NanoAPC deliver antigen, IL-2 and co-stimulatory molecules to antigen specific T cells and activate viral specific T cells in chronic infections

This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University.The study of the immune system has provided insight in the mechanism of protection induced by vaccination; primarily that most clinically protective vaccines are potent in generating neutralizing antibody responses. However, vaccination fails to protect against a wide range of acquired chronic infections caused by viruses, such as HIV, HBV and HCV. One of the major reasons for weak responses to therapeutic vaccine is the impaired function of effector T cells resulting from viral persistence. Although IL-2 can potently increase effect function of viral specific T cells, systemic administration of IL-2 induces organ pathology and expansion of Treg cells. In this study, we have now developed a novel vaccine delivery system IL-2-nanoAPC delivering antigen-MHC complexes (pMHC), co-stimulatory molecules and IL-2 to antigen specific T cells. NanoAPC are derived from the endoplasmic reticulum (ER) membranes of human B cell line 721.221 engineered with selected HLA allele and IL-2 as the ER retention proteins. The IL-2-nanoAPC interacted with antigen specific T cells, induced immune synapses and expression of high affinity IL-2 receptor and enhanced effector function of antigen specific T cells, but did not affect bystander T cells and Foxp3+ Treg cells. Together with pMHC, co-stimulatory molecules, the selective delivery of IL-2 not only increased the CD4 and CD8 T cell responses to viral antigens but also enhanced TCR proximal signalling and suppressed expression of PD1 molecules on IFNγ producing effector CD8 T cells. We also found that the co-induction of T helper responses by IL-2-nanoAPC in a mixed culture could increase CD8 T cell responses to viral antigen. The IL-2-nanoAPC effectively induced responses of CD4 and CD8 T cells from chronic HBV patients. The results demonstrate that selective delivery of IL-2, together with pMHC and co-stimulatory molecules, by nanoAPC to antigen specific T cells has potential to recover anti-viral immune responses in chronic HBV patients

Modeling Spatiotemporal Periodicity and Collaborative Signal for Local-Life Service Recommendation

Online local-life service platforms provide services like nearby daily essentials and food delivery for hundreds of millions of users. Different from other types of recommender systems, local-life service recommendation has the following characteristics: (1) spatiotemporal periodicity, which means a user's preferences for items vary from different locations at different times. (2) spatiotemporal collaborative signal, which indicates similar users have similar preferences at specific locations and times. However, most existing methods either focus on merely the spatiotemporal contexts in sequences, or model the user-item interactions without spatiotemporal contexts in graphs. To address this issue, we design a new method named SPCS in this paper. Specifically, we propose a novel spatiotemporal graph transformer (SGT) layer, which explicitly encodes relative spatiotemporal contexts, and aggregates the information from multi-hop neighbors to unify spatiotemporal periodicity and collaborative signal. With extensive experiments on both public and industrial datasets, this paper validates the state-of-the-art performance of SPCS.Comment: KDAH CIKM'23 Worksho

Long-term water use efficiency and non-structural carbohydrates of dominant tree species in response to nitrogen and water additions in a warm temperate forest

Nitrogen (N) deposition tends to accompany precipitation in temperate forests, and vegetation productivity is mostly controlled by water and N availability. Many studies showed that tree species response to precipitation or N deposition alone influences, while the N deposition and precipitation interactive effects on the traits of tree physiology, especially in non-structural carbohydrates (NSCs) and long-term water use efficiency (WUE), are still unclear. In this study, we measured carbon stable isotope (delta C-13), total soluble sugar and starch content, total phenols, and other physiological traits (e.g., leaf C:N:P stoichiometry, lignin, and cellulose content) of two dominant tree species (Quercus variabilis Blume and Liquidambar formosana Hance) under canopy-simulated N deposition and precipitation addition to analyze the changes of long-term WUE and NSC contents and to explain the response strategies of dominant trees to abiotic environmental changes. This study showed that N deposition decreased the root NSC concentrations of L. formosana and the leaf lignin content of Q. variabilis. The increased precipitation showed a negative effect on specific leaf area (SLA) and a positive effect on leaf WUE of Q. variabilis, while it increased the leaf C and N content and decreased the leaf cellulose content of L. formosana. The nitrogen-water interaction reduced the leaf lignin and total phenol content of Q. variabilis and decreased the leaf total phenol content of L. formosana, but it increased the leaf C and N content of L. formosana. Moreover, the response of L. formosana to the nitrogen-water interaction was greater than that of Q. variabilis, highlighting the differences between the two dominant tree species. The results showed that N deposition and precipitation obviously affected the tree growth strategies by affecting the NSC contents and long-term WUE. Canopy-simulated N deposition and precipitation provide a new insight into the effect of the nitrogen-water interaction on tree growth traits in a temperate forest ecosystem, enabling a better prediction of the response of dominant tree species to global change

Monolithic quantum-dot distributed feedback laser array on silicon

Electrically-pumped lasers directly grown on silicon are key devices interfacing silicon microelectronics and photonics. We report here, for the first time, an electrically-pumped, room-temperature, continuous-wave (CW) and single-mode distributed feedback (DFB) laser array fabricated in InAs/GaAs quantum-dot (QD) gain material epitaxially grown on silicon. CW threshold currents as low as 12 mA and single-mode side mode suppression ratios (SMSRs) as high as 50 dB have been achieved from individual devices in the array. The laser array, compatible with state-of-the-art coarse wavelength division multiplexing (CWDM) systems, has a well-aligned channel spacing of 20 0.2 nm and exhibits a record wavelength coverage range of 100 nm, the full span of the O-band. These results indicate that, for the first time, the performance of lasers epitaxially grown on silicon is elevated to a point approaching real-world CWDM applications, demonstrating the great potential of this technology

Polar phase transitions in heteroepitaxial stabilized La0.5Y0.5AlO3 thin films

PAPER Polar phase transitions in heteroepitaxial stabilized La0.5Y0.5AlO3 thin films Shenghua Liu1, Chunfeng Zhang1, Mengya Zhu1, Qian He2, Jak Chakhalian3, Xiaoran Liu3,4, Albina Borisevich2, Xiaoyong Wang1 and Min Xiao1,4 Published 1 September 2017 • © 2017 IOP Publishing Ltd Journal of Physics: Condensed Matter, Volume 29, Number 40 Article PDF Figures References PDF 18 Total downloads Turn on MathJax Get permission to re-use this article Share this article Article information Abstract We report on the fabrication of epitaxial La0.5Y0.5AlO3 ultrathin films on (001) LaAlO3 substrates. Structural characterizations by scanning transmission electron microscopy and x-ray diffraction confirm the high quality of the film with a − b + c − AlO6 octahedral tilt pattern. Unlike either of the nonpolar parent compound, LaAlO3 and YAlO3, second harmonic generation measurements on the thin films suggest a nonpolar–polar phase transition at T c near 500 K, and a polar–polar phase transition at T a near 160 K. By fitting the angular dependence of the second harmonic intensities, we further propose that the two polar structures can be assigned to the Pmc2 1 and Pmn2 1 space group, while the high temperature nonpolar structure belongs to the Pbnm space group

Electrically pumped continuous-wave O-band quantum-dot superluminescent diode on silicon

High-power, broadband quantum-dot (QD) superluminescent diodes (SLDs) are ideal light sources for optical coherence tomography (OCT) imaging systems but have previously mainly been fabricated on native GaAs- or InP-based substrates. Recently, significant progress has been made to emigrate QD SLDs from native substrates to silicon substrates. Here, we demonstrate electrically pumped continuous-wave InAs QD SLDs monolithically grown on silicon substrates with significantly improved performance thanks to the achievement of a low density of defects in the III-V epilayers. The fabricated narrow-ridge-waveguide device exhibits a maximum 3 dB bandwidth of 103 nm emission spectrum centered at the O-band together with a maximum single facet output power of 3.8 mW at room temperature. The silicon-based SLD has been assessed for application in an OCT system. Under optimized conditions, a predicted axial resolution of ∼5.3µm is achieved with a corresponding output power of 0.66 mW/facet

Study on the impact frequency modulation of self-excited oscillating pulsed SC-CO2 jet

The SC-CO2 jet drilling and completion technology can ensure the stability of coalbed methane wells, improve drilling speed and rock breaking efficiency, and has a wide application prospect. However, the high energy consumption and complex system of coal breaking limit its engineering application. The impact frequency of self-excited oscillation pulse SC-CO2 jet is the same as the natural frequency of coal and rock mass or satisfies the phase relationship, which can give full play to the resonance effect and achieve a better coal breaking effect. The nozzle structure is the key to affect the jet impact frequency. The existing frequency modulation method of self-resonating pulsed water jet is not suitable for the SC-CO2 jet. In order to realize the modulation of the impact frequency of the SC-CO2 jet, a large eddy simulation was used to study the influence law of different nozzle structures on the impact frequency of self-excited oscillation pulse SC-CO2 jet, and the influence degree of different nozzle structure parameters on jet impact frequency was obtained by weight analysis. The influence rule of nozzle structure on the jet impact frequency and the reliability of jet impact frequency modulation method are verified by jet impact frequency measurement experiment and coal breaking experiment. The results show that the diameter and length of the oscillating cavity, and the angle of the collision wall are the key factors affecting the jet impact frequency. The jet impact frequency can be substantially modulated by adjusting the structure of the oscillating cavity, so as to achieve the resonance effect. By adjusting the oscillating cavity structure, the jet impact frequency forms resonance with the inherent frequency of coal, then the coal breaking effect is significantly improved, and the smaller the resonance multiplier, the better the coal breaking effect of the jet, which can effectively improve the coal breaking efficiency. When the natural frequency of coal is 25 Hz, the outlet diameter of the upstream and downstream nozzle is set as 2.5 mm and 3.0 mm, and the diameter, length and angle of the oscillating chamber are adjusted to 10 mm, 3 mm and 120° respectively. The jet impact frequency reaches 25051.83 Hz, which is 1002.0 times of the natural frequency of coal and forms a resonance effect with the natural frequency of coal, effectively improves the coal breaking efficiency

A study on the reasonable dietary trajectory of elderly people in the community and its correlation with body mass index

ObjectiveTo explore the reasonable dietary trajectory of elderly people in the community and to test the correlation between different dietary trajectories and body mass index (BMI) of the elderly people in the community to provide a reference for these individuals to formulate scientific interventions and cultivate healthy living habits.MethodsThe data of The Chinese Longitudinal Healthy Longevity Survey (CLHLS) from 2011 to 2018 were used to evaluate the dietary status of elderly people in the community according to their diet, and body mass index was calculated according to height and weight. The latent variable growth mixed (LGMM) model was used to analyze the development trajectory of diet in elderly people, and the multivariate logistic regression model was used to test the relationship between different dietary development trajectories and BMI changes as well as to test the correlation between different dietary trajectories and BMI of the elderly people in the community.ResultsThe LGMM fit four dietary trajectories of elderly individuals: the continuous reasonable diet group (37.81%), the dietary behavior decline group (28.84%), the continuous unreasonable diet group (20.16%), and the dietary behavior improvement group (13.19%). The results showed that factors including male sex, rural setting, being spouseless, nonformal education status, not being wealthy, living alone, and having tooth loss were more likely to be classified as the “persistently unreasonable diet group” (p < 0.05). The logistic regression results showed that the “continuous reasonable diet group” and the “dietary behavior improvement group” were significantly correlated with the development of obesity to a normal BMI.ConclusionThe dietary behavior of the elderly was significantly correlated with BMI value, and improving the reasonable dietary behavior of the elderly could reduce the high BMI to the normal range, but could not restore the low BMI to the normal range, indicating that reasonable dietary behavior is an important measure to prevent and improve overweight or obesity in the elderly. There is significant heterogeneity in the dietary behavior of the elderly, and community medical staff should identify the risk factors of various dietary behaviors of other groups as soon as possible, and provide corresponding intervention strategies to help them change their poor dietary behaviors and improve their nutritional status