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In this paper, a concise and fast 2D model of the roll tensioning process was built using the finite element method. Elastic thermal expansion is used to simulate rolling plastic deformation. A 3D model considering contact between roller and circular saw blade was also built. Through comparison of residual stress results obtained by the 2D model, 3D model, and X-ray stress test method, the correctness and feasibility of the 2D model were proven. While accounting for the diversity of circular saw blade structure, this paper provided an idea for rapidly predicting the residual stress field of a roll-tensioned circular saw blade.

Outside the explosive successful applications of deep learning (DL) in natural language processing, computer vision, and information retrieval, there have been numerous Deep Neural Networks (DNNs) based alternatives for common security-related scenarios with malware detection among more popular. Recently, adversarial learning has gained much focus. However, unlike computer vision applications, malware adversarial attack is expected to guarantee malwares’ original maliciousness semantics. This paper proposes a novel adversarial instruction learning technique, DeepMal, based on an adversarial instruction learning approach for static malware detection. So far as we know, DeepMal is the first practical and systematical adversarial learning method, which could directly produce adversarial samples and effectively bypass static malware detectors powered by DL and machine learning (ML) models while preserving attack functionality in the real world. Moreover, our method conducts small-scale attacks, which could evade typical malware variants analysis (e.g., duplication check). We evaluate DeepMal on two real-world datasets, six typical DL models, and three typical ML models. Experimental results demonstrate that, on both datasets, DeepMal can attack typical malware detectors with the mean F1-score and F1-score decreasing maximal 93.94% and 82.86% respectively. Besides, three typical types of malware samples (Trojan horses, Backdoors, Ransomware) prove to preserve original attack functionality, and the mean duplication check ratio of malware adversarial samples is below 2.0%. Besides, DeepMal can evade dynamic detectors and be easily enhanced by learning more dynamic features with specific constraints.

Facet regulation of the BiVO4 photoanode is an effective way to improve its charge separation efficiency. Herein, a BiVO4 photoanode structured by connecting a (040)-facet-oriented mono-grain layer...

Introduction Angiotensin Converting Enzyme Inhibitors (ACEI) are a common cause of Emergency Room presentation for angioedema. Although no treatment guidelines exist, C1 esterase inhibitor concentrate (C1-INH) is used on an off label basis for management of ACEI acquired angioedema (ACEI AAE). Objective To evaluate the efficacy of C1-INH in management of ACEI AAE at our local centers. Results Nine patients, from 3 academic sites, were identified through Allergy Service consultation data and records from Diagnostic Services Manitoba, Canada from 2010–2020. The majority of the patients (n = 8/9) required endotracheal intubation prior to the initiation of C1-INH. Overall, approximately 56% of patients (n = 5/9) had resolution of angioedema ranging between 12 and 17 h, with a median time of 13.5 h, and no recurrence after the administration of C1-INH concentrate. One patient had transient symptom resolution in 14 h, however, recurrence of angioedema required re-intubation. The remainder of patients (n = 4/9), had resolution of angioedema between 22 and 72 h, with a median time of 33.75 h. Conclusion Our findings demonstrate continued ambivalence of the efficacy and role of C1-INH concentrate in the treatment of ACEI AAE, secondary to multiple uncontrolled confounding factors. Further research into characterizing a subgroup of intubated patients in our study that responded to C1-INH concentrate needs to be completed.

A Cu2O/Pt/BiVO4 heterojunction was prepared by successively depositing Pt and Cu2O nanoparticles on {010} facets of BiVO4, showing much higher photocatalytic activity in hydrogen evolution than that constructed by random deposition of Cu2O on all facets of BiVO4 particles. Photoluminescence spectroscopy revealed that the facet-selective Cu2O/Pt/BiVO4 arrays effectively promoted charge separation of the BiVO4 host. A band alignment was consequently presented to illustrate the interface charge flow in the heterojunction. This work demonstrates the roles that facets played in semiconductor heterojunctions applied to photocatalytic reactions.

Tissue building does not occur exclusively during development. Even after a whole body is built from a single cell, tissue building can occur to repair and regenerate tissues of the adult body. This confers resilience and enhanced survival to multicellular organisms. However, this resiliency comes at a cost, as the potential for misdirected tissue building creates vulnerability to organ deformation and dysfunction-the hallmarks of disease. Pathological tissue morphogenesis is associated with fibrosis and cancer, which are the leading causes of morbidity and mortality worldwide. Despite being the priority of research for decades, scientific understanding of these diseases is limited and existing therapies underdeliver the desired benefits to patient outcomes. This can largely be attributed to the use of two-dimensional cell culture and animal models that insufficiently recapitulate human disease. Through the synergistic union of biological principles and engineering technology, organ-on-a-chip systems represent a powerful new approach to modeling pathological tissue morphogenesis, one with the potential to yield better insights into disease mechanisms and improved therapies that offer better patient outcomes. This Review will discuss organ-on-a-chip systems that model pathological tissue morphogenesis associated with (1) fibrosis in the context of injury-induced tissue repair and aging and (2) cancer.

Background Maternal stress is potentially a modifiable risk factor for spontaneous preterm birth (sPTB). However, epidemiologic findings on the maternal stress-sPTB relationship have been inconsistent. Methods To investigate whether the maternal stress-sPTB associations may be modified by genetic susceptibility, we performed genome-wide gene × stress interaction analyses in 1490 African-American women from the Boston Birth cohort who delivered term (n = 1033) or preterm (n = 457) infants. Genotyping was performed using Illumina HumanOmni 2.5 array. Replication was performed using data from the NICHD genomic and Proteomic Network (GPN) for PTB research. Results rs35331017, a T-allele insertion/deletion polymorphism in the protein-tyrosine phosphatase receptor Type D (PTPRD) gene, was the top hit that interacted significantly with maternal lifetime stress on risk of sPTB (PG × E = 4.7 × 10-8). We revealed a dose-responsive association between degree of stress and risk of sPTB in mothers carrying the insertion/insertion genotype, but an inverse association was observed in mothers carrying the heterozygous or deletion/deletion genotypes. This interaction was replicated in African-American (PG × E = 0.088) and Caucasian mothers (PG × E = 0.023) from the GPN study. Conclusion We demonstrated a significant maternal PTPRD × stress interaction on sPTB risk. This finding, if further confirmed, may provide new insight into individual susceptibility to stress-induced sPTB. Impact This was the first preterm study to demonstrate a significant genome-wide gene-stress interaction in African Americans, specifically, PTPRD gene variants can interact with maternal perceived stress to affect risk of spontaneous preterm birth.The PTPRD × maternal stress interaction was demonstrated in African Americans and replicated in both African Americans and Caucasians from the GPN study.Our findings highlight the importance of considering genetic susceptibility in assessing the role of maternal stress on spontaneous preterm birth.

Electrode materials of dielectric thin-film capacitors have significant effect on their energy storage properties. In this work, Ba0.53Sr0.47TiO3 thin films were successfully deposited on LaNiO3 or La0.7Sr0.3MnO3 buffered (001) SrTiO3 substrates by pulsed laser deposition method (abbreviated as BST/LNO/STO and BST/LSMO/STO, respectively). The effect of LNO or LSMO bottom electrode on energy storage properties of BST films was systematically studied. It was found that the recoverable energy density of BST/LSMO/STO films is 36.1 J/cm3 at 3400 kV/cm, which is 59.1% higher than that of BST/LNO/STO thin films, i.e., 22.7 J/cm3 at 2765 kV/cm. Besides, the breakdown strength of the BST/LSMO/STO thin films is 22.9% higher than that of the BST/LNO/STO films. Both films show the good thermal stability from 20 °C to 160 °C as well as excellent fatigue resistance after up to 109 electrical cycles. The results show that the lattice mismatch strain of the film, surface roughness of the electrode and Schottky barrier height at the electrode-dielectric interface greatly affect the energy storage properties of BST thin-film capacitors. Our work offers a practical methodology to enhance the energy storage performances of thin-film capacitors by optimizing bottom electrode materials.

Organ-level vascularization has been a long-standing challenge in the field of tissue engineering. Recent advances, particularly in the use of projection stereolithography and food colors as photoabsorbers are highlighted, as are several recent studies on the clinical translation of engineered vasculature.

Composite materials, especially carbon fiber-reinforced polymers (CFRPs), are high-performance class of structural materials now commonly used in aircraft, marine, and other applications, with emerging large-scale use in the automotive and civil engineering applications. The difficulty of recycling these materials is a key obstacle preventing their further application in larger markets. For decades, the engineering community has pursued physical methods to recover value from end-of-life composite waste. This work has generated scalable methods to recover modest value from CFRP waste, but because of their low value recovery, these are applied to a small fraction of CFRP waste. By contrast, relatively few methods to recycle CFRPs have been based on strategic approaches systematically to deconstruct the thermoset polymers that hold them together. In this Focus Article, we will show the emergence of these structure-focused approaches to CFRP recycling and illustrate the path of this research toward the ultimate realization of methods to recover both the reinforcing fibers and the thermoset materials that comprise modern CFRPs.

BackgroundMucosal Associated Invariant T Cells (MAIT cells) are unconventional T cells that recognize vitamin B metabolites derived from bacteria and are mainly present in mucosal tissues and peripheral blood.1 Their activation by T Cell Receptor (TCR)-dependent and -independent pathways can result in effector function that can either promote or inhibit cytotoxic effects.2 MAIT cells are known to be involved in the pathogenesis of multiple diseases that involve mucosal tissues, such as non-small cell lung cancer (NSCLC).2 Recently, studies have shown that disparate outcomes to SARS-CoV-2-infection between males and females may involve a differential activation of MAIT cells in the lung mucosa.3 It is therefore conceivable to hypothesize that sex differences of MAIT cells in NSCLC may also impact outcome, however their involvement in progression and subsequent treatment response of NSCLC has never been explored.MethodsTo study the transcriptional program of MAIT cells in NSCLC as a function of sex, peripheral blood and tissue biospecimens were obtained from the first-in-human clinical trial of neoadjuvant anti-PD-1 (nivolumab) in resectable non-small cell lung cancer; NCT02259621.4 Coupled single-cell RNAseq/TCRseq was performed on tumor infiltrating lymphocytes (TIL), paired adjacent normal lung, and tumor-draining lymph nodes (TDLN). MAIT cells were identified by expression of SLC4A10 and the invariant TRAV1-2 and TRAJ33/12/20 TCR. Computational analysis revealed 4 distinct MAIT cell clusters and differentially expressed genes in the tumors and healthy normal lung of males as compared to females.ResultsIn MAIT cells from females, we found upregulation of CD8A, GNLY, and NKG7 genes. These genes are involved with T cell activation and cytolytic function, suggesting that the activation of these genes in MAIT cells could be contributing towards their cytolytic activity in females. In MAIT cells from males, we found upregulation of PDE3B and PCBP2 genes, which are known to be involved with immunosuppression and downregulation of cytotoxic T lymphocyte (CTL) responses. These findings were consistent in the healthy normal lung, suggesting these transcriptional programs may be due to the normal lung biology and not necessarily a byproduct of carcinogenesis.ConclusionsThese results highlight the potential for dual characteristics of MAIT cells in neoadjuvant anti-PD-1-treated NSCLCs and provide an important foundation in our study of the often dichotomous responses between males and females to immunotherapy. Future analyses will focus on the interplay of MAIT cells with other cells in the tumor microenvironment (TME) as a function of immunotherapy treatment and clinical response.ReferencesChen Z, Wang H, D’Souza C, et al. Mucosal-associated invariant T-cell activation and accumulation after in vivo infection depends on microbial riboflavin synthesis and co-stimulatory signals. Mucosal Immunol 2017;10:58–68.Wen X, Zhang X, et al. Title of article: mucosal-associated invariant T cells in lung cancers. Elsevier 2021;94.Yu C, Littleton S, et al. Mucosal-associated invariant T cell responses differ by sex in COVID-19. CellPress 2021;2:755–772.Caushi JX, Zhang J, Ji Z, et al. Transcriptional programs of neoantigen-specific TIL in anti-PD-1-treated lung cancers. Nature 2021.Ethics ApprovalThis study was approved by the Institutional Review Boards (IRB) at Johns Hopkins University (JHU) and Memorial Sloan Kettering Cancer Center and was conducted in accordance with the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice guidelines. The patients described in this study provided written informed consent.

BackgroundMelanoma and lung cancers have two of the highest response rates to immune checkpoint inhibitors (ICIs).1 However, patients may respond unpredictably, partly due to heterogeneity in the quantity and quality of tumor-specific T cells. In this study, we performed an integrated transcriptomic analysis of anti-tumor CD8+ TIL from non-small cell lung cancer (NSCLC) and melanoma. Our goal was to study the global transcriptomic landscape of tumor-specific T cells and to compare their functional programming in lung cancer vs. melanoma.MethodsTIL from 19 patients (15 NSCLC and 3 melanoma) were sequenced using combined single-cell (sc) RNA-seq/TCR-seq. All NSCLC patients received neoadjuvant anti-PD-1 (nivolumab, NCT02259621) whereas melanoma patients received a personal neoantigen vaccine (NCT01970358). Neoantigen-, tumor-associated antigen-, and viral-specific CD8+ T cell clonotypes were identified using functional assays and were validated by TCR cloning as previously described.2 3 Transcriptional profiles of antigen-specific T cells were identified using the TCRβ CDR3 as a barcode to link with the antigen specificity output from the functional assays. The prevalence, phenotype, and differentiation trajectory of tumor-specific T cells were compared between the two cancer types.ResultsA total of 175,826 CD8+ TIL were analyzed, of which 30,174 single cells were from the melanoma cohort and 145,652 were from the NSCLC cohort. Tumor-specific T cells were detected at variable frequencies among CD8+ TIL (median=1.2%, range 0.01%–35.8%) across nine patients, with melanoma having more clonal tumor-specific T cells as compared to NSCLC. CD8+ TIL from melanoma were more enriched in an activated tissue resident T cell (TRM) cluster characterized by upregulated expression of CXCL13, CRTAM, 4-1BB, XCL1/2, and FABP5, whereas those from NSCLC have a greater representation of a cytotoxic TRM cluster with an exhaustion signature (coexpression of GZMB, GZMH, PDCD1, and CTLA4). Distinct from EBV-specific T cells and flu-specific T cells, tumor-specific T cells primarily resided in TRM clusters in both cancers. More MANA-specific TIL from melanoma presented with an effector phenotype and were more proliferative as compared to those from NSCLC. To reveal the differentiation trajectory and regulatory programs of tumor-specific T cells upon tumor recognition and association with response to ICIs, pseudotime/velocity analysis of tumor-specific TIL is underway.ConclusionsThis is the first analysis to inform on the global transcriptomic landscape of tumor-specific CD8+ TIL in lung cancer and melanoma at single cell resolution. This provides a useful framework to study the underlying mechanisms of T cell exhaustion and dysfunction in human cancer.Trial RegistrationNCT02259621,NCT01970358ReferencesYarchoan M, Hopkins A, Jaffee EM. Tumor mutational burden and response rate to PD-1 inhibition. The New England Journal of Medicine 2017;377(25):2500.Caushi JX, et al. Transcriptional programs of neoantigen-specific TIL in anti-PD-1-treated lung cancers. Nature 2021;1–7.Oliveira G, et al. Phenotype, specificity and avidity of antitumour CD8+ T cells in melanoma. Nature 2021;1–7.Ethics ApprovalThe melanoma clinical trial was approved by the Dana-Farber/Harvard Cancer Center Institutional Review Board (IRB) (NCT01970358). The NSCLC clinical trial was approved by the Institutional Review Boards (IRB) at Johns Hopkins University (JHU) and Memorial Sloan Kettering Cancer Center (NCT02259621). All participants gave informed consent before taking part.ConsentWritten informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.

More and more attention has been given in the field of mechanical engineering to a material’s R-value, a parameter that characterizes the ability of sheet metal to resist thickness strain. Conventional methods used to determine R-value are based on experiments and an assumption of constant volume. Because the thickness strain cannot be directly measured, the R-value is currently determined using experimentally measured strains in the width, and loading directions in combination with the constant volume assumption, to determine the thickness strain indirectly. This paper provides an alternative method for determining the R-value without any assumptions. This method is based on the use of a multi-camera DIC system to measure strains in three directions simultaneously. Two sets of stereo-vision DIC measurement systems, each comprised of two GigE cameras, are placed on the front and back sides of the sample. Use of the double-sided calibration strategy unifies the world coordinate system of the front and back DIC measurement systems to one coordinate system, allowing for the measurement of thickness strain and direct calculation of R-value. The Random Sample Consensus (RANSAC) algorithm is used to eliminate noise in the thickness strain data, resulting in a more accurate R-value measurement.

Robot-assisted minimally invasive surgery (MIS) has received increasing attention, both in the academic field and clinical operation. Master/slave control is the most widely adopted manipulation mode for surgical robots. Thus, sensing the force of the surgical instruments located at the end of the slave manipulator through the main manipulator is critical to the operation. This study mainly addressed the force detection of the surgical instrument and force feedback control of the serial surgical robotic arm. A measurement device was developed to record the tool end force from the slave manipulator. An elastic element with an orthogonal beam structure was designed to sense the strain induced by force interactions. The relationship between the acting force and the output voltage was obtained through experiment, and the three-dimensional force output was decomposed using an extreme learning machine algorithm while considering the nonlinearity. The control of the force from the slave manipulator end was achieved. An impedance control strategy was adopted to restrict the force interaction amplitude. Modeling, simulation, and experimental verification were completed on the serial robotic manipulator platform along with virtual control in the MATLAB/Simulink software environment. The experimental results show that the measured force from the slave manipulator can provide feedback for impedance control with a delay of 0.15 s.

The precise segmentation of forest areas is essential for monitoring tasks related to forest exploration, extraction, and statistics. However, the effective and accurate segmentation of forest images will be affected by factors such as blurring and discontinuity of forest boundaries. Therefore, a Pyramid Feature Extraction-UNet network (PFE-UNet) based on traditional UNet is proposed to be applied to end-to-end forest image segmentation. Among them, the Pyramid Feature Extraction module (PFE) is introduced in the network transition layer, which obtains multi-scale forest image information through different receptive fields. The spatial attention module (SA) and the channel-wise attention module (CA) are applied to low-level feature maps and PFE feature maps, respectively, to highlight specific segmentation task features while fusing context information and suppressing irrelevant regions. The standard convolution block is replaced by a novel depthwise separable convolutional unit (DSC Unit), which not only reduces the computational cost but also prevents overfitting. This paper presents an extensive evaluation with the DeepGlobe dataset and a comparative analysis with several state-of-the-art networks. The experimental results show that the PFE-UNet network obtains an accuracy of 94.23% in handling the real-time forest image segmentation, which is significantly higher than other advanced networks. This means that the proposed PFE-UNet also provides a valuable reference for the precise segmentation of forest images.

T-cell receptor sequencing (TCRseq) enables tracking of T-cell clonotypes recognizing the same antigen over time and across biological compartments. TCRseq has been used to test if cross-reactive antitumor T cells are responsible for development of immune-related adverse events (irAEs) following immune checkpoint blockade. Prior studies have interpreted T-cell clones shared among the tumor and irAE as evidence supporting this, but interpretations of these findings are challenging, given the constraints of TCRseq. Here we capitalize on a rare opportunity to understand the impact of potential confounders, such as sample size, tissue compartment, and collection batch/timepoint, on the relative proportion of shared T-cell clones between an irAE and tumor specimens. TCRseq was performed on tumor-involved and -uninvolved tissues, including an irAE, that were obtained throughout disease progression and at the time of rapid autopsy from a patient with renal cell carcinoma treated with programmed death-1 (PD-1) blockade. Our analyses show significant effects of these confounders on our ability to understand T-cell receptor overlap, and we present mitigation strategies and study design recommendations to reduce these errors. Implementation of these strategies will enable more rigorous TCRseq-based studies of immune responses in human tissues, particularly as they relate to antitumor T-cell cross-reactivity in irAEs following checkpoint blockade.

The Karst collapse pillar (KCP) is a special geological structure, which is easy to form the fissure channels between the coal seam working face and the aquifer to cause the water inrush disasters. The KCP was sampled on site in this paper. The confined uniaxial compression test was carried out on the KCP to simulate its field consolidation, and seepage test on the KCP under different axial loads was conducted by using self-developed seepage test system. The KCP connecting to the underground Ordovician limestone aquifer in the sampling area was considered; the difference in the seepage properties between the KCP and the broken limestone was analyzed. The results show that the water-resisting capacity of the KCPs in 3# coal seam floor is 6.24–13.74 MPa, which is far greater than the water pressure of aquifer on 3# coal seam. The water-resisting capacity of the KCPs in 15# coal seam floor is in the range of 1.89–4.71 MPa, which is less than the water pressure of aquifer on 15# coal seam. The specific measures were conducted to prevent the water inrush during the mining process. Before exposing the X3 KCP, the roof drainage borehole drained the roof water to avoid the excessive water inflow in a short time. The grouting holes were arranged to reinforce the floor of sandstone aquifer. According to these treatment methods, the mining work safely passed through the X3 KCP, ensuring engineering safety and economic production. It is not recommended to directly expose the X3 KCP in the roadway or working face of 15# coal seam, and the floor of 15# coal seam should be grouted and reinforced in the future.

Glucagon-like peptide-1 receptor (GLP-1R) agonists, widely used to treat type 2 diabetes, reduce blood pressure (BP) in hypertensive patients. Whether this action involves central mechanisms is unknown. We here report that repeated lateral ventricular (LV) injection of GLP-1R agonist, liraglutide, once daily for 15 days counteracted the development of hypertension in spontaneously hypertensive rats (SHR). In parallel, it suppressed urinary norepinephrine excretion, and induced c-Fos expressions in the area postrema (AP) and nucleus tractus solitarius (NTS) of brainstem including the NTS neurons immunoreactive to dopamine beta-hydroxylase (DBH). Acute administration of liraglutide into fourth ventricle, the area with easy access to the AP and NTS, transiently decreased BP in SHR and this effect was attenuated after lesion of NTS DBH neurons with anti-DBH conjugated to saporin (anti-DBH-SAP). In anti-DBH-SAP injected SHR, the antihypertensive effect of repeated LV injection of liraglutide for 14 days was also attenuated. These findings demonstrate that the central GLP-1R signaling via NTS DBH neurons counteracts the development of hypertension in SHR, accompanied by attenuated sympathetic nerve activity.

The complicated and constrained reconfiguration optimisation for unmanned aerial vehicles (UAVs) is a challenge, particularly when multi-mission requirements are taken into account. In this study, we evaluate the use of the adaptive differential evolution-based centralised receding horizon control approach to achieve the formation reconfiguration along a given formation group trajectory for multiple unmanned aerial vehicles in a three-dimensional (3D) environment. A rolling optimisation approach which combines the receding horizon control method with the adaptive differential evolution algorithm is proposed, where the receding horizon control method divides the global control problem into a series of local optimisations and each local optimisation problem is solved by an adaptive differential evolution algorithm. Furthermore, a novel quadratic reconfiguration cost function with the topology information of UAVs is presented, and the asymptotic convergence of the rolling optimisation is analysed. Finally, simulation examples are provided to illustrate the validity of the proposed control structure.

BACKGROUND: While stress and the absence of social support during pregnancy have been linked to poor health outcomes, the underlying biological mechanisms are unclear. METHODS: We examined whether adverse experiences during pregnancy alter DNA methylation (DNAm) in maternal epigenomes. Analyses included 250 African-American mothers from the Boston Birth Cohort. Genome-wide DNAm profiling was performed in maternal blood collected after delivery, using the Infinium HumanMethylation450 Beadchip. Linear regression models, with adjustment of pertinent covariates, were applied. RESULTS: While self-reported maternal psychosocial lifetime stress and stress during pregnancy was not associated with DNAm alterations, we found that absence of support from the baby’s father was significantly associated with maternal DNAm changes in TOR3A, IQCB1, C7orf36, and MYH7B, and that lack of support from family and friends was associated with maternal DNA hypermethylation on multiple genes, including PRDM16 and BANKL. CONCLUSIONS: This study provides intriguing results suggesting biological embedding of social support during pregnancy on maternal DNAm, warranting additional investigation, and replication.

Background Maternal smoking affects more than half a million pregnancies each year in the US and is known to result in fetal growth restriction as measured by lower birthweight and its associated long-term consequences. Maternal smoking also has been linked to altered fetal DNA methylation (DNAm). However, what remains largely unexplored is whether these DNAm alterations are merely markers of smoking exposure or if they also have implications for health outcomes. This study tested the hypothesis that fetal DNAm mediates the effect of maternal smoking on newborn birthweight. Methods This study included mother–newborn pairs from a US predominantly urban, low-income multi-ethnic birth cohort. DNAm in cord blood were determined using the Illumina Infinium MethylationEPIC BeadChip. After standard quality control and normalization procedures, an epigenome-wide association study (EWAS) of maternal smoking was performed using linear regression models, controlling for maternal age, education, race, parity, pre-pregnancy body mass index, alcohol consumption, gestational age, maternal pregestational/gestational diabetes, child sex, cord blood cell compositions and batch effects. To quantify the degree to which cord DNAm mediates the smoking-birthweight association, the VanderWeele-Vansteelandt approach for single mediator and structural equational model for multiple mediators were used, adjusting for pertinent covariates. Results The study included 954 mother–newborn pairs. Among mothers, 165 (17.3%) ever smoked before or during pregnancy. Newborns with smoking exposure had on average 258 g lower birthweight than newborns without exposure (P GFI1, AHRR, CYP1A1, and CNTNAP2; 8 of those, located in the first three genes, were Bonferroni significantly associated with newborn birthweight and mediated the smoking-birthweight association. The combined mediation effect of the three genes explained 67.8% of the smoking-birthweight association. Conclusions Our study not only lends further support that maternal smoking alters fetal DNAm in a multiethnic population, but also suggests that fetal DNAm substantially mediates the maternal smoking–birthweight association. Our findings, if further validated, indicate that DNAm modification is likely an important pathway by which maternal smoking impairs fetal growth and, perhaps, even long-term health outcomes.

In autonomous vehicles (AVs), a critical stage of perception system is to leverage multi-modal fusion (MMF) detectors which fuse data from LiDAR (Light Detection and Ranging) and camera sensors to perform 3D object detection. While single-modal (LiDAR-based and camera-based) models are found to be vulnerable to adversarial attacks, there are limited studies on the adversarial robustness of MMF models. Recent work has proposed a general spoofing attack on LiDAR-based perception, based on the defect of ignored occlusion patterns in point clouds. In this paper, we are inspired to attack LiDAR channel alone to fool the MMF model into detecting a fake near-front object with high confidence score. We perform the first study to analyze the roubustness of a popular MMF model against the above attack and discover it is invalid due to the correction of camera. We propose a black-box attack method to generate adversarial point clouds with few points and prove the defect still exists in MMF architecture. We evaluate the attack effectiveness of different combinations of points and distances and generate universal adversarial examples at the best distance of 4m, which achieve attack success rates of more than 95% and average confidence scores over 0.9 on the KITTI validation set when the points exceed 30. Furthermore, we verify the generality of our attack and the transferability of generated universal adversarial point clouds across models.

Recent black-box adversarial attacks can take advantage of transferable adversarial examples generated by a similar substitute model to successfully fool the target model. However, these substitute models are either pre-trained models or trained with the target model’s training examples, which is hard to obtain because of the security and privacy of training data. In this paper, we proposed a zero-shot adversarial black-box attack method that can generate high-quality training examples for the substitute models, which are balanced among the classification labels and close to the distribution of the real training examples of the target models. The experiments demonstrate the effectiveness of our method that significantly improves the non-target black-box attack success rate around 20%–30% of the adversarial examples generated by the substitute models.

Vulnerability is one of the main causes of network intrusion. An effective way to mitigate security threats is to find and repair vulnerabilities as soon as possible. Traditional vulnerability detection methods are limited by expert knowledge. Existing deep learning-based methods neglect the connection between semantic graphs and cannot effectively deal with the structure information. Graph neural network brings new insight into vulnerability detection. However, benign nodes on the graph account for a large proportion, resulting in vulnerability information could be disturbed by them. To address the limitations of existing vulnerability detection approaches, in this paper, we propose ACGVD, a vulnerability detection method by constructing a graph network with attention. We first combine multiple semantic graphs together to form a more comprehensive graph. We then adopt the Graph neural network instead of the sequence-based model to automatically analyze the comprehensive graph. In order to solve the problem that the vulnerability information could be covered up, we add a double-level attention mechanism to the graph model. We also add a novel classification layer to extract the high-level features of the code. To make the experiment more realistic, the model is trained over the latest published real-world dataset. The experiment results demonstrate that compared with state-of-the-art methods, our model ACGVD achieves 5.01%, 13.89%, and 8.27% improvement in accuracy, recall and F1-score, respectively.

We propose a dual shearing shearography system based on a spatial light modulator (SLM). Compared to spatial phase shift shearography, the advantages of this system include its simple structure, relatively high light efficiency, and good phase map quality. Digital shearography is a fast, practical, non-contact, whole-field, and anti-turbulent optical approach to non-destructive testing (NDT) and strain measurement. Because the shearing direction determines the strain direction being measured, tests using multiple shearing directions are sometimes required to obtain strain in different directions and detect all defects. Various setups, based on the spatial phase shift method, have been proposed to solve the issue. While some of these setups perform well, they may also introduce new problems, such as poor phase map quality and low light efficiency. We present a sequential dual shearing shearographic system with good phase map quality and high light efficiency. Due to the SLM’s high-speed response, capable of reaching hundreds of hertz, SLM-based dual shearing direction shearography allows for fast temporal phase shifting and shearing direction switching while providing very good phase map quality. Unlike the spatial phase shift method, which has low light efficiency due to its need for a small aperture to enable a relatively large speckle size to cover multiple pixels, the proposed method is based on a fast temporal phase shift and does not have this limitation. In addition, SLM can provide a programmable and adjustable shearing method in any direction and distance, which is beneficial for strain measurements and NDT requiring strain measurements in different directions using a small and precise shearing distance. We describe in detail the theory derivation and non-destructive testing application results for the SLM-based dual shearing direction shearography system.

With the development of computing and communication technologies, extremely large amount of data has been collected, stored, utilized, and shared, while new security and privacy challenges arise. Existing platforms do not provide flexible and practical access control mechanisms for big data analytics applications. In this paper, we present GuardSpark++, a fine-grained access control mechanism for secure data sharing and analysis in Spark. In particular, we first propose a purpose-aware access control (PAAC) model, which introduces new concepts of data processing/operation purposes to conventional purpose-based access control. An automatic purpose analysis algorithm is developed to identify purposes from data analytics operations and queries, so that access control could be enforced accordingly. Moreover, we develop an access control mechanism in Spark Catalyst, which provides unified PAAC enforcement for heterogeneous data sources and upper-layer applications. We evaluate GuardSpark++ with five data sources and four structured data analytics engines in Spark. The experimental results show that GuardSpark++ provides effective access control functionalities with a very small performance overhead (average 3.97%).

Background Preeclampsia and preterm delivery (PTD) are believed to affect women’s long-term health including cardiovascular disease (CVD), but the biological underpinnings are largely unknown. We aimed to test whether maternal postpartum metabolomic profiles, especially CVD-related metabolites, varied according to PTD subtypes with and without preeclampsia, in a US urban, low-income multi-ethnic population. Methods This study, from the Boston Birth Cohort, included 980 women with term delivery, 79 with medically indicated PTD (mPTD) and preeclampsia, 52 with mPTD only, and 219 with spontaneous PTD (sPTD). Metabolomic profiling in postpartum plasma was conducted by liquid chromatography-mass spectrometry. Linear regression models were used to assess the associations of each metabolite with mPTD with preeclampsia, mPTD only, and sPTD, respectively, adjusting for pertinent covariates. Weighted gene coexpression network analysis was applied to investigate interconnected metabolites associated with the PTD/preeclampsia subgroups. Bonferroni correction was applied to account for multiple testing. Results A total of 380 known metabolites were analyzed. Compared to term controls, women with mPTD and preeclampsia showed a significant increase in 36 metabolites, mainly representing acylcarnitines and multiple classes of lipids (diacylglycerols, triacylglycerols, phosphocholines, and lysophosphocholines), as well as a decrease in 11 metabolites including nucleotides, steroids, and cholesteryl esters (CEs) (P −4). Alterations of diacylglycerols, triacylglycerols, and CEs in women with mPTD and preeclampsia remained significant when compared to women with mPTD only. In contrast, the metabolite differences between women with mPTD only and term controls were only seen in phosphatidylethanolamine class. Women with sPTD had significantly different levels of 16 metabolites mainly in amino acid, nucleotide, and steroid classes compared to term controls, of which, anthranilic acid, bilirubin, and steroids also had shared associations in women with mPTD and preeclampsia. Conclusion In this sample of US high-risk women, PTD/preeclampsia subgroups each showed some unique and shared associations with maternal postpartum plasma metabolites, including those known to be predictors of future CVD. These findings, if validated, may provide new insight into metabolomic alterations underlying clinically observed PTD/preeclampsia subgroups and implications for women’s future cardiometabolic health.

To date, traditional visual-based event-related potential brain-computer interface (ERP-BCI) systems continue to dominate the mainstream BCI research. However, these conventional BCIs are unsuitable for the individuals who have partly or completely lost their vision. Considering the poor performance of gaze independent ERP-BCIs, it is necessary to study techniques to improve the performance of these BCI systems. In this paper, we developed a novel 36-class bimodal ERP-BCI system based on tactile and auditory stimuli, in which six-virtual-direction audio files produced via head related transfer functions (HRTF) were delivered through headphones and location-congruent electro-tactile stimuli were simultaneously delivered to the corresponding position using electrodes placed on the abdomen and waist. We selected the eight best channels, trained a Bayesian linear discriminant analysis (BLDA) classifier and acquired the optimal trial number for target selection in online process. The average online information transfer rate (ITR) of the bimodal ERP-BCI reached 11.66 bit/min, improvements of 35.11% and 36.69% compared to the auditory (8.63 bit/min) and tactile approaches (8.53 bit/min), respectively. The results demonstrate the performance of the bimodal system is superior to each unimodal system. These facts indicate that the proposed bimodal system has potential utility as a gaze-independent BCI in future real-world applications.

Preeclampsia, which disproportionately affects Black women, is a leading cause of preterm delivery and risk for future hypertension and chronic kidney disease (CKD). Apolipoprotein L1 (APOL1) kidney risk alleles, common among Black individuals, contribute substantially to CKD disparities. Given the strong link between preeclampsia and CKD, we investigated whether maternal and fetal APOL1 risk alleles can jointly influence preeclampsia risk, and explored potential modifiers of the association between APOL1 and preeclampsia.Nested case-control study.426 Black mother-infant pairs (275 African Americans and 151 Haitians) from the Boston Birth Cohort.Maternal and fetal APOL1 risk alleles.Preeclampsia.Logistic regression models with adjustment for demographic characteristics were applied to analyze associations between fetal and maternal APOL1 risk alleles and risk of preeclampsia and to investigate the effects of modification by maternal country of origin.Fetal APOL1 risk alleles tended to be associated with an increased risk of preeclampsia, which was not statistically significant in the total genotyped population. However, this association was modified by maternal country of origin (P0.05 for interaction tests): fetal APOL1 risk alleles were significantly associated with an increased risk of preeclampsia among African Americans under recessive (odds ratio [OR], 3.6 [95% CI, 1.3-9.7]; P=0.01) and additive (OR, 1.7 [95% CI, 1.1-2.6]; P=0.01) genetic models but not in Haitian Americans. Also, maternal-fetal genotype discordance at the APOL1 locus was associated with a 2.6-fold higher risk of preeclampsia (P0.001) in African Americans.Limited sample size in stratified analyses; self-reported maternal country of origin; pre-pregnancy estimated glomerular filtration rate (eGFR) and proteinuria data in mothers were not collected; unmeasured confounding social and/or environmental factors; no replication study.This study supports the hypothesis that fetal APOL1 kidney risk alleles are associated with increased risk for preeclampsia in a recessive mode of inheritance in African Americans and suggests that maternal-fetal genotype discordance is also associated with this risk. These conclusions underscore the need to better understand maternal-fetal interaction and their genetic and environmental factors as contributors to ethnic disparities in preeclampsia.

In this paper, the normality test of charging behavior and K-means clustering are used to analyze the distribution law, and the linear programming model is established to obtain the optimal ratio of different charging power levels. The cuckoo search algorithm is used to simulate the vehicle queuing charging problem. With the maximum profit of the charging station in the next 24 hours, the cost optimization model is combined with the power system power flow equation to establish a dual-objective optimization model to obtain an optimal charging and discharging scheme.

Extreme learning machine (ELM) is a well-known cognitive model, that has been extended to cross-domain tasks. Nonetheless, most existing paradigms that are based on ELM either concern about a case in which a specific number of instances are labelled in the target domain or a learner is trained without sufficient capacity to eliminate the gap between domains. To cope with the scenario in which there are no target labels and to acquire a better adaptive learner, we propose a joint unsupervised cross-domain model via scalable discriminative ELM, which is abbreviated as JUC-SDELM. Within the framework, the scalable factor is integrated into discriminative ELM (DELM) to adjust the output margin, which strengthens the discriminative capacity of the ELM classifier. In addition, we follow the basic strategy of joint distribution adaptation (JDA) to align the subspaces generated by JUC-SDELM in terms of their statistics. The discrepancy across domains is alleviated after a few iterations. Moreover, a metric on the outputs of ELM is utilized to filter unreliable pseudo labels in the target domain, with the aim of eliminating the negative transfer effect. Results are obtained by comparing JUC-SDELM with state-of-the-art baseline methods on 16 cross-domain benchmarks that were constructed based on three combined datasets. Likewise, the outcomes in terms of key parameters are also examined. According to the experiments, our proposed model achieves competitive overall performance.

In this paper, a novel single camera three dimensional digital image correlation (3D-DIC) system, using a polarized pseudo-stereo system, is proposed. Compared to traditional 3D-DIC systems using stereovision, it has a more compact structure and better vibration resistance. Compared to the conventional single camera pseudo-stereo system that splits the CCD sensor into two halves to capture the stereo views, the proposed system achieves both views using the entire CCD chip without reduction of the spatial resolution. In addition, the center of the two views stands in the center of the CCD chip, similarly to conventional 3D-DIC systems, thus minimizing the image distortion compared to the conventional pseudo-stereo system. The two overlapped views in the CCD sensor are separated using the different polarization states, and the standard 3D-DIC algorithm can be utilized directly to perform the evaluation. The principal and experimental setup are described in detail, and multiple tests are performed to validate the system.

Ensemble trick has been widely used in extreme learning machine (ELM), and most paradigms concern about the training phase with expectation of improving their generalization ability. Unlike traditional strategies, this paper pays more attention to the prediction phase and proposes a discriminatory approach called ensemble based reactivated regularization ELM (ER2-ELM). In short, the novel literature consists of two interrelated steps where the probability density estimation is first conducted to show the degree of difficulty of identifying an instance, and then a random factor is adopted to determine whether the ELM base learner is sequentially reactivated. As such, instances easily to identify cost less computing burden, while the vague ones are taken carefully consideration. Compared with other ensemble methods, the prediction computation overhead decreases. In the end, a number of examples, including UCI benchmark datasets, handwritten digits, object detection, etc., are employed so as to illustrate its state-of-the-art performance.

Objective Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Protein kinase D1 (PKD1) is recognized as a key regulator in the progression in several solid cancers, while its clinical role in HCC is unclear. This study aimed to evaluate the correlation of PKD1 with clinical features and prognosis in HCC patients. Methods A total of 218 HCC patients who underwent resection were retrospectively enrolled. PKD1 expression in tumor (N = 218) and adjacent (N = 110) tissues was detected by immunohistochemical staining, scored by a semi-quantitative scoring method ranging from 0 to 12, and further classified as PKD1-, PKD1+, PKD1++ and PKD1+++ for analysis. Meanwhile, patients’ clinical features and survival data were acquired from the database. Results PKD1 was elevated in tumor tissues compared with adjacent tissues. Meanwhile, higher tumor PKD1 was correlated with elevated tumor size, Barcelona Clinic Liver Cancer (BCLC) stage, carbohydrate antigen 199 (CA199) level and alpha fetoprotein (AFP) level; while no correlation was found in tumor PKD1 with patients’ basic features or liver function indexes. Moreover, higher tumor PKD1 was correlated with worse overall survival (OS) in HCC patients, then further validated as an independent predictive factor for worse OS by multivariate Cox’s regression model analysis. Additionally, in Child-Pugh stage A, Child-Pugh stage B, BCLC stage 0/A, and BCLC stage B subgroups, higher tumor PKD1 was also correlated with worse OS. Conclusion Higher PKD1 in tumor tissues correlates with elevated BCLC stage, bigger tumor size, increased CA199 level, higher AFP level and worse OS in HCC patients.

BackgroundImmune-checkpoint blockade (ICB) has proved a major success, especially in highly mutated tumors such as lung cancer. Nevertheless, not all patients respond to ICB.1 It is possible that regulatory T cells (Tregs) play a role in this lack of response by suppressing tumor-reactive cytotoxic T cells,2 however the specific mechanisms that lead to this suppression remain elusive. Additionally, Tregs are necessary for protection against autoimmune disease3 and broadly depleting them could induce severe immune adverse events. It is therefore necessary to understand the functional programming and suppressive nature of Treg subsets in the tumor microenvironment to define targetable molecules for future biomarker-driven therapeutics.MethodsIn this study we performed single cell RNA-sequencing on T cells isolated from resected tissue and peripheral blood from 15 neoadjuvant nivolumab (anti-PD1)-treated and 10 untreated non-small cell lung cancer (NSCLC) patients. We identified and analyzed 71,251 CD4+ FoxP3+ Tregs. Refined clustering was performed, and we used pseudotime and differential gene analyses to understand the transcriptional relationship between clusters and patient groups. We plan to relate our Treg subcluster compositions and enriched gene sets with previously defined mouse models of ICB response as well as human head and neck squamous cell carcinoma (HNSCC).ResultsWith our highly refined clustering approach, we identified 7 distinct Treg clusters that could reflect differing functionalities within the tumor microenvironment. We demonstrate two separate Treg subsets that diverge towards either an activated state, expressing members of the tumor necrosis factor receptor (TNFR) superfamily: OX40, 41BB, GITR, or a resting state. These lineages separate ICB responders from non-responders, whose tumors are enriched in activated Tregs. We plan to stimulate receptors associated with non-response using agonist ligands or antibodies and hypothesize that their induced signaling will result in transcriptional program changes leading to highly suppressive Tregs.ConclusionsTogether, this study provides an in-depth look at the Treg-derived suppressive mechanisms governing their function in the TME of anti-PD-1-treated vs. untreated tumors. Using biospecimens obtained from the neoadjuvant setting, we were also able to study the impact of PD-1 blockade on Treg intra-tumoral function. This in-depth analysis of tumor Tregs has identified specific targetable biomarkers which could be used to improve ICB response while mitigating off-target immune adverse events by specifically inhibiting a small subset of Tregs without disturbing systemic immune homeostasis.ReferencesForde PM, Chaft JE, Smith KN, Anagnostou V, Cottrell TR, Hellmann MD, et al. Neoadjuvant PD-1 blockade in resectable lung cancer. N Engl J Med [Internet] 2018 April 16;378(21):1976–86. Available from: https://doi.org/10.1056/NEJMoa1716078Bonertz A, Weitz J, Pietsch DK, Rahbari NN, Schlude C, Ge Y, et al. Antigen-specific tregs control T cell responses against a limited repertoire of tumor antigens in patients with colorectal carcinoma. J Clin Investig 2009;119(11).Montane J, Bischoff L, Soukhatcheva G, Dai DL, Hardenberg G, Levings MK, et al. Prevention of murine autoimmune diabetes by CCL22-mediated treg recruitment to the pancreatic islets. J Clin Invest [Internet] 2011/07/01. 2011 August 1;121(8):3024–8. Available from: https://www.ncbi.nlm.nih.gov/pubmed/21737880Ethics ApprovalThis study was approved by the Institutional Review Boards (IRB) at Johns Hopkins University (JHU) and Memorial Sloan Kettering Cancer Center (NA_00092076; NCT02259621) and was conducted in accordance with the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice guidelines. The patients described in this study provided written informed consent.

In this work, high-quality BiFeO3 (BFO), Bi2O3, Bi2O3/BFO films on indium tin oxide (ITO) substrates were prepared by pulse laser deposition (PLD). Photoelectrochemical measurements were carried out to determine their potential as photoelectrodes for photoelectrochemical water splitting. The photocurrent of Bi2O3 /BFO heterojunction film was found to be twice higher than that of pure BFO film, and the onset potential was positively shifted by 240 mV. To understand the mechanism of such improved performance, detailed characterization and analysis of the band alignment and charge-carrier dynamics for all of the samples were carried out. A type II junction was formed at the interface between Bi2O3 and BFO for the heterojunction film, which resulted in the promoted electron-hole separation process under AM 1.5G light simulation. The present study suggests that Bi2O3/BFO type II junction film with superior photoelectrochemical response could be applied for designing and fabricating high-performance photoelectrochemical cells.

Three Dimensional digital image correlation(3D-DIC) has been widely used by industry, especially for strain measurement. The traditional 3D-DIC system can accurately obtain the whole-field 3D deformation. However, the conventional 3D-DIC system can only acquire the displacement field on a single surface, thus lacking information in the depth direction. Therefore, the strain in the thickness direction cannot be measured. In recent years, multiple camera DIC (multi-camera DIC) systems have become a new research topic, which provides much more measurement possibility compared to the conventional 3D-DIC system. In this paper, a multi-camera DIC system used to measure the whole-field thickness strain is introduced in detail. Four cameras are used in the system. two of them are placed at the front side of the object, and the other two cameras are placed at the back side. Each pair of cameras constitutes a sub stereo-vision system and measures the whole-field 3D deformation on one side of the object. A special calibration plate is used to calibrate the system, and the information from these two subsystems is linked by the calibration result. Whole-field thickness strain can be measured using the information obtained from both sides of the object. Additionally, the major and minor strain on the object surface are obtained simultaneously, and a whole-field quasi 3D strain history is acquired. The theory derivation for the system, experimental process, and application of determining the thinning strain limit based on the obtained whole-field thickness strain history are introduced in detail.

To evaluate the utility of transthoracic contrast echocardiography (cTTE) using vitamin B6 and sodium bicarbonate as contrast agents for diagnosing right-to-left shunt (RLS) caused by patent foramen ovale (PFO) compared to that of transesophageal echocardiography (TEE). We investigated 125 patients admitted to our neurology department with unexplained cerebral infarction and migraine. All patients underwent cTTE using vitamin B6 and sodium bicarbonate as contrast agents, after which they underwent transthoracic echocardiography. The Doppler signal was recorded during the Valsalva maneuver, and TEE examinations were performed. The feasibility, diagnostic sensitivity, and safety of cTTE and TEE for PFO recognition were compared. Evidence of PFO was found in 49 (39.20%) patients with cTTE, more than were detected with TEE (39, 31.20%) (χ2=5.0625, P=0.0244). cTTE had a sensitivity of 92.31% and a specificity of 84.88% for diagnosing PFO, showing high concordance with TEE for PFO recognition (κ=0.72). Further, results of a semi-quantitative evaluation of PFO-RLS by cTTE were better than those with TEE (Z=-2.011, P=0.044). No significant adverse reaction was discovered during cTTE examination. cTTE using vitamin B6 and sodium bicarbonate as contrast agents has relatively good sensitivity and specificity for diagnosing RLS caused by PFO when compared with those for TEE. Using vitamin B6 and sodium bicarbonate as contrast agents to perform cTTE is recommended for detecting and diagnosing the PFO due to its simplicity, non-invasive character, low cost, and high feasibility.

Water and sand inrush is one of the most serious threats in some shallow coal mines in China. In order to understand the process of sand inrush, experiments were performed to obtain the criterion for sand inrush. First, seepage tests were carried out to study the hydraulic properties of granular sandstone. The results indicate that seepage velocity has a linear relation with the porosity and particle-size distribution parameter. Then, sand inrush tests were conducted to investigate the critical conditions for sand inrush occurrence. It is determined that the sand inrush zone can be clearly distinguished based on the values of porosity and particle-size distribution parameter. Additionally, sand inrush tended to happen in the conditions of high porosity, high seepage velocity, and large particle-size distribution parameter. Further, general principles for preventing the water and sand inrush were proposed, such as reducing the porosity, improving the pore structure, and decreasing the seepage velocity. The proposed principles have been successfully used in situ to control the water and sand inrush.

To curb the high cost of drug development, there is an urgent need to develop more predictive tissue models using human cells to determine drug efficacy and safety in advance of clinical testing. Recent insights gained through fundamental biological studies have validated the importance of dynamic cell environments and cellular communication to the expression of high fidelity organ function. Building on this knowledge, emerging organ-on-a-chip technology is poised to fill the gaps in drug screening by offering predictive human tissue models with methods of sophisticated tissue assembly. Organ-on-a-chip start-ups have begun to spawn from academic research to fill this commercial space and are attracting investment to transform the drug discovery industry. This review traces the history, examines the scientific foundation and envisages the prospect of these renowned organ-on-a-chip technologies. It serves as a guide for new members of this dynamic field to navigate the existing scientific and market space.

A wideband common-gate (CG) low-noise amplifier (LNA) with dual capacitor cross-coupled (CCC) feedback and negative impedance techniques is presented for multimode multiband wireless communication applications. Double CCC technique boosts the input transconductance of the LNA, and low power consumption is obtained by using current-reuse technique. Negative impedance technique is employed to alleviate the correlation between the transconductance of the matching transistors and input impedance. Meanwhile, it also allows us to achieve a lower noise figure (NF). Moreover, current bleeding technique is adopted to allow the choice of a larger load resistor without sacrificing the voltage headroom. The proposed architecture achieves low noise, low power and high gain simultaneously without the use of bulky inductors. Simulation results of a 0.18-µm CMOS implementation show that the proposed LNA provides a maximum voltage gain of 25.02dB and a minimum NF of 2.37dB from 0.1 to 2.25GHz. The input-referred third-order intercept point (IIP3) and input 1-dB compression point (IP1dB) are better than -7.8dBm and -19.2dBm, respectively, across the operating bandwidth. The circuit dissipates 3.24mW from 1.8V DC supply with an active area of 0.03mm2. We present a wideband common-gate CMOS low-noise amplifier (LNA) for multi-mode multi-band wireless communication applications.Double capacitor cross-coupled feedback and current-reuse/current bleeding techniques enable a low power and high gain designNegative impedance technique is employed to alleviate the correlation between the transconductance of the matching transistors and input impedance, and a lower NFmin can be achieved without the use of bulky inductors.

Spelling is an important application of braincomputer interface (BCI). However, the visual saccade-independent P300 BCI spellers generally are not suited for widespread use by people who have lost voluntary eye movement due to their poor performance. In this study, we propose a novel P300 BCI paradigm for spelling through auditory-tactile bimodal stimuli. The target number of speller is increased and thus the information transfer rate (ITR) is improved. Specifically, a BCI speller with 36 selectable items was developed by simultaneously and randomly presenting auditory and tactile stimuli from same one of six directions. With six participants, the average simulated online ITR of the bimodal-stimulus-BCI system increased by 30% and 34% compared with the auditory and tactile approach, respectively. These findings suggest the proposed bimodal BCI paradigm is exceedingly efficient, which is promising for achieving quick spelling in visual saccade-independent P300-BCI application.