19 research outputs found

    The Quark Propagator from the Dyson-Schwinger Equations: I. the Chiral Solution

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    Within the framework of the Dyson-Schwinger equations in the axial gauge, we study the effect that non-perturbative glue has on the quark propagator. We show that Ward-Takahashi identities, combined with the requirement of matching perturbative QCD at high momentum transfer, guarantee the multiplicative renormalisability of the answer. Technically, the matching with perturbation theory is accomplished by the introduction of a transverse part to the quark-gluon vertex. We show that this transverse vertex is crucial for chiral symmetry breaking, and that massless solutions exist below a critical value of the strong coupling constant. Using the gluon propagator that we previously calculated, we obtain small corrections to the quark propagator, which keeps a pole at the origin in the chiral phase.Comment: 21 pages, 6 figures; McGill/94-24, SHEP 93/94-26 We generalise our results by showing that they are not sensitive to the specific choice that we make for the transverse vertex. We illustrate that fact in two new figure

    The immune landscape of cancer

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    We performed an extensive immunogenomic analysis of more than 10,000 tumors comprising 33 diverse cancer types by utilizing data compiled by TCGA. Across cancer types, we identified six immune subtypes—wound healing, IFN-γ dominant, inflammatory, lymphocyte depleted, immunologically quiet, and TGF-β dominant—characterized by differences in macrophage or lymphocyte signatures, Th1:Th2 cell ratio, extent of intratumoral heterogeneity, aneuploidy, extent of neoantigen load, overall cell proliferation, expression of immunomodulatory genes, and prognosis. Specific driver mutations correlated with lower (CTNNB1, NRAS, or IDH1) or higher (BRAF, TP53, or CASP8) leukocyte levels across all cancers. Multiple control modalities of the intracellular and extracellular networks (transcription, microRNAs, copy number, and epigenetic processes) were involved in tumor-immune cell interactions, both across and within immune subtypes. Our immunogenomics pipeline to characterize these heterogeneous tumors and the resulting data are intended to serve as a resource for future targeted studies to further advance the field

    The Immune Landscape of Cancer

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    We performed an extensive immunogenomic anal-ysis of more than 10,000 tumors comprising 33diverse cancer types by utilizing data compiled byTCGA. Across cancer types, we identified six im-mune subtypes\u2014wound healing, IFN-gdominant,inflammatory, lymphocyte depleted, immunologi-cally quiet, and TGF-bdominant\u2014characterized bydifferences in macrophage or lymphocyte signa-tures, Th1:Th2 cell ratio, extent of intratumoral het-erogeneity, aneuploidy, extent of neoantigen load,overall cell proliferation, expression of immunomod-ulatory genes, and prognosis. Specific drivermutations correlated with lower (CTNNB1,NRAS,orIDH1) or higher (BRAF,TP53,orCASP8) leukocytelevels across all cancers. Multiple control modalitiesof the intracellular and extracellular networks (tran-scription, microRNAs, copy number, and epigeneticprocesses) were involved in tumor-immune cell inter-actions, both across and within immune subtypes.Our immunogenomics pipeline to characterize theseheterogeneous tumors and the resulting data areintended to serve as a resource for future targetedstudies to further advance the field

    Nonperturbative propagators in axial gauge QCD

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    SIGLEAvailable from British Library Document Supply Centre-DSC:DXN017570 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

    Identification of an atypical etiological head and neck squamous carcinoma subtype featuring the CpG island methylator phenotype

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    Head and neck squamous cell carcinoma (HNSCC) is broadly classified into HNSCC associated with human papilloma virus (HPV) infection, and HPV negative HNSCC, which is typically smoking-related. A subset of HPV negative HNSCCs occur in patients without smoking history, however, and these etiologically ‘atypical’ HNSCCs disproportionately occur in the oral cavity, and in female patients, suggesting a distinct etiology. To investigate the determinants of clinical and molecular heterogeneity, we performed unsupervised clustering to classify 528 HNSCC patients from The Cancer Genome Atlas (TCGA) into putative intrinsic subtypes based on their profiles of epigenetically (DNA methylation) deregulated genes. HNSCCs clustered into five subtypes, including one HPV positive subtype, two smoking-related subtypes, and two atypical subtypes. One atypical subtype was particularly genomically stable, but featured widespread gene silencing associated with the ‘CpG island methylator phenotype’ (CIMP). Further distinguishing features of this ‘CIMP-Atypical’ subtype include an antiviral gene expression profile associated with pro-inflammatory M1 macrophages and CD8+ T cell infiltration, CASP8 mutations, and a well-differentiated state corresponding to normal SOX2 copy number and SOX2OT hypermethylation. We developed a gene expression classifier for the CIMP-Atypical subtype that could classify atypical disease features in two independent patient cohorts, demonstrating the reproducibility of this subtype. Taken together, these findings provide unprecedented evidence that atypical HNSCC is molecularly distinct, and postulates the CIMP-Atypical subtype as a distinct clinical entity that may be caused by chronic inflammation

    Reducing the Computational Complexity of Information Theoretic Approaches for Reconstructing Gene Regulatory Networks

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    Information theoretic approaches are increasingly being used for reconstructing regulatory networks from microarray data. These approaches start by computing the pairwise mutual information (MI) between all gene pairs. The resulting MI matrix is then manipulated to identify regulatory relationships. A barrier to these approaches is the time-consuming step of computing the MI matrix. We present a method to reduce this computation time. We apply spectral analysis to re-order the genes, so that genes that share regulatory relationships are more likely to be placed close to each other. Then, using a “sliding window” approach with appropriate window size and step size, we compute the MI for the genes within the sliding window, and the remainder is assumed to be zero. Using both simulated data and microarray data, we demonstrate that our method does not incur performance loss in regions of high-precision and low-recall, while the computational time is significantly lowered. The proposed method can be used with any method that relies on the mutual information to reconstruct networks

    Long-term outcomes after first-onset arrhythmia in Fontan physiology

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    Objectives: Patients living with a Fontan circulation are prone to develop arrhythmias. However, their prognostic impact has been seldom studied. As such, we aimed to determine the incidence and predictors of arrhythmias after the Fontan procedure and the long-term outcomes after the first onset of arrhythmias

    Size matters: finding the most informative set of window lengths

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    Event sequences often contain continuous variability at different levels. In other words, their properties and characteristics change at different rates, concurrently. For example, the sales of a product may slowly become more frequent over a period of several weeks, but there may be interesting variation within a week at the same time. To provide an accurate and robust “view” of such multi-level structural behavior, one needs to determine the appropriate levels of granularity for analyzing the underlying sequence. We introduce the novel problem of finding the best set of window lengths for analyzing discrete event sequences. We define suitable criteria for choosing window lengths and propose an efficient method to solve the problem. We give examples of tasks that demonstrate the applicability of the problem and present extensive experiments on both synthetic data and real data from two domains: text and DNA. We find that the optimal sets of window lengths themselves can provide new insight into the data, e.g., the burstiness of events affects the optimal window lengths for measuring the event frequencies
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