Limit state analysis of rigid retaining structures against seismically induced passive failure in heterogeneous soils

Soils are not necessarily uniform and may present linearly varied or layered characteristics,for example the backfilled soils behind rigid retaining walls.In the presence of large lateral thrust imposed by arch bridge,passive soil failure is possible.A reliable prediction of passive earth pressure for the design of such wall is challenging in complicated soil strata,when adopting the conventional limit analysis method.In order to overcome the challenge for generating a kinematically admissible velocity field and a statically allowable stress field,finite element method is incorporated into limit analysis,forming finiteelement upper-bound(FEUB)and finite-element lower-bound(FELB)methods.Pseudo-static,original and modified pseudo-dynamic approaches are adopted to represent seismic acceleration inputs.After generating feasible velocity and stress fields within discretized elements based on specific criteria,FEUB and FELB formulations of seismic passive earth pressure(coefficient K_(P))can be derived from work rate balance equation and stress equilibrium.Resorting to an interior point algorithm,optimal upper and lower bound solutions are obtained.The proposed FEUB and FELB procedures are well validated by limit equilibrium as well as lower-bound and kinematic analyses.Parametric studies are carried out to investigate the effects of influential factors on seismic K_(P).Notably,true solution of K_(P) is well estimated based on less than 5%difference between FEUB and FELB solutions under such complex scenarios.

Bias correction of sea surface temperature retrospective forecasts in the South China Sea

Offline bias correction of numerical marine forecast products is an effective post-processing means to improve forecast accuracy. Two offline bias correction methods for sea surface temperature(SST) forecasts have been developed in this study: a backpropagation neural network(BPNN) algorithm, and a hybrid algorithm of empirical orthogonal function(EOF) analysis and BPNN(named EOF-BPNN). The performances of these two methods are validated using bias correction experiments implemented in the South China Sea(SCS), in which the target dataset is a six-year(2003–2008) daily mean time series of SST retrospective forecasts for one-day in advance, obtained from a regional ocean forecast and analysis system called the China Ocean Reanalysis(CORA),and the reference time series is the gridded satellite-based SST. The bias-correction results show that the two methods have similar good skills;however, the EOF-BPNN method is more than five times faster than the BPNN method. Before applying the bias correction, the basin-wide climatological error of the daily mean CORA SST retrospective forecasts in the SCS is up to-3°C;now, it is minimized substantially, falling within the error range(±0.5°C) of the satellite SST data.

REGULARITY OF WEAK SOLUTIONS TO A CLASS OF NONLINEAR PROBLEM

We study the regularity of weak solutions to a class of second order parabolic system under only the assumption of continuous coefficients.We prove that the weak solution u to such system is locally Holder continuous with any exponent α∈(0,1)outside a singular set with zero parabolic measure.In particular,we prove that the regularity point in Q_(T) is an open set with full measure,and we obtain a general criterion for the weak solution to be regular in the neighborhood of a given point.Finally,we deduce the fractional time and fractional space differentiability of D_(u),and at this stage,we obtain the Hausdorff dimension of a singular set of u.

Studies on the relationship of objective response by chemotherapy and senescence induced in vitro for non-small cells lung cancer

Objective： To investigate the relationship between the objective response to combination chemotherapy of taxanes plus cisplatin in non-small cell lung cancer （NSCLC） and docetaxel plus cisplatin （DC regime） induced senescence of tumor cells in vitro. And its relation to mutant P53 protein （m-P53） was also to be evaluated. Methods： Sixty-seven specimen obtained from NSCLC patients from January 1, 2003 to June 30, 2006. The patients consisted of 48 males and 19 females, ranging in age from 54 to 82 years （mean, 67.5 years）, 41 cases were diagnosed as pathological stage Ⅲb, 26 cases were diagnosed as stage Ⅳ. Thirty-nine tumors were confirmed to be adenocarcinomas, 28 were confirmed to be squamous cell carcinomas. All patients accepted 2-6 cycles combination chemotherapy of Taxanes （docetaxel 40 mg/m^2, d1; d8, or paclitaxel 175 mg/m^2, d1） plus cisplatin （CDDP, 25 mg/m^2, d2-4）. Patients were divided into chemoresponsive （CR ＋ PR） and chemoresistant （SD ＋ PD） groups according to objective response status which was evaluated by RECIST system. Tumor cells from specimens of bronchoscopic, surgical biopsy and pleural effusion cell collection had been cultured and treated with DC in vitro. The m-P53 of culture supernatant was measured by ABC-ELISA kit before DC treatment. The telomerase activity was determined by the telomeric repeat amplification protocol （TRAP） based PCR-ELISA kit and apoptosis was determined by TdT-mediated d-UTP-X nick-end labeling （TUNEL） assay. Data represent as both actual detected and positive value. The senescence of tumor cells defined as that, apoptosis rate increased more than 50% to control, and telomerase activity decreased less than 50% to control. Results： There was no significant difference between clinical treatment response and sex, pathological type, specimen origin, or m-P53 status in cultured cell supernatant. Telomerase activity and apoptosis rate was positive in 61.1% （41/67） and 25.4%（17/67） of all samples respectively. A significant difference of senescence of tumor cells treated by DC, was existed between chemoresponsive and chemoresistant patients groups （P 〈 0.05）. Multinomial logistic regression analyses shew that telomerase activity decreased less than 50% in vitro may be an indicator of clinical response for taxanes plus cisplatin chemotherapy. Odds ratio was 4.226, P 〈 0.05. Conclusion： For NSCLC, DC induce lung cancer tumor cells senesce in vitro may be a promising predicator for clinical response, but the relationship between objective response by chemotherapy and detectable m-P53 or DC induced apoptosis is still obscure.

Cytarabine and paclitaxel exhibit different cell-cycle specificities in different cell growing status

Objective： To investigate the cell-cycle specificities of cytarabine and paclitaxel in different growing status of target cell. Methods： Using flow cytometry, we tested the cell-cycle specificities of cytarabine and paclitaxel on acute lymphocyte leukemia cell line Molt-4 in different growing status and on clinical acute lymphocyte leukemia specimens in vitro as well as in leukemia patients in vivo. Results： Cytarabine induced S phase specific cebcyde blockage and apoptosis in exponentially growing Molt-4, but showed G0/G1 phase specificity in high-density cultured Molt-4 and in clinical specimens. Paclitaxel induced G2/M phase specific cell-cycle blockage and apoptosis in exponential Molt-4, but showed G0/G1 phase specificity in high-density cultured Molt-4 and S phase specificity in clinical specimens. In the first day of clinical chemotherapy, cytarabine induced G0/G1 with a little S phase apoptosis in leukemia cells of acute lymphocyte leukemia patient in vivo. Cytarabine plus paclitaxel together had almost the same effect in the second day. Conclusion： The cell-cycle effects of cytarabine and paditaxel were different in different target cell growing status. It should be noted that the in vivo effect of these agents may be different from people usually anticipated during clinical chemotherapy. So the combined chemotherapeutic regimens may need to be redesigned.

Erratum to:Discovery of Chrysoeriol,a PI3K-AKT-mTOR Pathway Inhibitor with Potent Antitumor Activity against Human Multiple Myeloma Cells In Vitro

The authors examined the original data of their work and noticed a misuse of the image of the bands of AKT and actin in fig.2A(as shown below on the upper panel).The error occurred during the preparation of the manuscript,mainly due to the wrongly labeling of image items or folders inadvertently.The correct one is shown in fig.2 on the lower panel.The authors sincerely apologize for the mistake and confirm that the change does not affect the scientific conclusion of the published work.

Chidamide plus prednisone,cyclophosphamide,and thalidomide for relapsed or refractory peripheral T-cell lymphoma:A multicenter phase II trial

Background:Although the treatment of peripheral T-cell lymphoma(PTCL)has undergone advancements during the past several years,the response rate and long-term effects with respect to patients with PTCL remain unsatisfactory—particularly for relapsed or refractory(R/R)patients.This phase II trial was designed to explore the efficacy and safety of an all-oral regimen of chidamide plus prednisone,cyclophosphamide,and thalidomide(CPCT)for R/R PTCL patients who could not tolerate the standard chemotherapy for a variety of reasons.Methods:We conducted a multicenter phase II clinical trial in which we combined chidamide(30 mg twice weekly)with prednisone(20 mg daily after breakfast),cyclophosphamide(50 mg daily after lunch),and thalidomide(100 mg daily at bedtime)(the CPCT regimen)for a total of fewer than 12 cycles as an induction-combined treatment period,and then applied chidamide as single-drug maintenance.Forty-five patients were ultimately enrolled from August 2016 to April 2021 with respect to Chinese patients at nine centers.Our primary objective was to assess the overall response rate(ORR)after the treatment with CPCT.Results:Of the 45 enrolled patients,the optimal ORR and complete response(CR)/CR unconfirmed(CRu)were 71.1%(32/45)and 28.9%(13/45),respectively,and after a median follow-up period of 56 months,the median progression-free survival(PFS)and overall survival(OS)were 8.5 months and 17.2 months,respectively.The five-year PFS and OS rates were 21.2%(95%confidence interval[CI],7.9-34.5%)and 43.8%(95%CI,28.3-59.3%),respectively.The most common adverse event was neutropenia(20/45,44.4%),but we observed no treatment-related death.Conclusion:The all-oral CPCT regimen was an effective and safe regimen for R/R PTCL patients who could not tolerate standard chemotherapy for various reasons.Trial Registration:ClinicalTrials.gov,NCT02879526.

Overview to the Hard X-ray Modulation Telescope (Insight-HXMT) Satellite

As China’s first X-ray astronomical satellite, the Hard X-ray Modulation Telescope (HXMT), which was dubbed as Insight-HXMT after the launch on June 15, 2017, is a wide-band(1-250 ke V) slat-collimator-based X-ray astronomy satellite with the capability of all-sky monitoring in 0.2-3 Me V. It was designed to perform pointing, scanning and gamma-ray burst(GRB)observations and, based on the Direct Demodulation Method (DDM), the image of the scanned sky region can be reconstructed.Here we give an overview of the mission and its progresses, including payload, core sciences, ground calibration/facility, ground segment, data archive, software, in-orbit performance, calibration, background model, observations and some preliminary results.

Single-cell transcriptomes of peripheral blood cells indicate and elucidate severity of COVID-19

The blood and immune system of coronavirus disease 2019(COVID-19)infected patients are dysfunctional,and numerous studies have been conducted to resolve their characteristics and pathogenic mechanisms.Nevertheless,the variations of immune responses along with disease severity have not been comprehensively documented.Here,we profiled the single-cell transcriptomes of 96,313 peripheral blood mononuclear cells(PBMCs)derived from 12 COVID-19 patients(including four moderate,four severe and four critical cases)and three healthy donors.We showed that proliferative CD8 effector T cells with declined immune functions and cytotoxicity accumulated in the critical stage.By contrast,the quantity of natural killer(NK)cells was significantly reduced,while they exhibited enhanced immune activities.Notably,a gradually attenuated responseto COVID-19 along with disease severity was observed in monocytes,in terms of cellular composition,transcriptional discrepancy and transcription factor regulatory network.Furthermore,we identified immune cell-type dependent cytokine signatures distinguishing the severity of COVID-19 patients.In addition,cell interactions between CD8 effector T/NK cells and monocytes mediated by inflammatory cytokines were enhanced in moderate and severe stages,but weakened in critical cases.Collectively,our work uncovers the cellular and molecular players underlying the disordered and heterogeneous immune responses associated with COVID-19 severity,which could provide valuable insights for the treatment of critical COVID-19 patients.

Locally enhanced electric field treatment (LEEFT) for water disinfection

Water disinfection is a critical step in water and wastewater treatment.The most widely used chlorination suffers from the formation of carcinogenic disinfection by-products(DBPs)while alternative methods(e.g.,UV,O3,and membrane filtration)are limited by microbial regrowth,no residual disinfectant,and high operation cost.Here,a nanowire-enabled disinfection method,locally enhanced electric field treatment(LEEFT),is introduced with advantages of no chemical addition,no DBP formation,low energy consumption,and efficient microbial inactivation.Attributed to the lightning rod effect,the electric field near the tip area of the nanowires on the electrode is significantly enhanced to inactivate microbes,even though a small external voltage(usually<5 V)is applied.In this review,after emphasizing the significance of water disinfection,the theory of the LEEFT is explained.Subsequently,the recent development of the LEEFT technology on electrode materials and device configurations are summarized.The disinfection performance is analyzed,with respect to the operating parameters,universality against different microorganisms,electrode durability,and energy consumption.The studies on the inactivation mechanisms during the LEEFT are also reviewed.Lastly,the challenges and future research of LEEFT disinfection are discussed.

Outcome of aggressive B-cell lymphoma with TP53 alterations administered with CAR T-cell cocktail alone or in combination with ASCT

TP53 gene alteration confers inferior prognosis in refractory/relapse aggressive B-cell non-Hodgkin lymphoma(r/r B-NHL).From September 2016 to September 2020,257 r/r B-NHL patients were assessed for eligibility for two trials in our center,assessing anti-CD19 and anti-CD22 chimeric antigen receptor(CAR19/22)T-cell cocktail treatment alone or in combination with autologous stem cell transplantation(ASCT).TP53 alterations were screened in 123 enrolled patients and confirmed in 60.CAR19/22 T-cell administration resulted in best objective(ORR)and complete(CRR)response rate of 87.1%and 45.2%in patients with TP53 alterations.

T cells expressing CD5/CD7 bispecific chimeric antigen receptors with fully human heavy-chain-only domains mitigate tumor antigen escape

Bispecific chimeric antigen receptor T-cell(CAR-T)therapies have shown promising results in clinical trials for advanced B-cell malignancies.However,it is challenging to broaden the success of bispecific CAR-T therapies to treat refractory/relapse(r/r)T-cell leukemia/lymphoma because targeting multiple T-cell-expressing antigens leads to exacerbated CAR-T cell fratricide and potential safety concerns.Fully human heavy chain variable(FHVH)antibodies that specifically target CD5 or CD7 were screened and constructed to CD5/CD7 bispecific CARs.A truncated Epidermal growth factor receptor were integrated into CAR constructs to address safety concerns.To tackle the fratricidal issue of CAR-T cells targeting T-cell-pan marker(s),CRISPR/Cas9-based CD5 and CD7 genes knockout were performed before lentiviral transduction of bispecific CARs.Functional comparison between different bispecific CAR structures:tandem CARs and dual CAR were performed in vitro and in vivo to determine the optimal construct suitable for addressing T-cell malignancy antigen escape in clinical setting.Knockout of CD5 and CD7 prevents fratricide of CD5/CD7 bispecific CAR-T cells,and FHVH-derived CD5/CD7 bispecific CAR-T cells demonstrate potent antitumor activity in vitro and in vivo.The fratricide-resistant FHVH-derived CD5/CD7 bispecific CAR-T cells have potent antitumor activity against T-cell malignancies,and tandem CARs are more effective than dual CAR in preventing tumor escape in heterogeneous leukemic cells.The meaningful clinical efficacy and safety of tandem CD5/CD7 CAR-T cells deserve to be explored urgently.

Qualification of Soybean Responses to Flooding Stress Using UAV-Based Imagery and Deep Learning

Soybean is sensitive to flooding stress that may result in poor seed quality and significant yield reduction.Soybean production under flooding could be sustained by developing flood-tolerant cultivars through breeding programs.Conventionally,soybean tolerance to flooding in field conditions is evaluated by visually rating the shoot injury/damage due to flooding stress,which is labor-intensive and subjective to human error.Recent developments of field high-throughput phenotyping technology have shown great potential in measuring crop traits and detecting crop responses to abiotic and biotic stresses.The goal of this study was to investigate the potential in estimating flood-induced soybean injuries using UAV-based image features collected at different flight heights.The flooding injury score(FIS)of 724 soybean breeding plots was taken visually by breeders when soybean showed obvious injury symptoms.Aerial images were taken on the same day using a five-band multispectral and an infrared(IR)thermal camera at 20,50,and 80 m above ground.Five image features,i.e.,canopy temperature,normalized difference vegetation index,canopy area,width,and length,were extracted from the images at three flight heights.A deep learning model was used to classify the soybean breeding plots to five FIS ratings based on the extracted image features.Results show that the image features were significantly different at three flight heights.The best classification performance was obtained by the model developed using image features at 20 m with 0.9 for the five-level FIS.The results indicate that the proposed method is very promising in estimating FIS for soybean breeding.

Irrigated pinto bean crop stress and yield assessment using ground based low altitude remote sensing technology

The pinto bean is one of widely consumed legume crop that constitutes over 42%of the U.S dry bean production.However,limited studies have been conducted in past to assess its quantitative and qualitative yield potentials.Emerging remote sensing technologies can help in such assessment.Therefore,this study evaluates the role of ground-based multispectral imagery derived vegetation indices(VIs)for irrigated the pinto bean stress and yield assessments.Studied were eight cultivars of the pinto bean grown under conventional and strip tillage treatments and irrigated at 52%and 100%of required evapotranspiration.Imagery data was acquired using a five-band multispectral imager at early,mid and late growth stages.Commonly used 25 broadband VIs were derived to capture crop stress traits and yield potential.Principal component analysis and Spearman’s rank correlation tests were conducted to identify key VIs and their correlation(rs)with abiotic stress at each growth stage.Transformed difference vegetation index,nonlinear vegetation index(NLI),modified NLI and infrared percentage vegetation index(IPVI)were consistent in accounting the stress response and crop yield at all growth stages(rs>0.60,coefficient of determination(R2):0.50–0.56,P<0.05).Ten other VIs significantly accounted for crop stress at early and late stages.Overall,identified key VIs may be helpful to growers for precise crop management decision making and breeders for crop stress response and yield assessments.

Generating universal chimeric antigen receptor expressing cell products from induced pluripotent stem cells:beyond the autologous CAR-T cells

Adoptive therapeutic immune cells, such as chimeric antigen receptor (CAR)-T cells and natural killer cells, have established a new generation of precision medicine based on which dramatic breakthroughs have been achieved in intractable lymphoma treatments. Currently, well-explored approaches focus on autologous cells due to their low immunogenicity, but they are highly restricted by the high costs, time consumption of processing, and the insufficiency of primary cells in some patients. Induced pluripotent stem cells (iPSCs) are cell sources that can theoretically produce indefinite well-differentiated immune cells. Based on the above facts, it may be reasonable to combine the iPSC technology and the CAR design to produce a series of highly controllable and economical "live" drugs. Manufacturing hypoimmunogenic iPSCs by inactivation or over-expression at the genetic level and then arming the derived cells with CAR have emerged as a form of "off-the-shelf" strategy to eliminate tumor cells efficiently and safely in a broader range of patients. This review describes the reasonability, feasibility, superiority, and drawbacks of such approaches, summarizes the current practices and relevant research progress, and provides insights into the possible new paths for personalized cell-based therapies.

CAR T-cell immunotherapy: a powerful weapon for fighting hematological B-cell malignancies

The current standard of care in hematological malignancies has brought considerable clinical benefits to patients.However,important bottlenecks still limit optimal achievements following a current medical practice.The genetic complexity of the diseases and the heterogeneity of tumor clones cause difficulty in ensuring long-term efficacy of conventional treatments for most hematological disorders.Consequently,new treatment strategies are necessary to improve clinical outcomes.Chimeric antigen receptor T-cell(CAR T)immunotherapy opens a new path for targeted therapy of hematological malignancies.In this review,through a representative case study,we summarize the current experience of CAR T-cell therapy,the management of common side effects,the causative mechanisms of therapy resistance,and new strategies to improve the efficacy of CAR T-cell therapy.

Global well-posedness for the 3-D MHD equations with partial diffusion in the periodic domain

In this paper, we prove the global well-posedness of the 3-D magnetohydrodynamics(MHD) equations with partial diffusion in the periodic domain when the initial velocity is small and the initial magnetic field is close to a background magnetic field satisfying the Diophantine condition.

Infection complications in febrile chimeric antigen receptor(CAR)-T recipients during the peri-CAR-T cell treatment period examined using metagenomic next-generation sequencing(mNGS)

Dear Editor,Chimeric antigen receptor-engineered(CAR)-T cell therapy has achieved unprecedented efficacy on refractory/relapsed B-cell malignancies[1].Yet,CAR-T recipients are highly susceptible to infection due to the immunodeficiency caused by B-cell aplasia and the pretreatment with chemotherapy.However,due to the systematic use of empirical broad-spectrum antibiotics and immunosuppressors to control cytokine release syndrome(CRS)reaction,microbiological diagnosis of infection has remained challenging in CAR-T recipients.

Modeling human pregastrulation development by 3D culture of blastoids generated from primed-to-naive transitioning intermediates

Human pluripotent stem cells provide an inexhaustible model to study human embryogenesis in vitro.Recent studies have provided diverse models to generate human blastoids by self-organization of different pluripotent stem cells or somatic reprogramming intermediates.However,whether blastoids can be generated from other cell types or whether they can recapitulate postimplantation development in vitro is unknown.Here,we develop a strategy to generate human blastoids from heterogeneous intermediates with epiblast,trophectoderm,and primitive endoderm signatures of the primed-to-naïve conversion process,which resemble natural blastocysts in morphological architecture,composition of cell lineages,transcriptome,and lineage differentiation potential.In addition,these blastoids reflect many features of human peri-implantation and pregastrulation development when further cultured in an in vitro 3D culture system.In summary,our study provides an alternative strategy to generate human blastoids and offers insights into human early embryogenesis by modeling peri-and postimplantation development in vitro.

Organ function support in patients with coronavirus disease 2019:Tongji experience

Coronavirus disease 2019(COVID-19)is a highly contagious disease and a serious threat to human health.COVID-19 can cause multiple organ dysfunction,such as respiratory and circulatory failure,liver and kidney injury,disseminated intravascular coagulation,and thromboembolism,and even death.The World Health Organization reports that the mortality rate of severe-type COVID-19 is over 50%.Currently,the number of severe cases worldwide has increased rapidly,but the experience in the treatment of infected patients is still limited.Given the lack of specific antiviral drugs,multi-organ function support treatment is important for patients with COVID-19.To improve the cure rate and reduce the mortality of patients with severe-and critical-type COVID-19,this paper summarizes the experience of organ function support in patients with severe-and criticaltype COVID-19 in Optical Valley Branch of Tongji Hospital,Wuhan,China.This paper systematically summarizes the procedures of functional support therapies for multiple organs and systems,including respiratory,circulatory,renal,hepatic,and hematological systems,among patients with severe-and critical-type COVID-19.This paper provides a clinical reference and a new strategy for the optimal treatment of COVID-19 worldwide.