Circuitry of nuclear factor κB signaling

Over the past few years, the transcription factor nuclear factor (NF)-κB and the proteins that regulate it have emerged as a signaling system of pre-eminent importance in human physiology and in an increasing number of pathologies. While NF-κB is present in all differentiated cell types, its discovery and early characterization were rooted in understanding B-cell biology. Significant research efforts over two decades have yielded a large body of literature devoted to understanding NF-κB's functioning in the immune system. NF-κB has been found to play roles in many different compartments of the immune system during differentiation of immune cells and development of lymphoid organs and during immune activation. NF-κB is the nuclear effector of signaling pathways emanating from many receptors, including those of the inflammatory tumor necrosis factor and Toll-like receptor superfamilies. With this review, we hope to provide historical context and summarize the diverse physiological functions of NF-κB in the immune system before focusing on recent advances in elucidating the molecular mechanisms that mediate cell type-specific and stimulus-specific functions of this pleiotropic signaling system. Understanding the genetic regulatory circuitry of NF-κB functionalities involves system-wide measurements, biophysical studies, and computational modeling

High Harmonic Generation Using Multicolour Fields

This thesis describes the phenomenon of high harmonic generation from atoms irradiated by intense, ultrashort laser pulses. Particular attention is paid to the benefits achieved by using multicolour driving fields. A theoretical description of few-cycle laser pulses is presented, together with their interaction with free-electrons and the role they play in various nonlinear optical processes. A number of numerical models are presented to simulate high harmonic generation from atomic systems. These are used to analyse and explain the temporal structure of the emitted high-frequency dipole radiation. Propagation of the macroscopic harmonic response through a gaseous volume is modelled and the role of phase-matching explained in detail. We consider focussing geometry in optimising the yield of particular harmonics, together with the effects of free-electrons within the interaction region. We discuss means by which multicolour fields may overcome some of the constraints of single-colour high harmonic generation. Using two delayed pulses of the same frequency and parallel polarisation we demonstrate significant cut-off extension without increasing total ionisation throughout the pulse, crucial for maintaining harmonic yield close to the saturation limit. We also explain the significant yield enhancements observed in recent experiments using two parallel colours of incommensurate frequency. Finally, we describe the use of a second, perpendicularly polarised colour in trajectory selection, allowing for a temporal filtering of harmonic emission. Using an ω + 1.5ω frequency ratio also allows for a reduction in the periodicity of emitted attosecond pulse trains, permitting the production of isolated attosecond pulses with longer driving fields. Furthermore, by controlling the relative phase between the two colours, the ellipticity of these attosecond pulses may also be controlled

Spectral analysis of two-dimensional Bose-Hubbard models

One-dimensional Bose-Hubbard models are well known to obey a transition from regular to quantum-chaotic spectral statistics. We are extending this concept to relatively simple two-dimensional many-body models. Also in two dimensions a transition from regular to chaotic spectral statistics is found and discussed. In particular, we analyze the dependence of the spectral properties on the bond number of the two-dimensional lattices and the applied boundary conditions. For maximal connectivity, the systems behave most regularly in agreement with the applicability of mean-field approaches in the limit of many nearest-neighbor couplings at each site.Comment: 6 pages, 6 figure

Intramolecular integration within Moloney murine leukemia virus DNA

By screening a library of unintegrated, circular Moloney murine leukemia virus (M-MuLV) DNA cloned in lambda phage, we found that approximately 20% of the M-MuLV DNA inserts contained internal sequence deletions or inversions. Restriction enzyme mapping demonstrated tht the deleted segments frequently abutted a long terminal repeat (LTR) sequence, whereas the inverted segments were usually flanked by LTR sequences, suggesting that many of the variants arose as a consequence of M-MuLV DNA molecules integrating within their own DNA. Nucleotide sequencing also suggested that most of the variant inserts were generated by autointegration. One of the recombinant M-MuLV DNA inserts contained a large inverted repeat of a unique M-MuLV sequence abutting an LTR. This molecule was shown by nucleotide sequencing to have arisen by an M-MuLV DNA Molecule integrating within a second M-MuLV DNA molecule before cloning. The autointegrated M-MuLV DNA had generally lost two base pairs from the LTR sequence at each junction with target site DNA, whereas a four-base-pair direct repeat of target site DNA flanked the integrated viral DNA. Nucleotide sequencing of preintegration target site DNA showed that this four-base-pair direct repeat was present only once before integration and was thus reiterated by the integration event. The results obtained from the autointegrated clones were supported by nucleotide sequencing of the host-virus junction of two cloned M-MuLV integrated proviruses obtained from infected rat cells. Detailed analysis of the different unique target site sequences revealed no obvious common features

Offense-defense theory, state size and posturing in the cyber domain: the case of the United Kingdom and the Republic of Estonia

The increasing relevance of the cyber domain has an impact on the national security of states. At current stage, states are in a phase of introducing the cyber approach that best coincides with their security needs. While all states share the same threat of becoming victim to devastating cyber-attacks, they need to consider whether they take an offensive or defensive cyber posture in order to increase security in the virtual domain. This thesis addresses the question of whether state size have an effect on the cyber posture of state. First, in an attempt to theorize cyber posturing, the study modifies traditional assumptions of the offense-defense balance theory and applies the logic of the balance to the cyber domain. In addition, this thesis elaborates state size as a specific element that could explain an offensive or defensive cyber posture. It analysis whether cyber posture of small and large states differs and examines the sensitivity of small and large states to the offense-defense balance. In an empirical analysis of the cyber posture of Estonia and the United Kingdom, the research examines theoretical assumptions in a comparative analysis. The thesis demonstrates that state size has an impact on the cyber posture of states. While the UK adopts an offensive cyber posture, Estonia’s strategic documents do not indicate the development of offensive cyber capabilities at present the time. Finally, the thesis points out that small states are more sensitive to the offense-defense balance in cyberspace and adjust their cyber posture according to the offensive or defensive advantage.https://www.ester.ee/record=b5192821*es

CEO narcissism: an upper echelons perspective on financial advisor involvement in M&A

This research examines the link between CEO narcissism and the engagement of financial advisors in M&A deals. Drawing on the definition and past findings of narcissistic CEOs conducting larger and more frequent M&As, this research expected that narcissistic CEOs would reduce the size of the financial advisor engagement and attempted to explore the moderators of this effect. In total, three hypotheses were tested on a sample of 157 deals. The results indicate that CEO narcissism can not explain the size of the financial advisor engagement. Never the less, for smaller deal sizes and longer process lengths, there seems to be an effect