Raf kinase inhibitor protein RKIP enhances signaling by glycogen synthase kinase-3β

Raf kinase inhibitory protein (RKIP) is a physiologic inhibitor of c-RAF kinase and nuclear factor ?B signaling that represses tumor invasion and metastasis. Glycogen synthase kinase-3ß (GSK3ß) suppresses tumor progression by downregulating multiple oncogenic pathways including Wnt signaling and cyclin D1 activation. Here, we show that RKIP binds GSK3 proteins and maintains GSK3ß protein levels and its active form. Depletion of RKIP augments oxidative stress-mediated activation of the p38 mitogen activated protein kinase, which, in turn, inactivates GSK3ß by phosphorylating it at the inhibitory T390 residue. This pathway de-represses GSK3ß inhibition of oncogenic substrates causing stabilization of cyclin D, which induces cell-cycle progression and ß-catenin, SNAIL, and SLUG, which promote epithelial to mesenchymal transition. RKIP levels in human colorectal cancer positively correlate with GSK3ß expression. These findings reveal the RKIP/GSK3 axis as both a potential therapeutic target and a prognosis-based predictor of cancer progression.

Ultra-long mode-locked Er-droped fibre lasers

The development of ultra-long (UL) cavity (hundreds of meters to several kilometres) mode-locked fibre lasers for the generation of high-energy light pulses with relatively low (sub-megahertz) repetition rates has emerged as a new rapidly advancing area of laser physics. The first demonstration of high pulse energy laser of this type was followed by a number of publications from many research groups on long-cavity Ytterbium and Erbium lasers featuring a variety of configurations with rather different mode-locked operations. The substantial interest to this new approach is stimulated both by non-trivial underlying physics and by the potential of high pulse energy laser sources with unique parameters for a range of applications in industry, bio-medicine, metrology and telecommunications. It is well known, that pulse generation regimes in mode-locked fibre lasers are determined by the intra-cavity balance between the effects of dispersion and non-linearity, and the processes of energy attenuation and amplification. The highest per-pulse energy has been achieved in normal-dispersion UL fibre lasers mode-locked through nonlinear polarization evolution (NPE) for self-modelocking operation. In such lasers are generated the so-called dissipative optical solitons. The uncompensated net normal dispersion in long-cavity resonatorsusually leads to very high chirp and, consequently, to a relatively long duration of generated pulses. This thesis presents the results of research Er-doped ultra-long (more than 1 km cavity length) fibre lasers mode-locked based on NPE. The self-mode-locked erbium-based 3.5-km-long all-fiber laser with the 1.7 µJ pulse energy at a wavelength of 1.55 µm was developed as a part of this research. It has resulted in direct generation of short laser pulses with an ultralow repetition rate of 35.1 kHz. The laser cavity has net normal-dispersion and has been fabricated from commercially-available telecom fibers and optical-fiber elements. Its unconventional linear-ring design with compensation for polarization instability ensures high reliability of the self-mode-locking operation, despite the use of a non polarization-maintaining fibers. The single pulse generation regime in all-fibre erbium mode-locking laser based on NPE with a record cavity length of 25 km was demonstrated. Modelocked lasers with such a long cavity have never been studied before. Our result shows a feasibility of stable mode-locked operation even for an ultra-long cavity length. A new design of fibre laser cavity – “y-configuration”, that offers a range of new functionalities for optimization and stabilization of mode-locked lasing regimes was proposed. This novel cavity configuration has been successfully implemented into a long-cavity normal-dispersion self-mode-locked Er-fibre laser. In particular, it features compensation for polarization instability, suppression of ASE, reduction of pulse duration, prevention of in-cavity wave breaking, and stabilization of the lasing wavelength. This laser along with a specially designed double-pass EDFA have allowed us to demonstrate anenvironmentally stable all-fibre laser system able to deliver sub-nanosecond high-energy pulses with low level of ASE noise.

Phenols and aromatic amines as thermal stabilizers in polyolefin processing

Scavenging of C- and O-centered free radicals is mandatory in processing stabilization of polypropylene. Phenolic antioxidants act principally as O-radical scavengers only. Aromatic amines, N,N'-disubstituted 1,4-phenylenediamines (PD) and 4,4'disubstituted diphenylamines (DPA), scavenge both C- and O-centered radicals and have consequently a broader activity spectrum. PD cannot be used, however, in polypropylene because of formation of strongly discoloring and staining sacrificial transformation products. Such products formed from DPA have even more discoloring properties. A good processing stability and acceptable extent of discoloration can be achieved by blends of phenols with 4,4'-di-tert.octyl DPA. The effect is considered as a beneficial cooperation between the two chain-breaking antioxidants involving interactions with amine-based transformation products.

Comments on multiple oscillatory solutions in systems with time-delay feedback

A complex Ginzburg-Landau equation subjected to local and global time-delay feedback terms is considered. In particular, multiple oscillatory solutions and their properties are studied. We present novel results regarding the disappearance of limit cycle solutions, derive analytical criteria for frequency degeneration, amplitude degeneration, frequency extrema. Furthermore, we discuss the influence of the phase shift parameter and show analytically that the stabilization of the steady state and the decay of all oscillations (amplitude death) cannot happen for global feedback only. Finally, we explain the onset of traveling wave patterns close to the regime of amplitude death.