Metastasis frequently develops years after the removal of a primary tumor, from a minority of disseminated cancer cells that survived as latent entities through unknown mechanisms. We isolated latency competent cancer (LCC) cells from early-stage human lung and breast carcinoma cell lines and defined the mechanisms that suppress outgrowth, support long-term survival, and maintain tumor-initiating potential in these cells during the latent metastasis stage. LCC cells show stem cell-like characteristics and express Sox2 and Sox9 transcription factors, which are essential for their survival in host organs under immune surveillance and for metastatic outgrowth under permissive conditions. Through expression of the WNT inhibitor DKK1, LCC cells self-impose a slow-cycling state with broad downregulation of ULBP ligands for NK cells and evasion of NK cell-mediated clearance. By expressing a Sox-dependent stem-like state and actively silencing WNT signaling, LCC cells can enter quiescence and evade innate immunity to remain latent for extended periods.

Metastasis-initiating cells with stem-like properties drive cancer lethality, yet their origins and relationship to primary-tumorinitiating stem cells are not known. We show that L1CAM + cells in human colorectal cancer (CRC) have metastasis-initiating capacity, and we define their relationship to tissue regeneration. L1CAM is not expressed in the homeostatic intestinal epithelium, but is induced and required for epithelial regeneration following colitis and in CRC organoid growth. By using human tissues and mouse models, we show that L1CAM is dispensable for adenoma initiation but required for orthotopic carcinoma propagation, liver metastatic colonization and chemoresistance. L1CAM high cells partially overlap with LGR5 high stem-like cells in human CRC organoids. Disruption of intercellular epithelial contacts causes E-cadherin-REST transcriptional derepression of L1CAM, switching chemoresistant CRC progenitors from an L1CAM low to an L1CAM high state. Thus, L1CAM dependency emerges in regenerative intestinal cells when epithelial integrity is lost, a phenotype of wound healing deployed in metastasisinitiating cells.

As(III) specifically interacts with an arsenic-binding aptamer to form an As(III)-aptamer complex, so that the following cationic polymer can aggregate gold nanoparticles (AuNPs) and cause a remarkable change in color, which enables the colorimetric detection of As(III) with high selectivity and a detection limit of 5.3 ppb.

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A new criterion for the direct initiation of cylindrical or spherical detonations by a localized energy source is presented. The analysis is based on nonlinear curvature effects on the detonation structure. These effects are first studied in a quasi-steady-state approximation valid for a characteristic timescale of evolution much larger than the reaction timescale. Analytical results for the square-wave model and numerical results for an Arrhenius law of the quasi-steady equations exhibit two branches of solutions with a C-shaped curve and a critical radius below which generalized Chapman–Jouguet (CJ) solutions cannot exist. For a sufficiently large activation energy this critical radius is much larger than the thickness of the planar CJ detonation front (typically 300 times larger at ordinary conditions) which is the only intrinsic lengthscale in the problem. Then, the initiation of gaseous detonations by an ideal point energy source is investigated in cylindrical and spherical geometries for a one-step irreversible reaction. Direct numerical simulations show that the upper branch of quasi-steady solutions acts as an attractor of the unsteady blast waves originating from the energy source. The critical source energy, which is associated with the critical point of the quasi-steady solutions, corresponds approximately to the boundary of the basin of attraction. For initiation energy smaller than the critical value, the detonation initiation fails, the strong detonation which is initially formed decays to a weak shock wave. A successful initiation of the detonation requires a larger energy source. Transient phenomena which are associated with the intrinsic instability of the quasi-steady detonations branch develop in the induction timescale and may induce additional mechanisms close to the critical condition. In conditions of stable or weakly unstable planar detonations, these unsteady phenomena are important only in the vicinity of the critical conditions. The criterion of initiation derived in this paper works to a good approximation and exhibits the huge numerical factor, 106–108, which has been experimentally observed in the critical value of the initiation energy.