Reconfigurable Flows and Defect Landscape of Confined Active Nematics

Using novel micro-printing techniques, we develop a versatile experimental setup that allows us to study how lateral confinement tames the active flows and defect properties of the microtubule/kinesin active nematic system. We demonstrate that the active length scale that determines the self-organization of this system in unconstrained geometries loses its relevance under strong lateral confinement. Dramatic transitions are observed from chaotic to vortex lattices and defect-free unidirectional flows. Defects, which determine the active flow behavior, are created and annihilated on the channel walls rather than in the bulk, and acquire a strong orientational order in narrow channels. Their nucleation is governed by an instability whose wavelength is effectively screened by the channel width. All these results are recovered in simulations, and the comparison highlights the role of boundary conditions

Active boundary layers

The role of boundary layers in conventional liquid crystals is commonly subsumed in their anchoring on confining walls. In the classical view, anchoring enslaves the orientational field of the passive material under equilibrium conditions. In this work, we experimentally explore the role of confining walls in the behavior of an active nematic. We find that, under slip boundary conditions, the wall induces the accumulation of negatively charged topological defects in its vicinity, resulting in the formation of a topological boundary layer that polarizes the wall. While the dynamics of wall and bulk defects are decoupled, we find that the active boundary layer influences the overall dynamics of the system, to the point of fully controlling the behavior of the active nematic in situations of strong confinement. Finally, we show that wall defects exhibit behaviors that are essentially different from those of their bulk counterparts, such as high motility or the ability to recombine with another defect of like-sign topological charge. These exotic behaviors result from a change of symmetry induced by the wall in the director field around the defect. Finally, we show that the collective dynamics of wall defects can be described in terms of a one-dimensional Kuramoto-Sivashinsky -like description of spatio-temporal chaos.Comment: 10 pages, 6 figures in main text, 5 figures in S

Active boundary layers in confined active nematics

The roleofboundary layers inconventional liquidcrystals is commonly related to the mesogen anchoring on confining walls. In the classical view, anchoring enslaves the orientational field of the passive material under equilibrium conditions. In this work, we show that an active nematic can develop active boundary layers that topologically polarize the confining walls. We find that negatively-charged defects accumulate in the boundary layer, regardless of the wall curvature, and they influence the overall dynamics of the system to the point of fully controlling the behavior of the active nematic in situations of strong confinement. Further, we show that wall defects exhibit behaviors that are essentially different from those of their bulk counterparts, such as high motility or the ability to recombinewith another defect of like-sign topological charge. These exotic behaviors result from a change of symmetry induced by the wall in the director field around the defect. Finally, we suggest that the collective dynamics of wall defects might be described in terms of a model equation for one-dimensional spatio-temporal chaos

Downregulation of 26S proteasome catalytic activity promotes epithelial-mesenchymal transition.

The epithelial-mesenchymal transition (EMT) endows carcinoma cells with phenotypic plasticity that can facilitate the formation of cancer stem cells (CSCs) and contribute to the metastatic cascade. While there is substantial support for the role of EMT in driving cancer cell dissemination, less is known about the intracellular molecular mechanisms that govern formation of CSCs via EMT. Here we show that β2 and β5 proteasome subunit activity is downregulated during EMT in immortalized human mammary epithelial cells. Moreover, selective proteasome inhibition enabled mammary epithelial cells to acquire certain morphologic and functional characteristics reminiscent of cancer stem cells, including CD44 expression, self-renewal, and tumor formation. Transcriptomic analyses suggested that proteasome-inhibited cells share gene expression signatures with cells that have undergone EMT, in part, through modulation of the TGF-β signaling pathway. These findings suggest that selective downregulation of proteasome activity in mammary epithelial cells can initiate the EMT program and acquisition of a cancer stem cell-like phenotype. As proteasome inhibitors become increasingly used in cancer treatment, our findings highlight a potential risk of these therapeutic strategies and suggest a possible mechanism by which carcinoma cells may escape from proteasome inhibitor-based therapy

LSST: from Science Drivers to Reference Design and Anticipated Data Products

(Abridged) We describe here the most ambitious survey currently planned in the optical, the Large Synoptic Survey Telescope (LSST). A vast array of science will be enabled by a single wide-deep-fast sky survey, and LSST will have unique survey capability in the faint time domain. The LSST design is driven by four main science themes: probing dark energy and dark matter, taking an inventory of the Solar System, exploring the transient optical sky, and mapping the Milky Way. LSST will be a wide-field ground-based system sited at Cerro Pach\'{o}n in northern Chile. The telescope will have an 8.4 m (6.5 m effective) primary mirror, a 9.6 deg$^2$ field of view, and a 3.2 Gigapixel camera. The standard observing sequence will consist of pairs of 15-second exposures in a given field, with two such visits in each pointing in a given night. With these repeats, the LSST system is capable of imaging about 10,000 square degrees of sky in a single filter in three nights. The typical 5$\sigma$ point-source depth in a single visit in $r$ will be $\sim 24.5$ (AB). The project is in the construction phase and will begin regular survey operations by 2022. The survey area will be contained within 30,000 deg$^2$ with $\delta<+34.5^\circ$, and will be imaged multiple times in six bands, $ugrizy$, covering the wavelength range 320--1050 nm. About 90\% of the observing time will be devoted to a deep-wide-fast survey mode which will uniformly observe a 18,000 deg$^2$ region about 800 times (summed over all six bands) during the anticipated 10 years of operations, and yield a coadded map to $r\sim27.5$. The remaining 10\% of the observing time will be allocated to projects such as a Very Deep and Fast time domain survey. The goal is to make LSST data products, including a relational database of about 32 trillion observations of 40 billion objects, available to the public and scientists around the world.Comment: 57 pages, 32 color figures, version with high-resolution figures available from https://www.lsst.org/overvie

The structure of the caspase recruitment domain of BinCARD reveals that all three cysteines can be oxidized

The caspase recruitment domain (CARD) is present in death-domain superfamily proteins involved in inflammation and apoptosis. BinCARD is named for its ability to interact with Bcl10 and inhibit downstream signalling. Human BinCARD is expressed as two isoforms that encode the same N-terminal CARD region but which differ considerably in their C-termini. Both isoforms are expressed in immune cells, although BinCARD-2 is much more highly expressed. Crystals of the CARD fold common to both had low symmetry (space group P1). Molecular replacement was unsuccessful in this low-symmetry space group and, as the construct contains no methionines, first one and then two residues were engineered to methionine for MAD phasing. The double-methionine variant was produced as a selenomethionine derivative, which was crystallized and the structure was solved using data measured at two wavelengths. The crystal structures of the native and selenomethionine double mutant were refined to high resolution (1.58 and 1.40 Å resolution, respectively), revealing the presence of a cis-peptide bond between Tyr39 and Pro40. Unexpectedly, the native crystal structure revealed that all three cysteines were oxidized. The mitochondrial localization of BinCARD-2 and the susceptibility of its CARD region to redox modification points to the intriguing possibility of a redox-regulatory role

A school-based resilience intervention to decrease tobacco, alcohol and marijuana use in high school students

<p>Abstract</p> <p>Background</p> <p>Despite schools theoretically being an ideal setting for accessing adolescents and preventing initiation of substance use, there is limited evidence of effective interventions in this setting. Resilience theory provides one approach to achieving such an outcome through improving adolescent mental well-being and resilience. A study was undertaken to examine the potential effectiveness of such an intervention approach in improving adolescent resilience and protective factor scores; and reducing the prevalence of adolescent tobacco, alcohol and marijuana use in three high schools.</p> <p>Methods</p> <p>A non-controlled before and after study was undertaken. Data regarding student resilience and protective factors, and measures of tobacco, alcohol and marijuana use were collected from grade 7 to 10 students at baseline (n = 1449) and one year following a three year intervention (n = 1205).</p> <p>Results</p> <p>Significantly higher resilience and protective factors scores, and significantly lower prevalence of substance use were evident at follow up.</p> <p>Conclusions</p> <p>The results suggest that the intervention has the potential to increase resilience and protective factors, and to decrease the use of tobacco, alcohol and marijuana by adolescents. Further more rigorous research is required to confirm this potential.</p

Placemaking from Interstitial Spaces: Participatory planning and collaborative community design as strategies to revitalize a service alleyway in Montreal (Bishop/Mackay)

This project explores participatory planning and community design methodologies (i.e. pattern language design, placemaking, community planning charrettes, planning-in-situ, open planning and peer to peer urbanism) to revitalize a service alleyway in downtown Montreal. The objective of this project is to democratize planning and urban design practices and to engage ordinary citizens in the planning of their own spaces. After a series of visioning workshops, brainstorming sessions and a community planning charrette, this project incorporates inputs from stakeholders, students and ordinary citizens into a collaborative urban design project. The project proposes interventions such as a woonerf, a planning committee, a cubic/fractal scaffolding structure, art murals and wall projections (among others). With the objective of encouraging future adaptations and transformations, this project is published under a Creative Commons license. Adopt and adapt these ideas (but cite and acknowledge accordingly)