277 research outputs found

    The effects of autocatalytic trade cycles on economic growth

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    This paper shows that autocatalytic trade cycles can be a positive feedback system for innovation and thus for economic growth. Using United Nations data, a trade network is proposed and a set of variables that represent the participation of countries in autocatalytic trade cycles is constructed. A clear relationship between these variables and economic growth is found since more innovation is produced in countries that are part of trade cycles. However, the relationship changes with autocatalytic trade cycle sizes, categories of goods and time scales. Moreover, autocatalytic trade cycles also have a positive effect for the trade flows involved, although this effect differs significantly depending on the size of the cycles. This new approach based on autocatalytic trade cycles emphasizes the benefits that countries can extract from trade cycles and points out the need of policies that foster these benefits. These conclusions strengthen existing literature, and also add new insights to innovation policy and the pursuit of economic prosperity

    Cluster Beam Study of (MgSiO3)+-Based Monomeric Silicate Species and Their Interaction with Oxygen: Implications for Interstellar Astrochemistry

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    Silicates are ubiquitously found as small dust grains throughout the universe. These particles are frequently subject to high-energy processes and subsequent condensation in the interstellar medium (ISM), where they are broken up into many ultrasmall silicate fragments. These abundant molecular-sized silicates likely play an important role in astrochemistry. By approximately mimicking silicate dust grain processing occurring in the diffuse ISM by ablation/cooling of a Mg/Si source material in the presence of O2, we observed the creation of stable clusters based on discrete pyroxene monomers (MgSiO3+), which traditionally have only been considered possible as constituents of bulk silicate materials. Our study suggests that such pyroxene monomer-based clusters could be highly abundant in the ISM from the processing of larger silicate dust grains. A detailed analysis, by infrared multiple-photon dissociation (IR-MPD) spectroscopy and density functional theory (DFT) calculations, reveals the structures and properties of these monomeric silicate species. We find that the clusters interact strongly with oxygen, with some stable cluster isomers having a silicate monomeric core bound to an ozone-like moiety. The general high tendency of these monomeric silicate species to strongly adsorb O2 molecules also suggests that they could be relevant to the observed and unexplained depletion of oxygen in the ISM. We further find clusters where a Mg atom is bound to the MgSiO3 monomer core. These species can be considered as the simplest initial step in monomer-initiated nucleation, indicating that small ionized pyroxenic clusters could also assist in the reformation of larger silicate dust grains in the ISM

    First Experience With The GoBack-Catheter For Successful Crossing of Complex Chronic Total Occlusions in Lower Limb Arteries

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    Purpose: To evaluate the use of the GoBack-catheter (Upstream Peripheral Technologies) in complex revascularizations in lower limb arteries. Materials and Methods: In this retrospective single-center study, the results of the first 100 consecutive patients including 101 limb-revascularizations, performed between May 2018 and July 2020 with the study device, were analyzed. In all cases, guidewire-crossing failed, and all lesions were chronic total occlusions (CTO), either de novo, reocclusions, or in-stent reocclusions. Successful crossing was defined as passing the CTO using the study device. Patency at discharge and after 30 days was defined as less than 50% restenosis on duplex sonography, without target lesion revascularization. Results: Median lesion length was 24 cm and 38 patients (37.6%) had a calcium grading according to the peripheral arterial calcium scoring system (PACSS) of 4 or 5. In 20.8% of patients, an occluded stent was treated. CTOs involved the femoropopliteal segment in 91.1%, iliac arteries in 5.9%, and tibial arteries in 7.9%. The GoBackcatheter was employed for entering into or crossing through parts or the full length of a CTO or an occluded stent as well as for re-entering into the true lumen after subintimal crossing. The device was used via contralateral and ipsilateral antegrade as well as retrograde access with an overall technical success rate of 92.1%. In 3 patients minor bleeding occurred at the crossing or re-entry site, which were managed conservatively. Thirty-day adverse limb events comprised minor amputations in 4 patients (4.0%), 1 major amputation (1.0%), and reocclusions in 7 limbs (6.9%). Conclusion: The new GoBack-catheter offers versatile endovascular applicability for complex CTO recanalization in a broad range of peripheral vascular interventions with a high technical success and low complication rate

    Changes in membrane sphingolipid composition modulate dynamics and adhesion of integrin nanoclusters

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    Sphingolipids are essential constituents of the plasma membrane (PM) and play an important role in signal transduction by modulating clustering and dynamics of membrane receptors. Changes in lipid composition are therefore likely to influence receptor organisation and function, but how this precisely occurs is difficult to address given the intricacy of the PM lipid-network. Here, we combined biochemical assays and single molecule dynamic approaches to demonstrate that the local lipid environment regulates adhesion of integrin receptors by impacting on their lateral mobility. Induction of sphingomyelinase (SMase) activity reduced sphingomyelin (SM) levels by conversion to ceramide (Cer), resulting in impaired integrin adhesion and reduced integrin mobility. Dual-colour imaging of cortical actin in combination with single molecule tracking of integrins showed that this reduced mobility results from increased coupling to the actin cytoskeleton brought about by Cer formation. As such, our data emphasizes a critical role for the PM local lipid composition in regulating the lateral mobility of integrins and their ability to dynamically increase receptor density for efficient ligand binding in the process of cell adhesion

    Simultaneous Induction of Glycolysis and Oxidative Phosphorylation during Activation of Hepatic Stellate Cells Reveals Novel Mitochondrial Targets to Treat Liver Fibrosis

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    Upon liver injury, hepatic stellate cells (HSCs) transdifferentiate to migratory, proliferative and extracellular matrix-producing myofibroblasts (e.g., activated HSCs; aHSCs) causing liver fibrosis. HSC activation is associated with increased glycolysis and glutaminolysis. Here, we compared the contribution of glycolysis, glutaminolysis and mitochondrial oxidative phosphorylation (OXPHOS) in rat and human HSC activation. Basal levels of glycolysis (extracellular acidification rate similar to 3-fold higher) and particularly mitochondrial respiration (oxygen consumption rate similar to 5-fold higher) were significantly increased in rat aHSCs, when compared to quiescent rat HSC. This was accompanied by extensive mitochondrial fusion in rat and human aHSCs, which occurred without increasing mitochondrial DNA content and electron transport chain (ETC) components. Inhibition of glycolysis (by 2-deoxy-D-glucose) and glutaminolysis (by CB-839) did not inhibit rat aHSC proliferation, but did reduce Acta2 (encoding alpha-SMA) expression slightly. In contrast, inhibiting mitochondrial OXPHOS (by rotenone) significantly suppressed rat aHSC proliferation, as well as Col1a1 and Acta2 expression. Other than that observed for rat aHSCs, human aHSC proliferation and expression of fibrosis markers were significantly suppressed by inhibiting either glycolysis, glutaminolysis or mitochondrial OXPHOS (by metformin). Activation of HSCs is marked by simultaneous induction of glycolysis and mitochondrial metabolism, extending the possibilities to suppress hepatic fibrogenesis by interfering with HSC metabolism

    The Course of Quality of Life and Its Predictors in Nursing Home Residents With Young-Onset Dementia

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    OBJECTIVE: To explore the course of quality of life (QoL) and possible resident-related predictors associated with this course in institutionalized people with young-onset dementia (YOD). DESIGN: An observational longitudinal study. SETTING AND PARTICIPANTS: A total of 278 residents with YOD were recruited from 13 YOD special care units in the Netherlands. METHODS: Secondary analyses were conducted with longitudinal data from the Behavior and Evolution in Young-ONset Dementia (BEYOND)-II study. QoL was assessed with proxy ratings, using the Quality of Life in Dementia (QUALIDEM) questionnaire at 4 assessment points over 18 months. Predictors included age, gender, dementia subtype, length of stay, dementia severity, neuropsychiatric symptoms, and psychotropic drug use at baseline. Multilevel modeling was used to adjust for the correlation of measurements within residents and clustering of residents within nursing homes. RESULTS: The total QUALIDEM score (range: 0-111) decreased over 18 months with a small change of 0.65 (95% confidence interval -1.27, -0.04) points per 6 months. An increase in several domains of QoL regarding care relationship, positive self-image, and feeling at home was seen over time, whereas a decline was observed in the subscales positive affect, social relations, and having something to do. Residents with higher levels of QoL and more advanced dementia at baseline showed a more progressive decline in QoL over time. Sensitivity analyses indicated a more progressive decline in QoL for residents who died during the follow-up. CONCLUSION AND IMPLICATIONS: This study shows that although overall QoL in nursing home residents with YOD was relatively stable over 18 months, there were multidirectional changes in the QoL subscales that could be clinically relevant. Higher levels of QoL and more advanced stages of dementia at baseline predicted a more progressive decline in QoL over time. More longitudinal studies are needed to verify factors influencing QoL in YOD

    A genome-wide search for epigenetically regulated genes in zebra finch using MethylCap-seq and RNA-seq

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    Learning and memory formation are known to require dynamic CpG (de)methylation and gene expression changes. Here, we aimed at establishing a genome-wide DNA methylation map of the zebra finch genome, a model organism in neuroscience, as well as identifying putatively epigenetically regulated genes. RNA-and MethylCap-seq experiments were performed on two zebra finch cell lines in presence or absence of 5-aza-2'-deoxycytidine induced demethylation. First, the MethylCap-seq methodology was validated in zebra finch by comparison with RRBS-generated data. To assess the influence of (variable) methylation on gene expression, RNA-seq experiments were performed as well. Comparison of RNA-seq and MethylCap-seq results showed that at least 357 of the 3,457 AZA-upregulated genes are putatively regulated by methylation in the promoter region, for which a pathway analysis showed remarkable enrichment for neurological networks. A subset of genes was validated using Exon Arrays, quantitative RT-PCR and CpG pyrosequencing on bisulfite-treated samples. To our knowledge, this study provides the first genome-wide DNA methylation map of the zebra finch genome as well as a comprehensive set of genes of which transcription is under putative methylation control
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