Ring-opening polymerisation of 1,3-Dioxolan-4-ones

Polyesters have been realised as a viable replacement for slow or non-degrading petroleum derived polymers. A variety of aliphatic polyesters, e.g. poly(lactic acid), have received a lot of attention because they are produced from renewable feedstocks and have the ability to biodegrade and bioassimilate. Poly(lactic acid)’s broader family, poly(α-hydroxy acid)s, have been produced with a wide variety of properties, that has given polyesters the potential for a more diverse range of applications. However, their synthesis has proven difficult. This thesis investigates a family of 1,3-dioxolan-4-ones as a monomer source to ease difficulties in current synthetic routes. Polymerisation of the parent 1,3-dixoxolan-4-one was tested. The copolymerisation of Llactide and 1,3-dioxolan-4-one was conducted with various monomer feedstocks. Ringopening polymerisation of 1,3-dioxolan-4-one led to the formation of paraformaldehyde as a polymerisation by-product. The copolymerisation was found to be best controlled when using a coordination-insertion type catalyst. 1,3-dioxolan-4-one was also copolymerised with ε- caprolactone and β-butyrolactone to produce copolymers with various compositions. The formation of poly(lactic acid) and poly(mandelic acid) from 5-methyl-1,3-dioxolan- 4-one and 5-phenyl-1,3-dioxolan-4-one was investigated. Poly(lactic acid) and poly(mandelic acid) were synthesised with either isotactic or atactic tacticities. Molecular weights were found to be lower than the expected values. A variety of MeAl(salen) catalysts were explored for the polymerisation of 5-methyl-1,3-dioxolan-4-one and catalysts ligated with tertiary-butyl substituted salens were found to have higher rates of polymerisation and reached high conversions. Altering the diimine bridge in the ligand led to variations in rates of polymerisation and molecular weights. The cause of the decrease in molecular weight was found to be caused by a side reaction. The side reaction was bypassed by polymerising 2,2,5- trimethyl-1,3-dioxolan-4-one and 2,2-dimethyl-5-phenyl-1,3-dioxolan-4-one to form poly(lactic acid) and poly(mandelic acid), respectively, with the expulsion of acetone. The scope of 1,3-dioxolan-4-ones capable of being polymerised to form poly(α-hydroxy acid)s was expanded to include iso-propyl, cyclohexyl, normal-butyl, iso-butyl, propargyl, chloromethyl and benzyloxymethyl substituents at the five position. The glass transition temperatures accessible from this synthetic route was expanded (22-105 °C). Kinetic experiments revealed the impact of the substituents steric bulk on the rate of polymerisation and points toward a coordination-insertion mechanism. Poly(lactic acid-co-glycolic acid) was copolymerised with 5-propargyl-1,3-dioxolan-4-one to incorporate alkynyl functionality and hence Raman spectroscopy showed the polymer had a distinct peak at 2128 cm-1. Following post-polymerisation modification of poly(lactic acid-co-3-chloro-2-hydroxypropanoic acid) copolymers, acrylate functionalised polymers were produced. The copolymers were shown to be capable of crosslinking poly(α-hydroxy acid) and poly(methyl methacrylate)

Eutrophication Monitoring and Prediction

Changes in trophic status are often related to increases or decreases in the allocthonous inputs of nutrients from changes in land use and management practices. Lake and reservoir managers are continually faced with the questions of what to monitor, how to monitor it, and how much change is necessary to be considered significant. This study is a compilation of four manuscripts, addressing one of these questions, using data from six reservoirs in Texas

Do “attractive things work better”? An exploration of search tool visualisations

A study was conducted to explore associations that may exist between user perceptions of aesthetics and usability in an attempt to validate Norman’s assertion that “attractive things work better”. Participants were run in a semi between-subjects design study. Judgements for aesthetics and usability were elicited prior to and after each test run with a record kept of performance. Pre-use and post-use measures indicated strong relations between judgements of aesthetics and usability, but an association was not found between aesthetics and performance, leading us to conclude that “attractive things are perceived to work better” though attractive systems may not work any better than unattractive systems. These results resemble past research and partly support the work of Norman proposing that valued aesthetics lead to a positive affective response, which opens the mind to creative thinking altering judgements made but not actual behaviour. The findings stress the importance of aesthetics in HCI and design, as an influential factor on perceptions of usability, which in turn influence higher order decisions

Synthetically Diversified Protein Nanopores: Resolving Click Reaction Mechanisms

Nanopores are emerging as a powerful tool for the investigation of nanoscale processes at the single-molecule level. Here, we demonstrate the methionine-selective synthetic diversification of α-hemolysin (α-HL) protein nanopores and their exploitation as a platform for investigating reaction mechanisms. A wide range of functionalities, including azides, alkynes, nucleotides, and single-stranded DNA, were incorporated into individual pores in a divergent fashion. The ion currents flowing through the modified pores were used to observe the trajectory of a range of azide–alkyne click reactions and revealed several short-lived intermediates in Cu­(I)-catalyzed azide–alkyne [3 + 2] cycloadditions (CuAAC) at the single-molecule level. Analysis of ion-current fluctuations enabled the populations of species involved in rapidly exchanging equilibria to be determined, facilitating the resolution of several transient intermediates in the CuAAC reaction mechanism. The versatile pore-modification chemistry offers a useful approach for enabling future physical organic investigations of reaction mechanisms at the single-molecule level

Therapeutic interventions in children and adolescents with patellar tendon related pain: a systematic review

Objective: Evaluate effectiveness and harms of interventions for patellar tendon related pain in children and adolescents.Design: Systematic review and meta-analysis.Data sources: Medline via Pubmed, Embase via OVID, CINAHL via Ebsco, SportDiscus up until 24 November 2017 were searched.Eligibility criteria for selecting studies: Inclusion criteria were (1) controlled or randomised controlled clinical trials (RCTs), (2) participants with diagnosis of patellar tendon related disorder, (3) participants≤18 years of age at enrolment and (4) published in a peer-reviewed English or Scandinavian language journal.Results: Of 530 studies identified, eight were included after screening, with three included in data synthesis. To be included in data synthesis, we required studies to have included (and have data available for) a minimum of 10 participants under 18 years. All studies were rated as being at high risk of bias. For adolescents with patellar tendinopathy, one RCT compared eccentric exercises to usual care and found no difference between groups. In adolescents with Osgood-Schlatter disease (OSD), injection of local anaesthetic with dextrose proved superior to either usual care or local anaesthetic alone (three armed RCTs). In a retrospective case controlled study in adolescents with OSD, surgery provided no benefit over conservative management in terms of persistent symptoms and had a higher complication rate.Conclusion: There is weak evidence to support the use of dextrose injection with local anaesthetic and no evidence to support the use of specific types of exercises to treat children/adolescents with OSD/patellar tendinopathy. Until further evidence arises, clinicians should include load modification and advise on a return to sport based on symptoms

Tautness for riemannian foliations on non-compact manifolds

For a riemannian foliation $\mathcal{F}$ on a closed manifold $M$, it is known that $\mathcal{F}$ is taut (i.e. the leaves are minimal submanifolds) if and only if the (tautness) class defined by the mean curvature form $\kappa_\mu$ (relatively to a suitable riemannian metric $\mu$) is zero. In the transversally orientable case, tautness is equivalent to the non-vanishing of the top basic cohomology group $H^{^{n}}(M/\mathcal{F})$, where n = \codim \mathcal{F}. By the Poincar\'e Duality, this last condition is equivalent to the non-vanishing of the basic twisted cohomology group $H^{^{0}}_{_{\kappa_\mu}}(M/\mathcal{F})$, when $M$ is oriented. When $M$ is not compact, the tautness class is not even defined in general. In this work, we recover the previous study and results for a particular case of riemannian foliations on non compact manifolds: the regular part of a singular riemannian foliation on a compact manifold (CERF).Comment: 18 page

CHiCAGO: robust detection of DNA looping interactions in Capture Hi-C data.

Capture Hi-C (CHi-C) is a method for profiling chromosomal interactions involving targeted regions of interest, such as gene promoters, globally and at high resolution. Signal detection in CHi-C data involves a number of statistical challenges that are not observed when using other Hi-C-like techniques. We present a background model and algorithms for normalisation and multiple testing that are specifically adapted to CHi-C experiments. We implement these procedures in CHiCAGO ( http://regulatorygenomicsgroup.org/chicago ), an open-source package for robust interaction detection in CHi-C. We validate CHiCAGO by showing that promoter-interacting regions detected with this method are enriched for regulatory features and disease-associated SNPs

Long-Range Enhancer Interactions Are Prevalent in Mouse Embryonic Stem Cells and Are Reorganized upon Pluripotent State Transition.

Transcriptional enhancers, including super-enhancers (SEs), form physical interactions with promoters to regulate cell-type-specific gene expression. SEs are characterized by high transcription factor occupancy and large domains of active chromatin, and they are commonly assigned to target promoters using computational predictions. How promoter-SE interactions change upon cell state transitions, and whether transcription factors maintain SE interactions, have not been reported. Here, we used promoter-capture Hi-C to identify promoters that interact with SEs in mouse embryonic stem cells (ESCs). We found that SEs form complex, spatial networks in which individual SEs contact multiple promoters, and a rewiring of promoter-SE interactions occurs between pluripotent states. We also show that long-range promoter-SE interactions are more prevalent in ESCs than in epiblast stem cells (EpiSCs) or Nanog-deficient ESCs. We conclude that SEs form cell-type-specific interaction networks that are partly dependent on core transcription factors, thereby providing insights into the gene regulatory organization of pluripotent cells.P.J.R.-G. is supported by the Wellcome Trust (WT093736), Biotechnology and Biological Sciences Research Council (BB/M022285/1 and BB/P013406/1), and the European Commission Network of Excellence EpiGeneSys (HEALTH-F4-2010-257082). This work was also supported by the following grants to P.F.: Medical Research Council (MR/L007150/1, MC_UP_1302/1, MC_UP_1302/3, MC_UP_1302/5), and Biotechnology and Biological Sciences Research Council (BB/J004480/1)