Synthesis of the heterocyclic core of the alkaloids martinelline and martinellic acid

The tricyclic core of martinelline and martinellic acid was rapidly assembled utilising an imino Diels-Alder reaction of an imine derived from cinnamaldehyde with a cyclic enamide. The cycloaddition was completely regioselective though the exo endo selectivity was poor. These diastercoisomers were readily separated by flash chromatography and the relative stereochemistry of the exo-isomer confirmed by single crystal X-ray crystallography. This intermediate was converted to the central core of the aforementioned alkaloids in five additional synthetic operations. (C) 2001 Elsevier Science Ltd. All rights reserved.

A ring-closing metathesis approach to the bicyclo[4.3.1]decane core of caryolanes

A synthesis of highly substituted and sterically congested bicyclo[4.3.1]decenes, a structure embedded in the core 4,7,6-tricyclic system of natural caryolanes, was successfully achieved via a ring-closing metathesis (RCM) reaction of syn-1,3-diene substituted cyclohexanols. The construction of the diene substrates, starting from 4-acetoxy-3-methyl-2-cyclohexen-1-one, employed diastereoselective copper-mediated conjugate addition and Grignard reactions. An X-ray crystal structure determination of a key synthetic intermediate confirmed the relative stereochemistry of the RCM bicyclic product.

A low-energy core-collapse supernova without a hydrogen envelope

The final fate of massive stars depends on many factors. Theory suggests that some with initial masses greater than 25 to 30 solar masses end up as Wolf-Rayet stars, which are deficient in hydrogen in their outer layers because of mass loss through strong stellar winds. The most massive of these stars have cores which may form a black hole and theory predicts that the resulting explosion of some of them produces ejecta of low kinetic energy, a faint optical luminosity and a small mass fraction of radioactive nickel. An alternative origin for low-energy supernovae is the collapse of the oxygen-neon core of a star of 7-9 solar masses. No weak, hydrogen-deficient, core-collapse supernovae have hitherto been seen. Here we report that SN 2008ha is a faint hydrogen-poor supernova. We propose that other similar events have been observed but have been misclassified as peculiar thermonuclear supernovae (sometimes labelled SN 2002cx-like events). This discovery could link these faint supernovae to some long-duration gamma-ray bursts, because extremely faint, hydrogen-stripped core-collapse supernovae have been proposed to produce such long gamma-ray bursts, the afterglows of which do not show evidence of associated supernovae.

Group Design-Build-Test Projects as the Core of an Integrated Curriculum in Product Design and Development

The School of Mechanical and Aerospace Engineering at Queen’s University Belfast introduced a new degree programme in Product Design and Development (PDD) in 2004. As well as setting out to meet all UK-SPEC requirements, the entirely new curriculum was developed in line with the syllabus and standards defined by the CDIO Initiative, an international collaboration of universities aiming to improve the education of engineering students. The CDIO ethos is that students are taught in the context of conceiving, designing, implementing and operating a product or system. Fundamental to this is an integrated curriculum with multiple Design-Build-Test (DBT) experiences at the core. Unlike most traditional engineering courses the PDD degree features group DBT projects in all years of the programme. The projects increase in complexity and challenge in a staged manner, with learning outcomes guided by Bloom’s taxonomy of learning domains. The integrated course structure enables the immediate application of disciplinary knowledge, gained from other modules, as well as development of professional skills and attributes in the context of the DBT activity. This has a positive impact on student engagement and the embedding of these relevant skills, identified from a stakeholder survey, has also been shown to better prepare students for professional practice. This paper will detail the methodology used in the development of the curriculum, refinements that have been made during the first five years of operation and discuss the resource and staffing issues raised in facilitating such a learning environment.

Inferring the conservative causal core of gene regulatory networks

Background
Inferring gene regulatory networks from large-scale expression data is an important problem that received much attention in recent years. These networks have the potential to gain insights into causal molecular interactions of biological processes. Hence, from a methodological point of view, reliable estimation methods based on observational data are needed to approach this problem practically.

Results
In this paper, we introduce a novel gene regulatory network inference (GRNI) algorithm, called C3NET. We compare C3NET with four well known methods, ARACNE, CLR, MRNET and RN, conducting in-depth numerical ensemble simulations and demonstrate also for biological expression data from E. coli that C3NET performs consistently better than the best known GRNI methods in the literature. In addition, it has also a low computational complexity. Since C3NET is based on estimates of mutual information values in conjunction with a maximization step, our numerical investigations demonstrate that our inference algorithm exploits causal structural information in the data efficiently.

Conclusions
For systems biology to succeed in the long run, it is of crucial importance to establish methods that extract large-scale gene networks from high-throughput data that reflect the underlying causal interactions among genes or gene products. Our method can contribute to this endeavor by demonstrating that an inference algorithm with a neat design permits not only a more intuitive and possibly biological interpretation of its working mechanism but can also result in superior results.

MicroRNA regulation of core apoptosis pathways in cancer

Recent research has demonstrated that microRNAs (miRNAs) are key regulators of many cell processes often deregulated in cancer, including apoptosis. Indeed, it is becoming clear that many miRNAs are anti-apoptotic and mediate this effect by targeting pro-apoptotic mRNAs or positive regulators of pro-apoptotic mRNAs. Conversely, many pro-apoptotic miRNAs target anti-apoptotic mRNAs or their positive regulators. We have reviewed the current knowledge in this area including evidence of miRNA involvement in cancer drug resistance. (C) 2010 Elsevier Ltd. All rights reserved.