Triggering change: Towards a conceptualisation of major change processes in farm decision-making

In this paper, we present a broad conceptualisation of major change in farm level trajectories. We argue that as a result of path dependency, major changes in farming practice primarily occur in response to 'trigger events', after which farm managers intensify their consideration of the options open to them, and may set a new course of action. In undertaking new actions, the farm system enters a period of instability, while new practices become established. Over time these new practices, if successfully achieving anticipated aims, lead to a further period of path dependency. Recognising and capitalising upon this pattern of events is important for the development of policies oriented towards incentivising major change in farming practices, and may explain why similar projects and/or policies influence some 'types' of farmers differently, and at different times. To illustrate our arguments, examples of this process are described in relation to empirical examples of major on-farm change processes, drawn from qualitative interviews with organic and conventional farmers in two English case study area

Triggering change: Towards a conceptualisation of major change processes in farm decision-making

In this paper, we present a broad conceptualisation of major change in farm level trajectories. We argue that as a result of path dependency, major changes in farming practice primarily occur in response to 'trigger events', after which farm managers intensify their consideration of the options open to them, and may set a new course of action. In undertaking new actions, the farm system enters a period of instability, while new practices become established. Over time these new practices, if successfully achieving anticipated aims, lead to a further period of path dependency. Recognising and capitalising upon this pattern of events is important for the development of policies oriented towards incentivising major change in farming practices, and may explain why similar projects and/or policies influence some 'types' of farmers differently, and at different times. To illustrate our arguments, examples of this process are described in relation to empirical examples of major on-farm change processes, drawn from qualitative interviews with organic and conventional farmers in two English case study area

Hyperentangled States

We investigate a new class of entangled states, which we call 'hyperentangled',that have EPR correlations identical to those in the vacuum state of a relativistic quantum field. We show that whenever hyperentangled states exist in any quantum theory, they are dense in its state space. We also give prescriptions for constructing hyperentangled states that involve an arbitrarily large collection of systems.Comment: 23 pages, LaTeX, Submitted to Physical Review

Plasmodium falciparum associated with severe childhood malaria preferentially expresses PfEMP1 encoded by group A var genes.

Parasite-encoded variant surface antigens (VSAs) like the var gene-encoded Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family are responsible for antigenic variation and infected red blood cell (RBC) cytoadhesion in P. falciparum malaria. Parasites causing severe malaria in nonimmune patients tend to express a restricted subset of VSA (VSA(SM)) that differs from VSA associated with uncomplicated malaria and asymptomatic infection (VSA(UM)). We compared var gene transcription in unselected P. falciparum clone 3D7 expressing VSA(UM) to in vitro-selected sublines expressing VSA(SM) to identify PfEMP1 responsible for the VSA(SM) phenotype. Expression of VSA(SM) was accompanied by up-regulation of Group A var genes. The most prominently up-regulated Group A gene (PFD1235w/MAL7P1.1) was translated into a protein expressed on the infected RBC surface. The proteins encoded by Group A var genes, such as PFD1235w/MAL7P1.1, appear to be involved in the pathogenesis of severe disease and are thus attractive candidates for a vaccine against life-threatening P. falciparum malaria

Galaxy and Mass Assembly: FUV, NUV, ugrizYJHK Petrosian, Kron and Sérsic photometry

In order to generate credible 0.1-2 μm spectral energy distributions, the Galaxy and Mass Assembly (GAMA) project requires many gigabytes of imaging data from a number of instruments to be reprocessed into a standard format. In this paper, we discuss the software infrastructure we use, and create self-consistent ugrizYJHK photometry for all sources within the GAMA sample. Using UKIDSS and SDSS archive data, we outline the pre-processing necessary to standardize all images to a common zero-point, the steps taken to correct for the seeing bias across the data set and the creation of gigapixel-scale mosaics of the three 4 × 12 deg2 GAMA regions in each filter. From these mosaics, we extract source catalogues for the GAMA regions using elliptical Kron and Petrosian matched apertures. We also calculate Sérsic magnitudes for all galaxies within the GAMA sample using sigma, a galaxy component modelling wrapper for galfit 3. We compare the resultant photometry directly and also calculate the r-band galaxy luminosity function for all photometric data sets to highlight the uncertainty introduced by the photometric method. We find that (1) changing the object detection threshold has a minor effect on the best-fitting Schechter parameters of the overall population (M*± 0.055 mag, α± 0.014, ϕ*± 0.0005 h3 Mpc−3); (2) there is an offset between data sets that use Kron or Petrosian photometry, regardless of the filter; (3) the decision to use circular or elliptical apertures causes an offset in M* of 0.20 mag; (4) the best-fitting Schechter parameters from total-magnitude photometric systems (such as SDSS modelmag or Sérsic magnitudes) have a steeper faint-end slope than photometric systems based upon Kron or Petrosian measurements; and (5) our Universe's total luminosity density, when calculated using Kron or Petrosian r-band photometry, is underestimated by at least 15 per cen

Determination of the Processes Driving the Acquisition of Immunity to Malaria Using a Mathematical Transmission Model

Acquisition of partially protective immunity is a dominant feature of the epidemiology of malaria among exposed individuals. The processes that determine the acquisition of immunity to clinical disease and to asymptomatic carriage of malaria parasites are poorly understood, in part because of a lack of validated immunological markers of protection. Using mathematical models, we seek to better understand the processes that determine observed epidemiological patterns. We have developed an age-structured mathematical model of malaria transmission in which acquired immunity can act in three ways (“immunity functions”): reducing the probability of clinical disease, speeding the clearance of parasites, and increasing tolerance to subpatent infections. Each immunity function was allowed to vary in efficacy depending on both age and malaria transmission intensity. The results were compared to age patterns of parasite prevalence and clinical disease in endemic settings in northeastern Tanzania and The Gambia. Two types of immune function were required to reproduce the epidemiological age-prevalence curves seen in the empirical data; a form of clinical immunity that reduces susceptibility to clinical disease and develops with age and exposure (with half-life of the order of five years or more) and a form of anti-parasite immunity which results in more rapid clearance of parasitaemia, is acquired later in life and is longer lasting (half-life of >20 y). The development of anti-parasite immunity better reproduced observed epidemiological patterns if it was dominated by age-dependent physiological processes rather than by the magnitude of exposure (provided some exposure occurs). Tolerance to subpatent infections was not required to explain the empirical data. The model comprising immunity to clinical disease which develops early in life and is exposure-dependent, and anti-parasite immunity which develops later in life and is not dependent on the magnitude of exposure, appears to best reproduce the pattern of parasite prevalence and clinical disease by age in different malaria transmission settings. Understanding the effector mechanisms underlying these two immune functions will assist in the design of transmission-reducing interventions against malaria

Synthesis of pyrazole containing α-amino acids via a highly regioselective condensation/aza-Michael reaction of β-aryl α,β-unsaturated ketones

A synthetic approach for the preparation of a new class of highly conjugated unnatural α-amino acids bearing a 5-arylpyrazole side-chain has been developed. Horner–Wadsworth–Emmons reaction of an aspartic acid derived β-keto phosphonate ester with a range of aromatic aldehydes gave β-aryl α,β-unsaturated ketones. Treatment of these with phenyl hydrazine followed by oxidation allowed the regioselective synthesis of pyrazole derived α-amino acids. As well as evaluating the fluorescent properties of the α-amino acids, their synthetic utility was also explored with the preparation of a sulfonyl fluoride derivative, a potential probe for serine proteases

A G1-like state allows HIV-1 to bypass SAMHD1 restriction in macrophages.

An unresolved question is how HIV-1 achieves efficient replication in terminally differentiated macrophages despite the restriction factor SAMHD1. We reveal inducible changes in expression of cell cycle-associated proteins including MCM2 and cyclins A, E, D1/D3 in macrophages, without evidence for DNA synthesis or mitosis. These changes are induced by activation of the Raf/MEK/ERK kinase cascade, culminating in upregulation of CDK1 with subsequent SAMHD1 T592 phosphorylation and deactivation of its antiviral activity. HIV infection is limited to these G1-like phase macrophages at the single-cell level. Depletion of SAMHD1 in macrophages decouples the association between infection and expression of cell cycle-associated proteins, with terminally differentiated macrophages becoming highly susceptible to HIV-1. We observe both embryo-derived and monocyte-derived tissue-resident macrophages in a G1-like phase at frequencies approaching 20%, suggesting how macrophages sustain HIV-1 replication in vivo Finally, we reveal a SAMHD1-dependent antiretroviral activity of histone deacetylase inhibitors acting via p53 activation. These data provide a basis for host-directed therapeutic approaches aimed at limiting HIV-1 burden in macrophages that may contribute to curative interventions

An extensible big data software architecture managing a research resource of real-world clinical radiology data linked to other health data from the whole Scottish population

Aim: To enable a world-leading research dataset of routinely collected clinical images linked to other routinely collected data from the whole Scottish national population. This includes more than 30 million different radiological examinations from a population of 5.4 million and &gt;2 PB of data collected since 2010.Methods: Scotland has a central archive of radiological data used to directly provide clinical care to patients. We have developed an architecture and platform to securely extract a copy of those data, link it to other clinical or social datasets, remove personal data to protect privacy, and make the resulting data available to researchers in a controlled Safe Haven environment.Results: An extensive software platform has been developed to host, extract, and link data from cohorts to answer research questions. The platform has been tested on 5 different test cases and is currently being further enhanced to support 3 exemplar research projects.Conclusions: The data available are from a range of radiological modalities and scanner types and were collected under different environmental conditions. These real-world, heterogenous data are valuable for training algorithms to support clinical decision making, especially for deep learning where large data volumes are required. The resource is now available for international research access. The platform and data can support new health research using artificial intelligence and machine learning technologies, as well as enabling discovery science.</p

The T7-Related Pseudomonas putida Phage ϕ15 Displays Virion-Associated Biofilm Degradation Properties

Formation of a protected biofilm environment is recognized as one of the major causes of the increasing antibiotic resistance development and emphasizes the need to develop alternative antibacterial strategies, like phage therapy. This study investigates the in vitro degradation of single-species Pseudomonas putida biofilms, PpG1 and RD5PR2, by the novel phage ϕ15, a ‘T7-like virus’ with a virion-associated exopolysaccharide (EPS) depolymerase. Phage ϕ15 forms plaques surrounded by growing opaque halo zones, indicative for EPS degradation, on seven out of 53 P. putida strains. The absence of haloes on infection resistant strains suggests that the EPS probably act as a primary bacterial receptor for phage infection. Independent of bacterial strain or biofilm age, a time and dose dependent response of ϕ15-mediated biofilm degradation was observed with generally a maximum biofilm degradation 8 h after addition of the higher phage doses (104 and 106 pfu) and resistance development after 24 h. Biofilm age, an in vivo very variable parameter, reduced markedly phage-mediated degradation of PpG1 biofilms, while degradation of RD5PR2 biofilms and ϕ15 amplification were unaffected. Killing of the planktonic culture occurred in parallel with but was always more pronounced than biofilm degradation, accentuating the need for evaluating phages for therapeutic purposes in biofilm conditions. EPS degrading activity of recombinantly expressed viral tail spike was confirmed by capsule staining. These data suggests that the addition of high initial titers of specifically selected phages with a proper EPS depolymerase are crucial criteria in the development of phage therapy