Large-area 2D selective area growth for photonic crystal surface emitting lasers

We report an investigation into large-area selective area growth of InGaAs/GaAs quantum wells by metalorganic vapour phase epitaxy. The emission wavelength tuning range, growth enhancement, and uniformity of material deposited within square masked regions with central square growth windows with widths in the range of 100–300 μm are studied. Micro-photoluminescence measurements at the centre point of each of the growth windows reveals a total wavelength tuning range of 86 nm across all samples, with a typical tuning range of 30 nm for a given window width, dependent upon dielectric mask width. The thickness enhancement in each of features, as determined by white-light interferometric profiling, indicates that centre point growth rate enhancements of between 1.19 and 2.23× are achieved with respect to the nominal epitaxial structure. By comparing the observed emission wavelengths with those simulated using the enhanced quantum well thicknesses, a range of indium concentrations between 12 and 17 % is calculated for the material at the centre of each feature. Two-dimensional analysis of selected features reveals that areas with uniform emission wavelength up to 100 × 100 μm2 in size can be achieved for the mask patterns used, indicating suitability for future applications in the fabrication of monolithically integrated multi-wavelength photonic crystal surface emitting laser arrays

Binding of an RNA trafficking response element to heterogeneous nuclear ribonucleoproteins A1 and A2

Heterogeneous nuclear ribonucleoprotein (hnRNP) A2 binds a 21-nucleotide myelin basic protein mRNA response element, the A2RE, and A2RE-like sequences in other localized mRNAs, and is a trans-acting factor in oligodendrocyte cytoplasmic RNA trafficking. Recombinant human hnRNPs A1 and A2 were used in a biosensor to explore interactions with A2RE and the cognate oligodeoxyribonucleotide. Both proteins have a single site that bound oligonucleotides with markedly different sequences but did not bind in the presence of heparin. Both also possess a second, specific site that bound only A2RE and was unaffected by heparin, hnRNP A2 bound A2RE in the latter site with a K-d near 50 nM, whereas the K-d for hnRNP A1 was above 10 muM. UV cross-linking assays led to a similar conclusion. Mutant A2RE sequences, that in earlier qualitative studies appeared not to bind hnRNP A2 or support RNA trafficking in oligodendrocytes, had dissociation constants above 5 muM for this protein. The two concatenated RNA recognition motifs (RRMs), but not the individual RRMs, mimicked the binding behavior of hnRNP A2. These data highlight the specificity of the interaction of A2RE with these hnRNPs and suggest that the sequence-specific A2RE-binding site on hnRNP A2 is formed by both RRMs acting in cis

IFITM3 restricts the morbidity and mortality associated with influenza

The 2009 H1N1 influenza pandemic showed the speed with which a novel respiratory virus can spread and the ability of a generally mild infection to induce severe morbidity and mortality in a subset of the population. Recent in vitro studies show that the interferon-inducible transmembrane (IFITM) protein family members potently restrict the replication of multiple pathogenic viruses1, 2, 3, 4, 5, 6, 7. Both the magnitude and breadth of the IFITM proteins’ in vitro effects suggest that they are critical for intrinsic resistance to such viruses, including influenza viruses. Using a knockout mouse model8, we now test this hypothesis directly and find that IFITM3 is essential for defending the host against influenza A virus in vivo. Mice lacking Ifitm3 display fulminant viral pneumonia when challenged with a normally low-pathogenicity influenza virus, mirroring the destruction inflicted by the highly pathogenic 1918 ‘Spanish’ influenza9, 10. Similar increased viral replication is seen in vitro, with protection rescued by the re-introduction of Ifitm3. To test the role of IFITM3 in human influenza virus infection, we assessed the IFITM3 alleles of individuals hospitalized with seasonal or pandemic influenza H1N1/09 viruses. We find that a statistically significant number of hospitalized subjects show enrichment for a minor IFITM3 allele (SNP rs12252-C) that alters a splice acceptor site, and functional assays show the minor CC genotype IFITM3 has reduced influenza virus restriction in vitro. Together these data reveal that the action of a single intrinsic immune effector, IFITM3, profoundly alters the course of influenza virus infection in mouse and human

Safety, immunogenicity, and reactogenicity of BNT162b2 and mRNA-1273 COVID-19 vaccines given as fourth-dose boosters following two doses of ChAdOx1 nCoV-19 or BNT162b2 and a third dose of BNT162b2 (COV-BOOST): a multicentre, blinded, phase 2, randomised trial

Background Some high-income countries have deployed fourth doses of COVID-19 vaccines, but the clinical need, effectiveness, timing, and dose of a fourth dose remain uncertain. We aimed to investigate the safety, reactogenicity, and immunogenicity of fourth-dose boosters against COVID-19.Methods The COV-BOOST trial is a multicentre, blinded, phase 2, randomised controlled trial of seven COVID-19 vaccines given as third-dose boosters at 18 sites in the UK. This sub-study enrolled participants who had received BNT162b2 (Pfizer-BioNTech) as their third dose in COV-BOOST and randomly assigned them (1:1) to receive a fourth dose of either BNT162b2 (30 µg in 0·30 mL; full dose) or mRNA-1273 (Moderna; 50 µg in 0·25 mL; half dose) via intramuscular injection into the upper arm. The computer-generated randomisation list was created by the study statisticians with random block sizes of two or four. Participants and all study staff not delivering the vaccines were masked to treatment allocation. The coprimary outcomes were safety and reactogenicity, and immunogenicity (antispike protein IgG titres by ELISA and cellular immune response by ELISpot). We compared immunogenicity at 28 days after the third dose versus 14 days after the fourth dose and at day 0 versus day 14 relative to the fourth dose. Safety and reactogenicity were assessed in the per-protocol population, which comprised all participants who received a fourth-dose booster regardless of their SARS-CoV-2 serostatus. Immunogenicity was primarily analysed in a modified intention-to-treat population comprising seronegative participants who had received a fourth-dose booster and had available endpoint data. This trial is registered with ISRCTN, 73765130, and is ongoing.Findings Between Jan 11 and Jan 25, 2022, 166 participants were screened, randomly assigned, and received either full-dose BNT162b2 (n=83) or half-dose mRNA-1273 (n=83) as a fourth dose. The median age of these participants was 70·1 years (IQR 51·6–77·5) and 86 (52%) of 166 participants were female and 80 (48%) were male. The median interval between the third and fourth doses was 208·5 days (IQR 203·3–214·8). Pain was the most common local solicited adverse event and fatigue was the most common systemic solicited adverse event after BNT162b2 or mRNA-1273 booster doses. None of three serious adverse events reported after a fourth dose with BNT162b2 were related to the study vaccine. In the BNT162b2 group, geometric mean anti-spike protein IgG concentration at day 28 after the third dose was 23 325 ELISA laboratory units (ELU)/mL (95% CI 20 030–27 162), which increased to 37 460 ELU/mL (31 996–43 857) at day 14 after the fourth dose, representing a significant fold change (geometric mean 1·59, 95% CI 1·41–1·78). There was a significant increase in geometric mean anti-spike protein IgG concentration from 28 days after the third dose (25 317 ELU/mL, 95% CI 20 996–30 528) to 14 days after a fourth dose of mRNA-1273 (54 936 ELU/mL, 46 826–64 452), with a geometric mean fold change of 2·19 (1·90–2·52). The fold changes in anti-spike protein IgG titres from before (day 0) to after (day 14) the fourth dose were 12·19 (95% CI 10·37–14·32) and 15·90 (12·92–19·58) in the BNT162b2 and mRNA-1273 groups, respectively. T-cell responses were also boosted after the fourth dose (eg, the fold changes for the wild-type variant from before to after the fourth dose were 7·32 [95% CI 3·24–16·54] in the BNT162b2 group and 6·22 [3·90–9·92] in the mRNA-1273 group).Interpretation Fourth-dose COVID-19 mRNA booster vaccines are well tolerated and boost cellular and humoral immunity. Peak responses after the fourth dose were similar to, and possibly better than, peak responses after the third dose

The Imperial Style of Inquiry in Twentieth-Century China

How have traditional Chinese ways of thinking affected problem solving in this century? The traditional, imperial style of inquiry is associated with the belief that the universe is a coherent, internally structured unity understandable through the similarly structured human mind. It involves a reliance on antecedent and authoritarian models, coupled with an introspective focus in investigations, at some cost to objective fact gathering. In contrast, emergent forms of inquiry are guided by the values of individual autonomy and new perspectives on objectivity. In the 1930s and 1940s, some liberal educators held the model of Western science in great esteem, and some scientists practicing objective inquiry helped to create an awareness in the urban areas of inquiry not directed by political values. Drawing on philosophical, social science, and popular culture materials, Donald Munro shows that the two strains coexisted in twentieth century China as mixed motives. Many important figures were motivated by a desire to act consistently with the social values associated with the premodern or received view of knowledge and inquiry. At the same time, these people often had other motives, such as utilitarian values, efficiency, and entrepreneurship. Munro argues that while many competing positions can coexist in the same person, the seeds of the positive, instrumental value of individual autonomy in Chinese inquiry are beginning to compete in both scholarly and popular culture with other, older approaches

The Imperial Style of Inquiry in Twentieth-Century China

How have traditional Chinese ways of thinking affected problem solving in this century? The traditional, imperial style of inquiry is associated with the belief that the universe is a coherent, internally structured unity understandable through the similarly structured human mind. It involves a reliance on antecedent and authoritarian models, coupled with an introspective focus in investigations, at some cost to objective fact gathering. In contrast, emergent forms of inquiry are guided by the values of individual autonomy and new perspectives on objectivity. In the 1930s and 1940s, some liberal educators held the model of Western science in great esteem, and some scientists practicing objective inquiry helped to create an awareness in the urban areas of inquiry not directed by political values. Drawing on philosophical, social science, and popular culture materials, Donald Munro shows that the two strains coexisted in twentieth century China as mixed motives. Many important figures were motivated by a desire to act consistently with the social values associated with the premodern or received view of knowledge and inquiry. At the same time, these people often had other motives, such as utilitarian values, efficiency, and entrepreneurship. Munro argues that while many competing positions can coexist in the same person, the seeds of the positive, instrumental value of individual autonomy in Chinese inquiry are beginning to compete in both scholarly and popular culture with other, older approaches