Validation of IKK beta as therapeutic target in airway inflammatory disease by adenoviral-mediated delivery of dominant-negative IKK beta to pulmonary epithelial cells - Catley, Matthew C.; Chivers, Joanna E.; Holden, Neil S.; Barnes, Peter J.; Newton, Robert
Asthma is an inflammatory disease of the lungs and the transcription factor NF-kappa B regulates the production of numerous inflammatory mediators that may have a role in the pathogenesis of asthma. Hence, the signalling pathways leading to NF-kappa B activation are considered prime targets for novel anti-inflammatory therapies. The prevention of NF-kappa B activity in mice, through the knockout of IKK beta or p65, causes fatal liver degeneration in utero making it difficult to determine the full implications of inhibiting NF-kappaB activity in tissues physiologically relevant to human diseases. This study used adenovirus delivery of a dominant inhibitor of NF-kappaB...
Analysis of the dissociated steroid RU24858 does not exclude a role for inducible genes in the anti-inflammatory actions of glucocorticoids. - Chivers, Joanna E.; Gong, Wei; King, Elizabeth M.; Seybold, Joachim; Mak, Judith C.; Donnelly, Louise E.; Holden, Neil S.; Newton, Robert
Although repression of inflammatory gene expression makes glucocorticoids powerful anti-inflammatory agents, side effects limit usage and drive the search for improved glucocorticoid receptor (GR) ligands. In A549 pulmonary cells, dexamethasone and the prototypical dissociated ligand RU24858 (Mol Endocrinol 11:1245-1255, 1997) repress interleukin (IL)-1beta-induced expression of cyclooxygenase (COX)-2 and IL-8. Although RU24858 is a weaker GR ligand, both glucocorticoids showed similar efficacies on transrepression of nuclear factor kappaB (NF-kappaB)-dependent transcription, whereas RU24858 yielded less than 12% of the response to dexamethasone on a classic glucocorticoid response element (GRE) reporter (transactivation). Modest NF-kappaB-dependent transrepression ( approximately 40%), along with analysis of IL-8...
Repression of inflammatory gene expression in human pulmonary epithelial cells by small-molecule IκB kinase inhibitors - Newton, Robert; Holden, Neil S.; Catley, Matthew C.; Oyelusi, Wale; Leigh, Richard; Proud, David; Barnes, Peter J.
The airway epithelium is critical in the pathogenesis of chronic inflammatory diseases, such as asthma and chronic obstructive pulmonary disease, and, by expressing numerous inflammatory genes, plays a prominent role in disease exacerbations. Since inflammatory gene expression often involves the transcription factor nuclear factor (NF)-κB, this signaling pathway represents a site for anti-inflammatory intervention. As the airway epithelium is targeted by inhaled therapeutic agents, for example corticosteroids, human A549 pulmonary cells and primary human bronchial epithelial (HBE) cells were selected to evaluate inhibitor of κB kinase (IKK) inhibitors. In A549 cells, interleukin (IL)-1β and tumor necrosis factor (TNF) α increased...
Separating transrepression and transactivation: a distressing divorce for the glucocorticoid receptor? - Newton, Robert; Holden, Neil S.
Glucocorticoids (corticosteroids) are highly effective in combating inflammation in the context of a variety of diseases. However, clinical utility can be compromised by the development of side effects, many of which are attributed to the ability of the glucocorticoid receptor (GR) to induce the transcription of, or transactivate, certain genes. By contrast, the anti-inflammatory effects of glucocorticoids are due largely to their ability to reduce the expression of pro-inflammatory genes. This effect has been predominantly attributed to the repression of key inflammatory transcription factors, including AP-1 and NF-kappaB, and is termed transrepression. The ability to functionally separate these transcriptional functions...
Equations of motion of rotating composite beam with a nonconstant rotation speed and an arbitrary preset angle - Georgiades, F.; Latalski, J.; Warminski, J.
In the presented paper the equations of motion of a rotating composite Timoshenko beam are derived by utilising the Hamilton principle. The non-classical effects like material anisotropy, transverse shear and both primary and secondary cross-section warpings are taken into account in the analysis. As an extension of the other papers known to the authors a nonconstant rotating speed and an arbitrary beam's preset (pitch) angle are considered. It is shown that the resulting general equations of motion are coupled together and form a nonlinear system of PDEs. Two cases of an open and closed box-beam cross-section made of symmetric laminate...
How can communication design make dance film accessible to the general public? - Breen, C. B.
By drawing on my own practice led research, literature and critiquing existing dance films, this paper aims to illustrate why dance film is not communicating to the general public. Dance film is one of the many offshoots that have occurred since the joining together of dance and screen media. At present, dance film is mostly seen by dancers, has low audience ratings, and is not shown in mainstream cinemas. (Towers, D, 2011, email, 2nd March) It is a highly theoretical and complex subject area in which there are many debates and definitions in circulation. What this paper aims to do...
Why isn't academic research free to everyone? - Berlatsky, Noah; Eve, Martin Paul
Scholarly articles, filled with indubitable knowledge and analysis, only exist for the general public behind pricey paywalls. So one lecturer is advocating for them to be free of charge.
Deliberation behind closed doors: transparency and lobbying in the European Union [by Daniel Naurin] - Parks, Louisa
This book makes a refreshingly empirical contribution to discussions of the European
Union and its democratic deficit, specifically on the possible role of increased transparency
in alleviating the latter. Naurin rightly challenges us to think about transparency and its
effects – to ‘take transparency seriously’ rather than merely assume its panacea-like
effects for European Union democracy and legitimacy. With this in mind, Naurin’s work
focuses on investigating what deliberative democracy theorists label the civilizing effect
Nilpotent groups admitting an almost regular automorphism of order four - Makarenko, N. Yu.; Khukhro, E. I.
We consider locally nilpotent periodic groups admitting an almost regular automorphism of order 4. The following are results are proved: (1) If a locally nilpotent periodic group G admits an automorphism Ï� of order 4 having exactly m < â�� fixed points, then (a) the subgroup G, Ï�2 contains a subgroup of m-bounded index in G, Ï�2 which is nilpotent of m-bounded class, and (b) the group G contains a subgroup V of m-bounded index such that the subgroup V, Ï�2 is nilpotent of m-bounded class (Theorem 1); (2) If a locally nilpotent periodic group G admits an automorphism Ï�...
Finite groups of bounded rank with an almost regular automorphism of prime order - Khukhro, E. I.
We prove that if a finite group G of rank r admits an automorphism Ï� of prime order having exactly m fixed points, then G has a Ï�-invariant subgroup of (r,m)-bounded index which is nilpotent of r-bounded class (Theorem 1). Thus, for automorphisms of prime order the previous results of Shalev, Khukhro, and Jaikin-Zapirain are strengthened. The proof rests, in particular, on a result about regular automorphisms of Lie rings (Theorem 3). The general case reduces modulo available results to the case of finite p-groups. For reduction to Lie rings powerful p-groups are also used. For them a useful fact...
On solvability of lie rings with an automorphism of finite order - Khukhro, E. I.
A new criterion for a Lie ring with a semisimple automorphism of finite order to be solvable is proved. It generalizes the effective version of Winter's criterion obtained earlier by Khukhro and Shumyatsky and by Bergen and Grzeszczuk in replacing the ideal generated by a certain set by the subring generated by this set. The proof is inspired by the original theorem of Kreknin on solvability of Lie rings with regular automorphisms of finite order and is conducted mostly in terms of Lie rings graded by a finite cyclic group.
The Andrews-Curtis conjecture and black box groups - Borovik, A. V.; Khukhro, E. I.; Myasnikov, A. G.
The paper discusses the Andrews-Curtis graph Î�Îº(G, N) of a normal subgroup N in a group G. The vertices of the graph are Îº-tuples of elements in N which generate N as a normal subgroup; two vertices are connected if one of them can be obtained from another by certain elementary transformations. This object appears naturally in the theory of black box finite groups and in the Andrews-Curtis conjecture in algebraic topology 3. We suggest an approach to the Andrews-Curtis conjecture based on the study of Andrews-Curtis graphs of finite groups, discuss properties of Andrews-Curtis graphs of some classes of...
Lie rings admitting an automorphism of order 4 with few fixed points. II - Makarenko, N.Yu.; Khukhro, E. I.
We consider a Lie ring (algebra) L that admits an automorphism Ï� of order 4 with a finite number m of fixed points (with a fixed-point subalgebra of finite dimension m). It is proved that L contains a subring S of m-bounded index in the additive group L (a subalgebra S of m-bounded codimension), which possesses a nilpotent ideal I of class bounded by some constant, such that the factor-ring S/I is nilpotent of class â�¤ 2. As a consequence, it is proved that, under the same conditions, L has a subring G of m-bounded index in the additive group...
Separate motion-detecting mechanisms for first- and second-order patterns revealed by rapid forms of visual motion priming and motion after effect - Pavan, Andrea; Campana, Gianluca; Guerreschi, Michele; Manassi, Mauro; Casco, Clara
Fast adaptation biases the perceived motion direction of a subsequently presented ambiguous test pattern (R. Kanai & F. A. Verstraten, 2005). Depending on both the duration of the adapting stimulus (ranging from tens to hundreds of milliseconds) and the duration of the adaptation-test blank interval, the perceived direction of an ambiguous test pattern can be biased towards the same or the opposite direction of the adaptation pattern, resulting in rapid forms of motion priming or motion aftereffect respectively. These findings were obtained employing drifting luminance gratings. Many studies have shown that first-order motion (luminance-defined) and second-order motion (contrast-defined) stimuli are...
The role of stationary and dynamic test patterns in rapid forms of motion after-effect - Pavan, Andrea; Skujevskis, Maris
Subsecond adaptation to directional motion can induce a rapid form of motion after-effect (rMAE). Unlike the characteristics of the classic motion after-effect (MAE), produced by adaptation of several seconds or minutes, the properties of the rMAE have been less well explored. In a series of experiments, we assessed the role of stationary and dynamic test patterns (counterphase flickering gratings) in generating rMAE. In particular, we varied the duration, temporal frequency, and spatial phase of the adapting stimuli. Our results show that rMAE is only generated by dynamic test patterns, exhibiting a strong dependence on the adaptation duration and temporal frequency...