95232 research outputs found

    Glioblastoma stem cells express non-canonical proteins and exclusive mesenchymal-like or non-mesenchymal-like protein signatures

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    Glioblastoma (GBM) cancer stem cells (GSCs) contribute to GBM's origin, recurrence, and resistance to treatment. However, the understanding of how mRNA expression patterns of GBM subtypes are reflected at global proteome level in GSCs is limited. To characterize protein expression in GSCs, we performed in-depth proteogenomic analysis of patient-derived GSCs by RNA-sequencing and mass-spectrometry. We quantified > 10 000 proteins in two independent GSC panels and propose a GSC-associated proteomic signature characterizing two distinct phenotypic conditions; one defined by proteins upregulated in proneural and classical GSCs (GPC-like), and another by proteins upregulated in mesenchymal GSCs (GM-like). The GM-like protein set in GBM tissue was associated with necrosis, recurrence, and worse overall survival. Through proteogenomics, we discovered 252 non-canonical peptides in the GSCs, i.e., protein sequences that are variant or derive from genome regions previously considered non-protein-coding, including variants of the heterogeneous ribonucleoproteins implicated in RNA splicing. In summary, GSCs express two protein sets that have an inverse association with clinical outcomes in GBM. The discovery of non-canonical protein sequences questions existing gene models and pinpoints new protein targets for research in GBM

    Early Release Science of the exoplanet WASP-39b with JWST NIRCam

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    Measuring the metallicity and carbon-to-oxygen (C/O) ratio in exoplanet atmospheres is a fundamental step towards constraining the dominant chemical processes at work and, if in equilibrium, revealing planet formation histories. Transmission spectroscopy (for example, refs. 1,2) provides the necessary means by constraining the abundances of oxygen- and carbon-bearing species; however, this requires broad wavelength coverage, moderate spectral resolution and high precision, which, together, are not achievable with previous observatories. Now that JWST has commenced science operations, we are able to observe exoplanets at previously uncharted wavelengths and spectral resolutions. Here we report time-series observations of the transiting exoplanet WASP-39b using JWST's Near InfraRed Camera (NIRCam). The long-wavelength spectroscopic and short-wavelength photometric light curves span 2.0-4.0 micrometres, exhibit minimal systematics and reveal well defined molecular absorption features in the planet's spectrum. Specifically, we detect gaseous water in the atmosphere and place an upper limit on the abundance of methane. The otherwise prominent carbon dioxide feature at 2.8 micrometres is largely masked by water. The best-fit chemical equilibrium models favour an atmospheric metallicity of 1-100-times solar (that is, an enrichment of elements heavier than helium relative to the Sun) and a substellar C/O ratio. The inferred high metallicity and low C/O ratio may indicate significant accretion of solid materials during planet formation (for example, refs. 3,4,) or disequilibrium processes in the upper atmosphere (for example, refs. 5,6).Astrophysics - Instrumentation and Methods for AstrophysicsAstrophysics - Solar and Stellar Astrophysic

    Efficient wireless power transfer via magnetic resonance coupling using automated impedance matching circuit

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    In this paper, an automated impedance matching circuit is proposed to match the impedance of the transmit and receive resonators for optimum wireless power transfer (WPT). This is achieved using a 2D open-circuited spiral antenna with magnetic resonance coupling in the low-frequency ISM band at 13.56 MHz. The proposed WPT can be adopted for a wide range of commercial applications, from electric vehicles to consumer electronics, such as tablets and smartphones. The results confirm a power transfer efficiency between the transmit and receive resonant circuits of 92%, with this efficiency being sensitive to the degree of coupling between the coupled pair of resonators

    In BCR-ABL1 Positive B-Cell Acute Lymphoblastic Leukemia, Steroid Therapy Induces Hypofibrinogenemia

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    Hypofibrinogenemia (HF) in adult acute lymphoblastic leukemia (ALL) of B lineage is uncommon and mostly associated with asparaginase (ASP) delivery. Since we noticed a significant reduction in fibrinogen (FBG) plasma levels even before the first ASP dose, we aim to assess the levels of FBG during induction treatment and explore if the FBG fall correlated with therapies other than asparaginase and/or specific leukemia biological features. We retrospectively analyzed FBG levels in 115 patients with B-ALL. In 74 (64%) out of 115 patients FBG decline occurred during the steroid prephase. In univariate analysis, such a steroid-related HF was significantly associated with BCR-ABL1 rearrangement (p = 0.00158). None of those experiencing HF had significant modifications of liver function tests during induction treatment. Our retrospective study suggests that in B-ALL, steroid therapy can also induce HF and that such an event is preferentially observed in patients carrying BCR-ABL1 rearrangements. The pathogenesis of this phenomenon is still unclear. We attempt to explain it by applying the International Society of Thrombosis and Hemostasis-Disseminated Intravascular Coagulation score (ISTH-DIC score); nonetheless additional studies are needed to clarify further the mechanisms of HF in this subset of patients

    Protecting consumers from collusive prices due to AI

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    The efficacy of a market system is rooted in competition. In striving to attract customers, firms are led to charge lower prices and deliver better products and services. Nothing more fundamentally undermines this process than collusion, when firms agree not to compete with one another and consequently consumers are harmed by higher prices. Collusion is generally condemned by economists and policymakers and is unlawful in almost all countries. But the increasing delegation of price-setting to algorithms (1) has the potential for opening a backdoor through which firms could collude lawfully (2). Such algorithmic collusion is when artificial intelligence (AI) algorithms learn to adopt collusive pricing rules without human intervention, oversight, or even knowledge. This possibility poses a challenge for policy. To meet this challenge, we propose below a direction for policy change and call for combined efforts of computer scientists, economists, and legal scholars to operationalize the proposed change

    Anosov diffeomorphisms, anisotropic BV spaces and regularity of foliations

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    Given any smooth Anosov map, we construct a Banach space on which the associated transfer operator is quasi-compact. The peculiarity of such a space is that, in the case of expanding maps, it reduces exactly to the usual space of functions of bounded variation which has proved to be particularly successful in studying the statistical properties of piecewise expanding maps. Our approach is based on a new method of studying the absolute continuity of foliations, which provides new information that could prove useful in treating hyperbolic systems with singularities

    Quark masses using twisted mass fermion gauge ensembles

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    We present a calculation of the up, down, strange, and charm quark masses performed within the lattice QCD framework. We use the twisted-mass fermion action and carry out simulations that include in the sea two light mass-degenerate quarks, as well as the strange and charm quarks. In the analysis, we use gauge ensembles simulated at three values of the lattice spacing and with light quarks that correspond to pion masses in the range from 350 MeV to the physical value, while the strange and charm quark masses are tuned approximately to their physical values. We use several quantities to set the scale in order to check for finite lattice spacing effects, and in the continuum limit, we get compatible results. The quark mass renormalization is carried out nonperturbatively using the (modified) Regularization Independent Momentum Subtraction (RI′−MOM) method converted into the ¯¯¯¯¯¯MS scheme. For the determination of the quark masses, we use physical observables from both the meson and the baryon sectors, obtaining mud=3.636(66)( +60−57)  MeV and ms=98.7(2.4)( +4.0−3.2)  MeV in the ¯¯¯¯¯¯MS(2  GeV) scheme and mc=1036(17)( +15−8)  MeV in the ¯¯¯¯¯¯MS(3  GeV) scheme, where the first errors are statistical and the second ones are combinations of systematic errors. For the quark mass ratios, we get ms/mud=27.17(32)( +56−38) and mc/ms=11.48(12)( +25−19)

    Oxidative Stress in the Pathogenesis of Aorta Diseases as a Source of Potential Biomarkers and Therapeutic Targets, with a Particular Focus on Ascending Aorta Aneurysms

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    : Aorta diseases, such as ascending aorta aneurysm (AsAA), are complex pathologies, currently defined as inflammatory diseases with a strong genetic susceptibility. They are difficult to manage, being insidious and silent pathologies whose diagnosis is based only on imaging data. No diagnostic and prognostic biomarkers or markers of outcome have been known until now. Thus, their identification is imperative. Certainly, a deep understanding of the mechanisms and pathways involved in their pathogenesis might help in such research. Recently, the key role of oxidative stress (OS) on the pathophysiology of aorta disease has emerged. Here, we describe and discuss these aspects by revealing some OS pathways as potential biomarkers, their underlying limitations, and potential solutions and approaches, as well as some potential treatments

    Giardia duodenalis in Wildlife: Exploring Genotype Diversity in Italy and across Europe

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    Fragmented data are so far available on genotype diversity of G. duodenalis in wildlife in different countries in Europe, in particular, in Italy. In the present study, G. duodenalis sequences obtained from different Italian wild animals [12 porcupines (Hystrix cristata), 4 wild boars (Sus scrofa), 1 wolf (Canis lupus italicus), 6 Alpine chamois (Rupicapra rupicapra rupicapra)] were compared with those available from wild host species in Europe to add new data on the geographic distribution of Giardia assemblages/sub-assemblages and their transmission patterns among natural hosts. Thirty-eight sequences were obtained by MLG analysis (SSU-rRNA, bg, gdh, and tpi genes) and subsequently compared by phylogenetic and network analyses with those from wild species monitored in the last decades in Europe. The results revealed the presence of potentially zoonotic (A-AI, A-AII from wild boar; B from porcupine) and host-adapted (D from wolf; E, A-AIII from chamois) assemblages and sub-assemblages and represent the first report for Italian wild boar. The analysis did not find any evidence of spatial or host segregation for specific genetic variants, mostly shared between different hosts from different European countries. However, conflicting evidence was found in genotypic assignment, advocating for data improvement and new genomic approaches


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