Uric Acid Is a Mediator of the Plasmodium falciparum-Induced Inflammatory Response

Malaria triggers a high inflammatory response in the host that mediates most of the associated pathologies and contributes to death. The identification of pro-inflammatory molecules derived from Plasmodium is essential to understand the mechanisms of pathogenesis and to develop targeted interventions. Uric acid derived from hypoxanthine accumulated in infected erythrocytes has been recently proposed as a mediator of inflammation in rodent malaria.We found that human erythrocytes infected with Plasmodium falciparum gradually accumulate hypoxanthine in their late stages of development. To analyze the role of hypoxanthine-derived uric acid induced by P. falciparum on the inflammatory cytokine response from human blood mononuclear cells, cultures were treated with allopurinol, to inhibit uric acid formation from hypoxanthine, or with uricase, to degrade uric acid. Both treatments significantly reduce the secretion of TNF, IL-6, IL-1beta and IL-10 from human cells.Uric acid is a major contributor of the inflammatory response triggered by P. falciparum in human peripheral blood mononuclear cells. Since the inflammatory reaction induced by P. falciparum is considered a major cause of malaria pathogenesis, identifying the mechanisms used by the parasite to induce the host inflammatory response is essential to develop urgently needed therapies against this disease

Business Model Innovation vs. Business Model Inertia: the Role of Disruptive Technologies

This contribution addresses the impact of disruptive technologies on business model innovation. While such technologies have the potential to significantly alter the way in which businesses operate, business model inertia hinders companies from adopting the new technological possibilities. Little research has focused on the difficulties incumbents face when innovating their business models. By reviewing current literature on business model innovation, this paper summarizes challenges companies face when dealing with potential disruptive technologies and creating viable business models

The upgrade of the ALICE TPC with GEMs and continuous readout

The upgrade of the ALICE TPC will allow the experiment to cope with the high interaction rates foreseen for the forthcoming Run 3 and Run 4 at the CERN LHC. In this article, we describe the design of new readout chambers and front-end electronics, which are driven by the goals of the experiment. Gas Electron Multiplier (GEM) detectors arranged in stacks containing four GEMs each, and continuous readout electronics based on the SAMPA chip, an ALICE development, are replacing the previous elements. The construction of these new elements, together with their associated quality control procedures, is explained in detail. Finally, the readout chamber and front-end electronics cards replacement, together with the commissioning of the detector prior to installation in the experimental cavern, are presented. After a nine-year period of R&D, construction, and assembly, the upgrade of the TPC was completed in 2020.publishedVersio

Inflammation and breast cancer. Metalloproteinases as common effectors of inflammation and extracellular matrix breakdown in breast cancer

Two rapidly evolving fields are converging to impact breast cancer: one has identified novel substrates of metalloproteinases that alter immune cell function, and the other has revealed a role for inflammation in human cancers. Evidence now shows that the mechanisms underlying these two fields interact in the context of breast cancer, providing new opportunities to understand this disease and uncover novel therapeutic strategies. The metalloproteinase class of enzymes is well studied in mammary gland development and physiology, but mostly in the context of extracellular matrix modification. Aberrant metalloproteinase expression has also been implicated in breast cancer progression, where these genes act as tumor modifiers. Here, we review how the metalloproteinase axis impacts mammary physiology and tumorigenesis and is associated with inflammatory cell influx in human breast cancer, and evaluate its potential as a regulator of inflammation in the mammary gland

The LHCb upgrade I

The LHCb upgrade represents a major change of the experiment. The detectors have been almost completely renewed to allow running at an instantaneous luminosity five times larger than that of the previous running periods. Readout of all detectors into an all-software trigger is central to the new design, facilitating the reconstruction of events at the maximum LHC interaction rate, and their selection in real time. The experiment's tracking system has been completely upgraded with a new pixel vertex detector, a silicon tracker upstream of the dipole magnet and three scintillating fibre tracking stations downstream of the magnet. The whole photon detection system of the RICH detectors has been renewed and the readout electronics of the calorimeter and muon systems have been fully overhauled. The first stage of the all-software trigger is implemented on a GPU farm. The output of the trigger provides a combination of totally reconstructed physics objects, such as tracks and vertices, ready for final analysis, and of entire events which need further offline reprocessing. This scheme required a complete revision of the computing model and rewriting of the experiment's software

Entwicklung neuartiger Feuchte-Sensorik und prozessorientierter Feuchtemesssysteme Schlussbericht zum Teilvorhaben 1

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