What can we learn from a race with one runner? A comment on Foreman-Peck and Zhou, ‘Late marriage as a contributor to the industrial revolution in England’

Foreman-Peck and Zhou’s claim that late marriage was a major contributor to the Industrial Revolution in England cannot be sustained. They consider neither other influences on English industrialisation nor other European economies where marriage age was high throughout the early modern period but industrialisation came much later. It is not possible to argue that late marriage age was a major contributor to English industrialisation without analysing other possible contributing factors. Any consideration of this question must assess marriage age alongside other causes of industrialisation and explain why other European economies with higher marriage age industrialised much later than England

Short linear motif candidates in the cell entry system used by SARS-CoV-2 and their potential therapeutic implications

The first reported receptor for SARS-CoV-2 on host cells was the angiotensin-converting enzyme 2 (ACE2). However, the viral spike protein also has an RGD motif, suggesting that cell surface integrins may be co-receptors. We examined the sequences of ACE2 and integrins with the Eukaryotic Linear Motif (ELM) resource and identified candidate short linear motifs (SLiMs) in their short, unstructured, cytosolic tails with potential roles in endocytosis, membrane dynamics, autophagy, cytoskeleton, and cell signaling. These SLiM candidates are highly conserved in vertebrates and may interact with the μ2 subunit of the endocytosis-associated AP2 adaptor complex, as well as with various protein domains (namely, I-BAR, LC3, PDZ, PTB, and SH2) found in human signaling and regulatory proteins. Several motifs overlap in the tail sequences, suggesting that they may act as molecular switches, such as in response to tyrosine phosphorylation status. Candidate LC3-interacting region (LIR) motifs are present in the tails of integrin β3 and ACE2, suggesting that these proteins could directly recruit autophagy components. Our findings identify several molecular links and testable hypotheses that could uncover mechanisms of SARS-CoV-2 attachment, entry, and replication against which it may be possible to develop host-directed therapies that dampen viral infection and disease progression. Several of these SLiMs have now been validated to mediate the predicted peptide interactions.Fil: Mészáros, Bálint. European Molecular Biology Laboratory; AlemaniaFil: Sámano Sánchez, Hugo. European Molecular Biology Laboratory; AlemaniaFil: Alvarado Valverde, Jesús. European Molecular Biology Laboratory; Alemania. Ruprecht Karls Universitat Heidelberg; AlemaniaFil: Čalyševa, Jelena. European Molecular Biology Laboratory; Alemania. Ruprecht Karls Universitat Heidelberg; AlemaniaFil: Martinez Perez, Elizabeth. Fundación Instituto Leloir; Argentina. European Molecular Biology Laboratory; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Alves, Renato. European Molecular Biology Laboratory; AlemaniaFil: Shields, Denis C.. Universidad de Dublin; IrlandaFil: Kumar, Manjeet. European Molecular Biology Laboratory; AlemaniaFil: Rippmann, Friedrich. Computational Chemistry & Biology; AlemaniaFil: Chemes, Lucia Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Gibson, Toby James. European Molecular Biology Laboratory; Alemani

Design agency:prototyping multi-agent systems in architecture

This paper presents research on the prototyping of multi-agent systems for architectural design. It proposes a design exploration methodology at the intersection of architecture, engineering, and computer science. The motivation of the work includes exploring bottom up generative methods coupled with optimizing performance criteria including for geometric complexity and objective functions for environmental, structural and fabrication parameters. The paper presents the development of a research framework and initial experiments to provide design solutions, which simultaneously satisfy complexly coupled and often contradicting objectives. The prototypical experiments and initial algorithms are described through a set of different design cases and agents within this framework; for the generation of façade panels for light control; for emergent design of shell structures; for actual construction of reciprocal frames; and for robotic fabrication. Initial results include multi-agent derived efficiencies for environmental and fabrication criteria and discussion of future steps for inclusion of human and structural factors

RNAi screen for NRF2 inducers identifies targets that rescue primary lung epithelial cells from cigarette smoke induced radical stress

Chronic Obstructive Pulmonary Disease (COPD) is a highly prevalent condition characterized by inflammation and progressive obstruction of the airways. At present, there is no treatment that suppresses the chronic inflammation of the disease, and COPD patients often succumb to the condition. Excessive oxidative stress caused by smoke inhalation is a major driving force of the disease. The transcription factor NRF2 is a critical player in the battle against oxidative stress and its function is impaired in COPD. Increasing NRF2 activity may therefore be a viable therapeutic option for COPD treatment. We show that down regulation of KEAP1, a NRF2 inhibitor, protects primary human lung epithelial cells from cigarette-smoke-extract (CSE) induced cell death in an established in vitro model of radical stress. To identify new potential drug targets with a similar effect, we performed a siRNA screen of the 'druggable' genome using a NRF2 transcriptional reporter cell line. This screen identified multiple genes that when down regulated increased NRF2 transcriptional activity and provided a survival benefit in the in vitro model. Our results suggest that inhibiting components of the ubiquitin-proteasome system will have the strongest effects on NRF2 transcriptional activity by increasing NRF2 levels. We also find that down regulation of the small GTPase Rab28 or the Estrogen Receptor ESRRA provide a survival benefit. Rab28 knockdown increased NRF2 protein levels, indicating that Rab28 may regulate NRF2 proteolysis. Conversely ESRRA down regulation increased NRF2 transcriptional activity without affecting NRF2 levels, suggesting a proteasome-independent mechanism

Methods for modelling and analysis of bendable photovoltaic modules on irregularly curved surfaces

Most photovoltaic modules are planar and as a result, research on panel layout for photovoltaic systems typically uses planar panels. However, the increased availability of thin-film photovoltaic modules opens up possibilities for the application of flexible solar panels on irregularly curved surfaces, including the integration of photovoltaic panels on building roofs with double curvature. In order to efficiently arrange photovoltaic panels on such surfaces, geometric CAD tools as well as radiation analysis tools are needed. This paper introduces a method to generate geometry for flexible photovoltaic modules on curved surfaces, as well as a method to arrange multiple of such modules on a surface. By automating the generation of possible photovoltaic panel arrangements and linking the geometric tools to solar analysis software, large numbers of design options can be analysed in a relatively short time. This combination of geometry generation and solar analysis provides data that is important for electrical design of photovoltaic systems. The merits of the methods we introduce are illustrated with a case study, for which hundreds of design configurations have been explored in an automated manner. Based on analysis of the numeric data generated for each of the configurations, the effects of panel dimensions and orientation on solar insolation potential and panel curvature have been established. The quantitative and qualitative conclusions resulting from this analysis have informed the design of the photovoltaic system in the case study project.ISSN:2251-6832ISSN:2008-916