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There have been many applications of drones in urban environments, such as delivery, rescue, and surveillance. In a persistent surveillance task, the drones sometimes cannot complete it independently when some regions are required to be covered on the ground. For this purpose, unmanned aerial vehicles and unmanned ground vehicles (UAVs & UGVs) system is introduced to perform such a task in this article, and the goal is to generate the circular paths for the drones and the UGVs, respectively, to minimize their travel time of realizing a complete coverage. First, the cooperative path planning problem of UAVs & UGVs is formulated into a large-scale 0–1 optimization problem, in which the on–off states of the discrete points are to be optimized. Second, a hybrid algorithm integrating the estimation of distribution algorithm (EDA) and the genetic algorithm (GA) algorithm is proposed to solve the problem. The advantages of EDA and GA in the global and local search are fully taken considering the demands in different phases of the iterative process. A simple sweep-based approach is employed to determine the optimal sequence of passing the open points. Then, an online local adjustment strategy is also applied to address the changes of the requirements on covering the ground area. Simulation results demonstrate that the UAVs & UGVs system can enhance the efficiency of the task. The hybrid EDA-GA algorithm can greatly improve the performance of EDA and GA in terms of the quality and the stability of solutions. The online adjustment strategy is effective to maintain a complete coverage while minimizing the impact on the circular paths.

Pakistan is one of those countries that are heavily dependent on hydrocarbon fuel for energy production. This results in severe CO2 emissions that lead to climate change. Although renewable energy resources such as wind are available in abundance, they have not been fully utilized and so energy crises in Pakistan increase every year. This study focuses on using wind energy as an alternative to thermal power sources as the main source of power generation in Pakistan. This research also helps in designing a project management tool to prioritize sources of power generation, including both renewables and nonrenewables, while also considering projects’ technical, environmental, social and economic criteria. An Analytical Hierarchy Process has been used to analyze the four main criteria and 12 subcriteria. The analysis revealed that wind energy is the best source among all options for power generation source, followed by solar. Oil, gas, and coal, the other three alternatives, were well below in a comparative analysis. Gas achieves overall better performance if only economic criteria are considered, but due to shortfalls in availability and diminishing reserves, this source is also not feasible. Relying on wind power as the only energy source will not be technically possible, but it can become a leading energy source inside Pakistan. This will reduce the burden on thermal energy sources and make the country more energy-secure, rather than relying heavily on imported oil and gas, as it currently does. Wind power generation capacity in Pakistan is increasing, so that the cumulative capacity is around 2118 MW installed and commissioned by the end of 2018.

We propose a causal framework to explain the catastrophic forgetting in Class-Incremental Learning (CIL) and then derive a novel distillation method that is orthogonal to the existing anti-forgetting techniques, such as data replay and feature/label distillation. We first 1) place CIL into the framework, 2) answer why the forgetting happens: the causal effect of the old data is lost in new training, and then 3) explain how the existing techniques mitigate it: they bring the causal effect back. Based on the framework, we find that although the feature/label distillation is storage-efficient, its causal effect is not coherent with the end-to-end feature learning merit, which is however preserved by data replay. To this end, we propose to distill the Colliding Effect between the old and the new data, which is fundamentally equivalent to the causal effect of data replay, but without any cost of replay storage. Thanks to the causal effect analysis, we can further capture the Incremental Momentum Effect of the data stream, removing which can help to retain the old effect overwhelmed by the new data effect, and thus alleviate the forgetting of the old class in testing. Extensive experiments on three CIL benchmarks: CIFAR-100, ImageNet-Sub&Full, show that the proposed causal effect distillation can improve various state-of-the-art CIL methods by a large margin (0.72%--9.06%).

Lipid metabolism is related to lymphomagenesis, and is a novel therapeutic target in some hematologic tumors. Apolipoprotein A (ApoA), the major protein of high-density lipoprotein (HDL), plays a crucial role in lipid transportation and protecting against cardiovascular disease, and takes effect on anti-inflammation and anti-oxidation. It is correlated with the prognosis of some solid tumors. Yet, there is no investigation involving the role of ApoA plays in chronic lymphocytic leukemia (CLL). Our retrospective study focuses on the prognostic value of ApoA in CLL and its therapeutic potential for CLL patients. Herein, ApoA is a favorable independent prognostic factor for both overall survival (OS) and progression-free survival (PFS) of CLL patients. ApoA is negatively associated with β2-microglobulin (β2-MG) and advanced stage, which are poor prognostic factors in CLL. Age, Rai stage, ApoA, and adenosine deaminase (ADA) are included in a new risk scoring system named ARAA-score. It is capable of assessing OS and PFS of CLL patients. Furthermore, cell proliferation assays show that the ApoA-I mimetic L-4F can inhibit the proliferation of CLL cell lines and primary cells. In conclusion, ApoA is of prognostic value in CLL, and is a potential therapy for CLL patients. The ARAA-score may optimize the risk stratification of CLL patients.

Real-world visual recognition requires handling the extreme sample imbalance in large-scale long-tailed data. We propose a "divide&conquer" strategy for the challenging LVIS task: divide the whole data into balanced parts and then apply incremental learning to conquer each one. This derives a novel learning paradigm: class-incremental few-shot learning, which is especially effective for the challenge evolving over time: 1) the class imbalance among the old-class knowledge review and 2) the few-shot data in new-class learning. We call our approach Learning to Segment the Tail (LST). In particular, we design an instance-level balanced replay scheme, which is a memory-efficient approximation to balance the instance-level samples from the old-class images. We also propose to use a meta-module for new-class learning, where the module parameters are shared across incremental phases, gaining the learning-to-learn knowledge incrementally, from the data-rich head to the data-poor tail. We empirically show that: at the expense of a little sacrifice of head-class forgetting, we can gain a significant 8.3% AP improvement for the tail classes with less than 10 instances, achieving an overall 2.0% AP boost for the whole 1,230 classes.

Increasing use of Unmanned Aerial Vehicle (UAV) in urban environments poses to an increased risk of fallen UAVs impacting people and vehicles on the ground, as well as colliding with manned aircraft in the vicinity of airports. Risk management of UAV flights for safe operations is essential. We proposed a comprehensive risk assessment model for UAV operation in urban environments. Three risk categories (people, vehicles, and manned aircraft) were considered and each risk cost was quantified using collision probability. We adjusted the risk costs in various magnitudes to a same scale and conducted a sensitivity analysis to determine the optimal coefficients of the three risk cost models. We then computed the total risk and generated a risk cost map for path planning. Modified path planning algorithms were used to produce a cost-effective path, and we compared their performances in terms of total risk cost and computational time. Lastly, we performed simulations to validate the feasibility and effectiveness of our proposed risk assessment model. The results show that the risk-cost-based path planning method can generate safer path for UAV operations than the traditional shortest-distance-based method. Our proposed model can be extended to complex urban environments by including more relevant parameters and data. Nanyang Technological University Published version This work was supported in part by the National Key R&D Program of China under Grant 2016YFB0502400, and in part by the UAS Programme in the Air Traffic Management Research Institute (ATMRI), Nanyang Technological University (NTU), Singapore.

Introduction: Waldenström macroglobulinaemia/ Lymphoplasmacytoid lymphoma (WM/LPL) is a rare lymphoproliferative neoplasm characterized by small B lymphocytes proliferation. Abnormalities of thyroid hormones are common in clinical courses. Yet, the role of thyroid complications has not been explored in WM/LPL. Hence, the aim of this study was to investigate the clinical significance of thyroid complications in WM/LPL. Methods: 105 clinically diagnostic WM/LPL patients from Shandong Provincial Hospital were enrolled with informed consents. Baseline and clinical data concerning sex, age, International Staging System Waldenstrom Macroglobulinemia (ISSWM) score et al were collected. Chi-square test was used for comparison of clinical characteristics. The Kaplan-Meier method was used for analysis of survival outcomes. Cox regression analyses were utilized to identify prognostic-related key factors associated with overall survival (OS) and progression-free survival (PFS) in WM/LPL patients. Microarray datasets GSE6691 were obtained from Gene Expression Omnibus. Results: Over the 105 WM/LPL patients, the median overall survival (OS) was not reached and median progression-free survival (PFS) was 96 months (Figure 1A, 1B). Patients classified as complete response (CR)/ partial response (PR)/ stable disease (SD), showed better OS and PFS than patients with progression disease (PD) (Figure 1C, D). There were 13.3% of enrolled patients with mixed thyroid complications. The results of Chi-square test showed that thyroid complications were significantly associated with reduced IgM level (p=0.036) and elevated β2-macroglobulin (p=0.032). Moreover, patients without thyroid comorbidities were more likely to get overall response (CR+PR) to the first-line treatment (p=0.004). Kaplan-Meier curves showed patients with thyroid complications had significantly shorter OS (p=0.02) and PFS (p In the univariate Cox regression model, age (p=0.022), ISSWM score (p=0.014) and thyroid complications (p Microarray dataset analysis was conducted to further investigate the role of thyroid-related genes in WM/LPL patients. A network of interactions among thyroid-related genes and critical factors in WM/LPL, including MYD88 and CXCR4, was shown in Figure 1G. Correlations were statistically significant between SLC5A5 (p Conclusion: Taken together, the present study was the first investigation on the role of thyroid complications in WM/LPL. Patients with thyroid complications showed worse clinical characteristics and conferred independent prognostic significance. The primary strength of this study is that it provides robust real-world evidence on the prognostic role of thyroid complications, highlighting the need to monitor and appropriately manage WM/LPL patients with thyroid complications in medical admissions. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

The demand on the public transportation in many cities has been increasing with the diversity of commuters’ activities that require the regular travelling across the urban and suburb areas. However, the public transport systems still suffer from the traffic congestion and detour, which will then reduce the efficiency. Accordingly, extensive efforts have been made for decades to optimize the operations of metro ground traffic with trains, subways, and buses (2D public transportation). On the other hand, unmanned aerial vehicles (UAVs) have been widely applied in the event-triggered tasks, such as delivery, rescue and surveillance in urban environments, and they have a great potential to relieve the pressure in 2D ground public transportation. Inspired from metro systems, AirMetro is a new concept proposed for future 3D public air transportation service, which carries the passengers commuting from a point to the destination, routinely and periodically. In this paper, the flight scheduling problem for AirMetro is studied based on the flight route of UAVs. The low-altitude airspace in urban environments is divided into several layers by altitude, and AirMetro is conducted in the allocated airspace as the public lanes. First, a pipeline-based route planning algorithm is proposed for the gridded urban environments to further reduce the length of a flight route generated by A* algorithm. The UAV is not required to pass through the centre of a cube in the pipeline-based algorithm when compared with the A* algorithm. This can then potentially result in a shorter flight route. As for resolving the conflict among UAVs, a minimum influence-based approach is developed to delay the flight and reduce the influence of adjustment on the follow-up flights of the UAV. By further introducing a modified simulated annealing (MSA) algorithm, the delay of flight can be further reduced by optimizing the UAV sequence conducting the conflict resolution. Results of the case studies demonstrate that the trajectory-based flight scheduling method can improve the flight efficiency by ensuring the flight safety of UAVs and reducing the average delay of UAVs as well in AirMetro. Ministry of Education (MOE) Nanyang Technological University This research work is supported by the Chongqing Research Program of Basic Research and Frontier Technology (grant number of cstc2020jcyj-msxmX0602) and the Fundamental Research Funds for the Central Universities (grant number of 2020 CDJ-LHZZ-066). Thanks are also due to China Scholarship Council (project reference number 201906055030) for the financial support of the research attachment of the first author to the ATMRI in the NTU, Singapore. This collaborative research, findings presented, and interactions among teams are also relevant to the Ministry of Education (MOE, Singapore) Tier-1 project research grant (Project ID: 2018-T1-002-124) and the UAS Program on “Urban Aerial Transport Traffic Management and Systems” in the ATMRI, NTU, Singapore. The current work also provides the basis and idea for the recently approved National Natural Science Foundation of China (grant number of 52102453).

Introduction: C-reactive protein (CRP), the most commonly used clinical indicator of inflammation, plays an important role in disease diagnosis and efficacy evaluation. Recent studies identified elevated CRP level and CRP kinetics, dynamic change of CRP level throughout treatment, were associated with decreased clinical outcome in some malignancies. Because of increased catabolism and the reduce of hepatic synthesis, albumin is oppositely associated with inflammatory. CRP/ albumin ratio (CAR) is a novel and superior prognostic factor involving inflammatory and nutritional factors in various cancers. However, the prognostic role of CRP, CRP kinetics and CRA in B-cell chronic lymphoproliferative diseases (B-CLPD) were not well characterized yet. Our study focused on the prognostic role of CRP, CRP kinetics and CRA in newly diagnosed B-CLPD. Methods: In total, 243 newly diagnosed B-CLPD patients from January 2012 to December 2019 at the Shandong provincial hospital in China were analyzed for overall survival (OS) and disease-free survival (DFS), depending on CRP, CRP kinetics and CRA. OS and DFS were determined by Kaplan-Meier curves and log-rank test. Cox proportional analysis was performed to examine the prognostic significance of clinicopathological variables in multivariate analyses. Results: The five-year OS of patients with elevated pretreatment CRP level (94.3% vs. 56.7%, p Multivariate analyses identified that elevated pretreatment CRP level (HR: 5.110, p=0.001) (Table 1), elevated post-treatment CRP level (HR: 5.826, p=0.006) (Table 2), continuously elevated CRP level (HR: 6.461, p Conclusions : We demonstrate that CRP level, CRP kinetics and CAR could be potential prognostic indicators with independent significance in patients with B-CLPD. CRP and CAR make an implementation for prognostic evaluation more easily and effectively in B-CLPD patients. Disclosures No relevant conflicts of interest to declare.

Introduction : microRNAs (miRNAs) could be released into the extracellular microenvironment and mediate cellular communication through exosomes. Circulation exosomal miRNAs have recently emerged as complimentary biomarkers and novel approaches for the non-invasive tests of early diagnosis or follow-up of neoplasms. Accumulating evidences have indicated that miR-107 plays vital functions in suppressing tumorigenesis. However, the significance of exosomal miR-107 in DLBCL remains unclear. Thus, this study aimed to explore candidate biomarkers and investigate the role of miR-107 in DLBCL as well as the molecular mechanisms involved. Methods : Differentially expressed miRNAs (DEMs) in DLBCL were identified based on Gene Expression Omnibus (GEO) datasets and verified in a cohort of DLBCL patients. The functions and biological pathways of DEMs were enriched by DAVID. Serum-derived exosomes of 42 DLBCL patients and 31 healthy volunteers were isolated with informed consents by Exo Easy Maxi Kit, and further detected by western blot and transmission electron microscopy (TEM). Receiver operating characteristic curves (ROC) were performed to evaluate the diagnostic value of DEMs. The biological function of miR-107 in DLBCL were evaluated by miR-107 Agomir. Survival analyses were performed by the Kaplan-Meier method. Potential targets genes of miR-107 were predicted by miRDB, PicTar, Targetscan and miRTarBase. Western blotting and confocal staining assay were used to detect the expression of YWHAH. Interaction of miR-107 and YWHAH was confirmed by dual-luciferase reporter assay. Results : 14 DEMs were identified in DLBCL through evaluating the miRNA microarray profile of GSE117063 (Fig. 1A-A) and GSE29493 (Fig. 1A-B). The biological processes of these DEMs mainly enriched in regulatory of transcription, protein phosphorylation and cell proliferation (Fig.1B). In order to explore candidate exosomal biomarkers for DLBCL, we then isolated serum-derived exosomes from DLBCL patients. As depicted in Fig.1C, exosomes not only expressed exosomal biomarkers Tsg101 and CD9 but also shown cup-shape morphology. We further assessed the expression of DEMs on exosomes by qRT-PCR. Compared with normal samples, only two down-regulated miRNAs (miR-107, miR-375) and one up-regulated miRNAs (miR-485) were statistically dysregulated in DLBCL patients (Fig.2A). ROC curve analysis demonstrated that exosomal miR-107, miR-375, and miR-485 might be potential biomarkers for DLBCL patients, with the AUC of 0.854, 0.769, and 0.703, respectively (Fig.2B). In addition, survival analysis revealed that low-expression of miR-107 in DLBCL patients significantly associated with undesirable clinical outcomes (Fig.2C, p Down-regulation of miR-107 was confirmed in DLBCL cell lines by qRT-PCR (Fig.3A). To validate our hypothesis, we up-regulated miR-107 expression by miRNA Agomir, which could significantly reduce cell proliferation and migration, and promote cell apoptosis (Fig.3B-D). The regulatory mechanisms of miR-107 in DLBCL was further explored. 28 target genes of miR-107 were identified and shown in Fig.4A. KEGG pathway analysis revealed that the targeted genes mainly enriched in the PI3K-Akt, Hippo, and AMPK signaling pathways (Fig.4B). We found out that the target gene YWHAH (14-3-3η) was significantly upregulated in the DLBCL cells (Fig.4C-D). Moreover, dual-luciferase assay revealed that miRNA-107 perform anti-tumor effect through targeting the 3'UTR region of YWHAH (Fig.4E-F). As previously reported, YWHAH associated with tumor metastasis, chemoresistance, apoptosis resistance and poor prognosis in DLBCL. Thus, we suggested that miR-107 antagonized DLBCL progression through downregulating YWHAH. Conclusion : In this study, we demonstrated for the first time that serum exosomal miR-107, miR-375, and miR-485 could be applied as potential non-invasive biomarkers in early diagnosis of DLBCL patients. Furthermore, miR-107 inhibited DLBCL progression by targeting YWHAH, which will provide a promising therapeutic approach for DLBCL. Disclosures No relevant conflicts of interest to declare.

Introduction CTP synthase 2 (CTPS2) is a critical regulator in lymphocytes proliferation and nucleotides synthesis. Yet, the role of CTPS2 has not been explored in chronic lymphocytic leukemia (CLL). Hence, the aim of this study was to investigate the clinical significance and functional mechanism of CTPS2 regulation in CLL pathogenesis and progression. Methods In the present study, 1030 clinically annotated CLL patients from multiple cohorts were enrolled with informed consents. Peripheral blood samples from 66 de novo CLL patients were collected at the Department of Hematology in Shandong Provincial Hospital. Expression levels of CTPS2 in CLL cells were determined by quantitative RT-PCR and western blotting. Lentiviral vectors were utilized to stably silence CTPS2. RNA-sequencing and functional enrichment analysis were performed. Besides, cell viability, apoptosis and cell cycle were assessed by cell counting kit-8, annexin V-PE/7AAD and PI/RNase staining, respectively. All investigators comply with the guiding principles for experimental procedures found in the Declaration of Helsinki of the World Medical Association. Results Aberrantly increased expression of CTPS2 was detected in CLL primary cells and cell lines (MEC1 and EHEB) at mRNA and protein level compared with normal B cells (p Kaplan-Meier curves showed stratified CTPS2high patients were observed with significantly shorter overall survival versus the CTPS2low group in 2 independent cohorts (cohort 1, HR=4.488, p=0.001, Figure 2A; cohort 2, HR=1.614, p=0.049, Figure 2B). Besides, enhanced expression of CTPS2 were revealed to predict inferior treatment-free survival (cohort 1, HR=2.715, p=0.003, Figure 2C; cohort 2, HR=1.909, p=0.008, Figure 2D). Univariate cox regression analysis suggested that CTPS2 high expression predicted adverse survival (HR=1.785, p=0.003). Moreover, multivariate cox regression analysis confirmed the prognostic value of CTPS2 overexpression in CLL patients independent of age and Binet stage (HR=1.724, p=0.007; Figure 2E). To investigate the biological processes of CTPS2 involving in CLL progression, functional assays were performed. CLL cells with CTPS2 silencing exhibited attenuated cell proliferation, increased fast-onset apoptosis and induced G2/M phase arrest (Figure 3A-E). Additionally, down-regulated Bcl-2 expression as well as promoted cleaved-PARP, Bax and p21 expression were observed in CTPS2 knock-down transfected CLL cells (Figure 3F). To further explore the mechanism of CTPS2 regulation in the tumorigenesis of CLL, RNA-sequencing was conducted in CLL transfected cells. Annotations of differentiated genes implicated that CTPS2 was functionally enriched in cell cycle, DNA replication activation and oncogenic pathways (Figure 4A). Accordantly, activation of p-ATM, p-BRAC1, p-H2AX were visibly elevated, illuminating the potential mechanism of CTPS2 regulating DNA damage in CLL pathogenesis (Figure 4B). Collectively, the interactive network of CTPS2 and its down-stream targets was established, illuminating the potential mechanism of CTPS2 regulation in CLL progression (Figure 4C). Conclusion Taken together, the present study was the first investigation on the role of CTPS2 in CLL tumorigenesis by in silico analysis and ex vivo evaluation. CTPS2 was up-regulated and conferred independent inferior prognostic significance, highlighting the effectiveness and potential of CTPS2 in risk stratification and targeted strategy in CLL patients. Disclosures No relevant conflicts of interest to declare.

6H-SiC single crystals have been successfully grown on (1015) plane seed by sublimation method. High density stacking faults (SFs) were observed by transmission synchrotron radiation X-ray topography. Based on the invisibility criteria of stacking faults, the displacement vectors of most SFs were determined to be the type of 1/6[1120]. Laser scanning confocal microscopy (LSCM) was used to observe the etching morphology of (0115) wafer. The etching steps of SFs were found and their density decreased from 3.6×103 cm-1 to 2.0×102 cm-1 along the projection direction. The inclination angles of the SFs etching step plane to (10-15) plane were measured by line scanning of LSCM. It was found that the inclination angles decreased from 20° to 10° along the projection direction. Different etching characteristics of SFs along radial direction of 6H-SiC (1015) wafer should be attributed to different displacement vectors and different stacking fault energies for these stacking faults. (© 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)