Impaired HA-specific T follicular helper cell and antibody responses to influenza vaccination are linked to inflammation in humans.

Funder: National Institute for Health Research (NIHR)Antibody production following vaccination can provide protective immunity to subsequent infection by pathogens such as influenza viruses. However, circumstances where antibody formation is impaired after vaccination, such as in older people, require us to better understand the cellular and molecular mechanisms that underpin successful vaccination in order to improve vaccine design for at-risk groups. Here, by studying the breadth of anti-haemagglutinin (HA) IgG, serum cytokines, and B and T cell responses by flow cytometry before and after influenza vaccination, we show that formation of circulating T follicular helper (cTfh) cells was associated with high-titre antibody responses. Using Major Histocompatability Complex (MHC) class II tetramers, we demonstrate that HA-specific cTfh cells can derive from pre-existing memory CD4+ T cells and have a diverse T cell receptor (TCR) repertoire. In older people, the differentiation of HA-specific cells into cTfh cells was impaired. This age-dependent defect in cTfh cell formation was not due to a contraction of the TCR repertoire, but rather was linked with an increased inflammatory gene signature in cTfh cells. Together, this suggests that strategies that temporarily dampen inflammation at the time of vaccination may be a viable strategy to boost optimal antibody generation upon immunisation of older people

Gaussian Boson Sampling with Pseudo-Photon-Number Resolving Detectors and Quantum Computational Advantage

We report new Gaussian boson sampling experiments with pseudo-photon-number-resolving detection, which register up to 255 photon-click events. We consider partial photon distinguishability and develop a more complete model for characterization of the noisy Gaussian boson sampling. In the quantum computational advantage regime, we use Bayesian tests and correlation function analysis to validate the samples against all current classical mockups. Estimating with the best classical algorithms to date, generating a single ideal sample from the same distribution on the supercomputer Frontier would take ~ 600 years using exact methods, whereas our quantum computer, Jiuzhang 3.0, takes only 1.27 us to produce a sample. Generating the hardest sample from the experiment using an exact algorithm would take Frontier ~ 3.1*10^10 years.Comment: submitted on 10 Apri

Therapeutic potential of transplanted placental mesenchymal stem cells in treating Chinese miniature pigs with acute liver failure

<p>Abstract</p> <p>Background</p> <p>Stem cell-based therapy to treat liver diseases is a focus of current research worldwide. So far, most such studies depend on rodent hepatic failure models. The purpose of this study was to isolate mesenchymal stem cells from human placenta (hPMSCs) and determine their therapeutic potential for treating Chinese experimental miniature pigs with acute liver failure (ALF).</p> <p>Methods</p> <p>hPMSCs were isolated and analyzed for their purity and differentiation potential before being employed as the donor cells for transplantation. ALF models of Chinese experimental miniature pigs were established and divided into four groups: no cell transplantation; hPMSCs transplantation via the jugular vein; X-ray-treated hPMSCs transplantation via the portal vein; and hPMSCs transplantation via the portal vein. The restoration of biological functions of the livers receiving transplantation was assessed via a variety of approaches such as mortality rate determination, serum biochemical analysis, and histological, immunohistochemical, and genetic analysis.</p> <p>Results</p> <p>hPMSCs expressed high levels of CD29, CD73, CD13, and CD90, had adipogenic, osteogenic, and hepatic differentiation potential. They improved liver functions <it>in vivo </it>after transplantation into the D-galactosamine-injured pig livers as evidenced by the fact that ALT, AST, ALP, CHE, TBIL, and TBA concentrations returned to normal levels in recipient ALF pigs. Meanwhile, histological data revealed that transplantation of hPMSCs via the portal vein reduced liver inflammation, decreased hepatic denaturation and necrosis, and promoted liver regeneration. These ameliorations were not found in the other three groups. The result of 7-day survival rates suggested that hPMSCs transplantation via the portal vein was able to significantly prolong the survival of ALF pigs compared with the other three groups. Histochemistry and RT-PCR results confirmed the presence of transplanted human cells in recipient pig livers (Groups III, IV).</p> <p>Conclusions</p> <p>Our data revealed that hPMSCs could not only differentiate into hepatocyte-like cells <it>in vitro </it>and <it>in vivo</it>, but could also prolong the survival time of ALF pigs. Regarding the transplantation pathways, the left branch of the portal vein inside the liver was superior to the jugular vein pathway. Thus, hPMSCs transplantation through the portal vein by B-ultrasonography may represent a superior approach for treating liver diseases.</p

Trends and predictions of malnutrition and obesity in 204 countries and territories: an analysis of the Global Burden of Disease Study 2019.

BackgroundMalnutrition and obesity are interdependent pathologies along the same spectrum. We examined global trends and projections of disability-adjusted life years (DALYs) and deaths from malnutrition and obesity until 2030.MethodsUsing data from the 2019 Global Burden of Disease study involving 204 countries and territories, trends in DALYs and deaths were described for obesity and malnutrition from 2000 to 2019, stratified by geographical regions (as defined by WHO) and Socio-Demographic Index (SDI). Malnutrition was defined according to the 10th revision of International Classification of Diseases codes for nutritional deficiencies, stratified by malnutrition type. Obesity was measured via body mass index (BMI) using metrics related to national and subnational estimates, defined as BMI ≥25 kg/m2. Countries were stratified into low, low-middle, middle, high-middle, and high SDI bands. Regression models were constructed to predict DALYs and mortality up to 2030. Association between age-standardised prevalence of the diseases and mortality was also assessed.FindingsIn 2019, age-standardised malnutrition-related DALYs was 680 (95% UI: 507-895) per 100,000 population. DALY rates decreased from 2000 to 2019 (-2.86% annually), projected to fall 8.4% from 2020 to 2030. Africa and low SDI countries observed highest malnutrition-related DALYs. Age-standardised obesity-related DALY estimates were 1933 (95% UI: 1277-2640). Obesity-related DALYs rose 0.48% annually from 2000 to 2019, predicted to increase by 39.8% from 2020 to 2030. Highest obesity-related DALYs were in Eastern Mediterranean and middle SDI countries.InterpretationThe ever-increasing obesity burden, on the backdrop of curbing the malnutrition burden, is predicted to rise further.FundingNone

Design of algorithm to optimize irregular geometries for 3D printing

The utilisation of the conventional extrusion based 3D printers in the medical industry has been rapidly increasing. However, there are limitations for medical applications that might be ignored in the traditional fabrication process. As an example, while printing a model by Fused Deposition Modelling (FDM), the Z-axis resolution is a limiting factor while printing irregular geometries where the gradient of the curve is non-linear producing a jagged surface which is not ideal. In this literature, curvature analysis techniques are utilised to determine a path where a seam will be made within the irregular geometrical object. The path, determined by feature extraction algorithms, will be marked for a cut to flatten the computer aided design (CAD) model using an add-on to facilitate the user experience for new users to the open sourced programme (Blender) before it is 3D printed. This approach allows the increase in resolution precision for 3D printing using conventional FDM machines and addresses one of the challenges faced in conventional extrusion-based 3D printers for 3D models with irregular curvature.Bachelor of Engineering (Chemical and Biomolecular Engineering

Combined Dynamic Voltage Scaling and Adaptive Body Biasing for Heterogeneous Distributed Real-time Embedded Systems

Abstract — Dynamic voltage scaling (DVS) is a powerful technique for reducing dynamic power consumption in a computing system. However, as technology feature size continues to scale, leakage power is increasing and will limit power savings obtained by DVS alone. Previous system-level real-time scheduling approaches use DVS alone to optimize power consumption without considering leakage power. To overcome this limitation, we propose a new scheduling algorithm that combines DVS and adaptive body biasing (ABB) to simultaneously optimize both dynamic power consumption and leakage power consumption for real-time distributed embedded systems. First, we derive an analytical expression to determine the optimal supply voltage and body bias voltage under a given clock frequency. Based on this expression, we compute the optimal energy consumption at a given clock frequency and analyze the tradeoff between energy consumption and execution time for a set of tasks with precedence relationships and real-time constraints. We then propose a scheduling algorithm to reduce total power consumption under given real-time constraints. This algorithm also considers variations in power consumption of different tasks and characteristics of different voltage-scalable processing elements (PEs) to maximize power reduction. Experimental results show that the average power reduction of our technique with respect to DVS alone is 34.7%, while the average saving compared to no voltage scaling is 68.3 % for the 0.07µm technology. I