A MDE-based process for the design, implementation and validation of safety critical systems

Distributed Real-Time Embedded (DRE) systems have critical requirements that need to be verified. They are either related to functional (e.g. stability of a furnace controller) or non-functional (e.g. meeting deadlines) aspects. Model-Driven Engineering (MDE) tools have emerged to ease DRE systems design. These tools are also capable of generating code. However, these tools either focus on the functional aspects or on the runtime architecture. Hence, the development cycle is partitioned into pieces with heterogeneous modeling notations and poor coordination. In this paper, we propose a MDE-based process to create DRE systems without manual coding. We show how to integrate functional and architecture concerns in a unified process. We use industry-proven modeling languages to design functional elements of the system, and automatically integrate them using our AADL toolchain

Shedding of host autophagic proteins from the parasitophorous vacuolar membrane of Plasmodium berghei

The hepatic stage of the malaria parasite Plasmodium is accompanied by an autophagy-mediated host response directly targeting the parasitophorous vacuolar membrane (PVM) harbouring the parasite. Removal of the PVM-associated autophagic proteins such as ubiquitin, p62, and LC3 correlates with parasite survival. Yet, it is unclear how Plasmodium avoids the deleterious effects of selective autophagy. Here we show that parasites trap host autophagic factors in the tubovesicular network (TVN), an expansion of the PVM into the host cytoplasm. In proliferating parasites, PVM-associated LC3 becomes immediately redirected into the TVN, where it accumulates distally from the parasite's replicative centre. Finally, the host factors are shed as vesicles into the host cytoplasm. This strategy may enable the parasite to balance the benefits of the enhanced host catabolic activity with the risk of being eliminated by the cell's cytosolic immune defence

The Process of Criminalizing Femicides: A Comparative Analysis between Mexico and Colombia

Femicides, the intentional killing of women because they are women, have been a rising issue within Latin America and the Caribbean for the past 30 years. This issue has caused many countries within the region to explore different processes for criminalizing femicide. Mexico and Colombia are two countries that have been leaders in the region by implementing expansive and inclusive penal codes. Throughout this paper, I will be discussing important background information concerning Mexico and Colombia to create an important context for the paper. Additionally, I will explore how Mexico and Colombia have criminalized femicide through three different factors: 1) international non-governmental organizations (NGOs); 2) domestic courts; and 3) legislators.&nbsp;</p

Marketing digital: a utilização das redes sociais como canal de comunicação pela Biblioteca Central da Universidade Federal do Rio Grande do Sul

A presente pesquisa é de abordagem quantitativa e quanto aos objetivos é exploratória e descritiva. Quanto aos procedimentos, foi adotada a pesquisa bibliográfica documental. Para a coleta de dados, foram utilizadas as redes sociais: Instagram, Facebook e Twitter. A coleta de dados foi realizada por meio de consulta manual acessando os endereços das páginas e registrando as atividades de todas as postagens realizadas entre o período de 01 de janeiro a 31 de dezembro do ano de 2021, analisando a quantidade de curtidas e comentários. A interpretação dos dados foi feita a partir da técnica de análise de conteúdo. Os resultados obtidos revelam que a divulgação dos produtos e serviços realizada nas redes sociais da biblioteca é insatisfatória, revela ainda a importância da utilização de outros canais informacionais na divulgação de produtos, serviços e disseminação do conhecimento e cultura.The purpose of this paper is to understand the contribution of the social networks Instagram, Facebook and Twitter in the dissemination of the services and products of the Central Library of the Federal University of Rio Grande do Sul. The research has a quantitative approach and in terms of objectives, it is exploratory and descriptive. As for the procedures, bibliographic, documentary and case study research was adopted and for data collection, social media was used: Instagram, Facebook and Twitter to analyze the performance of the central library of the Federal University of Rio Grande do Sul in the social networks. Data collection was carried out through manual consultation, accessing the addresses of the pages and recording the activities of all posts made between the period from January 1st to December 31st of the year 2021, analyzing the number of likes and comments. Data interpretation was performed using the content analysis technique. The results obtained reveal that the dissemination of products and services carried out in the library’s social networks is unsatisfactory, it also reveals the importance of using other informational channels in the dissemination of products, services and dissemination of knowledge and culture

Probing Plasmodium falciparum sexual commitment at the single-cell level

Background: Malaria parasites go through major transitions during their complex life cycle, yet the underlying differentiation pathways remain obscure. Here we apply single cell transcriptomics to unravel the program inducing sexual differentiation in Plasmodium falciparum. Parasites have to make this essential life-cycle decision in preparation for human-to-mosquito transmission. Methods: By combining transcriptional profiling with quantitative imaging and genetics, we defined a transcriptional signature in sexually committed cells. Results: We found this transcriptional signature to be distinct from general changes in parasite metabolism that can be observed in response to commitment-inducing conditions. Conclusions: This proof-of-concept study provides a template to capture transcriptional diversity in parasite populations containing complex mixtures of different life-cycle stages and developmental programs, with important implications for our understanding of parasite biology and the ongoing malaria elimination campaign

Investigation of model stacking for drug sensitivity prediction

Background: A significant problem in precision medicine is the prediction of drug sensitivity for individual cancer cell lines. Predictive models such as Random Forests have shown promising performance while predicting from individual genomic features such as gene expressions. However, accessibility of various other forms of data types including information on multiple tested drugs necessitates the examination of designing predictive models incorporating the various data types. Results: We explore the predictive performance of model stacking and the effect of stacking on the predictive bias and squarred error. In addition we discuss the analytical underpinnings supporting the advantages of stacking in reducing squared error and inherent bias of random forests in prediction of outliers. The framework is tested on a setup including gene expression, drug target, physical properties and drug response information for a set of drugs and cell lines. Coclusion: The performance of individual and stacked models are compared. We note that stacking models built on two heterogeneous datasets provide superior performance to stacking different models built on the same dataset. It is also noted that stacking provides a noticeable reduction in the bias of our predictors when the dominat eigenvalue of the principle axis of variation in the residuals is significantly higher than the remaining eigenvalues

Investigation of Trypanosoma-induced vascular damage sheds insights into Trypanosoma vivax sequestration

Multiple blood-borne pathogens infecting mammals establish close interactions with the host vascular endothelium as part of their life cycles. In this work, we investigate differences in the interactions of three Trypanosoma species: T. brucei, T. congolense and T. vivax with the blood vasculature. Infection with these species results in vastly different pathologies, including different effects on vascular homeostasis, such as changes in vascular permeability and microhemorrhages. While all three species are extracellular parasites, T. congolense is strictly intravascular, while T. brucei is capable of surviving both extra- and intravascularly. Our knowledge regarding T. vivax tropism and its capacity of migration across the vascular endothelium is unknown. In this work, we show for the first time that T. vivax parasites sequester to the vascular endothelium of most organs, and that, like T. congolense, T. vivax Y486 is largely incapable of extravasation. Infection with this parasite species results in a unique effect on vascular endothelium receptors including general downregulation of ICAM1 and ESAM, and upregulation of VCAM1, CD36 and E-selectin. Our findings on the differences between the two sequestering species (T. congolense and T. vivax) and the non-sequestering, but extravasating, T. brucei raise important questions on the relevance of sequestration to the parasite’s survival in the mammalian host, and the evolutionary relevance of both sequestration and extravasation.info:eu-repo/semantics/publishedVersio

Toolbox for in vivo imaging of host-parasite interactions at multiple scales

Animal models have for long been pivotal for parasitology research. Over the last few years, techniques such as intravital, optoacoustic and magnetic resonance imaging, optical projection tomography, and selective plane illumination microscopy developed promising potential for gaining insights into host-pathogen interactions by allowing different visualization forms in vivo and ex vivo. Advances including increased resolution, penetration depth, and acquisition speed, together with more complex image analysis methods, facilitate tackling biological problems previously impossible to study and/or quantify. Here we discuss advances and challenges in the in vivo imaging toolbox, which hold promising potential for the field of parasitology

Intravital microscopy: imaging host‐parasite interactions in lymphoid organs

Intravital microscopy allows imaging of biological phenomena within living animals, including host‐parasite interactions. This has advanced our understanding of both, the function of lymphoid organs during parasitic infections, and the effect of parasites on such organs to allow their survival. In parasitic research, recent developments in this technique have been crucial for the direct study of host –parasite interactions within organs at depths, speeds, and resolution previously difficult to achieve. Lymphoid organs have gained more attention as we start to understand their function during parasitic infections and the effect of parasites on them. In this review, we summarize technical and biological findings achieved by intravital microscopy with respect to the interaction of various parasites with host lymphoid organs, namely the bone marrow, thymus, lymph nodes, spleen, and the mucosa‐associated lymphoid tissue, and present a view into possible future applications