Advanced metastatic cancer poses utmost clinical challenges and may present molecular and cellular features distinct from an early-stage cancer. Herein, we present single-cell transcriptome profiling of metastatic lung adenocarcinoma, the most prevalent histological lung cancer type diagnosed at stage IV in over 40% of all cases. From 208,506 cells populating the normal tissues or early to metastatic stage cancer in 44 patients, we identify a cancer cell subtype deviating from the normal differentiation trajectory and dominating the metastatic stage. In all stages, the stromal and immune cell dynamics reveal ontological and functional changes that create a pro-tumoral and immunosuppressive microenvironment. Normal resident myeloid cell populations are gradually replaced with monocyte-derived macrophages and dendritic cells, along with T-cell exhaustion. This extensive single-cell analysis enhances our understanding of molecular and cellular dynamics in metastatic lung cancer and reveals potential diagnostic and therapeutic targets in cancer-microenvironment interactions.

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An eddy-viscosity based, subgrid-scale model for Large Eddy Simulations is derived from the analysis of the singular values of the resolved velocity gradient tensor. The proposed σ-model has by construction the property to automatically vanish as soon as the resolved field is either two-dimensional or two-component, including the pure shear and solid rotation cases. In addition, the model generates no subgrid-scale viscosity when the resolved scales are in pure axisymmetric or isotropic contraction/expansion. At last, it is shown analytically that it has the appropriate cubic behavior in the vicinity of solid boundaries without requiring any ad-hoc treatment. Results for two classical test cases (decaying isotropic turbulence and periodic channel flow) obtained from three different solvers with a variety of numerics (finite elements, finite differences or spectral methods) are presented to illustrate the potential of this model. The results obtained with the proposed model are systematically equivalent or slightly better than the results from the Dynamic Smagorinsky model. Still, the σ-model has a low computational cost, is easy to implement and does not require any homogeneous direction in space or time. It is thus anticipated that it has a high potential for the computation of non-homogeneous, wall-bounded flows.

The polarization of prompt J/ at the Fermilab Tevatron is calculated within the nonrelativistic QCD factorization framework. The contribution from radiative decays of P-wave charmonium states decreases, but does not eliminate, the transverse polarization at large transverse momentum. The angular distribution parameter ␣ for leptonic decays of the J/ is predicted to increase from near 0 at p T ϭ5 GeV to about 0.5 at p T ϭ20 GeV. The prediction is consistent with measurements by the CDF Collaboration at intermediate values of p T , but disagrees by about 3 standard deviations at the largest values of p T measured.PACS number͑s͒: 13.85.Ϫt, 13.85.Ni, 14.40.Gx The production of charmonium and bottomonium states in high-energy collisions probes both the hard-scattering parton processes that create heavy quark-antiquark (QQ ) pairs and the hadronization process that transforms them into colorsinglet bound states. One particularly sensitive probe is the polarization of the J PC ϭ1 ϪϪ quarkonium states. The nonrelativistic QCD ͑NRQCD͒ factorization approach to inclusive quarkonium production ͓1͔ makes the remarkable prediction that in hadron collisions these states should be transversely polarized at sufficiently large transverse momentum (p T ) ͓2͔. Recent measurements at the Tevatron by the Collider Detector at Fermilab ͑CDF͒ Collaboration seem to be in dramatic contradiction with this prediction ͓3͔.As first pointed out by Cho and Wise ͓2͔, the prediction of transverse polarization for 1 ϪϪ states at large p T follows from three simple features of the dynamics of massless partons and heavy quarks. First, the inclusive production of quarkonium ͑or any other hadron͒ at sufficiently large p T is dominated by fragmentation. In pp collisions at the Tevatron, the dominant contribution to the charmonium production rate at large p T comes from gluon fragmentation ͓4͔. The gluon is almost on shell and thus predominantly transversely polarized. Second, a QQ pair with small relative momentum created by the virtual gluon is, at leading order in ␣ s , in a color-octet 3 S 1 state ͓5͔ with the same transverse polarization as the gluon. Third, the spin symmetry of nonrelativistic heavy quarks implies the suppression of spin-flip transitions in the binding of the QQ pair into quarkonium. Thus, 1 ϪϪ states should have a large transverse polarization at sufficiently large p T . A convenient measure of the polarization is the variable ␣ϭ( T Ϫ2 L )/( T ϩ2 L ), where T and L are the transverse and longitudinal components of the cross section, respectively. Beneke and Rothstein studied the dominant fragmentation mechanisms for L ͓6͔, and concluded that, at sufficiently large p T , ␣ should be in the range 0.5-0.8.For charmonium production at the Tevatron, fragmentation does not yet dominate for most of the p T range that is experimentally accessible. In order to study the onset of the polarization effect, it is necessary to take into account the fusion contributions from parton processes i j→cc ϩk. Quantitative calculations of the polari...

We present two methods for computing dimensionally-regulated NRQCD heavy-quarkonium matrix elements that are related to the second derivative of the heavy-quarkonium wave function at the origin. The first method makes use of a hard-cutoff regulator as an intermediate step and requires knowledge only of the heavy-quarkonium wave function. It involves a significant cancellation that is an obstacle to achieving high numerical accuracy. The second method is more direct and yields a result that is identical to the Gremm-Kapustin relation, but it is limited to use in potential models. It can be generalized to the computation of matrix elements of higher order in the heavy-quark velocity and can be used to resum the contributions to decay and production rates that are associated with those matrix elements. We apply these methods to the Cornell potential model and compute a matrix element for the J/ψ state that appears in the leading relativistic correction to the production and decay of that state through the color-singlet quark-antiquark channel.