Optical Spin Initialization and Non-Destructive Measurement in a Quantum Dot Molecule

The spin of an electron in a self-assembled InAs/GaAs quantum dot molecule is optically prepared and measured through the trion triplet states. A longitudinal magnetic field is used to tune two of the trion states into resonance, forming a superposition state through asymmetric spin exchange. As a result, spin-flip Raman transitions can be used for optical spin initialization, while separate trion states enable cycling transitions for non-destructive measurement. With two-laser transmission spectroscopy we demonstrate both operations simultaneously, something not previously accomplished in a single quantum dot.Comment: Accepted for publication in Phys. Rev. Let

A New Radiocarbon Chronology for Ancient Iron Production in the Meroe Region of Sudan

Recent archaeometallurgical investigations in Sudan have provided 97 radiocarbon dates which are used here to present a new chronology for ancient iron production associated with the Kingdom of Kush. Understandings of the formation, stratigraphy and dating of metallurgical waste deposits are used to demonstrate that iron production was practiced in the Meroe area for more than 1000 years, potentially starting as early as the 25th Dynasty period. Likely dates for the emergence and ending of iron smelting are considered in relation to political, economic and socio-cultural developments. The value and potential of this new chronology are explored, for example, in terms of insights into scale of production over time and resulting indications of organisation and management of this ancient technology.Qatar Sudan Archaeology Project grant 037 UCL Qatar core fundin

Trading particle shape with fluid symmetry: on the mobility matrix in 3D chiral fluids

Chiral fluids - such as fluids under rotation or a magnetic field as well as synthetic and biological active fluids - flow in a different way than ordinary ones. Due to symmetries broken at the microscopic level, chiral fluids may have asymmetric stress and viscosity tensors, for example giving rise to a hydrostatic torque or non-dissipative (odd) and parity-violating viscosities. In this article, we investigate the motion of rigid bodies in such an anisotropic fluid in the incompressible Stokes regime through the mobility matrix, which encodes the response of a solid body to forces and torques. We demonstrate how the form of the mobility matrix, which is usually determined by particle geometry, can be analogously controlled by the symmetries of the fluid. By computing the mobility matrix for simple shapes in a three-dimensional anisotropic chiral fluid, we predict counter-intuitive phenomena such as motion perpendicular to applied forces and spinning under the force of gravity.Comment: 31 pages, 7 figure

Trading particle shape with fluid symmetry: on the mobility matrix in 3-D chiral fluids

Chiral fluids – such as fluids under rotation or a magnetic field as well as synthetic and biological active fluids – flow in a different way than ordinary ones. Due to symmetries broken at the microscopic level, chiral fluids may have asymmetric stress and viscosity tensors, for example giving rise to a hydrostatic torque or non-dissipative (odd) and parity-violating viscosities. In this article, we investigate the motion of rigid bodies in such an anisotropic fluid in the incompressible Stokes regime through the mobility matrix, which encodes the response of a solid body to forces and torques. We demonstrate how the form of the mobility matrix, which is usually determined by particle geometry, can be analogously controlled by the symmetries of the fluid. By computing the mobility matrix for simple shapes in a three-dimensional (3-D) anisotropic chiral fluid, we predict counterintuitive phenomena such as motion at an angle to the direction of applied forces and spinning under the force of gravity

Methylthioadenosine reprograms macrophage activation through adenosine receptor stimulation

Regulation of inflammation is necessary to balance sufficient pathogen clearance with excessive tissue damage. Central to regulating inflammation is the switch from a pro-inflammatory pathway to an anti-inflammatory pathway. Macrophages are well-positioned to initiate this switch, and as such are the target of multiple therapeutics. One such potential therapeutic is methylthioadenosine (MTA), which inhibits TNFα production following LPS stimulation. We found that MTA could block TNFα production by multiple TLR ligands. Further, it prevented surface expression of CD69 and CD86 and reduced NF-KB signaling. We then determined that the mechanism of this action by MTA is signaling through adenosine A2 receptors. A2 receptors and TLR receptors synergized to promote an anti-inflammatory phenotype, as MTA enhanced LPS tolerance. In contrast, IL-1β production and processing was not affected by MTA exposure. Taken together, these data demonstrate that MTA reprograms TLR activation pathways via adenosine receptors to promote resolution of inflammation. © 2014 Keyel et al

Mathematically modelling the dynamics of cholesterol metabolism and ageing

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the UK. This conditionbecomes increasingly prevalent during ageing; 34.1% and 29.8% of males and females respectively, over 75years of age have an underlying cardiovascular problem. The dysregulation of cholesterol metabolism isinextricably correlated with cardiovascular health and for this reason low density lipoprotein cholesterol(LDL-C) and high density lipoprotein cholesterol (HDL-C) are routinely used as biomarkers of CVD risk. Theaim of this work was to use mathematical modelling to explore how cholesterol metabolism is affectedby the ageing process. To do this we updated a previously published whole-body mathematical model ofcholesterol metabolism to include an additional 96 mechanisms that are fundamental to this biologicalsystem. Additional mechanisms were added to cholesterol absorption, cholesterol synthesis, reversecholesterol transport (RCT), bile acid synthesis, and their enterohepatic circulation. The sensitivity of themodel was explored by the use of both local and global parameter scans. In addition, acute cholesterolfeeding was used to explore the effectiveness of the regulatory mechanisms which are responsible formaintaining whole-body cholesterol balance. It was found that our model behaves as a hypo-responderto cholesterol feeding, while both the hepatic and intestinal pools of cholesterol increased significantly.The model was also used to explore the effects of ageing in tandem with three different cholesterolester transfer protein (CETP) genotypes. Ageing in the presence of an atheroprotective CETP genotype,conferring low CETP activity, resulted in a 0.6% increase in LDL-C. In comparison, ageing with a genotypereflective of high CETP activity, resulted in a 1.6% increase in LDL-C. Thus, the model has illustrated theimportance of CETP genotypes such as I405V, and their potential role in healthy ageing

Non-basic amino acids in the hemagglutinin proteolytic cleavage site of a European H9N2 avian influenza virus modulate virulence in turkeys

H9N2 avian influenza virus (AIV) is the most widespread low pathogenic (LP) AIV in poultry and poses a serious zoonotic risk. Vaccination is used extensively to mitigate the economic impact of the virus. However, mutations were acquired after long-term circulation of H9N2 virus in poultry, particularly in the hemagglutinin (HA) proteolytic cleavage site (CS), a main virulence determinant of AIV. Compared to chickens, little is known about the genetic determinants for adaptation of H9N2 AIV to turkeys. Here, we describe 36 different CS motifs in Eurasian H9N2 viruses identified from 1966 to 2019. The European H9N2 viruses specify unique HACS with particular polymorphism by insertion of non-basic amino acids at position 319. Recombinant viruses carrying single HACS mutations resembling field viruses were constructed (designated G319, A319, N319, S319, D319 and K319). Several viruses replicated to significantly higher titers in turkey cells than in chicken cells. Serine proteases were more efficient than trypsin to support multicycle replication in mammalian cells. Mutations affected cell-to-cell spread and pH-dependent HA fusion activity. In contrast to chickens, mutations in the HACS modulated clinical signs in inoculated and co-housed turkeys. G319 exhibited the lowest virulence, however, it replicated to significantly higher titers in contact-turkeys and in vitro. Interestingly, H9N2 viruses, particularly G319, replicated in brain cells of turkeys and to a lesser extent in mammalian brain cells independent of trypsin. Therefore, the silent circulation of potentially zoonotic H9N2 viruses in poultry should be monitored carefully. These results are important for understanding the adaptation of H9N2 in poultry and replication in mammalian cells

3D reconstruction of SARS-CoV-2 infection in ferrets emphasizes focal infection pattern in the upper respiratory tract: [Preprint]

The visualization of viral pathogens in infected tissues is an invaluable tool to understand spatial virus distribution, localization, and cell tropism in vivo. Commonly, virus-infected tissues are analyzed using conventional immunohistochemistry in paraffin-embedded thin sections. Here, we demonstrate the utility of volumetric three-dimensional (3D) immunofluorescence imaging using tissue optical clearing and light sheet microscopy to investigate host-pathogen interactions of pandemic SARS-CoV-2 in ferrets at a mesoscopic scale. The superior spatial context of large, intact samples (> 150 mm3) allowed detailed quantification of interrelated parameters like focus-to-focus distance or SARS-CoV-2-infected area, facilitating an in-depth description of SARS-CoV-2 infection foci. Accordingly, we could confirm a preferential infection of the ferret upper respiratory tract by SARS-CoV-2 and emphasize a distinct focal infection pattern in nasal turbinates. Conclusively, we present a proof-of-concept study for investigating critically important respiratory pathogens in their spatial tissue morphology and demonstrate the first specific 3D visualization of SARS-CoV-2 infection

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.