Regenerative design,socio-ecological systems and co-evolution

A key notion in regenerative design is the co-evolutionary, partnered relationship between socio-cultural and ecological systems, which requires an explicit engagement with the implications and consequences of future design decisions. However, despite the extensive literature in other disciplines regarding the co-evolution of socio-cultural and ecological systems, this approach has yet to receive serious scrutiny within the context of the built environment and within the emerging notions of regenerative development and design. Drawing on an interdisciplinary body of literature, a discussion is initiated on how socio-cultural and ecological systems and their co-evolution might connect to the concept of regenerative design. Following a critique of a relevant example highlighting the current practice of regenerative design, the new building for the Centre for Interactive Research on Sustainability at the University of British Columbia, Vancouver, potentially relevant aspects of a socio-ecological system and of evolution theories are examined for the built environment. Several observations are presented on how these may offer a stronger theoretical framing of regenerative design, particularly the shifts in design thinking: from buildings as artefacts to their dynamic role in adaptive processes over time; widening the boundary focus of a building from its site to the neighbourhood.

Une notion clé du design régénérateur est la relation coévolutionnaire de partenariat entre les systèmes socioculturels et écologiques, ce qui nécessite un engagement explicite à l'égard des implications et des conséquences des futures décisions en matière de design. Cependant, malgré la vaste littérature existant dans les autres disciplines concernant la coévolution des systèmes socioculturels et écologiques, cette approche doit encore faire l'objet d'un examen sérieux dans le contexte de l'environnement bâti et sous l'angle des notions émergentes de développement et de design régénérateurs. En s'appuyant sur un corpus interdisciplinaire de publications, une discussion est amorcée sur la manière dont les systèmes socioculturels et écologiques et leur coévolution pourraient être reliés au concept de design régénérateur. Après une critique portant sur un exemple pertinent mettant en évidence les pratiques actuelles du design régénérateur, le nouveau bâtiment du Centre de Recherche Interactive sur le Développement Durable de l'Université de Colombie Britannique, à Vancouver, sont examinés les aspects potentiellement pertinents d'un système socioécologique et des théories évolutionnistes, s'agissant de l'environnement bâti. Plusieurs observations sont présentées quant à la manière dont ceux-ci peuvent offrir un cadre théorique plus solide au design régénérateur, concernant en particulier les changements intervenant dans la façon de penser le design : des bâtiments envisagés en tant qu'artéfacts à leur rôle dynamique dans les processus adaptatifs au fil du temps, et un bâtiment dont les limites ne se focalisent plus sur son site, mais sont élargies à son quartier.

Mots clés: environnement bâti, coévolution, cadres conceptuels, évolution, design régénérateur, systèmes socioécologiques     

Orthogonal Peptide-Templated Labeling Elucidates Lateral ETAR/ETBR Proximity and Reveals Altered Downstream Signaling

Fine-tuning of G protein-coupled receptor (GPCR) signaling is important to maintain cellular homeostasis. Recent studies demonstrated that lateral GPCR interactions in the cell membrane can impact signaling profiles. Here, we report on a one-step labeling method of multiple membrane-embedded GPCRs. Based on short peptide tags, complementary probes transfer the cargo (e. g. a fluorescent dye) by an acyl transfer reaction with high spatial and temporal resolution within 5 min. We applied this approach to four receptors of the cardiovascular system: the endothelin receptor A and B (ET_AR and ET_BR), angiotensin II receptor type 1, and apelin. Wild type-like G protein activation after N-terminal modification was demonstrated for all receptor species. Using FRET-competent dyes, a constitutive proximity between hetero-receptors was limited to ET_AR/ET_BR. Further, we demonstrate, that ET_AR expression regulates the signaling of co-expressed ET_BR. Our orthogonal peptide-templated labeling of different GPCRs provides novel insight into the regulation of GPCR signaling.     

Gallium gradients in Cu(In,Ga)Se2 thin‐film solar cells

The gallium gradient in Cu(In,Ga)Se₂ (CIGS) layers, which forms during the two industrially relevant deposition routes, the sequential and co‐evaporation processes, plays a key role in the device performance of CIGS thin‐film modules. In this contribution, we present a comprehensive study on the formation, nature, and consequences of gallium gradients in CIGS solar cells. The formation of gallium gradients is analyzed in real time during a rapid selenization process by in situ X‐ray measurements. In addition, the gallium grading of a CIGS layer grown with an in‐line co‐evaporation process is analyzed by means of depth profiling with mass spectrometry. This gallium gradient of a real solar cell served as input data for device simulations. Depth‐dependent occurrence of lateral inhomogeneities on the µm scale in CIGS deposited by the co‐evaporation process was investigated by highly spatially resolved luminescence measurements on etched CIGS samples, which revealed a dependence of the optical bandgap, the quasi‐Fermi level splitting, transition levels, and the vertical gallium gradient. Transmission electron microscopy analyses of CIGS cross‐sections point to a difference in gallium content in the near surface region of neighboring grains. Migration barriers for a copper‐vacancy‐mediated indium and gallium diffusion in CuInSe₂ and CuGaSe₂ were calculated using density functional theory. The migration barrier for the In_Cu antisite in CuGaSe₂ is significantly lower compared with the Ga_Cu antisite in CuInSe₂, which is in accordance with the experimentally observed Ga gradients in CIGS layers grown by co‐evaporation and selenization processes. Copyright © 2014 John Wiley & Sons, Ltd.     

新型COCOON手动变形机

介绍了COCOON手动变形机的特点.COCOON采用ATT和导丝盘等新部件,变形加工效率提高,通过节能注重对自然资源的节约.COCOON变形机达到了新的水平,它能使DTY加工商和下游加工商都受益.     

Characterization of GPVI- or GPVI-CD39-Coated Nanoparticles and Their Impact on In Vitro Thrombus Formation

Traditional antithrombotic agents commonly share a therapy-limiting side effect, as they increase the overall systemic bleeding risk. A novel approach for targeted antithrombotic therapy is nanoparticles. In other therapeutic fields, nanoparticles have enabled site-specific delivery with low levels of toxicity and side effects. Here, we paired nanotechnology with an established dimeric glycoprotein VI-Fc (GPVI-Fc) and a GPVI-CD39 fusion protein, thereby combining site-specific delivery and new antithrombotic drugs. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles, NP-BSA, NP-GPVI and NP-GPVI-CD39 were characterized through electron microscopy, atomic force measurements and flow cytometry. Light transmission aggregometry enabled analysis of platelet aggregation. Thrombus formation was observed through flow chamber experiments. NP-GPVI and NP-GPVI-CD39 displayed a characteristic surface coating pattern. Fluorescence properties were identical amongst all samples. NP-GPVI and NP-GPVI-CD39 significantly impaired platelet aggregation. Thrombus formation was significantly impaired by NP-GPVI and was particularly impaired by NP-GPVI-CD39. The receptor-coated nanoparticles NP-GPVI and the bifunctional molecule NP-GPVI-CD39 demonstrated significant inhibition of in vitro thrombus formation. Consequently, the nanoparticle-mediated antithrombotic effect of GPVI-Fc, as well as GPVI-CD39, and an additive impact of CD39 was confirmed. In conclusion, NP-GPVI and NP-GPVI-CD39 may serve as a promising foundation for a novel therapeutic approach regarding targeted antithrombotic therapy.     

Loss of SDHB Induces a Metabolic Switch in the hPheo1 Cell Line toward Enhanced OXPHOS

Background: Enzymes of tricarboxylic acid (TCA) have recently been recognized as tumor suppressors. Mutations in the SDHB subunit of succinate dehydrogenase (SDH) cause pheochromocytomas and paragangliomas (PCCs/PGLs) and predispose patients to malignant disease with poor prognosis. Methods: Using the human pheochromocytoma cell line (hPheo1), we knocked down SDHB gene expression using CRISPR-cas9 technology. Results: Microarray gene expression analysis showed that >500 differentially expressed gene targets, about 54%, were upregulated in response to SDHB knock down. Notably, genes involved in glycolysis, hypoxia, cell proliferation, and cell differentiation were up regulated, whereas genes involved in oxidative phosphorylation (OXPHOS) were downregulated. In vitro studies show that hPheo1 proliferation is not affected negatively and the cells that survive by shifting their metabolism to the use of glutamine as an alternative energy source and promote OXPHOS activity. Knock down of SDHB expression results in a significant increase in GLUD1 expression in hPheo1 cells cultured as monolayer or as 3D culture. Analysis of TCGA data confirms the enhancement of GLUD1 in SDHB mutated/low expressed PCCs/PGLs. Conclusions: Our data suggest that the downregulation of SDHB in PCCs/PGLs results in increased GLUD1 expression and may represent a potential biomarker and therapeutic target in SDHB mutated tumors and SDHB loss of activity-dependent diseases.     

NGF Enhances CGRP Release Evoked by Capsaicin from Rat Trigeminal Neurons: Differential Inhibition by SNAP-25-Cleaving Proteases

Nerve growth factor (NGF) is known to intensify pain in various ways, so perturbing pertinent effects without negating its essential influences on neuronal functions could help the search for much-needed analgesics. Towards this goal, cultured neurons from neonatal rat trigeminal ganglia—a locus for craniofacial sensory nerves—were used to examine how NGF affects the Ca²⁺-dependent release of a pain mediator, calcitonin gene-related peptide (CGRP), that is triggered by activating a key signal transducer, transient receptor potential vanilloid 1 (TRPV1) with capsaicin (CAP). Measurements utilised neurons fed with or deprived of NGF for 2 days. Acute re-introduction of NGF induced Ca²⁺-dependent CGRP exocytosis that was inhibited by botulinum neurotoxin type A (BoNT/A) or a chimera of/E and/A (/EA), which truncated SNAP-25 (synaptosomal-associated protein with Mr = 25 k) at distinct sites. NGF additionally caused a Ca²⁺-independent enhancement of the neuropeptide release evoked by low concentrations (<100 nM) of CAP, but only marginally increased the peak response to ≥100 nM. Notably, BoNT/A inhibited CGRP exocytosis evoked by low but not high CAP concentrations, whereas/EA effectively reduced responses up to 1 µM CAP and inhibited to a greater extent its enhancement by NGF. In addition to establishing that sensitisation of sensory neurons to CAP by NGF is dependent on SNARE-mediated membrane fusion, insights were gleaned into the differential ability of two regions in the C-terminus of SNAP-25 (181–197 and 198–206) to support CAP-evoked Ca²⁺-dependent exocytosis at different intensities of stimulation.     

Airway Delivery of Hydrogel-Encapsulated Niclosamide for the Treatment of Inflammatory Airway Disease

Repurposing of the anthelminthic drug niclosamide was proposed as an effective treatment for inflammatory airway diseases such as asthma, cystic fibrosis, and chronic obstructive pulmonary disease. Niclosamide may also be effective for the treatment of viral respiratory infections, such as SARS-CoV-2, respiratory syncytial virus, and influenza. While systemic application of niclosamide may lead to unwanted side effects, local administration via aerosol may circumvent these problems, particularly when the drug is encapsulated into small polyethylene glycol (PEG) hydrospheres. In the present study, we examined whether PEG-encapsulated niclosamide inhibits the production of mucus and affects the pro-inflammatory mediator CLCA1 in mouse airways in vivo, while effects on mucociliary clearance were assessed in excised mouse tracheas. The potential of encapsulated niclosamide to inhibit TMEM16A whole-cell Cl⁻ currents and intracellular Ca²⁺ signalling was assessed in airway epithelial cells in vitro. We achieved encapsulation of niclosamide in PEG-microspheres and PEG-nanospheres (Niclo-spheres). When applied to asthmatic mice via intratracheal instillation, Niclo-spheres strongly attenuated overproduction of mucus, inhibited secretion of the major proinflammatory mediator CLCA1, and improved mucociliary clearance in tracheas ex vivo. These effects were comparable for niclosamide encapsulated in PEG-nanospheres and PEG-microspheres. Niclo-spheres inhibited the Ca²⁺ activated Cl⁻ channel TMEM16A and attenuated mucus production in CFBE and Calu-3 human airway epithelial cells. Both inhibitory effects were explained by a pronounced inhibition of intracellular Ca²⁺ signals. The data indicate that poorly dissolvable compounds such as niclosamide can be encapsulated in PEG-microspheres/nanospheres and deposited locally on the airway epithelium as encapsulated drugs, which may be advantageous over systemic application.