Transcriptional downregulation of agr expression in Staphylococcus aureus during growth in human serum can be overcome by constitutively active mutant forms of the sensor kinase AgrC

The temporal and cell density-dependent regulation of expression of virtually all the Staphylococcus aureus virulon is under the control of the agr (accessory gene regulatory) operon. The expression of the agr operon is subject to transcriptional regulation by the AgrA/C two-component response regulator/sensor kinase pair. During bacteraemia, a frequent syndrome caused by methicillin-resistant S. aureus (MRSA), the transcriptional downregulation of agr expression has been attributed to the sequestration of the quorum-signalling molecule auto-inducing peptide (AIP) by the human serum component apolipoprotein B as part of an innate immune response to infection. However, it is not known whether transcriptional downregulation of agr expression during growth in human serum is additionally subjected to regulation by transcription regulatory proteins that either directly or indirectly affect transcription from the agr operon promoters. Here, using chromosomal fluorescence reporters of agr expression in S. aureus, we show that the transcriptional downregulation of agr expression in human serum can be overcome using constitutive active mutant forms of AgrC. Therefore, it seems that the sequestration of the AIP is likely to be the only mechanism by which the host innate immune response limits agr expression at the transcriptional level to maintain the host–pathogen balance towards a noninvasive outcome

A framework for the simulation of regional decadal variability for agricultural and other applications

The SimGen software, including ancillary files and scripts, can be found at http://iri.columbia.edu/~amg/CCAFS/simgen/Climate prediction on decadal time scales is currently an active area of research. Although there are indications that predictions from dynamical models may have skill in some regions, assessment of this skill is still underway, and reliable model-based predictions of regional ‘near-term’ climate change, particularly for terrestrial regions, have not yet been demonstrated. Given the absence of such forecasts, synthetic data sequences that capture the statistical properties of observed near-term climate variability have potential value. Incorporation of a climate change component in such sequences can aid in estimating likelihoods for a range of climatic stresses, perhaps lying outside the range of past experience. Such simulations can be used to drive agricultural, hydrological or other application models, enabling resilience testing of adaptation or decision systems. The use of statistically-based methods enables the efficient generation of a large ensemble of synthetic sequences as well as the creation of well-defined probabilistic risk estimates. In this report we discuss procedures for the generation of synthetic climate sequences that incorporate both the statistics of observed variability and expectations regarding future regional climate change. Model fitting and simulation are conditioned by requirements particular to the decadal climate problem. A method for downscaling annualized simulations to the daily time step while preserving both spatial and temporal subannual statistical properties is presented and other possible methods discussed. A ‘case-study’ realization of the proposed framework is described

Left-shift vs the time value of money: unravelling the business case for systems engineering

The principle of left shift – increasing project expenditure in the early part of a project in order to reduce unanticipated costs later in the project – is advocated as a cornerstone of good systems engineering practice. In fact, the expenditure profile of a project, and in particular the proportion of the total spend attributed to early stage activities such as project definition, is often used as a proxy for the overall level of systems engineering effort expended in a project. In order to establish the business case for systems engineering, this level of systems engineering effort can be compared to the project performance relative to cost and schedule targets. A common premise is that projects that spend more early in the project achieve better outcomes than those that defer expenditure until later. This proactive approach to the management of risk seems sensible as it reduces the probability of unanticipated problems plaguing the project midway through, and recognises the lower cost of rectifying problems identified early on. To assume that such an expenditure profile will be attractive to non systems engineers, however, ignores three crucial factors. Firstly, project managers are judged on measurable progress. Often, these definition activities, whilst possibly preventing costs from being incurred, deliver little visible output. Secondly, in a competitive market, almost all successful project bids are under-costed and underestimate the time required to complete (otherwise they would not win the contract). This puts extreme pressure on choosing risky cost-cutting and timesaving measures. Thirdly, and most importantly, money available now is worth more than money available in the future, since this money could be invested in other projects in the meantime, generating returns typically in the range 10-25%. It is therefore rational for financial managers to insist on minimising early project expenditure. Worse still, the riskier the project, the more rational it is in financial terms to try to defer spending until later in the project. We have developed a model that takes into account financial and engineering risks to predict the optimum resource allocation profile for a given project. This generates some interesting conclusions on the level of up front systems engineering effort that can really be justified under different conditions

Wilson Loop Renormalization Group Flows

The locally BPS Wilson loop and the pure gauge Wilson loop map under AdS/CFT duality to string world-sheet boundaries with standard and alternate quantizations of the world-sheet fields. This implies an RG flow between the two operators, which we verify at weak coupling. Many additional loop operators exist at strong coupling, with a rich pattern of RG flows.Comment: 10 p, 2 figures. v3: Title change, expanded treatment of RG flow

Ice thickness and volume changes across the Southern Alps, New Zealand, from the little ice age to present

Rapid changes observed today in mountain glaciers need to be put into a longer-term context to understand global sea-level contributions, regional climate-glacier systems and local landscape evolution. In this study we determined volume changes for 400 mountain glaciers across the Southern Alps, New Zealand for three time periods; pre-industrial “Little Ice Age (LIA)” to 1978, 1978 to 2009 and 2009 to 2019. At least 60 km3 ± 12 km3 or between 41 and 62% of the LIA total ice volume has been lost. The rate of mass loss has nearly doubled from − 0.4 m w.e year−1 during 1,600 to 1978 to − 0.7 m w.e year−1 at present. In comparison Patagonia has lost just 11% of it’s LIA volume. Glacier ice in the Southern Alps has become restricted to higher elevations and to large debris-covered ablation tongues terminating in lakes. The accelerating rate of ice loss reflects regional-specific climate conditions and suggests that peak glacial meltwater production is imminent if not already passed, which has profound implications for water resources and riverine habitats

Reflexive Cones

Reflexive cones in Banach spaces are cones with weakly compact intersection with the unit ball. In this paper we study the structure of this class of cones. We investigate the relations between the notion of reflexive cones and the properties of their bases. This allows us to prove a characterization of reflexive cones in term of the absence of a subcone isomorphic to the positive cone of \ell_{1}. Moreover, the properties of some specific classes of reflexive cones are investigated. Namely, we consider the reflexive cones such that the intersection with the unit ball is norm compact, those generated by a Schauder basis and the reflexive cones regarded as ordering cones in a Banach spaces. Finally, it is worth to point out that a characterization of reflexive spaces and also of the Schur spaces by the properties of reflexive cones is given.Comment: 23 page

Who acquires infection from whom and how? Disentangling multi-host and multi-mode transmission dynamics in the 'elimination' era

Multi-host infectious agents challenge our abilities to understand, predict and manage disease dynamics. Within this, many infectious agents are also able to use, simultaneously or sequentially, multiple modes of transmission. Furthermore, the relative importance of different host species and modes can itself be dynamic, with potential for switches and shifts in host range and/ or transmission mode in response to changing selective pressures, such as those imposed by disease control interventions. The epidemiology of such multi-host, multi-mode infectious agents thereby can involve a multi-faceted community of definitive and intermediate/secondary hosts or vectors, often together with infectious stages in the environment, all of which may represent potential targets, as well as specific challenges, particularly where disease elimination is proposed. Here, we explore, focusing on examples fromboth human and animal pathogen systems, why and how we should aim to disentangle and quantify the relative importance of multi-host multi-mode infectious agent transmission dynamics under contrasting conditions, and ultimately, how this can be used to help achieve efficient and effective disease control. This article is part of the themed issue 'Opening the black box: re-examining the ecology and evolution of parasite transmission'

Prevention and treatment of cardiovascular instability during spinal anaesthesia for caesarean section

Spinal anaesthesia is the method of choice for caesarean section. There is however a significant associated morbidity and mortality in South Africa, particularly in inexperienced hands. This review provides recommendations for safe practice for anaesthetists at all levels of expertise, with particular reference to the management of haemodynamic instability. S Afr Med J 2004; 94: 367-372

Constructing a Stochastic Model of Bumblebee Flights from Experimental Data

PMCID: PMC3592844This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited