327 research outputs found
Nature's capacities: Schelling and contemporary power-based ontologies
This paper draws a number of parallels between Schelling’s Naturphilosophie and contemporary work in the metaphysics of powers. This concept is being applied to a range of debates, however a distinct lack of work exists focusing on extending this concept to ontology as a whole. I argue that Schelling’s Naturphilosophie provides insight into what this kind of system would look like. I begin with a brief outline of the characterisation and use of powers in the contemporary literature to show the marked similarities between these accounts and Schelling’s. I then present my reading of the Naturphilosophie as a power-based ontology, and gesture towards some ways in which this account could help to fill some of the gaps in the current literature. Because of the centrality of powers to the Naturphilosophie, and because of the holistic nature of Schelling’s work, the role of powers and relationship of powers to a range of other concepts is carefully specified here. Thus a number of the implications and advantages of this kind of view are already worked out and presented in the texts on Naturphilosophie. Finally, I argue that Schelling’s Naturphilosophie also demonstrates some possible problems that will arise for any ontology of this kind
Integrated health and care systems in England : can they help prevent disease?
Objectives: Over the past 12 months, there has been increasing policy rhetoric regarding the role of the NHS in preventing disease and improving population health. In particular, the NHS Long Term Plan sees integrated care systems (ICSs) and sustainability and transformation partnerships (STPs) as routes to improving disease prevention. Here, we place current NHS England integrated care plans in their historical context and review evidence on the relationship between integrated care and prevention. We ask how the NHS Long Term Plan may help prevent disease and explore the role of the 2019 ICS and STP plans in delivering this change.
Methods: We reviewed the evidence underlying the relationship between integrated care and disease prevention, and analysed 2016 STP plans for content relating to disease prevention and population health.
Results: The evidence of more integrated care leading to better disease prevention is weak. Although nearly all 2016 STP plans included a prevention or population health strategy, fewer than half specified how they will work with local government public health teams, and there was incomplete coverage across plans about how they would meet NHS England prevention priorities. Plans broadly focused on individual-level approaches to disease prevention, with few describing interventions addressing social determinants of health.
Conclusions: For ICSs and STPs to meaningfully prevent disease and improve population health, they need to look beyond their 2016 plans and fill the gaps in the Long Term Plan on social determinants
An evaluation of the kinematic approximation in helium atom scattering using wavepacket calculations
We use 2-D wavepacket calculations to examine the scattering of helium atoms from dynamic assemblies of surface adsorbates, and in particular to explore the validity of the widely used kinematic scattering approximation. The wavepacket calculations give exact results for quasi-elastic scattering that are closely analogous to time-of-flight (TOF) experiments and they are analysed as such. A scattering potential is chosen to represent 8 meV helium atoms scattering from sodium atoms adsorbed on a Cu(001) surface and the adsorbates in the model move according to an independent Langevin equation. The energy broadening in the quasi-elastic scattering is obtained as a function of parallel momentum transfer and compared with the corresponding results using the kinematic scattering approximation. Under most circumstances the kinematic approximation and the more accurate wavepacket method are in good agreement; however, there are cases where the two methods give different results. We relate these differences to pathological features in the scattering form-factor.EPSRC Studentship, Royal Society University Research Fellowshi
Direct liquid extraction surface analysis mass spectrometry of cell wall lipids from mycobacteria:Salt additives for decreased spectral complexity
Biosynthesis of mycobacterial arabinogalactan: identification of a novel (13)arabinofuranosyltransferase
The cell wall mycolyl-arabinogalactan-peptidoglycan complex is essential in mycobacterial species, such as Mycobacterium tuberculosis and is the target of several anti-tubercular drugs. For instance, ethambutol targets arabinogalactan biosynthesis through inhibition of the arabinofuranosyltransferases Mt-EmbA and Mt-EmbB. A bioinformatics approach identified putative integral membrane proteins, MSMEG2785 in Mycobacterium smegmatis, Rv2673 in Mycobacterium tuberculosis and NCgl1822 in Corynebacterium glutamicum, with 10 predicted transmembrane domains and a glycosyltransferase motif (DDX), features that are common to the GT-C superfamily of glycosyltransferases. Deletion of M. smegmatis MSMEG2785 resulted in altered growth and glycosyl linkage analysis revealed the absence of AG (13)-linked arabinofuranosyl (Araf) residues. Complementation of the M. smegmatis deletion mutant was fully restored to a wild type phenotype by MSMEG2785 and Rv2673, and as a result, we have now termed this previously uncharacterized open reading frame, arabinofuranosyltransferase C (aftC). Enzyme assays using the sugar donor -D-arabinofuranosyl-1-monophosphoryldecaprenol (DPA) and a newly synthesized linear (15)-linked Ara5 neoglycolipid acceptor together with chemical identification of products formed, clearly identified AftC as a branching (13) arabinofuranosyltransferase. This newly discovered glycosyltransferase sheds further light on the complexities of Mycobacterium cell wall biosynthesis, such as in M. tuberculosis and related species and represents a potential new drug target
EmbR2, a structural homologue of EmbR, inhibits the Mycobacterium tuberculosis kinase/substrate pair PknH/EmbR
International audienceEmbR is a transcriptional regulator that is phosphorylated by the cognate mycobacterial STPK (serine/threonine protein kinase) PknH. Recent studies demonstrated that PknH-dependent phosphorylation of EmbR enhances its DNA-binding activity and activates the transcription of the embCAB genes encoding arabinosyltransferases, which participate in arabinan biosynthesis. In the present study, we identified a genomic region of 4425 bp, which is present in Mycobacterium tuberculosis CDC1551, but absent from M. tuberculosis H37Rv, comprising the MT3428 gene, which is homologous with embR. Homology modelling of the MT3428 gene product illustrated its close relationship (56% identity) to EmbR, and it was hence termed EmbR2. In marked contrast with EmbR, EmbR2 was not phosphorylated by PknH, although it is a substrate of other M. tuberculosis kinases, including PknE and PknF. Tryptophan fluorescence emission of EmbR2 was monitored in the presence of three different PknH-derived phosphopeptides and demonstrated that EmbR2 binds to at least two of the threonine sites known to undergo autophosphorylation in PknH. We observed that the capacity of EmbR2 to interact physically with PknH without being phosphorylated was a result of EmbR2-mediated inhibition of kinase activity: incubation of PknH with increasing concentrations of EmbR2 led to a dose-response inhibition of the autokinase activity, similarly to O6-cyclohexylmethylguanine, a known inhibitor of eukaryotic cyclin-dependent kinases. Moreover, EmbR2 inhibited PknH-dependent phosphorylation of EmbR in a dose-dependent manner. Together, these results suggest that EmbR2 is a regulator of PknH activation, thus directly participating in the control of the PknH/EmbR pair and potentially in mycobacterial physiology/virulence of M. tuberculosis CDC1551
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