649 research outputs found
The Right to Resistance and the Western Sahara: A Twail Analysis of the International Legal Order and Its Constraints on Decolonization
The Western Sahara is often called the Last Colony in the World, in reference to its anachronistic status as a territory deemed to have self-determination by the United Nations and ICJ, but still under the rule of another country. Scholarship on the Western Sahara tends to concentrate on the protracted stalemate in their war of independence against Morocco, highlighting the roles of several individual actors, such as France, the United States, the United Nations, and the Polisario, and how these actors create a particular structure to the conflict. This Note focuses on the role of the International Legal Order, as created and upheld by actors such as the United Nations and the United States, in developing and maintaining the stalemate. First, this Note examines the way the rules on the prohibition on the use of force have asymmetrically limited the ability of the Sahrawi people and the Polisario to respond to colonial violence and to pursue their right to self-determination. Second, this Note examines how the principles of self-determination as defined by the International Legal Order further the power imbalances which allow the oppression of the Western Sahara to continue. Following in the tradition of Third World Approaches to International Law, this Note highlights the displacement of the local legal order in the Western Sahara, and aims to demonstrate that by stifling the right to resistance in the Western Sahara, the International Legal Order merely perpetuates the power imbalances of colonialism
Potent Single-Domain Antibodies that Arrest Respiratory Syncytial Virus Fusion Protein in its Prefusion State
Human respiratory syncytial virus (RSV) is the main cause of lower respiratory tract infections in young children. The RSV fusion protein (F) is highly conserved and is the only viral membrane protein that is essential for infection. The prefusion conformation of RSV F is considered the most relevant target for antiviral strategies because it is the fusion-competent form of the protein and the primary target of neutralizing activity present in human serum. Here, we describe two llama-derived single-domain antibodies (VHHs) that have potent RSV-neutralizing activity and bind selectively to prefusion RSV F with picomolar affinity. Crystal structures of these VHHs in complex with prefusion F show that they recognize a conserved cavity formed by two F protomers. In addition, the VHHs prevent RSV replication and lung infiltration of inflammatory monocytes and T cells in RSV-challenged mice. These prefusion F-specific VHHs represent promising antiviral agents against RSV
Potent single-domain antibodies that arrest respiratory syncytial virus fusion protein in its prefusion state
Human respiratory syncytial virus (RSV) is the main cause of lower respiratory tract infections in young children. The RSV fusion protein (F) is highly conserved and is the only viral membrane protein that is essential for infection. The prefusion conformation of RSV F is considered the most relevant target for antiviral strategies because it is the fusion-competent form of the protein and the primary target of neutralizing activity present in human serum. Here, we describe two llama-derived single-domain antibodies (VHHs) that have potent RSV-neutralizing activity and bind selectively to prefusion RSV F with picomolar affinity. Crystal structures of these VHHs in complex with prefusion F show that they recognize a conserved cavity formed by two F protomers. In addition, the VHHs prevent RSV replication and lung infiltration of inflammatory monocytes and T cells in RSV-challenged mice. These prefusion F-specific VHHs represent promising antiviral agents against RSV
The Claims Culture: A Taxonomy of Industry Attitudes
This paper presents an analysis of a familiar aspect of construction industry culture that we have dubbed 'the claims culture'. This is a culture of contract administration that lays a strong emphasis on the planning and management of claims. The principal elements of the analysis are two sets of distinctions. The first comprises economic and occupational orders, referring to two kinds of control that are exercised over the construction process; predicated respectively on economic ownership and occupational competence. The second refers to contrasting attitudes towards relationships and problem solving within these orders: respectively 'distributive' and 'integrative'. The concepts of economic and occupational order entail further sub-categories. The various attitudes associated with these categories and sub-categories are described. They are assessed as to their consequences for change initiatives in the industry
Recommended from our members
Closure Strategy for a Waste Disposal Facility with Multiple Waste Types and Regulatory Drivers at the Nevada Test Site
The U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office (NNSA/NSO) plans to close the waste and classified material storage cells in the southeast quadrant of the Area 5 Radioactive Waste Management Site (RWMS), informally known as the '92-Acre Area', by 2011. The 25 shallow trenches and pits and the 13 Greater Confinement Disposal (GCD) borings contain various waste streams including low-level waste (LLW), low-level mixed waste (LLMW), transuranic (TRU), mixed transuranic (MTRU), and high specific activity LLW. The cells are managed under several regulatory and permit programs by the U.S. Department of Energy (DOE) and the Nevada Division of Environmental Protection (NDEP). Although the specific closure requirements for each cell vary, 37 closely spaced cells will be closed under a single integrated monolayer evapotranspirative (ET) final cover. One cell will be closed under a separate cover concurrently. The site setting and climate constrain transport pathways and are factors in the technical approach to closure and performance assessment. Successful implementation of the integrated closure plan requires excellent communication and coordination between NNSA/NSO and the regulators
Recommended from our members
Closure Strategy for a Waste Disposal Facility with Multiple Waste Types and Regulatory Drivers at the Nevada Test Site
The U.S. Department of Energy, National Security Administration Nevada Site Office (NNSA/NSO) is planning to close the 92-Acre Area of the Area 5 Radioactive Waste Management Site (RWMS) at the Nevada Test Site (NTS), which is about 65 miles northwest of Las Vegas, Nevada. Closure planning for this facility must take into account the regulatory requirements for a diversity of waste streams, disposal and storage configurations, disposal history, and site conditions. This paper provides a brief background of the Area 5 RWMS, identifies key closure issues, and presents the closure strategy. Disposals have been made in 25 shallow excavated pits and trenches and 13 Greater Confinement Disposal (GCD) boreholes at the 92-Acre Area since 1961. The pits and trenches have been used to dispose unclassified low-level waste (LLW), low-level mixed waste (LLMW), and asbestiform waste, and to store classified low-level and low-level mixed materials. The GCD boreholes are intermediate-depth disposal units about 10 feet (ft) in diameter and 120 ft deep. Classified and unclassified high-specific activity LLW, transuranic (TRU), and mixed TRU are disposed in the GCD boreholes. TRU waste was also disposed inadvertently in trench T-04C. Except for three disposal units that are active, all pits and trenches are operationally covered with 8-ft thick alluvium. The 92-Acre Area also includes a Mixed Waste Disposal Unit (MWDU) operating under Resource Conservation and Recovery Act (RCRA) Interim Status, and an asbestiform waste unit operating under a state of Nevada Solid Waste Disposal Site Permit. A single final closure cover is envisioned over the 92-Acre Area. The cover is the evapotranspirative-type cover that has been successfully employed at the NTS. Closure, post-closure care, and monitoring must meet the requirements of the following regulations: U.S. Department of Energy Order 435.1, Title 40 Code of Federal Regulations (CFR) Part 191, Title 40 CFR Part 265, Nevada Administrative Code (NAC) 444.743, RCRA requirements as incorporated into NAC 444.8632, and the Federal Facility Agreement and Consent Order (FFACO). A grouping of waste disposal units according to waste type, location, and similarity in regulatory requirements identified six closure units: LLW Unit, Corrective Action Unit (CAU) 111 under FFACO, Asbestiform LLW Unit, Pit 3 MWDU, TRU GCD Borehole Unit, and TRU Trench Unit. The closure schedule of all units is tied to the closure schedule of the Pit 3 MWDU under RCRA
A Novel Humanized Chi3l1 Blocking Antibody Attenuates Acetaminophen-Induced Liver Injury in Mice
Acetaminophen (APAP) overdose is a leading cause of acute liver injury in the USA. The chitinase 3-like-1 (Chi3l1) protein contributes to APAP-induced liver injury (AILI) by promoting hepatic platelet recruitment. Here, we report the development of a Chi3l1-targeting antibody as a potential therapy for AILI. By immunizing a rabbit successively with the human and mouse Chi3l1 proteins, we isolated cross-reactive monoclonal antibodies (mAbs) from single memory B cells. One of the human and mouse Chi3l1 cross-reactive mAbs was humanized and characterized in bot
Continuous flexibility analysis of SARS-CoV-2 spike prefusion structures
Using a new consensus-based image-processing approach together with principal component analysis, the flexibility and conformational dynamics of the SARS-CoV-2 spike in the prefusion state have been analysed. These studies revealed concerted motions involving the receptor-binding domain (RBD), N-terminal domain, and subdomains 1 and 2 around the previously characterized 1-RBD-up state, which have been modeled as elastic deformations. It is shown that in this data set there are not well defined, stable spike conformations, but virtually a continuum of states. An ensemble map was obtained with minimum bias, from which the extremes of the change along the direction of maximal variance were modeled by flexible fitting. The results provide a warning of the potential image-processing classification instability of these complicated data sets, which has a direct impact on the interpretability of the results.The authors would like to acknowledge financial support from
CSIC (PIE/COVID-19 No. 202020E079), the Comunidad de
Madrid through grant CAM (S2017/BMD-3817), the Spanish
Ministry of Science and Innovation through projects SEV
2017-0712, FPU-2015/264 and PID2019-104757RB-I00/AEI/
FEDER, the Instituto de Salud Carlos III [PT17/0009/0010
(ISCIII-SGEFI/ERDF)], and the European Union and
Horizon 2020 through grants INSTRUCT–ULTRA
(INFRADEV-03-2016-2017, Proposal 731005), EOSC Life
(INFRAEOSC-04-2018, Proposal 824087), HighResCells
(ERC-2018-SyG, Proposal 810057), IMpaCT (WIDESPREAD-
03-2018, Proposal 857203), CORBEL
(INFRADEV-1-2014-1, Proposal 654248) and EOSC–Synergy
(EINFRA-EOSC-5, Proposal 857647). HDT and BF were
supported by NIH grant GM125769 and JSM was supported
by NIH grant R01-AI12752
- …