389 research outputs found

    Monitoring the dynamics of Src activity in response to anti-invasive dasatinib treatment at a subcellular level using dual intravital imaging

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    Optimising response to tyrosine kinase inhibitors in cancer remains an extensive field of research. Intravital imaging is an emerging tool, which can be used in drug discovery to facilitate and fine-tune maximum drug response in live tumors. A greater understanding of intratumoural delivery and pharmacodynamics of a drug can be obtained by imaging drug target-specific fluorescence resonance energy transfer (FRET) biosensors in real time. Here, we outline our recent work using a Src-FRET biosensor as a readout of Src activity to gauge optimal tyrosine kinase inhibition in response to dasatinib treatment regimens in vivo. By simultaneously monitoring both the inhibition of Src using FRET imaging, and the modulation of the surrounding extracellular matrix using second harmonic generation (SHG) imaging, we were able to show enhanced drug penetrance and delivery to live pancreatic tumors. We discuss the implications of this dual intravital imaging approach in the context of altered tumor-stromal interactions, while summarising how this approach could be applied to assess other combination strategies or tyrosine kinase inhibitors in a preclinical setting

    Self similar Barkhausen noise in magnetic domain wall motion

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    A model for domain wall motion in ferromagnets is analyzed. Long-range magnetic dipolar interactions are shown to give rise to self-similar dynamics when the external magnetic field is increased adiabatically. The power spectrum of the resultant Barkhausen noise is of the form 1/ωα1/\omega^\alpha, where α1.5\alpha\approx 1.5 can be estimated from the critical exponents for interface depinning in random media.Comment: 7 pages, RevTex. To appear in Phys. Rev. Let

    Abundance changes of neophytes and native species indicate a thermophilisation and eutrophisation of the Swiss flora during the 20th century

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    During the 20th century human activities drastically altered the natural environment at global and local scales by habitat destruction, urbanisation, intensive agriculture, and climate warming. This anthropogenic pressure has modified species distributions and abundances, and led to the increased spread of neophytes. However, the determination of the magnitude, direction, and drivers of changes remains challenging as comparable historic data is often lacking. Here, we analysed the floristic shifts during the 20th century based on a historic (1900–1930) and current (2000–2017) floristic survey of the canton of Zurich (Switzerland; 1729 km2) in combination with Landolt ecological indicator values (EIVs) for vascular plants. We used two complementary approaches to quantify the floristic shifts using EIVs for temperature, moisture, continentality, nutrients, soil pH and available light. 1) Regarding 244 map tiles with each a 3 × 3 km2 area, we compared the average EIVs for neophytes (i.e., novel species arriving of expanding in the study area) and native species (i.e., species present in Switzerland for centuries). 2) Based on standardized species abundances in the historic and the current flora, we analysed the directed changes by comparing the species’ EIVs of different frequency classes for both the historic and current floristic surveys. Our results showed, that neophyte species arriving or spreading in the study area indicate both a thermophilisation and an eutrophisation. The observed shift in average EIVs for temperature corresponded to about 2 ◦C, which is in line with the calculated difference in niche centroids for neophytes and native species based on their global distribution (1.78 ◦C). The indicated thermophilisation and eutrophisation relate to the decrease in abundances of cold-adapted species and species of nutrient poor environments as well as the increase of warm-adapted and nitrophilous/ruderal species. Directed changes in the flora of the study area are likely to be driven by both climatic changes and land-use changes. Increases in trade activity, anthropogenic habitat disturbances and rising temperatures facilitate the establishment and spread of neophytes from warmer and drier regions. In parallel, wetland area and wetland species strongly decreased as well as species thriving on nutrient-poor sites due to intensified agriculture and nitrogen deposition

    Rapid climate change results in long-lasting spatial homogenization of phylogenetic diversity

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    Scientific understanding of biodiversity dynamics, resulting from past climate oscillations and projections of future changes in biodiversity, has advanced over the past decade. Little is known about how these responses, past or future, are spatially connected. Analyzing the spatial variability in biodiversity provides insight into how climate change affects the accumulation of diversity across space. Here, we evaluate the spatial variation of phylogenetic diversity of European seed plants among neighboring sites and assess the effects of past rapid climate changes during the Quaternary on these patterns. Our work shows a marked homogenization in phylogenetic diversity across Central and Northern Europe linked to high climate change velocity and large distances to refugia. Our results suggest that the future projected loss in evolutionary heritage may be even more dramatic, as homogenization in response to rapid climate change has occurred among sites across large landscapes, leaving a legacy that has lasted for millennia

    The anatomical structure of leaf blade of the Siberian feather grasses (Poaceae: Stipa)

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    Results of studies of the anatomical structure of leaf blade of Siberian feather grasses are presented. A cross sections of leave blades were studied in 15 species: S. capillata, S. grandis, S. krylovii, S. baicalensis, S. praecapillata, S. consanguinea, S. orientalis, S. lessingiana, S. kirghisorum, S. dasyphylla, S. pennata, S. pulcherrima, S. zalesskii, S. glareosa, S. klemenzii. The following diagnostic characters were identified: relative height and degree of expressiveness of edges, quantity and type of veins, extent of development and arrangement of sclerenchyma as well as number and type of trichomes on the adaxial surface of leaves. Despite the uniformity of these features in many species within sections, they exhibit distinctive morphological patterns and have been proved to be taxonomically useful.В статье представлены результаты исследования анатомического строения листовой пластинки 15 видов сибирских ковылей: S. capillata, S. grandis, S. krylovii, S. baicalensis, S. praecapillata, S. consanguinea, S. orientalis, S. lessingiana, S. kirghisorum, S. dasyphylla, S. pennata, S. pulcherrima, S. zalesskii, S. glareosa, S. klemenzii. У исследованных видов были выявлены следующие диагностические признаки: относительная высота и степень выраженности ребер, их форма, количество и тип жилок, степень развития и расположение склеренхимы, количество и тип трихом на адаксиальной поверхности листьев. Несмотря на однородность этих признаков у многих видов в пределах секции, на секционном уровне они проявляют отличительные морфологические закономерности и имеют высокую таксономическую значимость

    Dynamics of a ferromagnetic domain wall and the Barkhausen effect

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    We derive an equation of motion for the the dynamics of a ferromagnetic domain wall driven by an external magnetic field through a disordered medium and we study the associated depinning transition. The long-range dipolar interactions set the upper critical dimension to be dc=3d_c=3, so we suggest that mean-field exponents describe the Barkhausen effect for three-dimensional soft ferromagnetic materials. We analyze the scaling of the Barkhausen jumps as a function of the field driving rate and the intensity of the demagnetizing field, and find results in quantitative agreement with experiments on crystalline and amorphous soft ferromagnetic alloys.Comment: 4 RevTex pages, 3 ps figures embedde
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