Littérature scientifique sur le sujet « FERRACCIU »

Neurons have high densities of voltage-gated Na+ channels that are restricted to axon initial segments and nodes of Ranvier, where they are responsible for initiating and propagating action potentials. New findings (Bréchet, A., M.-P. Fache, A. Brachet, G. Ferracci, A. Baude, M. Irondelle, S. Pereira, C. Leterrier, and B. Dargent. 2008. J. Cell Biol. 183:1101–1114) reveal that phosphorylation of several key serine residues by the protein kinase CK2 regulates Na+ channel interactions with ankyrin G. The presence of CK2 at the axon initial segment and nodes of Ranvier provides a mechanism to regulate the specific accumulation and retention of Na+ channels within these important domains.

Changes of the affective and cognitive function are usually associated with thyroid gland dysfunction. In autoimmune thyroid disease, these changes can be caused by thyroid dysfunction (hypo- or hyperthyroidism) or associated with the presence of antithyroid antibodies. Even a small change in thyroid hormone concentration is associated with change of cognitive function. In euthyroid older males, variation of total and free thyroxin accounts for about 10% of Wechsler adult intelligence test variance. In euthyroid females, lower cognitive function, measured by Mini Mental test, also correlates with blood thyroxin. Short-term (4 weeks) hypothyroidism induces clinically significant cognitive dysfunction, which is reversible by thyroid hormone substitution. Mild hypothyroidism (TSH less than 10) also induces reversible cognitive dysfunction. In hypothyroidism, PET scanning shows global reduction of brain blood flow and glucose metabolism. Hashimoto?s encephalopathy is characterized by corticosteroid reversible encephalopathy associated with the presence of antithyroid antibodies. Encephalopathy can be manifested as multiple stroke-like episodes (vasculitis like), or as diffuse, progressive type characterized by dementia and psychiatric symptoms. In euthyroid patients with Hashimoto?s thyroiditis and no evidence of neurological disease, SPECT showed brain perfusion abnormalities. Post mortem and brain biopsy findings can be normal or show perivascular lymphocytic infiltration. Recently, presence of antineuronal antibodies has been found in patients with Hashimoto?s thyroiditis. Specific high reactivity against human ?-enolase was high in patients with Hashimoto?s encephalopathy, but absent in patients with other neurological disorders and healthy subjects. Specific antineural antibodies were found in another group of Hashimoto?s encephalopathy patients. Furthermore, Ferracci et al, found antithyroid antibodies in the CSF of patients with Hashimoto?s encephalopathy.

BackgroundCancer of unknown primary (CUP) is a rare tumor type accounting for 2% of solid cancers. In the subset of CUP cases where tumor of origin is posited and treated as such, no clear clinical benefit has been demonstrated. Furthermore, CUP patients treated by empiric platinum-based regimens have low response and survival rates of approximately 20%.1 2 Support of tissue-agnostic marker-directed immunotherapy is growing because it targets the immune system rather than the tumor, with some efficacy evidence emerging for CUP.3 Identifying new targets for immunotherapeutic opportunities in this heterogeneous and difficult to treat patient group is a critical unmet need.MethodsComprehensive genomic and immune marker profiling by NGS4 was performed on FFPE tissue for CUP tumors (n=298) as indicated by physicians’ test orders from >100 clinical practice sites. Histology was verified by a molecular pathologist as part of pre-analytic test quality control, with cases representing tumors with adenocarcinoma (58%), carcinoma (26%), squamous (10%), and neuroendocrine (6%) histologic features. RNA-expression levels of immune genes that are current targets in non-CUP immunotherapy clinical trials (n=36) were ranked against a reference population (≥75th percentile=high), and described by histologic type, along with PD-L1 IHC (22C3) expression, tumor mutational burden (TMB) and genomic variants.Results90% of all CUP tumors had at least 1 highly expressed immune gene target in active immunotherapy trials, with the most frequent being TGFB1 (47%) and CCL2 (39%). 55% of CUP tumors were PD-L1 IHC 22C3 positive (>=1% TPS), and 21% had high TMB (>=10 mut/Mb) in CUP tumors with neuroendocrine (32%), carcinoma (30%), squamous cell (21%), and adenocarcinoma (17%) histologic features. Overall, 26% of CUP patient tumors, mostly adenocarcinomas (28%) and carcinomas (27%), harbored genomic variants (n=77) with FDA approved targeted therapies in other tumor types. The most frequently immunogenic CUP tumors were carcinomas, showing high RNA-seq expression of 26/36 genes in at least 20% of patients, most represented by CD20, CD27, TLR8, and PD-L1. High expression of CD40, CSF1R, TIM3, and VISTA was most common in adenocarcinomas. Squamous cell carcinomas were relatively immunogenic, with frequent high expression of 17/36 immune genes, uniquely including MAGEA4. Neuroendocrine tumors were the least immunogenic, with frequent high expression in only 4/36 genes, including ADORA2A (42%) and MAGEA1 (37%).ConclusionsCUP tumors diversely express both standard marker and novel immunotherapeutic targets based on histology and may benefit from selective access to clinical trials for these therapies.ReferencesNational Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Occult Primary (Cancer of Unknown Primary [CUP]), Version 2.2021. Fort Washington, Pennsylvania: National Comprehensive Cancer Network; 2021. https://www.nccn.org/professionals/physician_gls/pdf/occult.pdf.Laprovitera N, Riefolo M, Ambrosini E, Klec C, Pichler M, Ferracin M. Cancer of unknown primary: Challenges and progress in clinical management. Cancers (Basel) 2021;13(3):1–30. doi:10.3390/cancers130304513.Naing A, Meric-Bernstam F, Stephen B, et al. Phase 2 study of pembrolizumab in patients with advanced rare cancers. J Immunother Cancer 2020;8(1):e000347. doi:10.1136/jitc-2019-0003474.Conroy JM, Pabla S, Glenn ST, et al. Analytical validation of a next-generation sequencing assay to monitor immune responses in solid tumors. J Mol Diagnostics 2018;20(1):95–109. doi:10.1016/j.jmoldx.2017.10.001

In questo lavoro si analizzerà come l’evoluzione del contesto digitale e la crisi economica mondiale abbiano influenzato il commercio di capi di abbigliamento in questi ultimi anni e di conseguenza l’attività della Ferracin srl che è stata presa come caso aziendale. Allo scopo di porre in essere nuove strategie che permettano di aumentare la redditività aziendale, si cercherà di delineare il settore in cui questa opera e le rispettive problematiche aziendali.

The ANIMOSA project explores potential responses to what has been recently described as a detached human experience. Embodying vibrant matter, artworks can potentially activate and expand environmental awareness. This type of enchantment is generated principally through experimenting with organic and inorganic material inherent in natural phenomena. Employing in my practice the developments in the contemporary arts and sciences, I explore the ways in which the natural environment increasingly exhibits its own material agency. In this existential, cultural and environmental quest, I consider the work of various theorists, including modern French philosopher Maurice Merleau-Ponty and contemporary American political theorist Jane Bennett. While I remain grounded in their thought, I expand it into new areas of phenomenological and material engagement within my own practice. I question the proximities and boundaries between the animate, the inanimate and the immanent. I embrace materiality, specifically the autonomous trajectory of organic materials, while also providing an opportunity for reflecting on what it means to be a sentient being in the 21st century. Sentient (2017), the final artwork in the series is an immersive multimedia installation that engages both organic material and natural phenomena, intertwined with a time-lapse video, as well as sound and light effects. Composed of many multinucleate, unicellular[1] bright yellow Physarum polycephalum cultures fed with oats and growing in enclosed containers within a semi-dark environment, it has a life of its own. The Sentient (2017) habitat is subtly animated by a natural, self-regulating process in which the organic cells grow and transform themselves, and by an automatic, LED timed light system that gradually dims and brightens to best reveal the wondrous branching growth of the cell. Sentient (2017) aims to enchant by staging unexpected and intimate encounters with matter, and to reflect on organic spatial intelligence. In an alchemic interplay of positive and negative attractions, Sentient (2017) aligns human and nonhuman responsiveness with an environmental awareness. This work also anticipates the future direction of my research: the observation of smart living organisms capable of adapting to their surroundings and creating synergies within environments, and of phenomena that can contribute to an eco-phenomenological awareness by stimulating the development of an organic knowledge with an emphasis on sensory responses to it. [1] Dr M Beekman and Mr J Smith-Ferguson, 2018, in discussion with the author about Physarum polycephalum’s definition, February 1, 2018

Seguendo l’approccio metodologico della storia dei concetti (Begriffsgeschichte), l’elaborato mira a descrivere i cambiamenti dell’assetto politico-costituzionale italiano attraverso l’evoluzione semantica di sintagmi linguistici come ‘governo parlamentare’, ‘governo rappresentativo’, ‘governo costituzionale’, ‘parlamentarismo’. Tale analisi si concentra grossomodo in un periodo di tempo che va dalla seconda metà dell’Ottocento, fino alla prima metà del Novecento. Come fonti, accanto ai classici prodotti della dottrina politico-costituzionale, quali monografie accademiche, corsi universitari, prolusioni e discorsi parlamentari, si sono utilizzate voci di dizionari e enciclopedie, opuscoli, fonti giornalistiche, periodici e riviste di taglio più o meno specialistico e di orientamento politico diverso (liberale/moderato, cattolico, socialista, repubblicano, nazionalista, fascista). L’evoluzione concettuale di lemmi-cardine come ‘governo parlamentare’ e altri sintagmi ad esso finitimi permette di ricostruire i mutamenti della forma di governo italiana, evitando anche spiacevoli anacronismi a livello storiografico. Infatti la forma di governo non dovrebbero essere descritta attraverso quadri concettuali elaborati nella nostra contemporaneità e poi applicati retrospettivamente al passato, ma con sintagmi e concetti appartenenti alla realtà storica che si intende prendere in esame.