A framework to optimize compilation task

Nowadays, compiler construction is supported by several tools, many of them are based on frameworks, composed by several components that can be combined or instantiated to build new components or even entire compilers. This paper is a software engineering exercise applied to the compiler construction tools. It is used a concrete framework for compilers development - the Dolphin, that supplies several components that work over a single code representation model, to show that the simple composition of such components is not enough. It raises serious obstacles that make the compilers construction more arduous. The exercise evolves for a reformulation of the framework, resulting on an independent architecture that could be adapted to similar frameworks. Defining the behaviour and the relationship of several elements of the framework, this architecture allows to surpass most of the obstacles, but also releases the compilers developer from some duties, making the construction of compilers more accessible. It also promotes the development of compilers that are more stable and efficient that is, they can run faster using fewer resources

Inflammatory Tumor Microenvironment

This entry belongs to Entry Collection "Immunotherapy in Solid Tumors "This entry is adapted from https://doi.org/10.3390/immuno1020007ReviewThe development of tumors requires an initiator event, usually exposure to DNA damaging agentes that cause genetic alterations such as gene mutations or chromosomal abnormalities, leading to deregulated cell proliferation. Although the mere stochastic accumulation of further mutations may cause tumor progression, it is now clear that an inflammatory microenvironment has a major tumor promoting influence on initiated cells, in particular when a chronic inflammatory reaction already existed before the initiated tumor cell was formed. Moreover, inflammatory cells become mobilized in response to signals emanating from tumor cells. In both cases, the microenvironment provides signals that initiated tumor cells perceive by membrane receptors and transduce via downstream kinase cascades to modulate multiple cellular processes and respond with changes in cell gene expression, metabolism, and morphology. Cytokines, chemokines, and growth factors are examples of major signals secreted by immune cells, fibroblast, and endothelial cells and mediate an intricate cell-cell crosstalk in an inflammatory microenvironment, which contributes to increased cancer cell survival, phenotypic plasticity and adaptation to surrounding tissue conditions. Eventually, consequente changes in extracellular matrix stiffness and architecture, coupled with additional genetic alterations, further fortify the malignant progression of tumor cells, priming them for invasion and metastasis.info:eu-repo/semantics/publishedVersio

Impact of Geo-distribution and Mining Pools on Blockchains: A Study of Ethereum

Given the large adoption and economical impact of permissionless blockchains, the complexity of the underlying systems and the adversarial environment in which they operate, it is fundamental to properly study and understand the emergent behavior and properties of these systems. We describe our experience on a detailed, one-month study of the Ethereum network from several geographically dispersed observation points. We leverage multiple geographic vantage points to assess the key pillars of Ethereum, namely geographical dispersion, network efficiency, blockchain efficiency and security, and the impact of mining pools. Among other new findings, we identify previously undocumented forms of selfish behavior and show that the prevalence of powerful mining pools exacerbates the geographical impact on block propagation delays. Furthermore, we provide a set of open measurement and processing tools, as well as the data set of the collected measurements, in order to promote further research on understanding permissionless blockchains.Comment: To appear in 50th IEEE/IFIP International Conference on Dependable Systems and Networks (DSN), 202

Plasma membrane-specific interactome analysis reveals calpain 1 as a druggable modulator of rescued Phe508del-CFTR cell surface stability

Cystic fibrosis (CF) is a genetic disease caused by mutations in the gene encoding CF transmembrane conductance regulator (CFTR), a chloride channel normally expressed at the surface of epithelial cells. The most frequent mutation, resulting in Phe-508 deletion, causes CFTR misfolding and its premature degradation. Low temperature or pharmacological correctors can partly rescue the Phe508del-CFTR processing defect and enhance trafficking of this channel variant to the plasma membrane (PM). Nevertheless, the rescued channels have an increased endocytosis rate, being quickly removed from the PM by the peripheral protein quality-control pathway. We previously reported that rescued Phe508del-CFTR (rPhe508del) can be retained at the cell surface by stimulating signaling pathways that coax the adaptor molecule ezrin (EZR) to tether rPhe508del–Na+/H+-exchange regulatory factor-1 (NHERF1) complexes to the actin cytoskeleton, thereby averting the rapid internalization of this channel variant. However, the molecular basis for why rPhe508del fails to recruit active EZR to the PM remains elusive. Here, using a proteomics approach, we characterized and compared the core components of wt-CFTR– or rPhe508del–containing macromolecular complexes at the surface of human bronchial epithelial cells. We identified calpain 1 (CAPN1) as an exclusive rPhe508del interactor that prevents active EZR recruitment, impairs rPhe508del anchoring to actin, and reduces its stability in the PM. We show that either CAPN1 downregulation or its chemical inhibition dramatically improves the functional rescue of Phe508del-CFTR in airway cells. These observations suggest that CAPN1 constitutes an attractive target for pharmacological intervention, as part of CF combination therapies restoring Phe508del-CFTR function.This work was supported by a center grant UID/MULTI/04046/2019 to BioISI and project PTDC/BIA-CEL/28408/2017 and IF2012 to PM, both from FCT, Portugal. AMM was recipient of fellowship SFRH/BD/52490/2014 from BioSYS PhD programme PD65-2012, and PB of fellowship SFRH/BPD/94322/2013.N/

NEETin with ICT

Science and Technology Advisory Council (STAC) outlines that 49% of EU citizens identified “job creation” and 33% identified “education and skills” as the top priorities for science and technology innovation over the next fifteen years. Both documents justify the needs in Europe for the ICT field especially for the NEET (not in education, employment or training) citizens. On the other hand, Grand Coalition for Digital Jobs (GC4DJ) in Europe identifies: the training and matching digital jobs; certification; innovative learning and teaching; mobility; awareness raising; increasing effectiveness of education; increasing equity and producing positive impact in the economy, as a priority for European countries. NEETin is a project directed to NEET citizens, to be developed by Higher Education Institutions, VET providers and Enterprises in order to help to overcome a social European dimension through lifelong learning. By creating a Joint Vocational Education Training in Digital Competences in a collaboration between VET providers and the Enterprises, widening the access to higher education, in an innovative student-centred learning model to apply in a European level, we aim to contribute to improve the quality of Education. Through this certified JVET, NEET citizens will develop their digital skills and the success of employability of these learners will be enhanced.info:eu-repo/semantics/publishedVersio

Identification and characterization of iImprovement opportunities in industrial processes

Flexibility in responding to demand has become a major challenge for industries today. To achieve customer expectations, organizations must be flexible enough to offer a wide range of products and services that are available at any time and with the quality expected by customers. Digitization and Industry 4.0 have a strong impact on today's production environment. Established lean production methods are part of this flexibilization process and can be improved through new technologies. Any digitization must deal with waste and reduce it more effectively than a classic lean approach could. When compared to conventional automation, lean automation spaces are smaller, system prices are cheaper, inventory and energy use are lower. The system designer and operator, however, must have higher skills and knowledge. The integration of innovative automation technology along with lean production is an up-to-date and promising topic as industry 4.0 will not solve the problems of poorly organized and managed manufacturing systems. Furthermore, its tools must be applied to lean activities that are already successful even before automation.info:eu-repo/semantics/publishedVersio

Identification and characterization of iImprovement opportunities in industrial processes

Flexibility in responding to demand has become a major challenge for industries today. To achieve customer expectations, organizations must be flexible enough to offer a wide range of products and services that are available at any time and with the quality expected by customers. Digitization and Industry 4.0 have a strong impact on today’s production environment. Established lean production methods are part of this flexibilization process and can be improved through new technologies. Any digitization must deal with waste and reduce it more effectively than a classic lean approach could. When compared to conventional automation, lean automation spaces are smaller, system prices are cheaper, inventory and energy use are lower. The system designer and operator, however, must have higher skills and knowledge. The integration of innovative automation technology along with lean production is an up-to-date and promising topic as industry 4.0 will not solve the problems of poorly organized and managed manufacturing systems. Furthermore, its tools must be applied to lean activities that are already successful even before automation.info:eu-repo/semantics/publishedVersio