Evaluating Models Of The Relationship Between Accounting Profitability Measures And Internal Rate Of Return

Researchers have investigated the relationship between the internal rate of return (IRR) and accounting-based profitability measures using analytical and indirect empirical methodologies.  The current study employs computer simulation to complement the other two methodologies and corroborate their results. The results indicate that the accounting rate of return (ARR) and the conditional estimate of internal rate of return (CIRR) are strongly associated with IRR; however, the length of the estimation period and formulation used for CIRR appear to affect its relationship to IRR.  ARR’s relationship to IRR appears to be unaffected by the length of the estimation period

Antimicrobial susceptibility of Gram-positive bacteria isolated from European medical centres: results of the Daptomycin Surveillance Programme (2002-2004)

The antimicrobial susceptibility patterns of 9322 contemporary (2002-2004) Gram-positive bacterial isolates collected from 31 medical centres in 14 countries in Europe were evaluated by broth microdilution methods according to CLSI guidelines. the isolates collected comprised Staphylococcus aureus (4842 isolates), coagulase-negative staphylococci (CoNS; 1942 isolates), Enterococcus faecalis (1147 isolates), Enterococcus faecium (391 isolates), beta-haemolytic streptococci (660 isolates) and viridans group streptococci (340 isolates). the organisms were tested against daptomycin and more than 20 comparator agents in Mueller-Hinton broth, supplemented with calcium to 50 mg/L when testing daptomycin. Overall, methicillin (oxacillin) resistance rates were 26.7% and 77.0% for S. aureus (MRSA) and CoNS, respectively, and the vancomycin resistance rate among enterococci was 6.1%. MRSA rates varied from 0.6% in Sweden to 40.2-43.0% in Belgium, Greece, Ireland, the UK and Israel, and VRE rates varied from 0% in Switzerland to 21.2% in Ireland. More than 99.9% of isolates tested were considered susceptible to daptomycin according to breakpoints established by the United States Food and Drug Administration and the CLSI. Daptomycin was active against all Gram-positive species, with the highest MIC being 2, 8, 0.5 and 2 mg/L for staphylococci, enterococci, beta-haemolytic streptococci and viridans group streptococci, respectively. Daptomycin activity was not influenced adversely by resistance to other agents among staphylococci or enterococci. This novel lipopeptide (daptomycin) appears to be an excellent alternative therapeutic option for serious infections caused by multidrug-resistant Gram-positive organisms isolated in Europe.JMI Labs Inc, N Liberty, IA 52317 USAUniversidade Federal de São Paulo, São Paulo, BrazilTufts Univ, Sch Med, Boston, MA 02111 USAUniversidade Federal de São Paulo, São Paulo, BrazilWeb of Scienc

Effects of RAF inhibitors on PI3K/AKT signalling depend on mutational status of the RAS/RAF signalling axis

Targeted therapies within the RAS/RAF/MEK/ERK signalling axis become increasingly popular, yet cross-talk and feedbacks in the signalling network lead to unexpected effects. Here we look systematically into how inhibiting RAF and MEK with clinically relevant inhibitors result in changes in PI3K/AKT activation. We measure the signalling response using a bead-based ELISA, and use a panel of three cell lines, and isogenic cell lines that express mutant forms of the oncogenes KRAS and BRAF to interrogate the effects of the MEK and RAF inhibitors on signalling. We find that treatment with the RAF inhibitors have opposing effects on AKT phosphorylation depending on the mutational status of two important oncogenes, KRAS and BRAF. If these two genes are in wildtype configuration, RAF inhibitors reduce AKT phosphorylation. In contrast, if BRAF or KRAS are mutant, RAF inhibitors will leave AKT phosphorylation unaffected or lead to an increase of AKT phosphorylation. Down-regulation of phospho-AKT by RAF inhibitors also extends to downstream transcription factors, and correlates with apoptosis induction. Our results show that oncogenes rewire signalling such that targeted therapies can have opposing effects on parallel pathways, which depend on the mutational status of the cell

Magneto-Coulomb Oscillation in Ferromagnetic Single Electron Transistors

The mechanism of the magneto-Coulomb oscillation in ferromagnetic single electron transistors (SET's) is theoretically considered. Variations in the chemical potentials of the conduction electrons in the ferromagnetic island electrode and the ferromagnetic lead electrodes in magnetic fields cause changes in the free energy of the island electrode of the SET. Experimental results of the magneto-Coulomb oscillation in a Ni/Co/Ni ferromagnetic SET are presented and discussed. Possible applications of this phenomenon are also discussed.Comment: 24 pages Latex, 5 figures in GIF files, style files included. Revised version: some errors are corrected and further discussions are added. To be published in J. Phys. Soc. Jpn. Vol.67 (1998) No.

DNA methylation in human gastric epithelial cells defines regional identity without restricting lineage plasticity

BACKGROUND: Epigenetic modifications in mammalian DNA are commonly manifested by DNA methylation. In the stomach, altered DNA methylation patterns have been observed following chronic Helicobacter pylori infections and in gastric cancer. In the context of epigenetic regulation, the regional nature of the stomach has been rarely considered in detail. RESULTS: Here, we establish gastric mucosa derived primary cell cultures as a reliable source of native human epithelium. We describe the DNA methylation landscape across the phenotypically different regions of the healthy human stomach, i.e., antrum, corpus, fundus together with the corresponding transcriptomes. We show that stable regional DNA methylation differences translate to a limited extent into regulation of the transcriptomic phenotype, indicating a largely permissive epigenetic regulation. We identify a small number of transcription factors with novel region-specific activity and likely epigenetic impact in the stomach, including GATA4, IRX5, IRX2, PDX1 and CDX2. Detailed analysis of the Wnt pathway reveals differential regulation along the craniocaudal axis, which involves non-canonical Wnt signaling in determining cell fate in the proximal stomach. By extending our analysis to pre-neoplastic lesions and gastric cancers, we conclude that epigenetic dysregulation characterizes intestinal metaplasia as a founding basis for functional changes in gastric cancer. We present insights into the dynamics of DNA methylation across anatomical regions of the healthy stomach and patterns of its change in disease. Finally, our study provides a well-defined resource of regional stomach transcription and epigenetics. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13148-022-01406-4