Atherogenic ω-6 Lipids Modulate PPAR- EGR-1 Crosstalk in Vascular Cells

Atherogenic ω-6 lipids are physiological ligands of peroxisome proliferator-activated receptors (PPARs) and elicit pro- and antiatherogenic responses in vascular cells. The objective of this study was to investigate if ω-6 lipids modulated the early growth response-1 (Egr-1)/PPAR crosstalk thereby altering vascular function. Rat aortic smooth muscle cells (RASMCs) were exposed to ω-6 lipids, linoleic acid (LA), or its oxidized form, 13-HPODE (OxLA) in the presence or absence of a PPARα antagonist (MK886) or PPARγ antagonist (GW9662) or PPAR-specific siRNA. Our results demonstrate that ω-6 lipids, induced Egr-1 and monocyte chemotactic protein-1 (MCP-1) mRNA and protein levels at the acute phase (1–4 hrs) when PPARα was downregulated and at subacute phase (4–12 hrs) by modulating PPARγ, thus resulting in altered monocyte adhesion to RASMCs. We provide novel insights into the mechanism of action of ω-6 lipids on Egr-1/PPAR interactions in vascular cells and their potential in altering vascular function

La incidencia del aspecto lingüístico en los proyectos de cooperación sur-sur: el caso de Argentina en África (2010-2020)

El presente trabajo desarrolla un estudio de caso focalizado en las relaciones de cooperación horizontal entre la República Argentina, donde el español es lengua predominante, y países africanos de las áreas de expresión francesa y portuguesa. Se pretende esclarecer si la difusión del francés y el portugués entre los actores argentinos de esa cooperación ha incidido en el desarrollo de los proyectos de cooperación con los países en los cuales esos idiomas son relevantes y si la difusión del español en esos estados africanos juega algún papel en el mismo sentido, con el fin de establecer si la difusión doméstica de una lengua extranjera en un país afecta la cooperación Sur-Sur (CSS) con países que hablan esa lengua. El proceso de investigación se sostiene en una arquitectura teórica que apela al concepto de soft power para desprender e ilustrar la noción de política lingüística exterior y aplicarla al caso analizado. A partir del análisis documental y de la aplicación de cuestionarios y la realización de entrevistas a los agentes participantes, se circunscribe el perímetro de la CSS entre Argentina y África para identificar tipos de agentes según sus funciones en el marco de los proyectos y las consecuentes situaciones de comunicación verificadas en la implementación de estos. De este modo, se presentan informaciones sobre el capital y las prácticas lingüísticas de los agentes y se relevan las percepciones acerca de la relación entre sus propias competencias lingüísticas y las de sus interlocutores africanos, y el desarrollo de los proyectos de CSS en los que participaron

Calcium Handling Defects and Cardiac Arrhythmia Syndromes

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Aryl Hydrocarbon Receptor Ligands Inhibit IGF-II and Adipokine Stimulated Breast Cancer Cell Proliferation

Obesity increases human cancer risk and the risk for cancer recurrence. Adipocytes secrete paracrine factors termed adipokines that stimulate signaling in cancer cells that induce proliferation. The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that plays roles in tumorigenesis, is regulated by exogenous lipophilic chemicals, and has been explored as a therapeutic target for cancer therapy. Whether exogenous AHR ligands modulate adipokine stimulated breast cancer cell proliferation has not been investigated. We provide evidence that adipocytes secrete insulin-like growth factor 2 (IGF-2) at levels that stimulate the proliferation of human estrogen receptor (ER) positive breast cancer cells. Using highly specific AHR ligands and AHR short interfering RNA (AHR-siRNA), we show that specific ligand-activated AHR inhibits adipocyte secretome and IGF-2-stimulated breast cancer cell proliferation. We also report that a highly specific AHR agonist significantly ( \u3c 0.05) inhibits the expression of E2F1, CCND1 (known as Cyclin D1), MYB, SRC, JAK2, and JUND in breast cancer cells. Collectively, these data suggest that drugs that target the AHR may be useful for treating cancer in human obesity

A Tight Local Algorithm for the Minimum Dominating Set Problem in Outerplanar Graphs

We show that there is a deterministic local algorithm (constant-time distributed graph algorithm) that finds a 5-approximation of a minimum dominating set on outerplanar graphs. We show there is no such algorithm that finds a (5-ε)-approximation, for any ε > 0. Our algorithm only requires knowledge of the degree of a vertex and of its neighbors, so that large messages and unique identifiers are not needed

Effects of aspirin on risks of vascular events and cancer according to bodyweight and dose:analysis of individual patient data from randomised trials

Background A one-dose-fits-all approach to use of aspirin has yielded only modest benefits in long-term prevention of cardiovascular events, possibly due to underdosing in patients of large body size and excess dosing in patients of small body size, which might also affect other outcomes. Methods Using individual patient data, we analysed the modifying effects of bodyweight (10 kg bands) and height (10 cm bands) on the effects of low doses (≤100 mg) and higher doses (300–325 mg or ≥500 mg) of aspirin in randomised trials of aspirin in primary prevention of cardiovascular events. We stratified the findings by age, sex, and vascular risk factors, and validated them in trials of aspirin in secondary prevention of stroke. Additionally, we assessed whether any weight or height dependence was evident for the effect of aspirin on 20-year risk of colorectal cancer or any in-trial cancer. Results Among ten eligible trials of aspirin in primary prevention (including 117 279 participants), bodyweight varied four-fold and trial median weight ranged from 60·0 kg to 81·2 kg (pand#60;0·0001). The ability of 75–100 mg aspirin to reduce cardiovascular events decreased with increasing weight (pinteraction=0·0072), with benefit seen in people weighing 50–69 kg (hazard ratio [HR] 0·75 [95% CI 0·65–0·85]) but not in those weighing 70 kg or more (0·95 [0·86–1·04]; 1·09 [0·93–1·29] for vascular death). Furthermore, the case fatality of a first cardiovascular event was increased by low-dose aspirin in people weighing 70 kg or more (odds ratio 1·33 [95% CI 1·08–1·64], p=0·0082). Higher doses of aspirin (≥325 mg) had the opposite interaction with bodyweight (difference pinteraction=0·0013), reducing cardiovascular events only at higher weight (pinteraction=0·017). Findings were similar in men and women, in people with diabetes, in trials of aspirin in secondary prevention, and in relation to height (pinteraction=0·0025 for cardiovascular events). Aspirin-mediated reductions in long-term risk of colorectal cancer were also weight dependent (pinteraction=0·038). Stratification by body size also revealed harms due to excess dosing: risk of sudden death was increased by aspirin in people at low weight for dose (pinteraction=0·0018) and risk of all-cause death was increased in people weighing less than 50 kg who were receiving 75–100 mg aspirin (HR 1·52 [95% CI 1·04–2·21], p=0·031). In participants aged 70 years or older, the 3-year risk of cancer was also increased by aspirin (1·20 [1·03–1·47], p=0·02), particularly in those weighing less than 70 kg (1·31 [1·07–1·61], p=0·009) and consequently in women (1·44 [1·11–1·87], p=0·0069). Interpretation Low doses of aspirin (75–100 mg) were only effective in preventing vascular events in patients weighing less than 70 kg, and had no benefit in the 80% of men and nearly 50% of all women weighing 70 kg or more. By contrast, higher doses of aspirin were only effective in patients weighing 70 kg or more. Given that aspirin's effects on other outcomes, including cancer, also showed interactions with body size, a one-dose-fits-all approach to aspirin is unlikely to be optimal, and a more tailored strategy is required

Integrating the data envelopment analysis and the balanced scorecard approaches for enhanced performance assessment

This article presents the development of a conceptual framework which aims to assess Decision Making Units (DMUs)from multiple perspectives. The proposed conceptual framework combines the Balanced Scorecard(BSC)method with the non-parametric technique known as Data Envelopment Analysis (DEA) by using various interconnected models which try to encapsulate four perspectives of performance (financial, customers, internal processes,learning and growth). The practical relevance of the conceptual model has been tested by using it to assess the performance of DMUs in a multinational company which operates in two business areas.Various models were developed with the collaboration of the directors of the company in order to conceive an appropriate and consensual framework, which may provide useful information for the company.The application of the conceptual framework provides structured information regarding the performance of each DMU(from multiple perspectives)and ways to improve it.By integrating the BSC and the DEA approaches this research helps to identify where there is room for improving organisational performance and points out opportunities for reciprocal learning between DMUs.In doing so,this article provides a set of recommendations relating to the successful application of DEA and its integration with the BSC,in order to promote a continuous learning process and to bring about improvements in performance

Attachment Predicts College Students’ Knowledge, Attitudes, and Skills for Working with Infants, Toddlers, and Families

Research Findings:Adults’ attitudes about attachment relationships are central to how they perceive and respond to children. However, little is known about how attachment styles are related to teachers’ attitudes toward and interactions with infants and toddlers. From a survey of 207 students taking early childhood (EC) courses at 4 U.S. universities, we report relations among students’ attachment styles and their (a) career goals, (b) attitudes about caring for and educating infants and young children, and (c) interaction skills for responding in developmentally supportive ways. Overall, attachment security was positively associated with career goals focused on working with younger children, knowledge about infant/toddler development, attitudes that acknowledge the importance of adult support in children’s development, and developmentally supportive interaction skills. Students who scored high on attachment fearfulness minimized the importance of adults in children’s lives, minimized the importance of the early years for later learning, and endorsed strict and controlling forms of child guidance. Practice or Policy: A conceptual mediation model linking a path from attachment to caregiving skill through knowledge and attitudes is articulated. We propose a person-centered pedagogy for infant/toddler professional preparation that provides opportunities for reflection on one’s own attachment and its effects on work with young childre

Aryl Hydrocarbon Receptor Ligands Inhibit IGF-II and Adipokine Stimulated Breast Cancer Cell Proliferation

Obesity increases human cancer risk and the risk for cancer recurrence. Adipocytes secrete paracrine factors termed adipokines that stimulate signaling in cancer cells that induce proliferation. The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that plays roles in tumorigenesis, is regulated by exogenous lipophilic chemicals, and has been explored as a therapeutic target for cancer therapy. Whether exogenous AHR ligands modulate adipokine stimulated breast cancer cell proliferation has not been investigated. We provide evidence that adipocytes secrete insulin-like growth factor 2 (IGF-2) at levels that stimulate the proliferation of human estrogen receptor (ER) positive breast cancer cells. Using highly specific AHR ligands and AHR short interfering RNA (AHR-siRNA), we show that specific ligand-activated AHR inhibits adipocyte secretome and IGF-2-stimulated breast cancer cell proliferation. We also report that a highly specific AHR agonist significantly (P < 0.05) inhibits the expression of E2F1, CCND1 (known as Cyclin D1), MYB, SRC, JAK2, and JUND in breast cancer cells. Collectively, these data suggest that drugs that target the AHR may be useful for treating cancer in human obesity

Using data envelopment analysis to support the design of process improvement interventions in electricity distribution

A significant number of studies have documented the use of Data Envelopment Analysis (DEA) for efficiency measurement in the context of electricity distribution, particularly at the level of the distribution utilities. However, their aim has been predominantly descriptive and classificatory, without any attempt to ‘open’ the black box of the transformation process. In contrast, our aim is to explore the potential of DEA to contribute to the design of effective process improvement interventions within a distribution utility. In particular, in this paper, we study an important question within the context of DEA analysis: that is, to investigate whether differences in efficiency can be attributed to a particular managerial programme or design feature. We use two different methodologies to undertake this type of analysis. Firstly, we apply Mann–Whitney rank statistics to the scores obtained from DEA in order to evaluate the statistical significance of the differences observed between an intervention programme and its control group programme. Secondly, we undertake dynamic analysis with the Malmquist Productivity Index in order to study the impact of the introduction of a new technology on a group of units. Our case study focuses on the performance evaluation of medium-voltage power lines belonging to one of the service areas in the Public Electricity Distribution System in Portugal. The results from our case study show that the application of DEA for process improvement interventions has great potential and should be explored in other contexts