20 research outputs found
Radiofluorinated quinoxalinedione derivatives as putative ligands of the AMPA receptor Development of synthetic strategies and labeling
Vital organising : capitalism’s ontological turn and the role of management consulting
This thesis sets out to develop an approach to capitalism that locates its contemporary practice at the level of ontology. It evolves around the argument that contemporary capitalism is itself becoming ontological, that capital has in some sense moved into being. In order to argue thus, the analysis adopts a perspective of process-ontology that is influenced to a great extent by the recent resurgence of vitalism in disciplines such as sociology and cultural studies. Such a vitalist approach can be productively linked to an influential strain of Marxist theory that approaches contemporary capitalism in terms of real subsumption, understood as capital's full penetration of and its becoming operative within the process by which social life (re)creates itself. This thesis develops the notion of vital organising as a concrete strategy enabling capital's displacement into the process of social life. Vital organising conceptualises the widely observed transformations in the field of economic organisation, a) in terms of their ontological significance, and b) in such a way that they can be located within a theory of contemporary capitalism. Moreover, this thesis embeds its abstract conceptual considerations within an empirical exploration of capital's ontological turn in the field of economic organisation. In concrete terms, empirical research into the theory and practice of management consulting identifies trajectories of vital organising in the contemporary practice of economic organisation
Culture as an objective for, and a means of achieving, a Wellbeing Economy
The world faces multiple intersecting crises, several of which are existential. The
current dominant economic design is at their root cause, leading to increased
advocacy for alternative economic approaches, including Wellbeing Economy.
However, the role of culture, both as an objective and as a means of achieving a
Wellbeing Economy, is largely absent. In this article, we review how culture has
been misunderstood as being dependent on the attainment of basic needs rather
than an ever-present, vital, but undervalued attribute of all societies. We discuss
how neoliberal economics has individualised and commodified culture, valuing it
only as an engine of economic growth and tradeable capital, all of which has led
to a substantial diminution and fraying of the social fabric which any positive
social transformation will rely upon. Finally, we demonstrate why culture is an
essential precondition for the creation of momentum for change through the
conversations, shared understandings, new narratives, and communal spaces of
all forms which cultural flourishing creates. We conclude by arguing that
advocates for a Wellbeing Economy, and similar economic models, such as
Doughnut Economics and Foundational Economies, should prioritise and embed
support for cultural development as a non-commodified social asset if we are to
adequately respond to current crises and navigate to a flourishing and habitable
future for ourselves and our descendants
Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry Identification of Yeasts Is Contingent on Robust Reference Spectra
BACKGROUND: Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) for yeast identification is limited by the requirement for protein extraction and for robust reference spectra across yeast species in databases. We evaluated its ability to identify a range of yeasts in comparison with phenotypic methods. METHODS: MALDI-TOF MS was performed on 30 reference and 167 clinical isolates followed by prospective examination of 67 clinical strains in parallel with biochemical testing (total n = 264). Discordant/unreliable identifications were resolved by sequencing of the internal transcribed spacer region of the rRNA gene cluster. PRINCIPAL FINDINGS: Twenty (67%; 16 species), and 24 (80%) of 30 reference strains were identified to species, (spectral score ≥2.0) and genus (score ≥1.70)-level, respectively. Of clinical isolates, 140/167 (84%) strains were correctly identified with scores of ≥2.0 and 160/167 (96%) with scores of ≥1.70; amongst Candida spp. (n = 148), correct species assignment at scores of ≥2.0, and ≥1.70 was obtained for 86% and 96% isolates, respectively (vs. 76.4% by biochemical methods). Prospectively, species-level identification was achieved for 79% of isolates, whilst 91% and 94% of strains yielded scores of ≥1.90 and ≥1.70, respectively (100% isolates identified by biochemical methods). All test scores of 1.70-1.90 provided correct species assignment despite being identified to "genus-level". MALDI-TOF MS identified uncommon Candida spp., differentiated Candida parapsilosis from C. orthopsilosis and C. metapsilosis and distinguished between C. glabrata, C. nivariensis and C. bracarensis. Yeasts with scores of <1.70 were rare species such as C. nivariensis (3/10 strains) and C. bracarensis (n = 1) but included 4/12 Cryptococcus neoformans. There were no misidentifications. Four novel species-specific spectra were obtained. Protein extraction was essential for reliable results. CONCLUSIONS: MALDI-TOF MS enabled rapid, reliable identification of clinically-important yeasts. The addition of spectra to databases and reduction in identification scores required for species-level identification may improve its utility
Vital organising : capitalism’s ontological turn and the role of management consulting
EThOS - Electronic Theses Online ServiceGBUnited Kingdo
Radiofluorinated quinoxalinedione derivatives as putative ligands of the AMPA receptor
Labeling of physiologically relevant molecules with no carrier added (n.c.a.) [F]fluoride is performed with the aim of an application of these “radiotracers” in positron emission tomography. In order to find Flabeled radioligands of the AMPA receptor on the basis of the urea structure, the first task of this work was to develop a synthesis of 4-[F]fluorophenyl urea derivatives. A direct labeling of the electron rich, i.e. not activated, 4-fluorophenyl ureas by an SAr-reaction is not possible. Thus, radiosyntheses involving three or four step procedures were developed. 4-[F]Fluoroaniline was produced in the first two steps, whose synthesis has already been described several times in the literature. All those concepts were combined to give an optimum method regarding efficiency and duration. The reaction of para-dinitrobenzene with n.c.a. [F]fluoride, activated by the potassium-Kryptofix-complex, in DMSO at 120°C leads to 4-[F]fluoronitrobenzene. For the subsequent reduction of the nitro-group, palladium (black) and phosphoric acid in methanol under reflux conditions proved to be the best system to yield 4-[F]fluoroaniline. The time of synthesis until this step was 30 min with a radiochemical yield of at least 80%. Subsequent transformation to the 4-[F]fluorophenyl ureas was performed via carbamate-4-nitrophenylesters, whereas strategies involving isocyanate compounds failed. In general, reactions of carbamate-4-nitrophenylesters with an amine yielded the corresponding urea. Hence, two different ways for the radiosynthesis are possible. One is to produce the carbamate in a reaction of [F]fluoroaniline with 4-nitrophenyl chloroformate, followed by addition of an amine of choice. To avoid one radiosynthetic step, the [F]fluoroaniline can alternatively be reacted directly with the 4-nitrophenyl carbamate of the amine. The yields of the [F]fluorophenylcarbamate-4-nitrophenylester from [F]fluoroaniline are nearby quantitative. Subsequent reaction with n-propyl amine, cyclo-hexyl amine, benzyl amine or aniline leads to the corresponding ureas with an overall radiochemical yield of more than 70%. The shorter radiosyntheses with [F]fluoroaniline and phenylcarbamate, benzylcarbamate or cyclo-hexylcarbamate gave generally a lower RCY in the range of 50 to 70%. With the n-propylcarbamate nearly no conversion to the urea is detectable. A direct application of this general method to preparation of n.c.a. [F]fluorophenyl ureas for the synthesis of two putative AMPA-receptor ligands of the quinoxalinedione-family (QX) failed. Even the synthesis of the stable reference substances was not successful. Therefore a change to less complex quinoxalinediones appeared necessary, and those labeling approaches led to success. Dinitro- and cyano-nitro-QX are established antagonists of the AMPA-receptor. The aromatic rings in these molecules are activated by the nitro- or cyano-group, respectively, for the SNAr-reaction with [F]fluoride, whereas one nitro-group might function as leaving group. The relevant stable analogues fluoro-nitro-QX (FNQX) and fluoro-cyano-QX (FCQX) were synthesized as reference substances. The radiosynthesis of [F]FNQX was performed with DNQX as precursor and Kryptofix-activation in DMSO at 180°C and a reaction time of 20 min. With the low RCY of 5 – 10% and a molar activity of 1.5 GBq/μmol there was enough labeled product for first pharmacological experiments. F-labeling of FCQX was only possible by an isotopic exchange reaction. Therefore, the [F]FNQX contains carrier, and the RCY with about 5% is again very low. For the general evaluation of the affinity of FNQX and FCQX the stable reference substances were utilized in competition studies with tritiated AMPA in vitro. Their affinities in form of the inhibition constants Ki were determined with 1.4 μmol and 3.9 μmol, respectively, which are clearly lower than those of CNQX (0.5 μmol) or AMPA (0.06 μmol). Nevertheless, the general mode of structur-activity-relationship in QX-derivatives could be affirmed by these studies. Blocking experiments with rat brain slices showed that the binding of [3H]AMPA or [F]FNQX can be neither completely blocked by an excess of stable FNQX nor by an excess of stable FCQX. This is an evidence for a large fraction of unspecific binding of the ligand in brain tissue. Finally, the extremely low brain uptake of [F]FNQX, which was determined in ex vivo examinations, led to the conclusion that these substances are not suited for radiopharmaceutical application of in vivo imaging
Drie hobbels op het pad naar 'brede welvaart': Hervorming economisch systeem noodzakelijk: winst minder van belang
Opinieartikel over het belang van kunst en cultuur voor de brede welvaart, met name in Noord-Brabant