Failure of human rhombic lip differentiation underlies medulloblastoma formation

Medulloblastoma (MB) comprises a group of heterogeneous paediatric embryonal neoplasms of the hindbrain with strong links to early development of the hindbrain 1–4. Mutations that activate Sonic hedgehog signalling lead to Sonic hedgehog MB in the upper rhombic lip (RL) granule cell lineage 5–8. By contrast, mutations that activate WNT signalling lead to WNT MB in the lower RL 9,10. However, little is known about the more commonly occurring group 4 (G4) MB, which is thought to arise in the unipolar brush cell lineage 3,4. Here we demonstrate that somatic mutations that cause G4 MB converge on the core binding factor alpha (CBFA) complex and mutually exclusive alterations that affect CBFA2T2, CBFA2T3, PRDM6, UTX and OTX2. CBFA2T2 is expressed early in the progenitor cells of the cerebellar RL subventricular zone in Homo sapiens, and G4 MB transcriptionally resembles these progenitors but are stalled in developmental time. Knockdown of OTX2 in model systems relieves this differentiation blockade, which allows MB cells to spontaneously proceed along normal developmental differentiation trajectories. The specific nature of the split human RL, which is destined to generate most of the neurons in the human brain, and its high level of susceptible EOMES +KI67 + unipolar brush cell progenitor cells probably predisposes our species to the development of G4 MB

DeepCwind semi-submersible floating offshore wind turbine platform with a nonlinear multi-segment catenary mooring line and intermediate buoy

In this paper, to improve the mechanical behavior of DeepCwind semi-submersible floating offshore wind turbine (FOWT) platform mooring lines, the nonlinear catenary cables of the platform were divided into multi-segment and intermediate buoys. Mathematical formulations of the boundary element method (BEM) governing the dynamics of mooring line systems with buoy devices were described. This study was applied to the OC4-DeepCwind semi-submersible FOWT platform, which is designed for a 200-meter water depth with mooring lines consisting of three catenary steel chain cables at 120° angles to each other. The dynamic response of the multi-segment catenary mooring lines with different buoy radiuses and different positions along the cables was investigated. The full-scale platform was modeled in ANSYS-AQWA software, and the simulations were performed under harsh offshore conditions. The mooring line’s general arrangement, tension, strain and uplift force for different buoy radiuses and their position along the cable are presented and discussed. Moreover, platform motions in three directions (surge, heave, and pitch) were also analyzed. It was concluded that by correctly selecting the buoy volume and position along the cable, the tension of the cable may be reduced by up to 45%. By incorrectly selecting the buoy, the results caused adverse effects

The Effect of miR-155 on DNA Damage in Mesenchymal Stem Cells

Abstract: Considering the crucial role of miR-155 in DNA repair regulation, the aim of this study was to evaluate the effect of miR-155 on the expression of DNA repair factors involved in single- and double-strand DNA breaks (SSBs and DSBs) and mismatch repair (MMR) in mesenchymal stem cells (MSCs). MSCs were isolated from the bone marrow of a healthy individual, and then confirmed by their adipogenic/osteogenic differentiation and flow cytometric analysis of surface markers of MSCs (CD105, CD90, and CD73). MSCs transfection by green fluorescent protein (GFP) plasmid bearing miR-155 was verified by fluorescent microscope, and was measured via analyzing the percentage of transfected cells compared to non-transfected by flow cytometry. The expression of miR-155 and mRNAs related to DNA repair response system, i.e. XRCC1, XRCC5, XRCC6, and RAD51, were assessed by real-time PCR. Overexpression of miR-155 in MSCs was significant compared to control (p = 0.034). Increase in the expression of DNA repair genes, including XRCC1, XRCC6, XRCC5, and RAD51 was not significant (p = 0.066, 0.108, 0.092, 0.631, and 0.262, respectively). In conclusion, although the expression of DNA repair genes by miR-155 overexpression was not significant, it has the potential to affect DNA repair genes expression. © 2020, Pleiades Publishing, Ltd

Calculating the second-order hydrodynamic force on fixed and floating tandem cylinders

In this paper, the second-order hydrodynamic force on fixed and floating tandem cylinders has been calculated and different parameters have been taken into consideration. An incident wave is diffracted by the fixed cylinder, and as a result low-frequency waves radiate toward the floating cylinder and cause low-frequency second-order hydrodynamic forces to act on the surface of the floating cylinder. The interactions between the fixed and floating cylinders have been investigated by changing the distance between them, as well as the draft and radius of the floating cylinder. By employing perturbation series analysis over the wetted surface, the second-order wave excitation force has been calculated. The maximum force applied on the floating cylinder becomes non-dimensional when considering it with and without the fixed cylinder. The results showed the effect that the existence of the fixed cylinder had on the increase in the second-order forces is quite evident where, for a significant parameter of the floating cylinder, the force in the heave direction was enhanced by up to 1.55 times

Evaluation of Quantitative and Qualitative Characteristics of Persian Walnut (Juglans regia L.) Genotypes in the West of Meshkin-Shahr

The Persian walnut (Juglans regia L.) is one of the most valuable resources in Iran because of its multi benefits. The present study was conducted in Meshkin-Shahr in Ardabil province to investigate the important quantitative and qualitative characteristics of 31 walnut genotypes. Classification of genotypes was analyzed using the cluster method. The results showed that among selected walnut genotypes, SS genotype had the highest kernel weight (7.03 g), and fruits weight (12.65 g), and RM3 had the best kernel percentage 63.73%. The walnut genotypes were clustered into three groups using UPGMA cluster method. This preliminary study demonstrated that quantitative and qualitative characteristics were effective in evaluating the genetic diversity of walnut genotypes

Designing and Fabrication of a New Radiofrequency Planar microcoil for mini-Nuclear Magnetic Resonance

Introduction Radiofrequency planar microcoils are used to increase the resolution of magnetic resonance images of small samples. In this study, we aimed to design and fabricate a spiral planar microcoil constructed on a double-sided printed circuit board (PCB). It has four rings with an internal diameter of 241 microns tuned and matched at 63.8 MHz. Materials and Methods To achieve the maximum signal-to- noise ratio (SNR) and quality factor of the coil, its geometry was optimized based on parameters such as width (w) and thickness (h) of the copper rings, the distance between the rings, inner radius of the microcoil  (Ri), and the number (N) of coil rings by using COMSOL, ADS, and MATLAB software packages. Results Our findings indicated that the Q factor and SNR of the coil at resonance frequency of 63.8 MHz are 63.149 and 168.23, respectively, which are higher than the equivalent features of the pervious coils. In addition, to evaluate the function of matching and tuning circuit, reflection coefficient factor (S11) of the coil was experimentally measured to be -48 dB at resonance frequency of 63.8 MHz, which is consistent with the simulated value. Conclusion In this study, a new microcoil was designed and fabricated to produce images of very small samples and volumes in microliter dimensions. The results showed that this new microcoil has superior capability in imaging very small samples compared to the conventional coils applied in magnetic resonance imaging devices