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L’oltraggio a p.u. nuovamente al vaglio della Consulta: non manifestamente sproporzionato il minimo di pena di sei mesi di reclusione
No full textWith the judgment under comment, the Constitutional Court n. 166/2024 has declared unfounded
a new q.l.c. concerning the offence of contempt to a public official provided for under Article 341-
bis, ruling out that the provision of a minimum sentence of six months’ imprisonment is in conflict
with the fundamental principle of proportionality of punishment. The solution adopted by the
Court - which was careful not to trespass on strictly political evaluations - is, in our opinion,
acceptable. However, serious doubts remain as to the very appropriateness of criminalising
outrage against a public official in light of the changing relationship between the person and
public authorit
Characterization of a global navigation satellite system's vertical measurement system for sea state monitoring
No full textThis study investigates the effectiveness of Global Navigation Satellite System (GNSS) signals for measuring vertical displacement (or heave) in dry conditions, using a controlled pendulum to create a wave-like motion. The experiment was conducted using three GNSS receivers operating in different measurement modes: Single Point (SP), Differential GNSS (DGNSS), and Real Time Kinematics (RTK). An Inertial Navigation System (INS), with high precision for navigation applications, was previously verified, then used as a reference in the experiment. The vertical motion, or heave, was obtained from the three receivers, considering the position measurements or by integrating the velocity measurements over time. Results indicate that GNSS velocity measurements are effective, but precision is limited by sensor characteristics. The RTK mode provided the highest accuracy, with a deviation of 2.5 % from the reference signal, followed by DGNSS at 3.5 %, and SP mode at 4 %. Altitude-based heave estimations showed similar trends, with RTK being the most accurate. However, signal loss in the RTK mode poses challenges in the management of measurement data, impacting measurement stability. The findings suggest that, while GNSS-based heave estimation is feasible, improvements in velocity precision and correction signal reliability are necessary for enhanced accuracy. This study provides insights into GNSS-based motion measurement techniques, highlighting their potential and limitations in marine applications
Classifying ARDS by dynamic or static oxygenation impairment or are other approaches needed for greater value
No full textSulfavant A: Dissecting immunomodulatory mechanisms in vitro and in vivo for translational immunotherapy
No full textSulfavant A (SA), un nuovo adiuvante sulfolipidico sintetico derivato da alghe marine, rappresenta un approccio trasformativo nell’immunomodulazione e nella tecnologia degli adiuvanti. Questo studio esplora le proprietà immunomodulatorie di Sulfavant A, con particolare attenzione ai suoi effetti sulle cellule natural killer (NK). Esaminando la modulazione della risposta immunitaria in funzione della concentrazione e del contesto, attraverso l’espressione dei recettori, l'attivazione e la funzionalità delle cellule, la ricerca chiarisce il potenziale di Sulfavant A come agente promettente per l'immunoterapia contro il cancro, lo sviluppo di vaccini e la regolazione immunitaria.
È stato dimostrato che Sulfavant A induce la maturazione delle cellule dendritiche in modo dose- e tempo-dipendente, evidenziata dalla sovraregolazione di CD80, CD86 e HLA-DR, migliorando così la presentazione dell'antigene, l'attivazione delle cellule T e facilitando la migrazione delle cellule dendritiche nei tessuti linfoidi (ref). Sulfavant A stimola inoltre le cellule presentanti l'antigene (APC) e le risposte immunitarie adattive, indicando la sua capacità di collegare l’immunità innata e adattativa (1).
In diversi esperimenti, pubblicati di recente, le risposte delle cellule T hanno mostrato una regolazione peculiare dopo la stimolazione con SA, con basse concentrazioni che promuovono la proliferazione e concentrazioni più elevate che sopprimono l'attivazione (2), indicando una modulazione dose-dipendente dell’immunità adattativa. Questa modulazione contestuale potrebbe essere cruciale per identificare nuovi adiuvanti, poiché fornisce flessibilità nel modulare le risposte immunitarie in base alle esigenze terapeutiche, mirando a evitare gli effetti pro-infiammatori indotti dagli adiuvanti convenzionali.
Le seguenti proprietà indicano che SA può essere un candidato come adiuvante.
Le intuizioni meccanicistiche sul crosstalk NK-DC hanno rivelato che Sulfavant A facilita le interazioni recettore-ligando, inclusa NKG2D-MICA/B, promuovendo l'attivazione delle cellule NK e la maturazione delle cellule dendritiche. Questa attivazione bidirezionale di cellule NK e DC rafforza la sinapsi immunologica, amplificando le risposte immunitarie cruciali per l’eliminazione dei patogeni e la sorveglianza tumorale. In particolare, le interazioni tra NKG2A e HLA-E svolgono un ruolo cruciale nel mantenere l’omeostasi immunitaria, prevenendo risposte infiammatorie eccessive—un'altra caratteristica essenziale per gli adiuvanti, che bilancia l'attivazione e la regolazione immunitaria.
Sulfavant A presenta diverse caratteristiche chiave di un promettente adiuvante, grazie alla sua capacità di stimolare sia le risposte immunitarie innate che adattative, modulare l’espressione dei recettori immunitari in modo dose- e contesto-dipendente e regolare finemente l’equilibrio tra attivazione e regolazione immunitaria. La sua capacità di promuovere la maturazione delle cellule dendritiche, l'attività delle cellule NK e le risposte delle cellule T, senza indurre tossicità immunitaria eccessiva, ne evidenzia il potenziale come adiuvante di nuova generazione per l’immunoterapia contro il cancro, le malattie autoimmuni, l’infiammazione e lo sviluppo di vaccini.Sulfavant A (SA), a novel synthetic sulfolipid adjuvant derived from marine algae, represents a transformative approach in immunomodulation and adjuvant technology. This study reports an exploitation of Sulfavant A’s immunomodulatory properties, with a particular focus on its effects on natural killer (NK) cells. By exploring concentration- and context-dependent modulation of immune cell receptor expression, activation, and functionality, the research elucidates Sulfavant A’s potential as a promising agent for cancer immunotherapy, vaccine development, and immune regulation.
It has been shown that Sulfavant A induced maturation of dendritic cells, in a dose- and time-dependent manner, marked by upregulation of CD80, CD86, and HLA-DR, thus enhancing antigen presentation and T cell activation and facilitating DC migration to lymphoid tissues (ref). Sulfavant A also stimulate antigen-presenting cells (APCs) and adaptive immune responses indicating its capacity to bridge innate and adaptive immunity (1).
In several experiments, published recently, T cell responses exhibited a peculiar regulation upon SA stimulation, with low concentrations promoting proliferation and higher concentrations suppressing activation (2), indicating a dose-dependent modulation of adaptive immunity. This context-dependent modulation may be critical to identify new adjuvants, as it provides flexibility in tailoring immune responses according to therapeutic needs, aiming to avoid proinflammatory effects induced by conventional adjuvant.
The following properties indicate that SA can be a candidate to be used as adjuvant.
Mechanistic insights into NK-DC crosstalk revealed that Sulfavant A facilitated receptor-ligand interactions, including NKG2D-MICA/B promoting NK cell activation and DC maturation. This bidirectional activation of NK cells and DCs enhances the immunological synapse, amplifying immune responses crucial for pathogen clearance and tumor surveillance. Notably, interactions between NKG2A and HLA-E play a critical role in maintaining immune homeostasis, preventing excessive inflammatory responses—another essential feature for adjuvants to balance immune activation and regulation.
Sulfavant A exhibits several key features of a promising adjuvant due to its ability to stimulate both innate and adaptive immune responses, modulate immune receptor expression in a context- and dose-dependent manner, and fine-tune the balance between immune activation and regulation. Its capacity to promote dendritic cell maturation, NK cell activity, and T cell responses, without inducing excessive immune toxicity, highlights its potential as a next-generation adjuvant for cancer immunotherapy, autoimmune diseases, inflammation, and vaccine development
The improvement of reliability of circuits based on operational amplifiers in piezoelectric shunt
No full textPiezoelectric shunt is an approach useful in different fields, such as vibration control and isolation as well as structural health monitoring. In several applications, the shunt circuits include one or more operational amplifiers. This can be due either to the ease of implementation of some electrical components (e.g. inductances with high value, negative resistances to compensate possible parasitic ones) or to increase the performance of the system. Indeed, increasing the coupling between the hosting structure and the piezoelectric element improves the performance of the system. A common approach for the increase of the coupling is the use of negative capacitances in the shunt circuit, which are based on operational amplifiers. A main issue when dealing with these types of circuits is related to the risk of saturation of the outputs of the operational amplifiers, which can lead to non-proper functioning of the piezoelectric system and even to system instability. This manuscript focuses on shunt circuits based on negative capacitance to propose two different approaches, which can be even employed together, for lowering the outputs of operational amplifiers without affecting the system behaviour and performance. The two methods are described analytically and are then shown to be reliable and feasible through an experimental campaign. The first proposed method allows a reduction of 50 % of the voltage output of the operational amplifier, while the benefit provided by the second proposed method can be larger or smaller depending on the modal data of the system. As mentioned, the two methods can be coupled to reach a voltage output reduction larger than 50 %
Cladophialophora boppii Causing Onychomycosis: The Burden of Identifying Unusual Pathogenic Molds
No full textStratigraphy, paleontology, and depositional setting of the Late Eocene (Priabonian) lower Pagat Member, Tanjung Formation, in the Asem Asem Basin, South Kalimantan, Indonesia
No full textMarine sedimentary rocks of the late Eocene Pagat Member of the Tanjung Formation in the Asem Asem Basin near Satui, Kalimantan, provide an important geological archive for understanding the paleontological evolution of southern Kalimantan (Indonesian Borneo) in the interval leading up the development of the Central Indo-Pacific marine biodiversity hotspot. In this paper, we describe a moderately diverse assemblage of marine invertebrates within a sedimentological and stratigraphical context. In the studied section, the Pagat Member of the Tanjung Formation records an interval of overall marine transgression and chronicles a transition from the marginal marine and continental siliciclastic succession in the underlying Tambak Member to the carbonate platform succession in the overlying Berai Formation.The lower part of the Pagat Member contains heterolithic interbedded siliciclastic sandstone and glauconitic shale, with thin bioclastic floatstone and bioclastic rudstone beds. This segues into a calcareous shale succession with common foraminiferal packstone/rudstone lenses interpreted as low-relief biostromes. A diverse trace fossil assemblage occurs primarily in a muddy/glauconitic sandstone, sandy mudstone, and bioclastic packstone/rudstone succession, constraining the depositional setting to a mid-ramp/mid to distal continental shelf setting below fair-weather wave base but above storm wave base.Each biostrome rests upon a storm-generated ravinement surface characterized by a low-diversity Glossifungites or Trypanites trace fossil assemblage. The erosional surfaces were colonized by organisms that preferred stable substrates, including larger benthic foraminifera, solitary corals, oysters, and serpulid annelid worms.The biostromes comprised islands of high marine biodiversity on the mud-dominated Pagat coastline. Together, the biostromes analyzed in this study contained 13 genera of symbiont-bearing larger benthic foraminifera, similar to 40 mollusk taxa, at least 5 brachyuran decapod genera, and 6 coral genera (Anthemiphyllia, Balanophyllia, Caryophyllia, Cycloseris, Trachyphyllia, and Trochocyathus), as well as a variety of bryozoans, serpulids, echinoids, and asterozoans. High foraminiferal and molluscan diversity, coupled with modest coral diversity, supports the hypothesis that the origin of the diverse tropical invertebrate faunas that characterize the modern Indo-Australian region may have occurred in the latest Eocene/earliest Oligocene
La valutazione di compatibilità degli aiuti di Stato alla luce del criterio di sostenibilità ambientale “Do No Significant Harm”
No full textIl presente contributo indaga la possibile adozione del criterio DNSH quale parametro generale per valutare la compatibilità degli aiuti di Stato al mercato interno, al fine di garantire che l’intervento pubblico nell’economia sia allineato agli obiettivi di tutela ambientale dell’Unione, in ossequio al principio di integrazione. Premessa una sintetica ricostruzione della disciplina degli aiuti di Stato a finalità ambientale (par. 2), sono approfondite le attestazioni e l’evoluzione del concetto di DNSH nel diritto dell’Unione (par. 3) e, specificamente, nella disciplina degli aiuti di Stato (par. 4), sottolineando l’opportunità di inquadramento sistematico del DNSH quale criterio di applicazione in concreto del principio di integrazione piuttosto che come principio autonomo. Successivamente, è approfondita la prassi decisionale sull’applicazione del criterio DNSH nella procedura di controllo degli aiuti, evidenziando alcuni rischi di greenwashing (par. 5). In conclusione, sono discusse le possibili implicazioni derivanti da una più ampia applicazione del criterio DNSH nel controllo degli aiuti, sia in prospettiva ex ante (valutazione di compatibilità) che ex post (monitoraggio e trasparenza, par. 6).The paper investigates the possible adoption of the DNSH criterion as a general parameter for assessing the compatibility of State aid with the internal market, in order to ensure that public intervention in the economy is aligned with the EU environmental protection objectives, according to the integration principle. After outlining the legal framework applicable to environmental State aid (para. 2), the paper traces back the origins of the DNSH concept and its evolution in EU secondary legislation (para. 3) and, specifically, in the State aid regime (para. 4), supporting the systematic framing of DNSH as a criterion for implementing the integration principle rather than as an autonomous principle. Then, some examples of the Commission’s practice on the application of the DNSH criterion in State aid procedure are examined, emphasizing some risks of greenwashing (para. 5). In conclusion, the possible implications of a broader application of the DNSH criterion in State aid control are discussed, both from an ex ante (compatibility assessment) and an ex post perspective (monitoring and transparency, para. 6)
