| 51. |
- Barry, Antonia, et al.
(author)
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Investigating the effects of arginine methylation inhibitors on microdissected brain tumour biopsies maintained in a miniaturised perfusion system
- 2023
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In: Lab on a Chip. - 1473-0197 .- 1473-0189. ; 23:11, s. 2664-2682
-
Journal article (peer-reviewed)abstract
- Arginine methylation is a post-translational modification that consists of the transfer of one or two methyl (CH3) groups to arginine residues in proteins. Several types of arginine methylation occur, namely monomethylation, symmetric dimethylation and asymmetric dimethylation, which are catalysed by different protein arginine methyltransferases (PRMTs). Inhibitors of PRMTs have recently entered clinical trials to target several types of cancer, including gliomas (NCT04089449). People with glioblastoma (GBM), the most aggressive form of brain tumour, are among those with the poorest quality of life and likelihood of survival of anyone diagnosed with cancer. There is currently a lack of (pre)clinical research on the possible application of PRMT inhibitors to target brain tumours. Here, we set out to investigate the effects of clinically-relevant PRMT inhibitors on GBM biopsies. We present a new, low-cost, easy to fabricate perfusion device that can maintain GBM tissue in a viable condition for at least eight days post-surgical resection. The miniaturised perfusion device enables the treatment of GBM tissue with PRMT inhibitors ex vivo, and we observed a two-fold increase in apoptosis in treated samples compared to parallel control experiments. Mechanistically, we show thousands of differentially expressed genes after treatment, and changes in the type of arginine methylation of the RNA binding protein FUS that are consistent with hundreds of differential gene splicing events. This is the first time that cross-talk between different types of arginine methylation has been observed in clinical samples after treatment with PRMT inhibitors.
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| 52. |
- Beltran, Catherine, et al.
(author)
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Paleoenvironmental conditions for the development of calcareous nannofossil acme during the late Miocene in the eastern equatorial Pacific
- 2014
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In: Paleoceanography. - 0883-8305 .- 1944-9186. ; 29:3, s. 210-222
-
Journal article (peer-reviewed)abstract
- Repeated monospecific coccolithophore dominance intervals (acmes) of specimens belonging to the Noelaerhabdaceae familyincluding the genus Reticulofenestra and modern descendants Emiliania and Gephyrocapsaoccurred during the Neogene. Such acme was recognized during the late Miocene (similar to 8.6Ma), at a time of a major reorganization of nannofossil assemblages resulting in a worldwide temporary disappearance of larger forms of the genus Reticulofenestra (R. pseudoumbilicus) and the gradual recovery and dominance of its smaller forms (< 5 mu m). In this study we present a multiproxy investigation of late Miocene sediments from the east equatorial Pacific Integrated Ocean Drilling Program Site U1338 where small reticulofenestrid-type placoliths with a closed central areaknown as small Dictyococcites spp. (< 3 mu m)formed an acme. We report on oxygen and carbon stable isotope records of multispecies planktic calcite and alkenone-derived sea surface temperature. Our data indicate that, during this 100 kyr long acme, the east equatorial Pacific thermocline remained deep and stable. Local surface stratification state fails to explain this acme and thus contradicts the model-based hypothesis of a Southern Ocean high-latitude nutrient control of the surface waters in the east equatorial Pacific. Instead, our findings suggest that external forcing such as an extended period of low eccentricity may have created favorable conditions for the small Dictyococcites spp. growth. Key Points < list list-type=bulleted id=palo20081-list-0001> < list-item id=palo20081-li-0001> EEP thermocline deep during the late Miocene small Dictyococcites acme Low eccentricity favorable for the small Dictyococcites spp. growth
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| 53. |
- Beltran Jimenez, Jose, et al.
(author)
-
Coincident general relativity
- 2018
-
In: Physical Review D. - : American Physical Society. - 2470-0010 .- 2470-0029. ; 98:4
-
Journal article (peer-reviewed)abstract
- The metric-affine variational principle is applied to generate teleparallel and symmetric teleparallel theories of gravity. From the latter we discover an exceptional class which is consistent with a vanishing affine connection. Based on this remarkable property, this work proposes a simpler geometrical formulation of general relativity that is oblivious to the affine spacetime structure, thus fundamentally depriving gravity of any inertial character. The resulting theory is described by the Hilbert action purged from the boundary term and is more robustly underpinned by the spin-2 field theory, where an extra symmetry is now manifest, possibly related to the double-copy structure of the gravity amplitudes. This construction also provides a novel starting point for modified gravity theories, and the paper presents new and simple generalizations where analytical self-accelerating cosmological solutions arise naturally in the early-and late-time Universe.
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| 54. |
- Beltran Jimenez, Jose, et al.
(author)
-
Cosmology in f (Q) geometry
- 2020
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In: Physical Review D. - : American Physical Society (APS). - 1550-7998 .- 1550-2368. ; 101:10
-
Journal article (peer-reviewed)abstract
- The universal character of the gravitational interaction provided by the equivalence principle motivates a geometrical description of gravity. The standard formulation of general relativity a la Einstein attributes gravity to the spacetime curvature, to which we have grown accustomed. However, this perception has masked the fact that two alternative, though equivalent, formulations of general relativity in flat spacetimes exist, where gravity can be fully ascribed either to torsion or to nonmetricity. The latter allows a simpler geometrical formulation of general relativity that is oblivious to the affine spacetime structure. Generalizations along this line permit us to generate teleparallel and symmetric teleparallel theories of gravity with exceptional properties. In this work we explore modified gravity theories based on nonlinear extensions of the nonmetricity scalar. After presenting some general properties and briefly studying some interesting background cosmologies (including accelerating solutions with relevance for inflation and dark energy), we analyze the behavior of the cosmological perturbations. Tensor perturbations feature a rescaling of the corresponding Newton's constant, while vector perturbations do not contribute in the absence of vector sources. In the scalar sector we find two additional propagating modes, hinting that f(Q) theories introduce, at least, 2 additional degrees of freedom. These scalar modes disappear around maximally symmetric backgrounds because of the appearance of an accidental residual gauge symmetry corresponding to a restricted diffeomorphism. We finally discuss the potential strong coupling problems of these maximally symmetric backgrounds caused by the discontinuity in the number of propagating modes.
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| 55. |
- Beltran Jimenez, Jose, et al.
(author)
-
Teleparallel Palatini theories
- 2018
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In: Journal of Cosmology and Astroparticle Physics. - : Institute of Physics Publishing (IOPP). - 1475-7516. ; :8
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Journal article (peer-reviewed)abstract
- The Palatini formalism, which assumes the metric and the affine connection as independent variables, is developed for gravitational theories in flat geometries. We focus on two particularly interesting scenarios. First, we fix the connection to be metric compatible, as done in the usual teleparallel theories, but we follow a completely covariant approach by imposing the constraints with suitable Lagrange multipliers. For a general quadratic theory we show how torsion naturally propagates and we reproduce the Teleparallel Equivalent of General Relativity as a particular quadratic action that features an additional Lorentz symmetry. We then study the much less explored theories formulated in a geometry with neither curvature nor torsion, so that all the geometrical information is encoded in the non-metricity. We discuss how this geometrical framework leads to a purely inertial connection that can thus be completely removed by a coordinate gauge choice, the coincident gauge. From the quadratic theory we recover a simpler formulation of General Relativity in the form of the Einstein action, which enjoys an enhanced symmetry that reduces to a second linearised diffeomorphism at linear order. More general theories in both geometries can be formulated consistently by taking into account the inertial connection and the associated additional degrees of freedom. As immediate applications, the new cosmological equations and their Newtonian limit are considered, where the role of the lapse in the consistency of the equations is clarified, and the Schwarzschild black hole entropy is computed by evaluating the corresponding Euclidean action. We discuss how the boundary terms in the usual formulation of General Relativity are related to different choices of coordinates in its coincident version and show that in isotropic coordinates the Euclidean action is finite without the need to introduce boundary or normalisation terms. Finally, we discuss the double-copy structure of the gravity amplitudes and the bootstrapping of gravity within the framework of coincident General Relativity.
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| 56. |
- Beltran Jimenez, Jose, et al.
(author)
-
The canonical frame of purified gravity
- 2019
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In: International Journal of Modern Physics D. - : World Scientific Publishing Co. Pte Ltd. - 0218-2718. ; 28:14
-
Journal article (peer-reviewed)abstract
- In the recently introduced gauge theory of translations, dubbed Coincident General Relativity (CGR), gravity is described with neither torsion nor curvature in the spacetime affine geometry. The action of the theory enjoys an enhanced symmetry and avoids the second derivatives that appear in the conventional Einstein-Hilbert action. While it implies the equivalent classical dynamics, the improved action principle can make a difference in considerations of energetics, thermodynamics and quantum theory. This paper reports on possible progress in those three aspects of gravity theory. In the so-called purified gravity, (1) energy-momentum is described locally by a conserved, symmetric tensor, (2) the Euclidean path integral is convergent without the addition of boundary or regulating terms and (3) it is possible to identify a canonical frame for quantization.
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| 57. |
- Beltran Jimenez, Jose, et al.
(author)
-
The Geometrical Trinity of Gravity
- 2019
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In: Universe. - : MDPI. - 2218-1997. ; 5:7
-
Journal article (peer-reviewed)abstract
- The geometrical nature of gravity emerges from the universality dictated by the equivalence principle. In the usual formulation of General Relativity, the geometrisation of the gravitational interaction is performed in terms of the spacetime curvature, which is now the standard interpretation of gravity. However, this is not the only possibility. In these notes, we discuss two alternative, though equivalent, formulations of General Relativity in flat spacetimes, in which gravity is fully ascribed either to torsion or to non-metricity, thus putting forward the existence of three seemingly unrelated representations of the same underlying theory. Based on these three alternative formulations of General Relativity, we then discuss some extensions.
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| 58. |
- Bolli, P., et al.
(author)
-
An international survey of front-end receivers and observing performance of telescopes for radio astronomy
- 2019
-
In: Publications of the Astronomical Society of the Pacific. - : IOP Publishing. - 0004-6280 .- 1538-3873. ; 131:1002
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Journal article (peer-reviewed)abstract
- © 2019. The Astronomical Society of the Pacific. This paper presents a survey of microwave front-end receivers installed at radio telescopes throughout the world. This unprecedented analysis was conducted as part of a review of front-end developments for Italian radio telescopes, initiated by the Italian National Institute for Astrophysics in 2016. Fifteen international radio telescopes have been selected to be representative of the instrumentation used for radio astronomical observations in the frequency domain from 300 MHz to 116 GHz. A comprehensive description of the existing receivers is presented and their characteristics are compared and discussed. The observing performances of the complete receiving chains are also presented. An overview of ongoing developments illustrates and anticipates future trends in front-end projects to meet the most ambitious scientific research goals.
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| 59. |
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| 60. |
- Evans, Matthew L., et al.
(author)
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Developments and applications of the OPTIMADE API for materials discovery, design, and data exchange
- 2024
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In: Digital Discovery. - : ROYAL SOC CHEMISTRY. - 2635-098X.
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Journal article (peer-reviewed)abstract
- The Open Databases Integration for Materials Design (OPTIMADE) application programming interface (API) empowers users with holistic access to a growing federation of databases, enhancing the accessibility and discoverability of materials and chemical data. Since the first release of the OPTIMADE specification (v1.0), the API has undergone significant development, leading to the v1.2 release, and has underpinned multiple scientific studies. In this work, we highlight the latest features of the API format, accompanying software tools, and provide an update on the implementation of OPTIMADE in contributing materials databases. We end by providing several use cases that demonstrate the utility of the OPTIMADE API in materials research that continue to drive its ongoing development. The Open Databases Integration for Materials Design (OPTIMADE) application programming interface (API) empowers users with holistic access to a federation of databases, enhancing the accessibility and discoverability of materials and chemical data.
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