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Our results demonstrate how microtubule dynamics can be modulated to achieve a dynamic balance between assembly and disassembly at opposite polymer ends, resulting in treadmilling over long periods of time. Overall, we show how the collective effects of multiple components give rise to complex microtubule behavior that may be used for global network remodeling in cells.Fine-resolution differentiation trajectories of adult human hematopoietic stem cells (HSCs) involved in the generation of red cells is critical for understanding dynamic developmental changes that accompany human erythropoiesis. Using single-cell RNA sequencing (scRNA-seq) of primary human terminal erythroid cells (CD34-CD235a+) isolated directly from adult bone marrow (BM) and umbilical cord blood (UCB), we documented the transcriptome of terminally differentiated human erythroblasts at unprecedented resolution. The insights enabled us to distinguish polychromatic erythroblasts (PolyEs) at the early and late stages of development as well as the different development stages of orthochromatic erythroblasts (OrthoEs). We further identified a set of putative regulators of terminal erythroid differentiation and functionally validated three of the identified genes, AKAP8L, TERF2IP, and RNF10, by monitoring cell differentiation and apoptosis. We documented that knockdown of AKAP8L suppressed the commitment of HSCs to erythroid lineage and cell proliferation and delayed differentiation of colony-forming unit-erythroid (CFU-E) to the proerythroblast stage (ProE). In contrast, the knockdown of TERF2IP and RNF10 delayed differentiation of PolyE to OrthoE stage. Taken together, the convergence and divergence of the transcriptional continuums at single-cell resolution underscore the transcriptional regulatory networks that underlie human fetal and adult terminal erythroid differentiation.The dielectric and magnetic polarizations of quantum paraelectrics and paramagnetic materials have in many cases been found to initially increase with increasing thermal disorder and hence, exhibit peaks as a function of temperature. A quantitative description of these examples of "order-by-disorder" phenomena has remained elusive in nearly ferromagnetic metals and in dielectrics on the border of displacive ferroelectric transitions. Here, we present an experimental study of the evolution of the dielectric susceptibility peak as a function of pressure in the nearly ferroelectric material, strontium titanate, which reveals that the peak position collapses toward absolute zero as the ferroelectric quantum critical point is approached. We show that this behavior can be described in detail without the use of adjustable parameters in terms of the Larkin-Khmelnitskii-Shneerson-Rechester (LKSR) theory, first introduced nearly 50 y ago, of the hybridization of polar and acoustic modes in quantum paraelectrics, in contrast to alternative models that have been proposed. Our study allows us to construct a detailed temperature-pressure phase diagram of a material on the border of a ferroelectric quantum critical point comprising ferroelectric, quantum critical paraelectric, and hybridized polar-acoustic regimes. Furthermore, at the lowest temperatures, below the susceptibility maximum, we observe a regime characterized by a linear temperature dependence of the inverse susceptibility that differs sharply from the quartic temperature dependence predicted by the LKSR theory. We find that this non-LKSR low-temperature regime cannot be accounted for in terms of any detailed model reported in the literature, and its interpretation poses an empirical and conceptual challenge.Natural environments can present diverse challenges, but some genotypes remain fit across many environments. Such "generalists" can be hard to evolve, outcompeted by specialists fitter in any particular environment. Here, inspired by the search for broadly neutralizing antibodies during B cell affinity maturation, we demonstrate that environmental changes on an intermediate timescale can reliably evolve generalists, even when faster or slower environmental changes are unable to do so. click here We find that changing environments on timescales comparable with evolutionary transients in a population enhance the rate of evolving generalists from specialists, without enhancing the reverse process. The yield of generalists is further increased in more complex dynamic environments, such as a "chirp" of increasing frequency. Our work offers design principles for how nonequilibrium fitness "seascapes" can dynamically funnel populations to genotypes unobtainable in static environments.The structural superlubricity (SSL), a state of near-zero friction between two contacted solid surfaces, has been attracting rapidly increasing research interest since it was realized in microscale graphite in 2012. An obvious question concerns the implications of SSL for micro- and nanoscale devices such as actuators. The simplest actuators are based on the application of a normal load; here we show that this leads to remarkable dynamical phenomena in microscale graphite mesas. Under an increasing normal load, we observe mechanical instabilities leading to dynamical states, the first where the loaded mesa suddenly ejects a thin flake and the second characterized by peculiar oscillations, during which a flake repeatedly pops out of the mesa and retracts back. The measured ejection speeds are extraordinarily high (maximum of 294 m/s), and correspond to ultrahigh accelerations (maximum of 1.1×1010 m/s2). These observations are rationalized using a simple model, which takes into account SSL of graphite contacts and sample microstructure and considers a competition between the elastic and interfacial energies that defines the dynamical phase diagram of the system. Analyzing the observed flake ejection and oscillations, we conclude that our system exhibits a high speed in SSL, a low friction coefficient of 3.6×10-6, and a high quality factor of 1.3×107 compared with what has been reported in literature. Our experimental discoveries and theoretical findings suggest a route for development of SSL-based devices such as high-frequency oscillators with ultrahigh quality factors and optomechanical switches, where retractable or oscillating mirrors are required.
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