From Component-Based Architectures to Microservices: A 25-years-long Journey in Designing and Realizing Service-Based Systems

Distributed information systems and applications are generally described in terms of components and interfaces among them. How these component-based architectures have been designed and implemented evolved over the years, giving rise to the so-called paradigm of Service-Oriented Computing (SOC). In this chapter, we will follow a 25-years-long journey on how design methodologies and supporting technologies influenced one each other, and we discuss how already back in the late 90s the ancestors of the SOC paradigm were there, already paving the way for the technological evolution recently leading to microservice architectures and serverless computing

On the Deployment of IoT Systems: An Industrial Survey

Internet of Things (IoT) systems are complex and multifaceted, and the design of their architectures needs to consider many aspects at a time. Design decisions concern, for instance, the modeling of software components and their interconnections, as well as where to deploy the components within the available hardware infrastructure in the Edge-Cloud continuum. A relevant and challenging task, in this context, is to identify optimal deployment models due to all the different aspects involved, such as extra-functional requirements of the system, heterogeneity of the hardware resources concerning their processing and storage capabilities, and constraints like legal issues and operational cost limits. To gain insights about the deployment decisions concerning IoT systems in practice, and the factors that influence those decisions, we report about an industrial survey we conducted with 66 IoT architects from 18 countries across the world. Each participant filled in a questionnaire that comprises 15 questions. By analyzing the collected data, we have two main findings: (i) architects rely on the Cloud more than the Edge for deploying the software components of IoT systems, in the majority of the IoT application domains; and (ii) the main factors driving deployment decisions are four: reliability, performance, security, and cost

Workload measurement in a communication application operated through a P300-based brain-computer interface

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Nuclear repositioning of the non-translocated HLXB9 allele in the leukaemia cell line GDM-1 harbouring a t(6;7)(q23;q36)

Background/Aims. Transcriptionally active and inactive topologically associated domains (TADs) occupy different areas in the cell nucleus, and chromosomal rearrangements relocating TADs could determine ectopic expression of the repositioned genes. In this study, we investigated the HLXB9 gene in a myeloid leukaemia cell line, GDM-1, known to harbour a rearrangement involving the chromosome 7 with breakpoint distal to HLXB9, highly expressed in these cells. Methods. We used fluorescence in situ hybridisation (FISH) to target the regions involved in the translocation and to distinguish the translocated chromosome from the non-translocated one in interphase nuclei. Results. Two-dimensional (2D) analysis of the interphase FISH data indicated that the two HLXB9 alleles had a different localisation in the cell nuclei, with the translocated allele consistently positioned in the nuclear periphery and the normal one in the more internal portion of the nucleus, known as the transcriptionally active compartment. Conclusion. Our data may indicate that HLXB9 transcripts in GDM-1 cell line do not arise from the allele located in the rearranged chromosome 7, suggesting that regulation of gene expression in cancer cells harbouring chromosomal translocations might be more complex than previously thought, paving the path to further investigations on mechanisms of gene expression

miR-29b sensitizes multiple myeloma cells to bortezomib-induced apoptosis through the activation of a feedback loop with the transcription factor Sp1

MicroRNAs (miRNAs) with tumor-suppressor potential might have therapeutic applications in multiple myeloma (MM) through the modulation of still undiscovered molecular pathways. Here, we investigated the effects of enforced expression of miR-29b on the apoptotic occurrence in MM and highlighted its role in the context of a new transcriptional loop that is finely tuned by the proteasome inhibitor bortezomib. In details, in vitro growth inhibition and apoptosis of MM cells was induced by either transient expression of synthetic miR-29b or its stable lentivirus-enforced expression. We identified Sp1, a transcription factor endowed with oncogenic activity, as a negative regulator of miR-29b expression in MM cells. Since Sp1 expression and functions are regulated via the 26S proteasome, we investigated the effects of bortezomib on miR-29b-Sp1 loop, showing that miR-29b levels were indeed upregulated by the drug. At the same time, the bortezomib/miR-29b combination produced significant pro-apoptotic effects. We also demonstrated that the PI3K/AKT pathway plays a major role in the regulation of miR-29b-Sp1 loop and induction of apoptosis in MM cells. Finally, MM xenografts constitutively expressing miR-29b showed significant reduction of their tumorigenic potential. Our findings indicate that miR-29b is involved in a regulatory loop amenable of pharmacologic intervention and modulates the anti-MM activity of bortezomib in MM cells

Diesel Exhaust Inhalation Elicits Acute Vasoconstriction in Vivo

BACKGROUND: Traffic-related air pollution is consistently associated with cardiovascular morbidity and mortality. Recent human and animal studies suggest that exposure to air pollutants affects vascular function. Diesel exhaust (DE) is a major source of traffic-related air pollution. OBJECTIVES: Our goal was to study the effects of short-term exposure to DE on vascular reactivity and on mediators of vascular tone. METHODS: In a double-blind, crossover, controlled exposure study, 27 adult volunteers (10 healthy and 17 with metabolic syndrome) were exposed in randomized order to filtered air (FA) and each of two levels of diluted DE (100 or 200 μg/m3 of fine particulate matter) in 2-hr sessions. Before and after each exposure, we assessed the brachial artery diameter (BAd) by B-mode ultrasound and collected blood samples for endothelin-1 (ET-1) and catecholamines. Postexposure we also assessed endothelium-dependent flow-mediated dilation (FMD). RESULTS: Compared with FA, DE at 200 μg/m3 elicited a decrease in BAd (0.11 mm; 95% confidence interval, 0.02–0.18), and the effect appeared linearly dose related with a smaller effect at 100 μg/m3. Plasma levels of ET-1 increased after 200 μg/m3 DE but not after FA (p = 0.01). There was no consistent impact of DE on plasma catecholamines or FMD. CONCLUSIONS: These results demonstrate that short-term exposure to DE is associated with acute endothelial response and vasoconstriction of a conductance artery. Elucidation of the signaling pathways controlling vascular tone that underlie this observation requires further study

The risk stratification of adverse neonatal outcomes in women with gestational diabetes (STRONG) study

Aims: To assess the risk of adverse neonatal outcomes in women with gestational diabetes (GDM) by identifying subgroups of women at higher risk to recognize the characteristics most associated with an excess of risk. Methods: Observational, retrospective, multicenter study involving consecutive women with GDM. To identify distinct and homogeneous subgroups of women at a higher risk, the RECursive Partitioning and AMalgamation (RECPAM) method was used. Overall, 2736 pregnancies complicated by GDM were analyzed. The main outcome measure was the occurrence of adverse neonatal outcomes in pregnancies complicated by GDM. Results: Among study participants (median age 36.8 years, pre-gestational BMI 24.8 kg/m2), six miscarriages, one neonatal death, but no maternal death was recorded. The occurrence of the cumulative adverse outcome (OR 2.48, 95% CI 1.59–3.87), large for gestational age (OR 3.99, 95% CI 2.40–6.63), fetal malformation (OR 2.66, 95% CI 1.00–7.18), and respiratory distress (OR 4.33, 95% CI 1.33–14.12) was associated with previous macrosomia. Large for gestational age was also associated with obesity (OR 1.46, 95% CI 1.00–2.15). Small for gestational age was associated with first trimester glucose levels (OR 1.96, 95% CI 1.04–3.69). Neonatal hypoglycemia was associated with overweight (OR 1.52, 95% CI 1.02–2.27) and obesity (OR 1.62, 95% CI 1.04–2.51). The RECPAM analysis identified high-risk subgroups mainly characterized by high pre-pregnancy BMI (OR 1.68, 95% CI 1.21–2.33 for obese; OR 1.38 95% CI 1.03–1.87 for overweight). Conclusions: A deep investigation on the factors associated with adverse neonatal outcomes requires a risk stratification. In particular, great attention must be paid to the prevention and treatment of obesity

Novel Insights Into Breast Cancer Copy Number Genetic Heterogeneity Revealed by Single-Cell Genome Sequencing

Copy number alterations (CNAs) play an important role in molding the genomes of breast cancers and have been shown to be clinically useful for prognostic and therapeutic purposes. However, our knowledge of intra-tumoral genetic heterogeneity of this important class of somatic alterations is limited. Here, using single-cell sequencing, we comprehensively map out the facets of copy number alteration heterogeneity in a cohort of breast cancer tumors. Ou/var/www/html/elife/12-05-2020/backup/r analyses reveal: genetic heterogeneity of non-tumor cells (i.e. stroma) within the tumor mass; the extent to which copy number heterogeneity impacts breast cancer genomes and the importance of both the genomic location and dosage of sub-clonal events; the pervasive nature of genetic heterogeneity of chromosomal amplifications; and the association of copy number heterogeneity with clinical and biological parameters such as polyploidy and estrogen receptor negative status. Our data highlight the power of single-cell genomics in dissecting, in its many forms, intra-tumoral genetic heterogeneity of CNAs, the magnitude with which CNA heterogeneity affects the genomes of breast cancers, and the potential importance of CNA heterogeneity in phenomena such as therapeutic resistance and disease relapse

Interoperability framework of virtual factory and business innovation

Interoperability framework of virtual factory and business innovationTask T51 Design a common schema and schema evolution framework for supporting interoperabilityTask T52 Design interoperability framework for supporting datainformation transformation service composition and business process cooperation among partnersA draft version is envisioned for month 44 which will be updated to reflect incremental changes driven by the other working packages for month 72 deliverable 7.