Establishment of an astronomical time scale for the Shizigou Formation in the Qaidam Basin,Inner Asia and orbital forced evolution of lakes during The Pliocene

The Qaidam Basin,as the largest inland basin within the Tibetan Plateau,has accumulated more than 10,000 m of Cenozoic continental sediments.It serves as a crucial research area for documenting Cenozoic climate changes and plateau uplift processes in the Asian interior.Additionally,the basin holds vast reserves of oil and gas resources,making high-resolution drilling data invaluable for studying paleoclimate.In this study,the longsequence lacustrine deposits of JS1 drill core across the Shizigou Formation in the Yiliping Depression at the western center of the basin were studied,aiming to establish an astronomical timescale for the Shizigou Formation and investigate the characteristics of paleoclimatic changes during the late Miocene to the Pliocene for the Asian interior.The analysis was carried out using high-resolution natural gamma ray(GR)data sequences,employing techniques such as spectral analysis,filtering,and wavelet analysis in cyclostratigraphy.The results indicated the presence of a stable Milankovitch orbital signal was perfectly recorded in the Shizigou Formation,primarily influenced by eccentricity cycles,with weaker obliquity and precession cycles.Using the stable and continuous 405 ka eccentricity cycle in astronomical tuning,a"floating"astronomical timescale with a duration of 6.1 Ma for the Yiliping depression's Shizigou Formation has been established.With reference to previously established stratigraphic age anchor points,an absolute astronomical timescale(2.5–8.6 Ma)has been ultimately provided for the Shizigou Formation.Simultaneously,a clear 100 ka short eccentricity cycle record has been identified during the Pliocene(5.3–2.5 Ma),which corresponds in time with the aridification within the basin during this Pliocene period.In addition,a comparison of the Pliocene natural gamma ray curve of the Qaidam Basin with global ice volume variations indicated that the basin's aridification was influenced by global cooling,with eccentricity-modulated precession cycles controlling solar radiation and subsequently affecting the evolution of lakes in the arid region of Inner Asia.

Super Resolution Perception for Improving Data Completeness in Smart Grid State Estimation

The smart grid is an evolving critical infrastructure,which combines renewable energy and the most advanced information and communication technologies to provide more economic and secure power supply services.To cope with the intermittency of ever-increasing renewable energy and ensure the security of the smart grid,state estimation,which serves as a basic tool for understanding the true states of a smart grid,should be performed with high frequency.More complete system state data are needed to support high-frequency state estimation.The data completeness problem for smart grid state estimation is therefore studied in this paper.The problem of improving data completeness by recovering highfrequency data from low-frequency data is formulated as a super resolution perception(SRP)problem in this paper.A novel machine-learning-based SRP approach is thereafter proposed.The proposed method,namely the Super Resolution Perception Net for State Estimation(SRPNSE),consists of three steps:feature extraction,information completion,and data reconstruction.Case studies have demonstrated the effectiveness and value of the proposed SRPNSE approach in recovering high-frequency data from low-frequency data for the state estimation.

Bevacizumab biosimilar LY01008 compared with bevacizumab(Avastin)as first-line treatment for Chinese patients with unresectable,metastatic,or recurrent non-squamous non-small-cell lung cancer:A multicenter,randomized,double-blinded,phase Ⅲ trial

Background:Previous studies have demonstrated the preclinical pharmacological and toxicological consistency,and clinical pharmacokinetic equivalence of bevacizumab biosimilar LY01008 with reference bevacizumab(Avastin).This randomized controlled trial aimed to compare the efficacy and safety of LY01008 with Avastin in first-line treatment of Chinese patients with advanced or recurrent non-squamous non-small cell lung cancer(NSCLC).Methods:StageⅢB-ⅣNSCLC patients with evaluable lesions,good physical status,and adequate organ functions from 67 centers across China were randomized in a ratio of 1:1 to receive LY01008 or Avastin 15 mg/kg intravenously in combination with paclitaxel/carboplatin(combined treatment)for 4-6 cycles,followed by maintenance monotherapy with LY01008 until disease progression,intolerable toxicity,or death.The primary endpoint was objective response rate(ORR)in accordance with Response Evaluation Criteria in Solid Tumors(RECIST)version 1.1 confirmed by independent radiological review committees(IRRC).Secondary endpoints included disease control rate(DCR),duration of response(DoR),progression-free survival(PFS),overall survival(OS),and safety.This study was registered in Clinical Trials.gov(NCT03533127).Results:Between December 15^(th),2017,and May 15^(th),2019,a total of 649 patients were randomized to the LY01008(n=324)or Avastin(n=325)group.As of September 25th,2019 for primary endpoint analysis,589 patients received ORR evaluation,with a median number of combined treatment cycles of 5(range 1-6)andmedian duration of treatment of 3.0(range 0.0-5.1)months.ORRof responseevaluable patients in the LY01008 and Avastin groups were 48.5% and 53.0%,respectively.The stratified ORR ratio was 0.91(90%CI 0.80-1.04,within the prespecified equivalence margin of 0.75-1.33).Up to May 15^(th),2020,with a median follow-up of 13.6(range 0.8-28.4)months,no notable differences in DCR,median DoR,median PFS,median OS,and 1-year OS rate were observed between the LY01008 and Avastin groups.There were no clinically meaningful differences in safety and immunogenicity across treatment groups.Conclusions:LY01008 demonstrated similarity to Avastin in terms of efficacy and safety in Chinese patients with advanced or recurrent non-squamous NSCLC.LY01008 combined with paclitaxel/carboplatin is expected to become a new treatment option for unresectable,metastatic,LY01008 and Avastin groups.There were no clinically meaningful differences in safety and immunogenicity across treatment groups.Conclusions:LY01008 demonstrated similarity to Avastin in terms of efficacy and safety in Chinese patients with advanced or recurrent non-squamous NSCLC.LY01008 combined with paclitaxel/carboplatin is expected to become a new treatment option for unresectable,metastatic,or recurrent non-squamous NSCLC patients in the first-line setting.

Gonadal mosaicism mediated female-biased gender control in mice

Dear Editor, In nature or during artificial breeding,evolutionary interven-tion or desirable trait selection could be achieved by means of gender control in an organism.Previously reported approaches including sex-sorted semen and genetic manipulation of a certain gene(Holden and Butler,2018;Yosef et al.,2019).In mice,a recent study demonstrated a genetic system for biasing sex ratio through crossing two genetically engineered mouse lines(Yosef et al.,2019).The maternal line encodes functional Cas9 protein on an auto-somal chromosome,whereas the paternal encodes guide RNAs on Y chromosome targeting vital genes.After fertil-ization,males carrying both Cas9 and guide RNAs were self-destructed,resulting in a female biased sex ratio.However,the litter size is proximate half of normal size since half of the progeny are eliminated.Moreover,a reproductive reservoir of males and females must be maintained for crossing.Here,we established a mouse line carrying Hspa2 promoted Cas9 and constitutively expressed sgRNA targeting repetitive sequences on Y chromosome.In those mice,spermatogenic cells carrying Y chromosome were eliminated during sper-matogenesis,resulting in female biased sex ratio in proge-nies whereas the total number was unaffected.