Development of new chemical biological tools to probe splice site selection

RNA splicing is a key process in gene expression and regulation in Eukaryotes and involves the processing of pre-mRNA sequences into mature mRNA. Pre-mRNA consists of exons (protein coding regions) and introns (non-protein coding regions). The introns of the pre-mRNA are excised and the exons ligate to form mature mRNA ready for export from the nucleus. Within the pre-mRNA there are numerous splice sites, some of which are conserved whilst others are alternative splice sites. RNA splicing can follow two different pathways: constitutive or alternative and in humans around 90% of pre mRNA is alternatively spliced which accounts for the formation of multiple isoforms of a single gene. The regulation of splicing involves cis-acting factors which are enhancer/silencer sequences within the pre-mRNA and trans-acting factors comprising of cellular factors including RNA and proteins, combined together they enhance or silence splicing. A major challenge in the field is to determine the interplay between the various factors associated with the promotion or silencing of specific splice sites. Two putative models for the utilization of splice sites have been proposed; firstly, a looping mechanism whereby the enhancers randomly collide with each other by 3D diffusion forming a loop. Secondly, enhancer mediated splicing occurs by a cooperative protein binding process. However, due to the limitations of current biochemical tools, it is not possible to determine the exact mode of action. In this thesis, a new chemical biological approach has been developed which addresses this question, involving the construction of tripartite RNA constructs separated by a non-RNA tether. Using these model systems, compelling evidence is provided which demonstrates splice site selection does not proceed via a looping mechanism which is the widely accepted model in the field

Comparison of laminite fracture features at different scales

<p>Laminites (NE Brazil) are well laminated carbonates that provide insight into the geomechanical behaviour of layered systems, especially when comparing deformation characteristics observed in the laboratory with outcrop / field scale deformations. </p> <p>This is useful in order to </p> <p>a)  validate where laboratory experiments can reproduce field scale deformation types </p> <p>b)  understand which feature characteristics can or cannot be scaled</p

Twelve tips for turning quality assurance data into undergraduate teaching awards: A quality improvement and student engagement initiative

<p>Data on teaching awards in undergraduate medical education are sparse. The benefits of an awards system may seem obvious at first glance. However, there are also potential problems relating to fairness, avoidance of bias, and alignment of the awards system with a wider strategy for quality improvement and curriculum development. Here, we report five- year single center experience with establishing undergraduate teaching awards in a large academic teaching hospital. Due to lack of additional funding we based our awards not on peer review but mainly on existing and very comprehensive quality assurance (QA) data. Our 12 tips describe practical points but also pitfalls with awards categories and criteria, advertising and disseminating the awards, the actual awards ceremony and finally embedding the awards in the hospital’s wider strategy. To be truly successful, teaching awards and prizes need to be carefully considered, designed and aligned with a wider institutional strategy of rewarding enthusiastic educators.</p

Supplementary file 1: Workflow model for the digitization of mudrocks

Typical workflows based on the specific software used

Supplementary file 3: Workflow model for the digitization of mudrocks

Typical workflows based on the specific software used

Supplementary file 2: Workflow model for the digitization of mudrocks

Typical workflows based on the specific software used

Network Connectivity in low-permeability Carbonates

<p><b>Open</b> fracture networks flow paths in low permeability rocks, are highly sensitive to changes in aperture. Even high resolution X-ray tomography-derived aperture distributions and connectivities cannot accurately predict bulk or local     flow characteristics, especially if matrix pore systems contribute. </p> <p><b>Here</b> XRT reconstructions of experimentally-fractured low-permeability laminites are accompanied by neutron beam radiography and tomography, where first dense then normal water are injected into the sample base. </p> <p><b>To </b>our knowledge this is the first identification of fluid front movement through fracture arrays using neutron tomography.</p><p><b>Samples</b> of a very fine-grained laminite, a lacustrine layered carbonate rock “grain size” 5µm, were deformed experimentally to represent 1 to 2 km burial depth, creating a partially interconnected series of shear- and extension-fractures (Fig. 1) that the XRT indicated were partly open under atmospheric conditions.</p><p> <br></p><p><b>Continuous</b> radiography and periodic (3D) tomography (Figs 2 & 3) are used to record movement of dense (deuterated) water, injected at the base under pressure control, until this water reaches the sample top. Distilled water is then injected and progression of normal water through the (mostly) deuterated water saturated sample is monitored. </p><p> <br></p><p><br></p><p><br></p> <p> </p> <p> </p

Electroinitiated polymerization

peer reviewedaudience: researcherElectroinitiated polymerization, a method particularly relevant in coating technology, offers the unique opportunity of imparting permanent functionality/reactivity to a variety of surfaces, provided that the solid substrate is (semi)conducting. By focusing on the electroinitiation of acrylic monomers, basic concepts and some tools dedicated to the analysis of this peculiar polymerization process are discussed in this chapter. The important role of this polymerization method in the field of conjugated polymers is also highlighted. Finally, this chapter concludes with the opportunities and future challenges of this technology

Study flow diagram.

<p>Study flow diagram.</p

Pharmacological Intervention Categories.

<p>Pharmacological Intervention Categories.</p