80 research outputs found

    How does technological development and adoption occur In the media? A cultural determinist model

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    The thesis hereby submitted, ‘How Does Technological Development And Adoption Occur In The Media? A Cultural Determinist Model’ was originally published in Media Technology and Society A History: from the telegraph to the Internet (London: Routledge 1998) and Technologies of Seeing: Photography, Cinematography and Television (London: British Film Institute 1996). The argument outlined in those two books is further supported and updated by six other texts published between 1995 and 2005 on the same topic. Media Technology and Society A History: from the telegraph to the Internet deals with the development of electrical and electronic mass media proposing a model for the nature of such developments. It is a final iteration of an approach to this history which has its origins in work first begun in the 1970s. Technologies of Seeing: Photography, Cinematography and Television applies the same model to photographic and cinematographic technologies. The thesis argues that all these media developments can only be understood in a social context; that they are to be understood as examples of what has become known as ‘socially shaped technology’ (or, in terms of the thesis, ‘cultural determinism’). This is contrary to the received dominant view that technology itself is the driver determining social formation – termed the ‘technological determinist’, ‘technicist’ or ‘diffusion theory’ approach. In rejecting technicism, ‘How Does Technological Development And Adoption Occur In The Media? A Cultural Determinist Model’ proposes instead an original, pioneering contribution to a revisionist cultural determinist/SST historiography as well as outlining a model to explicate at a theoretical level how such innovations and adoptions occur

    Targeting of the Hedgehog Signaling Pathway in Cancer Treatment

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    The Hedgehog (Hh) signaling pathway is a developmental pathway that is highly conserved evolutionarily. While typically only displaying high activity during embryogenesis, overactivation of the Hh pathway in adults has been linked to multiple forms of cancer including acute myeloid leukemia, myelofibrosis, basal-cell carcinoma, pancreatic ductal adrenal carcinoma, and triple negative breast cancer. The prevalence of Hh activation in many different cancers has made it a prime target for inhibition of these cancers through novel therapies. This literature review sought to assess the current state of cancer treatment through inhibition of Hh signaling. Most current clinical trials involving the pathway use Smoothened (SMO) antagonists to limit GLI1 production and ultimately inhibit Hh signaling. Currently, the FDA has approved the use of the SMO antagonists vismodegib, sonidegib, and glasdegib for cancer treatment. While only these small molecule inhibitors of Hh signaling have been approved for cancer treatment at this point, inhibition of the Hh signaling has shown to be a promising avenue for novel cancer therapies, particularly for future treatment of basal-cell carcinoma

    A new Robertsonian translocation in Holstein-Friesian cattle

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    A new Robertsonian translocation was found in a cow of the Holstein-Friesian breed. GTG-banding allowed us to elucidate the anomaly as a centric fusion between chromosomes 19 and 21. CBG-banding demonstrated that the translocated chromosome was dicentric. Cytogenetic investigation of the relatives of the translocated animal revealed two other carriers.Une nouvelle translocation robertsonienne a Ă©tĂ© mise en Ă©vidence chez une vache de race Holstein. La coloration en bandes GTG nous a permis d’identifier les chromosomes impliquĂ©s dans la translocation. Il s’agit des chromosomes 19 et 21. La coloration en bandes CBG montre que le chromosome transloquĂ© est dicentrique. Une analyse cytogĂ©nĂ©tique des apparentĂ©s de l’animal porteur a permis de mettre en Ă©vidence aux autres animaux porteurs

    Zebrafish Cyclin-Dependent Protein Kinase–Like 1 (zcdkl1): Identification and Functional Characterization

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    The cyclin-dependent protein kinase family regulates a wide range of cellular functions such as cell cycle progression, differentiation, and apoptosis. In this study, we identified a zebrafish cyclin-dependent protein kinase-like 1 protein called zebrafish cdkl1 (zcdkl1), which shared a high degree of homology and conserved synteny with mammalian orthologs. zcdkl1 exhibited abilities for phosphorylation of myelin basic protein and histone H1. RT-PCR analysis revealed that zcdkl1 was expressed starting from fertilization and continuing thereafter. In adult tissues, zcdkl1 was predominantly detected in brain, ovary, and testis, and was expressed at low levels in other tissues. At 50% epiboly stage, zcdkl1 was widely expressed. At 12 to 48 h post-fertilization, zcdkl1 was predominantly expressed in the hypochord, the medial and lateral floor plate, and the pronephric duct. Interference of zcdkl1 expression resulted in abnormalities, such as brain and eye malformation, pericardial edema, and body axis curvature. Disruption of zcdkl1 reduced neurogenin-1 in the brain and sonic hedgehog expression in the floor plate region. These deformities were apparently rescued by co-injection of zcdkl1 mRNA. Findings of this study indicate that zcdkl1 plays an essential role in zebrafish development

    Pharmacokinetics of esomeprazole in goats (Capra aegagrus hircus) after intravenous and subcutaneous administration

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    Background: Stressed and hospitalized goats are at risk of developing abomasal (gastric) ulceration, but there is a paucity of pharmacokinetic studies for proton pump inhibiting drugs, such as, esomeprazole in goats. Objectives: The objectives for this study were to estimate plasma pharmacokinetic parameters for esomeprazole in adult goats after intravenous (IV) and subcutaneous (SQ) administration. A secondary objective was to describe the plasma kinetics of the metabolite esomeprazole sulfone after IV and SC administration in goats. Materials and methods: Esomeprazole was administered to 5 adult goats in a crossover study at doses of 1 mg/kg IV or 2 mg/kg SC. Plasma samples were collected over 36 h and analyzed via reverse phase HPLC to determine concentrations of esomeprazole and esomeprazole sulfone. Pharmacokinetic parameters were derived via non-compartmental analysis. Results: Following IV administration, mean values for plasma clearance (Cl), elimination half-life [T1/2 (λz)], C0, and volume of distribution (Vz) of esomeprazole were estimated at 24.9 mL/min/kg, 6 min, 2.324 Όg/mL, and 0.23 L/kg, respectively. After SC administration elimination half-life, maximum concentration (Cmax) and time to maximum concentration (Tmax) of esomeprazole were estimated at 29 min, 1.038 Όg/mL, and 22 minutes respectively. Maximum concentrations of the sulfone metabolite were 32 and 18 ng/mL after IV and SC administration. Conclusion: Esomeprazole was rapidly eliminated from plasma after both IV and SC injection in goats. The elimination half-life in goats appears to be shorter than reported in dogs, as well as less than that reported for pantoprazole in goats. The sulfone metabolite was detected and also rapidly eliminated from the plasma after both IV and SC administration. Additional pharmacodynamic investigations are needed to determine the efficacy of esomeprazole on abomasal (gastric) acid suppression in goats and could include larger doses or additional routes of administration

    Liturgia jako "przestrzeƄ" ƛwiadectwa na rzecz jednoƛci

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    L’articolo sopra presentato vuole essere un valido contributo all’opera della maturazione della consapevolezza cristiana, riguardante il fatto che ogni celebrazione liturgica costituisce un evento pieno del dinamismo salvifico. Essendo il memoriale del mistero salvifico di Cristo, la liturgia rimane una fonte dell’unione fraterna, basata sul fondamento della santificazione che rigenera in noi la dignitĂ  dei figli di Dio e dei veri fratelli di Cristo. Occorre quindi ristudiare il tema concernente la base teologica dell’unitĂ , rivissuta e riconsolidata ogni qual volta, quando accediamo alla celebrazione liturgica. Tale celebrazione – essendo la fonte dell’unione fraterna – fa crescere dentro di noi la capacitĂ  di diventare sempre piĂč compatti nello sperimentare la nostra personale unitĂ  soggettiva, e cioĂš l’armonia tra sentimenti interiori (sperimentati nel nostro intimo) ed esperienze esteriori (vissute grazie alle diverse attivitĂ , compiute durante la liturgia). All’unitĂ , di cui viene trattato nell’articolo, contribuiscono sia fattori personali, che non personali. Tra le persone attive nella celebrazione liturgica ci sono: membri dell’intera assemblea liturgica, il presidente della celebrazione e altre persone che svolgono il loro servizio liturgico. Tra gli elementi non personali, i quali aiutano l’assemblea a sentirsi davvero unita, ci sono: atteggiamenti e gesti, testi biblici, eucologici e agiografici – proclamati o ascoltati. In conclusione dell’articolo viene sottolieneato il fatto che la liturgia crea davvero un privilegiato „spazio” della testimonianza dell’unitĂ  tra i cristiani che – dopo aver partecipato alla celebrazione liturgica – si sentono mandati nel mondo per radicarvi il vero senso della comunione fraterna

    Factors for Hematopoietic Toxicity of Carboplatin: Refining the Targeting of Carboplatin Systemic Exposure

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    Purpose Area under the curve (AUC) dosing is routinely carried out for carboplatin, but the chosen target AUC values remain largely empirical. This multicenter pharmacokinetic-pharmacodynamic (PK-PD) study was performed to determine the covariates involved in the interindividual variability of carboplatin hematotoxicity that should be considered when choosing individual target AUCs.Patients and Methods Three hundred eighty-three patients received carboplatin as part of established regimens. A semi-physiologic population PK-PD model was applied to describe separately the time course of absolute neutrophil and platelet counts using NONMEM software. The plasma ultrafiltrable carboplatin concentration (CCarbo) was assumed to inhibit the proliferation of blood cell precursors through a linear model: drug effect = slope × CCarbo. The slope corresponds to the patients\u27 sensitivity to carboplatin hematotoxicity. The relationships between the patients\u27 sensitivity to the neutropenic or thrombopenic effects of carboplatin and various covariates, including associated chemotherapies, demographic, biologic, and pharmacogenetic data, were studied. Results The sensitivity of carboplatin-induced thrombocytopenia decreased in the case of concomitant paclitaxel chemotherapy (slope decreased by 24%), whereas it increased with coadministration of etoposide and gemcitabine (slope increased by 45% and 133%, respectively). For neutropenia, the sensitivity increased when carboplatin was combined with other cytotoxics (slope increased by 76%). Conclusion This study provides useful information to clinicians to better estimate the hematopoietic toxicity of carboplatin and thus choose more rationally carboplatin target AUCs as a function of pretreatment or concomitantly administered chemotherapies. For example, an AUC of 5 mg/mL · min is associated with a risk of grade 3 or 4 thrombocytopenia of 2% in combination with paclitaxel versus 38% with gemcitabine in a non-pretreated patient
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