The development of Th1 lymphocytes is essential for cell-mediated immunity and resistance against intracellular pathogens. However, if left unregulated, the same response can cause serious damage to ...host tissues and lead to mortality. A number of different paracrine regulatory mechanisms involving distinct myeloid and lymphoid subpopulations have been implicated in controlling excessive secretion of inflammatory cytokines by Th1 cells. Much of this work has focused on interleukin (IL)-10, a cytokine with broad anti-inflammatory properties, one of which is to counteract the function of Th1 lymphocytes. While studying the role of IL-10 in regulating immunopathology during infection with the intracellular parasite Toxoplasma gondii, we discovered that the host-protective IL-10 derives in an autocrine manner from conventional interferon-gamma (IFN-gamma)-producing T-bet(+) Foxp3(neg) Th1 cells. In the following review, we will discuss these findings that support the general concept that production of IL-10 is an important self-regulatory function of CD4(+) T lymphocytes.
Measles and rubella persist in the World Health Organization European Region despite long-standing and widespread use of vaccines against them. Our aim was to review the epidemiology of measles and ...rubella in relation to the goal of eliminating these diseases from the Region by 2015. We report on the number of measles and rubella cases by country in 2012 and present an analysis of preliminary measles and rubella surveillance data for 2013. We analysed data of these diseases for 2013 by age group, diagnosis confirmation (clinical, laboratory-confirmed and epidemiologically linked), and vaccination, hospitalization and importation status. We also report on measles-related deaths. For 2012, there were 27 134 measles cases and 29 601 rubella cases reported in the Region. For 2013, these figures were 31 520 and 39 367 respectively. Most measles cases in 2013 (96%; n = 30 178) were reported by nine countries: Georgia (7830), Germany (1773), Italy (2216), the Netherlands (2499), Romania (1074), the Russian Federation (2174), Turkey (7404), Ukraine (3308) and the United Kingdom (1900). In 2013, most measles cases were among unvaccinated persons and over one in three patients were aged 20 years and older. For 2013, almost all rubella cases were reported by Poland (n = 38 585; 98%). High population immunity and high-quality surveillance are the cornerstones to eliminate measles and rubella. Without sustained political commitment and accelerated action by Member States and partners, the elimination of measles and rubella in the WHO European Region may not be achieved.
This research investigates the benefits of different Machine Learning (ML) approaches in production systems, with respect to the given use case of considering the forming process and different ...friction conditions on hydraulic press response in between the phases of the sheet metal bending cycle, i.e. bending, levelling and movement. A framework for enhancing production systems with ML facilitates the transition to smarter processes and enables fast, accurate predictions integrated into decision-making and adaptive control. Comparative ML analysis provides insights into predictive regression models for hydraulic press condition recognition, enhancing process improvement. Our results are supported by performance evaluation metrics of predictive accuracy RMSE, MAE, MSE and R2 for Linear Regression (LR), Decision Trees (DT), Support Vector Machine (SVM), Gaussian Process Regression (GPR) and Neural Network (NN) models. Given the remarkable predictive accuracy of the regression models with R2 values between 0.9483 and 0.9995, it is noteworthy that less complex models exhibit significantly shorter training times, up to 437 times shorter than more complex models. In addition, simpler models have up to 36 times better prediction rates, compared to more complex models. The fundamentals illustrate the trade-offs between model complexity, accuracy and computational training and prediction rate.
Globally measles remains one of the leading causes of death among young children even though a safe and cost-effective vaccine is available. The World Health Organization (WHO) European Region has ...seen a decline in measles and rubella cases in recent years. The recent outbreaks have primarily affected adolescents and young adults with no vaccination or an incomplete vaccination history. Eliminating measles and rubella is one of the top immunization priorities of the European Region as outlined in the European Vaccine Action Plan 2015–2020. Following the 2010 decision by the Member States in the Region to initiate the process of verifying elimination, the European Regional Verification Commission for Measles and Rubella Elimination (RVC) was established in 2011. The RVC meets every year to evaluate the status of measles and rubella elimination in the Region based on documentation submitted by each country’s National Verification Committees. The verification process was however modified in late 2014 to assess the elimination status at the individual country level instead of at regional level. The WHO European Region has made substantial progress towards measles and rubella elimination over the past 5 years. The RVC’s conclusion in 2016 that 70% and 66% of the 53 Member States in the Region had interrupted the endemic transmission of measles and rubella, respectively, by 2015 is a testament to this progress. Nevertheless, where measles and rubella remain endemic, challenges in vaccination service delivery and disease surveillance will need to be addressed through focused technical assistance from WHO and development partners.
Friedreich's ataxia, an autosomal cardio- and neurodegenerative disorder that affects 1 in 50 000 humans, is caused by decreased levels of the protein frataxin. Although frataxin is nuclear-encoded, ...it is targeted to the mitochondrial matrix and necessary for proper regulation of cellular iron homeostasis. Frataxin is required for the cellular production of both heme and iron−sulfur (Fe−S) clusters. Monomeric frataxin binds with high affinity to ferrochelatase, the enzyme involved in iron insertion into porphyrin during heme production. Monomeric frataxin also binds to Isu, the scaffold protein required for assembly of Fe−S cluster intermediates. These processes (heme and Fe−S cluster assembly) share requirements for iron, suggesting that monomeric frataxin might function as the common iron donor. To provide a molecular basis to better understand frataxin's function, we have characterized the binding properties and metal-site structure of ferrous iron bound to monomeric yeast frataxin. Yeast frataxin is stable as an iron-loaded monomer, and the protein can bind two ferrous iron atoms with micromolar binding affinity. Frataxin amino acids affected by the presence of iron are localized within conserved acidic patches located on the surfaces of both helix-1 and strand-1. Under anaerobic conditions, bound metal is stable in the high-spin ferrous state. The metal−ligand coordination geometry of both metal-binding sites is consistent with a six-coordinate iron−(oxygen/nitrogen) based ligand geometry, surely constructed in part from carboxylate and possibly imidazole side chains coming from residues within these conserved acidic patches on the protein. On the basis of our results, we have developed a model for how we believe yeast frataxin interacts with iron.
In this article, we propose a new method for analyzing longitudinal data which contain responses that are missing at random. This method consists in solving the generalized estimating equation (GEE) ...of 8 in which the incomplete responses are replaced by values adjusted using the inverse probability weights proposed in 17. We show that the root estimator is consistent and asymptotically normal, essentially under the some conditions on the marginal distribution and the surrogate correlation matrix as those presented in 15 in the case of complete data, and under minimal assumptions on the missingness probabilities. This method is applied to a real-life data set taken from 13, which examines the incidence of respiratory disease in a sample of 250 pre-school age Indonesian children which were examined every 3 months for 18 months, using as covariates the age, gender, and vitamin A deficiency.
The main goal of this paper is to show how it is possible to modify a previously created model of a software-intensive system for the production of stereoscopic multimedia content defined by ...generalized nets (GN) without disturbing its static structure. When the system is structurally complex, any disruption of the static structure of the system can produce side effects on the rest of the system’s functionality. Generalized nets, as a powerful theoretical mathematical tool widely accepted for modeling systems from educational and biological to industrial and organisational ones, enable the analysis of static, dynamic and temporal characteristics of the modeled system. The existing GN model, according to the theory of generalized nets, can be modified by dropping or adding places, even entire transitions. This assumes a disruption of the static structure of a GN model and cannot be suitable for situations when similar but essentially different solutions need to be made using the GN model. For this purpose, the possibility of generalized nets to manage the capacities of places in transition have been used in this paper. In order to solve this problem, five most common cases of stereoscopic content production have been defined here: real-time studio production (live programme from the studio), realization of a sports event—live, post-production services (processing of other people’s stereoscopic material), subtitling/over synchronization and realization of a film programme—showing. For each case of the model usage non-necessary characteristics received by tokens in different places are defined. In accordance with GN methodology places with corresponding characteristics are eliminated for particular use-case by setting capacity function to zero.
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