1,721,001 research outputs found

    General null asymptotics and superrotation-compatible configuration spaces in d≥4

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    We address the problem of consistent Campiglia-Laddha superrotations in d > 4 by solving Bondi-Sachs gauge vacuum Einstein equations at the non-linear level with the most general boundary conditions preserving the null nature of infinity. We discuss how to generalise the boundary structure to make the configuration space compatible with supertanslation-like and superrotation-like transformations. One possibility requires the time-independent boundary metric on the cuts of I\mathscr{I} to be non-Einstein, while the other sticks to Einstein but time-dependent metrics. Both are novel features with respect to the four-dimensional case, where time-dependence of the two-dimensional cross-sectional metric is not required and the Einstein condition is trivially satisfied. Other cases are also discussed. These conditions imply that the configuration spaces are not asymptotically flat in the standard sense. We discuss the implications on the construction of the phase space and the relationship with soft scattering theorems. We show that in even spacetime dimensions, the initial data compatible with such asymptotic symmetries produce maximally polyhomogeneous expansions of the metric and we advance a potential interpretation of this structure in terms of AdS/CFT and realizations of Ricci-flat holography

    A DUEL OF FATES: THE ROLE OF KETONE BODIES IN HEART FAILURE WITH PRESERVED EJECTION FRACTION

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    RATIONALE: More than half of patients with heart failure have preserved ejection fraction (HFpEF), a deadly syndrome where pathophysiology is unclear and therapeutic options are limited. Cardiac metabolism derangements and the role of ketone bodies in HFpEF are still under investigation. OBJECTIVE: To explore, in a mouse model of cardiometabolic HFpEF, the dual fate of β-hydroxybutyrate (BOH) as both an energy substrate and a signaling molecule. METHODS AND RESULTS: In the “2-hit” HFpEF model, we observed a reduction in both glucose and BOH oxidative pathways. In HFpEF, BOH drove a significant increase in a novel post translational modification (PTM) called lysine (K) β-hydroxybutyrylation (Kbhb). Among the Kbhb targets, we identified 2 components of the malate-aspartate shuttle (MAS), namely the mitochondrial enzymes MDH2 and GOT2. Both MAS and GOT2 activity were increased in HFpEF. Modeling Kbhb in vitro, we described a role for this post translational modification in restoring GOT2 activity under hypoxia, arguably contributing to the modulation of MAS activity in HFpEF. CONCLUSIONS: In a mouse model of cardiometabolic HFpEF, glucose and ketone bodies oxidation are defective. BOH promotes Kbhb, a new PTM, arguably involved in the increase in MAS activity

    Aspects of Holography beyond AdS BMS superrotations in higher dimensions

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    A crucial role in the problem of four-dimensional asymptotically flat spacetime holographyis long believed to be played by the Bondi-Metzner-(van der Burg)-Sachs (BMS) asymptotic symmetry group. The discovery of deep relationships between such symmetries andgravitational infrared effects - pertrubative soft theorems and gravitational wave memories - has sparkled new interest in the problem. In this context, superrotations extendthe standard general relativistic definition of BMS group. While there has been somedebate on the extension of BMS to higher dimensions (d > 4), very little has been saidabout superrotations. In this thesis we initiate a systematic study of such structures. We provide evidence that consistency of superrotation Killing fields with a fully non-lineard > 4 gravitational configuration space requires different boundary conditions than thoseconsidered in literature. The first such evidence comes from cosmic (d − 3)-branes, whichare conjectured to be related to superrotations in d > 4 as a natural generalization ofthe relationship between cosmic strings in d = 4 and d = 4 superrotations. The generalboundary conditions may be taken to define asymptotically locally Minkowski spacetimes.The first part of the thesis recaps fundamentals of AdS/CFT - the most well known example of holographic duality - and the second moves to asymptotically flat spacetimes. Thereview material marks the conceptual and technical differences between AdS holographyand the attempts at flat holography. A recurring theme is that of variational principlesand asymptotic charges. Their mutual consistency is pivotal in dynamically realisingAdS/CFT. We take this requirement as the basis of asymptotically flat holography andthe analysis of the configuration space is fundamental to the construction of well-defined variational principles and the phase space

    BMS Symmetries and Holography: An Introductory Overview

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    A short overview of the role of BMS symmetries in various approaches to the flat spacetime holography problem is given. The relevance of BMS symmetries to the infrared structure of gravity is motivated and described at an introductory level with some details, but also the relation between the BMS group and the Carroll group is pointed out. The BMS group—and its proposed extensions—is reviewed in four-dimensional spacetimes in parallel with a discussion of the difficulties related to its definition in higher dimensional spacetimes. The Bondi–Sachs integration scheme is discussed with some details. A short discussion of canonical charges associated to the BMS transformations and the possible relation between superrotations and transition from asymptotically flat to locally asymptotically flat spacetimes is also summarised

    Cosmic branes and asymptotic structure

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    Superrotations of asymptotically flat spacetimes in four dimensions can be interpreted in terms of including cosmic strings within the phase space of allowed solutions. In this paper we explore the implications of the inclusion of cosmic branes on the asymptotic structure of vacuum spacetimes in dimension d > 4. We first show that only cosmic (d-3)-branes are Riemann flat in the neighbourhood of the brane, and therefore only branes of such dimension passing through the celestial sphere can respect asymptotic local flatness. We derive the asymptotically locally flat boundary conditions associated with including cosmic branes in the phase space of solutions. We find the asymptotic expansion of vacuum spacetimes in d=5 with such boundary conditions; the expansion is polyhomogenous, with logarithmic terms arising at subleading orders in the expansion. The asymptotically locally flat boundary conditions identified here are associated with an extended asymptotic symmetry group, which may be relevant to soft scattering theorems and memory effects

    Vademecum di medicina interna

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    Il Vademecum di Medicina Interna è una raccolta sintetica delle principali nozioni e procedure diagnostiche e terapeutiche che un medico può aver bisogno di ricordare nella pratica clinica. Il volume è nato come ausilio nella gestione delle urgenze e degli scenari che si presentano quotidianamente nella gestione di pazienti affetti da un’ampia gamma di patologie. Il Vademecum di Medicina Interna è destinato sia al medico all’inizio del percorso professionale che allo specialista esperto: al suo interno sono contenute sia indicazioni cliniche basate sulla più recente letteratura scientifica che posologie e schemi terapeutici di innumerevoli farmaci di frequente utilizzo in ambito clinico ospedaliero e ambulatoriale

    Charge and Antipodal Matching across Spatial Infinity

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    We derive the antipodal matching relations used to demonstrate the equivalence between soft graviton theorems and BMS charge conservation across spatial infinity. To this end we provide a precise map between Bondi data at null infinity I\mathscr{I} and Beig-Schmidt data at spatial infinity i0i^0 in a context appropriate to the gravitational scattering problem and celestial holography. In addition, we explicitly match the various proposals of BMS charges at I\mathscr{I} found in the literature with the conserved charges at i0i^0.Comment: 26 pages + appendices. v2: added references. v3: added references and comments. v4: corrected analysis for the antipodal matching of the angular momentum aspect, in agreement with recent observations made by Compere et al. in 2303.1712

    Beyond weight loss: the emerging role of incretin-based treatments in cardiometabolic HFpEF

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    PURPOSE OF REVIEW: Incretin-based drugs are potent weight-lowering agents, emerging as potential breakthrough therapy for the treatment of obesity-related phenotype of heart failure with preserved ejection fraction (HFpEF). In this review article, we will discuss the contribution of weight loss as part of the benefits of incretin-based medications in obese patients with HFpEF. Furthermore, we will describe the potential effects of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonists on the heart, particularly in relation to HFpEF pathophysiology. RECENT FINDINGS: In the STEP-HFpEF trial, the GLP-1 receptor agonist semaglutide significantly improved quality of life outcomes in obese HFpEF patients. Whether the beneficial effects of semaglutide in obese patients with HFpEF are merely a consequence of body weight reduction is unclear. Considering the availability of other weight loss strategies (e.g., caloric restriction, exercise training, bariatric surgery) to be used in obese HFpEF patients, answering this question is crucial to provide tailored therapeutic options in these subjects. SUMMARY: Incretin-based drugs may represent a milestone in the treatment of obesity in HFpEF. Elucidating the contribution of weight loss in the overall benefit observed with these drugs is critical in the management of obese HFpEF patients, considering that other weight-lowering strategies are available and might represent potential alternative options for these patients
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