RNA interference for the treatment of cancer

RNA interference (RNAi) is the latest new technology in the field of genetic medicine in which specific genes can be turned off, or silenced, so as to affect a therapeutic outcome. It can be highly specific, works in the nanomolar range and is far more effective than the antisense approaches popular 10-15 years ago. Here we review the field and explore the potential role of RNAi in cancer therapy, highlighting recent progress and examining the hurdles that must be overcome before this promising technology is ready for clinical use. (C) 2006 Prous Science. All rights reserved.

RNA interference-inducing hairpin RNAs in plants act through the viral defence pathway

RNA interference (RNAi) is widely used to silence genes in plants and animals. it operates through the degradation of target mRNA by endonuclease complexes guided by approximately 21 nucleotide (nt) short interfering RNAs (siRNAs). A similar process regulates the expression of some developmental genes through approximately 21 nt microRNAs. Plants have four types of Dicer-like (DCL) enzyme, each producing small RNAs with different functions. Here, we show that DCL2, DCL3 and DCL4 in Arabidopsis process both replicating viral RNAs and RNAi-inducing hairpin RNAs (hpRNAs) into 22-, 24- and 21 nt siRNAs, respectively, and that loss of both DCL2 and DCL4 activities is required to negate RNAi and to release the plant's repression of viral replication. We also show that hpRNAs, similar to viral infection, can engender long-distance silencing signals and that hpRNA-induced silencing is suppressed by the expression of a virus-derived suppressor protein. These findings indicate that hpRNA-mediated RNAi in plants operates through the viral defence pathway.

Interference between propagating changes and its effect on system failure

Computer-based, socio-technical systems projects are frequently failures. In particular, computer-based information systems often fail to live up to their promise. Part of the problem lies in the uncertainty of the effect of combining the subsystems that comprise the complete system; i.e. the system's emergent behaviour cannot be predicted from a knowledge of the subsystems. This paper suggests uncertainty management is a fundamental unifying concept in analysis and design of complex systems and goes on to indicate that this is due to the co-evolutionary nature of the requirements and implementation of socio-technical systems. The paper shows a model of the propagation of a system change that indicates that the introduction of two or more changes over time can cause chaotic emergent behaviour.

The Role of the big five personality traits, proactive behaviour, and socialisation influences in newcomer adjustment

During the early stages of employment, newly hired employees find out what their new organisations are like. Their first impressions are extremely important in determining the course of subsequent attitudes and behaviour. Recently, a considerable progress has been made towards the understanding of adjustment process, however, the literature remain divided along a number of fronts. Moreover, newcomer research has been conducted independent and irrespective of newcomer personality individual differences. This seems to be a critical oversight because there is overlap in predictions involving these constructs. The current research extended the previous one by examining these multiple antecedents, including Big Five personality traits of newcomer to the tandem process of adjustment as well as outcomes that immediate, or ?proximal? to the process of newcomer adjustment. Following a cross sectional pilot study of recent college graduate, a three- wave longitudinal study of newcomers in seven organisations examined Big Five personality traits, proactive behaviour, and socialisation influence (formal training, leaders, co-workers) as antecedents of proximal adjustment outcomes (group integration, political knowledge of organisation, and task performance). The main study results suggested that personality traits were related to proximal adjustment outcomes, specifically, Conscientiousness was positively related to all proximal adjustment outcomes. Openness to experience was related to task performance and political knowledge. Group integration is independently related to Agreeableness, Extraversion and Neuroticism. The socialisation influence moderate these relations, for example, leader socialisation moderate Conscientiousness as it relates to political knowledge and group integration, while co-worker moderate Extraversion as it relates to task performance. Finally, it was found that, the relationship between proximal adjustment outcomes and the personality dimensions Openness was mediated by proactive behaviour. Overall, the results suggested that individual differences have a role in newcomer adjustment as it facilitate the socialisation influence, and Big Five was one of the key determinants of newcomer adjustment.

All-fiber polarization interference filters based on 45°-tilted fiber gratings

We report all-fiber polarization interference filters, known as Lyot and Lyot-Ohman filters, based on alternative concatenation of UV-inscribed fiber gratings with structure tilted at 45° and polarization maintaining (PM) fiber cavities. Such filters generate comb-like transmission of linear polarization output. The free spectral range (FSR) of a single-stage (Lyot) filter is PM fiber cavity length dependent, as a 20 cm long cavity showed a 26.6 nm FSR while the 40 cm one exhibited a 14.8 nm FSR. Furthermore, we have theoretically and experimentally demonstrated all-fiber 2-stage and 3-stage Lyot-Ohman filters, giving more freedom in tailoring the transmission characteristics.

The Kinematics of interference mechanisms in certain machining operations

The mechanism of "Helical Interference" in milled slots is examined and a coherent theory for the geometry of such surfaces is presented. An examination of the relevant literature shows a fragmented approach to the problem owing to its normally destructive nature, so a complete analysis is developed for slots of constant lead, thus giving a united and exact theory for many different setting parameters and a range of cutter shapes. For the first time, a theory is developed to explain the "Interference Surface" generated in variable lead slots for cylindrical work and attention is drawn to other practical surfaces, such as cones, where variable leads are encountered. Although generally outside the scope of this work, an introductory analysis of these cases is considered in order to develop the cylindrical theory. Special emphasis is laid upon practical areas where the interference mechanism can be used constructively and its application as the rake face of a cutting tool is discussed. A theory of rake angle for such cutting tools is given for commonly used planes, and relative variations in calculated rake angle between planes is examined. Practical tests are conducted to validate both constant lead and variable lead theories and some design improvements to the conventional dividing head are suggested in order to manufacture variable lead workpieces, by use of a "superposed" rotation. A prototype machine is manufactured and its kinematic principle given for both linear and non-linearly varying superposed rotations. Practical workpieces of the former type are manufactured and compared with analytical predictions,while theoretical curves are generated for non-linear workpieces and then compared with those of linear geometry. Finally suggestions are made for the application of these principles to the manufacture of spiral bevel gears, using the "Interference Surface" along a cone as the tooth form.