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Lohs, Jacopo. „Subiectio e Oboedientia: Lessico e fondamento del potere in Francesco di Meyronnes (XIV sec.)“. Rivista Italiana di Filosofia Politica, Nr. 6 (05.10.2024): 169–90. http://dx.doi.org/10.36253/rifp-2469.
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La riflessione politica di Francesco di Meyronnes (m. 1328) contiene un’elaborazione personale connessa ai concetti di sottomissione (subiectio) e obbedienza (oboedientia), e si inscrive all’interno del pensiero teologico-politico del suo tempo, dove il dibattito sul potere assume forme e direzioni molto diverse. Nei suoi scritti, la concezione politica di Meyronnes è espressa attraverso analogie cosmologiche, naturalistiche e metafisiche, in cui il dato filosofico e quello religioso si riverberano all’interno di un discorso circolare che da Dio va all’uomo e dall’uomo a Dio. L’interrogazione dell’uomo, rivolta al funzionamento di ciò che sta al di sopra, ricerca l’ordine migliore tra i vari tipi di potere. Tra potere spirituale e potere temporale esiste un nesso che muove il secondo termine al primo “sicut ad finem”, e grazie ad esso viene nobilitato. L’obbedienza (oboedientia) di uno all’altro, che implica sottomissione (subiectio) – pur trovando il proprio fondamento implicito nello ius naturale e nella lex divina – non avviene se non per mezzo di un atto volontario.
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Kotecki, Dariusz. „Władza świecka w świetle Apokalipsy św. Jana“. Verbum Vitae 14 (14.12.2008): 173–97. http://dx.doi.org/10.31743/vv.1487.
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L'articolo affronta il tema della relazione dei cristiani al potere temporale civile alla luce dell'Apocalisse di san Giovanni. L'autore dell'Apocalisse presenta il potere civile come un sistema terrestre che vuole escludere dalla vita sociale Dio stesso. Giovanni lo fa tramite tre immagini: una bestia dal mare (13,1-10), un'altra bestia dalla terra (13,11-18) e la grande prostituta (17-18). Questi tre personaggi vengono descritti come i servi di satana. L'analisi delia simbologia di tutti i tre quadri ci ha portato alla conclusiane che il primo personaggio rappresenta lo stato che vuole essere adorato e cosi occuppare il posto appartenente a Dio stesso, il secondo si riferisce alla propaganda di tale stato, infine la figura della grande prostituta e una descrizione dell'aspetto consumistico della societa umana. L'emanazione storica di questi tre immagini fu sicuramante nei tempi dell'Apocalisse l'impero romano. Il cristiano vivendo in tale sistema deve essere consapevole della sua potenza e sapere che cosa bisogna fare con questo sistema che crea un contesto omogeno negativo e trova la sua ultima manifestziane nella consumistica citta di Babilonia. Il potere dello stato, della sua propaganda, del consumismo non possano occupare nella vita dei cristiani il posto di Gesu Cristo, l'unico salvatore de l mondo.
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Battista, Ludovico. „Mosè typus papae nel decreto Moyses vir Dei (1439). II parte: Le radici nella dottrina teocratica.“ De Medio Aevo 12, Nr. 2 (11.10.2023): 243–76. http://dx.doi.org/10.5209/dmae.91170.
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Il presente saggio si propone di prendere in esame la trattatistica filo-papale di Pietro del Monte e Juan de Torquemada, per evidenziare come l’applicazione tipologica al papa del modello di Mosè testimoni una lenta ma significativa trasformazione ideologica del suo potere, che lo ha portato a modificare la propria proiezione universalistica adattandola al nuovo contesto delle potenze europee, e a sdoppiarsi in due nature: una sempre spirituale e sacerdotale, l’altra apertamente temporale e principesca, con la nascita di un vero e proprio principato ecclesiastico. Per comprendere le specificità di questa evoluzione ideologica, il paper ne rileva tuttavia anche gli elementi di continuità con la trattatistica teocratica precedente, che la resero possibile e la fecero sviluppare a partire dalle tradizionali istanze universalistiche. In questo senso, dimostrando come i passi sull’interpretazione tipologica di Mosè come figura papale fossero in larga parte dipendenti da autori come Egidio Romano, Giacomo da Viterbo e Agostino d’Ancona, ci si propone di evidenziare su quali basi ideologiche si innestasse quest’evoluzione e su quali aspetti essa facesse perno. Ne emerge così una nuova immagine dei motivi teorici e delle condizioni di possibilità della trasformazione della sovranità papale sul modello di Mosè, ruotante in particolare attorno alla straordinaria elaborazione teologico-politica di Egidio Romano, che aveva tematizzato la supremazia assoluta del pontefice come riserva di potere d’eccezione rispetto alla legge e all’ordine che egli pone, quindi la legittimità dell’utilizzo straordinario della spada temporale al fine di difendere il bene spirituale.
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De Cristofaro, Ernesto. „La sovranità nei corsi di Foucault al Collège de France“. Italian Review of Legal History, Nr. 8 (21.12.2022): 313–40. http://dx.doi.org/10.54103/2464-8914/19256.
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Tra i temi di carattere giuridico e politico quello della sovranità è il più presente nei corsi che Michel Foucault ha tenuto presso il Collège de France dal 1970 al 1984. L’insegnamento presso questa istituzione – intitolato, nel suo caso, Storia dei sistemi di pensiero - obbedisce a regole particolari. Una tra queste è l’obbligo gravante sui docenti a non riproporre, di anno in anno, lo stesso corso di lezioni svolte in precedenza, ma di cambiare argomento. Al netto di questa clausola, negli anni che vanno dal 1973 al 1979, Foucault si occupa ripetutamente e intensamente di questioni che hanno una connessione molto esplicita e diretta con la dimensione del potere. Alcuni dei corsi tenuti costituiscono la base di opere che egli pubblica in questo periodo come Sorvegliare e punire o La volontà di sapere. È, certamente, all’interno dei corsi che si viene profilando l’idea del potere che attraversa la sua ricerca in questa fase temporale ed è grazie a questo laboratorio trasparente del suo lavoro che è possibile seguire l’analisi e la rielaborazione che egli svolge sull’argomento “sovranità”. Sebbene questo termine non sia mai espressamente presente nei titoli delle annualità didattiche, molte delle lezioni che impegnano l’insegnamento affidato a Foucault convergono su questa categoria. Foucault riceve dalla teoria giuridica e dalla politologia una parola alla quale si attribuisce pacificamente un preciso significato. Il titolare del potere sovrano è rappresentato, da una lunghissima e importante tradizione, come colui attorno al quale ruota il funzionamento dello Stato. Il sovrano è posto “in alto” e “al centro” della mappa del potere come il punto a partire dal quale e verso il quale si muovono tutti gli ingranaggi essenziali che fanno funzionare la macchina statuale. Inoltre, il sovrano è colui che esercita il proprio potere attraverso l’uso di una forza eminente, idonea a far rispettare le leggi, mantenere l’ordine e inibire qualunque ipotesi di sedizione. Foucault intende, viceversa, mettere in discussione questa lettura. L’itinerario che egli segue punta verso una fenomenologia dei rapporti di potere colti nella loro multiformità e disseminazione. Si tratta di osservare il potere rinunciando alla prospettiva della verticalità, come se esso fosse collocato presso una sola sede, alla prospettiva della patrimonialità, come se esso fosse posseduto esclusivamente da qualcuno e, infine, alla prospettiva della repressione, come se l’unica lingua che esso sapesse parlare fosse quella dell’intimidazione, della sanzione e delle armi. Per rileggere il potere bisogna, al contrario, studiarne il funzionamento presso apparati parziali della società, distribuiti trasversalmente e in grado di implementare una tecnologia che non si fonda sull’interdizione ma, al contrario, sulla sollecitazione della disciplina. Lungo il suo itinerario Foucault incontra lo sviluppo storico della penalità, nel cui perimetro viene sviluppandosi un potere fortemente individualizzante, capace di perseguire un incasellamento degli individui che si serve di molteplici tecniche di osservazione e descrizione operanti a vari livelli della struttura sociale; la storia della psichiatria, grazie alla quale la distinzione normale/anormale, e le conseguenti misure di monitoraggio e controllo della condotta deviante, hanno potuto avvalersi dell’uso di parametri “scientifici” e, pertanto, più cogenti; infine, la biopolitica, che ha ricollocato il tema della sottoposizione dei corpi a regole e vincoli, in vista della massimizzazione delle loro prestazioni, dalla scala degli individui a quella delle popolazioni, lasciando apparire dietro la figura tralatizia del sovrano che esprime la propria egemonia decidendo chi possa vivere e chi debba morire, l’immagine assai più concreta del potere anonimo delle regole di alimentazione, igiene e profilassi che stabiliscono come un’intera collettività debba essere curata e protetta.
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Fiorentino, Carlo M. „Lo stato della chiesa dal Congresso di Vienna alla fine del potere temporale“. Römische Historische Mitteilungen 1 (2016): 213–22. http://dx.doi.org/10.1553/rhm58s213.
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De La Hera, Alberto. „RENATO MORI, Il tramonto del potere temporale, 1866-1870, 1 vol. de 618 págs., n.º 15 de la Colec. "Politica e Storia. Raccolta di studi e testi a cura di Gabriele De Rosa", Edizioni di Storia e Letteratura, Roma, 1967“. Ius Canonicum 9, Nr. 17 (13.04.2018): 293–94. http://dx.doi.org/10.15581/016.9.22616.
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Martinelli, Monica, und Mauro Magatti. „Autorità, potere e spirito del capitalismo. Stili di leadership in impresa“. SOCIOLOGIA DEL LAVORO, Nr. 162 (März 2022): 98–120. http://dx.doi.org/10.3280/sl2022-162005.
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Autorità, potere e spirito sono tre categorie che vengono diversamente comprese e articolate. Nello sviluppo dei modelli di capitalismo e nelle varie forme di leadership, la dimensione trascendente (evocata dall'autorità) arretra a favore di quella immanente (che contrassegna il potere), lasciando tuttavia irrisolte questioni cruciali per le organizzazioni e il modello di sviluppo socio-economico, nei loro (imprescindibili) nessi con la dimensione antropologica che il termine ‘spirito', in senso weberiano, manifesta. Il testo ripercorre l'evoluzione dei modelli gestionali nelle imprese dentro le diverse forme di capitalismo attorno a tre passaggi temporali: gli albori del capitalismo occidentale moderno, le trasformazioni avvenute nel ‘900 e soprattutto a inizio del XXI secolo con il capitalismo delle piattaforme, le possibili alternative verso un nuovo spirito del capitalismo. In questi passaggi, l'articolazione ‘autorità-potere', nonostante apparentemente irrilevante, in realtà sopravvive mettendo in luce la cruciale questione del riferimento a una dimensione ‘spirituale' che riguarda le forme organizzate.
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Okhrimenko, Valeriia. „LINGUOPRAGMATIC FEATURES OF THE MEANING FIELD OF DESCRIPTIVE TEXTS (ON THE MATERIAL OF DESCRIPTION OF THE CHARACTER OF UNKNOWN IN THE NOVEL OF A. MANZONI “BETROTHED”)“. PROBLEMS OF SEMANTICS, PRAGMATICS AND COGNITIVE LINGUISTICS, Nr. 45 (2024): 79–93. http://dx.doi.org/10.17721/2663-6530.2024.45.08.
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The linguopragmatic features of descriptive texts devoted to the description of the negative character Nameless in A. Manzoni's novel "Betrothed" are analyzed. It has been established that the regularities of information quantization in the semantic field of descriptive texts can be schematically presented in the following way: referent-subject – quality of the referent (evaluation) – locative markers (peculiarities of perception) – temporal markers (sequence of referent-subject’s potential actions, repetition), unfolding of causal structures. It has been established that the organization of meaning-making of a descriptive text is determined by the modal meaning of intrinsic possibility that implies a connection between a subject and its immanent quality. Such connection determines subject’s typical behavior and is related to generalization and evaluability. Tha modal meaning of intrinsic possibility is based on the connection “generalized quality – potential ability”. The connection between subject and its immanent characteristics determines the quantization of information in a microtext and counteracts the openness of channels of information deployment. Temporal relations in descriptive texts are usually expressed through Imperfetto (repeatability, generalization), Modo Condizionale (evaluation), Periodo Ipotetico (unfolding of causal structures). In the semantic space of A. Manzoni’s novel “Betrothed” denotative lexical units (evaluatively neutral vocabulary, locative markers) can acquire an evaluative meaning under the influence of sense field of descriptive texts. Descriptive texts verbalize system-forming meanings “immanent property”, “potential ability”, “evaluation”, “conditionality”, “generalization”. The various linguistic means that verbalize the specified system-forming meanings include Imperfetto (repeatability, generalization), Modo Condizionale, lexical units of evaluative semantics (immanent property, evaluability), Periodo Ipotetico (potential ability, conditionality), existential predicate “essere”, verbs of semantics of movement being part of stylistic device of personification, verbs of causal semantics, modal units of intrinsic possibility “potere”, “ardire”. The dominance of statics over dynamics in descriptive text determines the peculiarities of the functioning of verbs of movement being part of stylistic device of personifications when describing natural phenomena (“saliva”, “si spiegava”, “scorreva”). Verbs to indicate actions of referent-subject as potentially possible in the unfolding of causal structures are introduced not directly but through the modal verbs of intrinsic possibility “potere”, “ardire”. Temporal markers are used to show the sequence of referent-subject’s typical actions. To describe the image of the Nameless in the novel “Betrothed”, A. Manzoni chooses stylistic devices that are organized according to the principle of relevant salience. Synonymous series of lexical units with evaluative connotation creates a negative evaluation in the semantic field of descriptive texts. Descriptive text models top-down perception that is determined by subject’s immanent quality. Personification performs the function of emphasis (“sporge in fuori”), metonymy – generalization (quantifiers of totality: “tutto”, “nessuno”), simile and epithet – evaluation. Perception is verbalized in the direction "from top to bottom" through antithesis and gradation. The main stylistic device is antithesis reflecting the opposition between the negative character and the environment. Metonymy and synecdoche form an antithesis that accentuates the contrast between the omnipotence of the Nameless and the powerlessness of his enemies.
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Bottalico, Francesca, Valentina Colonna, Simona Teresa Di Ruvo und Rossella Perillo. „I primi 1000 giorni delle famiglie: l'esperienza de La Casa della Genitorialità“. MINORIGIUSTIZIA, Nr. 3 (April 2023): 59–68. http://dx.doi.org/10.3280/mg2022-003007.
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La Casa della Genitorialità e un progetto innovativo di sostegno e accompagnamento per neogenitori. I primi 1000 giorni di vita costituiscono una finestra temporale decisiva per costruire le basi per un adeguato sviluppo fisico e psichico del bambino e attivare tempestivamente interventi di prevenzione e protezione in situazioni di fragilita e di pregiudizio, per tutelare e migliorare la qualita di vita del bambino con effetti duraturi anche in eta adulta. Una famiglia adottiva, al pari di una famiglia biologica, ha necessita di 1000 giorni (e oltre), indipendentemente dall'eta anagrafica del bambino, per settare e declinare uno spazio di vita funzionale alla crescita del figlio e, al pari di un bambino appena venuto al mondo, un bambino gia nato e rinato all'interno di una nuova famiglia, non biologica ma adottiva, ha bisogno di 1000 giorni (e oltre) per poter destrutturare e ristrutturare la sua vita e i suoi legami.
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Fantozzi, Donatella. „Insegnare e apprendere nella scuola secondaria: paradigmi teorici e declinazioni operative per una scuola inclusiva“. EDUCATION SCIENCES AND SOCIETY, Nr. 1 (Juni 2021): 164–77. http://dx.doi.org/10.3280/ess1-2021oa11861.
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La necessità di pensare ad un percorso formativo che permetta al futuro insegnante di sperimentare il proprio apprendimento teorico attraverso modalità operative quali il tirocinio, le attività laboratoriali, l'affiancamento di colleghi esperti durante il primo periodo di servizio, la formazione continua per tutto l'arco temporale dello svolgimento della professione, emerge a chiare note sia dalla ricerca scientifica che dai monitoraggi internazionali OCSE sullo status della scuola e sulle competenze dei docenti; emerge del resto anche dalle risposte dagli aspiranti insegnanti che esprimono, nelle risposte all'indagine presentata, l'esigenza di acquisire competenze specifiche circa la didattica inclusiva, la collegialità e l'interdisciplinarità, dispositivi ritenuti irrinunciabili per poter e saper declinare l'insegnamento in apprendimento. Il contributo presenta i risultati di un'indagine esplorativa svolta tra gli iscritti presso l'Università di Pisa, negli aa.aa. 2018/2019 e 2019/2020, al Percorso Formativo per l'acquisizione dei 24 Crediti Formativi Universitari necessari per accedere all'insegnamento, indagine volta a misurare la soddisfazione e i desiderata dei partecipanti.
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Cesqui, Elisabetta. „Osservazioni asistematiche sul primo quadriennio di applicazione del nuovo sistema disciplinare“. QUESTIONE GIUSTIZIA, Nr. 5 (Januar 2011): 63–111. http://dx.doi.org/10.3280/qg2010-005007.
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Dal 19 giugno del 2006 il sistema disciplinare introdotto dal d.lgs 109/ 2006, in attuazione dell'art. 1, comma 1, lett. f della legge 25 luglio 2005 n. 150 č entrato in vigore. Privo originariamente di qualunque disposizione transitoria, esso č stato modificato in alcuni punti essenziali dalla legge 24 ottobre 2006 n. 269, che ha smussato le maggiori asperitŕ del testo originario (con riferimento soprattutto ad alcuni degli illeciti tipizzati e al potere di intervento del ministro in dibattimento) e ha introdotto, per la fase di transizione dal vecchio al nuovo regime, il principio dell'applicazione della norma di maggior favore limitatamente ai procedimenti disciplinari iniziati dopo la sua entrata in vigore ed esclusivamente per i fatti verificatisi in un momento precedente a essa (Cass., sez. unite, 26 ottobre 2006 n. 27172). Le cadenze temporali imposte al procedimento disciplinare dall'art. 15 (un anno dalla conoscenza del fatto per l'inizio nell'azione, due anni per le indagini e due anni per il dibattimento) e i tempi rilevabili dalla esperienza concreta, consentono di dire che i quattro anni della consigliatura appena conclusa rappresentano un campione significativo e che la fase di transizione, fatti salvi i procedimenti (non molti) per i quali la sospensione per pregiudiziale penale ha congelato il procedimento e quelli (pochi) che dovessero eventualmente nascere per fatti antecedenti venuti a conoscenza dei titolari dell'azione disciplinare con molto ritardo (fermo restando il limite decennale di decadenza dell'azione introdotto dal comma 1 bis dell'art. 15), č ormai sostanzialmente conclusa.
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Bagul, S., und D. Laefer. „THREE-DIMENSIONAL ENABLEMENT OF PLACE-BASED, PANDEMIC BEHAVIORS“. ISPRS Annals of the Photogrammetry, Remote Sensing and Spatial Information Sciences X-4/W2-2022 (14.10.2022): 21–28. http://dx.doi.org/10.5194/isprs-annals-x-4-w2-2022-21-2022.
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Abstract. Harvesting usable and meaningful disaster-related, spatio-temporal data at a highly granular level poses major challenges in its cleaning and aggregation. This paper presents a strategy related to those challenges with respect to individual behavior near COVID-19 laden healthcare facilities. This is done to enable the visualizing of egress behavior data as interactive, three-dimensional (3D) scenes to investigate human behavior patterns regarding touch-based, disease transmission. Therefore, the aim is to demonstrate how this concept of 3D epidemiology may provide new mechanisms to understand the relative risk and exposure prevalence for data analysis. This paper demonstrates 3D enablement of disaster-related field data through use of first-hand observations of 1,936 individuals egressing New York City healthcare facilities during the onset of COVID-19 in the Spring of 2020. The observations capture egress behavior in terms of where people go (e.g. coffee shop, Subway) and how they physically interact with the surroundings (i.e. what they touch and how long they remain). This paper introduces a mechanism for automated extraction and 3D visualization of such data in Potree, an open-source Web Graphics Library (WebGL) point cloud viewer. Distinctive vertex shaders are used to distinguish specific destination selection and behavioral patterns (e.g. personal protective equipment usage). Two-dimensional heatmaps are paired with 3D scenes to demonstrate the potential of using 3D visualization of spatio-temporal patterns for visualizing disease transmission potential.
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Pamart, A., R. Roussel, E. Hubert, A. Colombini, R. Saleri, E. M. Mouaddib, Y. Castro, G. Le Goïc und A. Mansouri. „A SEMANTICALLY ENRICHED MULTIMODAL IMAGING APPROACH DEDICATED TO CONSERVATION AND RESTORATION STUDIES“. International Archives of the Photogrammetry, Remote Sensing and Spatial Information Sciences XLVI-2/W1-2022 (25.02.2022): 415–20. http://dx.doi.org/10.5194/isprs-archives-xlvi-2-w1-2022-415-2022.
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Abstract. For the past decades, Cultural Heritage (CH) is commonly documented by digital-based imaging and analytical techniques. This documentation is used as a support by heritage scientists to study and help the preservation of CH objects. Multiple techniques or modalities are usually required and applied to complete the documentation and the possible diagnostic from it. In this paper we explored multimodal imaging strategies to survey, analyse and share semantically enriched digital replicas. Three challenging case-studies from the SUMUM research project aims to illustrate efficient multi-source approaches in multi-scalar, multi-temporal and multi-spectral contexts. From multimodal data acquisitions, a photogrammetric-based registration method (TACO) has been developed in order to exploit a 2D/3D semantic annotation process implemented into a CH oriented collaborative web platform (AIOLI). In the exemples showed, the structure and the content of the annotations work is based from condition reports provided by conservation and restoration experts. To this end, all the documentation gathered on CH objects are either directly merged by image based registration while complementary analysis can be spatially anchored to annotations as linked resources. The dissemination part is explored by built-in AIOLI’s collaborative features or external Potree-based viewer, to enhance the accessibility of the final 3D annotated scenes for further expertises or wide-public events and purposes.
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Eslava, Nora, Leo Walter González Cabellos, Francisco Guevara und Juan Miguel Rodríguez. „Caracterización y desempeño de la pesca artesanal del pulpo (Octopus vulgaris) usando potes en Venezuela“. TECNOCIENCIA Chihuahua 11, Nr. 1 (17.03.2017): 33–41. http://dx.doi.org/10.54167/tch.v11i1.168.
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La captura artesanal del pulpo (Octopus vulgaris) en el nororiente de Venezuela es importante desde el punto de vista socioeconómico en algunas comunidades pesqueras como El Tirano, isla de Margarita. La pesca del pulpo se realiza con línea de mano modificado llamado potera y últimamente con una línea de potes o tubos colocada en fondos de conchales, pero su uso no está permitido. En tal sentido, con el fin de proporcionar respuesta a los usuarios y a la administración pesquera sobre la práctica de este nuevo método de pesca, se planteó la necesidad de caracterizar el aparejo, y estimar el ingreso neto (πjt) como variable económica de desempeño, calculado en función de los ingresos totales por concepto del valor de las capturas (ITjt) menos el costo total (CTjt): πjt = ITjt– CTjt. Para alcanzar los objetivos, se realizaron entrevistas in situ y se tomó información de los desembarques en playas de El Tirano que faenan en el archipiélago Los Frailes, durante la temporada de pesca julio-diciembre de 2015. Los resultados obtenidos demostraron que este sistema de pesca es rentable y demanda poco esfuerzo, debido a su estructura y funcionabilidad. Se sugiere estudiar el impacto de la pesca con potes en el stock de pulpo. DOI: https://doi.org/10.54167/tch.v11i1.168
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Schreiber, Taylor, und Eckhard Podack. „TNFRSF25 agonists as potent cancer vaccine adjuvants (131.25)“. Journal of Immunology 184, Nr. 1_Supplement (01.04.2010): 131.25. http://dx.doi.org/10.4049/jimmunol.184.supp.131.25.
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Abstract Signaling through TNFRSF25 by its natural ligand, TNFSF15, or agonistic antibodies enhances cytokine production and effector function by antigen-activated T cells. Paradoxically, we recently discovered that TNFRSF25 signaling induces rapid and specific proliferation of CD4+FoxP3+ regulatory T cells (Treg) in vivo in the absence of exogenous antigen. When TNFRSF25 agonistic antibody, clone 4C12, was used in combination with heat shock protein (gp96-Ig) based vaccination, 4C12 treatment led to synergistic antigen-specific CTL expansion when given together with the vaccine, which occurred simultaneously with Treg expansion in vivo. The frequency of CTL and Treg reached 65% of total CD8+ cells and 45% of total CD4+ cells, respectively, within the same tissue following combined administration of 4C12 and gp96-Ig. TNFR25 driven synergism with gp96-Ig vaccination was dependent upon mTOR signaling. In a therapeutic setting, combined administration of 4C12 and gp96-Ig enhanced rejection of established EG7, LLC and 3-MCA induced sarcoma tumors. These data indicate that TNFRSF25 agonists enhance vaccine-induced anti-tumor immunity which correlates with increased magnitude and duration of tumor-specific CTL expansion, systemically. These findings illustrate that TNFRSF25 signaling may enhance either inflammatory or regulatory immunity depending on the temporal availability of its ligand and the inflammatory milieu.
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Elis, Avishay, David Pereg, Dror Dicker, Natalie Gevrielov-Yusim, Ilan Goldenberg, Shlomi Matetzky, Eran Kopel und Robert Klempfner. „Temporal Trends in the Use of High-Dose Potent Statins following Acute Coronary Syndrome in Israel“. Cardiology 128, Nr. 3 (2014): 266–72. http://dx.doi.org/10.1159/000358378.
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Tfelt-Hansen, Peer, Inger Jansen und Lars Edvinsson. „Methylergometrine is more Potent than Methysergide as a 5-Hydro-Xytryptamine Receptor Antagonist on Human Temporal Arteries“. Cephalalgia 5, Nr. 3_suppl (Juli 1985): 56. http://dx.doi.org/10.1177/03331024850050s315.
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Jansen, Inger, Lars Edvinsson, Anders Mortensen und Jes Olesen. „Sumatriptan is a Potent Vasoconstrictor of Human Dural Arteries Via a 5-HT1-Like Receptor“. Cephalalgia 12, Nr. 4 (August 1992): 202–5. http://dx.doi.org/10.1046/j.1468-2982.1992.1204202.x.
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The action of sumatriptan, putatively a selective 5-HT 1D or 5-HT 1 -like receptor agonist which is effective in the treatment of migraine, has been studied on fresh human dural (middle meningeal) arteries. In low concentrations (10-8 -10-7 M) it was found to be a significantly stronger vasoconstrictor of dural arteries compared to cerebral and temporal arteries. However, its potency was less than that of 5-HT. The sumatriptan-induced vasoconstriction was antagonized by methiothepin (10-9 -10-8 M), but not by ketanserin (10-7 M). The observations suggest that the sumatriptan-induced contraction of the dural artery is mediated via activation of 5-HT 1D or 5-HT 1 -like receptors, whereas it does not appear to activate the 5-HT 2 receptors.
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Sinha-Hikim, A. P., und R. S. Swerdloff. „Temporal and stage-specific changes in spermatogenesis of rat after gonadotropin deprivation by a potent gonadotropin-releasing hormone antagonist treatment.“ Endocrinology 133, Nr. 5 (November 1993): 2161–70. http://dx.doi.org/10.1210/endo.133.5.8404667.
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Beltramello, A., G. Viola, A. Borsato, G. Tassinari, D. Campara, R. Cerini, M. Pregarz, G. Puppini und A. G. Bricolo. „Risonanza magnetica funzionale encefalica Razionale della metodica ed esperienze applicative su magnete per uso clinico“. Rivista di Neuroradiologia 8, Nr. 3 (Juni 1995): 345–70. http://dx.doi.org/10.1177/197140099500800303.
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La Risonanza Magnetica funzionale (fMRI) si sta di recente affermando come nuova metodica di indagine del «cervello al lavoro», occupando progressivamente un suo spazio nell'armamentario strumentale a disposizione dei Neurofisiologi per poter investigare la localizzazione e le inter-connessioni di differenti aree encefaliche funzionalmente coinvolte nella esecuzione di varie performance. L'fMRI indaga le modificazioni di segnale del tessuto encefalico indotte dalle variazioni perfusionali e di ossigenazione che si verificano nella sostanza grigia durante differenti stati funzionali (riposo/attività). Tali modificazioni sono rivelate con RM grazie alle variazioni che il transito nel letto vascolare encefalico di una sostanza para-magnetica è in grado di indurre sul rilassamento trasversale T2 degli spin protonici tissutali in prossimità dei capillari e mediante l'impiego di sequenze GE T2*-pesate. Due principali tecniche di studio sono state utilizzate: la prima, più complessa, richiede l'iniezione di un bolo di Gadolinio ed il monitoraggio, mediante sequenze eco-planari, del suo primo passaggio nel letto capillare encefalico; la seconda, realizzabile anche con magneti per uso clinico, utilizza come mdc para-magnetico endogeno la desossi-emoglobina e registra le variazioni di ossigenazione ematica correlate allo stato di attività corticale (tecnica BOLDc — Blood Oxygenation Level Dependent contrast). La nostra esperienza è stata effettuata con un magnete superconduttivo da 1,5 T, adottando la tecnica BOLDc e sequenze GE FLASH con TE lungo. Sono stati sottoposti ad indagine 19 volontari ed effettuati 11 studi di attivazione della corteccia motoria e 13 studi di attivazione della corteccia visiva. In 10 studi di attivazione motoria e 10 studi di attivazione visiva è stata osservata una buona o sod-disfacente variazione areale del segnale, localizzata nella regione corticale coinvolta dal paradigma di attivazione. Uno studio di attivazione motoria e 3 studi di attivazione visiva sono invece risultati insoddisfacenti, non essendosi riscontrata alcuna variazione di segnale o, quando presente, non essendo stato possibile attribuirla ad alcuna regione corticale di interesse. La RM, metodica che attualmente fornisce al Neuroradiologo le migliori informazioni anatomo-strutturali sul SNC, sta estendendo il suo campo di indagine, prima esclusivo appannaggio della Medicina Nucleare, ad alcuni aspetti delle funzioni cerebrali, avvantaggiandosi, rispetto alla SPET ed alla PET, in qualità delle sue prerogative di più elevata risoluzione spaziale e temporale, di assoluta innocuità, di rapida integrazione delle immagini funzionali con quelle anatomiche e di minori costi.
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Escamilo Cárdenas, Simón. „El shámbar: antigua comida para peones de hacienda (departamento de La libertad)“. Investigaciones Sociales 17, Nr. 31 (11.06.2014): 237–46. http://dx.doi.org/10.15381/is.v17i31.7911.
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La investigación aborda el estudio de un antiguo potaje llamado shámbar, creado para comida de peones que laboraban al interior de las haciendas serranas de las provincias de Santiago de Chuco y José Faustino Sánchez Carrión, en el departamento de La Libertad; extendiendo sus influencias a las provincias de Cajabamba (Cajamarca) y Pallasca (Ancash). Consolidado en los Andes el régimen de hacienda, fueron instalados en su interior nuevos cultivos importados por el sistema colonial. Luego de una experiencia temporal exitosa en el cultivo de cereales en la costa, a consecuencia del cambio climático (1780), que volvió húmedo no adecuado para el cultivo del trigo, este cereal subió a los Andes estableciéndose en zonas yungas caracterizadas por su ambiente seco y abrigado. Las haciendas serranas de La Libertad, así como las demás haciendas conformadas en nuestro territorio, siempre necesitaron mano de obra numerosa para atender las labores de cultivo y producción de productos diversos; esta «peonada», a fin de no distraer su labor y aprovechar el máximo que dura una jornada, requería ser alimentada al mediodía en el mismo escenario donde se realizaban las labores, o sea la chacra. Esta comida además de ser barata y de fácil preparación, colocado en el plato debería ser generosa en su abundancia; asimismo, de fácil y rápida distribución entre todos los peones comensales. Posiblemente por la conjunción de estas características, además de ser un plato sabroso y nutritivo, el shámbar logró mantenerse en el tiempo, movilizándose desde su territorio de origen, pasando y deteniéndose con mucho aplomo en áreas urbanas del interior de la región, para luego, junto con la migración de un sector de la población iniciada alrededor de los años 50 del pasado siglo, bajar a la costa, posesionándose con seguridad en fondos, picanterías, restaurantes pequeños de la ciudad de Trujillo.
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Verheggen, Raphaela, Katja Bumann und Alberto J. Kaumann. „BIBN4096BS is a potent competitive antagonist of the relaxant effects of α-CGRP on human temporal artery: comparison with CGRP(8-37)“. British Journal of Pharmacology 136, Nr. 1 (Mai 2002): 120–26. http://dx.doi.org/10.1038/sj.bjp.0704682.
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Pearl, Jocelynn, Fyodor D. Urnov und John A. Stamatoyannopoulos. „Potent and Timed Epigenetic Repression of PD-1 in Human T Cells“. Blood 132, Supplement 1 (29.11.2018): 3493. http://dx.doi.org/10.1182/blood-2018-99-119011.
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Abstract T cell exhaustion mediated by checkpoint genes - most prominently PD-1 - is believed to play a major role in limiting the efficacy of chimeric antigen receptor (CAR) T cell therapies of hematologic malignancies. Clinically durable responses to CAR-T therapy of B cell malignancies almost invariably occur in patients who achieve a complete remission by day 28 post infusion. Accumulating data indicate that the impact of T cell exhaustion is most prominent during the early post-infusion interval. PD-1 has recently been found to function as a tumor suppressor in T cells; as such permanent disablement of PD-1 expression via genetic knockout may thus increase long term adverse events from cell therapy. We sought to develop an approach for increasing the potency and efficacy of CAR-T cell therapy of B cell and other hematologic malignancies by timed epigenetic abrogation of PD-1 expression that was limited to the critical early (21-28d) therapeutic interval. To accomplish this we engineered synthetic transcription factors coupled to a modified KRAB repressive domain that densely tiled the transcriptional regulatory regions of PD-1 at up to single-base resolution. To identify TF-repressors that were both potent and specific, we transiently transduced each engineered TF-repressors separately into primary total CD3+, CD4+, or CD8+ human T-cells. These experiments revealed striking position dependence of TF-repressor activity, indicating that spatial and rotational positioning of the repressive domain was critical for function. We identified several TF-repressors that exhibited highly potent repression (>90%), and screened these for gene selectivity using transcriptome-wide deep RNA-seq. These studies yielded a TF-repressor with both high potency (>90%) and true single-gene (PD-1) specificity on a genomic scale. Next we examined the durability of expression. Transduction of TF-repressor mRNA resulted in rapid expression and activity, with PD-1 repression observable beginning at 12 hours and peaking by 48 hours post transduction. Experiments with tagged TF-repressors revealed that substantially all translated protein had dissipated within 72 hours post transduction. Remarkably, however, potent PD-1 repression reliably persisted for >3 weeks post-transduction. Collectively, our studies show the feasibility of generating highly potent and single-gene-selective epigenome editing reagents capable of reprogramming clinically relevant genes over a defined temporal interval. This approach should be broadly applicable to other key regulators of clinical response to produce genome-targeted medicines without incurring the genotoxic consequences of double-stranded DNA breaks. Disclosures No relevant conflicts of interest to declare.
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Schneider, Peleg, Re’ella Brill, Iftach Schouten, Einat Nissim-Eliraz, Inna Lysnyansky und Nahum Shpigel. „Lipoproteins Are Potent Activators of Nuclear Factor Kappa B in Mammary Epithelial Cells and Virulence Factors in Mycoplasma bovis Mastitis“. Microorganisms 10, Nr. 11 (08.11.2022): 2209. http://dx.doi.org/10.3390/microorganisms10112209.
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Mastitis due to Mycoplasma bovis is a worldwide problem, which leads to significant economic losses and affects animal welfare. However, the mechanisms by which M. bovis establishes and maintains intra-mammary infections (IMI) in dairy cows are largely unknown. To study in further detail the pathogenesis of M. bovis IMI, time- and cost-effective experimental models are needed. To this end, we established and characterized an in vitro murine mammary alveolar epithelial (EpH4) cell-based model and an in vivo murine mastitis model. Our results showed that live and UV-treated M. bovis field strain 161791 and its lipid-associated membrane proteins (LAMP) activated nuclear factor kappa B (NF-kB) in EpH4 cells in a dose-dependent manner. In the murine mastitis model, temporal and spatial dynamics of inflammation in the mammary tissues were evident. Live M. bovis elicited diffuse inflammation affecting the whole challenged gland peaking at 48 h post infection (pi) in contrast to LAMP challenge, which elicited only focal inflammation peaking at 24 h and resolving at 48 h pi. Inflammation was characterized by massive neutrophil recruitment into the milk spaces and by elevated expression of the inflammatory mediators TNF-α, KC, iNOS and NF-kB dependent genes: A20 and IkBα. Moreover, the presence of intraepithelial bacterial communities in glands challenged with live M. bovis bacteria was shown. The developed models can be used efficiently for future characterization of M. bovis virulence factors and host immune response to IMI.
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Kim, Miyeon, Dongsu Kim, Kyeong Jin Yoon, Yeejin Jeon, Dohyun Park, Mijung Lee, Dahye Jeon et al. „Abstract 4032: Discovery of a potent, selective, and orally available SHP2 inhibitor that can penetrate blood-brain barrier“. Cancer Research 83, Nr. 7_Supplement (04.04.2023): 4032. http://dx.doi.org/10.1158/1538-7445.am2023-4032.
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Abstract Src homology region 2-containing protein tyrosine phosphatase 2 (SHP2/PTPN11) is one of the key signaling proteins in many oncogenic receptor tyrosine kinase (RTK) pathways. It mediates RAS-driven downstream signaling and activates gene expression for tumorigenesis. Importantly, a critical role of SHP2 has been found during the process of temporal adaptation and ERK re-activation after the treatment of RAS/RAF/MEK/ERK inhibitors, which means that SHP2 could be a promising therapeutic target to shut down the oncogenic RAS pathway, especially in combination with RAS/RAF/MEK/ERK inhibitors. Here we present preclinical data of an allosteric small-molecule SHP2 inhibitor that is highly potent, selective, and brain-permeable. In vitro biochemical and cellular assays showed excellent potency against SHP2 protein. In addition, we confirmed exceptional in vivo activity in mouse xenograft models, and demonstrated combination effects with a KRAS G12C inhibitor. Most importantly, the BBB penetration and anti-tumor activity in brain was confirmed both in vitro and in vivo, supporting the great potential in treating brain-metastasized tumors. In summary, we have successfully discovered and developed a potent and blood-brain barrier permeable SHP2 inhibitor that provides a novel therapeutic option for diverse cancers associated in the RAS pathway. Citation Format: Miyeon Kim, Dongsu Kim, Kyeong Jin Yoon, Yeejin Jeon, Dohyun Park, Mijung Lee, Dahye Jeon, Soyeon Jang, Jinhwan Kim, Eunji Kim, Jihoon Park, Victor Hong, Sang Kyun Lim, Sungpil Choi. Discovery of a potent, selective, and orally available SHP2 inhibitor that can penetrate blood-brain barrier. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4032.
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Chen, Hong, Bo Zhu, Junya Fujimoto, Yanhua Tian, Jian-Rong Li, Pingjun Chen, Alexandre Reuben et al. „Abstract 6524: Single-cell transcriptomic analysis reveals immune landscape in the malignant transformation of normal lung to lung adenocarcinoma in genetic murine models“. Cancer Research 83, Nr. 7_Supplement (04.04.2023): 6524. http://dx.doi.org/10.1158/1538-7445.am2023-6524.
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Abstract Background: Our understanding of the initiation and progression of lung precancers is rudimentary, which has impeded advance for lung cancer prevention and interception. Although human specimens are the gold standard to study human cancer biology, lung precancer specimens designated for research are often very limited. Furthermore, human specimens are not amendable for preclinical intervention studies. We sought to establish and characterize human-relevant murine lung precancer models to study evolution of lung precancers and to provide insights for lung cancer interception. Methods: We established two mouse models, KrasG12D (a genetically engineered mouse model with KrasG12D activating mutation) and CITMs (a carcinogen urethane-induced model) in the same 129S4 background. We performed single-cell transcriptome sequencing of lung tissues collected at 5 time points after induction for each model to characterize the dynamics of immune response along with the initiation and progression of lung adenocarcinoma. Results: A total of 82,198 immune cells were analyzed and 23 immune cell subpopulations were identified. The results demonstrated dynamic changes of immune cell compositions and cell states along with the evolution from normal lung to lung precancers, and to lung adenocarcinomas in both models. CD4+ effector T cells, CD4+ regulatory T cells, mucosal associated invariant T cells (MAIT) and macrophages progressively increased during tumor progression, in contrast to progressively decreasing naive CD4+ T cells, naive CD8+ T cells and naive B cells. In contrast to CITMs, KrasG12D model harbors a clear decrease in conventional dendritic cells (cDCs) and activated B cells, but significantly more neutrophils (Wilcoxon test, P < 0.01). Conclusion: These data provide a temporal atlas of lung cancer evolution during early lung carcinogenesis and a resource for interception preclinical study. Our results revealed progressive immunosuppression along with progression of lung precancers in both genetic and carcinogen-induced models, but the immune features underlying immunosuppression may be different. Citation Format: Hong Chen, Bo Zhu, Junya Fujimoto, Yanhua Tian, Jian-Rong Li, Pingjun Chen, Alexandre Reuben, Monique B. Nilsson, Xiuning Le, Alissa Poteete, Shawna M. Hubert, Don L. Gibbons, Ignacio I. Wistuba, Jia Wu, Chao Cheng, John V. Heymach, Jianjun Zhang. Single-cell transcriptomic analysis reveals immune landscape in the malignant transformation of normal lung to lung adenocarcinoma in genetic murine models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6524.
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Falchi, Lorenzo, Ya-Hui Lin, Lauren Melendez, Paola Ghione, Colette Owens, Paul A. Hamlin, Jennifer Kimberly Lue et al. „Potent CD8+ T-Cell Proliferation and Effector Differentiation Following Subcutaneous (SC) Mosunetuzumab Administration in Patients with Untreated, High Tumor-Burden Follicular Lymphoma (FL)“. Blood 142, Supplement 1 (28.11.2023): 6116. http://dx.doi.org/10.1182/blood-2023-189638.
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Introduction: Bispecific antibodies (BsAb) have emerged as a potent therapeutic option for patients with B-cell non-Hodgkin lymphoma, including FL. These drugs leverage endogenous CD3+ T-cells to enable cytotoxic tumor cell killing. While their mode of action has been hypothesized in in vitro and animal models, the mechanisms by which these drugs promote both initial and long-term immune-dependent disease control remains unknown. We recently initiated a multicenter phase 2 trial of the CD20xCD3 BsAb mosunetuzumab (mosun) as first-line therapy for patients with high-burden FL (NCT05389293). As part of this study, we performed serial sampling of both blood and lymph node tissues in order to elucidate T-cell changes associated with response and outcome. Here we present the first analysis of peripheral blood immune profiling. Methods: Patients with untreated, high-burden stage 2-4 FL in need of treatment received SC mosun at the dose of 5 mg on D1 and 45 mg on D8 and D15 of C1, and 45 mg on D1 of each subsequent 21-day cycle. Peripheral blood samples were obtained on C1D1, C1D8, C1D15, C2D1, C3D1, C5D1, and end of treatment (EOT, 24w from C1D1). Peripheral blood mononuclear cells (PBMCs) and plasma were isolated and cryopreserved. Samples were later thawed in batches and processed as follows: CITE-Seq + single-cell TCR sequencing was performed on viable CD11b-/CD19-/CD56-/CD3+ T-cells using the 10x Genomics Single Cell Immune Profiling Platform. RNA was extracted from 1 x 10 6 viable PBMCs using TriZol, followed by phenol/chloroform-based extraction, followed by bulk TCR sequencing using an in-house platform developed by MSKCC's Integrated Genomics Operation. The remaining cells were stained with antibodies targeting CD45RA, CD8, CD45, CD45RO, CD38, CD27, CD28, CXCR3, LAG-3, CD3, CD4, HLA-DR, CXCR5, CCR6, CD56, CD11b, CD19, CD39, PD-1, OX40, Tim-3, CCR4, Granzyme B, T-bet, FoxP3, Ki-67, and CTLA-4 and analyzed using a Cytek Aurora Spectral Cytometer. Flow cytometry analysis was performed using OMIQ. Statistical analyses were performed using a paired t-test. Results: A total of 45 samples obtained from 8 patients were analyzed, including samples from C1D1 (8), C1D8 (6), C1D15 (3), C2D1 (7), C3D1 (8), C5D1 (6), and EOT (7). High dimensional clustering of spectral cytometry data using the FlowSOM algorithm revealed 9 clusters of CD8+ T-cells corresponding to known CD8+ T-cell subsets. Among these subsets, we observed two distinct temporal patterns of CD8+ T-cells within the blood. On C1D8 there was a profound drop in circulating effector CD8+ T-cells as well as terminally differentiated CD8+ Temra cells (Figure 1), with a corresponding enrichment of naïve CD8+ T-cells (Figure). We also observed significant proliferation of newly activated T-cells on C1D8, followed by expansion of CD8+ T-cells expressing several activation and exhaustion markers including PD-1, Tim-3, and CD39, peaking on C2D1 (Figure 2). CD4+ T-cell responses were more modest with a small early increase in CD28+OX40+PD-1+ CD4+ T-cells on C1D8 and a drop in circulating GzmB+OX40+ CD4+ T-cells on C1D15. Conclusion: SC mosun therapy for newly diagnosed FL was associated with a unique peripheral blood immune profile, with early mobilization of pre-differentiated CD8+ T-cell effector cells and subsequent activation and expansion of newly primed CD8+ T-cells. Further immune phenotyping, including scRNA-seq and TCR clonal dynamics in the peripheral blood over time, as well as TCR clonality of distinct CD8+ and CD4+ T-cell populations are currently being analyzed on these and additional samples, and will be presented in detail.
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Lizardo, Michael M., Christopher Hughes, Yue Zhou Huang, Alberto Delaidelli, Taras Shyp, Haifeng Zhang, Sol Snir Shaool und Poul H. Sorensen. „Abstract A024: A potent eIF4A1/2 inhibitor CR-1-31B down-modulates the antioxidant stress response in osteosarcoma cells and inhibits in vivo lung metastases“. Cancer Research 83, Nr. 2_Supplement_2 (15.01.2023): A024. http://dx.doi.org/10.1158/1538-7445.metastasis22-a024.
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Abstract Background: Effective treatment of metastatic disease remains a major challenge in the improvement of patient outcomes in osteosarcoma (OS). Novel anti-metastatic therapies are needed to treat distant metastases. To this end, the current research evaluates whether targeting the dysregulated mRNA translation machinery in OS can inhibit metastases. Hypothesis: We hypothesize that mRNA translation factors present at an abnormally high abundance in OS cells support the rapid synthesis of cytoprotective proteins that are needed to survive in the oxidative stress-rich microenvironment of the lung. Experimental Approach: Databases of OS cell lines and patient tumor data (A. Sweet-Cordero, UCSF) were queried to identify mRNA translation factors with abnormal transcript levels. A limited drug screen of small molecule inhibitors (SMIs) against identified candidates was carried out to evaluate IC50 values in metastatic OS cells. A candidate inhibitor identified from these data was further characterized for synergy with chemical inducers of oxidative stress (e.g. tert-butylhydroquinone [tBHQ]) that mimics conditions encountered in the lung. Drug combination studies examined 2D and 3D tumor spheroid growth, cellular oxidative stress, and PARP-cleavage, under +/- inhibitor and +/- oxidative stress conditions. Metastatic OS cells were engineered to express an antioxidant response element (ARE)-mCherry fluorescent reporter to directly monitor the antioxidant response by fluorescence microscopy. Polysome profiling was used to assess inhibitor-mediated changes in global mRNA translation. The anti-metastatic activity of the inhibitor was tested in the ex vivo pulmonary metastasis assay (PuMA) and in in vivo metastasis models. Results: From cell and patient sample screening, eIF4A1/2 was identified as being abnormally regulated in metastatic OS cells. The SMI, CR-1-31B, specifically targets eIF4A1/2 and was found to have an IC50 of just 8 nM. CR-1-31B was found to inhibit tumor cell growth in 2D and 3D, increase cellular oxidative stress, and enhance PARP-cleavage, but only under oxidative stress conditions. Western analysis of tBHQ-treated metastatic OS cells with the ARE-mCherry reporter confirmed that the temporal expression of mCherry correlated with the upregulation of Nuclear factor erythroid 2-related factor-2 (Nrf2), a key transcriptional regulator of the antioxidant response. CR-1-31B blunted the upregulation of the antioxidant response in 2D and 3D tumor growth conditions with oxidative stress. CR-1-31B, in a dose-dependent manner, decreased the amount of polysomal mRNAs. CR-1-31B reduced the lung tumor burden in the ex vivo PuMA model, delayed primary tumor growth, and reduced lung metastases in in vivo xenograft OS models. Conclusions: Our data demonstrates that dysregulated mRNA translation is a metastatic vulnerability that can be exploited with SMIs. Altogether, these data support the inhibition of metastatic OS by CR-1-31B, highlighting the potential therapeutic utility of this selective translation inhibitor. Citation Format: Michael M. Lizardo, Christopher Hughes, Yue Zhou Huang, Alberto Delaidelli, Taras Shyp, Haifeng Zhang, Sol Snir Shaool, Poul H. Sorensen. A potent eIF4A1/2 inhibitor CR-1-31B down-modulates the antioxidant stress response in osteosarcoma cells and inhibits in vivo lung metastases [abstract]. In: Proceedings of the AACR Special Conference: Cancer Metastasis; 2022 Nov 14-17; Portland, OR. Philadelphia (PA): AACR; Cancer Res 2022;83(2 Suppl_2):Abstract nr A024.
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Domianello, Sara. „“Pluralismo religioso e democrazia transculturale”: un ricostituente per il sistema costituzionale delle fonti in materia religiosa“. Stato, Chiese e pluralismo confessionale, 21.11.2022. http://dx.doi.org/10.54103/1971-8543/19071.
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1 - Questo incontro mi offre l’opportunità di esprimere qui oggi, anche in qualità di allieva più anziana di una scuola nutrita, il profondo e sincero compiacimento per aver goduto della fortuna di poter attingere ininterrottamente, ormai da più di quarant'anni, a una sorgente tanto preziosa di conoscenza e di riflessione scientifica.
Proverò a sfruttare l’occasione di una coincidenza temporale del tutto casuale per evidenziare, in sintesi, uno dei principali meriti che sono stati nel tempo e sono ancora riconosciuti da più parti al professore Salvatore Berlingò e agli scritti raccolti nel volume di cui discutiamo.
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Pradhan, Rashmita. „Serum FOXO3A: A potent marker for early diagnosis of Alzheimer’s disease“. Alzheimer's & Dementia 19, S15 (Dezember 2023). http://dx.doi.org/10.1002/alz.074495.
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AbstractBackgroundAlzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline. In any ageing society it’s a major health concern and a public health challenge. Diagnosis of Alzheimer’s disease (AD) is often difficult because of distinct and subjective clinical features, especially in the early stage. FOXO3a protein present in the cognitive centre of brain in inferior temporal region and parahippocampus. FOXO3a can be a potential novel target against AD.MethodAD, Mild Cognitive impairment (MCI) and Geriatric Control (GC) were recruited after diagnosis by clinical assessment, MRI, Tau PET and FDG PET. We have quantified serum FOXO3a by surface plasmon resonance (SPR) and compare with Tau PET between of AD, MCI patients and GC.ResultSerum FOXO3A was significantly lower in AD (1.42 ± 0.09 ng/μl) compare to MCI (1.61 ± 0.14 ng/μl) and GC (1.89 ± 0.07 ng/μl). ROC curve for FOXO3A protein level was plotted and showed a reasonably good sensitivity and specificity at the cut‐off value for detecting cognitively impaired patients (AD and MCI) in compared to control older subjects. For Tau PET in inferior temporal region, the AUC for predicting AD from GC was 0.72 and AD from MCI was 0.71.ConclusionSerum FOXO3A could significantly differentiate AD vs MCI, MCI vs GC and AD vs GC. It may serve as novel blood marker for early detection for AD and target for therapeutic intervention.
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Chandra, Jyotsna, und Mahmoud A. Ghannoum. „CD101, a Novel Echinocandin, Possesses Potent Antibiofilm Activity against Early and Mature Candida albicans Biofilms“. Antimicrobial Agents and Chemotherapy 62, Nr. 2 (13.11.2017). http://dx.doi.org/10.1128/aac.01750-17.
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ABSTRACT Currently available echinocandins are generally effective against Candida biofilms, but the recent emergence of resistance has underscored the importance of developing new antifungal agents that are effective against biofilms. CD101 is a long-acting novel echinocandin with distinctive pharmacokinetic properties and improved stability and safety relative to other drugs in the same class. CD101 is currently being evaluated as a once-weekly intravenous (i.v.) infusion for the treatment of candidemia and invasive candidiasis. In this study, we determined (i) the effect of CD101 against early and mature phase biofilms formed by C. albicans in vitro and (ii) the temporal effect of CD101 on the formation of biofilms using time-lapse microscopy (TLM). Early- or mature-phase biofilms were formed on silicone elastomer discs and were exposed to the test compounds for 24 h and quantified by measuring their metabolic activity. Separate batches were observed under a confocal microscope or used to capture TLM images from 0 to 16 h. Measurements of their metabolic activity showed that CD101 (0.25 or 1 μg/ml) significantly prevented adhesion-phase cells from developing into mature biofilms (P = 0.0062 or 0.0064, respectively) and eradicated preformed mature biofilms (P = 0.04 or 0.01, respectively) compared to those of untreated controls. Confocal microscopy showed significant reductions in biofilm thicknesses for both early and mature phases (P < 0.05). TLM showed that CD101 stopped the growth of adhesion- and early-phase biofilms within minutes. CD101-treated hyphae failed to grow into mature biofilms. These results suggest that CD101 may be effective in the prevention and treatment of biofilm-associated nosocomial infections.
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Saha, Barnan K., Vivek Roy, Jayanti Saha, Abhik Chatterjee und Ayon Pal. „Study of mercury resistance and Fourier transform infrared spectroscopy‐based metabolic profiling of a potent Bacillus tropicus strain from forest soil“. Journal of Basic Microbiology, 17.10.2023. http://dx.doi.org/10.1002/jobm.202300351.
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AbstractMercury (Hg) is a highly toxic heavy metal and Hg‐resistant indigenous bacterial isolates may offer a green and cost‐effective bioremediation strategy to counter Hg contamination. In this study, a potent Hg‐resistant bacterium was isolated from the forest soil of a bird sanctuary. Identification using matrix‐assisted laser desorption ionization‐time of flight mass spectrometry depicted the isolate as a strain of Bacillus tropicus, validated by morphological, biochemical, and molecular studies. The isolate demonstrated biological Hg removal efficiency and capacity of 50.67% and 19.76 mg g−1, respectively. The plasmid borne resistance determinant, merA, encoding mercuric reductase, was detected in the bacterium endowing it with effective Hg volatilization and resistance capability. A Fourier‐transform infrared spectroscopic comparative metabolic profiling revealed the involvement of various functional groups like –COOH, ‐CH2, ‐OH, PO4− and so on, resulting in differential spectral patterns of the bacterium both in control and Hg‐exposed situations. A temporal variance in metabolic signature was also observed during the early and mid‐log phase of growth in the presence of Hg. The bacterium described in this study is the first indigenous Hg‐resistant strain isolated from the Uttar Dinajpur region, which could be further explored and exploited as a potent bioresource for Hg remediation.