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Neoantigens are peptides derived from non-synonymous mutations presented by human leukocyte antigens (HLAs), which are recognized by antitumour T cells1-14. The large HLA allele diversity and limiting clinical samples have restricted the study of the landscape of neoantigen-targeted T cell responses in patients over their treatment course. Here we applied recently developed technologies15-17 to capture neoantigen-specific T cells from blood and tumours from patients with metastatic melanoma with or without response to anti-programmed death receptor 1 (PD-1) immunotherapy. We generated personalized libraries of neoantigen-HLA capture reagents to single-cell isolate the T cells and clone their T cell receptors (neoTCRs). Multiple T cells with different neoTCR sequences (T cell clonotypes) recognized a limited number of mutations in samples from seven patients with long-lasting clinical responses. These neoTCR clonotypes were recurrently detected over time in the blood and tumour. Samples from four patients with no response to anti-PD-1 also demonstrated neoantigen-specific T cell responses in the blood and tumour to a restricted number of mutations with lower TCR polyclonality and were not recurrently detected in sequential samples. Reconstitution of the neoTCRs in donor T cells using non-viral CRISPR-Cas9 gene editing demonstrated specific recognition and cytotoxicity to patient-matched melanoma cell lines. Thus, effective anti-PD-1 immunotherapy is associated with the presence of polyclonal CD8+ T cells in the tumour and blood specific for a limited number of immunodominant mutations, which are recurrently recognized over time.

In this paper the band gap of one-dimensional electromagnetic band gap (1D-EBG) structures will be determined analytically using the dispersion diagram method. Next, we propose a 1D-EBG antenna design to improve the directivity at 3.5 GHz for WiMax applications. The primary goal of this endeavor is to validate the method and the directive EBG antenna's design at the resonant frequency 3.5 GHz with optimal adaptation and to demonstrate the effect of the dielectric substrates on increasing the directivity up to 20 dB. The proposed antenna with 1D-EBG shows 14 dBi enhancement in comparison to the conventional antenna without EBG and a very good adaptation is obtained. The design parameters of the antenna were optimized. [ABSTRACT FROM AUTHOR]

Electromyography (EMG) is a technique used to measure the electrical activity in muscles during movement. Doctors commonly employ this method to quickly evaluate and identify conditions such as muscle problems, dystrophy, and neuropathies. The main objective of this study was to provide a reliable and effective method for preprocessing EMG signals. EMG signals are often affected by natural noise, which can make analysis challenging. To address this issue, a new method called the empirical wavelet transform (EWT) was used in this study to remove and clean the noise. Conventional methods like time domain and frequency domain analysis are limited when dealing with the non-stationary nature of EMG signals, as they do not provide sufficient information about the signals. Therefore, a time-frequency analysis tool was necessary. This research employed three time-frequency analysis techniques: periodogram, Choi-Williams, and smoothed pseudo-Wigner-Ville. The denoising and time-frequency applications demonstrated that the periodogram and EWT methods outperformed other previously published techniques regarding performance and accuracy. The results indicate the effectiveness of the periodogram and EWT methods in achieving this objective. [ABSTRACT FROM AUTHOR]

This paper presents the design of highly efficient rectifiers that can operate at WiFi frequencies (2.45 GHz and 5.8 GHz) and match low input power. The designed dual-band rectifiers use multi-stage dickson voltage multipliers (DVM) (from 1 to 6 stages), and the main idea of this paper is to find the number of stages that offers the best performance and that can be used by applications that operate within the same constraints (operating frequencies, input power). The efficiency and the output voltage (Vout) are the parameters studied to analyze the designed rectifiers. The results showed that as the number of DVM stages increased, the efficiency curves for both frequencies shifted to the higher input power range, even when using the same diode (SMS7630) and the same load (5 KO). We concluded that the rectifier with 1-stage DVM is the most suitable to be used for low input power at the selected frequencies since it provides an efficiency of 57.734% at 0 dBm for 2.45 GHz and 36.225% at 1 dBm of input power for 5.8 GHz. [ABSTRACT FROM AUTHOR]

Neoantigens are peptides derived from non-synonymous mutations presented by human leukocyte antigens (HLAs), which are recognized by antitumour T cells1–14. The large HLA allele diversity and limiting clinical samples have restricted the study of the landscape of neoantigen-targeted T cell responses in patients over their treatment course. Here we applied recently developed technologies15–17 to capture neoantigen-specific T cells from blood and tumours from patients with metastatic melanoma with or without response to anti-programmed death receptor 1 (PD-1) immunotherapy. We generated personalized libraries of neoantigen–HLA capture reagents to single-cell isolate the T cells and clone their T cell receptors (neoTCRs). Multiple T cells with different neoTCR sequences (T cell clonotypes) recognized a limited number of mutations in samples from seven patients with long-lasting clinical responses. These neoTCR clonotypes were recurrently detected over time in the blood and tumour. Samples from four patients with no response to anti-PD-1 also demonstrated neoantigen-specific T cell responses in the blood and tumour to a restricted number of mutations with lower TCR polyclonality and were not recurrently detected in sequential samples. Reconstitution of the neoTCRs in donor T cells using non-viral CRISPR–Cas9 gene editing demonstrated specific recognition and cytotoxicity to patient-matched melanoma cell lines. Thus, effective anti-PD-1 immunotherapy is associated with the presence of polyclonal CD8+ T cells in the tumour and blood specific for a limited number of immunodominant mutations, which are recurrently recognized over time.Effective anti-PD-1 immunotherapy is associated with the presence of polyclonal CD8+ T cells in the tumour and blood specific for a limited number of immunodominant mutations, which are recurrently recognized over time. [ABSTRACT FROM AUTHOR]

The changes in air quality were investigated in six megacities during the shutdown phases in 2020 and were compared to the same time periods in the previous 10 years (2010-2019) using the data of Modern-Era Retrospective Analysis and Research and Application, version 2 (MERRA-2). The concentrations of PM10 and PM2.5 were greatly reduced in all megacities during the lockdown in 2020 when compared to the same period in 2019 and in the previous ten years. The highest reduction in PM10 was recorded in Delhi, and São Paulo (21%, and 15% and by 27%, and 9%), when compared with the con- centrations in 2019 and in the period 2010-2019, respectively. Similarly, levels of PM2.5 in Delhi, São Paulo, Beijing, and Mumbai decreased by 20%, 14%, 12%, and 10%, respectively in 2020 when compared to the last ten years. Results indicated that the lockdown is an effective mitigation measure to improve air quality. The MERRA-2 reanalysis dataset could be a vital tool in air quality studies in places with a lack of In-situ observations. [ABSTRACT FROM AUTHOR]

Background: Human noroviruses (HuNoV) are the leading cause of gastroenteritis. No vaccine is currently available to prevent norovirus illness or infection. Safe, infectious challenge strains are needed to assess vaccine efficacy in the controlled human infection model (CHIM).Methods: A stock of HuNoV strain Norwalk virus ([NV] GI.1) was prepared. Healthy, genetically susceptible adults were inoculated with NV Lot 001-09NV and monitored for infection, gastroenteritis symptoms, and immune responses.Results: Lot 001-09NV induced gastroenteritis in 9 (56%) and infection in 11 (69%) of 16 genetically susceptible subjects. All infected subjects developed strong immune responses to GI.1 with a 30-fold (geometric mean titer) increase in blocking titers (BT50) and a 161-fold increase in GI.1-specific immunoglobulin (Ig)G titers when compared with baseline. GI.1-specific cellular responses in peripheral blood were observed 9 days postchallenge with an average of 3253 IgA and 1227 IgG antibody-secreting cells per million peripheral blood mononuclear cells.Conclusions: GI.1 Lot 001-09NV appears to be similar in virulence to previous passages of NV strain 8fIIa. The safety profile, attack rate, and duration of illness make GI.1 Lot 001-09NV a useful challenge strain for future vaccine studies aimed at establishing immune correlates. [ABSTRACT FROM AUTHOR]

New series of heteroannulated chromeno[2,3- b]pyridines were easily and efficiently synthesized from DBU-catalyzed condensation of 2-amino-6-methylchromone-3-carboxaldehyde with a variety of heterocyclic enols and enamines, namely, 4-hydroxycoumarin, 4-hydroxy-1-methylquinolin-2(1 H)-one, 2-hydroxy-4 H-pyrido[1,2- a]pyrimidin-4-one, 4-hydroxy-2 H-pyrano[3,2- c]quinoline-2,5(6 H)-dione, 4(6)-aminouracil and 5-amino-3-methyl-1 H-pyrazole. Structures of the new synthesized products were deduced on the basis of their analytical and spectral data. [ABSTRACT FROM AUTHOR]

Neoantigens are peptides derived from non-synonymous mutations presented by human leukocyte antigens (HLAs), which are recognized by antitumour T cells 1-14 . The large HLA allele diversity and limiting clinical samples have restricted the study of the landscape of neoantigen-targeted T cell responses in patients over their treatment course. Here we applied recently developed technologies 15-17 to capture neoantigen-specific T cells from blood and tumours from patients with metastatic melanoma with or without response to anti-programmed death receptor 1 (PD-1) immunotherapy. We generated personalized libraries of neoantigen-HLA capture reagents to single-cell isolate the T cells and clone their T cell receptors (neoTCRs). Multiple T cells with different neoTCR sequences (T cell clonotypes) recognized a limited number of mutations in samples from seven patients with long-lasting clinical responses. These neoTCR clonotypes were recurrently detected over time in the blood and tumour. Samples from four patients with no response to anti-PD-1 also demonstrated neoantigen-specific T cell responses in the blood and tumour to a restricted number of mutations with lower TCR polyclonality and were not recurrently detected in sequential samples. Reconstitution of the neoTCRs in donor T cells using non-viral CRISPR-Cas9 gene editing demonstrated specific recognition and cytotoxicity to patient-matched melanoma cell lines. Thus, effective anti-PD-1 immunotherapy is associated with the presence of polyclonal CD8 + T cells in the tumour and blood specific for a limited number of immunodominant mutations, which are recurrently recognized over time., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)