise fluorescent protein (mTFP). We demonstrated phosphorylation-dependent TR-FRET readout of complex formation between mTFP.nSH2 and GyrB.FGFR1KD.TC. By further application of TR-FRET, we also demonstrated formation of the GyrB.FGFR1KD.TC homodimer by coumermycin-induced dimerization. Herein, we present a spectroscopic FRET approach to facilitate and propagate studies that would provide structural and functional insights for FGFR and other tyrosine kinases

The Chemical Sensitivity of Stratospheric Ozone to N₂O and CH₄ through the 21st century

Through the 21st century, global-mean stratospheric ozone abundances are projected to increase due to decreasing chlorine and bromine concentrations (as a consequence of the Montreal Protocol for Substances that Deplete the Ozone Layer), and continued CO₂-induced cooling of the stratosphere. Along with CO₂, anthropogenic emissions of the greenhouse gases N₂O and CH₄ are projected to increase, thus increasing their atmospheric concentrations. Consequently, reactive nitrogen species produced from N₂O and reactive hydrogen species produced from CH₄ are expected to play an increasingly important role in determining stratospheric ozone concentrations. Chemistry-climate model simulations were performed using the NIWA-SOCOL (National Institute of Water and Atmospheric Research - SOlar Climate Ozone Links) model, which tracks the contributions to ozone loss from a prescribed set of catalytic cycles, including the ozone-depleting nitrogen and hydrogen cycles, over latitude, longitude, pressure and time. The results provide a comprehensive picture of how stratospheric ozone may evolve through the 21st century under a range of greenhouse gas emissions scenarios, and quantitatively extend concepts that had previously been understood only qualitatively

Visualizing stromal cell dynamics in different tumor microenvironments by spinning disk confocal microscopy

The tumor microenvironment consists of stromal cells and extracellular factors that evolve in parallel with carcinoma cells. To gain insights into the activities of stromal cell populations, we developed and applied multicolor imaging techniques to analyze the behavior of these cells within different tumor microenvironments in the same live mouse. We found that regulatory T-lymphocytes (Tregs) migrated in proximity to blood vessels. Dendriticlike cells, myeloid cells and carcinoma-associated fibroblasts all exhibited higher motility in the microenvironment at the tumor periphery than within the tumor mass. Since oxygen levels differ between tumor microenvironments, we tested if acute hypoxia could account for the differences in cell migration. Direct visualization revealed that Tregs ceased migration under acute systemic hypoxia, whereas myeloid cells continued migrating. In the same mouse and microenvironment, we experimentally subdivided the myeloid cell population and revealed that uptake of fluorescent dextran defined a low-motility subpopulation expressing markers of tumor-promoting, alternatively activated macrophages. In contrast, fluorescent anti-Gr1 antibodies marked myeloid cells patrolling inside tumor vessels and in the stroma. Our techniques allow real-time combinatorial analysis of cell populations based on spatial location, gene expression, behavior and cell surface molecules within intact tumors. The techniques are not limited to investigations in cancer, but could give new insights into cell behavior more broadly in development and disease

Dioxin Exposure Blocks Lactation Through a Direct Effect on Mammary Epithelial Cells Mediated by the Aryl Hydrocarbon Receptor Repressor

In mammals, lactation is a rich source of nutrients and antibodies for newborn animals. However, millions of mothers each year experience an inability to breastfeed. Exposure to several environmental toxicants, including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), has been strongly implicated in impaired mammary differentiation and lactation. TCDD and related polyhalogenated aromatic hydrocarbons are widespread industrial pollutants that activate the aryl hydrocarbon receptor (AHR). Despite many epidemiological and animal studies, the molecular mechanism through which AHR signaling blocks lactation remains unclear. We employed in vitro models of mammary differentiation to recapitulate lactogenesis in the presence of toxicants. We demonstrate AHR agonists directly block milk production in isolated mammary epithelial cells. Moreover, we define a novel role for the aryl hydrocarbon receptor repressor (AHRR) in mediating this response. Our mechanistic studies suggest AHRR is sufficient to block transcription of the milk gene β-casein. Since TCDD is a prevalent environmental pollutant that affects women worldwide, our results have important public health implications for newborn nutrition