Piattaforme digitali: tra criticità concorrenziali e prospettive di regolamentazione

È indubbio che le piattaforme digitali abbiano oggi un impatto tale da condizionare in maniera trasversale tutti gli aspetti delle relazioni umane, personali ed economiche, così rendendo le predette piattaforme dei veri e propri giganti della nostra società, attraverso i quali si rapportano quotidianamente miliardi di persone, eleggendo i social network quale luogo digitale di incontro, le piattaforme di e-commerce a nuovi mercati, i motori di ricerca a porte sullo scibile umano. In tale contesto, è sorto però il dibattito circa la necessità di una regolamentazione unitaria e teleologicamente orientata del fenomeno delle piattaforme digitali. Invero, da più parti è stato sollevato il dubbio che l’inarrestabile sviluppo delle piattaforme digitali sia proprio dovuto alla mancanza di un quadro regolamentare in grado di porre freno ai comportamenti opportunistici di questi nuovi giganti digitali. Su tali premesse, scopo della presente trattazione sarà quello di andare ad analizzare le problematiche concorrenziali che caratterizzano i mercati animati dalle piattaforme digitali. Ciò al fine di verificare se gli strumenti e gli schemi del diritto antitrust siano in grado di rispondere alle sfide concorrenziali poste dalle piattaforme digitali o se, viceversa, sia necessario approntare un quadro regolamentare ad hoc. Pertanto, nella prima parte della trattazione si cercherà di connotare il concetto di piattaforma digitale, in modo da individuare i contorni di una nozione all'apparenza, e nella sostanza, complessa. Nella seconda parte verrà esaminata la possibilità di adoperare gli strumenti generalmente utilizzati per la definizione del mercato rilevante anche in contesti fluidi come quelli in cui operano le piattaforme in questione. Nella terza e nella quarta parte si esamineranno le sfide che i mercati della new economy pongono agli operatori del diritto antitrust, rispettivamente nell’applicazione del divieto di intese anticoncorrenziali, di cui all’art. 101 del Trattato sul Funzionamento dell’Unione europea (di seguito “TFUE”) e dell’abuso di posizione dominante, ai sensi dell’art. 102 TFUE. L’ultimo parte della trattazione sarà invece dedicata ad esaminare le problematiche concorrenziali scaturenti dalle operazioni di concentrazione che coinvolgono le piattaforme digitali

Prognostic value of combined use of biomarkers of inflammation, endothelial dysfunction, and myocardiopathy in patients with ESRD

Prognostic value of combined use of biomarkers of inflammation, endothelial dysfunction, and myocardiopathy in patients with ESRD.BackgroundCardiovascular risk stratification is important in the clinical management of patients with end-stage renal diseases (ESRD) and biomarkers are increasingly used in these patients.MethodsIn a cohort of 246 dialysis patients without heart failure at baseline we tested the combined prognostic power of three well-established biomarkers: brain natriuretic peptide (BNP), C-reactive protein (CRP), and asymmetric dimethyl arginine (ADMA). The independent prognostic value of individual and combined biomarkers was estimated in separate Cox models, including standard risk factors in dialysis patients and comorbidities.ResultsWhen the prediction power of the three biomarkers was evaluated individually, BNP, ADMA, and CRP added significant predictive value (P≤ 0.01) to all-cause and cardiovascular mortality models and the explanatory gain attributable to these biomarkers were of similar degree (ranging from 3.3% to 5.7%). When the biomarkers were evaluated jointly, a score based on the BNP-CRP combination, increased by 9.9% (all-cause) and by 10.5% (cardiovascular) the explained mortality variance of standard Cox models and such gain in power was similar to that achieved by the CRP-ADMA combination (all-cause death 9.0% and cardiovascular death 8.4%). Of note, the explanatory gain derived by the simultaneous use of the three biomarkers was very similar (all-cause death 11.6% and cardiovascular death 10.5%) to that achieved by the use of two biomarkers.ConclusionThese findings indicate a potential role for CRP, BNP, and ADMA to be incorporated into diagnostic and therapeutic strategies aimed at detection and treatment of atherosclerotic complications and at preventing heart failure in the dialysis population

The Estrogen Receptor α Signaling Pathway Controls Alternative Splicing in the Absence of Ligands in Breast Cancer Cells.

BACKGROUND: The transcriptional activity of estrogen receptor α (ERα) in breast cancer (BC) is extensively characterized. Our group has previously shown that ERα controls the expression of a number of genes in its unliganded form (apoERα), among which a large group of RNA-binding proteins (RBPs) encode genes, suggesting its role in the control of co- and post-transcriptional events. METHODS: apoERα-mediated RNA processing events were characterized by the analysis of transcript usage and alternative splicing changes in an RNA-sequencing dataset from MCF-7 cells after siRNA-induced ERα downregulation. RESULTS: ApoERα depletion induced an expression change of 681 RBPs, including 84 splicing factors involved in translation, ribonucleoprotein complex assembly, and 3'end processing. ApoERα depletion results in 758 isoform switching events with effects on 3'end length and the splicing of alternative cassette exons. The functional enrichment of these events shows that post-transcriptional regulation is part of the mechanisms by which apoERα controls epithelial-to-mesenchymal transition and BC cell proliferation. In primary BCs, the inclusion levels of the experimentally identified alternatively spliced exons are associated with overall and disease-free survival. CONCLUSION: Our data supports the role of apoERα in maintaining the luminal phenotype of BC cells by extensively regulating gene expression at the alternative splicing level

The Adaptive Immune System in Multiple Sclerosis: An Estrogen-Mediated Point of View

Multiple sclerosis (MS) is a chronic central nervous system inflammatory disease that leads to demyelination and neurodegeneration. The third trimester of pregnancy, which is characterized by high levels of estrogens, has been shown to be associated with reduced relapse rates compared with the rates before pregnancy. These effects could be related to the anti-inflammatory properties of estrogens, which orchestrate the reshuffling of the immune system toward immunotolerance to allow for fetal growth. The action of these hormones is mediated by the transcriptional regulation activity of estrogen receptors (ERs). Estrogen levels and ER expression define a specific balance of immune cell types. In this review, we explore the role of estradiol (E2) and ERs in the adaptive immune system, with a focus on estrogen-mediated cellular, molecular, and epigenetic mechanisms related to immune tolerance and neuroprotection in MS. The epigenome dynamics of immune systems are described as key molecular mechanisms that act on the regulation of immune cell identity. This is a completely unexplored field, suggesting a future path for more extensive research on estrogen-induced coregulatory complexes and molecular circuitry as targets for therapeutics in MS

Plasma adrenomedullin during acute changes in intravascular volume in hemodialysis patients

Plasma adrenomedullin during acute changes in intravascular volume in hemodialysis patients.BackgroundAdrenomedullin, is a potent vasorelaxant that is highly expressed in the adrenal medulla, kidney, heart and lung. Since there is indirect evidence that hypervolemia enhances the release of this peptide, we measured plasma adrenomedullin in 9 uremic patients on chronic dialysis treatment and in 10 healthy subjects matched for age and gender.MethodsMeasurements were performed in baseline conditions, after isotonic fluid subtraction (by isolated ultrafiltration) and during a 70° tilt. Tilt was performed in volume-depleted state, that is, after isolated ultrafiltration (UF). In the control experiment patients underwent sham UF (UF = 0) followed by a period of supine resting identical to the one they had spent in tilted position in the active experiment. Adrenomedullin was measured on pre-extracted plasma samples (Sep-Pak C-18 cartridges) by a specific RIA for human adrenomedullin 1-52.ResultsThe average plasma adrenomedullin was 2.6 times higher (P < 0.01) in uremic patients (103 ± 8pg/ml) than in healthy subjects (39 ± 7pg/ml). After fluid subtraction (-2.6 ± 0.2 liter) adrenomedullin fell to 79. ± 8pg/ml (P = 0.02) but remained well above the upper limit of the 95% CI in normal subjects (52pg/ml). There was no relationship between adrenomedullin and ANF changes. In the control experiment sham UF did not modify plasma adrenomedullin. Tilt did not significantly change plasma adrenomedullin either in dialysis patients or healthy subjects.ConclusionsPlasma adrenomedullin is markedly raised in uremic patients on dialysis, which confirms that the kidney has a major role in the clearance of this peptide. However, the fall in plasma adrenomedullin after isolated UF indicates that the plasma concentration of this peptide is influenced by the body fluid volume status. Whether or not adrenomedullin participates in the counter-regulatory response to fluid subtraction in uremic patients remains to be explored by specific antagonists of this substance

Transients Analysis of a Tidal Currents Self-balancing Kinetic Turbine with on Shore Basement

Abstract The aim of increasing the share of renewable energy sources to the total energy production has brought a significant increase of the interest in marine energies over the last years. Within them, tidal currents resources have been gaining ground for their advantages in terms of predictability, nonexistence of extreme flows, high load factor, minimal land occupation and visual impact. The authors, working in this field since many years, have been designing a new turbine able to work in the water like a kite, with no support structures, but easily connected to the coast by a rope. The constructive easiness, together with lower installation costs, are the main machine characteristics. Moreover it is able to overturn itself when the tidal current changes direction. The turbine equilibrium and mainly the transients related to the sink and surface phases, machine overturning, represent a critical aspect of the design. In the present work, starting from a phenomenological analysis, a simulation of the transients has been carried out in Simulink ® environment. The study, related to the center of gravity, has pointed out the importance of the correct floating stabilizer design which helps the turbine to reach the equilibrium conditions even in case of flow instability

Activation of diacylglycerol kinase alpha is required for VEGF-induced angiogenic signaling in vitro.

Vascular endothelial growth factor-A (VEGF-A) promotes angiogenesis by stimulating migration, proliferation and organization of endothelium, through the activation of signaling pathways involving Src tyrosine kinase. As we had previously shown that Src-mediated activation of diacylglycerol kinase-alpha (Dgk-alpha) is required for hepatocytes growth factor-stimulated cell migration, we asked whether Dgk-alpha is involved in the transduction of angiogenic signaling. In PAE-KDR cells, an endothelial-derived cell line expressing VEGFR-2, VEGF-A165, stimulates the enzymatic activity of Dgk-alpha: activation is inhibited by R59949, an isoform-specific Dgk inhibitor, and is dependent on Src tyrosine kinase, with which Dgk-alpha forms a complex. Conversely in HUVEC, VEGF-A165-induced activation of Dgk is only partially sensitive to R59949, suggesting that also other isoforms may be activated, albeit still dependent on Src tyrosine kinase. Specific inhibition of Dgk-alpha, obtained in both cells by R59949 and in PAE-KDR by expression of Dgk-alpha dominant-negative mutant, impairs VEGF-A165-dependent chemotaxis, proliferation and in vitro angiogenesis. In addition, in HUVEC, specific downregulation of Dgk-alpha by siRNA impairs in vitro angiogenesis on matrigel, further suggesting the requirement for Dgk-alpha in angiogenic signaling in HUVEC. Thus, we propose that activation of Dgk-alpha generates a signal essential for both proliferative and migratory response to VEGF-A165, suggesting that it may constitute a novel pharmacological target for angiogenesis control.