SystemC Model Generation for Realistic Simulation of Networked Embedded Systems

Verification and design-space exploration of today's embedded systems require the simulation of heterogeneous aspects of the system, i.e., software, hardware, communications. This work shows the use of SystemC to simulate a model-driven specification of the behavior of a networked embedded system together with a complete network scenario consisting of the radio channel, the IEEE 802.15.4 protocol for wireless personal area networks and concurrent traffic sharing the medium. The paper describes the main issues addressed to generate SystemC modules from Matlab/Stateflow descriptions and to integrate them in a complete network scenario. Simulation results on a healthcare wireless sensor network show the validity of the approach

Framing Cutting-Edge Integrative Deep-Sea Biodiversity Monitoring via Environmental DNA and Optoacoustic Augmented Infrastructures

Deep-sea ecosystems are reservoirs of biodiversity that are largely unexplored, but their exploration and biodiscovery are becoming a reality thanks to biotechnological advances (e.g., omics technologies) and their integration in an expanding network of marine infrastructures for the exploration of the seas, such as cabled observatories. While still in its infancy, the application of environmental DNA (eDNA) metabarcoding approaches is revolutionizing marine biodiversity monitoring capability. Indeed, the analysis of eDNA in conjunction with the collection of multidisciplinary optoacoustic and environmental data, can provide a more comprehensive monitoring of deep-sea biodiversity. Here, we describe the potential for acquiring eDNA as a core component for the expanding ecological monitoring capabilities through cabled observatories and their docked Internet Operated Vehicles (IOVs), such as crawlers. Furthermore, we provide a critical overview of four areas of development: (i) Integrating eDNA with optoacoustic imaging; (ii) Development of eDNA repositories and cross-linking with other biodiversity databases; (iii) Artificial Intelligence for eDNA analyses and integration with imaging data; and (iv) Benefits of eDNA augmented observatories for the conservation and sustainable management of deep-sea biodiversity. Finally, we discuss the technical limitations and recommendations for future eDNA monitoring of the deep-sea. It is hoped that this review will frame the future direction of an exciting journey of biodiscovery in remote and yet vulnerable areas of our planet, with the overall aim to understand deep-sea biodiversity and hence manage and protect vital marine resources

Mucosal immunization with PspA (Pneumococcal surface protein A)-adsorbed nanoparticles targeting the lungs for protection against pneumococcal infection

Burden of pneumonia caused by Streptococcus pneumoniae remains high despite the availability of conjugate vaccines. Mucosal immunization targeting the lungs is an attractive alternative for the induction of local immune responses to improve protection against pneumonia. Our group had previously described the development of poly(glycerol adipate-co-ω-pentadecalactone) (PGA-co-PDL) polymeric nanoparticles (NPs) adsorbed with Pneumococcal surface protein A from clade 4 (PspA4Pro) within L-leucine microcarriers (nanocomposite microparticles-NCMPs) for mucosal delivery targeting the lungs (NP/NCMP PspA4Pro). NP/NCMP PspA4Pro was now used for immunization of mice. Inoculation of this formulation induced anti-PspA4Pro IgG antibodies in serum and lungs. Analysis of binding of serum IgG to intact bacteria showed efficient binding to bacteria expressing PspA from clades 3, 4 and 5 (family 2), but no binding to bacteria expressing PspA from clades 1 and 2 (family 1) was observed. Both mucosal immunization with NP/NCMP PspA4Pro and subcutaneous injection of the protein elicited partial protection against intranasal lethal pneumococcal challenge with a serotype 3 strain expressing PspA from clade 5 (PspA5). Although similar survival levels were observed for mucosal immunization with NP/NCMP PspA4Pro and subcutaneous immunization with purified protein, NP/NCMP PspA4Pro induced earlier control of the infection. Conversely, neither immunization with NP/NCMP PspA4Pro nor subcutaneous immunization with purified protein reduced bacterial burden in the lungs after challenge with a serotype 19F strain expressing PspA from clade 1 (PspA1). Mucosal immunization with NP/NCMP PspA4Pro targeting the lungs is thus able to induce local and systemic antibodies, conferring protection only against a strain expressing PspA from the homologous family 2

ApoB siRNA-induced Liver Steatosis is Resistant to Clearance by the Loss of Fatty Acid Transport Protein 5 (Fatp5)

The association between hypercholesterolemia and elevated serum apolipoprotein B (APOB) has generated interest in APOB as a therapeutic target for patients at risk of developing cardiovascular disease. In the clinic, mipomersen, an antisense oligonucleotide (ASO) APOB inhibitor, was associated with a trend toward increased hepatic triglycerides, and liver steatosis remains a concern. We found that siRNA-mediated knockdown of ApoB led to elevated hepatic triglycerides and liver steatosis in mice engineered to exhibit a human-like lipid profile. Many genes required for fatty acid synthesis were reduced, suggesting that the observed elevation in hepatic triglycerides is maintained by the cell through fatty acid uptake as opposed to fatty acid synthesis. Fatty acid transport protein 5 (Fatp5/Slc27a5) is required for long chain fatty acid (LCFA) uptake and bile acid reconjugation by the liver. Fatp5 knockout mice exhibited lower levels of hepatic triglycerides due to decreased fatty acid uptake, and shRNA-mediated knockdown of Fatp5 protected mice from diet-induced liver steatosis. Here, we evaluated if siRNA-mediated knockdown of Fatp5 was sufficient to alleviate ApoB knockdown-induced steatosis. We determined that, although Fatp5 siRNA treatment was sufficient to increase the proportion of unconjugated bile acids 100-fold, consistent with FATP5's role in bile acid reconjugation, Fatp5 knockdown failed to influence the degree, zonal distribution, or composition of the hepatic triglycerides that accumulated following ApoB siRNA treatment

Small airways obstruction and its risk factors in the Burden of Obstructive Lung Disease (BOLD) study: a multinational cross-sectional study

© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.Background: Small airways obstruction is a common feature of obstructive lung diseases. Research is scarce on small airways obstruction, its global prevalence, and risk factors. We aimed to estimate the prevalence of small airways obstruction, examine the associated risk factors, and compare the findings for two different spirometry parameters. Methods: The Burden of Obstructive Lung Disease study is a multinational cross-sectional study of 41 municipalities in 34 countries across all WHO regions. Adults aged 40 years or older who were not living in an institution were eligible to participate. To ensure a representative sample, participants were selected from a random sample of the population according to a predefined site-specific sampling strategy. We included participants' data in this study if they completed the core study questionnaire and had acceptable spirometry according to predefined quality criteria. We excluded participants with a contraindication for lung function testing. We defined small airways obstruction as either mean forced expiratory flow rate between 25% and 75% of the forced vital capacity (FEF25-75) less than the lower limit of normal or forced expiratory volume in 3 s to forced vital capacity ratio (FEV3/FVC ratio) less than the lower limit of normal. We estimated the prevalence of pre-bronchodilator (ie, before administration of 200 μg salbutamol) and post-bronchodilator (ie, after administration of 200 μg salbutamol) small airways obstruction for each site. To identify risk factors for small airways obstruction, we performed multivariable regression analyses within each site and pooled estimates using random-effects meta-analysis. Findings: 36 618 participants were recruited between Jan 2, 2003, and Dec 26, 2016. Data were collected from participants at recruitment. Of the recruited participants, 28 604 participants had acceptable spirometry and completed the core study questionnaire. Data were available for 26 443 participants for FEV3/FVC ratio and 25 961 participants for FEF25-75. Of the 26 443 participants included, 12 490 were men and 13 953 were women. Prevalence of pre-bronchodilator small airways obstruction ranged from 5% (34 of 624 participants) in Tartu, Estonia, to 34% (189 of 555 participants) in Mysore, India, for FEF25-75, and for FEV3/FVC ratio it ranged from 5% (31 of 684) in Riyadh, Saudi Arabia, to 31% (287 of 924) in Salzburg, Austria. Prevalence of post-bronchodilator small airways obstruction was universally lower. Risk factors significantly associated with FEV3/FVC ratio less than the lower limit of normal included increasing age, low BMI, active and passive smoking, low level of education, working in a dusty job for more than 10 years, previous tuberculosis, and family history of chronic obstructive pulmonary disease. Results were similar for FEF25-75, except for increasing age, which was associated with reduced odds of small airways obstruction. Interpretation: Despite the wide geographical variation, small airways obstruction is common and more prevalent than chronic airflow obstruction worldwide. Small airways obstruction shows the same risk factors as chronic airflow obstruction. However, further research is required to investigate whether small airways obstruction is also associated with respiratory symptoms and lung function decline.National Heart and Lung Institute and Wellcome Trust. Supported by Wellcome Trust grant 085790/Z/08/Z for the BOLD studyinfo:eu-repo/semantics/publishedVersio

Divergence across mitochondrial genomes of sympatric members of the Schistosoma indicum group and clues into the evolution of Schistosoma spindale

Schistosoma spindale and Schistosoma indicum are ruminant-infecting trematodes of the Schistosoma indicum group that are widespread across Southeast Asia. Though neglected, these parasites can cause major pathology and mortality to livestock leading to significant welfare and socio-economic issues, predominantly amongst poor subsistence farmers and their families. Here we used mitogenomic analysis to determine the relationships between these two sympatric species of schistosome and to characterise S. spindale diversity in order to identify possible cryptic speciation. The mitochondrial genomes of S. spindale and S. indicum were assembled and genetic analyses revealed high levels of diversity within the S. indicum group. Evidence of functional changes in mitochondrial genes indicated adaptation to environmental change associated with speciation events in S. spindale around 2.5 million years ago. We discuss our results in terms of their theoretical and applied implications

Resolving taxonomic uncertainty in vulnerable elasmobranchs : are the Madeira skate (Raja maderensis) and the thornback ray (Raja clavata) distinct species?

Skates and rays constitute the most speciose group of chondrichthyan fishes, yet are characterised by remarkable levels of morphological and ecological conservatism. They can be challenging to identify, which makes monitoring species compositions for fisheries management purposes problematic. Owing to their slow growth and low fecundity, skates are vulnerable to exploitation and species exhibiting endemism or limited ranges are considered to be the most at risk. The Madeira skate Raja maderensis is endemic and classified as ‘Data Deficient’ by the IUCN, yet its taxonomic distinctiveness from the morphologically similar and more wide-ranging thornback ray Raja clavate is unresolved. This study evaluated the sequence divergence of both the variable control region and cytochrome oxidase I ‘DNA barcode’ gene of the mitochondrial genome to elucidate the genetic differentiation of specimens identified as R. maderensis and R. clavate collected across much of their geographic ranges. Genetic evidence was insufficient to support the different species designations. However regardless of putative species identification, individuals occupying waters around the Azores and North African Seamounts represent an evolutionarily significant unit worthy of special consideration for conservation management

Establishment of a coastal fish in the Azores : recent colonisation or suddenexpansion of an ancient relict population?

The processes and time scales associated with ocean-wide changes in the distribution of marinespecies have intrigued biologists since Darwin’s earliest insights into biogeography. The Azores, amid-Atlantic volcanic archipelago located more than 1000 km off the European continental shelf,offers ideal opportunities to investigate phylogeographic colonization scenarios. The benthopelagicsparid fish known as the common two-banded seabream (Diplodus vulgaris) is now relativelycommon along the coastline of the Azores archipelago, but was virtually absent prior to the 1990s.We employed a multiple genetic marker approach to test whether the successful establishment of theAzorean population derives from a recent colonization from western continental/island populationsor from the demographic explosion of an ancient relict population.Results from nuclear and mtDNA sequences show that all Atlantic and Mediterranean populationsbelong to the same phylogroup, though microsatellite data indicate significant genetic divergencebetween the Azorean sample and all other locations, as well as among Macaronesian, westernIberian and Mediterranean regions. The results from Approximate Bayesian Computation indicatethat D. vulgaris has likely inhabited the Azores for approximately 40 (95% C.I.: 5.5─83.6) to 52(95% C.I.; 6.32─89.0) generations, corresponding to roughly 80-150 years, which suggests nearcontemporary colonisation, followed by a more recent demographic expansion which could havebeen facilitated by changing climate conditions. Moreover, the lack of previous records of thisspecies over the past century, together with the absence of lineage separation and the presence ofrelatively few private alleles, do not exclude the possibility of an even more recent colonisationevent

Cohort Profile: Burden of Obstructive Lung Disease (BOLD) study

The Burden of Obstructive Lung Disease (BOLD) study was established to assess the prevalence of chronic airflow obstruction, a key characteristic of chronic obstructive pulmonary disease, and its risk factors in adults (≥40 years) from general populations across the world. The baseline study was conducted between 2003 and 2016, in 41 sites across Africa, Asia, Europe, North America, the Caribbean and Oceania, and collected high-quality pre- and post-bronchodilator spirometry from 28 828 participants. The follow-up study was conducted between 2019 and 2021, in 18 sites across Africa, Asia, Europe and the Caribbean. At baseline, there were in these sites 12 502 participants with high-quality spirometry. A total of 6452 were followed up, with 5936 completing the study core questionnaire. Of these, 4044 also provided high-quality pre- and post-bronchodilator spirometry. On both occasions, the core questionnaire covered information on respiratory symptoms, doctor diagnoses, health care use, medication use and ealth status, as well as potential risk factors. Information on occupation, environmental exposures and diet was also collected

A design and veri\ufb01cation methodology for networked embedded systems

Oggigiorno i Sistemi Dedicati di Rete (Networked Embeddedd Systems \u2013 NES) sono una tecnologia pervasiva. Il loro utilizzo comprende applicazioni per il monitoraggio, per l\u2019automazione delle case, e per compiti in ambienti critici. La loro crescente complessit\ue0 richiede nuove metodologie per poter effettuare ef\ufb01cientemente le fasi di progettazione e veri\ufb01ca. Questo lavoro presenta un \ufb02usso di sviluppo generico per NES, supportato dall\u2019implementazione di programmi per la loro applicazione. Il \ufb02usso di sviluppo sfrutta il linguaggio SystemC, e considera la rete come una dimensione dello spazio di progetto. La metodologia di base comprende estensioni per considerare anche i casi in cui il NES sia implementato usando un middleware o in cui siano presenti dei requisiti di af\ufb01dabilit\ue0. Inoltre, sono stati implementati dei programmmi di traduzione per consentire l\u2019adozione della metodologia proposta con design scritti in altri linguaggi per la descrizione dell'hardware.Nowadays, Networked Embedded Systems (NES\u2019s) are a pervasive technology. Their use ranges from communication, to home automation, to safety critical \ufb01elds. Their increasing complexity requires new methodologies for ef\ufb01cient design and veri\ufb01cation phases. This work presents a generic design \ufb02ow for NES\u2019s, supported by the implementation of tools for its application. The design \ufb02ow exploits the SystemC language, and considers the network as a design space dimension. Some extensions to the base methodology have been performed to consider the presence of a middleware as well as dependability requirements. Translation tools have been implemented to allow the adoption of the proposed methodology with designs written in other HW description languages