Gradual depletion of CD4 T cells is a typical characteristic of pathogenic SIV infection. Intriguingly, we find a spontaneous CD4 T-cell homeostasis in northern pig-tailed macaques (Macaca leonina) during SIVmac239 infection.
The northern pig-tailed macaques (NPMs) lack TRIM5α, an antiviral restriction factor, and instead have TRIM5-CypA. In our previous study, we demonstrated that HIV-1NL4−3 successfully infected NPMs and formed a long-term viral reservoir in vivo. However, the HIV-1-infected NPMs showed relatively high viremia in the first 6 weeks of infection, which declined thereafter suggesting that HIV-1 NL4−3 infection in these animals was only partly permissive. To optimize HIV-1 infection in NPMs therefore, we generated HIV-1NL4−R3A and stHIV-1sv, and infected NPMs with these viruses. HIV-1NL4−R3A and stHIV-1sv can replicate persistently in NPMs during 41 weeks of acute infection stage. Compared to the HIV-1NL4−R3A, stHIV-1sv showed a notably higher level of replication, and the NPMs infected with the latter induced a more robust neutralizing antibody but a weaker cellular immune response. In addition, IFN-I signaling was significantly up-regulated with the viral replication, and was higher in the stHIV-1sv infected macaques. Consequently, the sequences of pro-viral env showed fewer G-A hyper-mutations in stHIV-1sv, suggesting that vif gene of SIV could antagonize the antiviral effects of APOBEC3 proteins in NPMs. Taken together, NPMs infected with HIV-1NL4−R3A and stHIV-1sv show distinct virological and immunological features. Furthermore, interferon-related gene expression might play a role in controlling primary HIV-1NL4−R3A and stHIV-1sv replication in NPMs. This result suggests NPM is a potential HIV/AIDS animal model.
In-Memory Computing (IMC), which takes advantage of analog multiplication-accumulation (MAC) insides memory, is promising to alleviate the Von-Neumann bottleneck and improve the energy efficiency of deep neural networks (DNNs). Since the time-domain (TD) computing is also an energy-efficient analog computing paradigm, we present an 8kb mixed-signal IMC macro, TD-SRAM, by combining IMC with TD computing. A dual-edge single input (DESI) TD computing topology is proposed, which can significantly improve the area and power efficiencies of TD cell. The TD-SRAM bitcell consisting of a 6T DESI based TD cell and a 6T-SRAM cell supports binary DNNs. In the IMC mode, 60 columns work in parallel and 96-input binary-MAC operations are processed in each column. Implemented in a standard 40-nm CMOS process, the TD-SRAM achieves the high energy efficiency of 537 TOPS/W at 0.9-V supply. With different DNN topologies, the test chips achieve the accuracy of 95.90%-98.00% with a dual 2-bit time-to-digital converter (TDC) in the MNIST dataset.
Macaca leonina (northern pig-tailed macaques, NPMs) have variable disease progression during SIVmac239 infection. In the present study, we analysed, for the first time, the correlations between T-cell phenotypes and disease progression in NPMs during SIVmac239 infection. In comparison to normal progressors (NPs), slow progressors (SPs) had lower chronic T-cell activation and exhaustion levels. In addition, SPs showed higher peripheral CD4 T-cell count and CD4 : CD8 ratio, and lower plasma viral load than NPs. CD4 T-cell count and CD4 : CD8 ratio decreased more sharply in NPs than in SPs. Furthermore, T cells in NPs were more highly differentiated, at least in acute infection, than in SPs. These results indicated that T-cell phenotypes were correlated with disease progression in SIVmac239-infected NPMs and these correlations may provide valuable guidance for the improvement of therapeutic strategies tested in NPMs.
Freestanding perovskite thin films display many unprecedented properties and exhibit the potential to be easily integrated on other non-oxide substrates or layers. In this work, we demonstrated a pathway to synthesis freestanding perovskite oxide thin films by using brownmillerite SrCoO2.5 as a sacrificial layer. Four representative freestanding perovskite oxide films, e.g., ferromagnetic SrRuO3, La0.7Sr0.3MnO3, dielectric SrTiO3, and ferroelectric Pb(Zr0.2Ti0.8)O3, were produced by etching SrCoO2.5 in Fe(NO3)3 weak acidic solution at room temperature. A 80 nm SrRuO3, which served as an H+ conduction channel, was deposited as a bottom layer of SrCoO2.5 to trigger a quick dissolution for the exfoliation of SrTiO3 and Pb(Zr0.2Ti0.8)O3 poor H+ conductor. Their crystal structure and physical properties were well retained in transferred films. Our work demonstrated the wide applicability of SrCoO2.5 as a sacrificial layer on the synthesis of freestanding perovskite oxide thin films.
Large-area, continuous monolayer WS2 exhibits great potential for future micro-nanodevice applications due to its special electrical properties and mechanical flexibility. In this work, the front opening quartz boat is used to increase the amount of sulfur (S) vapor under the sapphire substrate, which is critical for achieving large-area films during the chemical vapor deposition processes. COMSOL simulations reveal that the front opening quartz boat will significantly introduce gas distribute under the sapphire substrate. Moreover, the gas velocity and height of substrate away from the tube bottom will also affect the substrate temperature. By carefully optimizing the gas velocity, temperature, and height of substrate away from the tube bottom, a large-scale continues monolayered WS2 film was achieved. Field-effect transistor based on the as-grown monolayer WS2 showed a mobility of 3.76 cm2V−1 s−1 and ON/OFF ratio of 106. In addition, a flexible WS2/PEN strain sensor with a gauge factor of 306 was fabricated, showing great potential for applications in wearable biosensors, health monitoring, and human–computer interaction.
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