Evolution of T-cell clonality in a patient with Ph-negative acute lymphocytic leukemia occurring after interferon and imatinib therapy for Ph-positive chronic myeloid leukemia

<p>Abstract</p> <p>Introduction</p> <p>The development of Philadelphia chromosome (Ph) negative acute leukemia/myelodysplastic syndrome (MDS) in patients with Ph-positive chronic myeloid leukemia (CML) is very rare. The features of restrictive usage and absence of partial T cell clones have been found in patients with CML. However, the T-cell clonal evolution of Ph-negative malignancies during treatment for CML is still unknown.</p> <p>Objective</p> <p>To investigate the dynamic change of clonal proliferation of T cell receptor (TCR) Vα and Vβ subfamilies in one CML patient who developed Ph-negative acute lymphoblastic leukemia (ALL) after interferon and imatinib therapy.</p> <p>Methods</p> <p>The peripheral blood mononuclear cells (PBMC) samples were collected at the 3 time points (diagnosis of Ph-positive chronic phase (CP) CML, developing Ph-negative ALL and post inductive chemotherapy (CT) for Ph-negative ALL, respectively). The CDR3 size of TCR Vα and Vβ repertoire were detected by RT-PCR. The PCR products were further analyzed by genescan to identify T cell clonality.</p> <p>Results</p> <p>The CML patient who achieved complete cytogenetic remission (CCR) after 5 years of IFN-α therapy suddenly developed Ph-negative ALL 6 months following switch to imatinib therapy. The expression pattern and clonality of TCR Vα/Vβ T cells changed in different disease stages. The restrictive expression of Vα/Vβ subfamilies could be found in all three stages, and partial subfamily of T cells showed clonal proliferation. Additionally, there have been obvious differences in Vα/Vβ subfamily of T cells between the stages of Ph-positive CML-CP and Ph-negative ALL. The Vα10 and Vβ3 T cells evolved from oligoclonality to polyclonality, the Vβ13 T cells changed from bioclonality to polyclonality, when Ph-negative ALL developed.</p> <p>Conclusions</p> <p>Restrictive usage and clonal proliferation of different Vα/Vβ subfamily T cells between the stages of Ph-positive CP and Ph-negative ALL were detected in one patient. These changes may play a role in Ph- negative leukemogenesis.</p

SPAN: A Stochastic Projected Approximate Newton Method

Second-order optimization methods have desirable convergence properties. However, the exact Newton method requires expensive computation for the Hessian and its inverse. In this paper, we propose SPAN, a novel approximate and fast Newton method. SPAN computes the inverse of the Hessian matrix via low-rank approximation and stochastic Hessian-vector products. Our experiments on multiple benchmark datasets demonstrate that SPAN outperforms existing first-order and second-order optimization methods in terms of the convergence wall-clock time. Furthermore, we provide a theoretical analysis of the per-iteration complexity, the approximation error, and the convergence rate. Both the theoretical analysis and experimental results show that our proposed method achieves a better trade-off between the convergence rate and the per-iteration efficiency.Comment: Appeared in the AAAI 2020, 25 pages, 6 figure

Two-Stage Differential Hydrocarbon Enrichment Mode of Maokou Formation in Southeastern Sichuan Basin, Southwestern China

AbstractSichuan Basin is one of the most potential areas for natural gas exploration and development in China. The Maokou Formation in the basin is one of the important gas-bearing layers in southeastern Sichuan. In recent years, several exploration wells have obtained industrial gas flow in the first member of the Middle Permian Maokou Formation (hereinafter referred to as the Permian Mao-1 member of Maokou Formation), revealing that it may become a new field of oil and gas exploration in Sichuan Basin. Drilling and field survey results show that the shale of Maokou Formation in southeastern Sichuan contains eyeball-shaped limestone. Early studies suggest that the Permian Mao-1 member of Maokou Formation in Sichuan Basin is a set of high-quality carbonate source rocks, but ignoring its oil and gas exploration potential as an unconventional shale reservoir similar to the shale. The enrichment regularity of unconventional natural gas has not been studied from the perspective of source-internal accumulation. And there is a lack of analysis of oil and gas enrichment mode. In this study, we took the Permian Mao-1 member of Maokou Formation in southeastern Sichuan as the target layer. Through macroscopic outcrop observation and geochemical analysis and based on unconventional oil and gas enrichment theory, we carried out a study on natural gas enrichment mode of eyeball-shaped limestone of the Permian Mao-1 member of Maokou Formation in Sichuan Basin. The results show that the hydrocarbon enrichment pattern of the Maokou Formation in southeastern Sichuan is different from the accumulation and occurrence process of common unconventional shale gas reservoirs and conventional carbonate reservoirs. It is a special new hydrocarbon accumulation mode between the above two. According to the difference in the charging time of the hydrocarbon, the background of the reservoiring dynamics, and the occurrence state of oil and gas, we divide the two-stage differential enrichment mode of oil and gas, that is, “early intralayer near-source enrichment” and “late interlayer pressure relief adjustment.

Synthesizing Hypercrosslinked Polymers with Deep Eutectic Solvents to Enhance CO2/N2 Selectivity

Hypercrosslinked polymers (HCPs) are widely used in ion exchange, water purification, and gas separation. However, HCP synthesis typically requires hazardous halogenated solvents e.g., dichloroethane, dichloromethane and chloroform which are toxic to human health and environment. Herein we hypothesize that the use of halogenated solvents in HCP synthesis can be overcome with deep eutectic solvents (DES) comprising metal halides – FeCl3, ZnCl2 that can act as both the solvent hydrogen bond donor and catalyst forpolymer crosslinking via Friedel Crafts alkylation. We validated our hypothesis by synthesizing HCPs in DESs via internal and external crosslinking strategies. [ChCl][ZnCl2]2 and [ChCl][FeCl3]2 was more suitable for internal and external hypercrosslinking, respectively. The specific surface areas of HCPs synthesized in DES were 20 – 60 % lower than those from halogenated solvents, but their CO2/N2 selectivities were up to 453 % higher (CO2/N2 selectivity of poly-α,α’-dichloro-p-xylene synthesized in [ChCl][ZnCl2]2 via internal crosslinking reached a value of 105). This was attributed to the narrower pore size distributions of HCPs synthesized in DESs

Profiles of cyclin B and cdc2 during ovarian and embryonic development in <em>Exopalaemon carinicauda</em>

Mitosis-promoting factor (MPF) is a complex formed by cyclin B (cyclin B) and cyclin-dependent kinase (cdc2). To investigate the role of MPF in the reproduction of Exopalaemon carinicauda, we cloned its full-length cDNA of the Ec-cyclin B and Ec-cdc2 genes. We analyzed their molecular characteristics and expression profiles during ovarian and embryonic development. The results showed that the Ec-cyclin B gene was 1194 bp long and encoded a 397 amino acid (aa) long protein. However, Ec-cdc2 was 900 bp long, which encoded 299 aa with a conserved cyclin binding motif PSTAIRE. The phylogenetic tree analysis showed that Ec-cyclin B had the highest homology with the cyclin B of Macrobrachium rosenbergii (81.06%). In comparison, Ec-cdc2 had the highest homology with the cdc2 of E. modestus (96.80%). Ec-cyclin B showed the highest expression in the ovary, whereas Ec-cdc2 was the highest in the hepatopancreas, followed by the ovary. In the five stages of ovarian development, Ec-cyclin B and Ec-cdc2 expression levels reach the highest at stage Ⅴ(p < 0.05). Overall, the expression of these two genes first increased and then decreased at different embryonic developmental stages. Therefore, these findings suggested that cyclin B and cdc2 played an essential role in the ovarian and embryonic development of E. carinicauda