89 research outputs found
Malthus vs. Wordsworth: Perspectives on humankind, nature and economy
In this paper the view of humankind and nature upon which the thinking of Malthus is founded will be reflected on and contrasted with the opposed understanding of his contemporary Wordsworth. We show that the economic considerations of both are based decidedly on the premise of these views, and that their alternative interpretations of the contemporary economy and the relationship between economy and nature may thus be explained. From the comparison of Malthus and Wordsworth we draw conclusions for modern ecological economics, identifying its Malthusian understanding of nature and reflecting on the capacities and limits implied for further research. We ascribe a central role in the conceptual history of ecological economics to Wordsworth and present his philosophical presumptions as a fruitful alternative for ecological economics. Finally, attention will be drawn to the principle importance of the philosophical foundations underpinning this field of research
Die unterschiedlichen Sichtweisen von Malthus und Wordsworth auf Mensch, Natur und Wirtschaft
Dieser Aufsatz reflektiert das Verständnis von Mensch und Natur, welches dem Denken von Malthus zugrunde liegt und kontrastiert es mit dem völlig anderen Verständnis seines Zeitgenossen William Wordsworth. Wir zeigen, dass die ökonomischen Überlegungen beider entscheidend durch diese Voraussetzungen ihres Denkens bedingt sind und sich hieraus auch ihre unterschiedlichen Analysen zur zeitgenössischen Ökonomie erklären. Aus der Gegenüberstellung von Malthus und Wordsworth ziehen wir schließlich Schlussfolgerungen für die heutige Ökologische Ökonomik. Wir identifizieren das malthusianische Naturverständnis innerhalb dieser Wissenschaft und diskutieren dessen Tragfähigkeit für die weitere Forschung. Wir messen Wordsworth eine bedeutende Rolle in der Ideengeschichte der Ökologischen Ökonomik zu und beschreiben die philosophischen Voraussetzungen seines Denkens als eine fruchtbare alternative Grundlage für die Ökologische Ökonomik. Schließlich betonen wir die prinzipielle Bedeutung einer Grundlagenreflexion im Rahmen dieser Forschungsrichtung
Fremtiden for fag, forsknings- og uddannelsesbibliotekerne er nu
De store universitetsbiblioteker fusionerer. Hensigten er at centralisere en række områder, f.eks. licensområdet og systemarkitektur, og herved opnå en mulig stordriftsfordel. Set ud fra et samfundsøkonomisk perspektiv, kan det give god mening, men der er tale om store omvæltninger i biblioteksverdenen
Assay and heterologous expression in Pichia pastoris of plant cell wall type-II membrane anchored glycosyltransferases
Two Arabidopsis xylosyltransferases, designated RGXT1 and RGXT2, were recently expressed in Baculovirus transfected insect cells and by use of the free sugar assay shown to catalyse transfer of D-xylose from UDP-α-D-xylose to L-fucose and derivatives hereof. We have now examined expression of RGXT1 and RGXT2 in Pichia pastoris and compared the two expression systems. Pichia transformants, expressing soluble, secreted forms of RGXT1 and RGXT2 with an N- or C-terminal Flag-tag, accumulated recombinant, hyper-glycosylated proteins at levels between 6 and 16 mg protein • L-1 in the media fractions. When incubated with 0.5 M L-fucose and UDP-D-xylose all four RGXT1 and RGXT2 variants catalyzed transfer of D-xylose onto L-fucose with estimated turnover numbers between 0.15 and 0.3 sec-1, thus demonstrating that a free C-terminus is not required for activity. N- and O-glycanase treatment resulted in deglycosylation of all four proteins, and this caused a loss of xylosyltransferase activity for the C-terminally but not the N-terminally Flag-tagged proteins. The RGXT1 and RGXT2 proteins displayed an absolute requirement for Mn2+ and were active over a broad pH range. Simple dialysis of media fractions or purification on phenyl Sepharose columns increased enzyme activities 2-8 fold enabling direct verification of the product formed in crude assay mixtures using electrospray ionization mass spectrometry. Pichia expressed and dialysed RGXT variants yielded activities within the range 0.011 to 0.013 U (1 U = 1 nmol conversion of substrate • min-1 • µl medium-1) similar to those of RGXT1 and RGXT2 expressed in Baculovirus transfected insect Sf9 cells. In summary, the data presented suggest that Pichia is an attractive host candidate for expression of plant glycosyltransferases
High-throughput Proteomics Identifies THEMIS2 as Independent Biomarker of Treatment-free Survival in Untreated CLL
It remains challenging in chronic lymphocytic leukemia (CLL) to distinguish between patients with favorable and unfavorable time-to-first treatment (TTFT). Additionally, the downstream protein correlates of well-known molecular features of CLL are not always clear. To address this, we selected 40 CLL patients with TTFT ≤24 months and compared their B cell intracellular protein expression with 40 age- and sex-matched CLL patients with TTFT >24 months using mass spectrometry. In total, 3268 proteins were quantified in the cohort. Immunoglobulin heavy-chain variable (IGHV) mutational status and trisomy 12 were most impactful on the CLL proteome. Comparing cases to controls, 5 proteins were significantly upregulated, whereas 3 proteins were significantly downregulated. Of these, only THEMIS2, a signaling protein acting downstream of the B cell receptor, was significantly associated with TTFT, independently of IGHV and TP53 mutational status (hazard ratio, 2.49 [95% confidence interval, 1.62-3.84]; P < 0.001). This association was validated on the mRNA and protein level by quantitative polymerase chain reaction and ELISA, respectively. Analysis of 2 independently generated RNA sequencing and mass spectrometry datasets confirmed the association between THEMIS2 expression and clinical outcome. In conclusion, we present a comprehensive characterization of the proteome of untreated CLL and identify THEMIS2 expression as a putative biomarker of TTFT.</p
Polyglutamine-expanded ataxin-3: a target engagement marker for spinocerebellar ataxia type 3 in peripheral blood
Background:
Spinocerebellar ataxia type 3 is a rare neurodegenerative disease caused by a CAG repeat expansion in the ataxin-3 gene. Although no curative therapy is yet available, preclinical gene-silencing approaches to reduce polyglutamine (polyQ) toxicity demonstrate promising results. In view of upcoming clinical trials, quantitative and easily accessible molecular markers are of critical importance as pharmacodynamic and particularly as target engagement markers.
Objective:
We aimed at developing an ultrasensitive immunoassay to measure specifically polyQ-expanded ataxin-3 in plasma and cerebrospinal fluid (CSF).
Methods:
Using the novel single molecule counting ataxin-3 immunoassay, we analyzed cross-sectional and longitudinal patient biomaterials.
Results:
Statistical analyses revealed a correlation with clinical parameters and a stability of polyQ-expanded ataxin-3 during conversion from the pre-ataxic to the ataxic phases.
Conclusions:
The novel immunoassay is able to quantify polyQ-expanded ataxin-3 in plasma and CSF, whereas ataxin-3 levels in plasma correlate with disease severity. Longitudinal analyses demonstrated a high stability of polyQ-expanded ataxin-3 over a short period. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder SocietyFunding agencies: This project is supported by the EU Joint Programme—Neurodegenerative Disease Research (JPND) through the following funding organizations under the aegis of JPND: Germany, Federal Ministry of Education and Research (BMBF; funding codes 01ED1602A/B); Netherlands, The Netherlands Organisation for Health Research and Development; Portugal, Foundation for Science and Technology (FCT, grant number JPCOFUND/0001/2015), and Regional Fund for Science and Technology of the Azores; and United Kingdom, Medical Research Council. This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement number 643417. In addition, support has been received by the BIONIC project (number 733050822, which has been made possible by ZonMW as part of “Memorabel,” the research and innovation program for dementia, as part of the Dutch national “Deltaplan for Dementia”: zonmw.nl/dementiaresearch), the CAF[1]E project (the National Institutes of Health, USA, grant number 5R01NS104147-02), and a grant from the Selfridges Group Foundation (NR170024). The BIONIC project is a consortium of Radboudumc, LUMC, ADX Neurosciences, and Rhode Island University
CANDELS Visual Classifications: Scheme, Data Release, and First Results
We have undertaken an ambitious program to visually classify all galaxies in the five CANDELS fields down to H \u3c 24.5 involving the dedicated efforts of over 65 individual classifiers. Once completed, we expect to have detailed morphological classifications for over 50,000 galaxies spanning 0 \u3c z \u3c 4 over all the fields, with classifications from 3 to 5 independent classifiers for each galaxy. Here, we present our detailed visual classification scheme, which was designed to cover a wide range of CANDELS science goals. This scheme includes the basic Hubble sequence types, but also includes a detailed look at mergers and interactions, the clumpiness of galaxies, k-corrections, and a variety of other structural properties. In this paper, we focus on the first field to be completed—GOODS-S, which has been classified at various depths. The wide area coverage spanning the full field (wide+deep+ERS) includes 7634 galaxies that have been classified by at least three different people. In the deep area of the field, 2534 galaxies have been classified by at least five different people at three different depths. With this paper, we release to the public all of the visual classifications in GOODS-S along with the Perl/Tk GUI that we developed to classify galaxies. We present our initial results here, including an analysis of our internal consistency and comparisons among multiple classifiers as well as a comparison to the Sérsic index. We find that the level of agreement among classifiers is quite good (\u3e70% across the full magnitude range) and depends on both the galaxy magnitude and the galaxy type, with disks showing the highest level of agreement (\u3e50%) and irregulars the lowest (k-corrections between the V-band and H-band observations and find that a small fraction (84 galaxies in total) are classified as being very different between these two bands. These galaxies typically have very clumpy and extended morphology or are very faint in the V-band
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