Gate defined quantum dot realized in a single crystalline InSb nanosheet

Single crystalline InSb nanosheet is an emerging planar semiconductor material with potential applications in electronics, infrared optoelectronics, spintronics and topological quantum computing. Here we report on realization of a quantum dot device from a single crystalline InSb nanosheet grown by molecular-beam epitaxy. The device is fabricated from the nanosheet on a Si/SiO2 substrate and the quantum dot confinement is achieved by top gate technique. Transport measurements show a series of Coulomb diamonds, demonstrating that the quantum dot is well defined and highly tunable. Tunable, gate-defined, planar InSb quantum dots offer a renewed platform for developing semiconductor-based quantum computation technology.Comment: 12 pages, 4 figure

The role of EGFR double minutes in modulating the response of malignant gliomas to radiotherapy.

EGFR amplification in cells having double minute chromosomes (DM) is commonly found in glioblastoma multiforme (GBM); however, how much it contributes to the current failure to treat GBM successfully is unknown. We studied two syngeneic primary cultures derived from a GBM with and without cells carrying DM, for their differential molecular and metabolic profiles, in vivo growth patterns, and responses to irradiation (IR). Each cell line has a distinct molecular profile consistent with an invasive "go" (with DM) or angiogenic "grow" phenotype (without DM) demonstrated in vitro and in intracranial xenograft models. Cells with DM were relatively radio-resistant and used higher glycolytic respiration and lower oxidative phosphorylation in comparison to cells without them. The DM-containing cell was able to restore tumor heterogeneity by mis-segregation of the DM-chromosomes, giving rise to cell subpopulations without them. As a response to IR, DM-containing cells switched their respiration from glycolic metabolism to oxidative phosphorylation and shifted molecular profiles towards that of cells without DM. Irradiated cells with DM showed the capacity to alter their extracellular microenvironment to not only promote invasiveness of the surrounding cells, regardless of DM status, but also to create a pro-angiogenic tumor microenvironment. IR of cells without DM was found primarily to increase extracellular MMP2 activity. Overall, our data suggest that the DM-containing cells of GBM are responsible for tumor recurrence due to their high invasiveness and radio-resistance and the mis-segregation of their DM chromosomes, to give rise to fast-growing cells lacking DM chromosomes

Current and future precipitation extremes over Mississippi and Yangtze River basins as simulated in CMIP5 models

Both central-eastern U.S. and China are prone to increasing flooding from Mississippi River and Yangtze River basins respectively. This paper contrasts historical and projected spatialtemporal distribution of extreme precipitation in these two large river basins using 31 CMIP5 (coupled model intercomparison project phase 5) models' historical and RCP8.5 (representative concentration pathway) experiments. Results show that (1) over both river basins, the heaviest rainfall events have increased in recent decades while the lightest precipitation reduced in frequency. Over Mississippi River Basin, both the lightest precipitation (< 2.5 mm/day) and heaviest (> 50 mm/day) would decrease in frequency notably after mid-2020s while intermediate events occur more frequently in future; whereas over the Yangtze River Basin, all categories of precipitation are projected to increase in frequency over the coming decades. (2) Although the consensus of CMIP5 models was able to reproduce well domain-time mean and even time-averaged spatial distribution of precipitation, they failed to simulate precipitation trends both in spatial distribution and time means. In a similar fashion, models captured well statistics of precipitation but they had difficulty in representing temporal variations of different precipitation intensity categories. (3) The well-documented 2nd half of the 20th century surface summer cooling over the two river basins showed different associations with precipitation trends with higher anti-correlation between them over the U.S. region, implying different processes contributing to the cooling mechanisms of the two river basins

Investigating Morphology and Breakage Evolution Characteristics of Railroad Ballasts over Distinct Supports Subjected to Impact Loading

The ballast bed constantly degrades under the repeated applications of impact loading exerted by passing trains in terms of the particle size, shape, breakage, fouling, etc., thus significantly jeopardizing the in-service performance and operational safety of ballasted tracks. In this study, the morphology and breakage evolution characteristics of railroad ballasts of single- and multiple-size ranges were investigated from laboratory impact-load tests. Both a concrete block and sand layer were placed to mimic the distinct under-ballast supports. The degradation trends of the typical shape and breakage indices were comparatively quantified for different combinations of ballast particle sizes and shapes, under-ballast supports, impact energies, and number of impact-load applications (N). The results show that both shape and size affect ballast particle breakage, with shape being more influential. The breakage severity of flake-like particles is about 1.5–1.66 times and 1.25–1.5 times higher than those of regular and needle-like particles, respectively. Under impact loading, large and small single-size ballasts degrade mainly by breakage and abrasion, respectively. The modified fouling index (FI) of flake-like particles within 31.5–40 mm is about 3.6 times that of regular particles within 50–63 mm. The shape indices of the ballast particles within 31.5–40 mm exhibit the most profound changes. The severities of the ballast breakage and fines generation (or modified FI) increased by 50% and 74%, respectively, due to the increase in the under-ballast support stiffness by 100 times and the drop height of 80 cm, respectively. The convexity and ballast breakage index (BBI) are promising for quantifying particle-degradation trends, and their statistical correlation found herein is potentially useful for the transition of ballast-bed-maintenance management from the current plan-based scheduling to condition-based upgrading

DataSheet_1_Immune subtype identification and multi-layer perceptron classifier construction for breast cancer.zip

IntroductionBreast cancer is a heterogeneous tumor. Tumor microenvironment (TME) has an important effect on the proliferation, metastasis, treatment, and prognosis of breast cancer.MethodsIn this study, we calculated the relative proportion of tumor infiltrating immune cells (TIICs) in the breast cancer TME, and used the consensus clustering algorithm to cluster the breast cancer subtypes. We also developed a multi-layer perceptron (MLP) classifier based on a deep learning framework to detect breast cancer subtypes, which 70% of the breast cancer research cohort was used for the model training and 30% for validation.ResultsBy performing the K-means clustering algorithm, the research cohort was clustered into two subtypes. The Kaplan-Meier survival estimate analysis showed significant differences in the overall survival (OS) between the two identified subtypes. Estimating the difference in the relative proportion of TIICs showed that the two subtypes had significant differences in multiple immune cells, such as CD8, CD4, and regulatory T cells. Further, the expression level of immune checkpoint molecules (PDL1, CTLA4, LAG3, TIGIT, CD27, IDO1, ICOS) and tumor mutational burden (TMB) also showed significant differences between the two subtypes, indicating the clinical value of the two subtypes. Finally, we identified a 38-gene signature and developed a multilayer perceptron (MLP) classifier that combined multi-gene signature to identify breast cancer subtypes. The results showed that the classifier had an accuracy rate of 93.56% and can be robustly used for the breast cancer subtype diagnosis.ConclusionIdentification of breast cancer subtypes based on the immune signature in the tumor microenvironment can assist clinicians to effectively and accurately assess the progression of breast cancer and formulate different treatment strategies for different subtypes.</p

Anti-EGFR function of EFEMP1 in glioma cells and patient prognosis.

EGFR is one of the key oncogenes subjected to targeted therapy for several cancers, as it is known to be amplified and/or mutated in up to 40% of malignant gliomas. EFEMP1, a fibulin-like extracellular protein, exerts both tumor suppressive and oncogenic effects in various cancers and glioma cell models. Although EFEMP1's anti-cancer activity has most commonly been attributed to its anti-angiogenic effects, we showed for gliomas that EFEMP1's binding to EGFR accounts for its suppression of the intracranial tumorigenicity of glioma cells expressing high levels of EGFR. In gliomas where EFEMP1 expression, and thus the anti-EGFR effect of EFEMP1, was suppressed, heightened levels of EGFR expression were associated with unfavorable patient outcomes in prognostic models. Results from the current study clearly demonstrate the impact that the anti-EGFR function of EFEMP1 has on the expression of EGFR and patient prognosis. A glioma prognostic model also suggests EFEMP1's context-dependent oncogenic function in gliomas expressing low levels of EGFR. Hence the level of EFEMP1 expression may have a predictive value for choosing patients for anti-EGFR therapy

Anti-EGFR function of EFEMP1 in glioma cells and patient prognosis.

EGFR is one of the key oncogenes subjected to targeted therapy for several cancers, as it is known to be amplified and/or mutated in up to 40% of malignant gliomas. EFEMP1, a fibulin-like extracellular protein, exerts both tumor suppressive and oncogenic effects in various cancers and glioma cell models. Although EFEMP1's anti-cancer activity has most commonly been attributed to its anti-angiogenic effects, we showed for gliomas that EFEMP1's binding to EGFR accounts for its suppression of the intracranial tumorigenicity of glioma cells expressing high levels of EGFR. In gliomas where EFEMP1 expression, and thus the anti-EGFR effect of EFEMP1, was suppressed, heightened levels of EGFR expression were associated with unfavorable patient outcomes in prognostic models. Results from the current study clearly demonstrate the impact that the anti-EGFR function of EFEMP1 has on the expression of EGFR and patient prognosis. A glioma prognostic model also suggests EFEMP1's context-dependent oncogenic function in gliomas expressing low levels of EGFR. Hence the level of EFEMP1 expression may have a predictive value for choosing patients for anti-EGFR therapy