Institutionalizing alternative economic spaces? An interpretivist perspective on diverse economies

This article offers an approach that helps geographers and others to carefully and critically reexamine prospects for diverse economies. We propose an interpretative institutionalist perspective is useful for elucidating overlooked opportunities for creating alternative economic visions and practices by revealing the process of ‘meaning making’ undertaken by actors in the process of developing policy responses to various dilemmas. We explore this notion in the context of de-growth or post-growth. De-growth is a way of thinking about the economy in ways that are not growth oriented, or fixated on GDP, but on the redistribution of wealth and living within the Earth’s ecosystems

Physiological Phenomenology of Neurally-Mediated Syncope with Management Implications

BACKGROUND: Due to lack of efficacy in recent trials, current guidelines for the treatment of neurally-mediated (vasovagal) syncope do not promote cardiac pacemaker implantation. However, the finding of asystole during head-up tilt -induced (pre)syncope may lead to excessive cardioinhibitory syncope diagnosis and treatment with cardiac pacemakers as blood pressure is often discontinuously measured. Furthermore, physicians may be more inclined to implant cardiac pacemakers in older patients. We hypothesized that true cardioinhibitory syncope in which the decrease in heart rate precedes the fall in blood pressure is a very rare finding which might explain the lack of efficacy of pacemakers in neurally-mediated syncope. METHODS: We studied 173 consecutive patients referred for unexplained syncope (114 women, 59 men, 42 ± 1 years, 17 ± 2 syncopal episodes). All had experienced (pre)syncope during head-up tilt testing followed by additional lower body negative suction. We classified hemodynamic responses according to the modified Vasovagal Syncope International Study (VASIS) classification as mixed response (VASIS I), cardioinhibitory without (VASIS IIa) or with asystole (VASIS IIb), and vasodepressor (VASIS III). Then, we defined the exact temporal relationship between hypotension and bradycardia to identify patients with true cardioinhibitory syncope. RESULTS: Of the (pre)syncopal events during tilt testing, 63% were classified as VASIS I, 6% as VASIS IIb, 2% as VASIS IIa, and 29% as VASIS III. Cardioinhibitory responses (VASIS class II) progressively decreased from the youngest to the oldest age quartile. With more detailed temporal analysis, blood pressure reduction preceded the heart-rate decrease in all but six individuals (97%) overall and in 10 out of 11 patients with asystole (VASIS IIb). CONCLUSIONS: Hypotension precedes bradycardia onset during head-up tilt-induced (pre)syncope in the vast majority of patients, even in those classified as cardioinhibitory syncope according to the modified VASIS classification. Furthermore, cardioinhibitory syncope becomes less frequent with increasing age

A focus on critical aspects of uptake and transport of milk-derived extracellular vesicles across the Caco-2 intestinal barrier model

Bovine milk-derived extracellular vesicles (EVs) hold promises as oral drug delivery systems. Since EV bioavailability studies are difficult to compare, key factors regarding EV uptake and intestinal permeability remain little understood. This work aims to critically study uptake and transport properties of milk-derived EVs across the intestinal barrier in vitro by standardization approaches. Therefore, uptake properties were directly compared to liposomes in intestinal Caco-2 cells. Reliable staining results were obtained by the choice of three distinct EV labeling sites, while non-specific dye transfer and excess dye removal were carefully controlled. A novel fluorescence correction factor was implemented to account for different labelling efficiencies. Both EV and liposome uptake occurred mainly energy dependent with the neonatal Fc receptor (FcRn) providing an exclusive active pathway for EVs. Confocal microscopy revealed higher internalization of EVs whereas liposomes rather remained attached to the cell surface. Internalization could be improved when changing the liposomal formulation to resemble the EV lipid composition. In a Caco-2/HT29-MTX co-culture liposomes and EVs showed partial mucus penetration. For transport studies across Caco-2 monolayers we further established a standardized protocol considering the distinct requirements for EVs. Especially insert pore sizes were systematically compared with 3 µm inserts found obligatory. Obtained apparent permeability coefficients (Papp) reflecting the transport rate will allow for better comparison of future bioavailability testing

The accretion disk corona and disk atmosphere of 4U 1624-490 as viewed by the Chandra-HETGS

We present a detailed spectral study (photoionization modelling and variability) of the "Big Dipper" 4U 1624-490 based on a \chandra-High Energy Transmission Gratings Spectrometer (HETGS) observation over the $\sim76$ ks binary orbit of 4U 1624-490. While the continuum spectrum can be modeled using a blackbody plus power-law, a slightly better fit is obtained using a single $\Gamma=2.25$ power-law partially (71%) covered by a local absorber of column density $N_{\rm H, Local}=8.1_{-0.6}^{+0.7}\times 10^{22} \rm cm^{-2}$. The data show a possible quasi-sinusoidal modulation with period $43_{-9}^{+13}$ ks that might be due to changes in local obscuration. Photoionization modeling with the {\sc xstar} code and variability studies of the observed strong \ion{Fe}{25} and \ion{Fe}{26} absorption lines point to a two-temperature plasma for their origin: a highly ionized component of ionization parameter $\xi_{\rm hot} \approx 10^{4.3} {\rm ergs cm s^{-1}}$ ($T\sim 3.0\times 10^{6}$ K) associated with an extended accretion disk corona of radius $R \sim3\times10^{10}$ cm, and a less ionized more variable component of $\xi \approx 10^{3.4} {\rm ergs cm s^{-1}}$ ($T\sim 1.0\times 10^{6}$ K) and $\rm \xi \approx 10^{3.1} ergs cm s^{-1}$ ($T\sim 0.9\times 10^{6}$ K) coincident with the accretion disk rim. We use this, with the observed \ion{Fe}{25} and \ion{Fe}{26} absorption line variations (in wavelength, strength, and width) to construct a viewing geometry that is mapped to changes in plasma conditions over the 4U 1624-490 orbital period.Comment: 27 pages, 7 figures, 6 tables, accepted for publication in Ap

Exploring the spreading layer of GX 9+9 using RXTE and INTEGRAL

We have fitted ~200 RXTE and INTEGRAL spectra of the neutron star LMXB GX 9+9 from 2002-2007 with a model consisting of a disc blackbody and another blackbody representing the spreading layer (SL), i.e. an extended accretion zone on the NS surface as opposed to the more traditional disc-like boundary layer. Contrary to theory, the SL temperature was seen to increase towards low SL luminosities, while the approximate angular extent had a nearly linear luminosity dependency. Comptonization was not required to adequately fit these spectra. Together with the ~70 degree upper bound of inclination implied by the lack of eclipses, the best-fitting normalization of the accretion disc blackbody component implies a distance of ~10 kpc, instead of the usually quoted 5 kpc.Comment: 14 pages, 10 figures, accepted for publication in MNRA

Human Coronavirus NL63 Open Reading Frame 3 encodes a virion-incorporated N-glycosylated membrane protein

Background: Human pathogenic coronavirus NL63 (hCoV-NL63) is a group 1 (alpha) coronavirus commonly associated with respiratory tract infections. In addition to known non-structural and structural proteins all coronaviruses have one or more accessory proteins whose functions are mostly unknown. Our study focuses on hCoV-NL63 open reading frame 3 (ORF 3) which is a highly conserved accessory protein among coronaviruses. Results: In-silico analysis of the 225 amino acid sequence of hCoV-NL63 ORF 3 predicted a triple membranespanning protein. Expression in infected CaCo-2 and LLC-MK2 cells was confirmed by immunofluorescence and Western blot analysis. The protein was detected within the endoplasmatic reticulum/Golgi intermediate compartment (ERGIC) where coronavirus assembly and budding takes place. Subcellular localization studies using recombinant ORF 3 protein transfected in Huh-7 cells revealed occurrence in ERGIC, Golgi- and lysosomal compartments. By fluorescence microscopy of differently tagged envelope (E), membrane (M) and nucleocapsid (N) proteins it was shown that ORF 3 protein colocalizes extensively with E and M within the ERGIC. Using N-terminally FLAG-tagged ORF 3 protein and an antiserum specific to the C-terminus we verified the proposed topology of an extracellular N-terminus and a cytosolic C-terminus. By in-vitro translation analysis and subsequent endoglycosidase H digestion we showed that ORF 3 protein is N-glycosylated at the N-terminus. Analysis of purified viral particles revealed that ORF 3 protein is incorporated into virions and is therefore an additional structural protein. Conclusions: This study is the first extensive expression analysis of a group 1 hCoV-ORF 3 protein. We give evidence that ORF 3 protein is a structural N-glycosylated and virion-incorporated protein.Web of Scienc

Alternative global Cretaceous paleogeography

Plate tectonic reconstructions for the Cretaceous have assumed that the major continental blocks—Eurasia, Greenland, North America, South America, Africa, India, Australia, and Antarctica—had separated from one another by the end of the Early Cretaceous, and that deep ocean passages connected the Pacific, Tethyan, Atlantic, and Indian Ocean basins. North America, Eurasia, and Africa were crossed by shallow meridional seaways. This classic view of Cretaceous paleogeography may be incorrect. The revised view of the Early Cretaceous is one of three large continental blocks— North America–Eurasia, South America–Antarctica-India-Madagascar-Australia; and Africa—with large contiguous land areas surrounded by shallow epicontinental seas. There was a large open Pacific basin, a wide eastern Tethys, and a circum- African Seaway extending from the western Tethys (“Mediterranean”) region through the North and South Atlantic into the juvenile Indian Ocean between Madagascar-India and Africa. During the Early Cretaceous the deep passage from the Central Atlantic to the Pacific was blocked by blocks of northern Central America and by the Caribbean plate. There were no deep-water passages to the Arctic. Until the Late Cretaceous the Atlantic-Indian Ocean complex was a long, narrow, sinuous ocean basin extending off the Tethys and around Africa. Deep passages connecting the western Tethys with the Central Atlantic, the Central Atlantic with the Pacific, and the South Atlantic with the developing Indian Ocean appeared in the Late Cretaceous. There were many island land areas surrounded by shallow epicontinental seas at high sea-level stands

Prefrontal-Premotor Pathways and Motor Output in Well-Recovered Stroke Patients

Structural brain imaging has continuously furthered our knowledge how different pathways of the human motor system contribute to residual motor output in stroke patients. Tract-related microstructure of pathways between primary and premotor areas has been found to critically influence motor output. The motor network is not restricted in connectivity to motor and premotor areas but these brain regions are densely interconnected with prefrontal regions such as the dorsolateral (DLPFC) and ventrolateral (VLPFC) prefrontal cortex. So far, the available data about the topography of such direct pathways and their microstructural properties in humans are sparse. To what extent prefrontal-premotor connections might also relate to residual motor outcome after stroke is still an open question. The present study was designed to address this issue of structural connectivity of prefrontal-premotor pathways in 26 healthy, older participants (66 ± 10 years old, 15 male) and 30 well-recovered chronic stroke patients (64 ± 10 years old, 21 males). Probabilistic tractography was used to reconstruct direct fiber tracts between DLPFC and VLPFC and three premotor areas (dorsal and ventral premotor cortex and the supplementary motor area). Direct connections between DLPFC/VLPFC and the primary motor cortex were also tested. Tract-related microstructure was estimated for each specific tract by means of fractional anisotropy and alternative diffusion metrics. These measures were compared between the groups and related to residual motor outcome in the stroke patients. Direct prefrontal-premotor trajectories were successfully traceable in both groups. Similar in gross anatomic topography, stroke patients presented only marginal microstructural alterations of these tracts, predominantly of the affected hemisphere. However, there was no clear evidence for a significant association between tract-related microstructure of prefrontal-premotor connections and residual motor functions in the present group of well-recovered stroke patients. Direct prefrontal-motor connections between DLPFC/VLPFC and the primary motor cortex could not be reconstructed in the present healthy participants and stroke patients

Increased pore size of scaffolds improves coating efficiency with sulfated hyaluronan and mineralization capacity of osteoblasts

Background: Delayed bone regeneration of fractures in osteoporosis patients or of critical-size bone defects after tumor resection are a major medical and socio-economic challenge. Therefore, the development of more effective and osteoinductive biomaterials is crucial. Methods: We examined the osteogenic potential of macroporous scaffolds with varying pore sizes after biofunctionalization with a collagen/high-sulfated hyaluronan (sHA3) coating in vitro. The three-dimensional scaffolds were made up from a biodegradable three-armed lactic acid-based macromer (TriLA) by cross-polymerization. Templating with solid lipid particles that melt during fabrication generates a continuous pore network. Human mesenchymal stem cells (hMSC) cultivated on the functionalized scaffolds in vitro were investigated for cell viability, production of alkaline phosphatase (ALP) and bone matrix formation. Statistical analysis was performed using student's t-test or two-way ANOVA. Results: We succeeded in generating scaffolds that feature a significantly higher average pore size and a broader distribution of individual pore sizes (HiPo) by modifying composition and relative amount of lipid particles, macromer concentration and temperature for cross-polymerization during scaffold fabrication. Overall porosity was retained, while the scaffolds showed a 25% decrease in compressive modulus compared to the initial TriLA scaffolds with a lower pore size (LoPo). These HiPo scaffolds were more readily coated as shown by higher amounts of immobilized collagen (+ 44%) and sHA3 (+ 25%) compared to LoPo scaffolds. In vitro, culture of hMSCs on collagen and/or sHA3-coated HiPo scaffolds demonstrated unaltered cell viability. Furthermore, the production of ALP, an early marker of osteogenesis (+ 3-fold), and formation of new bone matrix (+ 2.5-fold) was enhanced by the functionalization with sHA3 of both scaffold types. Nevertheless, effects were more pronounced on HiPo scaffolds about 112%. Conclusion: In summary, we showed that the improvement of scaffold pore sizes enhanced the coating efficiency with collagen and sHA3, which had a significant positive effect on bone formation markers, underlining the promise of using this material approach for in vivo studies. © 2019 The Author(s)