Stratification of hospitalized COVID-19 patients into clinical severity progression groups by immuno-phenotyping and machine learning

Quantitative or qualitative differences in immunity may drive clinical severity in COVID-19. Although longitudinal studies to record the course of immunological changes are ample, they do not necessarily predict clinical progression at the time of hospital admission. Here we show, by a machine learning approach using serum pro-inflammatory, anti-inflammatory and anti-viral cytokine and anti-SARS-CoV-2 antibody measurements as input data, that COVID-19 patients cluster into three distinct immune phenotype groups. These immune-types, determined by unsupervised hierarchical clustering that is agnostic to severity, predict clinical course. The identified immune-types do not associate with disease duration at hospital admittance, but rather reflect variations in the nature and kinetics of individual patient's immune response. Thus, our work provides an immune-type based scheme to stratify COVID-19 patients at hospital admittance into high and low risk clinical categories with distinct cytokine and antibody profiles that may guide personalized therapy. Developing predictive methods to identify patients with high risk of severe COVID-19 disease is of crucial importance. Authors show here that by measuring anti-SARS-CoV-2 antibody and cytokine levels at the time of hospital admission and integrating the data by unsupervised hierarchical clustering/machine learning, it is possible to predict unfavourable outcome

Nickel nanoparticles-super yellow (PDY-132) nanoblends for organic light emitting devices

We report the synthesis of nickel nanoparticles (NPs) by wet chemical route and its blend with emissive PDY-132(super yellow) matrix for application in Organic Light-Emitting Devices (OLEDs). Wet Chemical Synthesis allows the successful synthesis of CTAB (Cetyl Trimethyl Ammonium Bromide) capped nickel (Ni) nanoparticles having a size of 5-7 nm. The synthesized colloidal having nanoparticles can be easily mixed with emissive polymer solutions to obtain a blend for OLED application. From the experimental results, it is observed that turn on voltage decreases to 3.54V from 9V and current increases to 14mA from 4mA after adding Ni NPs into the emissive layer. The narrowing and sharpening of electroluminescence were observed

Li-doped ZnO nanostructures for the organic light emitting diode application

ZnO and Li-doped ZnO nanoparticles have been synthesized by a simple wet chemical method for its potential application in Organic Light Emitting Diodes (OLED). Studies have been undertaken for structural as well as optical properties of ZnO after Li doping with various concentrations. Field Emission Scanning Electron Microscopy indicated the nanodots structure has formed. X-ray Diffraction reveals the pure hexagonal phase of the wurtzite structure. UV Visible suggested the exciton characteristic at room temperature while Photoluminescence spectra reveal two different regions (ultraviolet and blue). Synthesized materials have been blended with Poly [9, 9dioctylfluoreny1-2,7-diyl] (PFO) and prototype OLED has been fabricated using these materials as an emissive layer. Electroluminescence spectra show prominent blue emission at 435 nm at 8 V. Current-Voltage (I-V) curve reveal that the turn-on voltages reduce as compared with pristine PFO device

Study of injection and transport properties of metal/organic interface using HAT-CN molecules as hole injection layer

1,4,5,8,9,11-hexaazatriphenylene-hexacarbonitrile (HAT-CN) molecule have been studied as hole injection layer for application in organic semiconductor based devices with potential to modify the electronic properties of electrodes due to its strong electron-withdrawing property. Thermally stable hole transport material 2, 7-bis [N, N-bis (4-methoxy-phenyl) amino] -9, 9-spirobifluorene (MeO-Spiro-TPD) has been used to fabricate hole only devices. To make the injection efficient at metal/organic interface and to reduce the driving voltage of the organic devices, the interface has been modified with a thin layer of highly electron accepting HAT-CN material. Modified interface has been investigated at a different range of thicknesses of HAT-CN. This interface modification resulted in the switching of injection limited transport to space charge limited conduction mechanism with the introduction of HAT-CN layer at metal/organic interfaces. The hole injection property has been found to increase with an increase in HAT-CN thickness. When these modified substrates were used as a hole injecting contacts in organic light emitting diodes (OLEDs), they have shown an increase in current density and device efficiency

Mg-doped ZnO nanostructures for efficient Organic Light Emitting Diode

ZnO and Mg-doped ZnO nanostructures have been synthesized by a hydrothermal method for its potential application in Organic Light Emitting Diodes (OLED). Studies have been undertaken for structural as well as optical properties of ZnO after Mg doping with various concentrations. Field Emission Scanning Electron Microscopy with Energy-dispersive X-ray analysis reveals the morphology and chemical composition of nanostructures shows the formation of ZnO rod-like structure which, interestingly, converted into the multi-pod structure with Mg doping. X-ray diffraction reveals the hexagonal phase of the wurtzite structure of ZnO. UV-Visible absorption spectroscopy suggests the exciton characteristic, at room temperature, with band gap variation while Photoluminescence spectra reveal emission in two different spectral regions (ultraviolet and blue). Synthesized materials have been blended with Poly [9, 9-dioctylfluoreny1-2, 7-diyl] (PFO) and prototype OLED has been fabricated using these materials as an emissive layer. An electroluminescence spectrum shows prominent blue emission at 433 nm, 460 nm, and 490 nm at 6 V. Current-Voltage (I-V) characteristics indicate that the OLED device with 10% Mg doping in ZnO is most stable compared to others

Image_1_Ibrutinib directly reduces CD8+T cell exhaustion independent of BTK.tif

IntroductionCytotoxic CD8+ T cell (CTL) exhaustion is a dysfunctional state of T cells triggered by persistent antigen stimulation, with the characteristics of increased inhibitory receptors, impaired cytokine production and a distinct transcriptional profile. Evidence from immune checkpoint blockade therapy supports that reversing T cell exhaustion is a promising strategy in cancer treatment. Ibrutinib, is a potent inhibitor of BTK, which has been approved for the treatment of chronic lymphocytic leukemia. Previous studies have reported improved function of T cells in ibrutinib long-term treated patients but the mechanism remains unclear. We investigated whether ibrutinib directly acts on CD8+ T cells and reinvigorates exhausted CTLs. MethodsWe used an established in vitro CTL exhaustion system to examine whether ibrutinib can directly ameliorate T cell exhaustion. Changes in inhibitory receptors, transcription factors, cytokine production and killing capacity of ibrutinib-treated exhausted CTLs were detected by flow cytometry. RNA-seq was performed to study transcriptional changes in these cells. Btk deficient mice were used to confirm that the effect of ibrutinib was independent of BTK expression.ResultsWe found that ibrutinib reduced exhaustion-related features of CTLs in an in vitro CTL exhaustion system. These changes included decreased inhibitory receptor expression, enhanced cytokine production, and downregulation of the transcription factor TOX with upregulation of TCF1. RNA-seq further confirmed that ibrutinib directly reduced the exhaustion-related transcriptional profile of these cells. Importantly, using btk deficient mice we showed the effect of ibrutinib was independent of BTK expression, and therefore mediated by one of its other targets. DiscussionOur study demonstrates that ibrutinib directly ameliorates CTL exhaustion, and provides evidence for its synergistic use with cancer immunotherapy.</p