46 research outputs found

    Product costing and activity-based costing/management in BacalhĂŽa Vinhos de Portugal

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    The present Work Project introduces a case study addressing the adoption of an ABC/M system in a winemaking company. The system was implemented in only one area of the company, and its adoption allows the company to perform ABM analysis resorting to the ABC information. A mixed approach is used to cost the products: both traditional and ABC systems are used although in different areas of the company. ABC/M implementation was perceived as ‘successful’ despite not following recommendations prescribed in literature

    Functional loss of IÎșBΔ leads to NF-ÎșB deregulation in aggressive chronic lymphocytic leukemia

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    NF-ÎșB is constitutively activated in chronic lymphocytic leukemia (CLL); however, the implicated molecular mechanisms remain largely unknown. Thus, we performed targeted deep sequencing of 18 core complex genes within the NF-ÎșB pathway in a discovery and validation CLL cohort totaling 315 cases. The most frequently mutated gene was NFKBIE (21/315 cases; 7%), which encodes IÎșBΔ, a negative regulator of NF-ÎșB in normal B cells. Strikingly, 13 of these cases carried an identical 4-bp frameshift deletion, resulting in a truncated protein. Screening of an additional 377 CLL cases revealed that NFKBIE aberrations predominated in poor-prognostic patients and were associated with inferior outcome. Minor subclones and/or clonal evolution were also observed, thus potentially linking this recurrent event to disease progression. Compared with wild-type patients, NFKBIE-deleted cases showed reduced IÎșBΔ protein levels and decreased p65 inhibition, along with increased phosphorylation and nuclear translocation of p65. Considering the central role of B cell receptor (BcR) signaling in CLL pathobiology, it is notable that IÎșBΔ loss was enriched in aggressive cases with distinctive stereotyped BcR, likely contributing to their poor prognosis, and leading to an altered response to BcR inhibitors. Because NFKBIE deletions were observed in several other B cell lymphomas, our findings suggest a novel common mechanism of NF-ÎșB deregulation during lymphomagenesis

    Role of the Base in Buchwald–Hartwig Amination

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    The Buchwald–Hartwig amination has been investigated theoretically and experimentally to examine the scope of possible bases under different reaction conditions. Nonpolar solvents resist the formation of new charges. Therefore, the base should be anionic to be able to deprotonate the neutral palladium–amine complex and/or expel the anionic leaving group (bromide). The calculated barrier for the organic base DBU was found to be prohibitively high. In polar solvent, dissociation of bromide becomes possible, but here the base will instead form a complex with palladium, creating an overly stable resting state. The conclusions for both solvent classes hold for both a hindered monodentate phosphine and the labile bidentate ligand BINAP. The computational studies were supported by experimental testing of a range of bases using BINAP in two different solvents, toluene and DMF
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