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Locally constrained xylene-based cyclic mimetics of SOCS3 protein
No full textThe development of SOCS3 peptidomimetics targeting the JAK2 signaling pathway presents a promising strategy for modulating cytokine-driven diseases. In this study, we designed four novel monocyclic analogues of a previously reported linear lead compound (KIRCONG chim PEG), introducing local conformational constraints via regioselective thioether cyclization of either the KIR (thio-monoleft) or CONG (thio-monoright) regions. Each variant was synthesized with one or two PEG moieties (PEG1 or PEG2) to modulate solubility and flexibility. Microscale Thermophoresis (MST) revealed that thio-monoright PEG1 exhibited the highest affinity for the JAK2 catalytic domain, and inhibition assays further confirmed its superior ability to suppress JAK2 mediated phosphorylation. Circular dichroism (CD) and metadynamics simulations indicated enhanced structural organization and intramolecular hydrogen bonding in cyclic analogues, especially thio-monoright PEG1, as supported by Natural Bond Orbital (NBO) and Second Order Perturbation Theory (SOPT) analyses. Conversely, PEG2 analogues showed reduced activity and solubility, likely due to increased flexibility and aggregation arising from hydrophobic surface exposure, as demonstrated by fluorescence spectroscopy and solvent-accessibility calculations. Overall, thio-monoright PEG1 represents a promising conformationally stabilized SOCS3 mimetic with improved bioactivity, providing a rational foundation for further optimization of JAK2 targeting peptide therapeutics
Centro Studi sui Fondamenti del Diritto antico dell’Un. SuorOrsola Benincasa, Napoli, Dipartimento di Scienze giuridiche;
No full textComponente del LUPT, Laboratorio di Urbanistica e Pianificazione Territoriale, Centro interdipartimentale di ricerca dell’Università degli Studi di Napoli Federico II, responsabile dell’area Governo e gestione dei servizi e beni pubblici
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Unravelling the volcanic history of the Campanian Plain: A detailed study of mid-distance successions between 40 and 130 ka
No full textThe effectiveness of tephrochronology in reconstructing past events at high resolution relies heavily on accurate knowledge of the eruptive history of volcanic sources. For the Campanian Plain, southern Italy, distal and ultradistal tephra archives provide detailed geochemical and chronological records of its complex volcanism. In
contrast, proximal studies often depend on whole-rock geochemistry from outcrops that are frequently incomplete due to erosion or burial, limiting direct comparisons with glass-based datasets from distal sites. However, mid-distance buried successions offer a crucial archive, preserving volcanic layers often absent in proximal
settings. This study investigates two mid-distance successions retrieved from boreholes—Camaldoli della Torre (CdT) and San Marco Evangelista (SME)—and selected samples from the distal San Gregorio Magno (SGM) core covering the 130–40 ka interval. All three boreholes are located in the Campania region (Italy). Through a multimethod analytical approach, including major and trace elements, Sr-Nd isotopes, and new 40Ar/39Ar dating, we characterize key tephra layers and identify previously unrecognized correlations to widespread Mediterranean tephra markers. Additionally, we evaluate the potential of using whole-rock geochemical data for correlation with glass compositions from distal sites, in order to assess whether such comparisons can be reliably employed in tephrostratigraphic studies. Our findings highlight the pivotal role of buried successions in reconstructing a more complete volcanic record revealing the additional occurrences of key Mediterranean tephra markers
Algorithmic ethics and healthcare pluralism: rethinking care between automation and global inequality
No full textAlgorithmic systems in healthcare are increasingly recognised not only as technical devices but as infrastructures that embed,enact, and stabilise normative assumptions about care, clinical authority, and social worth. This article offers a comparativeanalysis of algorithmic governance across the Global North, addressing concerns about over-generalisation and insufficientengagement with Global South perspectives, with a case-study focus on Benin. The paper shows how algorithmic tools—when transplanted into African contexts—may reproduce or intensify forms of epistemic displacement, infrastructuraldependency, and digital paternalism, while simultaneously overlooking locally embedded, relational, and community-basedpractices of care. Integrating new empirical insights from field studies conducted by the author in Benin (2016–2024), thearticle reframes algorithmic normativity as a dynamic, contested process shaped by sociotechnical imaginaries, politicaleconomies, and situated practices of health provision. In response, it elaborates a solidarity-based governance frameworkbuilt around technological subsidiarity and epistemic solidarity, two principles that emerge directly from the comparativeanalysis rather than being externally imposed. This framework offers a means to align AI development with context-specificethical commitments, plural knowledges, and participatory forms of clinical judgment, particularly in low-resource settings.By explicitly integrating decolonial critiques, Global South authorship, and empirical evidence, the paper contributes arevised, theoretically coherent, and policy-relevant model for understanding and governing algorithmic care across unequalhealthcare ecologies
