Uropathogenic Escherichia Coli engages CD14-dependent signaling to enable bladder-macrophage-dependent control of acute urinary tract infection

Background CD14, a coreceptor for several pattern recognition receptors and a widely used monocyte/macrophage marker, plays a key role in host responses to gram-negative bacteria. Despite the central role of CD14 in the inflammatory response to lipopolysaccharide and other microbial products and in the dissemination of bacteria in some infections, the signaling networks controlled by CD14 during urinary tract infection (UTI) are unknown. Methods We used uropathogenic Escherichia coli (UPEC) infection of wild-type (WT) C57BL/6 and Cd14−/− mice and RNA sequencing to define the CD14-dependent transcriptional signature and the role of CD14 in host defense against UTI in the bladder. Results UPEC induced the upregulation of Cd14 and the monocyte/macrophage-related genes Emr1/F4/80 and Csf1r/c-fms, which was associated with lower UPEC burdens in WT mice, compared with Cd14−/− mice. Exacerbation of infection in Cd14−/− mice was associated with the absence of a 491-gene transcriptional signature in the bladder that encompassed multiple host networks not previously associated with this receptor. CD14-dependent pathways included immune cell trafficking, differential cytokine production in macrophages, and interleukin 17 signaling. Depletion of monocytes/macrophages in the bladder by administration of liposomal clodronate led to higher UPEC burdens. Conclusions This study identifies new host protective and signaling roles for CD14 in the bladder during UPEC UTI.

Duty and Control in Intermediary Copyright Liability: An Australian Perspective

In the internet age, copyright owners are increasingly looking to online intermediaries to take steps to prevent copyright infringement. Sometimes these intermediaries are closely tied to the acts of infringement; sometimes – as in the case of ISPs – they are not. In 2012, the Australian High Court decided the Roadshow Films v iiNet case, in which it held that an Australian ISP was not liable under copyright’s authorization doctrine, which asks whether the intermediary has sanctioned, approved or countenanced the infringement. The Australian Copyright Act 1968 directs a court to consider, in these situations, whether the intermediary had the power to prevent the infringement and whether it took any reasonable steps to prevent or avoid the infringement. It is generally not difficult for a court to find the power to prevent infringement – power to prevent can include an unrefined technical ability to disconnect users from the copyright source, such as an ISP terminating users’ internet accounts. In the iiNet case, the High Court eschewed this broad approach in favor of focusing on a notion of control that was influenced by principles of tort law. In tort, when a plaintiff asserts that a defendant should be liable for failing to act to prevent harm caused to the plaintiff by a third party, there is a heavy burden on the plaintiff to show that the defendant had a duty to act. The duty must be clear and specific, and will often hinge on the degree of control that the defendant was able to exercise over the third party. Control in these circumstances relates directly to control over the third party’s actions in inflicting the harm. Thus, in iiNet’s case, the control would need to be directed to the third party’s infringing use of BitTorrent; control over a person’s ability to access the internet is too imprecise. Further, when considering omissions to act, tort law differentiates between the ability to control and the ability to hinder. The ability to control may establish a duty to act, and the court will then look to small measures taken to prevent the harm to determine whether these satisfy the duty. But the ability to hinder will not suffice to establish liability in the absence of control. This chapter argues that an inquiry grounded in control as defined in tort law would provide a more principled framework for assessing the liability of passive intermediaries in copyright. In particular, it would set a higher, more stable benchmark for determining the copyright liability of passive intermediaries, based on the degree of actual, direct control that the intermediary can exercise over the infringing actions of its users. This approach would provide greater clarity and consistency than has existed to date in this area of copyright law in Australia.

Variation in BMPR1B, TGFRB1 and BMPR2 and control of dizygotic twinning

Genes in the TGF9 signaling pathway play important roles in the regulation of ovarian follicle growth and ovulation rate. Mutations in three genes in this pathway, growth differentiation factor 9 (GDF9), bone morphogenetic protein 15 (BMP15) and the bone morphogenetic protein receptor B 1 (BMPRB1), influence dizygotic (DZ) twinning rates in sheep. To date, only variants in GDF9 and BMP15, but not their receptors transforming growth factor ss receptor 1 (TGFBR1), bone morphogenetic protein receptor 2 (BMPR2) and BMPR1B, have been investigated with respect to their roles in human DZ twinning. We screened for rare and novel variants in TGFBR1, BMPR2 and BMPR1B in mothers of dizygotic twins (MODZT) from twin-dense families, and assessed association between genotyped and imputed variants and DZ twinning in another large sample of MODZT. Three novel variants were found: a deep intronic variant in BMPR2, and one intronic and one non-synonymous exonic variant in BMPRB1 which would result in the replacement of glutamine by glutamic acid at amino acid position 294 (p.Gln294Glu). None of these variants were predicted to have major impacts on gene function. However, the p.Gln294Glu variant changes the same amino acid as a sheep BMPR1B functional variant and may have functional consequences. Six BMPR1B variants were marginally associated with DZ twinning in the larger case-control sample, but these were no longer significant once multiple testing was taken into account. Our results suggest that variation in the TGF9 signaling pathway type II receptors has limited effects on DZ twinning rates in humans.

The social consequences of control: Accounting for indentured labour in Fiji 1879 - 1920

Purpose: This is a study of the social consequences of accounting controls over labour. It examines the system of tasking used to control Indian indentured workers using a governmentality approach in the historical context of Fijian sugar plantations during the British colonial period, from 1879 to 1920. Method/ Methodology: Archival data consisting of documents from the Colonial Secretary’s Office, reports and related literature on Indian indentured labour was accessed from the National Archives of Fiji. In addition, documented accounts of the experiences of indentured labourers over the period of the study give voice to the social costs of the indenture system, highlighting the social impact of accounting control systems. Findings: Accounting and management controls were developed to extract surplus value from Indian labour. The practice of tasking was implemented in a plantation structure where indentured labourers were controlled hierarchically through a variety of calculative monitoring practices. This resulted in the exploitation and consequent economic, social and racial marginalisation of indentured workers. Originality: The paper contributes to the growing body of literature highlighting the social effects of accounting control systems. It exposes the social costs borne by indentured workers employed on Fijian sugar plantations. Practice/ Research Implications: The study promotes better understanding of the practice and impact of accounting as a technology of government and control within a particular institutional setting, in this case the British colony of Fiji. By highlighting the social implications of these controls in their historical context, we alert corporations, government policy makers, accountants and workers to the socially damaging effects of exploitive management control systems.

A simple and fast two-locus quality control test to detect false positives due to batch effects in genome-wide association studies

The impact of erroneous genotypes having passed standard quality control (QC) can be severe in genome-wide association studies, genotype imputation, and estimation of heritability and prediction of genetic risk based on single nucleotide polymorphisms (SNP). To detect such genotyping errors, a simple two-locus QC method, based on the difference in test statistic of association between single SNPs and pairs of SNPs, was developed and applied. The proposed approach could detect many problematic SNPs with statistical significance even when standard single SNP QC analyses fail to detect them in real data. Depending on the data set used, the number of erroneous SNPs that were not filtered out by standard single SNP QC but detected by the proposed approach varied from a few hundred to thousands. Using simulated data, it was shown that the proposed method was powerful and performed better than other tested existing methods. The power of the proposed approach to detect erroneous genotypes was approximately 80% for a 3% error rate per SNP. This novel QC approach is easy to implement and computationally efficient, and can lead to a better quality of genotypes for subsequent genotype-phenotype investigations.

Quantitative Trait Loci for CD4:CD8 Lymphocyte Ratio Are Associated with Risk of Type 1 Diabetes and HIV-1 Immune Control

Abnormal expansion or depletion of particular lymphocyte subsets is associated with clinical manifestations such as HIV progression to AIDS and autoimmune disease. We sought to identify genetic predictors of lymphocyte levels and reasoned that these may play a role in immune-related diseases. We tested 2.3 million variants for association with five lymphocyte subsets, measured in 2538 individuals from the general population, including CD4+ T cells, CD8+ T cells, CD56+ natural killer (NK) cells, and the derived measure CD4:CD8 ratio. We identified two regions of strong association. The first was located in the major histocompatibility complex (MHC), with multiple SNPs strongly associated with CD4:CD8 ratio (rs2524054, p = 2.1 × 10−28). The second region was centered within a cluster of genes from the Schlafen family and was associated with NK cell levels (rs1838149, p = 6.1 × 10−14). The MHC association with CD4:CD8 replicated convincingly (p = 1.4 × 10−9) in an independent panel of 988 individuals. Conditional analyses indicate that there are two major independent quantitative trait loci (QTL) in the MHC region that regulate CD4:CD8 ratio: one is located in the class I cluster and influences CD8 levels, whereas the second is located in the class II cluster and regulates CD4 levels. Jointly, both QTL explained 8% of the variance in CD4:CD8 ratio. The class I variants are also strongly associated with durable host control of HIV, and class II variants are associated with type-1 diabetes, suggesting that genetic variation at the MHC may predispose one to immune-related diseases partly through disregulation of T cell homeostasis.

The level of FoxO1 and IL-15 in skeletal muscle, serum and synovial fluid in people with knee osteoarthritis: a case control study

Objectives Impaired muscle function is common in knee osteoarthritis (OA). Numerous biochemical molecules have been implicated in the development of OA; however, these have only been identified in the joint and serum. This study compared the expression of interleukin (IL-15) and Forkhead box protein-O1 (FoxO1) in muscle of patients with knee OA asymptomatic individuals, and examined whether IL-15 was also present in the joint and serum. Method Muscle and blood samples were collected from 19 patients with diagnosed knee OA and 10 age-matched asymptomatic individuals. Synovial fluid and muscle biopsies were collected from the OA group during knee replacement surgery. IL-15 and FoxO1were measured in the skeletal muscle. IL-15 abundance was also analysed in the serum of both groups and synovial fluid from the OA group. Knee extensor strength was measured and correlated with IL-15 and FoxO1 in the muscle. Results FoxO1 protein expression was higher (p=0.04), whereas IL-15 expression was lower (p=0.02) in the muscle of the OA group. Strength was also lower in the OA group, and was inversely correlated with FoxO1 expression. No correlation was found between IL-15 in the joint, muscle or serum. Conclusion Skeletal muscle, particularly the quadriceps, is affected in people with knee OA where elevated FoxO1 protein expression was associated with reduced muscle strength. While IL-15 protein expression in the muscle was lower in the knee OA group, no correlation was found between the expression of IL-15 protein in the muscle, joint and serum, which suggests that inflammation is regulated differently within these tissues.

Polymer encapsulation of magnesium to control biodegradability and biocompatibility

Clinical utility of biodegradable magnesium implants is undermined by the untimely degradation of these materials in vivo. Their high corrosion rate leads to loss of mechanical integrity, peri–implant alkalization and localised accumulation of hydrogen gas. Biodegradable coatings were produced on pure magnesium using RF plasma polymerisation. A monoterpene alcohol with known anti-inflammatory and antibacterial properties was used as a polymer precursor. The addition of the polymeric layer was found to reduce the degradation rate of magnesium in simulated body fluid. The in vitro studies indicated good cytocompatibility of non-adherent THP–1 cells and mouse macrophage cells with the polymer, and the polymer coated sample. The viability of THP–1 cells was significantly improved when in contact with polymer encapsulated magnesium compared to unmodified samples. Collectively, these results suggest plasma enhanced polymer encapsulation of magnesium as a suitable method to control degradation kinetics of this biomaterial.

Single household domestic water heater design and control utilising PV energy: The untapped energy storage solution

Photovoltaic (PV) panels and electric domestic water heater with storage (DWH) are widely used in households in many countries. However, DWH should be explored as an energy storage mechanism before batteries when households have excess PV energy. Through a residential case study in Queensland, Australia, this paper presents a new optimized design and control solution to reduce water heating costs by utilizing existing DWH energy storage capacity and increasing PV self-consumption for water heating. The solution is produced by evaluating the case study energy profile and numerically maximizing the use of PV for DWH. A conditional probability matrix for different solar insolation and hot water usage days is developed to test the solution. Compared to other tariffs, this solution shows cost reduction from 20.8% to 63.3% This new solution could encourage solar households move to a more economical and carbon neutral water heating method.

Surface Modification of Biomaterials for Biofilm Control

Amongst various methods to attain sound antibacterial and antifouling properties, surface modification of biomaterials combines efficiency, processing flexibility, and most importantly, the ability to preserve favourable bulk properties, such as mechanical strength and chemical inertness. This chapter will first briefly discuss key parameters by which the biomaterial surface can be described, namely surface chemistry and morphology, and their individual and combined contributions to cell-surface interactions. More emphasis will be placed on surface morphology as the area of much debate. The chapter will then describe a range of available methodologies for surface modification, with plasma-assisted modification as one of the foci.

Towards vision-based deep reinforcement learning for robotic motion control

This paper introduces a machine learning based system for controlling a robotic manipulator with visual perception only. The capability to autonomously learn robot controllers solely from raw-pixel images and without any prior knowledge of configuration is shown for the first time. We build upon the success of recent deep reinforcement learning and develop a system for learning target reaching with a three-joint robot manipulator using external visual observation. A Deep Q Network (DQN) was demonstrated to perform target reaching after training in simulation. Transferring the network to real hardware and real observation in a naive approach failed, but experiments show that the network works when replacing camera images with synthetic images.

The moderating effects of job control and selection, optimization, and compensation strategies on the age-work ability relationship

Work ability describes employees' capability to carry out their work with respect to physical and psychological job demands. This study investigated direct and interactive effects of age, job control, and the use of successful aging strategies called selection, optimization, and compensation (SOC) in predicting work ability. We assessed SOC strategies and job control by using employee self-reports, and we measured employees' work ability using supervisor ratings. Data collected from 173 health-care employees showed that job control was positively associated with work ability. Additionally, we found a three-way interaction effect of age, job control, and use of SOC strategies on work ability. Specifically, the negative relationship between age and work ability was weakest for employees with high job control and high use of SOC strategies. These results suggest that the use of successful aging strategies and enhanced control at work are conducive to maintaining the work ability of aging employees. We discuss theoretical and practical implications regarding the beneficial role of the use of SOC strategies utilized by older employees and enhanced contextual resources at work for aging employees.

Focus on opportunities as a boundary condition of the relationship between job control and work engagement: A multi-sample, multi-method study

The concept of focus on opportunities describes how many new goals, options, and possibilities employees believe to have in their personal future at work. In this multi-sample, multi-method study, the authors investigated relationships between focus on opportunities and general and daily work engagement and the moderating role of focus on opportunities on between- and within-person relationships between job control and work engagement. Based on a social cognitive theory framework on the motivating potential of a future temporal focus, it was hypothesized that focus on opportunities is positively related to work engagement. Further, consistent with the notion of compensatory resources, it was expected that job control is not related to work engagement among employees with a high focus on opportunities, whereas job control, as an external resource of the work environment, is positively related to work engagement among employees with a low focus on opportunities. Both a cross-sectional survey study (N=174) and a daily diary study (N=64) supported the hypotheses. The study contributes to research on the job demands-resources model as it emphasizes the role of focus on opportunities as a motivational factor in the relationship between job control and work engagement.

Locus of control

The construct known as locus of control (LOC) was introduced by J. B. Rotter in 1966 and refers to individuals' beliefs about the underlying main causes of events happening in their lives. Individuals with an internal LOC believe that the outcomes they experience are the result of their own actions. They are often described as believing themselves to be the masters of their own fate and to be in control of their own destinies. In contrast, individuals with an external LOC believe that external factors—such as fate, luck, God, or powerful others—determine the outcomes that they experience in their lives. They are often described as taking a passive approach toward their lives.