1,589 research outputs found
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
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
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