Catastrophic ecological regime shifts may be announced in advance by statistical early warning signals such as slowing return rates from perturbation and rising variance. The theoretical background ...for these indicators is rich, but real-world tests are rare, especially for whole ecosystems. We tested the hypothesis that these statistics would be early warning signals for an experimentally induced regime shift in an aquatic food web. We gradually added top predators to a lake over 3 years to destabilize its food web. An adjacent lake was monitored simultaneously as a reference ecosystem. Warning signals of a regime shift were evident in the manipulated lake during reorganization of the food web more than a year before the food web transition was complete, corroborating theory for leading indicators of ecological regime shifts.
Tendon and ligament imaging Hodgson, R J; O'Connor, P J; Grainger, A J
British journal of radiology
85, Issue:
1016
Journal Article
Peer reviewed
Open access
MRI and ultrasound are now widely used for the assessment of tendon and ligament abnormalities. Healthy tendons and ligaments contain high levels of collagen with a structured orientation, which ...gives rise to their characteristic normal imaging appearances as well as causing particular imaging artefacts. Changes to ligaments and tendons as a result of disease and injury can be demonstrated using both ultrasound and MRI. These have been validated against surgical and histological findings. Novel imaging techniques are being developed that may improve the ability of MRI and ultrasound to assess tendon and ligament disease.
Olaparib (Lynparza™) is a PARP inhibitor approved for advanced BRCA-mutated (BRCAm) ovarian cancer. PARP inhibitors may benefit patients whose tumours are dysfunctional in DNA repair mechanisms ...unrelated to BRCA1/2. We report exploratory analyses, including the long-term outcome of candidate biomarkers of sensitivity to olaparib in BRCA wild-type (BRCAwt) tumours.
Tumour samples from an olaparib maintenance monotherapy trial (Study 19, D0810C00019; NCT00753545) were analysed. Analyses included classification of mutations in genes involved in homologous recombination repair (HRR), BRCA1 promoter methylation status, measurement of BRCA1 protein and Myriad HRD score.
Patients with BRCAm tumours gained most benefit from olaparib; a similar treatment benefit was also observed in 21/95 patients whose tumours were BRCAwt but had loss-of-function HRR mutations compared to patients with no detectable HRR mutations (58/95). A higher median Myriad MyChoice
HRD score was observed in BRCAm and BRCAwt tumours with BRCA1 methylation. Patients without BRCAm tumours derived benefit from olaparib treatment vs placebo although to a lesser extent than BRCAm patients.
Ovarian cancer patients with tumours harbouring loss-of-function mutations in HRR genes other than BRCA1/2 may constitute a small, molecularly identifiable and clinically relevant population who derive treatment benefit from olaparib similar to patients with BRCAm.
Electrophilic N-F fluorination agents underpin the introduction of fluorine in aliphatic systems across drug and academic research. The choice of N-F reagent is currently determined through empirical ...experimentation in the absence of quantitative values for electrophilicities. Here we report an experimentally-determined kinetic reactivity scale for ten N-F fluorinating reagents, including Selectfluor™, NFSI, Synfluor™ and several
-fluoropyridinium salts, in CH
CN. The reactivity scale, which covers eight orders of magnitude, employs
-substituted 1,3-diaryl-1,3-dicarbonyl derivatives to measure relative and absolute rate constants. The
-substituted 1,3-diaryl-1,3-dicarbonyl scaffold delivers a convenient, sensitive spectrophotometric reporter of reactivity that also led to the discovery of a unique form of tautomeric polymorphism.
In this comprehensive review, we report on the preparation of graft-copolymers of cellulose and cellulose derivatives using atom transfer radical polymerization (ATRP) under homogeneous conditions. ...The review is divided into four sections according to the cellulosic material that is graft-copolymerised; (i) cellulose, (ii) ethyl cellulose, (iii) hydroxypropyl cellulose and (iv) other cellulose derivatives. In each section, the grafted synthetic polymers are described as well as the methods used for ATRP macro-initiator formation and graft-copolymerisation. The physical properties of the graft-copolymers including their self-assembly in solution into nanostructures and their stimuli responsive behaviour are described. Potential applications of the self-assembled graft copolymers in areas such as nanocontainers for drug delivery are outlined.
Abstract
Light harvesting is fundamental for production of ATP and reducing equivalents for CO
2
fixation during photosynthesis. However, electronic energy transfer (EET) through a photosystem can ...harm the photosynthetic apparatus when not balanced with CO
2
. Here, we show that CO
2
binding to the light-harvesting complex modulates EET in photosynthetic cyanobacteria. More specifically, CO
2
binding to the allophycocyanin alpha subunit of the light-harvesting complex regulates EET and its fluorescence quantum yield in the cyanobacterium
Synechocystis
sp. PCC 6803. CO
2
binding decreases the inter-chromophore distance in the allophycocyanin trimer. The result is enhanced EET in vitro and in live cells. Our work identifies a direct target for CO
2
in the cyanobacterial light-harvesting apparatus and provides insights into photosynthesis regulation.
Magnetic resonance imaging (MRI) allows the direct visualization of many bone and soft tissue changes in rheumatoid arthritis. Synovitis volume, bone marrow oedema and bone erosions are suitable for ...serial measurement. The outcome measures in rheumatoid arthritis clinical trials (OMERACT) rheumatoid arthritis magnetic resonance imaging (RAMRIS) system is designed to allow straightforward, reproducible scoring of all these features. Alternatively, synovial volumes may be directly and quickly measured using semi-automated techniques. There is the potential for similar systems for measuring erosions. Dynamic contrast enhanced MRI depends on the rate of enhancement of the synovium after intravenous contrast agent. Measurements depend on the underlying physiology of the inflamed synovium, in particular the vascularity and capillary permeability which are expected to closely mirror inflammatory activity in the joint. Measurements from MRI have been shown to correlate with clinical, laboratory, imaging and histological measures of inflammation, predict erosive progression and respond rapidly to various types of treatment. They are, therefore, expected to be good measures of disease activity, progression and response to therapy.
Aminonucleosides are used as key motifs in medicinal and bioconjugate chemistry; however, existing strategies toward 3′-hypernucleophilic amine systems do not readily deliver deoxyribo-configured ...products. We report diastereoselective syntheses of deoxyribo- and deoxyxylo-configured 3′-hydroxyamino- and 3′-methoxyamino-nucelosides from 3′-imine intermediates. The presence or absence of the 5′-hydroxyl-group protection dictates facial selectivity via inter- or intramolecular delivery of hydride from BH3 (borane). Protecting group screening gave one access to previously unknown 3′-methoxyamino-deoxyguanosine derivatives.
Bone marrow lesions (BMLs) on MRI are typically subchondral in location, however, a proportion occur at knee ligament attachments and also include a cyst-like component. Our aim was to determine ...whether the volume of BML subtypes and synovial tissue volume (STV) was associated with symptoms in symptomatic knee OA.
Images were acquired in a sub-sample who had taken part in a randomised trial of vitamin D therapy in knee OA (UK-VIDEO). Contrast-enhanced (CE) MRI was performed annually. In those who had ≥1 follow-up and a baseline scan (N = 50), STV and BML volume was assessed. BMLs were categorised by location and by the presence/absence of a cyst-like component. WOMAC was assessed annually. We used fixed-effects panel-regression modelling to examine the association between volume and symptoms.
There was no association between knee pain and total subchondral BML volume (b = 0.3 WOMAC units, 95% CI -0.3 to 1.0) or total ligament-based BML volume (b = 1.9, 95% CI -1.6 to 5.3). The volume of subchondral BMLs with a cyst-like component was not associated with pain (b = 0.8, 95% CI -0.5 to 2.1) however, the volume of the cyst-like component itself was associated with pain (b = 51.8, 95% CI 14.2 to 89.3). STV was associated with pain (b = 2.2, 95% CI 0.6 to 3.7).
The volume of the cyst-like component from subchondral BMLs with a cyst-like component was associated with knee pain. BML location, however, did not influence symptoms. STV was also associated with knee symptoms.
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