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LiteBIRD is a candidate satellite for a strategic large mission of JAXA. With its expected launch in the middle of the 2020s with a H3 rocket, LiteBIRD plans to map the polarization of the cosmic microwave background radiation over the full sky with unprecedented precision. The full success of LiteBIRD is to achieve δ r < 0.001 , where δ r is the total error on the tensor-to-scalar ratio r . The required angular coverage corresponds to 2 ≤ ℓ ≤ 200 , where ℓ is the multipole moment. This allows us to test well-motivated cosmic inflation models. Full-sky surveys for 3 years at a Lagrangian point L2 will be carried out for 15 frequency bands between 34 and 448 GHz with two telescopes to achieve the total sensitivity of 2.5 μ K arcmin with a typical angular resolution of 0.5 ∘ at 150 GHz. Each telescope is equipped with a half-wave plate system for polarization signal modulation and a focal plane filled with polarization-sensitive TES bolometers. A cryogenic system provides a 100 mK base temperature for the focal planes and 2 K and 5 K stages for optical components.

The British empire was a huge enterprise. To foreigners, it more or less defined Britain in the 19th and early 20th centuries. Its repercussions in the wider world are still with us today. It also had a great impact on Britain herself: for example, on her economy, security, population, and eating habits. One might expect this to have been reflected in her society and culture. Indeed, this has now become the conventional wisdom: that Britain was steeped in imperialism domestically, which affected (or infected) almost everything Britons thought, felt, and did. This book examines this assumption critically against the broader background of contemporary British society. It argues that the empire had a far lower profile in Britain than it did abroad. Although Britain was an imperial nation in this period, she was never a genuine imperial society. As well as showing how this was possible, the book also discusses the implications of this attitude for Britain and her empire, and for the relationship between culture and imperialism more generally, bringing his study up to date by including the case of the present-day United States.

Bacteria have evolved diverse immunity mechanisms to protect themselves against the constant onslaught of bacteriophages 1 – 3 . Similar to how eukaryotic innate immune systems sense foreign invaders through pathogen-associated molecular patterns 4 (PAMPs), many bacterial immune systems that respond to bacteriophage infection require phage-specific triggers to be activated. However, the identities of such triggers and the sensing mechanisms remain largely unknown. Here we identify and investigate the anti-phage function of CapRel SJ46 , a fused toxin–antitoxin system that protects Escherichia coli against diverse phages. Using genetic, biochemical and structural analyses, we demonstrate that the C-terminal domain of CapRel SJ46 regulates the toxic N-terminal region, serving as both antitoxin and phage infection sensor. Following infection by certain phages, newly synthesized major capsid protein binds directly to the C-terminal domain of CapRel SJ46 to relieve autoinhibition, enabling the toxin domain to pyrophosphorylate tRNAs, which blocks translation to restrict viral infection. Collectively, our results reveal the molecular mechanism by which a bacterial immune system directly senses a conserved, essential component of phages, suggesting a PAMP-like sensing model for toxin–antitoxin-mediated innate immunity in bacteria. We provide evidence that CapRels and their phage-encoded triggers are engaged in a ‘Red Queen conflict’ 5 , revealing a new front in the intense coevolutionary battle between phages and bacteria. Given that capsid proteins of some eukaryotic viruses are known to stimulate innate immune signalling in mammalian hosts 6 – 10 , our results reveal a deeply conserved facet of immunity. Genetic, biochemical and structural studies provide insights into the function of Escherichia coli CapRel SJ46 as a fused anti-phage toxin–antitoxin system that binds SECΦ27 Gp57 capsid protein.

To accurately interpret COVID-19 seroprevalence surveys, knowledge of serum-IgG responses to SARS-CoV-2 with a better understanding of patients who do not seroconvert, is imperative. This study aimed to describe serum-IgG responses to SARS-CoV-2 in a cohort of patients with both severe and mild COVID-19, including extended studies of patients who remained seronegative more than 90 days post symptom onset. SARS-CoV-2-specific IgG antibody levels were quantified using two clinically validated and widely used commercial serological assays (Architect, Abbott Laboratories and iFlash 1800, YHLO), detecting antibodies against the spike and nucleocapsid proteins. Forty-seven patients (mean age 49 years, 38% female) were included. All (15/15) patients with severe symptoms and 29/32 (90.6%) patients with mild symptoms of COVID-19 developed SARS-CoV-2-specific IgG antibodies in serum. Time to seroconversion was significantly shorter (median 11 vs. 22 days, P = 0.04) in patients with severe compared to mild symptoms. Of the three patients without detectable IgG-responses after >90 days, all had detectable virus-neutralizing antibodies and in two, spike-protein receptor binding domain-specific IgG was detected with an in-house assay. Antibody titers were preserved during follow-up and all patients who seroconverted, irrespective of the severity of symptoms, still had detectable IgG levels >75 days post symptom onset. Patients with severe COVID-19 both seroconvert earlier and develop higher concentrations of SARS-CoV-2-specific IgG than patients with mild symptoms. Of those patients who not develop detectable IgG antibodies, all have detectable virus-neutralizing antibodies, suggesting immunity. Our results showing that not all COVID-19 patients develop detectable IgG using two validated commercial clinical methods, even over time, are vital for the interpretation of COVID-19 seroprevalence surveys.

Neutrinos were assumed to be massless particles until the discovery of the neutrino oscillation process. This phenomenon indicates that the neutrinos have non-zero masses and the mass eigenstates ( ν 1 , ν 2 , ν 3 ) are mixtures of their flavour eigenstates ( ν e , ν μ , ν τ ). The oscillations between different flavour eigenstates are described by three mixing angles ( θ 12 , θ 23 , θ 13 ), two differences of the squared neutrino masses of the ν 2 / ν 1 and ν 3 / ν 1 pairs and a charge conjugation parity symmetry violating phase δ CP . The Double Chooz experiment, located near the Chooz Electricité de France reactors, measures the oscillation parameter θ 13 using reactor neutrinos. Here, the Double Chooz collaboration reports the measurement of the mixing angle θ 13 with the new total neutron capture detection technique from the full data set, yielding sin 2 (2 θ 13 ) = 0.105 ± 0.014. This measurement exploits the multidetector configuration, the isoflux baseline and data recorded when the reactors were switched off. In addition to the neutrino mixing angle measurement, Double Chooz provides a precise measurement of the reactor neutrino flux, given by the mean cross-section per fission 〈 σ f 〉 = (5.71 ± 0.06) × 10 −43  cm 2 per fission, and reports an empirical model of the distortion in the reactor neutrino spectrum. The Double Chooz collaboration reports the neutrino oscillation parameter θ 13 from a measurement of the disappearance of reactor anti-electron neutrinos with the total neutron capture technique.

Feedhorn- and orthomode transducer- (OMT) coupled transition edge sensor (TES) bolometers have been designed and micro-fabricated to meet the optical specifications of the LiteBIRD high frequency telescope (HFT) focal plane. We discuss the design and optical characterization of two LiteBIRD HFT detector types: dual-polarization, dual-frequency-band pixels with 195/280 GHz and 235/337 GHz band centers. Results show well-matched passbands between orthogonal polarization channels and frequency centers within 3% of the design values. The optical efficiency of each frequency channel is conservatively reported to be within the range 0.64 - 0.72, determined from the response to a cryogenic, temperature-controlled thermal source. These values are in good agreement with expectations and either exceed or are within 10% of the values used in the LiteBIRD sensitivity forecast. Lastly, we report a measurement of loss in Nb/SiN x /Nb microstrip at 100 mK and over the frequency range 200–350 GHz, which is comparable to values previously reported in the literature.

Antigenic epitopes differ in their immunogenicity. Yewdell and colleagues show that B cell and antibody responses to influenza A virus infection display reproducible dynamic immunodominance hierarchies to viral hemagglutinin epitopes. Immunodominance (ID) defines the hierarchical immune response to competing antigens in complex immunogens. Little is known regarding B cell and antibody ID despite its importance in immunity to viruses and other pathogens. We show that B cells and serum antibodies from inbred mice demonstrate a reproducible ID hierarchy to the five major antigenic sites in the influenza A virus hemagglutinin globular domain. The hierarchy changed as the immune response progressed, and it was dependent on antigen formulation and delivery. Passive antibody transfer and sequential infection experiments demonstrated 'original antigenic suppression', a phenomenon in which antibodies suppress memory responses to the priming antigenic site. Our study provides a template for attaining deeper understanding of antibody ID to viruses and other complex immunogens.

The contribution of host genetic and nongenetic factors to immunological differences in humans remains largely undefined. Here, we generated bacterial-, fungal-, and viral-induced immune transcriptional profiles in an age- and sex-balanced cohort of 1,000 healthy individuals and searched for the determinants of immune response variation. We found that age and sex affected the transcriptional response of most immune-related genes, with age effects being more stimulus-specific relative to sex effects, which were largely shared across conditions. Although specific cell populations mediated the effects of age and sex on gene expression, including CD8⁺ T cells for age and CD4⁺ T cells and monocytes for sex, we detected a direct effect of these intrinsic factors for the majority of immune genes. The mapping of expression quantitative trait loci (eQTLs) revealed that genetic factors had a stronger effect on immune gene regulation than age and sex, yet they affected a smaller number of genes. Importantly, we identified numerous genetic variants that manifested their regulatory effects exclusively on immune stimulation, including a Candida albicans-specific master regulator at the CR1 locus. These response eQTLs were enriched in disease-associated variants, particularly for autoimmune and inflammatory disorders, indicating that differences in disease risk may result from regulatory variants exerting their effects only in the presence of immune stress. Together, this study quantifies the respective effects of age, sex, genetics, and cellular heterogeneity on the interindividual variability of immune responses and constitutes a valuable resource for further exploration in the context of different infection risks or disease outcomes.

Antibiotic resistance is a global health challenge, involving the transfer of bacteria and genes between humans, animals and the environment. Although multiple barriers restrict the flow of both bacteria and genes, pathogens recurrently acquire new resistance factors from other species, thereby reducing our ability to prevent and treat bacterial infections. Evolutionary events that lead to the emergence of new resistance factors in pathogens are rare and challenging to predict, but may be associated with vast ramifications. Transmission events of already widespread resistant strains are, on the other hand, common, quantifiable and more predictable, but the consequences of each event are limited. Quantifying the pathways and identifying the drivers of and bottlenecks for environmental evolution and transmission of antibiotic resistance are key components to understand and manage the resistance crisis as a whole. In this Review, we present our current understanding of the roles of the environment, including antibiotic pollution, in resistance evolution, in transmission and as a mere reflection of the regional antibiotic resistance situation in the clinic. We provide a perspective on current evidence, describe risk scenarios, discuss methods for surveillance and the assessment of potential drivers, and finally identify some actions to mitigate risks.In this Review, Larsson and Flach discuss the drivers of and bottlenecks for environmental evolution and transmission of antibiotic resistance, and they explore environmental surveillance strategies that could complement clinical surveillance systems.