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

A novel single nucleotide polymorphism within the NOD2 gene is associated with pulmonary tuberculosis in the Chinese Han, Uygur and Kazak populations

<p>Abstract</p> <p>Background</p> <p>The present study aimed to investigate the genetic polymorphisms in exon 4 of the <it>NOD2 </it>gene in tuberculosis patients and healthy controls, in order to clarify whether polymorphisms in the <it>NOD2 </it>gene is associated with tuberculosis.</p> <p>Methods</p> <p>A case-control study was performed on the Chinese Han, Uygur and Kazak populations. Exon 4 of the <it>NOD2 </it>gene was sequenced in 425 TB patients and 380 healthy controls to identify SNPs.</p> <p>Results</p> <p>The frequency of T/G genotypes for the Arg587Arg (CGT → CGG) single nucleotide polymorphism (SNP) in <it>NOD2 </it>was found to be significantly higher in the Uygur (34.9%) and Kazak (37.1%) populations than the Han population (18.6%). Also, the frequency of G/G genotypes for the Arg587Arg SNP was significantly higher in the Uyghur (8.3%) and Kazak (5.4%) populations than the Han population (0.9%). Meanwhile, no significant difference was found in the Arg587Arg polymorphism between the tuberculosis patients and healthy controls in the Uyghur and Kazak populations (<it>P </it>> 0.05) whereas, a significant difference was observed in the Arg587Arg polymorphism between the tuberculosis patients and healthy controls in the Han population (<it>P </it>< 0.01). The odd ratio of 2.16 (95% CI = 1.31-3.58; <it>P </it>< 0.01) indicated that the Arg587Arg SNP in <it>NOD2 </it>may be associated with susceptibility to tuberculosis in the Chinese Han population.</p> <p>Conclusions</p> <p>Our study is the first to demonstrate that the Arg587Arg SNP in <it>NOD2 </it>is a new possible risk factor for tuberculosis in the Chinese Han population, but not in the Uyghur and Kazak populations. Our results may reflect racial differences in genetic susceptibility to tuberculosis.</p

3D bioactive composite scaffolds for bone tissue engineering

Bone is the second most commonly transplanted tissue worldwide, with over four million operations using bone grafts or bone substitute materials annually to treat bone defects. However, significant limitations affect current treatment options and clinical demand for bone grafts continues to rise due to conditions such as trauma, cancer, infection and arthritis. Developing bioactive three-dimensional (3D) scaffolds to support bone regeneration has therefore become a key area of focus within bone tissue engineering (BTE). A variety of materials and manufacturing methods including 3D printing have been used to create novel alternatives to traditional bone grafts. However, individual groups of materials including polymers, ceramics and hydrogels have been unable to fully replicate the properties of bone when used alone. Favourable material properties can be combined and bioactivity improved when groups of materials are used together in composite 3D scaffolds. This review will therefore consider the ideal properties of bioactive composite 3D scaffolds and examine recent use of polymers, hydrogels, metals, ceramics and bio-glasses in BTE. Scaffold fabrication methodology, mechanical performance, biocompatibility, bioactivity, and potential clinical translations will be discussed

Clustering Analysis of Wind Turbine Alarm Sequences Based on Domain Knowledge-Fused Word2vec

The alarm data contain abundant fault information related to almost all components of the wind turbine. Reasonable analysis and utilization of alarm data can assist wind farm maintenance personnel in quickly identifying the types of turbine faults, reducing operation and maintenance costs. This paper proposes a clustering analysis method that groups similar alarm sequences with the same fault type. Firstly, the alarm data are preprocessed, where alarm sequences are segmented, and redundant alarms are removed. Then, a domain knowledge-fused Word2vec (DK-Wrod2vec) method is introduced to transform non-numeric alarm codes into numeric vector representations. Finally, new distance metrics are incorporated into the K-means clustering algorithm to improve clustering performance. The performance of the proposed clustering method is assessed by applying it to labeled alarm sequences. The results demonstrate that the clustering performance is the best when using DK-Word2vec and the word rotator’s distance compared with other methods. Additionally, with the optimal parameter combination, the fault types of unlabeled alarm sequences are also analyzed

Facile Biofabrication of Heterogeneous Multilayer Tubular Hydrogels by Fast Diffusion-Induced Gelation

Multilayer (ML) hydrogels are useful to achieve stepwise and heterogeneous control over the organization of biomedical materials and cells. There are numerous challenges in the development of fabrication approaches toward this, including the need for mild processing conditions that maintain the integrity of embedded compounds and the versatility in processing to introduce desired complexity. Here, we report a method to fabricate heterogeneous multilayered hydrogels based on diffusion-induced gelation. This technique uses the quick diffusion of ions and small molecules (i.e., photoinitiators) through gel–sol or gel–gel interfaces to produce hydrogel layers. Specifically, ionically (e.g., alginate-based) and covalently [e.g., gelatin methacryloyl (GelMA-based)] photocross-linked hydrogels are generated in converse directions from the same interface. The ML (e.g., seven layers) ionic hydrogels can be formed within seconds to minutes with thicknesses ranging from tens to hundreds of micrometers. The thicknesses of the covalent hydrogels are determined by the reaction time (or the molecule diffusion time). Multiwalled tubular structures (e.g., mimicking branched multiwalled vessels) are mainly investigated in this study based on a removable gel core, but this method can be generalized to other material patterns. The process is also demonstrated to support the encapsulation of viable cells and is compatible with a range of thermally reversible core materials (e.g., gelatin and Pluronic F127) and covalently cross-linked formulations (e.g., GelMA and methacrylated hyaluronic acid). This biofabrication process enhances our ability to fabricate a range of structures that are useful for biomedical applications

Facile Biofabrication of Heterogeneous Multilayer Tubular Hydrogels by Fast Diffusion-Induced Gelation

Multilayer (ML) hydrogels are useful to achieve stepwise and heterogeneous control over the organization of biomedical materials and cells. There are numerous challenges in the development of fabrication approaches toward this, including the need for mild processing conditions that maintain the integrity of embedded compounds and the versatility in processing to introduce desired complexity. Here, we report a method to fabricate heterogeneous multilayered hydrogels based on diffusion-induced gelation. This technique uses the quick diffusion of ions and small molecules (i.e., photoinitiators) through gel–sol or gel–gel interfaces to produce hydrogel layers. Specifically, ionically (e.g., alginate-based) and covalently [e.g., gelatin methacryloyl (GelMA-based)] photocross-linked hydrogels are generated in converse directions from the same interface. The ML (e.g., seven layers) ionic hydrogels can be formed within seconds to minutes with thicknesses ranging from tens to hundreds of micrometers. The thicknesses of the covalent hydrogels are determined by the reaction time (or the molecule diffusion time). Multiwalled tubular structures (e.g., mimicking branched multiwalled vessels) are mainly investigated in this study based on a removable gel core, but this method can be generalized to other material patterns. The process is also demonstrated to support the encapsulation of viable cells and is compatible with a range of thermally reversible core materials (e.g., gelatin and Pluronic F127) and covalently cross-linked formulations (e.g., GelMA and methacrylated hyaluronic acid). This biofabrication process enhances our ability to fabricate a range of structures that are useful for biomedical applications

Preliminary utility of the retrospective IMERG precipitation product for large-scale drought monitoring over Mainland China

This study evaluated the suitability of the latest retrospective Integrated Multi-satellitE Retrievals for Global Precipitation Measurement V06 (IMERG) Final Run product with a relatively long period (beginning from June 2000) for drought monitoring over mainland China. First, the accuracy of IMERG was evaluated by using observed precipitation data from 807 meteorological stations at multiple temporal (daily, monthly, and yearly) and spatial (pointed and regional) scales. Second, the IMERG-based standardized precipitation index (SPI) was validated and analyzed through statistical indicators. Third, a light-extreme-light drought-event process was adopted as the case study to dissect the latent performance of IMERG-based SPI in capturing the spatiotemporal variation of drought events. Our results demonstrated a sufficient consistency and small error of the IMERG precipitation data against the gauge observations with the regional mean correlation coefficient (CC) at the daily (0.7), monthly (0.93), and annual (0.86) scales for mainland China. The IMERG possessed a strong capacity for estimating intra-annual precipitation changes; especially, it performed well at the monthly scale. There was a strong agreement between the IMERG-based SPI values and gauge-based SPI values for drought monitoring in most regions in China (with CCs above 0.8). In contrast, there was a comparatively poorer capability and notably higher heterogeneity in the Xinjiang and Qinghai-Tibet Plateau regions with more widely varying statistical metrics. The IMERG featured the advantage of satisfactory spatiotemporal accuracy in terms of depicting the onset and extinction of representative drought disasters for specific consecutive months. Furthermore, the IMERG has obvious drought monitoring abilities, which was also complemented when compared with the Precipitation Estimation from the Remotely Sensed Information using Artificial Neural Networks Climate Data Record (PERSIANN-CDR), Climate Hazards Group Infrared Precipitation with Stations (CHIRPS), and Tropical Rainfall Measuring Mission Multi-satellite Precipitation Analysis (TMPA) 3B42V7. The outcomes of this study demonstrate that the retrospective IMERG can provide a more competent data source and potential opportunity for better drought monitoring utility across mainland China, particularly for eastern China