Net Neutrality: Smart Cables or Dumb Pipes? An overview on the regulatory debate about how to govern the network. Research Paper in Law 03/2016

From the Introduction. On 30th April 2016 the provisions of the new Regulation on Open Internet Access1 will enter into force in the EU. This will be yet another chapter of the long debate –some would call it saga- on net neutrality and the desirable architecture of the internet. It is undeniable that the internet has become in a very short time a fundamental element of most people’s professional and personal lives. High speed access to the net is now considered as an indispensable tool for innovation, productivity and development in modern societies. What is more, the internet has proven during the last decade that it is a potentially limitless technology whose disruptive effects can alter almost every industry, even its own one

The Upper Bound Theorem in forging processes: Model of Triangular Rigid Zones on parts with horizontal symmetry

The analysis to determine the necessary forces with which to achieve a plastic deformation in metallic materials, in particular, in forging processes and under conditions of plain strain, has been raised over the years through a double approach; on the one hand, by analytical methods that involve a great complexity in their developments but that allow a direct understanding of the parameters that direct these processes. On the other hand, numerical methods, in which, thanks to the enormous development of computer technology, they provide solutions with a high approximation but, in most cases, do not allow to interpret independently the effect of each one of the parameters that come into play. The development of computers relegated analytical methods to the background. An alternative of great interest to apply these methods comes from the study of the Upper Bound Theorem by means of the Triangular Rigid Zones (TRZ) Model. One of the main limitations in the application of this model come from the fact that it is necessary to define a kinematically admissible velocity field and for complex geometric configurations of parts, this field becomes increasingly complicated. A new approach has delimited, from a theoretical perspective, a modular configuration based on a General Module formed by three TRZ that adapts to any geometry of flat surfaces of the part. Another limitation of the Upper Bound Method is the consideration of the plain strain represented by a flat section with double symmetry. Obviously, this imposition only allows to study a limited number of part configurations, which restricts its application in forging processes since the great majority of forged parts do not present geometrically this double symmetry. The present work releases one of these boundary conditions allowing to expand the possibilities of application of this method.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tec

Extracellular vesicle PD‑L1 dynamics predict durable response to immune‑checkpoint inhibitors and survival in patients with non‑small cell lung cancer

Background: Immune-checkpoint inhibitors (ICIs) changed the therapeutic landscape of patients with lung cancer. However, only a subset of them derived clinical benefit and evidenced the need to identify reliable predictive biomarkers. Liquid biopsy is the non-invasive and repeatable analysis of biological material in body fluids and a promising tool for cancer biomarkers discovery. In particular, there is growing evidence that extracellular vesicles (EVs) play an important role in tumor progression and in tumor-immune interactions. Thus, we evaluated whether extracellular vesicle PD-L1 expression could be used as a biomarker for prediction of durable treatment response and survival in patients with non-small cell lung cancer (NSCLC) undergoing treatment with ICIs. Methods: Dynamic changes in EV PD-L1 were analyzed in plasma samples collected before and at 9 ± 1 weeks during treatment in a retrospective and a prospective independent cohorts of 33 and 39 patients, respectively. Results: As a result, an increase in EV PD-L1 was observed in non-responders in comparison to responders and was an independent biomarker for shorter progression-free survival and overall survival. To the contrary, tissue PD-L1 expression, the commonly used biomarker, was not predictive neither for durable response nor survival. Conclusion: These findings indicate that EV PD-L1 dynamics could be used to stratify patients with advanced NSCLC who would experience durable benefit from ICIs.Center for Thoracic Oncology Icahn School of Medicine at Mount SinaiBorsa Dottorati FSE XXXII ciclo UnimeUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) P30CA016672University of Pittsburgh Hillman Cancer CenterHillman Cancer Center's NCI Cancer Center Support Grant (CCSG) P30CA047904A.S.S.O. (Associazione Siciliana Sostegno Oncologico) OnlusNational Cancer Institute-Cancer Center Support Grant (CCSG) P30CA134274Merck & Compan

Computation of the optimal relative pose between overlapping grid maps through discrepancy minimization

Grid maps are a common environment representation in mobile robotics. Many Simultaneous Localization and Mapping (SLAM) solutions divide the global map into submaps, forming some kind of graph or tree to represent the structure of the environment, while the metric details are captured in the submaps. This work presents a novel algorithm that is able to compute a physically feasible relative pose between two overlapping grid maps. Our algorithm can be used for correspondence search (data association), but also for integrating negative information in a unified way. This paper proposes a discrepancy measure between two overlapping grid maps and its application in a quasi Newton optimization algorithm, with the hypothesis that minimizing such discrepancy could provide useful information for SLAM. Experimental evidence is provided showing the high potential of the algorithm

Primordial Germ Cell Reprogramming

Primordial germ cells (PGCs) are the embryonic precursors of the gametes. Thus, they are unipotent cells. However, PGCs share some common features with pluripotent stem cells. Among them, PGCs show alkaline phosphatase activity and express stage-specific embryonic antigens and pluripotency factors Lin28, Oct4, Sox2, and Nanog. Under specific conditions, they undergo spontaneous reprogramming in vivo. Moreover, they can be easily reprogrammed in vitro into pluripotent embryonic germ cells (EGCs) by culturing them in the presence of basic fibroblast growth factor or the epigenetic modulator trichostatin A. Previous work in our laboratory has also proven that hypoxia alone can reprogram PGCs into hypoxia-induced embryonic germ-like cells, which have a pluripotent phenotype but which do not show self-renewal capacity. Therefore, PGCs are an interesting model to further comprehensively understand the process of cell reprogramming. This chapter reviews various methods to achieve PGC reprogramming, as well as the molecular pathways involved. We focus on soluble factors and genetic strategies to obtain pluripotent cells from PGCs. Special emphasis will be given to factors implied in energetic metabolism, epigenetics, and cell signaling transduction, both in vitro and in vivo