Self-interacting Dark Matter and Invisibly Decaying Higgs

Self-interacting dark matter has been suggested in order to overcome the difficulties of the Cold Dark Matter model on galactic scales. We argue that a scalar gauge singlet coupled to the Higgs boson, which could lead to an invisibly decaying Higgs, is an interesting candidate for this self-interacting dark matter particle. We also present estimates on the abundance of these particles today as well as consequences to non-Newtonian forces.Comment: 4 pages, Revte

Multidrug resistance plasmids commonly reprogram the expression of metabolic genes in <i>Escherichia coli</i>

Multidrug-resistant Escherichia coli is a leading cause of global mortality. Transfer of plasmids carrying genes encoding beta-lactamases, carbapenamases, and colistin resistance between lineages is driving the rising rates of hard-to-treat nosocomial and community infections. Multidrug resistance (MDR) plasmid acquisition commonly causes transcriptional disruption, and while a number of studies have shown strain-specific fitness and transcriptional effects of an MDR plasmid across diverse bacterial lineages, fewer studies have compared the impacts of different MDR plasmids in a common bacterial host. As such, our ability to predict which MDR plasmids are the most likely to be maintained and spread in bacterial populations is limited. Here, we introduced eight diverse MDR plasmids encoding resistances against a range of clinically important antibiotics into E. coli K-12 MG1655 and measured their fitness costs and transcriptional impacts. The scale of the transcriptional responses varied substantially between plasmids, ranging from &gt;650 to &lt;20 chromosomal genes being differentially expressed. However, the scale of regulatory disruption did not correlate significantly with the magnitude of the plasmid fitness cost, which also varied between plasmids. The identities of differentially expressed genes differed between transconjugants, although the expression of certain metabolic genes and functions were convergently affected by multiple plasmids, including the downregulation of genes involved in L-methionine transport and metabolism. Our data show the complexity of the interaction between host genetic background and plasmid genetic background in determining the impact of MDR plasmid acquisition on E. coli.IMPORTANCE: The increase in infections that are resistant to multiple classes of antibiotics, including those isolates that carry carbapenamases, beta-lactamases, and colistin resistance genes, is of global concern. Many of these resistances are spread by conjugative plasmids. Understanding more about how an isolate responds to an incoming plasmid that encodes antibiotic resistance will provide information that could be used to predict the emergence of MDR lineages. Here, the identification of metabolic networks as being particularly sensitive to incoming plasmids suggests the possible targets for reducing plasmid transfer. </p

Evolutionary responses to acquiring a multidrug resistance plasmid are dominated by metabolic functions across diverse <i>Escherichia coli</i> lineages

Multidrug resistance (MDR) plasmids drive the spread of antibiotic resistance between bacterial lineages. The immediate impact of MDR plasmid acquisition on fitness and cellular processes varies among bacterial lineages, but how the evolutionary processes enabling the genomic integration of MDR plasmids vary is less well understood, particularly in clinical pathogens. Using diverse Escherichia coli lineages experimentally evolved for ~700 generations, we show that the evolutionary response to gaining the MDR plasmid pLL35 was dominated by chromosomal mutations affecting metabolic and regulatory functions, with both strain-specific and shared mutational targets. The expression of several of these functions, such as anaerobic metabolism, is known to be altered upon acquisition of pLL35. Interactions with resident mobile genetic elements, notably several IS-elements, potentiated parallel mutations, including insertions upstream of hns that were associated with its upregulation and the downregulation of the plasmid-encoded extended-spectrum beta-lactamase gene. Plasmid parallel mutations targeted conjugation-related genes, whose expression was also commonly downregulated in evolved clones. Beyond their role in horizontal gene transfer, plasmids can be an important selective force shaping the evolution of bacterial chromosomes and core cellular functions. IMPORTANCE Plasmids drive the spread of antimicrobial resistance genes between bacterial genomes. However, the evolutionary processes allowing plasmids to be assimilated by diverse bacterial genomes are poorly understood, especially in clinical pathogens. Using experimental evolution with diverse E. coli lineages and a clinical multidrug resistance plasmid, we show that although plasmids drove unique evolutionary paths per lineage, there was a surprising degree of convergence in the functions targeted by mutations across lineages, dominated by metabolic functions. Remarkably, these same metabolic functions show higher evolutionary rates in MDR-lineages in nature and in some cases, like anaerobic metabolism, their expression is directly manipulated by the plasmid. Interactions with other mobile elements resident in the genomes accelerated adaptation by disrupting genes and regulatory sequences that they inserted into. Beyond their role in horizontal gene transfer, plasmids are an important selective force driving the evolution of bacterial genomes and core cellular functions

The effectiveness of Ultrasound guided Hydrodistension and physiotherapy in the treatment of Frozen shoulder/Adhesive Capsulitis in Primary Care: a single centre service evaluation

Background: Evidence for optimal non-operative treatment of frozen shoulder is lacking. The aim of this study is to evaluate a treatment strategy for stage II-III Frozen shoulder provided by the current primary care Musculoskeletal Service. Methods: GP referrals of shoulder pain to the musculoskeletal service diagnosed with stage II-III frozen shoulder and who opted for a treatment strategy of hydrodistension and guided physiotherapy exercise programme over a 12 month period were evaluated for 6 months. Thirty three patients were diagnosed with stage II-III frozen shoulder by specialist physiotherapists and opted for the treatment strategy. Outcome measures included SPADI and QuickDASH, pain score and range of movement. Data was collected at baseline, 6 weeks, 12 weeks and 6 months. Results: All patients significantly improved in shoulder symptoms on the SPADI and QuickDASH scores (p< 0.001). Pain scores and range of shoulder movement flexion, abduction, external rotation showed significant improvement at all time points (p<0.001). Conclusions: This service evaluation demonstrates that management of frozen shoulder stage II-III, by physiotherapists in a primary care setting utilizing hydrodistension and guided exercise programme is an effective non-operative treatment strategy. Level of evidence: Level III, Service evaluation

Mobilizing User-Generated Content for Canada’s Digital Content Advantage

The goal of the Mobilizing User-Generated Content for Canada’s Digital Content Advantage project is to define User-Generated Content (UGC) in its current state, identify successful models built for UGC, and anticipate barriers and policy infrastructure needed to sustain a model to leverage the further development of UGC to Canada\u27s advantage.This poster session is based on the report, Mobilizing User-Generated Content For Canada’s Digital Advantage (http://ir.lib.uwo.ca/fimspub/21/) and is related to the Brown Bag presentation also presented on March 23, 2011 (http://ir.lib.uwo.ca/fimspres/11/)

Characteristics of starch-based films with different amylose contents plasticised by 1-ethyl-3-methylimidazolium acetate

Starch-based films plasticised by an ionic liquid, 1-ethyl-3-methylimidazolium acetate ([Emim][OAc]), were prepared by a simple compression moulding process, facilitated by the strong plasticisation effect of [Emim][OAc]. The effects of amylose content of starch (regular vs. high-amylose maize) and relative humidity (RH) during ageing of the samples on a range of structural and material characteristics were investigated. Surprisingly, plasticisation by [Emim][OAc] made the effect of amylose content insignificant, contrary to most previous studies when other plasticisers were used. In other words, [Emim][OAc] changed the underlying mechanism responsible for mechanical properties from the entanglement of starch macromolecules (mainly amylose), which has been reported as a main responsible factor previously. The crystallinity of the plasticised starch samples was low and thus was unlikely to have a major contribution to the material characteristics, although the amylose content impacted on the crystalline structure and the mobility of amorphous parts in the samples to some extent. Therefore, RH conditioning and thus the sample water content was the major factor influencing the mechanical properties, glass transition temperature, and electrical conductivity of the starch films. This suggests the potential application of ionic liquid-plasticised starch materials in areas where the control of properties by environmental RH is desired

Towards Flexible, Fault Tolerant Hardware Service Wrappers for the Digital Manufacturing on a Shoestring Project

The adoption of digital manufacturing in small to medium enterprises (SMEs) in the manufacturing sector in the UK is low, yet these technologies offer significant promise to boost productivity. Two major causes of this lack of uptake is the high upfront cost of digital technologies, and the skill gap preventing understanding and implementation. This paper describes the development of software wrappers to facilitate the simple and robust use of a range of sensors and data sources. These form part of a common architecture for data acquisition in the Digital Manufacturing on a Shoestring project. We explain the existing Shoestring demonstrator architecture, and discuss how a'crash-only' microservices architecture would improve fault tolerance and adaptability of the system

Combinatorial microfluidic droplet engineering for biomimetic material synthesis

Although droplet-based systems are used in a wide range of technologies, opportunities for systematically customizing their interface chemistries remain relatively unexplored. This article describes a new microfluidic strategy for rapidly tailoring emulsion droplet compositions and properties. The approach utilizes a simple platform for screening arrays of droplet-based microfluidic devices and couples this with combinatorial selection of the droplet compositions. Through the application of genetic algorithms over multiple screening rounds, droplets with target properties can be rapidly generated. The potential of this method is demonstrated by creating droplets with enhanced stability, where this is achieved by selecting carrier fluid chemistries that promote titanium dioxide formation at the droplet interfaces. The interface is a mixture of amorphous and crystalline phases, and the resulting composite droplets are biocompatible, supporting in vitro protein expression in their interiors. This general strategy will find widespread application in advancing emulsion properties for use in chemistry, biology, materials and medicine

Non-antibiotic pharmaceuticals are toxic against <i>Escherichia coli</i> with no evolution of cross-resistance to antibiotics

Antimicrobial resistance can arise in the natural environment via prolonged exposure to the effluent released by manufacturing facilities. In addition to antibiotics, pharmaceutical plants also produce non-antibiotic pharmaceuticals, both the active ingredients and other components of the formulations. The effect of these on the surrounding microbial communities is less clear. We aimed to assess whether non-antibiotic pharmaceuticals and other compounds produced by pharmaceutical plants have inherent toxicity, and whether long-term exposure might result in significant genetic changes or select for cross-resistance to antibiotics. To this end, we screened four non-antibiotic pharmaceuticals (acetaminophen, ibuprofen, propranolol, metformin) and titanium dioxide for toxicity against Escherichia coli K-12 MG1655 and conducted a 30 day selection experiment to assess the effect of long-term exposure. All compounds reduced the maximum optical density reached by E. coli at a range of concentrations including one of environmental relevance, with transcriptome analysis identifying upregulated genes related to stress response and multidrug efflux in response ibuprofen treatment. The compounds did not select for significant genetic changes following a 30 day exposure, and no evidence of selection for cross-resistance to antibiotics was observed for population evolved in the presence of ibuprofen in spite of the differential gene expression after exposure to this compound. This work suggests that these compounds, at environmental concentrations, do not select for cross-resistance to antibiotics in E. coli