Neutralizing antibody vaccine for pandemic and pre-emergent coronaviruses

Betacoronaviruses (betaCoVs) caused the severe acute respiratory syndrome (SARS) and Middle East Respiratory Syndrome (MERS) outbreaks, and the SARS-CoV-2 pandemic1–4. Vaccines that elicit protective immunity against SARS-CoV-2 and betaCoVs circulating in animals have the potential to prevent future betaCoV pandemics. Here, we show that macaque immunization with a multimeric SARS-CoV-2 receptor binding domain (RBD) nanoparticle adjuvanted with 3M-052/Alum elicited cross-neutralizing antibody (cross-nAb) responses against batCoVs, SARS-CoV-1, SARS-CoV-2, and SARS-CoV-2 variants B.1.1.7, P.1, and B.1.351. Nanoparticle vaccination resulted in a SARS-CoV-2 reciprocal geometric mean neutralization ID50 titer of 47,216, and protection against SARS-CoV-2 in macaque upper and lower respiratory tracts. Importantly, nucleoside-modified mRNA encoding a stabilized transmembrane spike or monomeric RBD also induced SARS-CoV-1 and batCoV cross-nAbs, albeit at lower titers. These results demonstrate current mRNA vaccines may provide some protection from future zoonotic betaCoV outbreaks, and provide a platform for further development of pan-betaCoV vaccines

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Molecular beam epitaxial growth of novel semiconductor systems

SIGLEAvailable from British Library Document Supply Centre- DSC:D60670 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Subband occupancies and zero-field spin splitting in InSb-CdTe heterojunctions: magnetotransport experiments and self-consistent calculations

Contains fulltext : 112811.pdf (publisher's version ) (Open Access

Genetic influences on motion sickness susceptibility in adult women: a classical twin study

Background: Motion sickness is a common and potentially debilitating condition that characteristically occurs in situations of conflicting sensory input. While the precise stimuli that give rise to this trait are increasingly well characterized, the underlying determinants of individual susceptibility to motion sickness remain unclear. This study uses a classical twin design to assess the influence of genetic and environmental factors. Methods: A postal survey was conducted in an age-matched sample of 3652 monozygotic (MZ) and dizygotic (DZ) adult female twins selected from the TwinsUK Registry. Study participants were asked to complete items from a validated questionnaire relating to their lifetime susceptibility to motion sickness. The relative contribution of genetic and environmental factors to motion sickness susceptibility was assessed using variance components analysis. Results: The response rate to the questionnaire was 78%. Approximately 40% of respondents reported at least moderate susceptibility to motion sickness. The pattern of responses among twins indicated a significant genetic contribution with heritability for a motion sickness factor score estimated as 57% (95% CI: 51%, 63%). The heritability of recalled motion sickness was at its highest in childhood (70% [59%, 80%]) and declined through puberty and the early adult years. Discussion and Conclusions: The findings highlight the importance of genetic factors in determining an individual's underlying propensity to motion sickness and should stimulate the search for specific susceptibility genes

MBE of (Hg,Cd)Te Final report

SIGLEAvailable from British Library Document Supply Centre- DSC:0678.231F(AD-A--202448)(microfiche) / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Mid-wavelength infrared resonant cavity enhanced photodiodes for infrared spectroscopic sensing of chemicals and other narrow-band optical signals

Inserting an infrared detector architecture into an optical cavity between two high-reflectivity mirrors allows incident light to reflect and pass through the detector multiple times, thereby enhancing absorption within the active region. This allows for a 40-100x thinner optical absorbing region compared to conventional infrared detector structures which reduces the detector dark current and noise and enhances SNR. We report the design, growth, fabrication and characterization of resonant cavity enhanced MWIR photodiodes on GaSb substrates. Devices on GaSb use AlAsSb/GaSb mirrors, AlAsSb spacer layers, and a narrow 96 nm InAsSb absorber. Dark current and detectivity behavior better than equivalent broadband nBn detectors in the literature have been observed. 34nm linewidth detector response is observed. Resonant cavity-enhanced photodiodes with resonant wavelengths of 3.6μm and 3.72μm are demonstrated with dark currents equal to or lower than Rule 07 over the operating temperature range of the device. D∗ in excess of 1×10 10 cm Hz 1/2W -1 at 300K and 8×10 10 cm Hz 1/2W -1 at 250K have been achieved. Amethyst Research has produced packaged resonant-cavity detectors. The 3.6 μm resonant-cavity enhanced photodiode was packaged within an Amethyst Research designed pre-amplifier package with an integrated TEC for detector cooling