Chlamydia pneumoniae-induced foam cell formation requires MyD88-dependent and -independent signaling and is reciprocally modulated by liver X receptor activation.

Chlamydia pneumoniae is detected by macrophages and other APCs via TLRs and can exacerbate developing atherosclerotic lesions, but how that occurs is not known. Liver X receptors (LXRs) centrally control reverse cholesterol transport, but also negatively modulate TLR-mediated inflammatory pathways. We isolated peritoneal macrophages from wild-type, TLR2, TLR3, TLR4, TLR2/4, MyD88, TRIF, MyD88/TRIF, and IFN regulatory factor 3 (IRF3) KO mice, treated them with live or UV-killed C. pneumoniae in the presence or absence of oxidized LDL, then measured foam cell formation. In some experiments, the synthetic LXR agonist GW3965 was added to macrophages infected with C. pneumoniae in the presence of oxidized LDL. Both live and UV-killed C. pneumoniae induced IRF3 activation and promoted foam cell formation in wild-type macrophages, whereas the genetic absence of TLR2, TLR4, MyD88, TRIF, or IRF3, but not TLR3, significantly reduced foam cell formation. C. pneumoniae-induced foam cell formation was significantly reduced by the LXR agonist GW3965, which in turn inhibited C. pneumoniae-induced IRF3 activation, suggesting a bidirectional cross-talk. We conclude that C. pneumoniae facilitates foam cell formation via activation of both MyD88-dependent and MyD88-independent (i.e., TRIF-dependent and IRF3-dependent) pathways downstream of TLR2 and TLR4 signaling and that TLR3 is not involved in this process. This mechanism could at least partly explain why infection with C. pneumoniae accelerates the development of atherosclerotic plaque and lends support to the proposal that LXR agonists might prove clinically useful in suppressing atherogenesis

Global Production Increased by Spatial Heterogeneity in a Population Dynamics Model

Spatial and temporal heterogeneity are often described as important factors having a strong impact on biodiversity. The effect of heterogeneity is in most cases analyzed by the response of biotic interactions such as competition of predation. It may also modify intrinsic population properties such as growth rate. Most of the studies are theoretic since it is often difficult to manipulate spatial heterogeneity in practice. Despite the large number of studies dealing with this topics, it is still difficult to understand how the heterogeneity affects populations dynamics. On the basis of a very simple model, this paper aims to explicitly provide a simple mechanism which can explain why spatial heterogeneity may be a favorable factor for production.We consider a two patch model and a logistic growth is assumed on each patch. A general condition on the migration rates and the local subpopulation growth rates is provided under which the total carrying capacity is higher than the sum of the local carrying capacities, which is not intuitive. As we illustrate, this result is robust under stochastic perturbations

Investigating the Awareness of Onsite Mechanization in Malaysian Construction Industry

AbstractThe Malaysian construction industry is vital for the country economy and always played a key role towards the development of national infrastructure. The ever-increasing market competitiveness and the widespread adoption of Industrialized Building System (IBS) by the local contractors derive the industry to improve the existing processes for achieving higher levels of quality and products. This transition from traditional methods of construction give a momentum to the deployment of onsite mechanized equipments. The utilization of mechanized equipments increases construction productivity and as well as reduces the dependency on foreign labour. However, a large amount of construction company's capital is also invested in procuring these equipments. In addition to this, varieties of construction equipments are also required for carrying out these operations. Therefore, the aim of this paper is to investigate the current awareness and application of onsite mechanization in Malaysian construction industry. A questionnaire survey was conducted among a classified group of Construction Industry Development Board of Malaysia (CIDB) G7 Class ‘A’ contractors. The results of the survey show that there is a good understanding of Malaysian contractors towards mechanization. It is also revealed that the adoption of IBS have a direct correlation with the usage of onsite machineries and equipments. Results further indicate that excavation, earthworks, pilling works and structural works have high utilization of mechanized construction equipments. The study will help to find out the existing level of mechanization practices in Malaysian construction industry

Negotiating the selling price of hydropower energy using multi-agent systems in BOT

During the feasibility study of BOT (Build-Operate-Transfer) hydropower investments, the selling price of energy is the most critical parameter that impacts the net present value (NPV) estimated by the investors. Investors usually consider the price of energy guaranteed by the government during their feasibility studies which is the worst case scenario. However, it is apparent that negotiations that take place between investor and broker determine the price of energy which is affected by various sources of uncertainty associated with the energy demand and country conditions. The objective of this study was to make a realistic estimate of the investor’s selling price by modeling the negotiation process between investor and broker using a multi-agent system (MAS). Thus, the factors affecting the negotiation process were identified, a negotiation protocol between the parties was set up, negotiation scenarios were determined, and modelled by using a MAS. The model was tested on a hydropower investment in Turkey and generated more realistic results compared to the current practice. Investors and brokers may benefit from this study because it considers the potential changes in the market as well as the negotiating postures of parties under different scenarios

Caspase-1 Dependent IL-1β Secretion Is Critical for Host Defense in a Mouse Model of Chlamydia pneumoniae Lung Infection

Chlamydia pneumoniae (CP) is an important human pathogen that causes atypical pneumonia and is associated with various chronic inflammatory disorders. Caspase-1 is a key component of the ‘inflammasome’, and is required to cleave pro-IL-1β to bioactive IL-1β. Here we demonstrate for the first time a critical requirement for IL-1β in response to CP infection. Caspase-1−/− mice exhibit delayed cytokine production, defective clearance of pulmonary bacteria and higher mortality in response to CP infection. Alveolar macrophages harbored increased bacterial numbers due to reduced iNOS levels in Caspase-1−/− mice. Pharmacological blockade of the IL-1 receptor in CP infected wild-type mice phenocopies Caspase-1-deficient mice, and administration of recombinant IL-1β rescues CP infected Caspase-1−/− mice from mortality, indicating that IL-1β secretion is crucial for host immune defense against CP lung infection. In vitro investigation reveals that CP-induced IL-1β secretion by macrophages requires TLR2/MyD88 and NLRP3/ASC/Caspase-1 signaling. Entry into the cell by CP and new protein synthesis by CP are required for inflammasome activation. Neither ROS nor cathepsin was required for CP infection induced inflammasome activation. Interestingly, Caspase-1 activation during CP infection occurs with mitochondrial dysfunction indicating a possible mechanism involving the mitochondria for CP-induced inflammasome activation

Estimating the profitability of hydropower investments with a case study from Turkey

Energy demand has been increasing, but traditional sources of energy are depletable. New investments are needed in renewable energy production. Hydroelectric power plants are often considered a feasible renewable source of energy and are often organized as a public private partnerships (PPP). However, risk factors stemming from the macro environment as well as project conditions should be considered in performing feasibility studies. The objective of this study was to develop a method that can be used to predict the profitability of hydropower investments considering the relevant risk factors. To that end, a cash flow that represents the construction and operation period is set up, the risk fac­tors involved in such projects are identified, the impacts of these risk factors on the cash flow parameters are assessed, and Monte Carlo simulation is performed to estimate the net present value (NPV) of a hydropower investment. The proposed method was tested in a hydropower investment located in Turkey and generated credible results that could be of great benefit to potential investors operating in similar conditions. The primary contribution of this research is the creation of a method that allows investors to assess the profitability of a hydropower investment by using a stochastic approach

Deficiency of CCAAT/enhancer binding protein-epsilon reduces atherosclerotic lesions in LDLR-/- Mice

10.1371/journal.pone.0085341PLoS ONE91-POLN

Patients' experiences with cancer care in Switzerland: Results of a multicentre cross-sectional survey.

The objectives were to describe patients' experiences of cancer care in Switzerland and explore the variation of these experiences by type of cancer. The Swiss Cancer Patient Experiences (SCAPE) study was a cross-sectional, multicentre survey conducted in 2018. Adult patients (n = 7145) with breast, prostate, lung, colorectal, skin or haematological cancer from four large hospitals in French-speaking Switzerland were invited to complete a survey. Logistic regressions were used to assess whether experiences varied according to cancer type, adjusting for confounders. Of the 3121 persons who returned the survey (44% response rate), 2755 reporting an eligible cancer were included in the analyses. Participants' average score for overall care was 8.5 out of a maximum score of 10. Higher rates of positive experiences were found for nurse consultations (94%), diagnostic tests (85%) and inpatient care (82%). Lower positive responses were reported for support for people with cancer (70%), treatment decisions (66%), diagnosis (65%) and home care (55%). We observed non-systematic differences in experiences of care by cancer type. This large study identified that cancer patient experiences can be improved in relation to communication, information and supportive care aspects. Improvement efforts should target these areas of care to enhance responsiveness of cancer care