Optimal one-dimensional coverage by unreliable sensors

This paper regards the problem of optimally placing unreliable sensors in a one-dimensional environment. We assume that sensors can fail with a certain probability and we minimize the expected maximum distance from any point in the environment to the closest active sensor. We provide a computational method to find the optimal placement and we estimate the relative quality of equispaced and random placements. We prove that the former is asymptotically equivalent to the optimal placement when the number of sensors goes to infinity, with a cost ratio converging to 1, while the cost of the latter remains strictly larger.Comment: 21 pages 2 figure

Apeced in Turkey: a case report and insights on genetic and phenotypic variability

APECED is a rare monogenic recessive disorder caused by mutations in the AIRE gene. In this manuscript, we report a male Turkish patient with APECED syndrome who presented with chronic mucocutaneous candidiasis associated with other autoimmune manifestations developed over the years. The presence of the homozygous R257X mutation of the AIRE gene confirmed the diagnosis of APECED syndrome. We further performed literature review in 23 published Turkish APECED patients and noted that Finnish major mutation R257X is common in Turks. In particular, we assessed retrospectively how often the Ferre/Lionakis criteria would have resulted in earlier diagnosis in Finns, Sardinians and Turks in respect to the classic criteria. Since an earlier diagnosis could have been possible in 18.8% of Turkish, in 23.8% of Sardinian and 38.55% of Finnish patients we reviewed from literature, Ferre/Lionakis criteria could indeed allow in future earlier initiation of immunomodulatory treatments, if found effective in future studies

A novel homozygous mutation of the AIRE gene in an APECED patient from Pakistan: case report and review of the literature

Autoimmune-poly-endocrinopathy-candidiasis-ectodermal-dystrophy syndrome (APECED) is a rare monogenic recessive disorder caused by mutations in the autoimmune regulator (AIRE) gene. Criteria for the diagnosis of APECED are the presence of two of the following disorders: chronic mucocutaneous candidiasis (CMC), chronic hypoparathyroidism (CHP), and Addison's disease. APECED develops at high incidence in Finns, Sardinians, and Iranian Jews and presents with a wide range of clinical phenotypes and genotypes. In this manuscript, we report the clinical, endocrinological, and molecular features of a 16-year-old female patient from Pakistan living in Italy and presenting the major APECED clinical manifestations CMC, CHP, and primary adrenal insufficiency. Premature ovarian failure, chronic bronchopneumopathy, vitiligo, Hashimoto's thyroiditis emerged as associated diseases. In our patient, AIRE gene screening revealed the novel c.396G > C (p. Arg132Ser; p. R132S) mutation in homozygosity thus confirming APECED diagnosis. This is the first reported mutation within the nuclear localization signal (NLS) that is associated with APECED. The NLS mutation affects the nuclear import of classical transcription factors through nuclear pore by recognition of nuclear import receptors, the importin a molecules. By displaying crystal structures of the peptide containing the KRK basic residue cluster bound to a importins, we show that p. R132S replacement in 131-KRK-133 does not reproduce these interactions. Thus, we propose that the novel mutation exerts its pathogenetic effect by impairing the nuclear import of the Aire protein. The present case report is added to a limited series of Pakistani APECED patients who we reviewed from the scientific literature, mostly diagnosed on clinical findings

Distributed averaging on digital erasure networks

International audience; Iterative distributed algorithms are studied for computing arithmetic averages over networks of agents connected through memoryless broadcast erasure channels. These algorithms do not require the agents to have any knowledge about the global network structure or size. Almost sure convergence to state agreement is proved, and the communication and computational complexities of the algorithms are analyzed. Both the number of transmissions and the number of computations performed by each agent of the network are shown to grow not faster than poly-logarithmically in the desired precision. The impact of the graph topology on the algorithms' performance is analyzed as well. Moreover, it is shown how, in the presence of noiseless communication feedback, one can modify the algorithms, significantly improving their performance versus complexity trade-off

Neural Precursor Cells as a potential therapeutic approach for Rett Syndrome: identification of the involved molecular mechanisms

Rett syndrome (RTT) is a rare neurodevelopmental disorder, mostly caused by MECP2 mutations, representing the leading cause of severe intellectual disability in females. Unfortunately, no cure is available. Considering the effectiveness of NPCs in the treatment of other neurological and neurodevelopmental diseases, we decided to investigate their therapeutic potential in RTT. Our research demonstrated their efficacy in both RTT in vitro and in vivo mouse models. Through a transwell-based co-culture system, we observed that NPCs promote morphological and synaptic rescues in Mecp2 null neurons. In vivo, we demonstrated a significant amelioration of the cognitive and motor defects of RTT mice, together with an increased lifespan, after NPCs transplantation. The results highlighted that NPCs-mediated beneficial effects arise through “bystander” and paracrine mechanisms: by sensing the pathological environment, they secrete beneficial factors that promote immunomodulation, neuroprotection and brain plasticity. To identify the molecular mechanisms set in motion by NPCs, we performed bulk RNA sequencing analyses on both models. Even if one candidate molecule has been identified and its efficacy validated, more studies are ongoing to further clarify other pathways modulated in KO neurons in presence of NPCs. All data will be presented in the poster session to illustrate the value of this cellular approach in treating RTT and/or in identifying new defective pathways with putative therapeutic value

Individual based SIS models on (not so) dense large random networks

Starting from a stochastic individual-based description of an SIS epidemic spreading on a random network, we study the dynamics when the size n of the network tends to infinity. We recover in the limit an infinite-dimensional integro-differential equation studied by Delmas, Dronnier and Zitt (2022) for an SIS epidemic propagating on a graphon. Our work covers the case of dense and sparse graphs, provided that the number of edges grows faster than n, but not the case of very sparse graphs with O(n) edges. In order to establish our limit theorem, we have to deal with both the convergence of the random graphs to the graphon and the convergence of the stochastic process spreading on top of these random structures: in particular, we propose a coupling between the process of interest and an epidemic that spreads on the complete graph but with a modified infection rate. Keywords: random graph, mathematical models of epidemics, measure-valued process, large network limit, limit theorem, graphon.Comment: Acknowledgments: This work was financed by the Labex B\'ezout (ANR-10-LABX-58) and the COCOON grant (ANR-22-CE48-0011), and by the platform MODCOV19 of the National Institute of Mathematical Sciences and their Interactions of CNRS. 32 pages, including an appendix of 6 page

Tracing the path of Quorum sensing molecules in cystic fibrosis mucus in a biomimetic in vitro permeability platform

P. aeruginosa employs specific quorum sensing (QS) mechanisms to orchestrate biofilm formation, enhancing resistance to host defences. In physiological conditions, QS molecules permeate the lung environment and cellular membrane to reach the cytoplasmic Aryl Hydrocarbon Receptor (AhR) that is pivotal for activating the immune response against infection. In pathological conditions like cystic fibrosis (CF) this interkingdom communication is altered, favouring P. aeruginosa persistence and chronic infection. Here, we aim to investigate the molecular journey of QS molecules from CF-like environments to the cytoplasm by quantifying via HPLC-MS the permeability of selected QS molecules (quinolones, lactones, and phenazines) through in vitro models of the two main biological lung barriers: CF-mucus and cellular membrane. While QS molecules not activating AhR exhibit intermediate permeability through the cellular membrane model (PAMPA) (1.0–4.0 × 10−6 cm/s), the AhR-activating molecule (pyocyanin) shows significantly higher permeability (8.6 ± 1.4 × 10−6 cm/s). Importantly, combining the CF mucus model with PAMPA induces a 50% decrease in pyocyanin permeability, indicating a strong mucus-shielding effect with pathological implications in infection eradication. This study underscores the importance of quantitatively describing the AhR-active bacterial molecules, even in vitro, to offer new perspectives for understanding P. aeruginosa virulence mechanisms and for proposing new antibacterial therapeutic approaches

Potential Use of Tea Tree Oil as a Disinfectant Agent against Coronaviruses: A Combined Experimental and Simulation Study

: The COVID-19 pandemic has highlighted the relevance of proper disinfection procedures and renewed interest in developing novel disinfectant materials as a preventive strategy to limit SARS-CoV-2 contamination. Given its widely known antibacterial, antifungal, and antiviral properties, Melaleuca alternifolia essential oil, also named Tea tree oil (TTO), is recognized as a potential effective and safe natural disinfectant agent. In particular, the proposed antiviral activity of TTO involves the inhibition of viral entry and fusion, interfering with the structural dynamics of the membrane and with the protein envelope components. In this study, for the first time, we demonstrated the virucidal effects of TTO against the feline coronavirus (FCoVII) and the human coronavirus OC43 (HCoV-OC43), both used as surrogate models for SARS-CoV-2. Then, to atomistically uncover the possible effects exerted by TTO compounds on the outer surface of the SARS-CoV-2 virion, we performed Gaussian accelerated Molecular Dynamics simulations of a SARS-CoV-2 envelope portion, including a complete model of the Spike glycoprotein in the absence or presence of the three main TTO compounds (terpinen-4-ol, γ-terpinene, and 1,8-cineole). The obtained results allowed us to hypothesize the mechanism of action of TTO and its possible use as an anti-coronavirus disinfectant agent

Nasal Microbiota in RSV Bronchiolitis

Respiratory Syncytial Virus (RSV) is the leading cause of bronchiolitis, and the severity may be influenced by the bacterial ecosystem. Our aim was to analyze the nasal microbiota from 48 infants affected by bronchiolitis from RSV virus and 28 infants with bronchiolitis but negative for the virus. Results showed a significantly lower biodiversity in the RSV-positive group with respect to the RSV-negative group, a specific microbial profile associated with the RSV-positive group different from that observed in the negative group, and significant modifications in the relative abundance of taxa in the RSV-positive group, as well as in the RSV-A group, with respect to the negative group. Furthermore, microbial network analyses evidenced, in all studied groups, the presence of two predominant sub-networks characterized by peculiar inter- and intra-group correlation patterns as well as a general loss of connectivity among microbes in the RSV-positive group, particularly in the RSV-A group. Our results indicated that infants with more severe bronchiolitis disease, caused by RSV-A infection, present significant perturbations of both the nasal microbiota structure and the microbial relationships. Patients with a milder bronchiolitis course (RSV-B-infected and patients who have cleared the virus) presented less severe alterations