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The Web of Things (WoT) is rapidly growing in popularity getting the interest of not only technologist and scientific communities but industrial, system integrators and solution providers. The key aspect of the WoT to succeed is the relatively, easy-to-build ecosystems nature inherited from the web and the capacity for building end-to-end solutions. At the WoT connecting physical devices such as sensors, RFID tags or any devices that can send data through the Internet using the Web is almost automatic. The WoT shared data can be used to build smarter solutions that offer business services in the form of IoT applications. In this chapter, we review the main WoT challenges, with particular interest on highlighting those that rely on combining heterogeneous IoT data for the design of smarter services and applications and that benefit from data interoperability. Semantic web technologies help for overcoming with such challenges by addressing, among other ones the following objectives: 1) semantically annotating and unifying heterogeneous data, 2) enriching semantic WoT datasets with external knowledge graphs, and 3) providing an analysis of data by means of reasoning mechanisms to infer meaningful information. To overcome the challenge of building interoperable semantics-based IoT applications, the Machine-to-Machine Measurement (M3) semantic engine has been designed to semantically annotate WoT data, build the logic of smarter services and deduce meaningful knowledge by linking it to the external knowledge graphs available on the web. M3 assists application and business developers in designing interoperable Semantic Web of Things applications. Contributions in the context of European semantic-based WoT projects are discussed and a particular use case within FIESTA-IoT project is presented., 22 pages

The Internet of Things (IoT) concept is evolving rapidly and influencing newdevelopments in various application domains, such as the Internet of MobileThings (IoMT), Autonomous Internet of Things ( ...

The Internet of Things (IoT) is changing how industrial and consumer markets are developing. Robotic devices, drones and autonomous vehicles, blockchains, augmented and virtual reality, digital assistants and machine learning (artificial intelligence or AI) are the technologies that will provide the next phase of development of IoT applications. The combination of these disciplines makes possible the development of autonomous systems combining robotics and machine learning for designing similar systems. This new hyperconnected world offers many benefits to businesses and consumers, and the processed data produced by hyperconnectivity allows stakeholders in the IoT value network ecosystems to make smarter decisions and provide better customer experience.

10 p.-4 fig.-1 tab., The optimal recognition of penicillin determinants, including amoxicillin (AX), by specific IgE antibodies is widely believed to require covalent binding to a carrier molecule. The nature of the carrier and its contribution to the antigenic determinant is not well known. Here we aimed to evaluate the specific-IgE recognition of different AX-derived structures. We studied patients with immediate hypersensitivity reactions to AX, classified as selective or cross-reactors to penicillins. Competitive immunoassays were performed using AX itself, amoxicilloic acid, AX bound to butylamine (AXO-BA) or to human serum albumin (AXO-HSA) in the fluid phase, as inhibitors, and amoxicilloyl-poli-L-lysine (AXO-PLL) in the solid-phase. Two distinct patterns of AX recognition by IgE were found: Group A showed a higher recognition of AX itself and AX-modified components of low molecular weights, whilst Group B showed similar recognition of both unconjugated and conjugated AX. Amoxicilloic acid was poorly recognized in both groups, which reinforces the need for AX conjugation to a carrier for optimal recognition. Remarkably, IgE recognition in Group A (selective responders to AX) is influenced by the mode of binding and/or the nature of the carrier; whereas IgE in Group B (cross-responders to penicillins) recognizes AX independently of the nature of the carrier., The present study has been supported by Institute of Health “Carlos III” of the Ministry of Economy and Competitiveness (grants cofunded by European Regional Development Fund (ERDF): PI12/02529, PI15/01206, CP15/00103,Red de Reacciones Adversas a Alergenos y Farmacos RD12/0013/0001, RD12/0013/0003 and RD12/0013/0008,RD09/0076/00112 for the Biobank network and PT13/0010/0006 for the Biobank platform) and by State Secretariat for Research, Development and Innovation of the Ministry of Economy and Competitiveness (grants cofunded by European Regional Development Fund (ERDF): MINECO SAF2012-36519, SAF2015-68590-R/FEDER and CTQ2013-41339-P). Andalusian Regional Ministry of Economy and Knowledge (grants cofunded by European Regional Development Fund (ERDF): CTS-06603); Andalusian Regional Ministry Health (grants:PI-0699-2011, PI-0159-2013 and PI-0179-2014) and Merck-Serono Research Grant from Fundación Salud 2000. CM holds a ‘Nicolas Monardes’ research contract by Andalusian Regional Ministry Health: C-0044-2012 SAS 2013. MIM holds a ‘Miguel Servet I’ research contract by Institute of Health “Carlos III” of the Ministry of Economy and Competitiveness (grants cofunded by European Social Fund (ESF)): CP15/00103. AA thanks “pFIS fellowship” (FI08/00385) from ISCIII and Andalucia “Talent Hub Fellowship” (TAHUB/II-004) cofunded by the Junta de Andalucia and the European Union, VII Framework Programme of the European Commission (grant agreement No. 291780).

The nicotinamide adenine dinucleotide phosphate oxidase (NOX) family enzymes are involved in several physiological functions. However, their roles in keratinocyte responses to UV radiation have not been clearly elucidated. This study shows that, among other NOX family members, UVB irradiation results in a biphasic activation of NOX1 that plays a critical role in defining keratinocyte fate through the modulation of the DNA damage response network. Indeed, suppression of both bursts of UVB-induced NOX1 activation by using a specific peptide inhibitor of NOX1 (InhNOX1) is associated with increased nucleotide excision repair efficiency and reduction of apoptosis, which is finally translated into decreased photocarcinogenesis. On the contrary, when only the second peak of UVB-induced NOX1 activation is blocked, both nucleotide excision repair efficiency and apoptosis are decreased. Our results show that inhibition of NOX1 activation could be a promising target for the prevention and treatment of UVB-induced skin cancer in nucleotide excision repair-proficient and -deficient patients.

Ontology-based applications are becoming more and more popular and are usually domain-specific (e.g., eHealth or domotic). Designing ontologies and semantic-based applications manually is tedious and cumbersome for non-technical expert or semantic web beginners. Internet of Things (IoT) is a new field aiming to connect the physical world surrounded by devices such as sensors to the web to automatically interact with them and build innovative applications. The main challenges are to automate as much as possible the tasks of: (1) reusing the background knowledge previously designed by domain experts, (2) facilitating the tasks of IoT developers willing to integrate semantic web technologies into their applications, and (3) designing interoperable semantic-based IoT applications. Stemming from Linked Open Data and Linked Open Vocabularies, we designed Linked Open Vocabularies for Internet of Things (LOV4IoT), a catalogue of ontologies/datasets/rules relevant for IoT available online. LOV4IoT has been extended with more domains and ontology-based projects, a semantic-based dataset and a bot to enhance automation, and web services. Moreover, we demonstrate several use cases of the LOV4IoT dataset: (1) building Semantic Web of Things applications, (2) extracting frequent terms used in existing ontologies, and (3) stakeholders who can exploit, reuse and combine domain ontologies. Finally, we evaluated this dataset with users who exploit this dataset for their own purposes.

Semantic Web of Things is a new field combining Semantic Web and Internet of Things technologies to be surrounded by smart objects and applications connected to the Web. On one hand, one of the Linked Open Data applications, called DataHub aims at referencing datasets, on the other hand, the Linked Open Vocabularies (LOV) references more than 400 ontologies. However, we discovered that more than 200 ontology-based projects relevant for IoT are not referenced on such tools since domain experts are not aware of them nor of the semantic web best practices. We propose the Machine-to-Machine Measurement (M3) framework, available online, to rapidly design and develop semantic-based cross-domain IoT applications by reusing as much as possible the domain knowledge (ontologies, datasets and rules). To achieve this goal, there are challenging steps: (1) referencing and classifying semantic-based projects relevant for IoT, (2) re-engineering a dataset of interoperable domain rules to deduce high-level abstractions from sensor data, (3) re-engineering an interoperable cross-domain knowledge to combine domains, and (4) assisting developers in designing IoT applications by designing pre-defined templates. In this article, we are focused on referencing and classifying semantic-based projects relevant for IoT by designing the Linked Open Vocabularies for Internet of Things (LOV4IoT) dataset. We also design a dataset of interoperable domain rules to deduce high-level abstractions from sensor data by designing the Sensor-based Linked Open Rules (S-LOR). This work has been applied to two uses cases: (1) redesigning a security and cross-domain knowledge base to assist users in suggesting security mechanisms to secure their applications, and (2) designing semantic-based IoT applications embedded in Android-powered devices.

The endosomal sorting complexes required for transport (ESCRT) proteins have a critical function in abscission, the final separation of the daughter cells during cytokinesis. Here, we describe the structure and function of a previously uncharacterized ESCRT-III interacting protein, MIT-domain containing protein 1 (MITD1). Crystal structures of MITD1 reveal a dimer, with a microtubule-interacting and trafficking (MIT) domain at the N terminus and a unique, unanticipated phospholipase D-like (PLD) domain at the C terminus that binds membranes. We show that the MIT domain binds to a subset of ESCRT-III subunits and that this interaction mediates MITD1 recruitment to the midbody during cytokinesis. Depletion of MITD1 causes a distinct cytokinetic phenotype consistent with destabilization of the midbody and abscission failure. These results suggest a model whereby MITD1 coordinates the activity of ESCRT-III during abscission with earlier events in the final stages of cell division.

The plasma membrane is the final barrier that enveloped viruses must cross during their egress from the infected cell. Here, we review recent insights into the cell biology of retroviral assembly and release; these insights have driven a new understanding of the host proteins, such as the ESCRT machinery, that are used by retroviruses to promote their final separation from the host cell. We also review antiviral host factors such as tetherin, which can directly inhibit the release of retroviral particles. These studies have illuminated the role of the lipid bilayer as the unexpected target for virus restriction by the innate immune response.

The last steps of multivesicular body (MVB) formation, human immunodeficiency virus (HIV)-1 budding and cytokinesis require a functional endosomal sorting complex required for transport (ESCRT) machinery to facilitate topologically equivalent membrane fission events. Increased sodium tolerance (IST) 1, a new positive modulator of the ESCRT pathway, has been described recently, but an essential function of this highly conserved protein has not been identified. Here, we describe the previously uncharacterized KIAA0174 as the human homologue of IST1 (hIST1), and we report its conserved interaction with VPS4, CHMP1A/B, and LIP5. We also identify a microtubule interacting and transport (MIT) domain interacting motif (MIM) in hIST1 that is necessary for its interaction with VPS4, LIP5 and other MIT domain-containing proteins, namely, MITD1, AMSH, UBPY, and Spastin. Importantly, hIST1 is essential for cytokinesis in mammalian cells but not for HIV-1 budding, thus providing a novel mechanism of functional diversification of the ESCRT machinery. Last, we show that the hIST1 MIM activity is essential for cytokinesis, suggesting possible mechanisms to explain the role of hIST1 in the last step of mammalian cell division.

We investigated the regulation of the sphingosine kinase (SphK)/sphingosine-1-phosphate (S1P) axis and its role during pregnancy in the rat myometrium. SphK1 and SphK2 were coexpressed in myometrium during gestation. The levels and activity of SphK1/2 were modest at midgestation (d 12), increased at d 19 and progressively declined to low at postpartum. Similar patterns were observed for the phosphorylation of ERK and protein kinase C (PKC). Inhibition of PKC and ERK reduced SphK1/2 activity. In late pregnancy, levels of cyclooxygenase 2 (COX2) increased in parallel to SphK levels. Using a pharmacological approach, we demonstrated that in primary cultures of myometrial cells from d-19 pregnant rats, induction of COX2 was mediated by 4β-phorbol 12,13-dibutyrate and IL-1β through sequential activation of PKC, ERK1/2, and SphK1. S1P produced by SphK1 was released in the medium. Addition of S1P, IL-1β or 4β-phorbol 12,13-dibutyrate enhanced COX2 levels via Gi protein. Interestingly, S1P was also released by myometrial tissues at late gestation. This event was dependent on PKC/ERK/SphK1. By contrast, in d-12 myometrial tissues, the release of S1P was markedly reduced in association with low levels of SphK1 and COX2. However, prolonged incubation of myometrium from midgestation led to the induction of COX2. This effect was blocked by SphK inhibitors, providing evidence of the close relationship between SphK activity and COX2 induction in rat myometrium. Overall, our findings provided insight into the physiological relevance of the SphK activation and S1P release in uterine smooth muscle during gestation.

As part of the endosomal sorting complex required for transport (ESCRT) machinery, Tsg101 is essential for endosomal sorting, membrane receptor degradation and the final stages of cytokinesis. Depletion or overproduction of the protein can cause disruption of these vital processes and results in severe consequences for the cell. Tsg101 expression is thus controlled posttranslationally within a narrow range and this autoregulation has been mapped to the C-terminus of the protein. Here we elucidate further the mechanisms of this regulation and describe a novel function of Tsg101-associated ligase (Tal) in mediating this control. We show that Tal polyubiquitinates lysine residues in the C-terminus of uncomplexed Tsg101, resulting in proteasomal degradation. However, accessibility to these lysines is prevented by the presence of the other ESCRT-I proteins. We show that VPS28 is a limiting factor, and consequently Tsg101 expression surplus to ESCRT-I function is vulnerable to degradation. The role of Tal in the regulation of Tsg101 steady-state control is highlighted when Tsg101 is overexpressed; however, our data also suggest that additional ligases regulate Tsg101 expression under normal conditions. Lastly, we demonstrate that while the C-terminal lysines are targets for polyubiquitination, they are not required for any additional function necessary for ESCRT activity.

HIV and many other enveloped viruses encode a late budding domain (L-domain) that recruits the cellular machinery that mediates the separation of the nascent virion from the infected cell. The ubiquitin-proteasome system has been implicated in the L-domain activity, but the exact role of ubiquitin transfer and ubiquitin-binding proteins in the last step of viral replication remains elusive. It is now widely accepted that the class E vacuolar protein sorting pathway mediates both viral budding and vesicle budding into the multivesicular bodies and, remarkably, both budding events share the same topology and similar requirements for ubiquitin. In this review, the role of ubiquitin in viral budding is discussed in the light of recent advances in the understanding of the cellular mechanisms that assist the last step of HIV-1 release.

We discuss in this paper, semantic web methodologies, best practices and recommendations beyond the IERC Cluster Semantic Interoperability Best Practices and Recommendations (IERC AC4). The semantic web community designed best practices and methodologies which are unknown from the IoT community. In this paper, we synthesize and highlight the most relevant work regarding ontology methodologies, engineering, best practices and tools that could be applied to Internet of Things (IoT). To the best of our knowledge, this is the first work aiming at bridging such methodologies to the IoT community and go beyond the IERC AC4 cluster. This research is being applied to three uses cases: (1) the M3 framework assisting IoT developers in designing interoperable ontology-based IoT applications, (2) the FIESTA-IoT EU project encouraging semantic interoperability within IoT, and (3) a collaborative publication of legacy ontologies.

To report the long-term anatomical and functional outcomes of patients with choroidal neovascularization secondary to age-related macular degeneration treated with intravitreal bevacizumab (IVB).Retrospective case series. Patients diagnosed with subfoveal choroidal neovascularization secondary to age-related macular degeneration that were treated with at least 1 intravitreal injection of 1.25 mg of IVB and had a minimum follow-up of 60 months. Patients underwent best-corrected Snellen visual acuity testing, optical coherence tomography, and ophthalmoscopic examination at baseline and follow-up visits.Two hundred and forty-seven consecutive patients (292 eyes) were included. The mean number of IVB injections per eye was 10.9 ± 6.4. At 5 years, the BCVA decreased from 20/150 (logMAR 0.9 ± 0.6) at baseline to 20/250 (logMAR 1.1 ± 0.7) (P =0.0001). The mean CMT decreased from 343.1+ 122.3 μm at baseline to 314.7 ± 128.8 μm at 60 months of follow-up (P = 0.009). Geographic atrophy (GA) was observed at baseline in 47 (16%) of 292 eyes. By 5 years, GA developed or progressed in 124 (42.5%) of 292 eyes (P0.0001).The early visual gains obtained from IVB were not maintained at 5 years of follow-up. In addition, IVB may play a role in the development or progression of GA.

International audience; This paper presents an IoT architecture for the semantic interoperability of diverse IoT systems and applications in smart cities. The architecture virtualizes diverse IoT systems and ensures their modelling and representation according to common standards-based IoT ontologies. Furthermore, based on this architecture, the paper introduces a first-of-a-kind visual development environment which eases the development of semantically interoperable applications in smart citites. The development environment comes with a range of visual tools, which enable the assembly of non-trivial data-driven applications in smart cities, including applications that leverage data streams from diverse IoT systems. Moreover, these tools allow developers to leverage the functionalities and building blocks of the presented architecture. Overall, the introduced visual environment advances the state of the art in IoT developments for smart cities towards the direction of semantic interoperability for data driven applications

Background/aims To report the long-term anatomical and functional outcomes of patients with centre-involved diabetic macular oedema (DME) treated with intravitreal bevacizumab (IVB). Methods Retrospective case series. Patients diagnosed with centre-involved DME that were treated with at least one injection of 1.25 mg IVB and had a minimum follow-up of 60 months. Patients underwent measurement of best-corrected visual acuity (BCVA), ophthalmoscopy, optical coherence tomography and fluorescein angiography at baseline, 6-month, 12-month, 24-month, 36-month, 48-month and 60-month visits. The paired samples t test was used to compare the central macular thickness (CMT) and BCVA with baseline values. Statistical significance was indicated by p Results Two hundred and one consecutive patients (296 eyes) were included. The mean number of IVB injections per eye was 8.4±7.1 (range: 1–47 injections). At 5 years, the BCVA remained stable at 20/100 (logarithm of the minimum angle of resolution=0.7±0.4). Eighty-six (29%) eyes improved ≥2 lines of BCVA, 129 (43.6%) eyes remained stable and 81 (27.4%) eyes lost ≥2 lines of BCVA at 60 months. Mean CMT decreased from 403.5±142.2 μm at baseline to 313.7±117.7 μm over 5 years follow-up (p≤0.0001). Conclusions The early visual gains due to IVB were not maintained 5 years after treatment.

The endosomal sorting complexes required for transport (ESCRT) machinery mediates the physical separation between daughter cells during cytokinetic abscission. This process is regulated by the abscission checkpoint, a genome protection mechanism that relies on Aurora B and the ESCRT-III subunit CHMP4C to delay abscission in response to chromosome missegregation. In this study, we show that Unc-51-like kinase 3 (ULK3) phosphorylates and binds ESCRT-III subunits via tandem MIT domains, and thereby, delays abscission in response to lagging chromosomes, nuclear pore defects, and tension forces at the midbody. Our structural and biochemical studies reveal an unusually tight interaction between ULK3 and IST1, an ESCRT-III subunit required for abscission. We also demonstrate that IST1 phosphorylation by ULK3 is an essential signal required to sustain the abscission checkpoint and that ULK3 and CHMP4C are functionally linked components of the timer that controls abscission in multiple physiological situations.

The "class E" vacuolar protein sorting (VPS) pathway mediates sorting of ubiquitinated cargo into the forming vesicles of the multivesicular bodies (MVB), and it is essential for down-regulation of signaling by growth factors and budding of enveloped viruses such as Ebola and HIV-1. Work in yeast has identified DOA4 as a gene that is recruited by the class E machinery to remove ubiquitin from the endosomal cargo before it is incorporated into MVB vesicles, but the identity of the mammalian counterpart is unclear. Here we report the interaction of AMSH (associated molecule with the SH3 domain of STAM), an endosomal deubiquitinating enzyme, with the endodomal sorting complex required for transport (ESCRT-III) subunits CHMP1A, CHMP1B, CHMP2A, and CHMP3. We also show that a catalytically inactive AMSH inhibits retroviral budding in a dominant-negative manner and induces the accumulation of ubiquitinated forms of an endosomal cargo, namely murine leukemia virus Gag. Finally, VPS4 and AMSH compete for binding to the C-terminal regions of CHMP1A and CHMP1B, revealing a coordinated interaction with ESCRT-III. Taken together, these results are consistent with a role of AMSH in the deubiquitination of the endosomal cargo preceding lysosomal degradation.

Human immunodeficiency virus type 1 (HIV-1) Gag multimerization and membrane binding are required for particle formation. However, it is unclear what constitutes a minimal plasma membrane-specific targeting signal and what role the matrix (MA) globular head and other Gag domains play in membrane targeting. Here, we use membrane flotation and microscopic analysis of Gag deletion mutants to demonstrate that the HIV-1 MA globular head inhibits a plasma membrane-specific targeting signal contained within the six amino-terminal MA residues. MA-mediated inhibition is relieved by concentration-dependent Gag multimerization and imparts a high degree of cooperativity on Gag-membrane association. This cooperativity may confer temporal and spatial regulation on HIV-1 assembly.

Rupture of the nuclear envelope (NE) during interphase is thought to be an infrequent event in healthy cells. Two papers recently published in Science describe the transient disruption of the NE continuity in cells migrating through confined spaces, and uncover an essential role for the Endosomal Sorting Complex Required for Transport (ESCRT) machinery in the resealing of these nuclear discontinuities.

The release of enveloped viruses from infected cells often requires a virally encoded activity, termed a late-budding domain (L domain), encoded by essential PTAP, PPXY, or YPDL sequence motifs. PTAP-type L domains recruit one of three endosomal sorting complexes required for transport (ESCRT-I). However, subsequent events in viral budding are poorly defined, and neither YPDL nor PPXY-type L domains require ESCRT-I. Here, we show that ESCRT-I and other class E vacuolar protein sorting (VPS) factors are linked by a complex series of protein–protein interactions. In particular, interactions between ESCRT-I and ESCRT-III are bridged by AIP-1/ALIX, a mammalian orthologue of the yeast class E VPS factor, Bro1. Expression of certain ESCRT-III components as fusion proteins induces a late budding defect that afflicts all three L-domain types, suggesting that ESCRT-III integrity is required in a general manner. Notably, the prototype YPDL-type L domain encoded by equine infectious anemia virus (EIAV) acts by recruiting AIP-1/ALIX and expression of a truncated form of AIP-1/ALIX or small interfering RNA-induced AIP-1/ALIX depletion specifically inhibits EIAV YPDL-type L-domain function. Overall, these findings indicate that L domains subvert a subset of class E VPS factors to mediate viral budding, some of which are required for each of the L-domain types, whereas others apparently act as adaptors to physically link specific L-domain types to the class E VPS machinery.