1,721,060 research outputs found
Contract interpretation and relational contract theory : a comparison between common law and civil law approaches
No full textThe paper focuses on the main legacy of the relational contract theory in the context of contract interpretation and its influence on contemporary scholarship. First developed in the United States, the relational contract theory has had a significant resonance within common law countries, emphasisng the importance given to 'contextualism' and the 'implicit dimensions' of contract, whereas no equivalent doctrinal elaboration can be said to exist within civil law countries. The paper suggests however, that interestingly, at least one civil law country - Italy and, to a certain extent, the recent European soft law documents (PECL, DCFR, CESL) recognise rules on contract interpretation which indirectly reflect some of the main claims of the relational contract theory. These rules, in turn, are necessarily linked to the underlying values that each legal system emphasises, and the view of the contractual relationship as mainly 'adversarial' or 'cooperative' in character. The study of the relational contract theory may therefore serve as a testing ground for any legal system, posing the choice between a 'drastic' reform of the classical common law precepts of contract law and its underlying ethic, or the welcoming of a contextual approach which does not completely discard the model currently in place
THE ROLE OF NOTCH PATHWAY IN MULTIPLE MYELOMA PROGRESSION: CONTROL OF IL-6 EXPRESSION IN MALIGNANT PLASMA CELLS AND BONE MARROW NICHE
Full text linkMultiple myeloma (MM) is an incurable hematological tumor characterized by the accumulation of malignant plasma cells (PCs) within the bone marrow (BM). MM cells create a very strictly interaction with the surrounding BM niche that directly supports tumor growth through adhesion molecules and soluble factors, the most important of which is interleukin-6 (IL-6). IL-6 is probably the most important factor for MM cells growth and survival in vivo and it mainly produced by non-neoplastic cells of the BM microenvironment, and at less extent by malignant plasma cells.
Recent studies suggest the involvement of NOTCH pathway in the pathogenesis of multiple myeloma. The NOTCH pathway is composed by four isoforms of receptors (NOTCH1-4) and two family of ligands, the Serrate-like ligands (JAGGED1 and 2) and the Delta-like ligands (DLL1/3/4). NOTCH pathway plays an important role in several cellular processes such as proliferation, survival, differentiation and stemness in various tissues and tumors. Regarding MM, the up-regulation of NOTCH signaling is due to the over-expression of both receptors (NOTCH1 and NOTCH2) and ligands (JAGGED1 and JAGGED2): these alterations promote tumor growth, pharmacological resistance, and bone disease. Furthermore, NOTCH pathway plays an important role in the pathological interaction between malignant PCs and the BM niche.
This study indicates that there is a correlation between levels of NOTCH signaling members (JAGGED1, NOTCH2, HES5 and HES6) and the malignant progression of the disease. Indeed, NOTCH pathway is involved in multiple myeloma progression since it is able to increase the release of IL-6 produced by BM stromal cells (BMSCs). Our in vitro studies show that NOTCH pathway induces IL-6 gene expression in MM cells as well as in the surrounding BMSCs through the over-expression of JAGGED ligands. The activation of NOTCH pathway in the BMSCs renders these cells able to support tumor cells growth through the production of IL-6. These data are confirmed also by correlation analysis on gene expression profiles of MM patients and immunohistochemical studies. The ability of NOTCH pathway to positively regulate IL-6 in the non-neoplastic cells of BM microenvironment renders this pathway an important mediator of tumor-directed reprogramming of bone marrow niche. These results support the rationale for a NOTCH-direct therapeutic approach that can specifically target JAGGED ligands in order to reduce side effects associated with common NOTCH signaling inhibitor
La comunicazione interculturale in ambito aziendale: una chiave per l'internazionalizzazione
No full textDifferential effects of three herbal feed additives on growth and gut microbiota of weanling piglets
No full textSilymarin and lycopene administration in periparturient dairy cows: effects on milk production and oxidative status
No full textAIMS: To establish during late gestation and early lactation the effects of supplementing silymarin, a natural hepatoprotective substance, combined with a powerful antioxidant, lycopene, on milk production and on serum biomarkers of oxidative status. METHODS: Italian Friesian dairy cows were given individually a supplement containing a mixture of silymarin (7.77 g/day/cow) and lycopene (1.27 g/day/cow) (n=10) or no supplement (control; n=10). Treatment was administered from 7 days before the expected calving date to the first 14 days in milk. At 7 days before the expected calving date, at calving, and 7 days postpartum, body condition score (BCS) and concentrations in serum of reactive oxygen metabolites (ROM), total antioxidant capacity (OXY) and thiobarbituric acid reactive substances (TBARS) were evaluated. Bodyweight, milk production, and somatic cell count (SCC) were determined at 7, 14 and 21 days postpartum. RESULTS: The mean time of treatment prior to calving was 6.3 (min 4, max 11) days. Compared with control cows, treatment increased energy corrected milk yield (33.3 vs. 37.8 (SEM 1.10) kg/day; p=0.006) and milk fat yield (1.14 vs. 1.32 (SEM 0.06) kg/day; p=0.05) over the first 21 days of lactation. Treated cows had lower mean log10 SCC compared to control cows (4.9 vs. 5.24 (SEM 0.11) log10 cells/mL) and had lower overall concentration of TBARS (1.47 vs. 1.59 (SEM 0.016) nM/mL; p<0.001), but similar concentrations of ROM and OXY in serum. However there was a treatment by time interaction (p=0.09) for OXY, and at calving mean OXY was higher in treated cows compared with pre-calving values (p<0.001). CONCLUSIONS: Despite the acknowledged limitation of the study, i.e. the small number of animals, our results suggest that silymarin and lycopene, as health-beneficial feed supplements, may help dairy cows in metabolic adaptation during the first stages of lactation. CLINICAL RELEVANCE: During the peripartum period dairy cows suffer moderate-to-severe fatty liver and from an overproduction of free radicals. The supplementation of a mixture of silymarin and lycopene during these stressful days may be useful to mitigate these metabolic disorders with beneficial effects on the subsequent lactation
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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