9,015 research outputs found

    Deep generative modeling for single-cell transcriptomics.

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    Single-cell transcriptome measurements can reveal unexplored biological diversity, but they suffer from technical noise and bias that must be modeled to account for the resulting uncertainty in downstream analyses. Here we introduce single-cell variational inference (scVI), a ready-to-use scalable framework for the probabilistic representation and analysis of gene expression in single cells ( https://github.com/YosefLab/scVI ). scVI uses stochastic optimization and deep neural networks to aggregate information across similar cells and genes and to approximate the distributions that underlie observed expression values, while accounting for batch effects and limited sensitivity. We used scVI for a range of fundamental analysis tasks including batch correction, visualization, clustering, and differential expression, and achieved high accuracy for each task

    Modeling the Dust Properties of z ~ 6 Quasars with ART^2 -- All-wavelength Radiative Transfer with Adaptive Refinement Tree

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    The detection of large quantities of dust in z ~ 6 quasars by infrared and radio surveys presents puzzles for the formation and evolution of dust in these early systems. Previously (Li et al. 2007), we showed that luminous quasars at z > 6 can form through hierarchical mergers of gas-rich galaxies. Here, we calculate the dust properties of simulated quasars and their progenitors using a three-dimensional Monte Carlo radiative transfer code, ART^2 -- All-wavelength Radiative Transfer with Adaptive Refinement Tree. ART^2 incorporates a radiative equilibrium algorithm for dust emission, an adaptive grid for inhomogeneous density, a multiphase model for the ISM, and a supernova-origin dust model. We reproduce the SED and dust properties of SDSS J1148+5251, and find that the infrared emission are closely associated with the formation and evolution of the quasar host. The system evolves from a cold to a warm ULIRG owing to heating and feedback from stars and AGN. Furthermore, the AGN has significant implications for the interpretation of observation of the hosts. Our results suggest that vigorous star formation in merging progenitors is necessary to reproduce the observed dust properties of z~6 quasars, supporting a merger-driven origin for luminous quasars at high redshifts and the starburst-to-quasar evolutionary hypothesis. (Abridged)Comment: 26 pages, 22 figures, accepted by ApJ. Version with full resolution images is available at http://www.cfa.harvard.edu/~yxli/ARTDUST/astroph0706.3706.pd

    Tumor-Infiltrating Lymphocytes in the Tumor Microenvironment of Laryngeal Squamous Cell Carcinoma:Systematic Review and Meta-Analysis

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    The presence of tumor-infiltrating lymphocytes (TIL) in the tumor microenvironment has been demonstrated to be of prognostic value in various cancers. In this systematic review and meta-analysis, we investigated the prognostic value of TIL in laryngeal squamous cell carcinoma (LSCC). We performed a systematic search in PubMed for publications that investigated the prognostic value of TIL in LSCC. A meta-analysis was performed including all studies assessing the association between TIL counts in hematoxylin-eosin (HE)-stained sections, for CD8+ and/or CD3+/CD4+ TIL and overall survival (OS) or disease-free survival (DFS). The pooled meta-analysis showed a favorable prognostic role for stromal TIL in HE sections for OS (HR 0.57, 95% CI 0.36-0.91, p = 0.02), and for DFS (HR 0.56, 95% CI 0.34-0.94, p = 0.03). High CD8+ TIL were associated with a prolonged OS (HR 0.62, 95% CI 0.4-0.97, p = 0.04) and DFS (HR 0.73, 95% CI 0.34-0.94, p = 0.002). High CD3+/CD4+ TIL demonstrated improved OS (HR 0.32, 95% CI 0.16-0.9, p = 0.03) and DFS (HR 0.23, 95% CI 0.10-0.53, p = 0.0005). This meta-analysis confirmed the favorable prognostic significance of TIL in LSCC. High stromal TIL evaluated in HE sections and intra-tumoral and stromal CD3+, CD4+ and/or CD8+ TIL might predict a better clinical outcome

    The Kondo Effect in Non-Equilibrium Quantum Dots: Perturbative Renormalization Group

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    While the properties of the Kondo model in equilibrium are very well understood, much less is known for Kondo systems out of equilibrium. We study the properties of a quantum dot in the Kondo regime, when a large bias voltage V and/or a large magnetic field B is applied. Using the perturbative renormalization group generalized to stationary nonequilibrium situations, we calculate renormalized couplings, keeping their important energy dependence. We show that in a magnetic field the spin occupation of the quantum dot is non-thermal, being controlled by V and B in a complex way to be calculated by solving a quantum Boltzmann equation. We find that the well-known suppression of the Kondo effect at finite V>>T_K (Kondo temperature) is caused by inelastic dephasing processes induced by the current through the dot. We calculate the corresponding decoherence rate, which serves to cut off the RG flow usually well inside the perturbative regime (with possible exceptions). As a consequence, the differential conductance, the local magnetization, the spin relaxation rates and the local spectral function may be calculated for large V,B >> T_K in a controlled way.Comment: 9 pages, invited paper for a special edition of JPSJ "Kondo Effect -- 40 Years after the Discovery", some typos correcte

    Exoplanet Diversity in the Era of Space-based Direct Imaging Missions

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    This whitepaper discusses the diversity of exoplanets that could be detected by future observations, so that comparative exoplanetology can be performed in the upcoming era of large space-based flagship missions. The primary focus will be on characterizing Earth-like worlds around Sun-like stars. However, we will also be able to characterize companion planets in the system simultaneously. This will not only provide a contextual picture with regards to our Solar system, but also presents a unique opportunity to observe size dependent planetary atmospheres at different orbital distances. We propose a preliminary scheme based on chemical behavior of gases and condensates in a planet's atmosphere that classifies them with respect to planetary radius and incident stellar flux.Comment: A white paper submitted to the National Academy of Sciences Exoplanet Science Strateg

    IRX-2, a Novel Immunotherapeutic, Enhances Functions of Human Dendritic Cells

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    Background: In a recent phase II clinical trial for HNSCC patients, IRX-2, a cell-derived biologic, promoted T-cell infiltration into the tumor and prolonged overall survival. Mechanisms responsible for these IRX-2-mediated effects are unknown. We hypothesized that IRX-2 enhanced tumor antigen-(TA)-specific immunity by up-regulating functions of dendritic cells (DC). Methodology/Principal Findings: Monocyte-derived DC obtained from 18 HNSCC patients and 12 healthy donors were matured using IRX-2 or a mix of TNF-α, IL-1β and IL-6 ("conv. mix"). Multicolor flow cytometry was used to study the DC phenotype and antigen processing machinery (APM) component expression. ELISPOT and cytotoxicity assays were used to evaluate tumor-reactive cytotoxic T lymphocytes (CTL). IL-12p70 and IL-10 production by DC was measured by Luminex® and DC migration toward CCL21 was tested in transwell migration assays. IRX-2-matured DC functions were compared with those of conv. mix-matured DC. IRX-2-matured DC expressed higher levels (p<0.05) of CD11c, CD40, CCR7 as well as LMP2, TAP1, TAP2 and tapasin than conv. mix-matured DC. IRX-2-matured DC migrated significantly better towards CCL21, produced more IL-12p70 and had a higher IL12p70/IL-10 ratio than conv. mix-matured DC (p<0.05 for all). IRX-2-matured DC carried a higher density of tumor antigen-derived peptides, and CTL primed with these DC mediated higher cytotoxicity against tumor targets (p<0.05) compared to the conv. mix-matured DC. Conclusion: Excellent ability of IRX-2 to induce ex vivo DC maturation in HNSCC patients explains, in part, its clinical benefits and emphasizes its utility in ex vivo maturation of DC generated for therapy. © 2013 Schilling et al

    Study of the Effect of Mold Corner Shape on the Initial Solidification Behavior of Molten Steel Using Mold Simulator

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    The chamfered mold with a typical corner shape (angle between the chamfered face and hot face is 45 deg) was applied to the mold simulator study in this paper, and the results were compared with the previous results from a well-developed right-angle mold simulator system. The results suggested that the designed chamfered structure would increase the thermal resistance and weaken the two-dimensional heat transfer around the mold corner, causing the homogeneity of the mold surface temperatures and heat fluxes. In addition, the chamfered structure can decrease the fluctuation of the steel level and the liquid slag flow around the meniscus at mold corner. The cooling intensities at different longitudinal sections of shell are close to each other due to the similar time-average solidification factors, which are 2.392 mm/s1/2 (section A-A: chamfered center), 2.372 mm/s1/2 (section B-B: 135 deg corner), and 2.380 mm/s1/2 (section D-D: face), respectively. For the same oscillation mark (OM), the heights of OM roots at different positions (profile L1 (face), profile L2 (135 deg corner), and profile L3 (chamfered center)) are very close to each other. The average value of height difference (HD) between two OMs roots for L1 and L2 is 0.22 mm, and for L2 and L3 is 0.38 mm. Finally, with the help of metallographic examination, the shapes of different hooks were also discussed

    Optical techniques for 3D surface reconstruction in computer-assisted laparoscopic surgery

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    One of the main challenges for computer-assisted surgery (CAS) is to determine the intra-opera- tive morphology and motion of soft-tissues. This information is prerequisite to the registration of multi-modal patient-specific data for enhancing the surgeon’s navigation capabilites by observ- ing beyond exposed tissue surfaces and for providing intelligent control of robotic-assisted in- struments. In minimally invasive surgery (MIS), optical techniques are an increasingly attractive approach for in vivo 3D reconstruction of the soft-tissue surface geometry. This paper reviews the state-of-the-art methods for optical intra-operative 3D reconstruction in laparoscopic surgery and discusses the technical challenges and future perspectives towards clinical translation. With the recent paradigm shift of surgical practice towards MIS and new developments in 3D opti- cal imaging, this is a timely discussion about technologies that could facilitate complex CAS procedures in dynamic and deformable anatomical regions
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