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In this paper, we introduce a generalized continuous collision detection (CCD) framework for the mobile robot along the polynomial trajectory in cluttered environments including various static obstacle models. Specifically, we find that the collision conditions between robots and obstacles could be transformed into a set of polynomial inequalities, whose roots can be efficiently solved by the proposed solver. In addition, we test different types of mobile robots with various kinematic and dynamic constraints in our generalized CCD framework and validate that it allows the provable collision checking and can compute the exact time of impact. Furthermore, we combine our architecture with the path planner in the navigation system. Benefiting from our CCD method, the mobile robot is able to work safely in some challenging scenarios., Comment: 8 pages. Accepted by IEEE Robotics and Automation Letters. See video (CN) at https://bilibili.com/video/BV19t4y1b7av?share_source=copy_web

Chimeric antigen receptor-T (CAR-T) therapy remains to be investigated in T-cell malignancies. CD7 is an ideal target for T-cell malignancies but is also expressed on normal T cells, which may cause CAR-T cell fratricide. Donor-derived anti-CD7 CAR-T cells using endoplasmic reticulum retention have shown efficacy in patients with T-cell acute lymphoblastic leukemia (ALL). Here we launched a phase I trial to explore differences between autologous and allogeneic anti-CD7 CAR-T therapies in T-cell ALL and lymphoma. Ten patients were treated and 5 received autologous CAR-T therapies. No dose-limiting toxicity or neurotoxicity was observed. Grade 1–2 cytokine release syndrome occurred in 7 patients, and grade 3 in 1 patient. Grade 1–2 graft-versus-host diseases were observed in 2 patients. Seven patients had bone marrow infiltration, and 100% of them achieved complete remission with negative minimal residual disease within one month. Two-fifths of patients achieved extramedullary or extranodular remission. The median follow-up was 6 (range, 2.7–14) months and bridging transplantation was not administrated. Patients treated with allogeneic CAR-T cells had higher remission rate, less recurrence and more durable CAR-T survival than those receiving autologous products. Allogeneic CAR-T cells appeared to be a better option for patients with T-cell malignancies.

The spreading of disinformation in social media threatens cybersecurity and undermines market efficiency. Detecting disinformation is challenging due to large volumes of social media content and a rapidly changing environment. This research developed and validated a theory-based, novel deep-learning approach (called TRNN) to disinformation detection. Grounded in social and psychological theories, TRNN uses deep-learning and data-centric augmentation to enhance disinformation detection in financial social media. Temporal and contextual information is encoded as specific knowledge about human-validated disinformation, which was identified from our unique collection of 745,139 financial social media messages about four U.S. high-tech company stocks and their fine-grained trading data. TRNN uses multiple series of long short-term memory (LSTM) recurrent neurons to learn dynamic and hidden patterns to support disinformation detection. Our experimental findings show that TRNN significantly outperformed widely-used machine learning techniques in terms of precision, recall, F-score and accuracy, achieving consistently better classification performance in disinformation detection. A case study of Apple Inc.'s stock price movement demonstrates the potential usability of TRNN for secure knowledge management. The research contributes to developing novel approach and model, producing new information systems artifacts and dataset, and providing empirical findings of detecting online disinformation.

Visual tracking, one of the most favorable multimedia applications, has been widely used in unmanned aerial vehicle (UAV) for civil infrastructure monitoring, aerial cinematography, autonomous navigation, etc. Most existing trackers utilize deep convolutional feature to enhance tracking robustness in scenarios of various appearance variation. However, they commonly neglect speed which is crucial for UAV with restricted calculation resources. In this work, a novel correlation filter-based keyfilter-aware tracker with a new intermittent context learning strategy is proposed to efficiently and effectively alleviate the problems of background clutter, deficient description, occlusion, illumination change, etc. Specifically, context information is utilized to empower the filter higher discriminating ability through response repression of the omnidirectional context patches. Furthermore, keyfilter is produced from the periodically selected keyframe. The latest produced keyfilter is used to restrain the current filter's corrupted changes. Most importantly, context learning of correlation filter is implemented intermittently to fully increase the tracking efficiency. This intermittent learning strategy can ensure every filter maintain context awareness owing to the restriction of keyfilter, periodically enhancing the context awareness. Substantial experiments on three challenging UAV benchmarks totally with 213 image sequences have shown that our tracker surpasses the state-of-the-art results, and exhibits a remarkable generality in short-term and long-term UAV tracking tasks as well as a variety of challenging attributes.

A graph-theoretic system decomposition method based on modified cosine-based similarity is proposed to solve the current problem of system decomposition of industrial processes. The correlations between input variables and output variables are analyzed, the initial subgraphs are built according to their weights, and the smallest subgraphs are selected for trial fusion with other subgraphs. The trial fusion result with the largest fusion index is selected as the fusion result, and the termination judgment is made. The system decomposition is more accurate than the graph-theoretic system decomposition with Pearson's correlation coefficient. Finally, the validity is verified by the Shell heavy oil fractionation column.

T cell exhaustion has been recognized to play an immunosuppressive role in malignant diseases. Persistent tumor antigen stimulation, the presence of inhibitory immune cells and cytokines in tumor microenvironment (TME), upregulated expression of inhibitory receptors, changes in T cell-related transcription factors, and metabolic factors can all result in T cell exhaustion. Strategies dedicated to preventing or reversing T cell exhaustion are required to reduce the morbidity from cancer and enhance the effectiveness of adoptive cellular immunotherapy. Here, we summarize the current findings of T cell exhaustion in hematological malignancies and chimeric antigen receptor T (CAR-T) immunotherapy, as well as the value of novel technologies, to inverse such dysfunction. Our emerging understanding of T cell exhaustion may be utilized to develop personalized strategies to restore antitumor immunity.

Correlation filter-based tracking has been widely applied in unmanned aerial vehicle (UAV) with high efficiency. However, it has two imperfections, i.e., boundary effect and filter corruption. Several methods enlarging the search area can mitigate boundary effect, yet introducing undesired background distraction. Existing frame-by-frame context learning strategies for repressing background distraction nevertheless lower the tracking speed. Inspired by keyframe-based simultaneous localization and mapping, keyfilter is proposed in visual tracking for the first time, in order to handle the above issues efficiently and effectively. Keyfilters generated by periodically selected keyframes learn the context intermittently and are used to restrain the learning of filters, so that 1) context awareness can be transmitted to all the filters via keyfilter restriction, and 2) filter corruption can be repressed. Compared to the state-of-the-art results, our tracker performs better on two challenging benchmarks, with enough speed for UAV real-time applications., 2020 International Conference on Robotics and Automation (ICRA)

Background: T cell receptor(TCR)-engineered T cell therapy, by replacing the antigen recognition domain of TCR with an antibody-derived Fab fragment, is another active field of cellular immunotherapy for cancer. We previously developed a human anti-CD19 antibody (ET190L1), and found that ET190L1-TCR-T cells maintained comparable anti-tumor potency with less cytokine release to CD28-costimulated ET190L1-CAR and CD137-based CTL019 T cells (Cell Discov. 2018 Nov 20;4:62.). ET019003-T cells are novel anti-CD19 γδ TCR-T cells generated based on ET190L1-TCR-T cells by adding an independent chimeric signaling receptor(CSR) to further promote T cell activation and reduce cytokine release (Figure 1A). We report outcomes for adult patients with relapsed or refractory diffuse large B-cell lymphoma (RR DLBCL) treated with ET019003-T cells. Methods: Our first-in-human, single-center, phase 1 study (NCT04014894) was designed to evaluate the safety and efficacy of ET019003-T cells in patients with CD19 + malignancies, of whom 8 with RR DLBCL are reported here. Eligible patients must have (1) histologically confirmed DLBCL; (2) CD19 + on malignant cells by IHC; (3) refractory disease as defined in the SCHOLAR-1 study, or recurrent disease within 6 months or at least 2 times after CR; (4) prior therapy including an anti-CD20 monoclonal antibody and an anthracycline. Patients with CNS lymphoma were eligible. Bridging therapy wasn't allowed after apheresis. Cyclophosphamide 250 mg/m 2 on day -5 and fludarabine 25 mg/m 2 on day -5 to -3 were used as the conditioning regimen. Planned dose levels were 2, 4x10 6 TCR+T cells/kg, and repeated infusions were allowed. Primary objectives were incidence of adverse events (AEs) and overall response rate(ORR). CRS and neurotoxicity were graded using the ASTCT criteria, and other AEs using CTCAE v5.0. Response was assessed per Lugano Criteria (Cheson 2014). Results: 8 pts (median age 50, range 33-71) received infusion of ET019003-T cells (6 at 2x10 6/kg, and 2 at 4x10 6/kg) and were included in the study analysis. Patient enrollment was ceased in June, 2020. Pt1 had primary CNS lymphoma, and 62.5% had stage 4 disease against Ann Arbor staging. MYC/BCL2/BCL6 triple expression was detected in 50% of pts, and double expression in 25%. Pts had received a median of 4.5 (range 2-8) prior lines of treatment, and 37.5% received prior PD-1 inhibitors, and 62.5% had primary refractory disease. 3 pts (37.5%) experienced grade 1 CRS that resolved spontaneously; 1(pt2) developed grade 3 neurotoxicity (dose-limiting toxicity), manifested by confusion, barylalia, tremor and agitation, which occurred after CRS and responded to corticosteroids. The most common AE was neutropenia (100%), and 62.5% were related to conditioning regimen; other hematologic AEs included thrombocytopenia (37.5%) and anemia (12.5%). Pt8 had pulmonary infection on day 15, and pt1 experienced viral encephalitis at 18 months, and both were manageable. As of July 20, 2021, median follow-up after infusion was 15 months (range 2-24.7). 6 pts(75%) achieved a clinical response, and 5(62.5%) reached CR, of whom 80% kept ongoing CR (all at 18+ months). 3 pts received a second infusion, pt5 for consolidation therapy after CR, and pt2 and pt7 for salvage therapy after disease progression, but response wasn't observed (Figure 1B). Pt1 with primary CNS lymphoma got continuing CR, without CRS or neurotoxicity (Figure 1C). The rate of overall survival, progression-free survival, and duration of response at 12 months was 87.5%, 62.5% and 66.7%, respectively. ET019003 cells showed striking peak expansion during 10-20 days post infusion as measured as ET019003+ cells per milliliter of PB by flow cytometry and copies per microgram of genomic DNA by qPCR, but poor expansion was observed in the second infusions (Figure 1D). ET019003 cells were detectable in cerebrospinal fluid of pt1, and continued to be detectable at 12+ months in PB of pt3 and pt5. Serum cytokine levels increased mildly post-infusion, except elevated IL-6 (>10 folds of upper limit of normal) in 3 pts (pt1 with a high baseline level, coinciding with onset of CRS and neurotoxicity of pt2, and concurrent with pulmonary infection of pt8). Conclusion: These data suggest ET019003-T cells had a good safety profile and could induce durable remission in patients with RR DLBCL, even with primary CNS lymphoma. γ/δ TCR-T cells may present a potential therapeutic option for these patients. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Background ： Chimeric antigen receptor (CAR) T cells targeting CD19 have achieved great clinical responses in patients with relapsed or refractory acute B lymphoblastic leukemia (R/R B-ALL). However, severe adverse events such as cytokine release syndrome (CRS) and neurotoxicity restrict it to further application. Tocilizumab against human interleukin-6 (IL-6) receptor is a common treatment for CAR-T cell therapy associated cytokine release syndrome. Corticosteroids are used when remission is not reached after the application of tocilizumab as well as neurotoxicity occurs, according to the guidance. However, their suitable timing still remains unclear when taking their efficacy and side effects into consideration. Methods: From January 2016 to July 2020, in our phase 1/2 clinical trials (NCT02965092、NCT04008251), 55 patients with R/R B-ALL were enrolled and injected with anti-CD19 CAR-T cells. Clinical laboratory tests on day 0、4、7、10、14、21、28 after infusion as well as endpoints、adverse events and treatment were recorded. CRS and neurotoxicity were graded according to American Society for Transplantation and Cellular Therapy (ASTCT)，and infection severity was classified as mild, moderate, severe, life-threatening, or fatal. (Young et al. Biol Blood Marrow Transplant 2016; 22:359-70.) Patients were assigned to four cohorts based on the fold change of IL-6 and the use of Tocilizumab. We defined fold change as the ratio of peak before Tocilizumab given to baseline in Tocilizumab group and the ratio of peak within 28 days to baseline in non- Tocilizumab group. According to the statistics, two groups were separated into high level (fold change over 5) and low level (fold change below 5), respectively. Wilcoxon tests、Log-rank tests and Fisher's exact tests were used to analyze statistics in GraphPad Prism 9. Results: During the observation period of 28-day-postinfusion, the use of Tocilizumab or corticosteroids did not significantly reduce the response rate or increase infectious risk (P>0.99, P=0.052). Doing a median follow-up of 7 months, the use of corticosteroids was significantly associated with shorter overall survival (OS) and progression-free survival (PFS), while it did not appear when Tocilizumab was applied alone. In addition, significantly fold change of IL-6, IL-10 were observed among subjects suffering cytokine release syndrome before the use of Tocilizumab or corticosteroids and higher levels of TNF-α were observed in 3 subjects with mild neurotoxicity (P=0.0002, P In high level group, patients treated with Tocilizumab had mild CRS limiting to grade 1-2, with shorter duration of CRS (median=5) than non-Tocilizumab (median=6) , though it is without significant difference (P=0.874). In low level group, the use of Tocilizumab is associated with shorter PFS（P=0.0275）as well as severe cytokine release syndrome. Two patients developed grade 4 CRS after infusing Tocilizumab，with apparently increased level of IL-10 (fold change=200) or IFN-γ (fold change=114.24). Neurotoxicity occurred in four patients in Tocilizumab group, and their IL-6 levels increased significantly after treatment, reaching an average peak of 1000pg/ml (157-22001.9). No neurotoxicity were observed in non-Tocilizumab group. Conclusion: Our study demonstrate that severe and persistent CRS could be avoided by applying Tocilizumab when IL-6 has increased over 5-fold from baseline. Tocilizumab is not recommended to use with little change of IL-6 because it fails to suppress the inflammatory response, and may trigger the activation of other cytokines and accelerate the progress of disease recurrence in patients. Although corticosteroids were associated with relapse, we still suggested that corticosteroids should be administrated to antagonize neurotoxicity with symptoms and significantly increased IL-6 levels after the infusion of Tocilizumab. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Background The development of mRNA sequencing has contributed greatly to the mechanism exploration in hematologic malignancies disease. With the advent of revolutionized single-cell mRNA sequencing (scRNA-seq), it is now possible to characterize every subset of expression programs and functional states in a comprehensive and unbiased manner. Here, we present a systematic evaluation of engineered chimeric antigen receptor T (CAR-T) products and patient bone marrow profiles in terms of primary resistance and severe cytokine release syndrome (CRS) at the single-cell level. Methods Using single-cell mRNA sequencing in conjunction with flow cytometry (FCM), we performed characterization of CD19-targeted CAR-T and mononuclear bone marrow cells from 4 on-trial B acute lymphoblastic leukemia (B-ALL) patients (NCT02965092). Bioinformatics analysis was utilized to explore diversity between patients with different grades of response or CRS. Basing on marker genes, CAR-T products were divided into four groups, which were double-positive T (DPT), CD4 positive T (CD4), CD8 positive T (CD8), and double-negative T (DNT) cells. Meanwhile, both the mononuclear bone marrow cells before and after CAR-T infusion were grouped into six clusters, which were B-ALL, stem, progenitor, B, T, and myeloid cells. The expression and enrichment analyses results were calculated by R (version 3.6.3) and then verified in a 22-sample conventional transcription sequencing cohort of the same clinical trial. Patient efficacy was assessed by the national comprehension cancer network guidelines version 2.2020 for acute lymphoblastic leukemia, and CRS was graded by CTCAE 5.0. Results By FCM detection, the variances of CAR-T infusion products between patients with different clinical outcomes were limited, and nor did mononuclear bone marrow cells. The scRNA sequencing results showed that distinct CAR-T and bone marrow cell subsets indicated differentiated expression in proliferation, cytotoxicity, and intercellular signaling pathways. Expression differentiation variances in CAR-T infusion products were minor than in mononuclear bone marrow cells. CD8+ CAR-T products of complete response (CR) patients were still significantly enriched in pathways such as cell killing (p adjust=0.0012), antigen processing and presentation (p adjust=0.0027), and cell cycle (p adjust=0.0231), exhibiting greater immune function when compared with no response patients. Also, DPT CAR-T products of the non-CRS patients were meaningfully enriched in negative regulation of cytokine production pathway (p adjust=0.0127) when compared with CRS ones. In mononuclear bone marrow cells, B-ALL cells before CAR-T treatment of CR patients presented negatively in cell-cycle (p adjust=0.0019), leading to a low malignant cell proliferation level; and stem-progenitor cells after CAR-T treatment of CR patients showed a stronger ability of neutrophil activation (p adjust Conclusions Through single-cell RNA-seq profiling and unbiased canonical pathway analyses, our results unveil heterogeneities in the cell cycle, immune phenotype, and metabolic profiles of subsets during CAR-T therapy, providing a mechanistic basis for ameliorating clinical outcomes and individualized management. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Background CAR T-cell therapy has shown remarkable efficacy for the treatment of hematologic malignancy. However, this novel adoptive cell therapy is associated with toxicities such as cytokine release syndrome (CRS), CAR-T related encephalopathy syndrome (CRES/ICANS) and infection. While as one of the most common toxicities after CAR T-cell therapy in the first month, infectious complications have not been systematically studied. we aim to explore the incidence, clinical and microbiological characteristics and identify high risk factors for infection in patients with ALL, NHL, and MM. The trial was registered on the Chinese Clinical Trial Registry (ChiCTR-OIC-17011180; ChiCTR1800018143). Methods 72 patients with ALL, 56 patients with NHL and 42 patients with MM from January 2016 to December 2020 are involved in the cohort and the baseline data and the clinical characteristics of infection are retrospectively analyzed within 28 days. Infections were defined as a microbiologic, histopathologic, corroborating laboratory, radiographic or clinical diagnosis, and classified as bacterial (bacteremia or site infection), viral (respiratory or other), or fungal (proven or probable). Infection severity was classified as mild, moderate, severe, life-threatening, or fatal. (Young et al.Biol Blood Marrow Transplant 2016; 22:359-70.)CRS was graded by ASTCT. We used univariate and stepwise multivariable Poisson regression to identify associations between baseline clinical characteristics and infection density, and Cox proportional hazards regression to assess high-risk factors for infection. Results Among 170 patients, a total of 119 infections occurred in 99 patients within 28 days, with a cumulative infection rate of 58.2%. The incidence of infection in ALL patients is higher than that of MM and NHL patients. Among 72 ALL patients, 46 (63.9%) patients developed infections, and among 42 MM patients, 24 patients (53.1%) developed infections. The difference in infections between these two groups of patients was statistically significant (Chi-Square test, P=0.038 78 patients had 98 bacterial infections and the cumulative incidence of bacterial infection was 45.9%. The cumulative incidence of viral infection was 8.24%, and fungal infection was 4.12%. Bacterial infections are the main types of infections in patients with different tumors, followed by viral infections, and finally fungal infections. There was no statistic significant difference in the severity of infection among different tumors, whether it was the number of patients or events (Kruskal-Wallis test, P=0.646 ,P=0.605） 75 infection events occurred in patients who were agranulocytosis, and 90% of patients with bloodstream infections had neutropenia at the time of infection. When agranulocytosis lasted for 28 days, the cumulative infection rate was 38.8%. 91 patients had both CRS and infection. The cumulative incidence of CRS and infection was 68.8% and 58.2%, respectively. Among patients with grade 3-4 CRS, 18 of 30 infections (60%) occurred after the peak of CRS. The adjusted baseline characteristic model showed that ALL patients, previous 30 days of infection history, refractory disease, ANC Conclusions Infection is one of the common complications of CAR-T cell therapy in patients with hematological malignancy. Bacterial infections occur in most patients regardless of the type of disease. ALL patients, previous 30 days of infection history，refractory disease, ANC Keywords：chimeric antigen receptor t cell；hematological malignancy； bacterial infection Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

The measurement accuracy of MEMS gyroscope is relatively low. Starting from the software level, the multi-sensor information fusion technology of MEMS gyroscope array (MGA) is used to reduce the drift of MEMS gyroscope. Firstly, a signal acquisition and processing system for communicating with ADXRS810 gyroscope based on field-programmable gate array (FPGA) is designed. Secondly, the collected drift data of the gyroscope array is preprocessed. long-term drift trend terms are obtained by ensemble empirical mode decomposition (EEMD) and the linear function fitting, and the trend terms are filtered out to obtain a smooth and normal drift signal. Then, the data fusion model based on time series analysis is built for the gyroscope array and the error analysis is performed by Allan variance. Finally, based on the AR (1) model, the moving horizon optimization Kalman filter method is used to filter the drift data of the gyroscope array. The experiment shows that when the time domain length N=3, the bias instability of gyroscope 1, 2, 3 and 4 decreases from 9.716 o/h, 8.5682 o/h, 13.484 o/h and 26.414 o/h to 1.2922 o/h, 0.61147 o/h, 1.4184 o/h and 1.6964 o/h, respectively, and the average noise coefficient decreases by more than 85%. Compared with the ordinary Kalman filter method, the bias instability has been significantly improved.

We propose a survival life time-based key distribution scheme with Y-00 protocol in optical fiber physical layer. Simulation results shows that with the proposed scheme, the bit-error rate of keys can reach 1.3%.

Robust visual tracking for the unmanned aerial vehicle (UAV) is a challenging task in different types of civilian UAV applications. Although the classical correlation filter (CF) has been widely applied for UAV object tracking, the background of the object is not learned in the classical CF. In addition, the classical CF cannot estimate the object scale changes, and it is not able to cope with object occlusion effectively. Part-based tracking approach is often used for the visual tracker to solve the occlusion issue. However, its real-time performance for the UAV cannot be achieved due to the high cost of object appearance updating. In this paper, a novel robust visual tracker is presented for the UAV. The object is initially divided into multiple parts, and different background-aware correlation filters are applied for these divided object parts, respectively. An efficient coarse-to-fine strategy with structure comparison and Bayesian inference approach is proposed to locate object and estimate the object scale changes. In addition, an adaptive threshold is presented to update each local appearance model with a Gaussian process regression method. Qualitative and quantitative tests show that the presented visual tracking algorithm reaches real-time performance (i.e., more than twenty frames per second) on an i7 processor with 640×360 image resolution, and performs favorably against the most popular state-of-the-art visual trackers in terms of robustness and accuracy. To the best of our knowledge, it is the first time that this novel scalable part-based visual tracker is presented, and applied for the UAV tracking applications.

The Micro Electro Mechanical System (MEMS) gyroscopes are widely used in many applications for the compact size and low cost. However, since the MEMS gyroscopes usually have large drift which affects the measuring precision, we need to extract the trend of drift signal and eliminate the determinate trend to reduce the disadvantageous affection. Generally, gyro’s drifts are a weak nonlinear and non-stationary random process. Thus, non-stationary time series analysis is needed. In this paper, we propose a novel approach based on the ensemble empirical mode decomposition (EEMD) to extract the trend item of the MEMS Gyroscope’s drift. The non-linear and non-stationary drift signals are decomposed into a series of intrinsic mode functions and a residual trend item by the EEMD. The method overcomes the shortcomings of the mode mixing and represents an improvement of the EMD method. The concrete steps of the proposed approach are presented and applied to a MEMS Gyroscope’s drift signals. The experiment result indicates that the method can effectively extract the trend of the drift.