Accounting Experiential Learning Firm (AELF): Learning Accounting in an Office Setting

Accounting subject is a dull and difficult subject to learn. Combining real source documents, practitioner’s advices, lecturer supervisions, office setting and accounting software, Accounting Experiential Learning Firm (AELF) is set up to answer the call for more experiential learning which could help the accounting students to understand accounting subject better. Moving from classroom boredom to a more practical office setting, AELF aim to increase student understanding and also interest in accounting subject and the profession. This article describes details of the AELF project and reports the feedbacks from students

Organoiridium complexes : anticancer agents and catalysts

Iridium is a relatively rare precious heavy metal, only slightly less dense than osmium. Researchers have long recognized the catalytic properties of square-planar Ir(I) complexes, such as Crabtree's hydrogenation catalyst, an organometallic complex with cyclooctadiene, phosphane, and pyridine ligands. More recently, chemists have developed half-sandwich pseudo-octahedral pentamethylcyclopentadienyl Ir(III) complexes containing diamine ligands that efficiently catalyze transfer hydrogenation reactions of ketones and aldehydes in water using H2 or formate as the hydrogen source. Although sometimes assumed to be chemically inert, the reactivity of low-spin 5d(6) Ir(III) centers is highly dependent on the set of ligands. Cp* complexes with strong σ-donor C^C-chelating ligands can even stabilize Ir(IV) and catalyze the oxidation of water. In comparison with well developed Ir catalysts, Ir-based pharmaceuticals are still in their infancy. In this Account, we review recent developments in organoiridium complexes as both catalysts and anticancer agents. Initial studies of anticancer activity with organoiridium complexes focused on square-planar Ir(I) complexes because of their structural and electronic similarity to Pt(II) anticancer complexes such as cisplatin. Recently, researchers have studied half-sandwich Ir(III) anticancer complexes. These complexes with the formula [(Cp(x))Ir(L^L')Z](0/n+) (with Cp* or extended Cp* and L^L' = chelated C^N or N^N ligands) have a much greater potency (nanomolar) toward a range of cancer cells (especially leukemia, colon cancer, breast cancer, prostate cancer, and melanoma) than cisplatin. Their mechanism of action may involve both an attack on DNA and a perturbation of the redox status of cells. Some of these complexes can form Ir(III)-hydride complexes using coenzyme NAD(P)H as a source of hydride to catalyze the generation of H2 or the reduction of quinones to semiquinones. Intriguingly, relatively unreactive organoiridium complexes containing an imine as a monodentate ligand have prooxidant activity, which appears to involve catalytic hydride transfer to oxygen and the generation of hydrogen peroxide in cells. In addition, researchers have designed inert Ir(III) complexes as potent kinase inhibitors. Octahedral cyclometalated Ir(III) complexes not only serve as cell imaging agents, but can also inhibit tumor necrosis factor α, promote DNA oxidation, generate singlet oxygen when photoactivated, and exhibit good anticancer activity. Although relatively unexplored, organoiridium chemistry offers unique features that researchers can exploit to generate novel diagnostic agents and drugs with new mechanisms of action

Predictors of Paravalvular Regurgitation Following Implantation of the Fully Repositionable and Retrievable Lotus Transcatheter Aortic Valve (From the REPRISE II Trial Extended Cohort)

Paravalvular leak (PVL) following transcatheter aortic valve replacement (TAVR) is associated with worse long-term outcomes. The Lotus Valve incorporates an innovative adaptive seal designed to minimize PVL. This analysis evaluated the incidence and predictors of PVL following implantation of the Lotus transcatheter aortic valve. The REPRISE II study with Extended Cohort enrolled 250 high-surgical risk patients with severe symptomatic aortic stenosis. Aortic regurgitation was assessed by echocardiography pre-procedure, at discharge and 30 days by an independent core lab. Baseline and procedural predictors of mild or greater PVL at 30 days (or at discharge if 30-day data were not available) were determined using a multivariate regression model (N=229). Among 229 patients, 197 (86%) had no/trace PVL, 30 had mild, and 2 had moderate PVL; no patient had severe PVL. Significant predictors of mild/moderate PVL included device:annulus area ratio (odds ratio [OR]: 0.87 (95% CI: 0.83-0.92); P<0.001), LVOT calcium volume (OR:2.85;(1.44-5.63); P=0.003), and annulus area (OR:0.89(0.82-0.96); P=0.002). When the device:annulus area ratio was <1, the rate of mild/moderate PVL was 53.1% (17/32). The rates of mild/moderate PVL with 0-5%, 5-10%, and >10% annular oversizing by area were 17.5% (11/63), 2.9% (2/70), and 3.2% (2/63), respectively. Significant independent predictors of PVL included device:annulus area ratio and LVOT calcium volume. When the prosthetic valve was oversized by ≥5%, the rate of mild or greater PVL was only 3%. In conclusion, the overall rates of PVL with the Lotus Valve are low and predominantly related to device/annulus areas and calcium; these findings have implications for optimal device sizing

Darstellung und DNA-Wechselwirkungen von potentiell zytotoxischen OrganoiridiumIIIOrganoiridium^{III}-Bisinterkalatoren

Zielsetzung der Arbeit war das Design von neuartigen zytotoxisch-aktiven nicht kovalent-bindenden Bis-Organometallverbindungen, sowie die Charakterisierung und Untersuchung ihrer Wechselwirkung mit der DNA, wobei die mono- bzw. bis-interkalative Assoziation im Vordergrund stand. Mono- und Bis-Organometallkomplexen der Typen $[(\eta5-Cp^{*})Ir(N,N')L]_{n+}$ und $[{(\eta5-Cp^{*})M(N,N')}_{2}B]_{4+}$ (N,N' = dpq, Mphen, dppz und Mdppz; L = Cl (n=1), Pyridin (n=2), B = Pz, Bpy, Bpe, Edp und Dpph) wurden für diese Zielsetzung synthetisiert. Die Wirkung und Wirkungsmechanismus von den synthetisierten Komplexen wurden mittels analytische (UV/VIS-, CD-, 1 und 2D NOESY-NMR-Spektroskopie und Gelelektrophorese) und Biologische (Zytotoxizitäts-, Zellaufnahme-, Metabolismus-Studien, Messung der intrazellularen aktiven Sauerstoffspezies (ROS) und Annexinmessung) ermittelt

Organometallic half-sandwich iridium anticancer complexes

The low-spin 5d6 IrIII organometallic half-sandwich complexes [(η5-Cpx)Ir(XY)Cl]0/+, Cpx = Cp*, tetramethyl(phenyl)cyclopentadienyl (Cpxph), or tetramethyl(biphenyl)cyclopentadienyl (Cpxbiph), XY = 1,10-phenanthroline (4−6), 2,2′-bipyridine (7−9), ethylenediamine (10 and 11), or picolinate (12−14), hydrolyze rapidly. Complexes with N,N-chelating ligands readily form adducts with 9-ethylguanine but not 9-ethyladenine; picolinate complexes bind to both purines. Cytotoxic potency toward A2780 human ovarian cancer cells increases with phenyl substitution on Cp*: Cpxbiph > Cpxph > Cp*; Cpxbiph complexes 6 and 9 have submicromolar activity. Guanine residues are preferential binding sites for 4−6 on plasmid DNA. Hydrophobicity (log P), cell and nucleus accumulation of Ir correlate with cytotoxicity, 6 > 5 > 4; they distribute similarly within cells. The ability to displace DNA intercalator ethidium bromide from DNA correlates with cytotoxicity and viscosity of Ir−DNA adducts. The hydrophobicity and intercalative ability of Cpxph and Cpxbiph make a major contribution to the anticancer potency of their IrIII complexes

IDENTIFICATION OF AN IMPORTANT FACTOR INVOLVED IN CCHFV INFECTION

Despite intensive research, much of the molecular pathogenesis of CCHFV is still unknown. Genome-wide screening methods (particularly CRISPR/Cas9-based screens and insertional mutagenesis in haploid cell systems) have facilitated and accelerated the identification and characterization of host genes involved in infectious diseases. Combining haploid cells with genome saturating chemical mutagenesis using N-Ethyl-N-nitrosourea, we have developed an unbiased screening system that interrogates single nucleotide variants for their relevance in viral infections. To identify host factors involved in CCHFV infections, we performed resistant screens with a viral RNA replication competent vesicular stomatitis virus, pseudotyped with the glycoproteins of the CCHFV (VSV-CCHF_G). Resistant clones were individually selected, expanded and rescreened using the infectious CCHFV IbAr10200 laboratory strain. Subsequently, whole exome sequencing was conducted on the resistant clones. Three clones showing nearly 100% resistance to CCHFV displayed mutations in the gene encoding for protein we named X. Through the use of knocked out haploid and diploid cells as well as soluble form of this protein on VSV-CCHF_G, CCHFV IbAr 10200 and CCHFV isolate, we showed that this protein is important for CCHFV infection. These data were then confirmed in vivo, in a mice model. By using an unbiaised screening system, our study identified an important factor involved for CCHFV cell entry and infection