L1 scheme for solving an inverse problem subject to a fractional diffusion equation

This paper considers the temporal discretization of an inverse problem subject to a time fractional diffusion equation. Firstly, the convergence of the L1 scheme is established with an arbitrary sectorial operator of spectral angle $< \pi/2$, that is the resolvent set of this operator contains $\{z\in\mathbb C\setminus\{0\}:\ |\operatorname{Arg} z|< \theta\}$ for some $\pi/2 < \theta < \pi$. The relationship between the time fractional order $\alpha \in (0, 1)$ and the constants in the error estimates is precisely characterized, revealing that the L1 scheme is robust as $\alpha$ approaches $1$. Then an inverse problem of a fractional diffusion equation is analyzed, and the convergence analysis of a temporal discretization of this inverse problem is given. Finally, numerical results are provided to confirm the theoretical results

Influence of Fe-rich phases and precipitates on the mechanical behaviour of Al-Cu-Mn-Fe-Sc-Zr alloys studied by synchrotron X-ray and neutron

A multiscale methodology using scanning and transmission electron microscope, synchrotron X-ray nano-tomography and micro-tomography, small angle neutron scattering, and in situ synchrotron X-ray diffraction has been used, to reveal the effect of Fe-rich phases and precipitates on the mechanical behaviour of an Al-Cu-Mn-Fe-Sc-Zr alloy. The α-Al grains size is reduced from 185.1 μm (0 MPa) and 114.3 μm (75 MPa) by applied pressure. Moreover, it has been demonstrated that suitable heat treatments modify the 3D morphology of Fe-rich phases from interconnected to a disaggregated structure that improves the mechanical properties of the alloy. The size and morphology evolution of fine precipitates under different ageing temperature and time are revealed. At ageing temperature of 160 °C, the precipitates change from GP zones to θ' (around 75 nm in length) with ageing time increasing from 1 h to 24 h; the Vickers hardness increases from 72.0 HV to 110.7HV. The high ductility of the Sc, Zr modified Al-Cu alloy is related to the complex shape and the loss of interconnectivity of the Fe-rich particles due to the heat treatment. The evolution of the crystal lattice strains in α-Al, and β-Fe calculated during tensile test using in-situ synchrotron X-ray diffraction corroborates the influence of the microstructure in the ductility of the modified alloy.This work was financially supported by the Natural Science Foundation of China (Nos. 52104373 and 51901042), the Basic and Applied Basic Foundation of Guangdong Province, China (Nos. 2020B1515120065 and 2021B1515140028); the Guangdong Province Office of Education, China (No. 2018KQNCX256). We also would like to thank the WL13HB beamline and WL14B1 beamline of Shanghai Synchrotron Radiation Facility, SSRF, China; 4W1A beamline of Beijing Synchrotron Radiation Facility, BSRF, China for provision of synchrotron radiation beamtime; and Small Angle Neutron Scattering (SANS) Beamline in China Spallation Neutron Source (CSNS, Dongguan, China) for providing neutron beamtime

A unique role of GATA1S in down syndrome acute megakaryocytic leukemia biology and therapy

Background: Acute megakaryocytic leukemia (AMkL) in Down syndrome (DS) children is uniformly associated with somatic GATA1 mutations, which result in the synthesis of a shorter protein (GATA1s) with altered transactivation activity compared to the wild-type GATA1. It is not fully established whether leukemogenesis and therapeutic responses in DS AMkL patients are due to loss of the wild-type GATA1 or due to a unique function of GATA1s. Methodology: Stable clones of CMK cells with decreased GATA1s or Bcl-2 levels were generated by using GATA1- or BCL-2-specific lentivirus shRNAs. In vitro ara-C, daunorubicin, and VP-16 cytotoxicities of the shRNA stable clones were determined by using the Cell Titer-blue reagent. Apoptosis and cell cycle distribution were determined by flow cytometry analysis. Changes in gene transcript levels were determined by gene expression microarray and/or real-time RT-PCR. Changes in protein levels were measured by Western blotting. In vivo binding of GATA1s to IL1A promoter was determined by chromatin immunoprecipitation assays. Results: Lentivirus shRNA knockdown of the GATA1 gene in the DS AMkL cell line, CMK (harbors a mutated GATA1 gene and only expresses GATA1s), resulting in lower GATA1s protein levels, promoted cell differentiation towards the megakaryocytic lineage and repressed cell proliferation. Increased basal apoptosis and sensitivities to ara-C, daunorubicin, and VP-16 accompanied by down-regulated Bcl-2 were also detected in the CMK GATA1 shRNA knockdown clones. Essentially the same results were obtained when Bcl-2 was knocked down with lentivirus shRNA in CMK cells. Besides Bcl-2, down-regulation of GATA1s also resulted in altered expression of genes (e.g., IL1A, PF4, and TUBB1) related to cell death, proliferation, and differentiation. Conclusion: Our results suggest that GATA1s may facilitate leukemogenesis and potentially impact therapeutic responses in DS AMkL by promoting proliferation and survival, and by repressing megakaryocytic lineage differentiation, potentially by regulating expression of Bcl-2 protein and other relevant genes. © 2011 Xavier et al

Single-cell RNA analysis to identify five cytokines signaling in immune-related genes for melanoma survival prognosis

Melanoma is one of the deadliest skin cancers. Recently, developed single-cell sequencing has revealed fresh insights into melanoma. Cytokine signaling in the immune system is crucial for tumor development in melanoma. To evaluate melanoma patient diagnosis and treatment, the prediction value of cytokine signaling in immune-related genes (CSIRGs) is needed. In this study, the machine learning method of least absolute selection and shrinkage operator (LASSO) regression was used to establish a CSIRG prognostic signature of melanoma at the single-cell level. We discovered a 5-CSIRG signature that was substantially related to the overall survival of melanoma patients. We also constructed a nomogram that combined CSIRGs and clinical features. Overall survival of melanoma patients can be consistently predicted with good performance as well as accuracy by both the 5-CSIRG signature and nomograms. We compared the melanoma patients in the CSIRG high- and low-risk groups in terms of tumor mutation burden, infiltration of the immune system, and gene enrichment. High CSIRG-risk patients had a lower tumor mutational burden than low CSIRG-risk patients. The CSIRG high-risk patients had a higher infiltration of monocytes. Signaling pathways including oxidative phosphorylation, DNA replication, and aminoacyl tRNA biosynthesis were enriched in the high-risk group. For the first time, we constructed and validated a machine-learning model by single-cell RNA-sequencing datasets that have the potential to be a novel treatment target and might serve as a prognostic biomarker panel for melanoma. The 5-CSIRG signature may assist in predicting melanoma patient prognosis, biological characteristics, and appropriate therapy