Autoregulation of the human splice factor kinase CLK1 through exon skipping and intron retention

© 2018 Elsevier B.V. Alternative splicing is a key process required for the regulation of gene expression in normal development and physiology. It is regulated by splice factors whose activities are in turn regulated by splice factor kinases and phosphatases. The CDC-like protein kinases are a widespread family of splice factor kinases involved in normal physiology and in several diseases including cancer. In humans they include the CLK1, CLK2, CLK3 and CLK4 genes. The expression of CLK1 is regulated through alternative splicing producing both full-length catalytically active and truncated catalytically inactive isoforms, CLKT1 (arising from exon 4 skipping) and CLKT2 (arising from intron 4 retention). We examined CLK1 alternative splicing in a range of cancer cell lines, and report widespread and highly variable rates of exon 4 skipping and intron 4 retention. We also examined the effect of severe environmental stress including heat shock, osmotic shock, and exposure to the alkaloid drug harmine on CLK1 alternative splicing in DU145 prostate cancer cells. All treatments rapidly reduced exon 4 skipping and intron 4 retention, shifting the balance towards full-length CLK1 expression. We also found that the inhibition of CLK1 with the benzothiazole TG003 reduced exon 4 skipping and intron 4 retention suggesting an autoregulatory mechanism. CLK1 inhibition with TG003 also resulted in modified alternative splicing of five cancer-associated genes

Ambient solar wind's effect on ICME transit times

Most empirical and numerical models of Interplanetary Coronal Mass Ejection (ICME) propagation use the initial CME velocity as their primary, if not only, observational input. These models generally predict a wide spread of 1 AU transit times for ICMEs with the same initial velocity. We use a 3D coupled MHD model of the corona and heliosphere to determine the ambient solar wind's effect on the propagation of ICMEs from 30 solar radii to 1 AU. We quantitatively characterize this deceleration by the velocity of the upstream ambient solar wind. The effects of varying solar wind parameters on the ICME transit time are quantified and can explain the observed spread in transit times for ICMEs of the same initial velocity. We develop an adjustment formula that can be used in conjunction with other models to reduce the spread in predicted transit times of Earth-directed ICMEs

Aeroacoustic Characteristics of Externally Blown Flap Systems

Externally blown flap systems are known to be one measure to augment the overall lift during take-off and approach. The potential gain of overall lift depends highly on the way the engine exhaust jet interacts with the flap system. The most common way to design an externally blown flap system for civil transport aircraft is to generate additional lift by means of a thrust deflection. A thrust deflection directly implies the interaction of the highly turbulent jet flow with the solid flap surface which finally results in an airframe noise source. Within the German national founded research project HIT (High Lift Innovative Technologies) the effect of externally blown flaps on farfield radiated noise was investigated by means of dedicated experiments in DLR’s Acoustic Wind Tunnel Braunschweig. The noise tests were performded with a 2D 2-element high lift system and an exhaust jet simulator. By means of pressurized air jet flow speeds of up to Ma=0.67 were realized. The obtained results show a medium to high frequency noise level increase of up to 4 dB due to jet–flap interaction noise for the tested 2-element high lift system which was equipped with either a single slotted or a double slotted flap system

Copyright Protection of object-oriented software

language (such as C++ and Java). The model used allows to insert watermarks on three “orthogonal” levels. For the first level, watermarks are injected into objects. The second level watermarking is used to select proper variants of the source code. The third level uses transition function that can be used to generate copies with different functionalities. Generic watermarking schemes were presented and their security discussed