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

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

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

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

Efficient Thermal Conductance in Organometallic Perovskite CH3NH3PbI3 Films

Perovskite-based optoelectronic devices have shown great promise for solar conversion and other optoelectronic applications, but their long-term performance instability is regarded as a major obstacle to their widespread deployment. Previous works have shown that the ultralow thermal conductivity and inefficient heat spreading might put an intrinsic limit on the lifetime of perovskite devices. Here, we report the observation of a remarkably efficient thermal conductance, with conductivity of 11.2 +/- 0.8 W m^-1 K^-1 at room temperature, in densely-packed perovskite CH3NH3PbI3 films, via noncontact time-domain thermal reflectance measurements. The temperature-dependent experiments suggest the important roles of organic cations and structural phase transitions, which are further confirmed by temperature-dependent Raman spectra. The thermal conductivity at room temperature observed here is over one order of magnitude larger than that in the early report, suggesting that perovskite device performance will not be limited by thermal stability

Mediating effect of successful aging on the relationship between psychological resilience and death anxiety among middle-aged and older adults with hypertension

ObjectiveThe aging trend of China's population is severe and successful aging (SA) is imminent. Aging can lead to various chronic diseases, with hypertension being the most common. Due to this lifelong disease, patients suffer from many anxieties, as death anxiety (DA) can be the most prevalent. Studies have exhibited that middle-aged adults approaching the transition to an older state show more pronounced DA than the more senior. It has been suggested that psychological resilience (PR) can reduce DA. Therefore, this study aimed to analyze the mediating effect of SA between PR and DA in middle-aged and older adults with hypertension.MethodsA cross-sectional survey was designed. From August to December 2021, 298 middle-aged and older adults with hypertension were selected by multistage cluster random sampling in three districts (Ling he District, Gu ta District, and Tai He District) of Jinzhou City, Liaoning Province. They were surveyed using the demographic questionnaires, the Conner-Davidson Resilience Scale, the Successful Aging Inventory, and the Chinese version of a Likert-type Templer-Death Anxiety Scale. Descriptive analyses, independent sample T-test, and one-way analysis of variance (ANOVA) were used to describe demographic characteristics among hypertensive patients with different characteristics, respectively. Statistics were considered significant when P < 0.05. Pearson correlation coefficients describe the relationship between PR, SA, and DA. The research model was shaped through Structural Equation Modeling (SEM). SPSS PROCESS macro was used to verify the mediation model. A binary logistic regression model was used with DA as the dependent variable.ResultsThe scores for PR, SA, and DA in hypertensive patients are (49.52 ± 14.38) points, (51.22 ± 7.63) points, and (46.67 ± 9.03) points. PR was negatively correlated with DA (r = −0.307, P < 0.01). Moreover, incorporating SA as a mediating variable in PR and DA, SA was positively correlated with PR (r = 0.335, P < 0.01) and DA (r = 0.085, P > 0.05). The direct effect is opposite to the sign of the indirect effect. There is a suppression between PR and DA with a percentage of 20.7%. Good self-assessed health status [0.057 (0.018, 0.183)] may be a protective factor for DA.ConclusionHealthcare providers should improve the PR of middle-aged and older adults with hypertension through interventions that reduce DA and increase the likelihood of SA