Tales from two cities: COVID-19 and the localisation of tourism in London and Paris

Purpose - Drawing on empirical research conducted in London and Paris between July 2020 and June 2021, this research explores whether these two global metropolises may be able to take the COVID-19 crisis as an opportunity to develop more sustainable forms of urban tourism. More specifically, the study analyses whether new forms of localised tourism have developed as a result of the pandemic, how these have been nurtured and encouraged by the tourism industry in these two cities, and the implications of these trends for the sustainable development of tourism in these two cities. Design/methodology/approach - A combination of research methods was used: an online Delphi method, followed by in-depth one to one interviews with selected stakeholders and complemented by the analysis of media articles, policy documents and secondary data. Findings - The qualitative data analysis highlights some key findings: tourism sustainability gained a new importance after the pandemic, however the crisis did not bring the sustainable revolution some stakeholders wished or expected. Nonetheless in both cities tourism marketing adopted a new "hyper-local" approach with the objective of encouraging proximity tourism and involving local residents more, thus pointing to the need to review traditional definitions of the (urban) tourist. Originality/value – While the blurring between tourism and the everyday in cities has been widely discussed in tourism theory, this research provides empirical evidence from two world tourism cities, showing some of the wider, practical implications of these theoretical debates for industry and policy making in the context of the COVID-19 pandemic

New biochemical insights into the mechanisms of pulmonary arterial hypertension in humans

Diagnosis of pulmonary arterial hypertension (PAH) is difficult due to the lack of specific clinical symptoms and biomarkers, especially at early stages. We compared plasma metabolic fingerprints of PAH patients (n = 20) with matched healthy volunteers (n = 20) using, for the first time, untargeted multiplatform metabolomics approach consisting of high-performance liquid and gas chromatography coupled with mass spectrometry. Multivariate statistical analyses were performed to select metabolites that contribute most to groups' classification (21 from liquid in both ionization modes and 9 from gas chromatography-mass spectrometry). We found metabolites related to energy imbalance, such as glycolysis-derived metabolites, as well as metabolites involved in fatty acid, lipid and amino acid metabolism. We observed statistically significant changes in threitol and aminomalonic acid in PAH patients, which could provide new biochemical insights into the pathogenesis of the disease. The results were externally validated on independent case and control cohorts, confirming up to 16 metabolites as statistically significant in the validation study. Multiplatform metabolomics, followed by multivariate chemometric data analysis has a huge potential for explaining pathogenesis of PAH and for searching potential and new more specific and less invasive markers of the disease

A Smart Wireless Car Ignition System for Vehicle Security

Copyright: © 2017 Haider A, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.The paper proposes a novel car ignition system to replace the traditional wired technology and enhance vehicle security. This new system uses wireless transmissions to start the engine and hence eliminates the ignition wire behind the dashboard. It also allows the user to set a password of his/her choice to keep the system protected. A theft alarm that goes ‘’ON’’ when an unusual activity is sensed and/or when the wrong password is attempted to unlock the system is integrated in the system. Moreover, important factors such as economic feasibility, adaptability to the new vehicle technologies and customers’ preferences have been taken into consideration in the design of the proposed vehicle security system.Peer reviewedFinal Published versio

Interaction patterns for smart spaces: a confident interaction design solution for pervasive sensitive IoT services

Smart spaces represent a powerful tool for deploying the new pervasive sensitive services based on Internet of Things products and developed in current Information Society close to users. Researchers have focused their efforts on new techniques to improve systems and products in this area but neglecting the human factors related to psychological aspects of the user and their psycho-social relationship with the deployment space where they live. This research proposes to take into account these cognitive features in early stages of the design of smart spaces by defining a set of interaction patterns. By using this set of interaction patterns it is possible to influence over the confidence that users can develop during the use of IoT products and services based on them. An evaluative verification has been carried out to assess how this design engineering approach provide a real impact on the generation of confidence in the users of this kind of technology

Activation of ERK1/2 MAP kinases in familial amyloidotic polyneuropathy

J Neurochem. 2006 Apr;97(1):151-61. Epub 2006 Mar 3. Activation of ERK1/2 MAP kinases in familial amyloidotic polyneuropathy. Monteiro FA, Sousa MM, Cardoso I, do Amaral JB, Guimarães A, Saraiva MJ. Molecular Neurobiology, Instituto de Biologia Celular e Molecular, ICBAS, University of Porto, and Estomatology, Maxillofacial Surgery, Hospital Geral de Santo António, Portugal. Abstract Familial amyloidotic polyneuropathy (FAP) is a neurodegenerative disorder characterized by the extracellular deposition of transthyretin (TTR), especially in the PNS. Given the invasiveness of nerve biopsy, salivary glands (SG) from FAP patients were used previously in microarray analysis; mitogen-activated protein (MAP) kinase phosphatase 1 (MKP-1) was down-regulated in FAP. Results were validated by RT-PCR and immunohistochemistry both in SG and in nerve biopsies of different stages of disease progression. MKP-3 was also down-regulated in FAP SG biopsies. Given the relationship between MKPs and MAPKs, the latter were investigated. Only extracellular signal-regulated kinases 1/2 (ERK1/2) displayed increased activation in FAP SG and nerves. ERK1/2 kinase (MEK1/2) activation was also up-regulated in FAP nerves. In addition, an FAP transgenic mouse model revealed increased ERK1/2 activation in peripheral nerve affected with TTR deposition when compared to control animals. Cultured rat Schwannoma cell line treatment with TTR aggregates stimulated ERK1/2 activation, which was partially mediated by the receptor for advanced glycation end-products (RAGE). Moreover, caspase-3 activation triggered by TTR aggregates was abrogated by U0126, a MEK1/2 inhibitor, indicating that ERK1/2 activation is essential for TTR aggregates-induced cytotoxicity. Taken together, these data suggest that abnormally sustained activation of ERK in FAP may represent an early signaling cascade leading to neurodegeneration. PMID: 16515552 [PubMed - indexed for MEDLINE

The origin of large molecules in primordial autocatalytic reaction networks

Large molecules such as proteins and nucleic acids are crucial for life, yet their primordial origin remains a major puzzle. The production of large molecules, as we know it today, requires good catalysts, and the only good catalysts we know that can accomplish this task consist of large molecules. Thus the origin of large molecules is a chicken and egg problem in chemistry. Here we present a mechanism, based on autocatalytic sets (ACSs), that is a possible solution to this problem. We discuss a mathematical model describing the population dynamics of molecules in a stylized but prebiotically plausible chemistry. Large molecules can be produced in this chemistry by the coalescing of smaller ones, with the smallest molecules, the `food set', being buffered. Some of the reactions can be catalyzed by molecules within the chemistry with varying catalytic strengths. Normally the concentrations of large molecules in such a scenario are very small, diminishing exponentially with their size. ACSs, if present in the catalytic network, can focus the resources of the system into a sparse set of molecules. ACSs can produce a bistability in the population dynamics and, in particular, steady states wherein the ACS molecules dominate the population. However to reach these steady states from initial conditions that contain only the food set typically requires very large catalytic strengths, growing exponentially with the size of the catalyst molecule. We present a solution to this problem by studying `nested ACSs', a structure in which a small ACS is connected to a larger one and reinforces it. We show that when the network contains a cascade of nested ACSs with the catalytic strengths of molecules increasing gradually with their size (e.g., as a power law), a sparse subset of molecules including some very large molecules can come to dominate the system.Comment: 49 pages, 17 figures including supporting informatio

Transcription factor NRF2 as a therapeutic target for chronic diseases: a systems medicine approach

Systems medicine has a mechanism-based rather than a symptom- or organ-based approach to disease and identifies therapeutic targets in a nonhypothesis-driven manner. In this work, we apply this to transcription factor nuclear factor (erythroid-derived 2)-like 2 (NRF2) by cross-validating its position in a protein-protein interaction network (the NRF2 interactome) functionally linked to cytoprotection in low-grade stress, chronic inflammation, metabolic alterations, and reactive oxygen species formation. Multiscale network analysis of these molecular profiles suggests alterations of NRF2 expression and activity as a common mechanism in a subnetwork of diseases (the NRF2 diseasome). This network joins apparently heterogeneous phenotypes such as autoimmune, respiratory, digestive, cardiovascular, metabolic, and neurodegenerative diseases, along with cancer. Importantly, this approach matches and confirms in silico several applications for NRF2-modulating drugs validated in vivo at different phases of clinical development. Pharmacologically, their profile is as diverse as electrophilic dimethyl fumarate, synthetic triterpenoids like bardoxolone methyl and sulforaphane, protein-protein or DNA-protein interaction inhibitors, and even registered drugs such as metformin and statins, which activate NRF2 and may be repurposed for indications within the NRF2 cluster of disease phenotypes. Thus, NRF2 represents one of the first targets fully embraced by classic and systems medicine approaches to facilitate both drug development and drug repurposing by focusing on a set of disease phenotypes that appear to be mechanistically linked. The resulting NRF2 drugome may therefore rapidly advance several surprising clinical options for this subset of chronic diseases

Synthesis and characterization of a new norfloxacin/resorcinol cocrystal with enhanced solubility and dissolution profile

A new cocrystal of Norfloxacin, a poorly soluble fluoroquinolone antibiotic, has been synthetized by a solvent-mediated transformation experiment in toluene, using resorcinol as a coformer. The new cocrystal exists in both anhydrous and monohydrate forms with the same (1:1) Norfloxacin/resorcinol stoichiometry. The solubility of Norfloxacin and the hydrated cocrystal were determined by the shake-flask method. While Norfloxacin has a solubility of 0.32 ± 0.02 mg/mL, the cocrystal has a solubility of 2.64 ± 0.39 mg/mL, approximately 10-fold higher. The dissolution rate was tested at four biorelevant pH levels of the gastrointestinal tract: 2.0, 4.0, 5.5, and 7.4. In a first set of comparative tests, the dissolution rate of Norfloxacin and the cocrystal was determined separately at each pH value. Both solid forms showed the highest dissolution rate at pH 2.0, where Norfloxacin is totally protonated. Then, the dissolution rate decreases as pH increases. In a second set of experiments, the dissolution of the cocrystal was evaluated by a unique dissolution test, in which the pH dynamically changed from 2.0 to 7.4, stepping 30 min at each of the four biorelevant pH values. Results were quite different in this case, since dissolution at pH 2 affects the behavior of Norfloxacin at the rest of the pH values

Produção de memórias falsas com listas de associados : análise do efeito do nível de processamento e da natureza da prova de memória

As memórias falsas têm sido amplamente estudadas com base num procedimento experimental designado paradigma DRM (Deese/Roediger/McDermott). Esse paradigma promove a criação de ilusões de memória a partir da apresentação de listas de palavras associadas a um item que não consta da lista. Uma das linhas de investigação com o paradigma DRM visa identificar o momento da criação das falsas memórias e explicar os mecanismos que estão na sua origem. Neste artigo, pretendemos fazer uma revisão da investigação sobre o efeito do nível de processamento e da natureza da tarefa de memória na facilitação ou inibição da produção de memórias falsas com listas de associados semânticos.False memories have been widely studied using an experimental procedure called DRM paradigm (Deese/Roediger/McDermott). This paradigm produces memory illusions due to the presentation of lists of words associated to a critical nonpresented word. One line of research on this topic aims at identifying the moment when the false memories are created and the explanation of the mechanisms underling false memories. In this paper we present a review about the effect of level-of-processing and the nature of memory task for the boost or inhibition of false memories created by means of lists of semantic associates.Le paradigme DRM (Deese/Roediger/McDermott) est un des plus connus et plus robustes parmi les études des faux mémoires dans le contexte du laboratoire. Ce paradigme permet la création d illusions de mémoire à partir des mots sémantiquement associés à un item qui n a pas été présenté. Au milieu des investigations basées sur le paradigme DRM il y a des études dont l objectif est d identifier e d´expliquer les mécanismes qui sont à l origine de la production des faux mémoires. Plus spécifiquement, on a pour but de faire une révision de la recherche sur l effet du niveau de codification et de la nature des tâches de mémoire sur la facilitation ou l´inhibition de la production de faux mémoires à partir des mots sémantiquement associés.Los falsos recuerdos han sido muy estudiados mediante la aplicación del paradigma DRM (Deese/Roediger/McDermott). El paradigma permite producir ilusiones de memoria tras la presentación de listas de palabras asociadas a una palabra que no se incluye en la lista. Una de las líneas de investigación que utilizan el paradigma DRM busca identificar el preciso momento de la creación de falsos recuerdos y explicar los mecanismos que originan ese efecto. El objetivo de este artículo es hacer una revisión de la investigación sobre el efecto de los niveles de procesamiento y la naturaleza de la tarea de memoria en la facilitación y inhibición de la producción de falsos recuerdos con listas de asociados semánticos.Fundação para a Ciência e a Tecnologia (FCT)Centro de Investigação em Psicologia da Universidade do Minho (CIPsi