RanBP2-Mediated SUMOylation Promotes Human DNA Polymerase Lambda Nuclear Localization and DNA Repair

Cellular DNA is under constant attack by a wide variety of agents, both endogenous and exogenous. To counteract DNA damage, human cells have a large collection of DNA repair factors. Among them, DNA polymerase lambda (Polλ) stands out for its versatility, as it participates in different DNA repair and damage tolerance pathways in which gap-filling DNA synthesis is required. In this work we show that human Polλ is conjugated with Small Ubiquitin-like MOdifier (SUMO) proteins both in vitro and in vivo, with Lys27 being the main target of this covalent modification. Polλ SUMOylation takes place in the nuclear pore complex and is mediated by the E3 ligase RanBP2. This post-translational modification promotes Polλ entry into the nucleus, which is required for its recruitment to DNA lesions and stimulated by DNA damage induction. Our work represents an advance in the knowledge of molecular pathways that regulate cellular localization of human Polλ, which are essential to be able to perform its functions during repair of nuclear DNA, and that might constitute an important point for the modulation of its activity in human cells

TL1A and IL-18 synergy promotes GM-CSF-dependent thymic granulopoiesis in mice

Acute systemic inflammation critically alters the function of the immune system, often promoting myelopoiesis at the expense of lymphopoiesis. In the thymus, systemic inflammation results in acute thymic atrophy and, consequently, impaired T-lymphopoiesis. The mechanism by which systemic inflammation impacts the thymus beyond suppressing T-cell development is still unclear. Here, we describe how the synergism between TL1A and IL-18 suppresses T-lymphopoiesis to promote thymic myelopoiesis. The protein levels of these two cytokines were elevated in the thymus during viral-induced thymus atrophy infection with murine cytomegalovirus (MCMV) or pneumonia virus of mice (PVM). In vivo administration of TL1A and IL-18 induced acute thymic atrophy, while thymic neutrophils expanded. Fate mapping with Ms4a3-Cre mice demonstrated that thymic neutrophils emerge from thymic granulocyte-monocyte progenitors (GMPs), while Rag1-Cre fate mapping revealed a common developmental path with lymphocytes. These effects could be modeled ex vivo using neonatal thymic organ cultures (NTOCs), where TL1A and IL-18 synergistically enhanced neutrophil production and egress. NOTCH blockade by the LY411575 inhibitor increased the number of neutrophils in the culture, indicating that NOTCH restricted steady-state thymic granulopoiesis. To promote myelopoiesis, TL1A, and IL-18 synergistically increased GM-CSF levels in the NTOC, which was mainly produced by thymic ILC1s. In support, TL1A- and IL-18-induced granulopoiesis was completely prevented in NTOCs derived from Csf2r

Non-Blocking Synchronization Between Real-Time and Non-Real-Time Applications

Real-time systems where applications with timing requirements coexist with applications without timing constraints are increasingly common. Furthermore, the processors used in desktops, smart phones or embedded devices are mostly multi-core, allowing the execution of applications in parallel. This article presents a set of non-blocking synchronization mechanisms to share data between real-time and non-real-time applications executing in different cores of a shared memory multi-core system. Four typical producer/consumer scenarios have been explored; a) shared data object with real-time reader, b) shared data object with real-time writer, c) shared queue with real-time writer, and d) shared queue with real-time reader. For these scenarios we have developed different non-blocking protocols where the execution of the real-time application is always prioritized over the execution of the non-real-time part. In this way, the real-time applications never have to repeat their operations and, consequently, their execution times are bounded. Furthermore, to reduce the overhead caused by the copies of the information used in the non-blocking algorithms, we have imposed the limitation of a single real-time reader or a single real-time writerinthealgorithmsdeveloped.Finally,we have evaluated the response times of the developed protocols on a multi-core device with the Android operating system.This work was supported in part by the Spanish Government and FEDER funds (AEI/FEDER, UE) under Grant TIN2017-86520-C3-3-R (PRECON-I4)

Endpoint weak boundedness of some polynomial expansions

AbstractLet w(x) = (1 −x)α(1 + x)β on [− 1, 1], α,β⩾ − 12, and for each function f let Snf be the nth expansion in the corresponding orthonormal polynomials. We show that the operators f → uSn(u−1f) are not of weak (p, p)-type, where u is another Jacobi weight and p is an endpoint of the interval of mean convergence. The same result is shown for expansions associated to measures of the form dv = w(x) dx + Σki=1Miδai

Weighted Lp-boundedness of Fourier series with respect to generalized Jacobi weights

Let w be a generalized Jacobi weight on the interval [-1,1] and, for each function f, let Snf denote the n-th partial sum of the Fourier series of f in the orthogonal polynomials associated to w. We prove a result about uniform boundedness of the operators Sn in some weighted Lp spaces. The study of the norms of the kernels Kn related to the operators Sn allows us to obtain a relation between the Fourier series with respect to different generalized Jacobi weights

Weighted LpL^p-boundedness of Fourier series with respect to generalized Jacobi weights

Let w be a generalized Jacobi weight on the interval [-1,1] and, for each function f, let Snf denote the n-th partial sum of the Fourier series of f in the orthogonal polynomials associated to w. We prove a result about uniform boundedness of the operators Sn in some weighted Lp spaces. The study of the norms of the kernels Kn related to the operators Sn allows us to obtain a relation between the Fourier series with respect to different generalized Jacobi weights

Setup for Material Characterization in the 110-170 GHz Band.

This work outlines the procedure to establish a system for assessing materials' complex permittivity and permeability within the 110-170 GHz frequency range. We present the employed methodology and the calibration procedure for the system, incorporating a dual approach using TRL (Thru-Reflect-Line) and GRL (Gated-Reflect-Line) methods. Following that, a smoothing technique is used to enhance the accuracy of the results. Tests were conducted on a HIPS sample to validate the system's performance, demonstrating the results' reliability across the entire measured bandwidth.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech