ALBERT

Description: Geothermal energy is one of the cleanest sources of energy which is gaining importance as an alternative to hydrocarbons. Geothermal energy reserves in China are enormous and it has a huge potential for exploitation and utilization. However, the development of the geothermal industry in China lags far behind other renewable energy sources because of the lack of fiscal and taxation policy support. In this paper, we adopt the system dynamics method and use the causal loop diagram to explore the development mechanism of fiscal and taxation policies in the geothermal industry. The effect of the fiscal and taxation policy on the development of the geothermal industry is analyzed. In order to promote sustainable development of the geothermal industry in China, the government should pay more attention to subsidies for the geothermal industry in the life-cycle stage of the geothermal industry. Furthermore, a plan is necessary to provide a reasonable system of fiscal and taxation policies.

Description: We propose a compact 1-mm-radius microring resonator sensor based on a hybrid plasmonic waveguide on a silicon-on-insulator substrate. The hybrid waveguide is composed of a metal-gap-silicon structure, where the optical energy is greatly enhanced in the narrow gap. We use the finite element method to numerically analyze the device optical characteristics as a biochemical sensor. As the optical field in the hybrid micoring resonator has a large overlap with the upper-cladding sensing medium, the sensitivity is very high compared to other dielectric microring resonator sensors. The compactness of the hybrid microring resonator is resulted from the balance between bending radiation loss and metal absorption loss. The proposed hybrid microring resonator sensors have the main advantages of small footprint and high sensitivity and can be potentially integrated in an array form on a chip for highly-efficient lab-on-chip biochemical sensing applications.

Description: The objective of this work is to analyze the temporal and spatial variability of the total ozone column (TOC) trends over the Yangtze River Delta, the most populated region in China, during the last 35 years (1978–2013) using remote sensing-derived TOC data. Due to the lack of continuous and well-covered ground-based TOC measurements, little is known about the Yangtze River Delta. TOC data derived from the Total Ozone Mapping Spectrometer (TOMS) for the period 1978–2005 and Ozone Monitoring Instrument (OMI) for the period 2004–2013 were used in this study. The spatial, long-term, seasonal, and short-term variations of TOC in this region were analyzed. For the spatial variability, the latitudinal variability has a large range between 3% and 13%, and also represents an annual cycle with maximum in February and minimum in August. In contrast, the longitudinal variability is not significant and just varies between 2% and 4%. The long-term variability represented a notable decline for the period 1978–2013. The ozone depletion was observed significantly during 1978–1999, with linear trend from (−3.2 ± 0.7) DU/decade to (−10.5 ± 0.9) DU/decade. As for seasonal variability, the trend of TOC shows a distinct seasonal pattern, with maximum in April or May and minimum in October or November. The short-term analysis demonstrates the day-to-day changes as well as the six-week system persistence of the TOC. The results can provide comprehensive descriptions of the TOC variations in the Yangtze River Delta and benefit climate change research in this region.

Description: Sensors, Vol. 18, Pages 1950: An Optimization Routing Algorithm for Green Communication in Underground Mines Sensors doi: 10.3390/s18061950 Authors: Heng Xu Qiyue Li Jianping Wang Guojun Luo Chenghui Zhu Wei Sun With the long-term dependence of humans on ore-based energy, underground mines are utilized around the world, and underground mining is often dangerous. Therefore, many underground mines have established networks that manage and acquire information from sensor nodes deployed on miners and in other places. Since the power supplies of many mobile sensor nodes are batteries, green communication is an effective approach of reducing the energy consumption of a network and extending its longevity. To reduce the energy consumption of networks, all factors that negatively influence the lifetime should be considered. The degree constraint minimum spanning tree (DCMST) is introduced in this study to consider all the heterogeneous factors and assign weights for the next step of the evaluation. Then, a genetic algorithm (GA) is introduced to cluster sensor nodes in the network and balance energy consumption according to several heterogeneous factors and routing paths from DCMST. Based on a comparison of the simulation results, the optimization routing algorithm proposed in this study for use in green communication in underground mines can effectively reduce the network energy consumption and extend the lifetimes of networks.

Description: Assessing the failure potential of slopes is of great significance for land use and management. The objective of this paper is to develop a novel model for evaluating the failure probability of slopes based on a relevance vector machine (RVM), with a special attention to the characteristics of failed slopes along the lower reaches of the Jinsha River, close to the Wudongde dam site. Seven parameters that influence the occurrence of landslides were selected as environmental factors; namely lithology, slope angle, slope height, slope aspect, slope structure, distance from faults, and land use. A total of 55 landslides mapped in the study area were used to train and test the RVM model. The results suggest that the accuracy of the model in predicting the failure probability of slopes, using both training and testing data sets, is very high and deemed satisfactory. To validate the model performance, it was applied to 28 landslide cases identified in the upper reaches of the Jinsha River, where environmental and geological conditions are similar to those of the study area. An accuracy of approximately 92.9% was obtained, which demonstrates that the RVM model has a good generalization performance.

Description: IJERPH, Vol. 15, Pages 114: Spatiotemporal Patterns of Ground Monitored PM2.5 Concentrations in China in Recent Years International Journal of Environmental Research and Public Health doi: 10.3390/ijerph15010114 Authors: Junming Li Xiulan Han Xiao Li Jianping Yang Xuejiao Li This paper firstly explores the space-time evolution of city-level PM 2.5 concentrations showed a very significant seasonal cycle type fluctuation during the period between 13 May 2014 and 30 May 2017. The period from October to April following each year was a heavy pollution period, whereas the phase from April to October of the current year was part of a light pollution period. The average monthly PM 2.5 concentrations in mainland China based on ground monitoring, employing a descriptive statistics method and a Bayesian spatiotemporal hierarchy model. Daily and weekly average PM 2.5 concentrations in 338 cities in mainland China presented no significant spatial difference during the severe pollution period but a large spatial difference during light pollution periods. The severe PM 2.5 pollution areas were mainly distributed in the Beijing-Tianjin-Hebei urban agglomeration in the North China Plain during the beginning of each autumn-winter season (September), spreading to the Northeast Plains after October, then later continuing to spread to other cities in mainland China, eventually covering most cities. PM 2.5 pollution in China appeared to be a cyclic characteristic of first spreading and then centralizing in the space in two spring-summer seasons, and showed an obvious process of first diffusing then transferring to shrinkage alternation during the spring-summer season of 2015, but showed no obvious diffusion during the spring-summer season of 2016, maintaining a stable spatial structure after the shrinkage in June, as well as being more concentrated. The heavily polluted areas are continuously and steadily concentrated in East China, Central China and Xinjiang Province.

Description: Somatic mutations and chromosomal translocations of genes have emerged as major drivers in a range of hematopoietic malignancies. While ASXL1 is mutated in all forms of myeloid malignancies, ASXL2 is specifically mutated in t(8;21) AML patients. ASXL1 and ASXL2 mutations are mutually exclusive in t(8;21) AML. Despite the importance of ASXL2 mutations in clinical, it's role in leukemogenesis remain unknown. In the current study, we sought to dissect the role of ASXL2 in normal hematopoiesis and to identify the molecular mechanisms by which Asxl2 loss contributes to myeloid malignancies. In the current study, we utilized a mouse model of Asxl2 to characterize the hematopoietic features of in vivo. Asxl2-/- mice were characterized by pancytopenia and dysplastic features, including hyposegmented (bilobed) neutrophils with fine nuclear bridging (consistent with pseudo Pelger-Huët) and increased number of polychromatophilic red blood cells (RBCs), reminiscent of myelodysplastic syndrome (MDS). Flow cytometric analyses revealed that Asxl2-/- mice had an increased proportion of granulocytic/monocytic cells (Gr-1+/Mac1+) in the PB, BM and spleens compared to WT mice. The histologic analysis of the Asxl2+/- and Asxl2-/- spleen sections showed disrupted splenic architecture with an increased proportion of myeloid cells and massive accumulation of myeloperoxidase (MPO) positive cells in WT spleens. Asxl2-/- mice had an increased long-term (LH)-HSCs and granulocyte-macrophage progenitor (GMP) cells compared to WT mice.Consistently, the paired-daughter cell assays revealed that Asxl2-/- CD34-LSK BM cells had a higher proportion of cells with symmetric self-renewal capacity (SS, 62%) than WT cells (33%). In contrast, a significant reduction in the cells with symmetric differentiation potential was observed in Asxl2-/- HSCs (18%) compared to WT HSCs (40%), indicating a critical role of ASXL2 in the balance between the symmetric and asymmetric division of HSCs. Transplantation assays revealed that recipients transplanted with Asxl2-/- and Asxl2+/- bone marrow cells had shortened lifespan due to the development of MDS or AML, suggesting a cell-autonomous effect of Asxl2-loss in HSC/HPC functions. Furthermore, Asxl2-loss further increase the colony-forming potential and colony replating capacity of AML1-ETO expressing HSCs in vitro, suggesting a cooperative effect between AML1/ETO9a and Asxl2+/-to promote HSC self-renewal. RNA-seq analysis showed a unique signature of Asxl2-/- LK cells compared to WT LK cells. Gene set enrichment analysis revealed that altered expressed genes in Asxl2-/-LK cells were enriched in myeloid cell differentiation, hematopoiesis, apoptosis, and chromatin/nucleosome assembly signature. ChIP-seq analysis showed that differentially expressed genes were associated with dysregulated histone enhancer markers, including H3K27ac, H3K4me1, and H3K4me2. Further analysis demonstrated that the alteration of H3K27ac enrichment had a greater impact on gene expression, in comparison to H3K4me1/2. KEGG pathway analysis showed that genes with differential H3K27ac signals were enriched for hematopoietic cell lineage, cancer signaling pathway and myeloid leukemia development. IPA analysis further confirmed that genes with altered enrichment levels of were enriched in myeloid cell differentiation and apoptosis pathways. Altogether, these data suggest that ASXL2 regulates gene expression mainly through enhancer markers. Our results demonstrate that ASXL2 plays an important role in normal hematopoiesis, and Asxl2-loss in mice is sufficient to cause MDS-like disease and leukemia transformation. These results indicate that ASXL2 functions as a tumor suppressor in myelopoiesis. The Asxl2 knock-out mice present an ideal model for unveiling the mechanisms underlying the Asxl2-loss mediated multiple-step pathogenesis of myeloid malignancies and for testing novel therapeutic agents for myeloid malignant patients with ASXL2 alterations. Further studies to dissect the possible roles of ASXL2alterations in leukemogenesis and to identify therapeutic vulnerabilities they may create are ongoing. Disclosures No relevant conflicts of interest to declare.

Description: Background: With antivirus prophylaxis, reactivation of hepatitis B virus (HBV) also occurred in HBV carriers (hepatitis B surface antigen [HBsAg] positive) undergoing rituximab combination chemotherapy. It was reported that most HBV carriers with improved long-term outcomes were seropositive for hepatitis B e antibody (HBeAb). In this study on HBsAg-positive lymphoma patients with prophylaxis, the objectives were to determine the HBV reactivation rate in patients with HBeAb positive compared with the patients with HBeAb negative. Methods: We retrospectively analyzed the medical records of 113 HBV carriers with CD20(+) diffuse large B-cell lymphoma (DLBCL) received R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy with antivirus prophylaxis between August 1, 2002 and November 31, 2011 at Sun Yat-sen University Cancer Center, China. Results: Among 113 HBV carriers with CD20(+) DLBCL, 68(60.2%) were hepatitis B e antibody (HBeAb) positive. There was no significant difference in terms of sex distribution, age, ECOG PS, stage, baseline HBV DNA detectable rate, or ALT, AST, bilirubin, or LDH between the HBeAb positive group and the HBeAb negative group. However, there were a significantly higher proportion of HBeAg seronegativity (94.1%v 24.4%; P〈 .001), and HBcAb seropositivity (100.0%v 82.2%; P〈 .001) in the HBeAb positive group. All the patients received antiviral therapy before chemotherapy. The antiviral treatments were used as follows: lamivudine in 68 (60.2%) patients, entecavir in 18 (15.2%) patients, others in 27 (23.8%) patients. Other antiviral treatments were including adefovir, lamivudine plus entecavir, lamivudine at beginning and then entecavir, and so on. No significant difference was observed in the antiviral drugs between the two groups. After R-CHOP chemotherapy, HBV reactivation was found in 23.0% of HBV carriers (26/113). And its incidence rate was lower in HBsAg- positive / HBeAb positive patients than in HBsAg-positive/ HBeAb negative patients (16.1% versus 33.3%; P =.034). Multivariate analysis showed that patients positive for HBeAb before chemotherapy was the only significant and independent protective factor associated with hepatitis due to HBV reactivation after chemotherapy. Chemotherapy was continued when the serum HBV-DNA level reduced or liver function improved. Survival was not affected by the occurrence of HBV reactivation or the status of HBeAb. Conclusion: HBeAb positive before rituximab combination chemotherapy was associated with a lower risk of HBV reactivation in HBV carriers with CD20(+) DLBCL. A more effective antivirus prophylaxis may be considered in HBV carriers with HBeAb negative in order to reduce HBV reactivation. Disclosures No relevant conflicts of interest to declare.

Description: Despite improvements in chemotherapy that have increased the 5-year survival rates of pediatric ALL to close to 90%, 15-20% of patients may relapse with a very poor prognosis. Pediatric ALL patients, particularly those in relapse can harbor a specific point mutation (E1099K) in NSD2 (nuclear receptor binding SET domain protein 2) gene, also known as MMSET or WHSC1, which encodes a histone methyl transferase specific for H3K36me2. To understand the biology of mutant NSD2, we used CRISPR-Cas9 gene editing to disrupt the NSD2E1099K mutant allele in B-ALL cell lines (RCH-ACV and SEM) and T-ALL cell line (RPMI-8402) or insert the E1099K mutation into the NSD2WT T-ALL cell line (CEM) and B-ALL cell line (697). Cell lines in which the NSD2E1099K mutant allele is present display increased global levels of H3K36me2 and decreased H3K27me3. NSD2E1099Kcells demonstrate enhanced cell growth, colony formation and migration. NSD2E1099K mutant cell lines assayed by RNA-Seq exhibit an aberrant gene signature, mostly representing gene activation, with activation of signaling pathways, genes implicated in the epithelial mesenchymal transition and prominent expression of neural genes not generally found in hematopoietic tissues. Accordingly, NSD2E1099K cell lines showed prominent tropism to the central neural system in xenografts. To understand why this NSD2 mutations are identified prominently in children who relapse early from therapy for ALL, we performed high-throughput screening in our isogenic cell lines with the National Center for Advancing Translation Science (NCATS) Pharmaceutical Collection and other annotated chemical libraries and found that NSD2E1099K cells are resistant to glucocorticoids (GC) but not to other chemotherapeutic agents used to treat ALL such as vincristine, doxorubicin, cyclophosphamide, methotrexate, and 6-mercaptopurine. Accordingly, patient-derived-xenograft ALL cells with NSD2E1099K mutation were resistant to GC treatment. Reversion of NSD2E1099K mutation to NSD2WT restored GC sensitivity to both B- and T-ALL cell lines, which was accompanied by cell cycle arrest in G1 and induced-apoptosis. Furthermore, knock-in of the NSD2E1099K mutation conferred GC resistance to ALL cell lines by triggering cell cycle progression, proliferation and anti-apoptotic processes. Mice with NSD2E1099K xenografts were completely resistant to GC treatment while treatment of mice injected with isogenic NSD2WT cells led to significant tumor reduction and survival benefit. To illustrate these biological phenotypes and understand the molecular mechanism of GC resistance driven by NSD2E1099Kmutation, we investigated the GC-induced transcriptome, GC receptor (GR) binding sites and related epigenetic changes in isogenic ALL cell lines in response to GC treatment. RNA-Seq showed that GC transcriptional response was almost completely blocked in NSD2E1099K cells, especially in T-ALL cell lines, correlating with their lack of biological response. GC treatment activated apoptotic pathways and downregulated cell cycle and DNA repair pathways only in NSD2WT cells. The critical pro-apoptotic regulators BIM and BMF failed to be activated by GC in NSD2E1099K cells but were prominently activated when the NSD2 mutation was removed. Chromatin immunoprecipitation sequencing (ChIP-Seq) showed that, the NSD2E1099K mutation blocked the ability of GR and CTCF to bind most GC response elements (GREs) such as those within BIM and BMF. While GR binding in NSD2WT cells was accompanied by increased H3K27 acetylation and gene expression, this failed to occur in NSD2 mutant cells. Furthermore, we found that GR RNA and protein levels were repressed in ALL cells expressing NSD2E1099K and GC failed to induce GR expression in these cells. Paradoxically, while H3K27me3 levels were generally decreased in NSD2E1099K cells, we saw increased levels of H3K27me3 at the GRE within the GR gene body where GR itself and CTCF normally bind, suggesting a novel role for the polycomb repressive complex 2 and EZH2 inhibitors for this form of GC resistance. In conclusion, these studies demonstrate that NSD2E1099K mutation may play an important role in treatment failure of pediatric ALL relapse by interfering with the GR expression and its ability to bind and activate key target genes. Gene editing screens are being performed to understand how to overcome this resistance. Disclosures No relevant conflicts of interest to declare.

Description: Aplastic anemia (AA) is an immune-mediated bone marrow failure, resulting in reduced number of hematopoietic stem and progenitor cells and pancytopenia. The presence of paroxysmal nocturnal hemoglobinuria (PNH) clone in AA usually suggests an immunopathogenesis in patients. However, when and how PNH clone emerge in AA is still unclear. Hepatitis associated aplastic anemia (HAAA) is a special variant of AA with a clear disease course and relatively explicit immune pathogenesis, thus serves as a good model to explore the emergence and expansion of PNH clone. To evaluate the frequency and clonal evolution of PNH clones in AA, we retrospectively analyzed the clinical data of 90 HAAA patients that were consecutively diagnosed between August 2006 and March 2018 in Blood Diseases Hospital, and we included 403 idiopathic AA (IAA) patients as control. PNH clones were detected in 8 HAAA patients (8.9%,8/90) at the time of diagnosis, compared to 18.1% (73/403) in IAA. Eight HAAA patients had PNH clone in granulocytes with a median clone size of 3.90% (1.09-12.33%), and 3 patients had PNH clone in erythrocytes (median 4.29%, range 2.99-10.8%). Only one HAAA patients (1/8, 12.5%) had a PNH clone larger than 10%, while 24 out of 73 IAA patients (32.9%) had larger PNH clones. Taken together, we observed a less frequent PNH clone with smaller clone size in HAAA patients, compared to that in IAAs. We next attempted to find out factors that associated with PNH clones. We first split patients with HAAA into two groups based on the length of disease history (≥3 mo and 〈 3mo). There were more patients carried PNH clone in HAAA with longer history (21.4%, 3/14) than patients with shorter history (6.6%, 5/76), in line with higher incidence of PNH clone in IAA patients who had longer disease history. Then we compared the PNH clone incidence between HAAA patients with higher absolute neutrophil counts (ANC, ≥0.2*109/L) and lower ANC (〈 0.2*109/L). Interestingly, very few VSAA patients developed PNH clone (5%, 3/60), while 16.7% (5/30) of non-VSAA patients had PNH clone at diagnosis. We monitored the evolution of PNH clones after immunosuppressive therapy, and found increased incidence of PNH clone over time. The overall frequency of PNH clone in HAAA was 20.8% (15/72), which was comparable to that in IAA (27.8%, 112/403). Two thirds of those new PNH clones occurred in non-responders in HAAA. In conclusion, PNH clones are infrequent in HAAA compared to IAA at the time of diagnosis, but the overall frequency over time are comparable between the two groups of patients. In SAA/VSAA patients who are under the activated abnormal immunity, longer clinical course and relatively adequate residual hematopoietic cells serve as two important extrinsic factors for HSCs with PIGA-mutation to escape from immune attack and to expand. Disclosures No relevant conflicts of interest to declare.