Fully-automated production of [68Ga]Ga-PentixaFor on the module Modular Lab-PharmTracer

BACKGROUND: PentixaFor is a promising radiopharmaceutical for positron emission tomography in the detection of different tumor entities and other diseases. Until now, the synthesis of [68Ga]Ga-PentixaFor was reported for the automated synthesis module from Scintomics® only. Our aim was to evaluate the automated synthesis of this radiopharmaceutical on a different module in order to make it available for a broader community. RESULTS: The synthesis of [68Ga]Ga-PentixaFor with different amounts of PentixaFor (50 μg, 30 μg and 20 μg) on the Modular Lab PharmTracer (MLPT) from Eckert & Ziegler with the already established synthesis template for [68Ga]Ga-DOTATOC yielded best results with 50 μg PentixaFor for clinical multi-dose application. All different quality control parameters tested (e.g. sterility, stability and radiochemical purity) were in accordance with the European Pharmacopoeia. CONCLUSIONS: [68Ga]Ga-PentixaFor was successfully synthesized fully-automated on the synthesis module Modular Lab PharmTracer and can be used for multi-dose application in clinical settings

Teaching Kansas Environment and Culture in the KU Academic Accelerator Program

As Christopher Hitchings (2008) says in his seminal work, The Secret Life of Words, “A new word is a solution to a problem” (p. 5). This observation proved true many times in my year of directing and teaching international students in the Kansas University Academic Accelerator Program (KUAAP). In fact, that simple phrase became my touchstone and inspiration during the initial terms of the program in 2014-2015

Relevance of copper and organic cation transporters in the activity and transport mechanisms of an anticancer cyclometallated gold(III) compound in comparison to cisplatin

The molecular mechanisms of toxicity and cellular transport of anticancer metallodrugs, including platinum-based agents, have not yet been fully elucidated. The aim of our study was to investigate the relevance of copper transporters (CTR1 and ATP7A/B), organic cation transporters (OCT2) and the multidrug and toxin extrusion proteins (MATE) in the intracellular accumulation of a novel organometallic cytotoxic Au(III) compound in cancer cells in comparison to cisplatin. Specifically, the synthesis and characterization of the gold complex [Au(py(b)-H)(PPh2Ar)Cl]PF6 (PPh2Ar = 3-[4-(diphenylphosphino)pheny]7-methoxy-2H-chromen-2-one] (1), featuring a coumarin ligand endowed with "smart" fluorescence properties, have been achieved. Initially, the cytotoxic effects of both cisplatin and 1 were studied in a small panel of human cancer cells, and against a non-tumorigenic cell line in vitro. Thus, the human ovarian cancer cell line A2780 and its cisplatin resistant variant A2780cisR, were selected, being most sensitive to the treatment of the gold complex. Co-incubation of the metallodrugs with CuCl2 (a CTR1 substrate) increased the cytotoxic effects of both the Au(III) complex and cisplatin; while co-incubation with cimetidine (inhibitor of OCT2 and MATE) showed some effect only after 72 h incubation. ICP-MS (Inductively Coupled Plasma Mass Spectrometry) analysis of the cell extracts showed that co-incubation with CuCl2 increases Au and Cu accumulation in both cancer cell lines, in accordance with the enhanced antiproliferative effects. Conversely, for cisplatin, no increase in Pt content could be observed in both cell lines after co-incubation with either CuCl2 or cimetidine, excluding the involvement of CTR1, OCT2, and MATE in drug accumulation and overall anticancer effects. This result, together with the evidence for increased Cu content in A2780 cells after cisplatin co-treatment with CuCl2, suggests that copper accumulation is the reason for the observed enhanced anticancer effects in this cell line. Moreover, metal uptake studies in the same cell lines indicate that both 1 and cisplatin are not transported intracellularly by CTR1 and OCT2. Finally, preliminary fluorescence microscopy studies enabled the visualization of the sub-cellular distribution of the gold compound in A2780 cells, suggesting accumulation in specific cytosolic components/organelles

Exploring the potential of gold(iii) cyclometallated compounds as cytotoxic agents: variations on the C^N theme

A series of novel ((CN)-N-boolean AND) cyclometallated Au(III) complexes of general formula [Au(py(b)-H)(LL2)-L-1](n+) (py(b)-H = (CN)-N-boolean AND cyclometallated 2-benzylpyridine, L-1 and L-2 being chlorido, phosphane or glucosethiolato ligands, n = 0 or 1) have been synthesized and fully characterized using different techniques, including NMR, IR and far-IR, mass spectrometry, as well as elemental analysis. The crystal structure of one compound has been solved using X-ray diffraction methods. All compounds were tested in vitro in five human cancer cell lines including the lung, breast, colon and ovarian cancer cells. For comparison purposes, all compounds were also tested in a model of healthy human cells from the embryonic kidney. Notably, all new compounds were more toxic than their cyclometallated precursor bearing two chlorido ligands, and the derivative bearing one phosphane ligand presented the most promising toxicity profile in our in vitro screening, displaying a p53 dependent activity in colorectal cancer HCT116 cells. Finally, for the first time (CN)-N-boolean AND cyclometallated gold(III) complexes were shown to be potent inhibitors of the zinc finger protein PARP-1, involved in the mechanism of cisplatin resistance

Hosea as a religious pioneer

This item was digitized by the Internet Archive. Thesis (M.A.)--Boston Universityhttps://archive.org/details/hoseaasreligious00spr

Prospects of increase of efficiency of functioning of insurance companies through the development of information systems

Russian companies have already been solved (or solved) issues automated support of business processes of insurance. Another aspect of it application in the insurance, which to date remains one of the most important is to support decision-making in the claim process, as it depends largely on the economic condition of the insurance company. To resolve this problem, the development of information systems, the inclusion in their structure of intellectual component, reducing the probability of errors when making decisions. The work of this component is based on the principles of the decision theory and artificial intelligence, uses the mathematical apparatus of decision-making in conditions of uncertainty and risk and is a tool that interacts with the information system of the company

Green Buildings, Environmental Awareness, and Organizational Image

The paper reports a study that was conducted to understand the relationships between the occupants’ assessments of the environmental design features of a “green” building and their assessments of environmental awareness (EA) and organizational image (OI). The study hypothesized that the occupant’s assessments of individual workspace and departmental space features of a “green” building would directly affect their assessments of EA and OI, or that the occupant’s assessments of individual workspace and departmental space features would indirectly affect their assessments of EA and OI through their satisfaction with individual workspace, departmental spaces and/or the building. In order to test these hypotheses, data were collected from 175 occupants of the Gold‐level LEED‐certified “green” building using a questionnaire instrument. Using frequency, correlational, and regression analyses of the data, the study found little or no evidence for direct relationships between the occupant’s assessments of individual workspace and departmental space features and their assessments of EA and OI. The study, however, found some evidence for indirect relationships between the occupant’s assessments of individual workspace and departmental space features and their assessment of EA and OI. The evidence showed that the occupant’s assessments of individual workspace and departmental space features had affected their satisfaction with individual workspaces and the building, which then affected the occupants’ assessments of EA and OI. The study is important for it provides evidence for connecting green buildings to organizational benefits and values

Acridine-decorated cyclometallated gold(III) complexes: synthesis and anti-tumour investigations

(C^N) and (C^N^C) cyclometalated Au(III) represent a highly promising class of potential anticancer agents. We report here the synthesis of seven new cyclometalated Au(III) complexes with five of them bearing an acridine moiety attached via (N^O) or (N^N) chelates, acyclic amino carbenes (AAC) and N-heterocyclic carbenes (NHC). The antiproliferative properties of the different complexes were evaluated in vitro on a panel of cancer cells including leukaemia, lung and breast cancer cells. We observed a trend between the cytotoxicity and the intracellular gold uptake of some representative compounds of the series. Some of the acridine-decorated complexes were demonstrated to interact with ds-DNA using FRET-melting techniques