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Diabetes mellitus (DM) is a risk factor for cancer. The role of DM-induced hyperglycemic (HG) stress in blood cancer is poorly understood. Epidemiologic studies show that individuals with DM are more likely to have a higher rate of mutations in genes found in pre-leukemic hematopoietic stem and progenitor cells (pre-LHSPCs) including TET2. TET2-mutant pre-LHSPCs require additional hits to evolve into full-blown leukemia and/or an aggressive myeloproliferative neoplasm (MPN). Intrinsic mutations have been shown to cooperate with Tet2 to promote leukemic transformation. However, the extrinsic factors are poorly understood. Using a mouse model carrying Tet2 haploinsufficiency to mimic the human pre-LHSPC condition and HG stress, in the form of an [Ins2.sup.Akita/+] mutation, which induces hyperglycemia and type 1 DM, we show that the compound mutant mice developed a lethal form of MPN and/or acute myeloid leukemia (AML). RNA-Seq revealed that this was due in part to upregulation of proinflammatory pathways, thereby generating a feed-forward loop, including expression of the antiapoptotic, long noncoding RNA (lncRNA) Morrbid. Loss of Morrbid in the compound mutants rescued the lethality and mitigated MPN/AML. We describe a mouse model for age-dependent MPN/AML and suggest that hyperglycemia acts as an environmental driver for myeloid neoplasms, which could be prevented by reducing expression levels of the inflammation-related lncRNA Morrbid., Introduction Cancer and diabetes are prevalent diseases that share multiple common risk factors such as metabolic dysfunction, aging, and chronic inflammation. It has been hypothesized that diabetes is a risk [...]

Storing and extracting heat during different seasons of the year is possible through the utilization of a ground aquifer with an open loop Ground Source Heat Pump (GSHP) system. Being able to predict the hydrothermal performance of geothermal storage is required for an efficient operation of the system for cooling and heating of buildings. Complex 2D and 3D hydrothermal numerical models can simulate the thermal performance of geothermal storage accurately but often lack the desired computational speed for conducting large number of simulations for performance optimization. Instead, a 1D radial model can be used to conduct fast evaluation. However, it is important that the model computes the amount of heat loss from an aquifer into the overburden and underlying layers accurately to evaluate the amount of geothermal storage in the aquifer at different times. In this study, a source term is introduced into a 1D model to simulate the heat transfer between the aquifer and caprock/baserock in the vertical direction. The following two heat loss models are introduced in the heat advection-conduction equation: (i) Newton’s heating/cooling law, which leads to a closed form solution, and (ii) a conduction-based semi-analytical model, which requires a 1D finite element solution. When compared to a full 2D axisymmetric simulation result, it was found that the Newton’s heating/cooling law model with a constant heat transfer coefficient works well in cases of fast heat flow rate in thick aquifers of around 100 meters. But large errors in estimating heat dissipation are observed in cases with low heat flow rate in thin aquifers, especially for simulations exceeding two to five years. On the other hand, the model with the conduction-based semi-analytical solution gives a better match for these conditions.

Cuprous oxide (Cu2O) has a narrow band gap of 2.1–2.3 eV, which facilitates the absorption of visible light and the photocatalytic removal of pollutants from water. However, the catalytic efficiency of Cu2O has been affected by the rapidly compounding carriers in the photocatalytic process. In order to achieve adequate separation of the photogenerated carriers, a straightforward liquid‐phase reduction technique was used in this study to successfully obtain praseodymium‐doped cuprous oxide Pr : Cu2O (0, 1, 3, and 5 mol %). Praseodymium ions were successfully doped into the Cu2O lattice interstitial, as demonstrated by XRD and SEM studies, and the doped praseodymium ions decreased the crystallite size. The FT‐IR peak also confirmed the existence of Cu2O at 631 cm−1. With the increase of Pr doping to 3 %, the band gap gradually decreased to 2.12 eV. Experiments on the degradation of methyl orange (MO) under visible light irradiation showed that 3 % Pr : Cu2O photocatalyst showed the best photocatalytic performance. The Pr doping reduced the recombination of photogenerated electron‐hole pairs and enhanced the photocatalytic activity of Cu2O, according to the analysis results of PL, EIS and transient photocurrent response. Combining these results with active radical capture experiments, the functioning mechanism of the Pr : Cu2O photocatalyst was examined. [ABSTRACT FROM AUTHOR]

In many underground engineering projects, rocks are often subjected to cyclic loading and unloading, such as repeated excavation of roadway surrounding rock, which will lead to damage to underground rocks, and the energy of rocks also changes. Therefore, to study the energy evolution and damage characteristics of rocks under cyclic loading and unloading, different cyclic loading and unloading tests of bituminous sandstones under constant amplitude were conducted. Under cyclic loading and unloading, the lower limit stress was 40% of the rock peak intensity, the cyclic amplitude was 20–40% of the peak intensity, and the number of loading–unloading cycles was 10–30. The quantitative characterization of the damage degrees of bituminous sandstone was realized by the ultrasonic wave velocity and elasticity modulus methods. The energy evolution and damage characteristics of bituminous sandstone under different amplitudes and number of loading–unloading cycles were investigated through the energy dissipation method. Results showed that under cyclic loading and unloading, the ultrasonic wave velocity and elasticity modulus of bituminous sandstone decreased gradually; The damage variable shows a trend of rapid and then stable growth and has a power function relationship with the number of cycles; The input energy density and dissipation energy density curves were in L-shaped distribution, whereas the elastic energy density remained stable. The results of this study can provide some theoretical references to underground engineering construction. [ABSTRACT FROM AUTHOR]

To study the mechanical and energy evolution characteristics of sandstone under true triaxial cyclic loading, a sandstone mechanical test with different intermediate principal stress under true triaxial loading was conducted using the rock true triaxial disturbance unloading test system. The influence of axial load on the deformation, energy evolution, and macroscopic failure characteristics of sandstone under different intermediate principal stress in a true triaxial test was systematically analyzed, and the damage evolution law of sandstone under true triaxial cyclic load was revealed. Results showed that the failure mode of sandstone under true triaxial compression changed from tension–shear composite failure to tension failure. Grading cyclic load σ 1 greatly influenced maximum principal strain ε 1 and minimum principal strain ε 3 but had little influence on intermediate principal strain ε 2 . Under the same σ 2 condition, the input energy and elastic energy in σ 1 , σ 2 , and σ 3 directions increased nonlinearly. Under different σ 2 conditions, the dissipated energy in σ 1 , σ 2 , and σ 3 directions decreased with the increase in σ 2 . With the increase in σ 2 , graded cycles σ 1 , ε 2 , and ε 3 decreased considerably, and the failure mode changed from tensile failure to shear failure. When the cyclic loading rate increased, the σ 1 , ε 1 , ε 2 , ε 3 , and volume strain ε v of sandstone failure decreased, but the expansion point increased. Under true triaxial grading cyclic loading and unloading, the total dissipated energy of sandstone increased exponentially. The larger σ 2 was, the smaller the damage variable was. [ABSTRACT FROM AUTHOR]