The transcriptional landscape of Shh medulloblastoma

© The Author(s) 2021. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Sonic hedgehog medulloblastoma encompasses a clinically and molecularly diverse group of cancers of the developing central nervous system. Here, we use unbiased sequencing of the transcriptome across a large cohort of 250 tumors to reveal differences among molecular subtypes of the disease, and demonstrate the previously unappreciated importance of non-coding RNA transcripts. We identify alterations within the cAMP dependent pathway (GNAS, PRKAR1A) which converge on GLI2 activity and show that 18% of tumors have a genetic event that directly targets the abundance and/or stability of MYCN. Furthermore, we discover an extensive network of fusions in focally amplified regions encompassing GLI2, and several loss-of-function fusions in tumor suppressor genes PTCH1, SUFU and NCOR1. Molecular convergence on a subset of genes by nucleotide variants, copy number aberrations, and gene fusions highlight the key roles of specific pathways in the pathogenesis of Sonic hedgehog medulloblastoma and open up opportunities for therapeutic intervention.info:eu-repo/semantics/publishedVersio

Geometrical Parameter Effects on Solidification/Melting Processes Using Twin Concentric Helical Coil: Experimental Investigations

Moving the load peak to consume electrical power is valuable in air conditioning systems. Consequently, the current study presents an experimental thermal investigation of an ice storage system. For this purpose, a twin concentric helical coil (TCHC) is utilized. The coil is submerged in distilled water in an insulated tank. The main aim is to explore the effect of geometrical/operating conditions for the TCHC on percentage energy stored/regained, solidified/melted mass fraction, and average charging/discharging rate. The main parameters are twin coil pitch and tube diameter while keeping the cold heat transfer fluid (HTF) inlet conditions at −12 °C and 10 L/min. The results disclosed that the discharge time increases by about 79% for total energy gained as the coil pitch rises from 30 to 50 mm at a smaller tube diameter of 9.52 mm. At the same time, the discharge time is doubled when the tube diameter is 15.88 mm. Furthermore, the complete solidification needs half the time (time reduced to 50%) to be achieved as the tube diameter increases from 9.52 mm to 15.88 mm (68% increases in diameter) for lower pitch (P = 30 mm)

Geometrical Parameter Effects on Solidification/Melting Processes Using Twin Concentric Helical Coil: Experimental Investigations

Moving the load peak to consume electrical power is valuable in air conditioning systems. Consequently, the current study presents an experimental thermal investigation of an ice storage system. For this purpose, a twin concentric helical coil (TCHC) is utilized. The coil is submerged in distilled water in an insulated tank. The main aim is to explore the effect of geometrical/operating conditions for the TCHC on percentage energy stored/regained, solidified/melted mass fraction, and average charging/discharging rate. The main parameters are twin coil pitch and tube diameter while keeping the cold heat transfer fluid (HTF) inlet conditions at −12 °C and 10 L/min. The results disclosed that the discharge time increases by about 79% for total energy gained as the coil pitch rises from 30 to 50 mm at a smaller tube diameter of 9.52 mm. At the same time, the discharge time is doubled when the tube diameter is 15.88 mm. Furthermore, the complete solidification needs half the time (time reduced to 50%) to be achieved as the tube diameter increases from 9.52 mm to 15.88 mm (68% increases in diameter) for lower pitch (P = 30 mm)

Workspace Analysis and Path Planning of a Novel Robot Configuration with a 9-DOF Serial-Parallel Hybrid Manipulator (SPHM)

The development of serial or parallel manipulator robots is constantly increasing due to the need for faster productivity and higher accuracy. Therefore, researchers have turned to combining both mechanisms, sharing the advantage from serial to parallel or vice versa. This paper proposes a new configuration design for a serial-parallel hybrid manipulator (SPHM) using the industrial robotic KUKA Kr6 R900 and 3-DOF parallel spherical mechanism. The Kr6 R900 has six degrees of freedom (6-DOF) divided into three joints for translation (x, y, z) and another three joints for orientation (A, B, C) of the end-effector and the 3-DOF parallel spherical mechanism with three paired links. On the contrary, each limb of the parallel spherical mechanism consists of revolute–revolute–spherical joints (3-RRS). This mechanism allows translation movement along the Z-axis and orientation movements about the X- and Y- axes. The new hybrid will enrich the serial manipulator in movement flexibility and expand the workspace for serial and parallel manipulator robots. In addition, a complete conceptual design is presented in detail for the new robot configuration with a schematic and experimental setup. Then, a comprehensive mathematical model was derived and solved. The forward, inverse kinematics, and workspace analyses were derived using the graphical solution. Additionally, the new hybrid manipulator was tested for path planning. Moreover, an experimental setup was prepared to test the selected path. Finally, the new robot configuration can enlarge the workspace of both manipulators and the selected path matched to the experimental test