The depositional environments and structures of the Borrowdale Volcanic Group and the Windermere Supergroup in the Southern Lake District, England

Field studies have been undertaken on the Borrowdale Volcanic Group (BVG) and the Windermere super group (WS) in the southern Lake District. This study has been conducted to provide further work towards the understanding of the BVG’s emplacement and the depositional environments of the WS. Formal unit descriptions and stratigraphic columns are compiled from field data and accompanied by stereonet, cross section, and thin section analysis. Numerous depositional features, including asymmetric ripples and aligned clasts, found within the BVG are supportive of a sub aerial and lacustrine setting for emplacement. Bow tie fiamme and rheomorphic flow structures also hold similar implications, by the necessity of heat input, to the environment of emplacement. An unconformable contact between the WS and the BVG is concluded by observations of parasitic folds passing below the WS at High Pike Haw. This is further supported by bedding anomalies uncovered by stereonet analysis. Four transgressions are linked with the deposition of the WS and show correlation with eustasy fluctuations and global cooling events, including the Hirnantian glaciation. Southward verging, open folds through Low Long Beck predate WS deposition and hold similarities with pre-Bala folding. A D2 folding event occurred post deposition to produce isoclinal folding along Dow Crag and a slatey cleavage throughout both units

A novel approach to light-front perturbation theory

We suggest a possible algorithm to calculate one-loop n-point functions within a variant of light-front perturbation theory. The key ingredients are the covariant Passarino-Veltman scheme and a surprising integration formula that localises Feynman integrals at vanishing longitudinal momentum. The resulting expressions are generalisations of Weinberg's infinite-momentum results and are manifestly Lorentz invariant. For n = 2 and 3 we explicitly show how to relate those to light-front integrals with standard energy denominators. All expressions are rendered finite by means of transverse dimensional regularisation.Comment: 10 pages, 5 figure

An engineered E. coli strain for direct in vivo fluorination

This work was funded by the Industrial Biotechnology Innovation Centre (IBioIC) with support from GlaxoSmithKline, and also the EU Horizon 2020 (Sinfonia consortia).Selectively fluorinated compounds are found frequently in pharmaceutical and agrochemical products where currently 25–30 % of optimised compounds emerge from development containing at least one fluorine atom. There are many methods for the site‐specific introduction of fluorine, but all are chemical and they often use environmentally challenging reagents. Biochemical processes for C−F bond formation are attractive, but they are extremely rare. In this work, the fluorinase enzyme, originally identified from the actinomycete bacterium Streptomyces cattleya, is engineered into Escherichia coli in such a manner that the organism is able to produce 5′‐fluorodeoxyadenosine (5′‐FDA) from S‐adenosyl‐l‐methionine (SAM) and fluoride in live E. coli cells. Success required the introduction of a SAM transporter and deletion of the endogenous fluoride efflux capacity in order to generate an E. coli host that has the potential for future engineering of more elaborate fluorometabolites.PostprintPeer reviewe

Reference priors for high energy physics

Bayesian inferences in high energy physics often use uniform prior distributions for parameters about which little or no information is available before data are collected. The resulting posterior distributions are therefore sensitive to the choice of parametrization for the problem and may even be improper if this choice is not carefully considered. Here we describe an extensively tested methodology, known as reference analysis, which allows one to construct parametrization-invariant priors that embody the notion of minimal informativeness in a mathematically well-defined sense. We apply this methodology to general cross section measurements and show that it yields sensible results. A recent measurement of the single top quark cross section illustrates the relevant techniques in a realistic situation

Oligomerization engineering of the fluorinase enzyme leads to an active trimer that supports synthesis of fluorometabolites in vitro

This work was funded by The Novo Nordisk Foundation grant to the Center for Biosustainability (NNF10CC1016517). P.I.N. was funded by grants from The Novo Nordisk Foundation (NNF20CC0035580, and LiFe, NNF18OC0034818), the European Union’s Horizon 2020 Research and Innovation Programme under grant agreement No. 814418 (SinFonia) and the Danish Council for Independent Research (SWEET, DFF-Research Project 8021-00039B). T.K. and M.N.D. were funded by fellowships from the European Union's Horizon 2020 research and innovation program under a Marie Skłodowska Curie project under grant agreement No. 713683 (COFUNDfellowsDTU).The fluorinase enzyme represents the only biological mechanism capable of forming stable C–F bonds characterized in nature thus far, offering a biotechnological route to the biosynthesis of value-added organofluorines. The fluorinase is known to operate in a hexameric form, but the consequence(s) of the oligomerization status on the enzyme activity and its catalytic properties remain largely unknown. In this work, this aspect was explored by rationally engineering trimeric fluorinase variants that retained the same catalytic rate as the wild-type enzyme. These results ruled out hexamerization as a requisite for the fluorination activity. The Michaelis constant (KM) for S-adenosyl-l-methionine, one of the substrates of the fluorinase, increased by two orders of magnitude upon hexamer disruption. Such a shift in S-adenosyl-l-methionine affinity points to a long-range effect of hexamerization on substrate binding – likely decreasing substrate dissociation and release from the active site. A practical application of trimeric fluorinase is illustrated by establishing in vitro fluorometabolite synthesis in a bacterial cell-free system.Publisher PDFPeer reviewe

Iterative graph cuts for image segmentation with a nonlinear statistical shape prior

Shape-based regularization has proven to be a useful method for delineating objects within noisy images where one has prior knowledge of the shape of the targeted object. When a collection of possible shapes is available, the specification of a shape prior using kernel density estimation is a natural technique. Unfortunately, energy functionals arising from kernel density estimation are of a form that makes them impossible to directly minimize using efficient optimization algorithms such as graph cuts. Our main contribution is to show how one may recast the energy functional into a form that is minimizable iteratively and efficiently using graph cuts.Comment: Revision submitted to JMIV (02/24/13

Participatory budgeting, community engagement and impact on public services in Scotland

The institutional engagement and analysis needed to effectively integrate the requirements of equality legislation into participatory budgeting (PB) processes requires a transformational approach. Equality processes appear to exist in parallel with PB activity, rather than being operationalized as integral to the objectives and character of PB activity at local level. This paper proposes that PB and the Public Sector Equality Duty (PSED) in the Equality Act 2010 share a transformative intent and potential, but that this is undermined by siloed thinking on equalities and enduring discriminatory behaviour and practices. The paper concludes with propositions for aligning the conceptual links between equality and community empowerment and, thereby, participation in local financial decision-making in practice

Efficacy and Safety of Medicines Targeting Neurotrophic Factors in the Management of Low Back Pain: Protocol for a Systematic Review and Meta-Analysis (Preprint)

BACKGROUND Low back pain (LBP) is the leading cause of years lived with disability worldwide. Most people with LBP receive the diagnosis of nonspecific LBP or sciatica. Medications are commonly prescribed but have limited analgesic effects and are associated with adverse events. A novel treatment approach is to target neurotrophins such as nerve growth factor (NGF) to reduce pain intensity. NGF inhibitors have been tested in some randomized controlled trials (RCTs) in recent years, showing promise for the treatment of chronic LBP; however, their efficacy and safety need to be evaluated to guide regulatory actions. OBJECTIVE The aim of this study is to evaluate the efficacy and safety of medicines targeting neurotrophins in patients with LBP and sciatica. METHODS In this systematic review, we will include published and unpublished records of parallel RCTs and the first phase of crossover RCTs that compare the effects of medicines targeting neurotrophins with any control group. We will search the CENTRAL, MEDLINE, Embase, CINAHL, ClinicalTrials.gov, EU Clinical Trials Register, and WHO International Clinical Registry Platform databases from inception. Pairs of authors will independently screen the records for eligibility, and we will independently extract data in duplicate. We will conduct a quantitative synthesis (meta-analysis) with the studies that report sufficient data and compare the medicines of interest versus placebo. We will use random-effects models and calculate estimates of effects and heterogeneity for each outcome. We will assess the risk of bias for each study using the Cochrane Collaboration tool, and form judgments of confidence in the evidence according to GRADE recommendations. We will use the PRISMA statement to report the findings. We plan to conduct subgroup analyses by condition, type of medication, and time point. We will also assess the impact of a potential new trial on an existing meta-analysis. Data from studies that meet inclusion criteria but cannot be included in the meta-analysis will be reported narratively. RESULTS The protocol was registered on the Open Science Framework on May 19, 2020. As of December 2020, we have identified 1932 records. CONCLUSIONS This systematic review and meta-analysis will assess the evidence for the efficacy and safety of NGF inhibitors for pain in patients with nonspecific LBP and sciatica. The inclusion of new studies and unpublished data may improve the precision of the effect estimates and guide regulatory actions of the medications for LBP and sciatica. CLINICALTRIAL Open Science Framework; https://osf.io/b8adn/ INTERNATIONAL REGISTERED REPORT DERR1-10.2196/22905 </sec