50 research outputs found

    class_sz I: Overview

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    class_sz is a versatile and robust code in C and Python that can compute theoretical predictions for a wide range of observables relevant to cross-survey science in the Stage IV era. The code is public at https://github.com/CLASS-SZ/class_sz along with a series of tutorial notebooks (https://github.com/CLASS-SZ/notebooks). It will be presented in full detail in paper II. Here we give a brief overview of key features and usage.Comment: to appear in Proc. of the mm Universe 2023 conference, Grenoble (France), June 2023, published by F. Mayet et al. (Eds), EPJ Web of conferences, EDP Science

    Altered processing of sensory stimuli in patients with migraine

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    Migraine is a cyclic disorder, in which functional and morphological brain changes fluctuate over time, culminating periodically in an attack. In the migrainous brain, temporal processing of external stimuli and sequential recruitment of neuronal networks are often dysfunctional. These changes reflect complex CNS dysfunction patterns. Assessment of multimodal evoked potentials and nociceptive reflex responses can reveal altered patterns of the brain's electrophysiological activity, thereby aiding our understanding of the pathophysiology of migraine. In this Review, we summarize the most important findings on temporal processing of evoked and reflex responses in migraine. Considering these data, we propose that thalamocortical dysrhythmia may be responsible for the altered synchronicity in migraine. To test this hypothesis in future research, electrophysiological recordings should be combined with neuroimaging studies so that the temporal patterns of sensory processing in patients with migraine can be correlated with the accompanying anatomical and functional changes

    A Measurement of Gravitational Lensing of the Cosmic Microwave Background Using SPT-3G 2018 Data

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    We present a measurement of gravitational lensing over 1500 deg2^2 of the Southern sky using SPT-3G temperature data at 95 and 150 GHz taken in 2018. The lensing amplitude relative to a fiducial Planck 2018 Λ\LambdaCDM cosmology is found to be 1.020±0.0601.020\pm0.060, excluding instrumental and astrophysical systematic uncertainties. We conduct extensive systematic and null tests to check the robustness of the lensing measurements, and report a minimum-variance combined lensing power spectrum over angular multipoles of 50<L<200050<L<2000, which we use to constrain cosmological models. When analyzed alone and jointly with primary cosmic microwave background (CMB) spectra within the Λ\LambdaCDM model, our lensing amplitude measurements are consistent with measurements from SPT-SZ, SPTpol, ACT, and Planck. Incorporating loose priors on the baryon density and other parameters including uncertainties on a foreground bias template, we obtain a 1σ1\sigma constraint on σ8Ωm0.25=0.595±0.026\sigma_8 \Omega_{\rm m}^{0.25}=0.595 \pm 0.026 using the SPT-3G 2018 lensing data alone, where σ8\sigma_8 is a common measure of the amplitude of structure today and Ωm\Omega_{\rm m} is the matter density parameter. Combining SPT-3G 2018 lensing measurements with baryon acoustic oscillation (BAO) data, we derive parameter constraints of σ8=0.810±0.033\sigma_8 = 0.810 \pm 0.033, S8σ8(Ωm/0.3)0.5=0.836±0.039S_8 \equiv \sigma_8(\Omega_{\rm m}/0.3)^{0.5}= 0.836 \pm 0.039, and Hubble constant H0=68.81.6+1.3H_0 =68.8^{+1.3}_{-1.6} km s1^{-1} Mpc1^{-1}. Using CMB anisotropy and lensing measurements from SPT-3G only, we provide independent constraints on the spatial curvature of ΩK=0.0140.026+0.023\Omega_{K} = 0.014^{+0.023}_{-0.026} (95% C.L.) and the dark energy density of ΩΛ=0.7220.026+0.031\Omega_\Lambda = 0.722^{+0.031}_{-0.026} (68% C.L.). When combining SPT-3G lensing data with SPT-3G CMB anisotropy and BAO data, we find an upper limit on the sum of the neutrino masses of mν<0.30\sum m_{\nu}< 0.30 eV (95% C.L.)

    Inflammatory Components of the Thyroid Cancer Microenvironment: An Avenue for Identification of Novel Biomarkers

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    The incidence of thyroid cancer in the United States is on the rise with an appreciably high disease recurrence rate of 20-30%. Anaplastic thyroid cancer (ATC), although rare in occurrence, is an aggressive form of cancer with limited treatment options and bleak cure rates. This chapter uses discussions of in vitro models that are representative of papillary, anaplastic, and follicular thyroid cancer to evaluate the crosstalk between specific cells of the tumor microenvironment (TME), which serves as a highly heterogeneous realm of signaling cascades and metabolism that are associated with tumorigenesis. The cellular constituents of the TME carry out varying characteristic immunomodulatory functions that are discussed throughout this chapter. The aforementioned cell types include cancer-associated fibroblasts (CAFs), endothelial cells (ECs), and cancer stem cells (CSCs), as well as specific immune cells, including natural killer (NK) cells, dendritic cells (DCs), mast cells, T regulatory (Treg) cells, CD8+ T cells, and tumor-associated macrophages (TAMs). TAM-mediated inflammation is associated with a poor prognosis of thyroid cancer, and the molecular basis of the cellular crosstalk between macrophages and thyroid cancer cells with respect to inducing a metastatic phenotype is not yet known. The dynamic nature of the physiological transition to pathological metastatic phenotypes when establishing the TME encompasses a wide range of characteristics that are further explored within this chapter, including the roles of somatic mutations and epigenetic alterations that drive the genetic heterogeneity of cancer cells, allowing for selective advantages that aid in their proliferation. Induction of these proliferating cells is typically accomplished through inflammatory induction, whereby chronic inflammation sets up a constant physiological state of inflammatory cell recruitment. The secretions of these inflammatory cells can alter the genetic makeup of proliferating cells, which can in turn, promote tumor growth.This chapter also presents an in-depth analysis of molecular interactions within the TME, including secretory cytokines and exosomes. Since the exosomal cargo of a cell is a reflection and fingerprint of the originating parental cells, the profiling of exosomal miRNA derived from thyroid cancer cells and macrophages in the TME may serve as an important step in biomarker discovery. Identification of a distinct set of tumor suppressive miRNAs downregulated in ATC-secreted exosomes indicates their role in the regulation of tumor suppressive genes that may increase the metastatic propensity of ATC. Additionally, the high expression of pro-inflammatory cytokines in studies looking at thyroid cancer and activated macrophage conditioned media suggests the existence of an inflammatory TME in thyroid cancer. New findings are suggestive of the presence of a metastatic niche in ATC tissues that is influenced by thyroid tumor microenvironment secretome-induced epithelial to mesenchymal transition (EMT), mediated by a reciprocal interaction between the pro-inflammatory M1 macrophages and the thyroid cancer cells. Thus, targeting the metastatic thyroid carcinoma microenvironment could offer potential therapeutic benefits and should be explored further in preclinical and translational models of human metastatic thyroid cancer

    class_sz I: Overview

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    International audienceclass_sz is a versatile and robust code in C and Python that can compute theoretical predictions for a wide range of observables relevant to cross-survey science in the Stage IV era. The code is public at https://github.com/CLASS-SZ/class_sz along with a series of tutorial notebooks (https://github.com/CLASS-SZ/notebooks). It will be presented in full detail in paper II. Here we give a brief overview of key features and usage

    class_sz I: Overview

    No full text
    International audienceclass_sz is a versatile and robust code in C and Python that can compute theoretical predictions for a wide range of observables relevant to cross-survey science in the Stage IV era. The code is public at https://github.com/CLASS-SZ/class_sz along with a series of tutorial notebooks (https://github.com/CLASS-SZ/notebooks). It will be presented in full detail in paper II. Here we give a brief overview of key features and usage

    CTLA-4 blockade drives loss of T<sub>reg</sub> stability in glycolysis-low tumours.

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    Limiting metabolic competition in the tumour microenvironment may increase the effectiveness of immunotherapy. Owing to its crucial role in the glucose metabolism of activated T cells, CD28 signalling has been proposed as a metabolic biosensor of T cells &lt;sup&gt;1&lt;/sup&gt; . By contrast, the engagement of CTLA-4 has been shown to downregulate T cell glycolysis &lt;sup&gt;1&lt;/sup&gt; . Here we investigate the effect of CTLA-4 blockade on the metabolic fitness of intra-tumour T cells in relation to the glycolytic capacity of tumour cells. We found that CTLA-4 blockade promotes metabolic fitness and the infiltration of immune cells, especially in glycolysis-low tumours. Accordingly, treatment with anti-CTLA-4 antibodies improved the therapeutic outcomes of mice bearing glycolysis-defective tumours. Notably, tumour-specific CD8 &lt;sup&gt;+&lt;/sup&gt; T cell responses correlated with phenotypic and functional destabilization of tumour-infiltrating regulatory T (T &lt;sub&gt;reg&lt;/sub&gt; ) cells towards IFNγ- and TNF-producing cells in glycolysis-defective tumours. By mimicking the highly and poorly glycolytic tumour microenvironments in vitro, we show that the effect of CTLA-4 blockade on the destabilization of T &lt;sub&gt;reg&lt;/sub&gt; cells is dependent on T &lt;sub&gt;reg&lt;/sub&gt; cell glycolysis and CD28 signalling. These findings indicate that decreasing tumour competition for glucose may facilitate the therapeutic activity of CTLA-4 blockade, thus supporting its combination with inhibitors of tumour glycolysis. Moreover, these results reveal a mechanism by which anti-CTLA-4 treatment interferes with T &lt;sub&gt;reg&lt;/sub&gt; cell function in the presence of glucose
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