LXRα Regulates oxLDL-Induced Trained Immunity in Macrophages

Reprogramming of metabolic pathways in monocytes and macrophages can induce a proatherosclerotic inflammatory memory called trained innate immunity. Here, we have analyzed the role of the Liver X receptor (LXR), a crucial regulator of metabolism and inflammation, in oxidized low-density lipoprotein (oxLDL)-induced trained innate immunity. Human monocytes were incubated with LXR agonists, antagonists, and oxLDL for 24 h. After five days of resting time, cells were restimulated with the TLR-2 agonist Pam3cys. OxLDL priming induced the expression of LXRα but not LXRβ. Pharmacologic LXR activation was enhanced, while LXR inhibition prevented the oxLDL-induced inflammatory response. Furthermore, LXR inhibition blocked the metabolic changes necessary for epigenetic reprogramming associated with trained immunity. In fact, enrichment of activating histone marks at the IL-6 and TNFα promotor was reduced following LXR inhibition. Based on the differential expression of the LXR isoforms, we inhibited LXRα and LXRβ genes using siRNA in THP1 cells. As expected, siRNA-mediated knock-down of LXRα blocked the oxLDL-induced inflammatory response, while knock-down of LXRβ had no effect. We demonstrate a specific and novel role of the LXRα isoform in the regulation of oxLDL-induced trained immunity. Our data reveal important aspects of LXR signaling in innate immunity with relevance to atherosclerosis formation.     

Analyses of activity design in geometry in the light of student actions

Abstract

The goal of this study is to show that inquiry activities in a dynamic geometry environment, intentionally designed to confront students with contradictions and uncertainties, push them towards explanations that include deductive elements. Three different but dependent aspects of the activities are characterized and analysed: The epistemological, which includes all possible inquiry paths; the didactic, which involves only those paths that reflect the intention of the designer; and the cognitive, which accounts for actual student actions (conjectures and explanations) and their analyses. The research conclusions are based on the interplay among these three aspects. The analysis of students’ investigations and the analysis of their explanations fulfil, to a broad extent, the design goals.     

Hide-n-Sense: Preserving Privacy Efficiently in Wireless mHealth

As healthcare in many countries faces an aging population and rising costs, mobile sensing technologies promise a new opportunity. Using mobile health (mHealth) sensing, which uses medical sensors to collect data about the patients, and mobile phones to act as a gateway between sensors and electronic health record systems, caregivers can continuously monitor the patients and deliver better care. Furthermore, individuals can become better engaged in monitoring and managing their own health. Although some work on mHealth sensing has addressed security, achieving strong privacy for low-power sensors remains a challenge. We make three contributions. First, we propose an mHealth sensing protocol that provides strong security and privacy properties at the link layer, with low energy overhead, suitable for low-power sensors. The protocol uses three novel techniques: adaptive security, to dynamically modify transmission overhead; MAC striping, to make forgery difficult even for small-sized Message Authentication Codes; and asymmetric resource requirements, in recognition of the limited resources in tiny mHealth sensors. Second, we demonstrate its feasibility by implementing a prototype on a Chronos wrist device, and evaluating it experimentally. Third, we provide a security, privacy, and energy analysis of our system.     

Short communication: Passive shedding of Mycobacterium avium ssp. paratuberculosis in commercial dairy goats in Brazil

Goat farming is a low-cost alternative to dairy production in developing countries. In Brazil, goat production has increased in recent years due in part to the implementation of programs encouraging this activity. Mycobacterium avium ssp. paratuberculosis (MAP) is the causative agent of paratuberculosis, a disease that causes chronic granulomatous enteritis in ruminants, but MAP transmission dynamics are still poorly understood in goats. In a previously published study of our research group, 10 dairy goat farms (467 animals) from Minas Gerais state were analyzed for MAP detection; 2 fecal cultures and 11 milk samples tested positive for MAP by conventional PCR and were confirmed by sequencing. Because no clinical signs were observed over 1 yr of monitoring, we hypothesized that these MAP-positive goats could be passive shedders. Thus, in the present study, 4 positive goats (4/13) from the previous study were purchased and feces and milk samples were collected for evaluation (twice, with an interval of 3 mo between tests) by culture of MAP, IS900 PCR, or both. All analyses were negative for MAP. At the last time point, blood samples were collected for ELISA, the animals were killed, and tissues collected for tissue culture and histopathology. At necropsy, no macroscopic lesions related to paratuberculosis were observed. Similarly, no histological changes were observed and MAP in samples stained by Ziehl–Neelsen was not detected. These animals were characterized as potential passive shedders with upward contamination of the teat canal by MAP. This is the first report of the passive shedding phenomenon in goats in Brazil and it highlights the importance of identifying these animals for control programs and to ensure the quality of dairy products.     

Influence of compounding conditions,treatment of wood particles with fire-retardants and artificial weathering on properties of wood-polymer composites for façade applications

European Journal of Wood and Wood Products - Various fire-retardants (FR) for the pre-treatment of wood flour, for example, ammonium polyphosphate and different formulations based on phosphorus-...     

Identification and evaluation of uncertainties and errors in dynamic models of casted machine tool components

When calculating the dynamic properties of machine tools by means of the finite-element-analysis, highly correlated component models are needed for the derivation of an accurate model of the assembled machine tool structure. For casted machine tool components this cannot always be ensured due to the significant geometric and material uncertainties inherent in the casting process. In this paper, a stepwise modelling approach for casted machine tool components is proposed that allows the derivation of highly correlated models in a defined frequency range. Based on the assumption of superposition the uncertainties and errors involved in the modelling process are identified and evaluated by means of strain energy considerations. By applying this approach to a casted machine tool column, the initial frequency deviations for the considered first 15 structural modes of up to 15 % from the measured values could be reduced below 3 %. Also deeper insight was gained about the influence of the considered uncertainties and errors on the model correlation, as the deviations could be assigned to their sources.     

Storage technologies for wind power in the Columbia River Gorge

The transition from traditional energy sources to renewable has gained popularity and acceptance in recent years. This has been driven mainly by the current level of pollution, global warming, decommission of old nuclear power plants and the increasing cost of conventional energy sources. Nevertheless, one of the many steps to overcome is the seasonality or intermittency of renewable energy sources such as wind power. In recent years, new technologies have come up to address this problem, so the energy can be stored for future purposes. This paper analyses these energy storage alternatives for a specific case in the Columbia River Gorge for wind power. A hierarchical decision model is developed with criteria including political, social, environmental, technical and economical. The main conclusions highlight that the economical and technical criteria are among the most important ones for decision-makers.     

Evaluation of Antioxidative Constituents from Thyme

The non-polar fraction of thyme was examined for the occurrence of phenolic components and their antioxidative activity. In addition to carvacrol ( II ) and thymol ( III ), p -cymene-2,3-diol (I ; 2,3-dihydroxy-4-isopropyl-1-methylbenzene) was isolated for the first time from thyme. The structure of I was elucidated using ¹H nuclear magnetic resonance (NMR), ¹³C NMR, and mass spectrometry. Antioxidative activity was investigated with the Rancimat method (100°C) and the Schaal test (60°C). Compound I exhibited the strongest antioxidative activity which was greater than that of α-tocopherol and butylated hydroxyanisole. Five thyme species were analysed by means of HPLC with electrochemical detection for the concentration of compounds I – III . The highest amounts of I – III were found in Thymus vulgaris L.     

Prostaglandine und Prostaglandinvorstufen. Oxydative Spaltung von Olefinen durch Ozonisierung und Oxydation im Lösungsmittelsystem Aceton/tert-Butanol – eine Methode zur Gewinnung von substituierten Cyclopentylessigsäuren

Prostaglandins and Prostaglandin Intermediates. Oxidative Cleavage of Olefins by Ozonization and Oxidation in the Solvent System Acetone/tert. Butanol – a Method for Preparation of Substituted Cyclopentyl Acetic Acids Oxidative cleavage of olefinic double bonds by ozonization in acetone in the presence of tert. butanol followed by oxidation with JONES ' reagent in the same solvent system gives carboxylic acids and/or ketones in good yields. Acetic acid or water can be used instead of tert. butanol with the same success. This “one-pot” procedure was developed in connection with the synthesis of intermediates for the preparation of 8-methyl-prostaglandin C₂.