"Come s’uno schermo". Partecipazione a distanza, efficienza, garanzie, upgrade tecnologici

La nuova disciplina della partecipazione a distanza, introdotta dalla l. n. 103 del 2017, segna una svolta profonda nelle sintassi delle garanzie partecipative: la previsione, per default, di una modalità di aula giudiziaria “estesa” per lo svolgimento di ogni atto che comporti, a qualsiasi titolo, la partecipazione di soggetti in status custodiae per delitti particolarmente gravi muta in profondità le soglie qualitative dei modelli interrelazionali delle procedure giudiziarie e delle correlative garanzie. Il contributo si sofferma sulle risorse tecnologiche oggi adoperate nelle videoconferenze giudiziarie, avendo cura di raffrontarle con le ben più avanzate tecnologie già oggi disponibili in contesti extraprocessuali: l’incremento degli investimenti tecnologici circa gli apparati di supporto all’esame e alla partecipazione giudiziaria a distanza appare sentiero obbligato allo scopo di ridurre il gap, ancora cospicuo, tra le presenze fisiche e le modalità di telepresenza, così prevenendo rischi di ingiustificabili compressioni di primarie garanzie di contesto

Cercando un cielo. Legal Clinic, formazione del giurista e tutela della vulnerabilità

Il metodo clinico dell’insegnamento del diritto è un approccio ormai ampiamente diffuso a livello globale grazie alle esperienze delle cliniche legali: il contributo analizza i fondamenti teorici e valoriali di tale approccio che, a partire da una specifica declinazione del metodo casistico, è in grado di produrre una profonda modifica dei centri di gravità dell’educazione giuridica tradizionale

"Come s\u2019uno schermo". Partecipazione a distanza, efficienza, garanzie, upgrade tecnologici

La nuova disciplina della partecipazione a distanza, introdotta dalla l. n. 103 del 2017, segna una svolta profonda nelle sintassi delle garanzie partecipative: la previsione, per default, di una modalit\ue0 di aula giudiziaria \u201cestesa\u201d per lo svolgimento di ogni atto che comporti, a qualsiasi titolo, la partecipazione di soggetti in status custodiae per delitti particolarmente gravi muta in profondit\ue0 le soglie qualitative dei modelli interrelazionali delle procedure giudiziarie e delle correlative garanzie. Il contributo si sofferma sulle risorse tecnologiche oggi adoperate nelle videoconferenze giudiziarie, avendo cura di raffrontarle con le ben pi\uf9 avanzate tecnologie gi\ue0 oggi disponibili in contesti extraprocessuali: l\u2019incremento degli investimenti tecnologici circa gli apparati di supporto all\u2019esame e alla partecipazione giudiziaria a distanza appare sentiero obbligato allo scopo di ridurre il gap, ancora cospicuo, tra le presenze fisiche e le modalit\ue0 di telepresenza, cos\uec prevenendo rischi di ingiustificabili compressioni di primarie garanzie di contesto

Intravenous cocaine, morphine and amphetamine preferentially increase extracellular dopamine in the 'shell' as compared to the 'core' of the rat nucleus accumbens.

The nucleus accumbens is considered a critical target of the action of drugs of abuse. In this nucleus a "shell" and a "core" have been distinguished on the basis of anatomical and histochemical criteria. The present study investigated the effect in freely moving rats of intravenous cocaine, amphetamine, and morphine on extracellular dopamine concentrations in the nucleus accumbens shell and core by means of microdialysis with vertically implanted concentric probes. Doses selected were in the range of those known to sustain drug self-administration in rats. Morphine, at 0.2 and 0.4 mg/kg, and cocaine, at 0.5 mg/kg, increased extracellular dopamine selectivity in the shell. Higher doses of cocaine (1.0 mg/kg) and the lowest dose of amphetamine tested (0.125 mg/kg) increased extracellular dopamine both in the shell and in the core, but the effect was significantly more pronounced in the shell compared with the core. Only the highest dose of amphetamine (0.250 mg/kg) increased extracellular dopamine in the shell and in the core to a similar extent. The present results provide in vivo neurochemical evidence for a functional compartmentation within the nucleus accumbens and for a preferential effect of psychostimulants and morphine in the shell of the nucleus accumbens at doses known to sustain intravenous drug self-administration

Technology Emergence as a Structuring Process:A Complexity Theory Perspective on Blockchain

Drawing on complexity theory, we investigate the structuring processes and underlying mechanisms underpinning the emergence of a new technology. Empirically, we track the emergence of blockchain technology by examining international patents issued between 2009 and 2020. Our results indicate that technology emergence follows an evolutionary trajectory that progresses from disordered to structured interactions among the technological elements, culminating in the formation of a technological core that acts as a pole of attraction for further interactions and delineates boundaries within the technological domain. Technology structuring is fueled by what we term “technology fitness” and “self-reinforcing” mechanisms that progressively transform primitive structures into more complex, self-organized configurations. Our study offers a novel framework of technology emergence, highlighting how dispersed bits of technological knowledge gradually aggregate into complex structures that define the specific trajectory of a particular domain

Ranolazine Attenuates Trastuzumab-Induced Heart Dysfunction by Modulating ROS Production

The ErbB2 blocker trastuzumab improves survival in oncologic patients, but can cause cardiotoxicity. The late Na+ current inhibitor ranolazine has been shown to counter experimental HF, including doxorubicin cardiotoxicity (a condition characterized by derangements in redox balance), by lowering the levels of reactive oxygen species (ROS). Since ErbB2 can modulate ROS signaling, we tested whether trastuzumab cardiotoxicity could be blunted by ranolazine via redox-mediated mechanisms. Trastuzumab decreased fractional shortening and ejection fraction in mice, but ranolazine prevented heart dysfunction when co-administered with trastuzumab. Trastuzumab cardiotoxicity was accompanied by elevations in natriuretic peptides and matrix metalloproteinase 2 (MMP2) mRNAs, which were not elevated with co-treatment with ranolazine. Trastuzumab also increased cleavage of caspase-3, indicating activation of the proapoptotic machinery. Again, ranolazine prevented this activation. Interestingly, Neonatal Rat Ventricular Myocytes (NRVMs), labeled with MitoTracker Red and treated with trastuzumab, showed only a small increase in ROS compared to baseline conditions. We then stressed trastuzumab-treated cells with the beta-agonist isoproterenol to increase workload, and we observed a significant increase of probe fluorescence, compared with cells treated with isoproterenol alone, reflecting induction of oxidative stress. These effects were blunted by ranolazine, supporting a role for INa inhibition in the regulation of redox balance also in trastuzumab cardiotoxicity

BCR-ABL residues interacting with ponatinib are critical to preserve the tumorigenic potential of the oncoprotein

Patients with chronic myeloid leukemia in whom tyrosine kinase inhibitors (TKIs) fail often present mutations in the BCR-ABL catalytic domain. We noticed a lack of substitutions involving 4 amino acids (E286, M318, I360, and D381) that form hydrogen bonds with ponatinib. We therefore introduced mutations in each of these residues, either preserving or altering their physicochemical properties. We found that E286, M318, I360, and D381 are dispensable for ABL and BCR-ABL protein stability but are critical for preserving catalytic activity. Indeed, only a "conservative" I360T substitution retained kinase proficiency and transforming potential. Molecular dynamics simulations of BCR-ABLI360T revealed differences in both helix αC dynamics and protein-correlated motions, consistent with a modified ATP-binding pocket. Nevertheless, this mutant remained sensitive to ponatinib, imatinib, and dasatinib. These results suggest that changes in the 4 BCR-ABL residues described here would be selected against by a lack of kinase activity or by maintained responsiveness to TKIs. Notably, amino acids equivalent to those identified in BCR-ABL are conserved in 51% of human tyrosine kinases. Hence, these residues may represent an appealing target for the design of pharmacological compounds that would inhibit additional oncogenic tyrosine kinases while avoiding the emergence of resistance due to point mutations.This work was supported by an investigator grant to P.V. from Associazione Italiana per la Ricerca sul Cancro (AIRC) and by funding from the Biotechnology and Biological Sciences Research Council (BB/I023291/1 and BB/H018409/1 to AP and FF). P.B. is the recipient of an AIRC - Marie Curie fellowship

Paramagnetic defects in polycrystalline zirconia: An EPR and DFT study

The paramagnetic defects present in pristine zirconium dioxide (ZrO2) and those formed upon reductive treatments (either annealing or UV irradiation in H-2) are described and rationalized by the joint use of electron paramagnetic resonance (EPR) and DFT supercell calculations. Three types of Zr3+ reduced sites have been examined both in the bulk of the solid (one center) and at the surface (two centers). Trapping electron centers different from reduced Zr ions are also present, whose concentration increases upon annealing. A fraction of these sites are paramagnetic showing a symmetric signal at g = 2.0023, but the majority of them are EPR silent and are revealed by analysis of electron transfer from the reduced solid to oxygen. The presence of classic F-type centers (electrons in bulk oxygen vacancies) is disregarded on the basis of the g-tensor symmetry. This is expected, on the basis of theoretical calculations, to be anisotropic and thus incompatible with the observed signal. In general terms, ZrO2 has Some properties similar to typical reducible oxides, such as TiO2 and CeO2 (excess electrons stabilized at cationic sites), but it is much more resistant to reduction than this class of materials. While point defects in doped (Y3+, Ca2+) ZrO2 materials have been widely investigated for their role as ionic conductors, the defectivity of pristine ZrO2 is much less known; this paper presents a thorough analysis of this phenomenon