ALBERT

Description: Utilizing the data from the magnetometer instrument which is a part of the Electric and Magnetic Field Instrument Suite and Integrated Science (EMFISIS) instrument suite onboard the Van Allen Probe A from Sep. 2012 to Apr. 2014, when the apogee of the satellite has passed all the MLT sectors, we obtain the statistical distribution characteristic of EMIC waves in the inner magnetosphere over all local times from L =3 to L =6. Compared with the previous statistical results about EMIC waves, the occurrence rates of EMIC waves distribute relatively uniform in the MLT sectors in lower L -shells. On the other hand, in higher L -shells, there are indeed some peaks of the occurrence rate for the EMIC waves, especially in the noon, dusk and night sectors. EMIC waves appear at lower L -shells in the dawn sector than in other sectors. In the lower L -shells ( L 〈4), the occurrence rates of EMIC waves are significant in the dawn sector. This phenomenon may result from the distribution characteristic of the plasmasphere. The location of the plasmapause is usually lower in the dawn sector than that in other sectors, and the plasmapause is considered to be the favored region for the generation of EMIC waves. In higher L -shells ( L 〉4) the occurrence rates of EMIC waves are most significant in the dusk sector, implying the important role of the plasmapause or plasmaspheric plume in generating EMIC waves. We have also investigated the distribution characteristics of the hydrogen band and the helium band EMIC waves. Surprisingly, in the inner magnetosphere, the hydrogen band EMIC waves occur more frequently than the helium band EMIC waves. Both them have peaks of occurrence rate in noon, dusk and night sectors, and the hydrogen band EMIC waves have more obvious peaks than the helium band EMIC waves in the night sector, while the helium band EMIC waves are more concentrated than the hydrogen band EMIC waves in the dusk sector. Both them occur significantly in the noon sector, which implies the important role of the solar wind dynamic pressure.

Description: The 2017 Mw 6.5 Jiuzhaigou earthquake occurred at the southeastern boundary of the Bayankala block in Tibetan Plateau. Here we investigate the spatial and temporal seismicity rate changes in the Jiuzhaigou region using the finite-source epidemic-type aftershock sequence model and stochastic declustering method. The background probabilities of all events are obtained, and the cumulative background seismicity is extracted and fitted by a linear function. Following from this, we argue that there was a decrease of background seismicity in Jiuzhaigou region immediately after the occurrence of the 2008 Mw 7.9 Wenchuan earthquake. On the other hand, we also calculate the static and viscoelastic stress changes in the area around the hypocenter of the Jiuzhaigou earthquake induced by the Wenchuan earthquake. Although opposite results are resolved by previous studies, we infer a negative Coulomb failure stress change under reasonable assumptions of parameters for this case. Combining these two observed empirical relationships, we conclude that the 2017 Jiuzhaigou earthquake is delayed by the Wenchuan earthquake and the former event possibly results from the southeastward movement of the Bayankala block, which in turn arises from the collision of Indian-Australian Plate and the Eurasian Plate. These findings indicate that Bayankala block and its adjacent tectonic faults are still in the highly active seismic period that started in the 1990s. ©2018. American Geophysical Union. All Rights Reserved.

Description: Recent GPS observations show that slow slip events in south central Alaska are segmented along strike. Here we review several mechanisms that might contribute to this segmentation and focus on two: along-strike variation of slab geometry and effective normal stress. We then test them by running numerical simulations in the framework of rate-and-state friction with a nonplanar fault geometry. Results show that the segmentation is most likely related to the along-strike variation of the effective normal stress on the fault plane caused by the Yakutat Plateau. The Yakutat Plateau could affect the effective normal stress by either lowering the pore pressure in Upper Cook Inlet due to less fluids release or increasing the normal stress due to the extra buoyancy caused by the subducted Yakutat Plateau. We prefer the latter explanation because it is consistent with the relative amplitudes of the effective normal stress in Upper and Lower Cook Inlet and there is very little along-strike variation in V p /V s ratio in the fault zone from receiver function analysis. However, we cannot exclude the possibility that the difference in effective normal stress results from along-strike variation of pore pressure due to the uncertainties in the V p /V s estimates. Our work implies that a structural anomaly can have a long-lived effect on the subduction zone slip behavior and might be a driving factor on along-strike segmentation of slow slip events. ©2017. American Geophysical Union. All Rights Reserved.

Description: The Ms 6.0 earthquake in Changning, Sichuan, China, on 17 June 2019 was the largest recorded earthquake in the stable Sichuan basin. It occurred in a complicated region with salt mining and shale gas production. Whether this earthquake is induced raises concerns among the public and the scientific community. Furthermore, the relation between this earthquake and nearby industrial activities has also been of great interest. To address these questions, we estimated the nonstationary background seismicity rate and inverted for spatiotemporal stress changes. The results show that the background rate dramatically increased after hydraulic fracturing (HF) and remained at a high level until the present. Starting in 2005, the study region experienced an accelerating stress increase, and the rates of cumulative modified Coulomb stress changes were approximately 0.11  MPa/yr from January 2005 to January 2015 and 0.24  MPa/yr from January 2015 to December 2018. The 2019 Changning earthquake produced a stress step of 0.32 MPa. A clear difference between seismicity induced by salt mine injection and by HF is documented. Our results suggest that the Changning sequence might have been induced by long-term injection for salt production. Furthermore, the seismicity-stress inversion method provides a tool for using seismicity rate changes as a stress meter to monitor human-induced seismicity.

Description: Background: Immune checkpoints, including PD-1/PD-L1, play an important role in immunosuppression in various malignancies. Elevated levels of soluble programmed death-ligand1 (sPD-L1) are associated with worse prognosis in multiple myeloma and diffuse large B cell lymphoma. Herein, the purpose of this study is to investigate the relationships between plasma sPD-L1 levels and clinical response in peripheral T-cell lymphomas (PTCLs) patients. Methods: Data from three cohorts, including 11 ALCL patients, 28 PTCL-NOS patients and 81 matched normal control tissues, were also obtained from the ONCOMINE database (https://www.oncomine.org) for PD-L1 gene expression array. The comparison dataset analysis of PD-L1 mRNA levels among diverse PTCL subtypes and matched normal control tissues was performed. Other 37 PTCLs patients and 20 healthy volunteers were also enrolled in this study. Peripheral blood from patients was collected prior to systemic therapy. Plasma levels of sPD-L1 and IFN-γ were measured by enzyme-linked immunosorbent assay (ELISA). PD-L1 expression in tissues was detected by immunohistochemistry (IHC). Clinical response for patients was evaluated. Results: ONCOMINE database analyses showed that the PD-L1 mRNA expression was upregulated in PTCLs, which were significantly higher in PTCLs compared to matched normal control tissues (1 cohort, P=0.029; 2 cohort, P=0.020 and 3 cohort, P=0.021). Among another cohort of 37 PTCLs patients and 20 healthy volunteers, the median sPD-L1 level was respectively 0.729 ng/ml for 20 healthy volunteers and 1.696 ng/ml for PTCLs patients, which was significantly higher than that in healthy volunteers (P=0.000). The median IFN-γ level of PTCLs patients was 4.555 pg/ml, and that the levels of sPD-L1 was positively correlated with the level of IFN-γ (P=0.000, r=0.849) for PTCLs patients. We found that patients with elevated LDH level, advanced stage and elevated β2-MG level had higher sPD-L1 levels than those with normal LDH level, early stage and normal β2-MG level. The sPD-L1 level was also positively correlated with LDH levels (P=0.003), clinical staging (P=0.045) and β2-MG level (P=0.045). Patients with high sPD-L1 level had lower overall response rate than those with low sPD-L1 level (88.9% vs 50.0%, P= 0.022), suggesting that sPD-L1 levels was an underlying plasma biomarker to predict the clinical response in PTCL patients. The median PFS for high and low sPD-L1 level groups was 42.7 months (95% CI, 27.9-57.6) and 53 months (95% CI, 33.7-72.3), respectively. As well, the median OS for high and low sPD-L1 level groups was 48.3 months (95% CI, 35.2-61.2) and 71 months (95% CI, 51.0-90.9), respectively. Survival data suggested that patients with high sPD-L1 levels tended to have shorter PFS and OS than those with low sPD-L1 levels. We also found that plasma sPD-L1 level appeared to have a positive relationship with tissue PD-L1 expression in PTCLs patients, and both of them had a high matched rate each other (90.9%). Conclusions: PTCLs patients had higher sPD-L1 level compared with healthy volunteers. High sPD-L1 level was correlated with worse clinical response, suggesting that sPD-L1 level was an underlying plasma biomarker to predict the prognosis for PTCLs patients. Disclosures No relevant conflicts of interest to declare.

Description: Purpose De novo CD5+ DLBCL is increasingly recognized as a distinct pathologic phenomenon with a specific clinical picture. However, De novo CD5+ DLBCL has not been studied on a large scale in China. In this study, we evaluated the frequency, clinicopathological characteristics of de novo CD5+ DLBCL and prognostic impact of CD5 expression, and patient survival in our center. Methods In this study, we retrospectively investigated 745 DLBCL cases treated at Tianjin medical university cancer institute and hospital between 2000 and 2017, sub-classifying them as germinal center B cell-like (GCB) and non-GCB type by immunohistochemical staining with CD10, BCL6 and MUM-1, and then comparing the prognosis. We used a cutof ≥50% tumor cells for CD5 to be considered positive. Results In the enrolled DLBCL patients, 64 (9.2%) were CD5+ and 631 (90.8%) were CD5-. There was no significant difference in age, sex, extranodal involvement, serum LDH, C-myc overexpression and CNS relapse between these two groups. In the CD5+group, the cell of origin was non-GCB type in 46 cases (71.9%); the ratio of non-GCB type in the CD5+ group was higher than that in the CD5-group (P=0.033). Comparison of the clinical characteristics of CD5+ vs CD5-DLBCL patients showed that CD5+ DLBCL patients were more frequently elderly (〉60 years), and had B-symptoms, high performance status, stage III-IV, an IPI score 〉2, and BM involvement. 46.9% of the CD5+ patients, compared to 9.4% CD5-DLBCL patients, showed BM involvement at diagnosis. Almost 84.4% of CD5+DLBCL patients had concurrent overexpression (≥50% of the tumor cells) of antiapoptotic Bcl-2, an unfavorable biomarker. This frequency was significantly higher than that in CD5-DLBCL patients (67.2%, P=0.032). Similarly, the P53 positive rate (≥50% of the tumor cells) of CD5+DLBCL (46.9%) is significantly higher than that of CD5-DLBCL (17.6%, P=0.011). Univariate Cox analysis identified the following prognostic factors: CD5 positive, age 〉60 years, IPI≥3, BM/PB involvement, performance status and stage (III or IV). Intensive chemotherapy was not identified as significantly prognostic by univariate analysis. The CD5+GCB group showed no significant differences compared to CD5-GCB group for both PFS and OS, whereas the CD5+ non-GCB DLBCL and CD5- non-GCB DLBCL showed significantly worse prognosis compared to other groups. (P 〈 0.001, PFS and OS, respectively) (Fig.1A; 1B; 1C; 1D) In CD5+ DLBCL, PFS and OS in patients treated with rituximab were significantly better than those without rituximab. Three-year PFS was 41.1% for the former and 15.4% for the latter (P=0.036, Fig. 1E), and three-year OS were 60.7 and 46.2% (P=0.047, Fig. 1F). Next, we evaluated the therapeutic responses of different chemotherapy regiments. A total of 20 patients received treatment with R-CHOP and 24 patients received DA-EPOCH-R. Patients treated with R-CHOP showed similar PFS and OS compared with intensive treatment group (Fig. 1G,1H). Of the 631 cases of CD5- DLBCL, only 111 cases (17.6%) showed p53 overexpression. In contrast, p53 was overexpressed in 30 (46.9%) of 64 CD5+ DLBCL. As shown in Fig. 1, PFS and OS in patients with overexpression of either p53 or CD5 alone were significantly different from those in patients with p53- /CD5- DLBCL. However, patients with p53 and CD5 co-overexpression had the worst PFS and OS (P 〈 0.001, PFS and OS, respectively) (Fig. 1I, 1J). These data suggest that the negative prognostic impact of p53 and CD5 overexpression was augmented when both variables existed. In fact, all 30 patients with p53 and CD5 co-overexpression died within 40 months of diagnosis. Conclusion In summary, in this study we show that de novo CD5+ DLBCL, which occurs at a frequency (9.2%), was associated with unfavorable clinicopathologic variables and with inferior survival following R-CHOP and DA-EPOCH-R treatment. CD5+ DLBCL has a high frequency of p53 overexpression and CD5 augments the negative effect of p53 overexpression in DLBCL. Fig. 1 PFS (A) and OS (B) of patients with DLBCL according to the presence or absence of CD5. PFS (C) and OS (D) for the four DLBCL groups: CD5+ GCB DLBCL, CD5+ non-GCB DLBCL, CD5- GCB DLBCL and CD5- non-GCB DLBCL. PFS (E) and OS (F) of CD5+ DLBCL in the chemotherapy group and in the R-chemotherapy group. PFS (G) and OS (H) in CD5+ DLBCL treated with RCHOP and DA-EPOCH-R regimens. PFS (I) and OS (J) in patients with de novo DLBCL stratified according to p53 and CD5 immunostaining status. Figure 1 Disclosures No relevant conflicts of interest to declare.

Description: Background: The NT5E-adenosine axis constitutes one of the most promising immunosuppressive pathways in immune-oncology. NT5E is also named as CD73, which catalyzes the conversion of AMP to adenosine, and then the extracellular adenosine within tumor microenvironment bindings to A2a adenosine receptor (A2aR) to further dampen T cell-mediated immune responses and promote tumor immune escape. Several anti-CD73 or anti-A2aR antibodies are being evaluated in different types of malignancies in clinical trials. However, the prognostic significance and effect of NT5E-adenosine axis in diffuse large B-cell lymphoma (DLBCL) remain unclear. Methods: Multiplexed immunofluorescence staining, and a professionally and automatically assessed computer-assisted platform were applied to localize and quantify the markers from the DLBCL tumor and microenvironment cells. Gene expression status was analyzed according to the microarray data. The associations among marker expression patterns or their correlations with clinicopathological characteristics were estimated with the χ2 test and two-tailed Spearman analyses. Co-culture system of CD73 positive DLBCL cells and primary CD8 positive T cells was applied to evaluate the effect of NT5E-adenosine axis in DLBCL. Results: We found that CD73 was widely expressed on tumor and immune cells in DLBCL tissue. The CD73 positive rate on tumor cells was 52.31%, and CD73 expression on tumor cells was significantly associated with several clinicopathologic parameters, including IPI score (p = 0.020), LDH levels (p = 0.016) and Ki67 expression (p = 0.014). The A2aR positive rate on tumor-infiltrating lymphocytes (TILs) was 43.08%, and A2aR expression on TILs was significantly correlated with several clinicopathologic parameters, including IPI score (p = 0.036), clinical stage (p = 0.011), B symptom (p = 0.024) and Ki67 expression (p = 0.036). No significant difference in OS was observed in 233 DLBCL patients stratified by their CD73 gene expression status according to the microarray data (p = 0.267). There was also no significant effect of total CD73 protein expression on OS for the patients. However, a significant difference in OS was found when the patients were stratified by the CD73 expression on tumor cells, and the median survival times of the patients with CD73+/Pax-5+ and those with CD73-/Pax-5+ were 57.8 months (95% CI: 46.4-69.3) and 73.5 months (95% CI: 65.9-81.2), respectively. Patients with CD73+/Pax-5+ experienced significantly poorer outcomes than those with CD73-/Pax-5+ (p = 0.027). Furthermore, the median survival times of the patients with A2aR+ TILs and those with A2aR- TILs were respectively 53.3 months (95% CI: 40.6-66.0) and 74.5 months (95% CI: 67.5-81.5), and patients with A2aR+ TILs also had a significantly shorter survival time than those with A2aR- TILs (p = 0.003). Spearman's analysis revealed that CD73+/Pax-5+ tumor cells were positively correlated with A2aR+ TILs (R=0.395, p = 0.001). In a cohort, we found that 24 exhibited CD73-/Pax-5+ as well as A2aR- TILs, and 21 exhibited CD73+/Pax-5+ as well as A2aR+ TILs. Patients with CD73+/Pax-5+ and A2aR+TILs had poorer survival than those with CD73-/Pax-5+ and A2aR- TILs (p = 0.001). Residual patients were further classified into 2 groups, in which 7 exhibited CD73-/Pax-5+ as well as A2aR+ TILs, and 13 displayed CD73+/Pax-5+ as well as A2aR- TILs. There was a significant difference in survival among these four groups, and patients with CD73+/Pax-5+ and A2aR+ TILs had the worst outcome, with a 5-year OS rate of 57.1% (p = 0.017). We also found that CD73 positivity on tumor cells weakened the favorable prognosis for patients, which was correlated with the presence of CD8+ TILs. Patients with CD73+/Pax-5+ and CD8+ TILslow had the worst clinical outcome, with a 5-year OS rate of 50%. In contrast, patients with CD73-/Pax-5+ and CD8+ TILshigh had the best clinical outcome, with a 5-year OS rate of 100% (p = 0.002). Co-culture system displayed that CD73 being expressed on the DLBCL cells suppressed the growth of CD8 positive T cells through A2aR, but not A2aR negative T cells. Conclusions: Our findings uncovered that DLBCL patients with CD73+ on tumor cells as well as A2aR+ on TILs exhibited inferior survival and NT5E-adenosine axis inhibited the growth of CD8 positive T cells, supporting the potential combination strategies using CD73/A2aR immunosuppressive blockades as treatment options for DLBCL patients. Disclosures No relevant conflicts of interest to declare.