Enantioselective Organocatalytic α-Fluorination of Aldehydes

The first direct enantioselective catalytic α-fluorination of aldehydes has been accomplished. The use of enamine catalysis has provided a new organocatalytic strategy for the enantioselective fluorination of aldehydes to generate α-fluoro aldehydes, an important chiral synthon for medicinal agent synthesis. The use of imidazolidinone 1 as the asymmetric catalyst has been found to mediate the fluorination of a large variety of aldehyde substrates with N-fluorobenzenesulfonimide serving as the electrophilic source of fluorine. A diverse spectrum of aldehyde substrates can also be accommodated in this new organocatalytic transformation. While catalyst quantities of 20 mol % were generally employed in this study, successful halogenation can be accomplished using catalyst loadings as low as 2.5 mol %

Importance measures for non-coherent-system analysis

Component importance analysis is a key part of the system reliability quantification process. It enables the weakest areas of a system to be identified and indicates modifications, which will improve the system reliability. Although a wide range of importance measures have been developed, the majority of these measures are strictly for coherent system analysis. Non-coherent systems can occur and accurate importance analysis is essential. This paper extends four commonly used measures of importance, using the noncoherent extension of Birnbaum’s measure of component reliability importance. Since both component failure and repair can contribute to system failure in a noncoherent system, both of these influences need to be considered. This paper highlights that it is crucial to choose appropriate measures to analyze component importance. First the aims of the analysis must be outlined and then the roles that component failures and repairs can play in system state deterioration can be considered. For example, the failure/repair of components in safety systems can play only a passive role in system failure, since it is usually inactive, hence measures that consider initiator importance are not appropriate to analyze the importance of these components. Measures of importance must be chosen carefully to ensure analysis is meaningful and useful conclusions can be drawn

Birnbaum’s measure of component importance for noncoherent systems

Importance analysis of noncoherent systems is limited, and is generally inaccurate because all measures of importance that have been developed are strictly for coherent analysis. This paper considers the probabilistic measure of component importance developed by Birnbaum (1969). An extension of this measure is proposed which enables noncoherent importance analysis. As a result of the proposed extension the average number of system failures in a given interval for noncoherent systems can be calculated more efficiently. Furthermore, because Birnbaum’s measure of component importance is central to many other measures of importance; its extension should make the derivation of other measures possible

Calculating the failure intensity of a non-coherent fault tree using the BDD technique.

This paper considers a technique for calculating the unconditional failure intensity of any given non-coherent fault tree. Conventional Fault Tree Analysis (FTA) techniques involve the evaluation of lengthy series expansions and approximations are unavoidable even for moderate sized fault trees. The Binary Decision Diagram (BDD) technique overcomes some of the shortfalls of conventional FTA techniques enabling efficient and exact quantitative analysis of both coherent and non-coherent fault trees

Using Voice Recognition Software to improve communicative writing and social participation in an individual with severe acquired dysgraphia: an experimental single case therapy study

Background Two previous single-case studies have reported that voice recognition software (VRS) can be a powerful tool for circumventing impaired writing in aphasia (Bruce et al, 2003; Estes & Bloom, 2011). However, these studies report mixed results regarding transfer of skills to functional tasks, such as emailing. Method A single-case therapy study was conducted with “Stephen”, a 63 -year old man with fluent aphasia and severe acquired dysgraphia and dyslexia limiting his social participation and ability to return to work. Treatment consisted of 16 one-hour sessions. Stephen was trained to use Dragon NaturallySpeakingRTM VRS to assist writing and Read+WriteGoldRTM text-to-speech software to assist reading, and to develop computer skills required to use email. Outcome measures evaluated writing efficiency and communicative effectiveness, the functional impact of the intervention, and changes in participation. Results Training produced significant gains in the efficiency and communicative effectiveness of Stephen’s writing, despite his underlying writing impairment remaining unchanged. Gains generalised to everyday functional communication, leading to increased social participation with Stephen undertaking a wider range of social activities and increasing his social network following treatment. Gains were maintained at follow-up assessment. Discussion Results indicate that a relatively short training period with assistive technologies achieved extensive generalisation to independent, functional communicative writing. Indeed, for this case, VRS training may have exceeded the degree of improvement in functional text writing that could have been achieved through impairment therapy, since gains were not limited to treated vocabulary. Some challenges were encountered in training Stephen to use VRS but, through adaptations to the training process, were largely overcome. Importantly, regaining independent writing skills resulted in profound and life-changing improvements to social participation. This may have resulted in Stephen reconnecting with important aspects of his pre-stroke identity, and improving his self-esteem. Conclusion This case adds to a small evidence base indicating that training in the use of VRS, in combination with text-to-speech software, may be an effective way to address writing impairments in chronic aphasia for individuals with relatively well-preserved spoken output. Not only can these technologies improve the efficiency and communicative effectiveness of writing, they can also lead to significant gains in functional communication and social participation. Further research is needed trialing this approach with a larger group of people with aphasia

Bioenergetic Profiling of Zebrafish Embryonic Development

Many debilitating conditions are linked to bioenergetic defects. Developing screens to probe the genetic and/or chemical basis for such links has proved intractable. Furthermore, there is a need for a physiologically relevant assay of bioenergetics in whole organisms, especially for early stages in life where perturbations could increase disease susceptibility with aging. Thus, we asked whether we could screen bioenergetics and mitochondrial function in the developing zebrafish embryo. We present a multiplexed method to assay bioenergetics in zebrafish embryos from the blastula period (3 hours post-fertilization, hpf) through to hatching (48 hpf). In proof of principle experiments, we measured respiration and acid extrusion of developing zebrafish embryos. We quantified respiratory coupling to various bioenergetic functions by using specific pharmacological inhibitors of bioenergetic pathways. We demonstrate that changes in the coupling to ATP turnover and proton leak are correlated with developmental stage. The multiwell format of this assay enables the user to screen for the effects of drugs and environmental agents on bioenergetics in the zebrafish embryo with high sensitivity and reproducibility