Development of 15kA/cm2^2 Fabrication Process for Superconducting Integrated Digital Circuits

A new fabrication process for superconducting integrated digital circuits is reported. We have developed the "SIMIT Nb04" fabrication technique for superconducting integrated circuits with Nb-based Josephson junctions based on the validated "SIMIT Nb03" process and Chemical Mechanical Planarization (CMP) technology. Seven Nb superconducting layers and one Mo resistor layer are included in the "SIMIT Nb04" process with 19 mask levels. The device structure is composed of active layers including junctions at the bottom, two passive transmission line (PTL) layers in the middle and a DC power layer at the top. The circuit fabrication started with the fabrication of Mo resistors with a target sheet resistance Rsh of 3 $\Omega$, followed by the deposition of Nb/Al-AlO$_x$/Nb trilayer Josephson-junction with a target critical current density Jc at 15 kA/cm$^2$. To increase the Al-AlO$_x$ barrier layer etching's repeatability, an additional barrier protection layer was applied. To accomplish high-quality planarization, we created a planarization procedure coupled with dummy filling. To assess the process dependability and controllability, a set of process control monitors (PCMs) for monitoring fabrication and design parameters was designed and monitored. The successful manufacturing and testing of a few small-scale circuits, like our standard library cells, further attests to the viability of our fabrication process for superconducting integrated circuits

Identification of HLA-A2-Restricted Mycobacterial Lipoprotein Z Peptides Recognized by T CellsFrom Patients With ActiveTuberculosis Infection

Identification of HLA-restricted peptides derived from mycobacterial antigens that are endowed with high affinity and strong antigenicity is not only of interest in tuberculosis (TB) diagnostics and treatment efficacy evaluation, but might also provide potential candidates for the development of therapeutic vaccines against drug-resistant TB. Our previous work demonstrated that lipoprotein Z (LppZ) displayed high immunogenicity and antigenicity in active TB patients. In the present study, ten HLA-A2-restricted LppZ peptides (LppZp1-10) were predicted by bioinformatics, among which LppZp7 and LppZp10 were verified to possess high affinity to HLA-A2 molecules using T2 cell-based affinity binding assay. Moreover, results from ELISpot assay showed that both LppZp7 and LppZp10 peptides were able to induce more IFN-γ producing cells upon ex vivo stimulation of PBMC from HLA-A2+ active TB (ATB) patients as compared to those from healthy controls (HCs). Also, the numbers of LppZp7 and LppZp10-specific IFN-γ producing cells exhibited positive correlations with those of ESAT-6 peptide (E6p) or CFP-10 peptide (C10p) in ATB. Interestingly, stimulation with LppZp7/p10 mixture was able to induce higher intracellular expression of IFN-γ and IL-2 cytokines in CD8+ and CD4+ T cells from ATB as compared to HC, associated with lower expression of TNF-α in both CD8+ and CD4+ T cells. Taken together, HLA-A2-restricted LppZp7 and LppZp10 peptides display high immunoreactivity in HLA-matched ATB patients demonstrated by high responsiveness in both CD8+ and CD4+ T cells. With the ability to induce strong antigen-specific cellular responses, LppZp7 and LppZp10 are of potential value for the future applications in the prevention and control of TB

Aqueous Proton Transportation in Graphene-Based Nanochannels

Graphene oxide (GO) has been unveiled to exhibit high proton conductivity in a humidified or aqueous environment, making it a promising candidate to construct proton conduction nanochannels. In this work, we systematically investigate how the confinement effect and surface chemistry influence the proton transportation behavior in graphene-based nanochannels via extensive ReaxFF MD simulations. Graphene (GE), graphane (GA), and hydroxygraphane (HG) sheets were employed to mimic the graphitic and functionalized region of GO and construct nanochannels with different interlayer distances. We find that confined water molecules are stratified and their orientation is influenced by the surface chemistry, thus impacting the distribution of protons. Surface chemistry makes the compression of the hydrogen-bond network induced by the confinement effect more variable. The hydrogen-bond network between GE slabs is crushed by extreme confinement and ultrafast proton transportation behavior mainly achieved via vehicle mechanism. Meanwhile, the hydrogen-bond network and solvation structure can be kept more complete with the existence of functional groups. The hydrogen bonds formed with surface functional groups impede the transportation of water molecules but allow more Grotthuss hopping of protons to different extents. Our work clarified the proton transportation mechanism in graphene-based nanochannels with different interlayer distances and surface chemistry and can guide the future design of proton conduction devices such as proton exchange membranes

Improvement of transpiration estimation based on a two-leaf conductance-photosynthesis model with seasonal parameters for temperate deciduous forests

IntroductionConductance-photosynthesis (Gs-A) models, accompanying with light use efficiency (LUE) models for calculating carbon assimilation, are widely used for estimating canopy stomatal conductance (Gs) and transpiration (Tc) under the two-leaf (TL) scheme. However, the key parameters of photosynthetic rate sensitivity (gsu and gsh) and maximum LUE (ϵmsu and ϵmsh) are typically set to temporally constant values for sunlit and shaded leaves, respectively. This may result in Tc estimation errors, as it contradicts field observations.MethodsIn this study, the measured flux data from three temperate deciduous broadleaved forests (DBF) FLUXNET sites were adopted, and the key parameters of LUE and Ball-Berry models for sunlit and shaded leaves were calibrated within the entire growing season and each season, respectively. Then, the estimations of gross primary production (GPP) and Tc were compared between the two schemes of parameterization: (1) entire growing season-based fixed parameters (EGS) and (2) season-specific dynamic parameters (SEA).ResultsOur results show a cyclical variability of ϵmsu across the sites, with the highest value during the summer and the lowest during the spring. A similar pattern was found for gsu and gsh, which showed a decrease in summer and a slight increase in both spring and autumn. Furthermore, the SEA model (i.e., the dynamic parameterization) better simulated GPP, with a reduction in root mean square error (RMSE) of about 8.0 ± 1.1% and an improvement in correlation coefficient (r) of 3.7 ± 1.5%, relative to the EGS model. Meanwhile, the SEA scheme reduced Tc simulation errors in terms of RMSE by 3.7 ± 4.4%.DiscussionThese findings provide a greater understanding of the seasonality of plant functional traits, and help to improve simulations of seasonal carbon and water fluxes in temperate forests

Early‐like differentiation status of systemic PD‐1+CD8+ T cells predicts PD‐1 blockade outcome in non‐small cell lung cancer

Abstract Objectives Despite remarkable advances in the treatment of non‐small cell lung cancer (NSCLC) with anti‐programmed death (PD)‐1 therapy; only a fraction of patients derives durable clinical benefit. In this study, we investigated whether the differentiation status of systemic CD8+ T cells predicts the outcome of PD‐1 blockade in NSCLC. Methods We carried out a prospective study on a total of 77 NSCLC patients receiving anti‐PD‐1 blockers, among which 47 patients were assigned as a discovery cohort and 30 patients as a validation cohort. Peripheral blood samples were obtained at baseline and upon multiple therapy cycles and analyzed by multi‐parameter flow cytometry. Results We found that a higher baseline ratio of PD‐1+ early effector memory CD8+ T cells (CD28+CD27−CD45RO+, TEEM) to PD‐1+ effector CD8+ T cells (CD28−CD27−CD45RO−, TE) delineated responders to PD‐1 blockade from progressors and was associated with prolonged progression‐free survival (PFS) and durable clinical benefit. Moreover, PD‐1+CD8 TEEM cells exhibited early responses after anti‐PD‐1 therapy and was the major fraction of cycling PD‐1+Ki67+CD8+ T cells to expand specifically with positive impact on PFS. Conclusion These findings provide insights into how the baseline differentiation status of the peripheral immune system determines responses to PD‐1‐targeted therapies