2,235 research outputs found
La capsula del tempo. Phage resistance evolution induces the sensitivity of specific antibiotics in Pseudomonas aeruginosa PAO1.
No full textLa capsula del tempo. Dynamic regulation of airway surface liquid pH by TMEM16A and SLC26A4 in cystic fibrosis nasal epithelia with rare mutations
No full textThe Reproducibility of Lists of Differentially Expressed Genes in Microarray Studies
No full textReproducibility is a fundamental requirement in scientific experiments and clinical contexts. Recent publications raise concerns about the reliability of microarray technology because of the apparent lack of agreement between lists of differentially expressed genes (DEGs). In this study we demonstrate that (1) such discordance may stem from ranking and selecting DEGs solely by statistical significance (P) derived from widely used simple t-tests; (2) when fold change (FC) is used as the ranking criterion, the lists become much more reproducible, especially when fewer genes are selected; and (3) the instability of short DEG lists based on P cutoffs is an expected mathematical consequence of the high variability of the t-values. We recommend the use of FC ranking plus a non-stringent P cutoff as a baseline practice in order to generate more reproducible DEG lists. The FC criterion enhances reproducibility while the P criterion balances sensitivity and specificity
Potenziamento dell’efficacia del cetuximab mediante combinazione con cellule T ingegnerizzate con recettori Fc chimerici per il trattamento del carcinoma del colon retto K-ras mutato.
No full textINTRODUZIONE: L’impiego di anticorpi monoclonali (AM) diretti contro il recettore per il fattore di crescita epidermico (EGFR), tra cui il cetuximab, ha rappresentato un significativo avanzamento nel trattamento del carcinoma colorettale metastatico (mCRC). L’effetto anti-tumorale del cetuximab è dovuto a: i) blocco della proliferazione neoplastica; ii) attivazione di processi apoptotici; iii) induzione di citotossicità cellulare dipendente da anticorpo (ADCC) mediante il legame con i recettori Fc. Tuttavia, diversi fattori limitano l’efficacia terapeutica del cetuximab; tra questi la presenza di mutazioni nel gene Kras (Kras-mut) e la scarsa presenza di cellule Natural Killer, capaci di mediare ADCC, nel microambiente tumorale. In questo studio ipotizziamo di superare i limiti terapeutici del cetuximab attraverso la sua combinazione con cellule T ingegnerizzate con recettori chimerici Fc (Fc-CRs).
MATERIALI E METODI: Due Fc-CRs, denominati CD32-CR e CD16-CR, sono stati generati dalla fusione della regione extracellulare del FcRIIA (CD32) o del FcRIIIA (CD16) con il dominio transmembrana del CD8a e con i domini intracitoplasmatici del CD28 e del CD3. Linfociti T attivati sono stati trasdotti con le chimere e la corretta espressione è stata valutata mediante citofluorimetria e western blot. I recettori sono stati caratterizzati funzionalmente in vitro attraverso test di binding e saggi ELISA. L’attività anti-tumorale delle cellule T trasdotte in associazione al cetuximab è stata valutata in test di deplezione in vitro e in topi SCID xenotrapiantati con la linea cellulare di CRC Kras-mut HCT116.
RISULTATI: Entrambi i Fc-CRs sono espressi correttamente sulla superficie delle cellule T. Il CD32-CR, ma non il CD16-CR, lega in maniera specifica il frammento Fc degli AM anti-EGFR cetuximab e panitumumab. La dose massima di cetuximab necessaria per saturare tutti i CD32-CR che è pari a 10g/ml ed il binding è mantenuto anche in presenza di quantità crescenti di plasma umano. Sia il CD32-CR che il CD16-CR inducono rilascio di citochine in risposta a stimolazione con cetuximab o panitumumab. La combinazione del cetuximab con cellule T CD32-CR+: i) induce l’eliminazione di HCT116 in vitro; ii) riduce significativamente la crescita tumorale in vivo.
CONCLUSIONI: In questo studio preclinico dimostriamo che cellule T armate con CD32-CR potenziano l’efficacia del cetuximab contro CRC Kras-mutato
Le Corbeau et le Renard: 99 versions réinventées: Style d'exercices
No full textThis book represents a fascinating effort. At first I thought it was going to be a collection of various parodies of La Fontaine's FC. It is not that, but rather a creative presentation of some 97 different versions of La Fontaine created by the author. The first two versions are a French translation of the Greek prose of the most original FC text in the Aesopic manuscripts and then La Fontaine's verse. Thereafter the fun begins! The imagination and the execution of this project are both remarkable. Let me offer a sample of five approaches: (1) an acrostic, so that the opening letters of each verse spell "M Jean La Fontaine"; (2) a prose version after the manner of Balzac; (3) a scientific version needing more than a full page; (4) a tourist guide version; and (5) a rhyming version in English. T of C at the end. 136 pages. 5¼" x 8". Printed upon demand.Language note: FrenchNicolas Mille
FC Omniworld
No full textHet maken van een stedenbouwkundig plan voor de locatie Almere Poort in Almere. Hierbij is het programma van de Gemeente, zoals gespecificeerd voor de locatie, overgenomen. De kern van het nieuwe plan is een centrale (groene) as waaraan alle centrumfuncties voor deze wijk worden gerealiseerd. Deze nieuwe as zorgt, door de combinatie van functies met verschillende gebruikstijden, voor een continue drukte op deze centrale as. Aan een van de eindes van de as ligt een verhoogd maaiveld. Dit maaiveld gaat over het spoortalud zodat men het spoor over kan steken zonder tunnel of spoorwegovergang. In dit talud worden diverse functies gehuisvest welke normaal dichte dozen zijn (zoals parkeren, expo ruimten en sportzalen). Deze functies met voornaleijk dichte gevels worden omkleed met kleinschalige functies om continue activiteit bij het verhoogde maaiveld te genereren en om interessante gevelbeelden te hebben (i.p.v. dichte wanden van grootschalige functies). In het verhoogde maaiveld ligt verdiept het nieuwe stadion voor FC Omniworld. Dit stadion wordt zo opgenomen in een natuurlijke en groene omgeving. De dakconstructie bestaat uit houten spanten en een semi-transparant doek om zo goed mogelijk aan te sluiten op het park bovenop het nieuwe maaiveld. Bezoekers komen ook via het park binnen. Op dit niveau kan men rondlopen om versnaperingen te kopen en vervolgens af te dalen naar de tribunes. Het stadion is in de toekomst uit te breiden door nieuwe tribunes te positioneren boven de promenade van het stadion en onder het dak. Hiervoor zijn geen aanpassingen vereist. Tevens is het stadion multifuntioneel te gebruiken door verplaatsbare tribunedelen.Architectur
Differential profile of NK target structures (NKTS) of mouse fibroblasts and lymphoma cells
No full textPlant expression of cocaine hydrolase-Fc fusion protein for treatment of cocaine abuse
No full textBACKGROUND: A recently reported cocaine hydrolase (CocH3) fused with fragment crystallizable (Fc) region of human immunoglobulin G1, denoted as CocH3-Fc, is known as a promising therapeutic candidate for the treatment of cocaine overdose and addiction. A challenge for practical therapeutic use of this enzyme exists in the large-scale protein production and, therefore, it is interesting to identify a low-cost and feasible, sustainable source of CocH3-Fc production.
RESULTS: CocH3-Fc was transiently expressed in plant Nicotiana benthamiana leaves. The plant-expressed protein, denoted as pCocH3-Fc, was as active as that expressed in mammalian cells both in vitro and in vivo. However, compared to the mammalian-cell expressed CocH3-Fc protein, pCocH3-Fc had a shorter biological half-life, probably due to the lack of protein sialylation in plant. Nevertheless, the in vivo half-life was significantly extended upon the PEGylation of pCocH3-Fc. The Fc fusion did not prolong the biological half-life of the plant-expressed enzyme pCocH3-Fc, but increased the yield of the enzyme expression in the plant under the same experimental conditions.
CONCLUSIONS: It is feasible to express pCocH3-Fc in plants. Further studies on the pCocH3-Fc production in plants should focus on the development of vectors with additional genes/promoters for the complete protein sialylation and for a better yield
Fecal calprotectin to detect inflammatory bowel disease in juvenile idiopathic arthritis
No full textOBJECTIVE: This study aimed to test fecal calprotectin (FC) as a screening tool to identify inflammatory bowel disease (IBD) among patients with juvenile idiopathic arthritis (JIA). METHODS: FC level < 100 g/kg was considered normal. Patients with 2 consecutive FC dosage ≥ 100 g/kg underwent endoscopic evaluation.
RESULTS: There were 113 patients with JIA enrolled. FC was raised in 7 patients out of 113. All patients had IBD. In 3/7 patients, high FC levels were the only sign consistent with IBD. CONCLUSION: FC is a useful, economical, and noninvasive diagnostic tool to identify JIA patients with underlying IBD
Stable Foliage Cluster (FC), a Basic Unit of the Crown Structure of Tree Species and Its Application to Modeling of Tree and Forest Structure: Configuration of the FC Model
No full textThe "foliage cluster (FC) model" shows that the size (the amount of leaves, number of yearly shoots and total twig length), turnover time, and branching (i.e., forking) structure of a twig becomes stable in the top of the crown in an oak species by forming a "stable FC" [1]. A stable FC can be treated as a basic component of the crown structure and as an alternative to individual leaf or current-year shoot. The FC model is composed of several equations approximating the branching structure of twigs. Differences in size and branching morphology among twigs are represented by differences in values of the parameters of the equations. We described details of our analyses of data taken from real twigs and applied to the equations implemented in the FC model
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