An Improved Kernel for the Flip Distance Problem on Simple Convex Polygons

The complexity of computing the flip distance between two triangulations of a simple convex polygon is unknown. Here we approach the problem from a parameterized complexity perspective and improve upon the 2k kernel of Lucas [10]. Specifically, we describe a kernel of size 43k and then show how it can be improved to (1+?)k for every constant ? > 0. By ensuring that the kernel consists of a single instance our result yields a kernel of the same magnitude (up to additive terms) for the almost equivalent rotation distance problem on rooted, ordered binary trees. The earlier work of Lucas left the kernel as a disjoint set of instances, potentially allowing very minor differences in the definition of the size of instances to accumulate, causing a constant-factor distortion in the kernel size when switching between flip distance and rotation distance formulations. Our approach avoids this sensitivity

An Improved Kernel for the Flip Distance Problem on Simple Convex Polygons

The complexity of computing the flip distance between two triangulations of a simple convex polygon is unknown. Here we approach the problem from a parameterized complexity perspective and improve upon the 2k kernel of Lucas [10]. Specifically, we describe a kernel of size 43k and then show how it can be improved to (1+?)k for every constant ? > 0. By ensuring that the kernel consists of a single instance our result yields a kernel of the same magnitude (up to additive terms) for the almost equivalent rotation distance problem on rooted, ordered binary trees. The earlier work of Lucas left the kernel as a disjoint set of instances, potentially allowing very minor differences in the definition of the size of instances to accumulate, causing a constant-factor distortion in the kernel size when switching between flip distance and rotation distance formulations. Our approach avoids this sensitivity

Diseño de un sistema automático de organización de trabajadores de capacidades diversas en puestos de trabajo para un Centro Especial de Empleo (Espurna CEE, SLU)

[ES] El trabajo que se presenta consiste en el diseño de un sistema de organización para un centro especial de empleo. El documento constará de un análisis de la problemática del centro especial de empleo, un planteamiento de posibles soluciones, elección de una de ellas y desarrollo de esta. En el desarrollo se describirá el sistema de planificación y control que se ha diseñado para albergar los procesos y la herramienta de apoyo que permite automatizarlos. Posteriormente se describirá un plan de implantación y presupuesto. El problema principal que se intentará resolver es el de la distribución de los trabajadores del centro en los distintos enclaves en los que pueden ser enviados. Hay una gran cantidad de empleados para situar y el problema se vuelve complicado. Se resolverá aplicando un sistema de planificación para dividir el problema y definir las funciones de cada una de las partes y con la herramienta de apoyo se solucionará el reparto de los trabajadores. De esta manera el resultado será un plan de actuación, una herramienta para llevar a cabo esas instrucciones y un plan para poner en marcha todo el sistema.Bosch Calvo, M. (2019). Diseño de un sistema automático de organización de trabajadores de capacidades diversas en puestos de trabajo para un Centro Especial de Empleo (Espurna CEE, SLU). http://hdl.handle.net/10251/125742TFG

A 4/3 Approximation for 2-Vertex-Connectivity

The 2-Vertex-Connected Spanning Subgraph problem (2VCSS) is among the most basic NP-hard (Survivable) Network Design problems: we are given an (unweighted) undirected graph G. Our goal is to find a subgraph S of G with the minimum number of edges which is 2-vertex-connected, namely S remains connected after the deletion of an arbitrary node. 2VCSS is well-studied in terms of approximation algorithms, and the current best (polynomial-time) approximation factor is 10/7 by Heeger and Vygen [SIDMA\u2717] (improving on earlier results by Khuller and Vishkin [STOC\u2792] and Garg, Vempala and Singla [SODA\u2793]). Here we present an improved 4/3 approximation. Our main technical ingredient is an approximation preserving reduction to a conveniently structured subset of instances which are "almost" 3-vertex-connected. The latter reduction might be helpful in future work

Therapeutic Effect of IL-21 Blockage by Gene Therapy in Experimental Autoimmune Encephalomyelitis

Soluble receptor; Multiple sclerosisReceptor soluble; Esclerosis múltipleReceptor soluble; Esclerosi múltipleThe pathogenic role of the interleukin 21 (IL-21) in different autoimmune diseases, such as multiple sclerosis (MS), has been extensively studied. However, its pleiotropic nature makes it a cytokine that may exhibit different activity depending on the immunological stage of the disease. In this study, we developed a gene therapy strategy to block the interaction between IL-21 and its receptor (IL-21R) by using adeno-associated vectors (AAV) encoding a new soluble cytokine receptor (sIL21R) protein. We tested this strategy in a murine model of experimental autoimmune encephalomyelitis (EAE), obtaining different clinical effects depending on the time at which the treatment was applied. Although the administration of the treatment during the development of the immune response was counterproductive, the preventive administration of the therapeutic vectors showed a protective effect by reducing the number of animals that developed the disease, as well as an improvement at the histopathological level and a modification of the immunological profile of the animals treated with the AAV8.sIL21R. The beneficial effect of the treatment was also observed when inducing the expression of the therapeutic molecule once the first neurological signs were established in a therapeutic approach with a doxycyline (Dox)-inducible expression system. All these clinical results highlight the pleiotropicity of this cytokine in the different clinical stages and its key role in the EAE immunopathogenesis.Open Access Funding provided by Universitat Autonoma de Barcelona. This project was supported by the Ministerio Ciencia Innovación, retos Sociedad (PI15/0271). A.E was a recipient of a VHIR fellowship

Multiscale Phenomenology of the Cosmic Web

We analyze the structure and connectivity of the distinct morphologies that define the Cosmic Web. With the help of our Multiscale Morphology Filter (MMF), we dissect the matter distribution of a cosmological $\Lambda$CDM N-body computer simulation into cluster, filaments and walls. The MMF is ideally suited to adress both the anisotropic morphological character of filaments and sheets, as well as the multiscale nature of the hierarchically evolved cosmic matter distribution. The results of our study may be summarized as follows: i).- While all morphologies occupy a roughly well defined range in density, this alone is not sufficient to differentiate between them given their overlap. Environment defined only in terms of density fails to incorporate the intrinsic dynamics of each morphology. This plays an important role in both linear and non linear interactions between haloes. ii).- Most of the mass in the Universe is concentrated in filaments, narrowly followed by clusters. In terms of volume, clusters only represent a minute fraction, and filaments not more than 9%. Walls are relatively inconspicous in terms of mass and volume. iii).- On average, massive clusters are connected to more filaments than low mass clusters. Clusters with $M \sim 10^{14}$ M$_{\odot}$ h$^{-1}$ have on average two connecting filaments, while clusters with $M \geq 10^{15}$ M$_{\odot}$ h$^{-1}$ have on average five connecting filaments. iv).- Density profiles indicate that the typical width of filaments is 2\Mpch. Walls have less well defined boundaries with widths between 5-8 Mpc h$^{-1}$. In their interior, filaments have a power-law density profile with slope ${\gamma}\approx -1$, corresponding to an isothermal density profile.Comment: 28 pages, 22 figures, accepted for publication in MNRAS. For a high-res version see http://www.astro.rug.nl/~weygaert/webmorph_mmf.pd

Fossil evidence for spin alignment of SDSS galaxies in filaments

We search for and find fossil evidence that the distribution of the spin axes of galaxies in cosmic web filaments relative to their host filaments are not randomly distributed. This would indicate that the action of large scale tidal torques effected the alignments of galaxies located in cosmic filaments. To this end, we constructed a catalogue of clean filaments containing edge-on galaxies. We started by applying the Multiscale Morphology Filter (MMF) technique to the galaxies in a redshift-distortion corrected version of the Sloan Digital Sky Survey DR5. From that sample we extracted those 426 filaments that contained edge-on galaxies (b/a < 0.2). These filaments were then visually classified relative to a variety of quality criteria. Statistical analysis using "feature measures" indicates that the distribution of orientations of these edge-on galaxies relative to their parent filament deviate significantly from what would be expected on the basis of a random distribution of orientations. The interpretation of this result may not be immediately apparent, but it is easy to identify a population of 14 objects whose spin axes are aligned perpendicular to the spine of the parent filament (\cos \theta < 0.2). The candidate objects are found in relatively less dense filaments. This might be expected since galaxies in such locations suffer less interaction with surrounding galaxies, and consequently better preserve their tidally induced orientations relative to the parent filament. The technique of searching for fossil evidence of alignment yields relatively few candidate objects, but it does not suffer from the dilution effects inherent in correlation analysis of large samples.Comment: 20 pages, 19 figures, slightly revised and upgraded version, accepted for publication by MNRAS. For high-res version see http://www.astro.rug.nl/~weygaert/SpinAlignJones.rev.pd

A gene expression assay based on chronic lymphocytic leukemia activation in the microenvironment to predict progression

Gene expression; Chronic lymphocytic leukemiaExpresión génica; Leucemia linfocítica crónicaExpressió gènica; Leucèmia limfocítica crònicaSeveral gene expression profiles with a strong correlation with patient outcomes have been previously described in chronic lymphocytic leukemia (CLL), although their applicability as biomarkers in clinical practice has been particularly limited. Here we describe the training and validation of a gene expression signature for predicting early progression in patients with CLL based on the analysis of 200 genes related to microenvironment signaling on the NanoString platform. In the training cohort (n = 154), the CLL15 assay containing a 15-gene signature was associated with the time to first treatment (TtFT) (hazard ratio [HR], 2.83; 95% CI, 2.17-3.68; P < .001). The prognostic value of the CLL15 score (HR, 1.71; 95% CI, 1.15-2.52; P = .007) was further confirmed in an external independent validation cohort (n = 112). Notably, the CLL15 score improved the prognostic capacity over IGHV mutational status and the International Prognostic Score for asymptomatic early-stage (IPS-E) CLL. In multivariate analysis, the CLL15 score (HR, 1.83; 95% CI, 1.32-2.56; P < .001) and the IPS-E CLL (HR, 2.23; 95% CI, 1.59-3.12; P < .001) were independently associated with TtFT. The newly developed and validated CLL15 assay successfully translated previous gene signatures such as the microenvironment signaling into a new gene expression–based assay with prognostic implications in CLL.This work was supported by research funding from the Asociación Española Contra el Cáncer grant [5U01CA157581-05, ECRIN-M3 - A29370] and in part by the Instituto de Salud Carlos III, Fondo de Investigaciones Sanitarias [PI17/00950, M.C., PI17/00943, F.B, PI18/01392, P.A.], and the Spanish Ministry of Economy and Competitiveness [CIBERONC-CB16/12/00233], the Education Council or Health Council of the Junta de Castilla y León [GRS 2036/A/19], and Gilead Sciences [GLD15/00348]. This work was supported by research funding from the Asociación Española Contra el Cáncer grant [5U01CA157581-05, ECRIN-M3 - A29370] and in part by the Instituto de Salud Carlos III, Fondo de Investigaciones Sanitarias [PI17/00950, M.C., PI17/00943, F.B, PI18/01392, P.A.], and the Spanish Ministry of Economy and Competitiveness [CIBERONC-CB16/12/00233], the Education Council or Health Council of the Junta de Castilla y León [GRS 2036/A/19], Gilead Sciences [GLD15/00348] and Gilead Fellowships [GLD16/00144, GLD18/00047, F.B.], and Fundació la Marató de TV3 [201905-30-31 F.B]. All Spanish funding was cosponsored by the European Union FEDER program “Una manera de hacer Europa”. M.C. holds a contract from Ministerio de Ciencia, Innovación y Universidades [RYC-2012-2018]

Impact of a Primary Care Antimicrobial Stewardship Program on Bacterial Resistance Control and Ecological Imprint in Urinary Tract Infections

Antimicrobial stewardship programs (ASPs) are a central component in reducing the overprescription of unnecessary antibiotics, with multiple studies showing benefits in the reduction of bacterial resistance. Less commonly, ASPs have been performed in outpatient settings, but there is a lack of available data in these settings. We implemented an ASP in a large regional outpatient setting to assess its feasibility and effectiveness. Over a 5-year post-implementation period, compared to the pre-intervention period, a significant reduction in antibiotic prescription occurred, with a reduction in resistance in E. coli urinary isolates. ASP activities also were found to be cost-effective, with a reduction in medication prescription

Stratification of radiosensitive brain metastases based on an actionable S100A9/RAGE resistance mechanism

© The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Whole-brain radiotherapy (WBRT) is the treatment backbone for many patients with brain metastasis; however, its efficacy in preventing disease progression and the associated toxicity have questioned the clinical impact of this approach and emphasized the need for alternative treatments. Given the limited therapeutic options available for these patients and the poor understanding of the molecular mechanisms underlying the resistance of metastatic lesions to WBRT, we sought to uncover actionable targets and biomarkers that could help to refine patient selection. Through an unbiased analysis of experimental in vivo models of brain metastasis resistant to WBRT, we identified activation of the S100A9-RAGE-NF-κB-JunB pathway in brain metastases as a potential mediator of resistance in this organ. Targeting this pathway genetically or pharmacologically was sufficient to revert the WBRT resistance and increase therapeutic benefits in vivo at lower doses of radiation. In patients with primary melanoma, lung or breast adenocarcinoma developing brain metastasis, endogenous S100A9 levels in brain lesions correlated with clinical response to WBRT and underscored the potential of S100A9 levels in the blood as a noninvasive biomarker. Collectively, we provide a molecular framework to personalize WBRT and improve its efficacy through combination with a radiosensitizer that balances therapeutic benefit and toxicity.info:eu-repo/semantics/publishedVersio