Kindlin-3 loss curbs chronic myeloid leukemia in mice by mobilizing leukemic stem cells from protective bone marrow niches.

Kindlin-3 (K3)-mediated integrin adhesion controls homing and bone marrow (BM) retention of normal hematopoietic cells. However, the role of K3 in leukemic stem cell (LSC) retention and growth in the remodeled tumor-promoting BM is unclear. We report that loss of K3 in a mouse model of chronic myeloid leukemia (CML) triggers the release of LSCs from the BM into the circulation and impairs their retention, proliferation, and survival in secondary organs, which curbs CML development, progression, and metastatic dissemination. We found de novo expression of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) on CML-LSCs but not normal hematopoietic stem cells and this enabled us to specifically deplete K3 with a CTLA-4-binding RNA aptamer linked to a K3-siRNA (small interfering RNA) in CTLA-4+ LSCs in vivo, which mobilized LSCs in the BM, induced disease remission, and prolonged survival of mice with CML. Thus, disrupting interactions of LSCs with the BM environment is a promising strategy to halt the disease-inducing and relapse potential of LSCs

Методика локализации изображения лица для систем видеоконтроля на основе нейронной сети

Предлагается метод и алгоритм локализации лица человека для автоматизированных систем распознавания и видеоконтроля на базе сверточных нейронных сетей. Преимущество использования свёрточных нейронных сетей в том, что они обеспечивают устойчивость к изменениям масштаба, смещениям, поворотам, смене ракурса и другим искажениям входного изображения. Обосновывается топология используемой нейронной сети и методика ее обучения

Rhombic Patterns: Broken Hexagonal Symmetry

Landau-Ginzburg equations derived to conserve two-dimensional spatial symmetries lead to the prediction that rhombic arrays with characteristic angles slightly differ from 60 degrees should form in many systems. Beyond the bifurcation from the uniform state to patterns, rhombic patterns are linearly stable for a band of angles near the 60 degrees angle of regular hexagons. Experiments conducted on a reaction-diffusion system involving a chlorite-iodide-malonic acid reaction yield rhombic patterns in good accord with the theory.Energy Laboratory of the University of HoustonOffice of Naval ResearchU.S. Department of Energy Office of Basic Energy SciencesRobert A. Welch FoundationCenter for Nonlinear Dynamic

Rights Myopia in Child Welfare

For decades, legal scholars have debated the proper balance of parents\u27 rights and children\u27s rights in the child welfare system. This Article argues that the debate mistakenly privileges rights. Neither parents\u27 rights nor children\u27s rights serve families well because, as implemented, a solely rights-based model of child welfare does not protect the interests of parents or children. Additionally, even if well-implemented, the model still would not serve parents or children because it obscures the important role of poverty in child abuse and neglect and fosters conflict rather than collaboration between the state and families. In lieu of a solely rights-based model, this Article proposes a problem-solving model for child welfare and explores one embodiment of such a model, family group conferencing. This Article concludes that a problem-solving model holds significant potential to address many of the profound theoretical and practical shortcomings of the current child welfare system

Transition from the Couette-Taylor system to the plane Couette system

We discuss the flow between concentric rotating cylinders in the limit of large radii where the system approaches plane Couette flow. We discuss how in this limit the linear instability that leads to the formation of Taylor vortices is lost and how the character of the transition approaches that of planar shear flows. In particular, a parameter regime is identified where fractal distributions of life times and spatiotemporal intermittency occur. Experiments in this regime should allow to study the characteristics of shear flow turbulence in a closed flow geometry.Comment: 5 pages, 5 figure

Principle of Maximum Entropy Applied to Rayleigh-B\'enard Convection

A statistical-mechanical investigation is performed on Rayleigh-B\'enard convection of a dilute classical gas starting from the Boltzmann equation. We first present a microscopic derivation of basic hydrodynamic equations and an expression of entropy appropriate for the convection. This includes an alternative justification for the Oberbeck-Boussinesq approximation. We then calculate entropy change through the convective transition choosing mechanical quantities as independent variables. Above the critical Rayleigh number, the system is found to evolve from the heat-conducting uniform state towards the convective roll state with monotonic increase of entropy on the average. Thus, the principle of maximum entropy proposed for nonequilibrium steady states in a preceding paper is indeed obeyed in this prototype example. The principle also provides a natural explanation for the enhancement of the Nusselt number in convection.Comment: 13 pages, 4 figures; typos corrected; Eq. (66a) corrected to remove a double counting for $k_{\perp}=0$; Figs. 1-4 replace

Electrical signature in polar night cloud base variations

Layer clouds are globally extensive. Their lower edges are charged negatively by the fair weather atmospheric electricity current flowing vertically through them. Using polar winter surface meteorological data from Sodankyla ̈ (Finland) and Halley (Antarctica), we find that when meteorological diurnal variations are weak, an appreciable diurnal cycle, on average, persists in the cloud base heights, detected using a laser ceilometer. The diurnal cloud base heights from both sites correlate more closely with the Carnegie curve of global atmospheric electricity than with local meteorological measurements. The cloud base sensitivities are indistinguishable between the northern and southern hemispheres, averaging a (4.0 ± 0.5) m rise for a 1% change in the fair weather electric current density. This suggests that the global fair weather current, which is affected by space weather, cosmic rays and the El Nin ̃o Southern Oscillation, is linked with layer cloud properties

Onset of Surface-Tension-Driven Benard Convection

Experiments with shadowgraph visualization reveal a subcritical transition to a hexagonal convection pattern in thin liquid layers that have a free upper surface and are heated from below. The measured critical Marangoni number (84) and observation of hysteresis (3%) agree with theory. In some experiments, imperfect bifurcation is observed and is attributed to deterministic forcing caused in part by the lateral boundaries in the experiment.Comment: 4 pages. The RevTeX file has a macro allowing various styles. The appropriate style is "mypprint" which is the defaul

Asphodelus fistulosus L. (Liliaceae) subespontáneo en la Argentina (nota breve)

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Targeting quiescent leukemic stem cells using second generation autophagy inhibitors

In chronic myeloid leukemia (CML), tyrosine kinase inhibitor (TKI) treatment induces autophagy that promotes survival and TKI-resistance in leukemic stem cells (LSCs). In clinical studies hydroxychloroquine (HCQ), the only clinically approved autophagy inhibitor, does not consistently inhibit autophagy in cancer patients, so more potent autophagy inhibitors are needed. We generated a murine model of CML in which autophagic flux can be measured in bone marrow-located LSCs. In parallel, we use cell division tracing, phenotyping of primary CML cells, and a robust xenotransplantation model of human CML, to investigate the effect of Lys05, a highly potent lysosomotropic agent, and PIK-III, a selective inhibitor of VPS34, on the survival and function of LSCs. We demonstrate that long-term haematopoietic stem cells (LT-HSCs: Lin−Sca-1+c-kit+CD48−CD150+) isolated from leukemic mice have higher basal autophagy levels compared with non-leukemic LT-HSCs and more mature leukemic cells. Additionally, we present that while HCQ is ineffective, Lys05-mediated autophagy inhibition reduces LSCs quiescence and drives myeloid cell expansion. Furthermore, Lys05 and PIK-III reduced the number of primary CML LSCs and target xenografted LSCs when used in combination with TKI treatment, providing a strong rationale for clinical use of second generation autophagy inhibitors as a novel treatment for CML patients with LSC persistence