Exploring the role of materials in policy change: innovation in low energy housing in the UK

There remains uncertainty in models of the policy process about how and when radical change takes place. Most policy authors focus on explaining incremental change, and yet in practice a pattern of change described as punctuated equilibrium has been observed, with periods of stability interspersed with periods of rapid, abrupt change. It is argued here that the influence of materials and technologies—the substance of policy—must be incorporated into models of the policy process in order to help further our understanding of radical change. Concepts from science and technology studies concerning the inseparability of social and technical spheres are used to explore how people and materials interact to create opportunities for radical change. These ideas are particularly relevant to policy sectors comprising durable, capital-intensive infrastructure, such as housing. Drawing on examples from the UK housing sector, ideas about policy networks and large technical systems are synthesised to develop a more holistic, interdisciplinary account of policy change

INTERLOCUÇÕES SOBRE A PRÁTICA PSICANALÍTICA NUMA CLÍNICA-ESCOLA

International audienceProducing soluble proteins in Escherichia coli is still a major bottleneck for structural proteomics. Therefore, screening for soluble expression on a small scale is an attractive way of identifying constructs that are likely to be amenable to structural analysis. A variety of expression-screening methods have been developed within the Structural Proteomics In Europe (SPINE) consortium and to assist the further refinement of such approaches, eight laboratories participating in the network have benchmarked their protocols. For this study, the solubility profiles of a common set of 96 His(6)-tagged proteins were assessed by expression screening in E. coli. The level of soluble expression for each target was scored according to estimated protein yield. By reference to a subset of the proteins, it is demonstrated that the small-scale result can provide a useful indicator of the amount of soluble protein likely to be produced on a large scale (i.e. sufficient for structural studies). In general, there was agreement between the different groups as to which targets were not soluble and which were the most soluble. However, for a large number of the targets there were wide discrepancies in the results reported from the different screening methods, which is correlated with variations in the procedures and the range of parameters explored. Given finite resources, it appears that the question of how to most effectively explore ;expression space' is similar to several other multi-parameter problems faced by crystallographers, such as crystallization

The Hexamer Structure of the Rift Valley Fever Virus Nucleoprotein Suggests a Mechanism for its Assembly into Ribonucleoprotein Complexes

Rift Valley fever virus (RVFV), a Phlebovirus with a genome consisting of three single-stranded RNA segments, is spread by infected mosquitoes and causes large viral outbreaks in Africa. RVFV encodes a nucleoprotein (N) that encapsidates the viral RNA. The N protein is the major component of the ribonucleoprotein complex and is also required for genomic RNA replication and transcription by the viral polymerase. Here we present the 1.6 Å crystal structure of the RVFV N protein in hexameric form. The ring-shaped hexamers form a functional RNA binding site, as assessed by mutagenesis experiments. Electron microscopy (EM) demonstrates that N in complex with RNA also forms rings in solution, and a single-particle EM reconstruction of a hexameric N-RNA complex is consistent with the crystallographic N hexamers. The ring-like organization of the hexamers in the crystal is stabilized by circular interactions of the N terminus of RVFV N, which forms an extended arm that binds to a hydrophobic pocket in the core domain of an adjacent subunit. The conformation of the N-terminal arm differs from that seen in a previous crystal structure of RVFV, in which it was bound to the hydrophobic pocket in its own core domain. The switch from an intra- to an inter-molecular interaction mode of the N-terminal arm may be a general principle that underlies multimerization and RNA encapsidation by N proteins from Bunyaviridae. Furthermore, slight structural adjustments of the N-terminal arm would allow RVFV N to form smaller or larger ring-shaped oligomers and potentially even a multimer with a super-helical subunit arrangement. Thus, the interaction mode between subunits seen in the crystal structure would allow the formation of filamentous ribonucleocapsids in vivo. Both the RNA binding cleft and the multimerization site of the N protein are promising targets for the development of antiviral drugs

Africa’s response to the COVID-19 pandemic : A review of the nature of the virus, impacts and implications for preparedness

Background: COVID-19 continues to wreak havoc in different countries across the world, claiming thousands of lives, increasing morbidity and disrupting lifestyles. The global scientific community is in urgent need of relevant evidence, to understand the challenges and knowledge gaps, as well as the opportunities to contain the spread of the virus. Considering the unique socio-economic, demographic, political, ecological and climatic contexts in Africa, the responses which may prove to be successful in other regions may not be appropriate on the continent. This paper aims to provide insight for scientists, policy makers and international agencies to contain the virus and to mitigate its impact at all levels. Methods: The Affiliates of the African Academy of Sciences (AAS), came together to synthesize the current evidence, identify the challenges and opportunities to enhance the understanding of the disease. We assess the potential impact of this pandemic and the unique challenges of the disease on African nations. We examine the state of Africa’s preparedness and make recommendations for steps needed to win the war against this pandemic and combat potential resurgence. Results: We identified gaps and opportunities among cross-cutting issueswhich must be addressed or harnessed in this pandemic. Factors such as the nature of the virus and the opportunities for drug targeting, point of care diagnostics, health surveillance systems, food security, mental health, xenophobia and gender-based violence, shelter for the homeless, water and sanitation, telecommunications challenges, domestic regional coordination and financing. Conclusion: Based on our synthesis of the current evidence, while there are plans for preparedness in several African countries, there are significant limitations. A multi-sectoral efforts from the science, education, medical, technology, communication, business, and industry sectors, as well as local communities, must work collaboratively to assist countries in order to win this fight

The European Virus Archive goes global: A growing resource for research

The European Virus Archive (EVA) was created in 2008 with funding from the FP7-EU Infrastructure Programme, in response to the need for a coordinated and readily accessible collection of viruses that could be made available to academia, public health organisations and industry. Within three years, it developed from a consortium of nine European laboratories to encompass associated partners in Africa, Russia, China, Turkey, Germany and Italy. In 2014, the H2020 Research and Innovation Framework Programme (INFRAS projects) provided support for the transformation of the EVA from a European to a global organization (EVAg). The EVAg now operates as a non-profit consortium, with 26 partners and 20 associated partners from 21 EU and non-EU countries. In this paper, we outline the structure, management and goals of the EVAg, to bring to the attention of researchers the wealth of products it can provide and to illustrate how end-users can gain access to these resources. Organisations or individuals who would like to be considered as contributors are invited to contact the EVAg coordinator, Jean-Louis Romette, at [email protected]

Evidence for Novel Hepaciviruses in Rodents

Hepatitis C virus (HCV) is among the most relevant causes of liver cirrhosis and hepatocellular carcinoma. Research is complicated by a lack of accessible small animal models. The systematic investigation of viruses of small mammals could guide efforts to establish such models, while providing insight into viral evolutionary biology. We have assembled the so-far largest collection of small-mammal samples from around the world, qualified to be screened for bloodborne viruses, including sera and organs from 4,770 roden

The crystal structure of a cardiovirus RNA-dependent RNA polymerase reveals an unusual conformation of the polymerase active site.

Contains fulltext : 137306.pdf (publisher's version ) (Open Access)Encephalomyocarditis virus (EMCV) is a member of the Cardiovirus genus within the large Picornaviridae family, which includes a number of important human and animal pathogens. The RNA-dependent RNA polymerase (RdRp) 3Dpol is a key enzyme for viral genome replication. In this study, we report the X-ray structures of two different crystal forms of the EMCV RdRp determined at 2.8- and 2.15-A resolution. The in vitro elongation and VPg uridylylation activities of the purified enzyme have also been demonstrated. Although the overall structure of EMCV 3Dpol is shown to be similar to that of the known RdRps of other members of the Picornaviridae family, structural comparisons show a large reorganization of the active-site cavity in one of the crystal forms. The rearrangement affects mainly motif A, where the conserved residue Asp240, involved in ribonucleoside triphosphate (rNTP) selection, and its neighbor residue, Phe239, move about 10 A from their expected positions within the ribose binding pocket toward the entrance of the rNTP tunnel. This altered conformation of motif A is stabilized by a cation-pi interaction established between the aromatic ring of Phe239 and the side chain of Lys56 within the finger domain. Other contacts, involving Phe239 and different residues of motif F, are also observed. The movement of motif A is connected with important conformational changes in the finger region flanked by residues 54 to 63, harboring Lys56, and in the polymerase N terminus. The structures determined in this work provide essential information for studies on the cardiovirus RNA replication process and may have important implications for the development of new antivirals targeting the altered conformation of motif A. IMPORTANCE: The Picornaviridae family is one of the largest virus families known, including many important human and animal pathogens. The RNA-dependent RNA polymerase (RdRp) 3Dpol is a key enzyme for picornavirus genome replication and a validated target for the development of antiviral therapies. Solving the X-ray structure of the first cardiovirus RdRp, EMCV 3Dpol, we captured an altered conformation of a conserved motif in the polymerase active site (motif A) containing the aspartic acid residue involved in rNTP selection and binding. This altered conformation of motif A, which interferes with the correct positioning of the rNTP substrate in the active site, is stabilized by a number of residues strictly conserved among picornaviruses. The rearrangements observed suggest that this motif A segment is a dynamic element that can be modulated by external effectors, either activating or inhibiting enzyme activity, and this type of modulation appears to be general to all picornaviruses.1 mei 201

The right to infrastructure: a prototype for open-source urbanism

This article develops an analytical framework to place the rise of open source urbanism in context, and develops the concept of the ‘right to infrastructure’ as expressive of new ecologies of urban relations that are heretofore coming into being. It describes, first, a genealogy for open source technology, focusing in particular on how open source urban hardware projects may challenge urban theory. It moves then to describe in detail various dimensions and implications of an open source infrastructural project in Madrid. In all, the article analyses three challenges that the development of open source urban infrastructures are posing to the institutions of urban governance and property: regarding the evolving shape and composition of urban ecologies; the technical and design challenges brought about by open source urban projects, and; the social organisation of the ‘right to infrastructure’ as a political active voice in urban governance. In the last instance, the right to infrastructure, I shall argue, signals the rise of the ‘prototype’ as an emerging figure for contemporary socio-technical designs in and for social theory.Peer reviewe