A new anode material for oxygen evolution in molten oxide electrolysis

Molten oxide electrolysis (MOE) is an electrometallurgical technique that enables the direct production of metal in the liquid state from oxide feedstock and compared with traditional methods of extractive metallurgy offers both a substantial simplification of the process and a significant reduction in energy consumption. MOE is also considered a promising route for mitigation of CO[subscript 2] emissions in steelmaking, production of metals free of carbon, and generation of oxygen for extra-terrestrial exploration. Until now, MOE has been demonstrated using anode materials that are consumable (graphite for use with ferro-alloys and titanium) or unaffordable for terrestrial applications (iridium for use with iron). To enable metal production without process carbon, MOE requires an anode material that resists depletion while sustaining oxygen evolution. The challenges for iron production are threefold. First, the process temperature is in excess of 1,538 degrees Celsius. Second, under anodic polarization most metals inevitably corrode in such conditions. Third, iron oxide undergoes spontaneous reduction on contact with most refractory metals and even carbon. Here we show that anodes comprising chromium-based alloys exhibit limited consumption during iron extraction and oxygen evolution by MOE. The anode stability is due to the formation of an electronically conductive solid solution of chromium(iii) and aluminium oxides in the corundum structure. These findings make practicable larger-scale evaluation of MOE for the production of steel, and potentially provide a key material component enabling mitigation of greenhouse-gas emissions while producing metal of superior metallurgical quality.American Iron and Steel Institut

Restricting HIV-1 pathways for escape using rationally designed anti–HIV-1 antibodies

Recently identified broadly neutralizing antibodies (bNAbs) that potently neutralize most HIV-1 strains are key to potential antibody-based therapeutic approaches to combat HIV/AIDS in the absence of an effective vaccine. Increasing bNAb potencies and resistance to common routes of HIV-1 escape through mutation would facilitate their use as therapeutics. We previously used structure-based design to create the bNAb NIH45-46G54W, which exhibits superior potency and/or breadth compared with other bNAbs. We report new, more effective NIH45-46^(G54W) variants designed using analyses of the NIH45-46–gp120 complex structure and sequences of NIH45-46^(G54W)–resistant HIV-1 strains. One variant, 45-46m2, neutralizes 96% of HIV-1 strains in a cross-clade panel and viruses isolated from an HIV-infected individual that are resistant to all other known bNAbs, making it the single most broad and potent anti–HIV-1 antibody to date. A description of its mechanism is presented based on a 45-46m2–gp120 crystal structure. A second variant, 45-46m7, designed to thwart HIV-1 resistance to NIH45-46G54W arising from mutations in a gp120 consensus sequence, targets a common route of HIV-1 escape. In combination, 45-46m2 and 45-46m7 reduce the possible routes for the evolution of fit viral escape mutants in HIV-1_(YU-2)–infected humanized mice, with viremic control exhibited when a third antibody, 10–1074, was added to the combination

Complex-type N-glycan recognition by potent broadly neutralizing HIV antibodies

Broadly neutralizing HIV antibodies (bNAbs) can recognize carbohydrate-dependent epitopes on gp120. In contrast to previously characterized glycan-dependent bNAbs that recognize high-mannose N-glycans, PGT121 binds complex-type N-glycans in glycan microarrays. We isolated the B-cell clone encoding PGT121, which segregates into PGT121-like and 10-1074–like groups distinguished by sequence, binding affinity, carbohydrate recognition, and neutralizing activity. Group 10-1074 exhibits remarkable potency and breadth but no detectable binding to protein-free glycans. Crystal structures of unliganded PGT121, 10-1074, and their likely germ-line precursor reveal that differential carbohydrate recognition maps to a cleft between complementarity determining region (CDR)H2 and CDRH3. This cleft was occupied by a complex-type N-glycan in a “liganded” PGT121 structure. Swapping glycan contact residues between PGT121 and 10-1074 confirmed their importance for neutralization. Although PGT121 binds complex-type N-glycans, PGT121 recognized high-mannose-only HIV envelopes in isolation and on virions. As HIV envelopes exhibit varying proportions of high-mannose- and complex-type N-glycans, these results suggest promiscuous carbohydrate interactions, an advantageous adaptation ensuring neutralization of all viruses within a given strain

‘New and important careers’: how women excelled at the BBC, 1923–1939

From its beginnings in 1923, the BBC employed a sizeable female workforce. The majority were in support roles as typists, secretaries and clerks but, during the 1920s and 1930s, a significant number held important posts. As a modern industry, the BBC took a largely progressive approach towards the ‘career women’ on its staff, many of whom were in jobs that were developed specifically for the new medium of broadcasting. Women worked as drama producers, advertising representatives and Children’s Hour Organisers. They were talent spotters, press officers and documentary makers. Three women attained Director status while others held significant administrative positions. This article considers in what ways it was the modernity and novelty of broadcasting, combined with changing employment possibilities and attitudes towards women evident after the First World War, that combined to create the conditions in which they could excel

HIV therapy by a combination of broadly neutralizing antibodies in humanized mice

Human antibodies to human immunodeficiency virus-1 (HIV-1) can neutralize a broad range of viral isolates in vitro and protect non-human primates against infection. Previous work showed that antibodies exert selective pressure on the virus but escape variants emerge within a short period of time. However, these experiments were performed before the recent discovery of more potent anti-HIV-1 antibodies and their improvement by structure-based design. Here we re-examine passive antibody transfer as a therapeutic modality in HIV-1-infected humanized mice. Although HIV-1 can escape from antibody monotherapy, combinations of broadly neutralizing antibodies can effectively control HIV-1 infection and suppress viral load to levels below detection. Moreover, in contrast to antiretroviral therapy the longer half-life of antibodies led to control of viraemia for an average of 60 days after cessation of therapy. Thus, combinations of potent monoclonal antibodies can effectively control HIV-1 replication in humanized mice, and should be re-examined as a therapeutic modality in HIV-1-infected individuals

Enhanced HIV-1 immunotherapy by commonly arising antibodies that target virus escape variants

Antibody-mediated immunotherapy is effective in humanized mice when combinations of broadly neutralizing antibodies (bNAbs) are used that target nonoverlapping sites on the human immunodeficiency virus type 1 (HIV-1) envelope. In contrast, single bNAbs can control simian–human immunodeficiency virus (SHIV) infection in immune-competent macaques, suggesting that the host immune response might also contribute to the control of viremia. Here, we investigate how the autologous antibody response in intact hosts can contribute to the success of immunotherapy. We find that frequently arising antibodies that normally fail to control HIV-1 infection can synergize with passively administered bNAbs by preventing the emergence of bNAb viral escape variants

Anatomical heterogeneity of tendon: Fascicular and interfascicular tendon compartments have distinct proteomic composition

This study was funded by the BBSRC (BB/K008412/1)

Leo Strauss and International Relations: The politics of modernity's abyss

This article argues that an engagement with the political philosophy of Leo Strauss is of considerable value in International Relations (IR), in relation to the study of both recent US foreign policy and contemporary IR theory. The question of Straussian activities within and close to the foreign policy-making establishment in the United States during the period leading up to the 2003 invasion of Iraq has been the focus of significant scholarly and popular attention in recent years. This article makes the case that several individuals influenced by Strauss exercised considerable influence in the fields of intelligence production, the media and think tanks, and traces the ways in which elements of Strauss’ thought are discernible in their interventions in these spheres. It further argues that Strauss’ political philosophy is of broader significance for IR insofar as it can be read as a securitising response to the dangers he associated with the foundationlessness of the modern condition. The article demonstrates that the politics of this response are of crucial importance for contemporary debates between traditional and critical IR theorists

The 'knowledge politics' of democratic peace theory

How do academic ideas influence US foreign policy, under what conditions and with what consequences? This article traces the rise, ‘securitisation’ and political consequences of democratic peace theory (DPT) in the United States by exploring the work of Doyle, Diamond and Fukuyama. Ideas influence US foreign policy under different circumstances, but are most likely to do either during and after crises when the policy environment permits ‘new thinking’, or when these ideas have been developed through state-connected elite knowledge networks, or when they are (or appear paradigmatically congenial to) foreign policymakers’ mindsets, or, finally, when they become institutionally-embedded. The appropriation of DPT by foreign policymakers has categorised the world into antagonistic blocs – democratic/non-democratic zones of peace/turmoil – as the corollary to a renewed American mission to make the world ‘safer’ through ‘democracy’ promotion. The roles of networked organic intellectuals – in universities and think tanks, for instance – were particularly important in elevating DPT from the academy to national security managers

Loss-of-function mutations in the X-linked biglycan gene cause a severe syndromic form of thoracic aortic aneurysms and dissections.

Thoracic aortic aneurysm and dissection (TAAD) is typically inherited in an autosomal dominant manner, but rare X-linked families have been described. So far, the only known X-linked gene is FLNA, which is associated with the periventricular nodular heterotopia type of Ehlers-Danlos syndrome. However, mutations in this gene explain only a small number of X-linked TAAD families. We performed targeted resequencing of 368 candidate genes in a cohort of 11 molecularly unexplained Marfan probands. Subsequently, Sanger sequencing of BGN in 360 male and 155 female molecularly unexplained TAAD probands was performed. We found five individuals with loss-of-function mutations in BGN encoding the small leucine-rich proteoglycan biglycan. The clinical phenotype is characterized by early-onset aortic aneurysm and dissection. Other recurrent findings include hypertelorism, pectus deformity, joint hypermobility, contractures, and mild skeletal dysplasia. Fluorescent staining revealed an increase in TGF-β signaling, evidenced by an increase in nuclear pSMAD2 in the aortic wall. Our results are in line with those of prior reports demonstrating that Bgn-deficient male BALB/cA mice die from aortic rupture. In conclusion, BGN gene defects in humans cause an X-linked syndromic form of severe TAAD that is associated with preservation of elastic fibers and increased TGF-β signaling.Genet Med 19 4, 386-395