126 research outputs found

    A hierarchical AI-based control plane solution for multitechnology deterministic networks

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    Following the Industry 4.0 vision of a full digitiSation of the industry, time-critical services and applications, allowing network infrastructures to deliver information with determinism and reliability, are becoming more and more relevant for a set of vertical sectors. As a consequence, deterministic network solutions are progressively emerging, albeit they are still bounded to specific technological domains. Even considering the existence of interconnected deterministic networks, the provision of an end-to-end (E2E) deterministic service over them must rely on a specific control plane architecture, capable of seamlessly integrate and control the underlying multi-technology data plane. In this work, we envision such a control plane solution, extending previous works and exploiting several innovations and novel architectural concepts. The proposed control architecture is service-centric, in order to provide the necessary flexibility, scalability, and modularity to deal with a heterogenous data plane. The architecture is hierarchical and encompasses a set of management platforms to interact with specific network technologies overarched by an E2E platform for the management, monitoring, and control of E2E deterministic services. Furthermore, Artificial Intelligence (AI) and Digital Twinning are used to enable network predictability and automation, as well as smart resource allocation, to ensure service reliability in dynamic scenarios where existing services may terminate and new ones may need to be deployed

    Novel analgesic/anti-inflammatory agents: 1,5-diarylpyrrole nitrooxyalkyl ethers and related compounds as cyclooxygenase-2 inhibiting nitric oxide donors

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    A series of 3-substituted 1,5-diarylpyrroles bearing a nitrooxyalkyl side chain linked to different spacers were designed. New classes of pyrrole-derived nitrooxyalkyl inverse esters, carbonates, and ethers (7-10) as COX-2 selective inhibitors and NO donors were synthesized and are herein reported. By taking into account the metabolic conversion of nitrooxyalkyl ethers (9, 10) into corresponding alcohols, derivatives 17 and 18 were also studied. Nitrooxy derivatives showed NO-dependent vasorelaxing properties, while most of the compounds proved to be very potent and selective COX-2 inhibitors in in vitro experimental models. Further in vivo studies on compounds 9a,c and 17a highlighted good anti-inflammatory and antinociceptive activities. Compound 9c was able to inhibit glycosaminoglycan (GAG) release induced by interleukin-1β (IL-1β), showing cartilage protective properties. Finally, molecular modeling and (1)H- and (13)C-NMR studies performed on compounds 6c,d, 9c, and 10b allowed the right conformation of nitrooxyalkyl ester and ether side chain of these molecules within the COX-2 active site to be assessed

    Characterization of Brain Lysosomal Activities in GBA-Related and Sporadic Parkinson’s Disease and Dementia with Lewy Bodies

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    Mutations in the GBA gene, encoding the lysosomal hydrolase glucocerebrosidase (GCase), are the most common known genetic risk factor for Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). The present study aims to gain more insight into changes in lysosomal activity in different brain regions of sporadic PD and DLB patients, screened for GBA variants. Enzymatic activities of GCase, β-hexosaminidase, and cathepsin D were measured in the frontal cortex, putamen, and substantia nigra (SN) of a cohort of patients with advanced PD and DLB as well as age-matched non-demented controls (n = 15/group) using fluorometric assays. Decreased activity of GCase (− 21%) and of cathepsin D (− 15%) was found in the SN and frontal cortex of patients with PD and DLB compared to controls, respectively. Population stratification was applied based on GBA genotype, showing substantially lower GCase activity (~ − 40%) in GBA variant carriers in all regions. GCase activity was further significantly decreased in the SN of PD and DLB patients without GBA variants in comparison to controls without GBA variants. Our results show decreased GCase activity in brains of PD and DLB patients with and without GBA variants, most pronounced in the SN. The results of our study confirm findings from previous studies, suggesting a role for GCase in GBA-associated as well as sporadic PD and DLB

    Proteomics Comparison of Cerebrospinal Fluid of Relapsing Remitting and Primary Progressive Multiple Sclerosis

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    Background: Based on clinical representation of disease symptoms multiple sclerosis (MScl) patients can be divided into two major subtypes; relapsing remitting (RR) MScl (85-90%) and primary progressive (PP) MScl (10-15%). Proteomics analysis of cerebrospinal fluid (CSF) has detected a number of proteins that were elevated in MScl patients. Here we specifically aimed to differentiate between the PP and RR subtypes of MScl by comparing CSF proteins. Methodology/Principal Findings: CSF samples (n = 31) were handled according to the same protocol for quantitative mass spectrometry measurements we reported previously. In the comparison of PP MScl versus RR MScl we observed a number of differentially abundant proteins, such as protein jagged-1 and vitamin D-binding protein. Protein jagged-1 was over three times less abundant in PP MScl compared to RR MScl. Vitamin D-binding protein was only detected in the RR MScl samples. These two proteins were validated by independent techniques (western blot and ELISA) as differentially abundant in the comparison between both MScl types. Conclusions/Significance: The main finding of this comparative study is the observation that the proteome profiles of CSF in PP and RR MScl patients overlap to a large extent. Still, a number of differences could be observed. Protein jagged-1 is a ligand for multiple Notch receptors and involved in the mediation of Notch signaling. It is suggested in literature that the Notch pathway is involved in the remyelination of MScl lesions. Aberration of normal homeostasis of Vitamin D, of which approximately 90% is bound to vitamin D-binding protein, has been widely implicated in MScl for some years now. Vitamin D directly and indirectly regulates the differentiation, activation of CD4+ T-lymphocytes and can prevent the development of autoimmune processes, and so it may be involved in neuroprotective elements in MScl

    Insight of brain degenerative protein modifications in the pathology of neurodegeneration and dementia by proteomic profiling

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    New 1-[quinolyl(4)]-1,2,3-triazoles: synthesis and evaluation of antiinflammatory and analgesic properties. II

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    Several 1-[quinolyl(4)]-1,2,3-triazoles were synthesized by 1,3-dipolar cycloaddition of 4-azidoquinolines with activated methylene compounds. The synthesized compounds, tested for antiinflammatory and analgesic activities, resulted moderately active as antiinflammatories, but with a very interesting analgesic activity, sometimes higher than that of indomethacin, used as reference drug. Some of the triazole derivatives were evaluated also as antimicrobial, but none of them exhibited activity
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