719 research outputs found
Urban fashion policies: lessons from the Barcelona catwalks
Since at least a decade, Barcelona is on the world map of fashion: Antonio MirĂČ, Mango, Desigual, Agatha Ruiz de la Prada are famous Barcelona-based stylists teaming up with other large Spanish fashion firms, like Zara, and commercial outlets, like El Corte Ingles, to attract a large interest on local fashion and fashion-based events. Thus, Barcelona has become a straightforward âshopping destinationâ for millions of international visitors, developing a shopping-related image, various specialised âfashion clustersâ for different market targets, and a number of fashion-related events attracting both professionals and a dedicated general audience, like the 080 Barcelona and Bread & Butter. Barcelonaâs liberal and leisure-related image can be easily associated with fashion, so if the national capital Madrid retains its role of business capital of the country even in relation to fashion, Barcelona could be considered the emergent âcatwalkâ of the Mediterranean, challenging other fashion capitals of Europe like Milan and Paris. The article analyses the urban strategy to foster the fashion industry in Barcelona through a redefinition of the âsoftâ factors establishing the substance of a fashion capital: image, place qualities, events, connectedness and social embeddedness. Tourism, unsurprisingly, is an important component of such strategy. The growth of Barcelona to the stardom of international leisure and cultural tourism is mostly about the âliminalâ nature and the symbolically-charged activities of visitors that can be easily extended to fashion and fashion buying behaviour. Through a number of interviews and the analysis of strategy documents and reports, the authors unravel this relationship and assess the effectiveness of this strategy face to other factors playing against a more enduring rooting of fashion industries in the city, like the volatility of the sector, the insufficient international connectedness of the city and its business orientation, and the reorientation of the tourist supply towards low-cost visitors segments.
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"We Don't Do That Here": Calling Out Deficit Discourse in the Writing Center to Reframe Multilingual Graduate Support
Over the years, as writing center tutors, graduate assistants, and administrators, we have witnessed the challenges facing multilingual graduate student writers on their quest for academic writing support. We have spent our time researching campus resources only to find that holistic (and whole-istic) approaches to working with the particular needs of graduate multilingual writers (GMLWs) are lacking. One common narrative that we witness repeatedly is concerned with GMLWs: the âwe donât do grammarâ frame that many writing centers endorse. In the example from narrative one, which is based on a client with whom Erica has been working, Yifan left embarrassed, as she was made to feel like she had been using the writing center fraudulently. In Ericaâs next meeting with Yifan, she explained why writing centers are so resistant to changing this frame for their work. While her explanation may have mediated Yifanâs embarrassment somewhat, Yifan was still hesitant to work with anyone besides Erica. A similar sense of guilt and embarrassment is felt by Sam, the tutor in narrative three, who focuses on local concerns in longterm, high stakes projects that graduate students typically bring to the center. All three narratives echo what we identify as particular obstacles faced not only by our GMLWs when seeking out resources to improve their communication skills, but also by tutors and administrators who wish to identify best practices in serving multilingual students.University Writing Cente
T Cell Migration from Inflamed Skin to Draining Lymph Nodes Requires Intralymphatic Crawling Supported by ICAM-1/LFA-1 Interactions.
T cells are the most abundant cell type found in afferent lymph, but their migration through lymphatic vessels (LVs) remains poorly understood. Performing intravital microscopy in the murine skin, we imaged T cell migration through afferent LVs in vivo. T cells entered into and actively migrated within lymphatic capillaries but were passively transported in contractile collecting vessels. Intralymphatic T cell number and motility were increased during contact-hypersensitivity-induced inflammation and dependent on ICAM-1/LFA-1 interactions. In vitro, blockade of endothelial cell-expressed ICAM-1 reduced T cell adhesion, crawling, and transmigration across lymphatic endothelium and decreased T cell advancement from capillaries into lymphatic collectors in skin explants. In vivo, T cell migration to draining lymph nodes was significantly reduced upon ICAM-1 or LFA-1 blockade. Our findings indicate that T cell migration through LVs occurs in distinct steps and reveal a key role for ICAM-1/LFA-1 interactions in this process
Taking the lymphatic route: dendritic cell migration to draining lymph nodes
In contrast to leukocyte migration through blood vessels, trafficking via lymphatic vessels (LVs) is much less well characterized. An important cell type migrating via this route is antigen-presenting dendritic cells (DCs), which are key for the induction of protective immunity as well as for the maintenance of immunological tolerance. In this review, we will summarize and discuss current knowledge of the cellular and molecular events that control DC migration from the skin towards, into, and within LVs, followed by DC arrival and migration in draining lymph nodes. Finally, we will discuss potential strategies to therapeutically target this migratory step to modulate immune responses
Comparative Structural Analysis of GFRP, Reinforced Concrete, and Steel Frames under Seismic Loads
Fibre-reinforced polymer composites in general, and especially glass fibre-reinforced polymer (GFRP), have increasingly been used in recent decades in construction. The advantages of GFRP as an alternative construction material are its high strength-to-weight ratio, corrosive resistance, high durability, and ease of installation. The main purpose of this study is to evaluate the response of GFRP under dynamic conditions (more specifically, under seismic loads) and to compare the performance of this composite material with that of two traditional building materials: reinforced concrete and structural steel. To this aim, a finite element analysis is carried out on a two-dimensional frame modelled with steel, reinforced concrete (RC), or GFRP pultruded materials and subjected to a seismic input. The dynamic response of the structure is evaluated for the three building materials in terms of displacements, inter-storey drift, base shear, and stress. The results show a good performance of the GFRP frame, with stress distribution and displacements halfway between those of RC and steel. Most importantly, the GFRP frame outperforms the other materials in terms of reduced weight and, thus, base shear (-40% compared to steel and -88.5% compared to RC)
Dendritic Cells and T Cells Interact Within Murine Afferent Lymphatic Capillaries
Afferent lymphatic vessels contribute to immunity by transporting antigen and leukocytes to draining lymph nodes (LNs) and are emerging as new players in the regulation of peripheral tolerance. Performing intravital microscopy in inflamed murine ear skin we found that migrating dendritic cells (DCs) and antigen-experienced effector T cells spend considerable time arresting or clustering within afferent lymphatic capillaries. We also observed that intralymphatic T cells frequently interacted with DCs. When imaging polyclonal T cells during an ongoing contact-hypersensitivity response, most intralymphatic DC-T cell interactions were short-lived. Conversely, during a delayed-type-hypersensitivity response, cognate antigen-bearing DCs engaged in long-lived MHCII-(I-A/I-E)-dependent interactions with antigen-specific T cells. Long-lived intralymphatic DC-T cell interactions reduced the speed of DC crawling but did not delay overall DC migration to draining LNs. While further consequences of these intralymphatic interactions still need to be explored, our findings suggest that lymphatic capillaries represent a unique compartment in which adaptive immune interaction and modulation occur
Characterization of Antibodies against Receptor Activity-Modifying Protein 1 (RAMP1): A Cautionary Tale
Calcitonin gene-related peptide (CGRP) is a key component of migraine pathophysiology, yielding effective migraine therapeutics. CGRP receptors contain a core accessory protein subunit: receptor activity-modifying protein 1 (RAMP1). Understanding of RAMP1 expression is incomplete, partly due to the challenges in identifying specific and validated antibody tools. We profiled antibodies for immunodetection of RAMP1 using Western blotting, immunocytochemistry and immunohistochemistry, including using RAMP1 knockout mouse tissue. Most antibodies could detect RAMP1 in Western blotting and immunocytochemistry using transfected cells. Two antibodies (844, ab256575) could detect a RAMP1-like band in Western blots of rodent brain but not RAMP1 knockout mice. However, cross-reactivity with other proteins was evident for all antibodies. This cross-reactivity prevented clear conclusions about RAMP1 anatomical localization, as each antibody detected a distinct pattern of immunoreactivity in rodent brain. We cannot confidently attribute immunoreactivity produced by RAMP1 antibodies (including 844) to the presence of RAMP1 protein in immunohistochemical applications in brain tissue. RAMP1 expression in brain and other tissues therefore needs to be revisited using RAMP1 antibodies that have been comprehensively validated using multiple strategies to establish multiple lines of convincing evidence. As RAMP1 is important for other GPCR/ligand pairings, our results have broader significance beyond the CGRP field
A proof-of-concept study on the genomic evolution of Sars-Cov-2 in molnupiravir-treated, paxlovid-treated and drug-naĂŻve patients
Little is known about SARS-CoV-2 evolution under Molnupiravir and Paxlovid, the only antivirals approved for COVID-19 treatment. By investigating SARS-CoV-2 variability in 8 Molnupiravir-treated, 7 Paxlovid-treated and 5 drug-naive individuals at 4 time-points (Days 0-2-5-7), a higher genetic distance is found under Molnupiravir pressure compared to Paxlovid and no-drug pressure (nucleotide-substitutions/site mean & PLUSMN;Standard error: 18.7 x 10(-4) & PLUSMN; 2.1 x 10(-4) vs. 3.3 x 10(-4) & PLUSMN; 0.8 x 10(-4) vs. 3.1 x 10(-4) & PLUSMN; 0.8 x 10(-4), P = 0.0003), peaking between Day 2 and 5. Molnupiravir drives the emergence of more G-A and C-T transitions than other mutations (P = 0.031). SARS-CoV-2 selective evolution under Molnupiravir pressure does not differ from that under Paxlovid or no-drug pressure, except for orf8 (dN > dS, P = 0.001); few amino acid mutations are enriched at specific sites. No RNA-dependent RNA polymerase (RdRp) or main proteases (Mpro) mutations conferring resistance to Molnupiravir or Paxlovid are found. This proof-of-concept study defines the SARS-CoV-2 within-host evolution during antiviral treatment, confirming higher in vivo variability induced by Molnupiravir compared to Paxlovid and drug-naive, albeit not resulting in apparent mutation selection
Postnatal Deletion of Podoplanin in Lymphatic Endothelium Results in Blood Filling of the Lymphatic System and Impairs Dendritic Cell Migration to Lymph Nodes
OBJECTIVE
The lymphatic vascular system exerts major physiological functions in the transport of interstitial fluid from peripheral tissues back to the blood circulation and in the trafficking of immune cells to lymph nodes. Previous studies in global constitutive knockout mice for the lymphatic transmembrane molecule podoplanin reported perinatal lethality and a complex phenotype with lung abnormalities, cardiac defects, lymphedema, blood-filled lymphatic vessels, and lack of lymph node organization, reflecting the importance of podoplanin expression not only by the lymphatic endothelium but also by a variety of nonendothelial cell types. Therefore, we aimed to dissect the specific role of podoplanin expressed by adult lymphatic vessels.
APPROACH AND RESULTS
We generated an inducible, lymphatic-specific podoplanin knockout mouse model (PdpnÎLEC) and induced gene deletion postnatally. PdpnÎLEC mice were viable, and their lymphatic vessels appeared morphologically normal with unaltered fluid drainage function. Intriguingly, PdpnÎLEC mice had blood-filled lymph nodes and vessels, most frequently in the neck and axillary region, and displayed a blood-filled thoracic duct, suggestive of retrograde filling of blood from the blood circulation into the lymphatic system. Histological and fluorescence-activated cell sorter analyses revealed normal lymph node organization with the presence of erythrocytes within lymph node lymphatic vessels but not surrounding high endothelial venules. Moreover, fluorescein isothiocyanate painting experiments revealed reduced dendritic cell migration to lymph nodes in PdpnÎLEC mice.
CONCLUSIONS
These results reveal an important role of podoplanin expressed by lymphatic vessels in preventing postnatal blood filling of the lymphatic vascular system and in contributing to efficient dendritic cell migration to the lymph nodes
Prognostic significance of KRAS mutation rate in metastatic colorectal cancer patients.
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