Distributionally Robust LQG control under Distributed Uncertainty

A new paradigm is proposed for the robustification of the LQG controller against distributional uncertainties on the noise process. Our controller optimizes the closed-loop performances in the worst possible scenario under the constraint that the noise distributional aberrance does not exceed a certain threshold limiting the relative entropy pseudo-distance between the actual noise distribution the nominal one. The main novelty is that the bounds on the distributional aberrance can be arbitrarily distributed along the whole disturbance trajectory. We discuss why this can, in principle, be a substantial advantage and we provide simulation results that substantiate such a principle

Molecular dynamics simulation of human LOX-1 provides an explanation for the lack of OxLDL binding to the Trp150Ala mutant

<p>Abstract</p> <p>Background</p> <p>Dimeric lectin-like oxidized low-density lipoprotein receptor-1 LOX-1 is the target receptor for oxidized low density lipoprotein in endothelial cells. <it>In vivo </it>assays revealed that in LOX-1 the basic spine arginine residues are important for binding, which is lost upon mutation of Trp150 with alanine. Molecular dynamics simulations of the wild-type LOX-1 and of the Trp150Ala mutant C-type lectin-like domains, have been carried out to gain insight into the severe inactivating effect.</p> <p>Results</p> <p>The mutation does not alter the dimer stability, but a different dynamical behaviour differentiates the two proteins. As described by the residues fluctuation, the dynamic cross correlation map and the principal component analysis in the wild-type the two monomers display a symmetrical motion that is not observed in the mutant.</p> <p>Conclusion</p> <p>The symmetrical motion of monomers is completely damped by the structural rearrangement caused by the Trp150Ala mutation. An improper dynamical coupling of the monomers and different fluctuations of the basic spine residues are observed, with a consequent altered binding affinity.</p

Binding to DPF-motif by the POB1 EH domain is responsible for POB1-Eps15 interaction

<p>Abstract</p> <p>Background</p> <p>Eps15 homology (EH) domains are protein interaction modules binding to peptides containing Asn-Pro-Phe (NPF) motifs and mediating critical events during endocytosis and signal transduction. The EH domain of POB1 associates with Eps15, a protein characterized by a striking string of DPF triplets, 15 in human and 13 in mouse Eps15, at the C-terminus and lacking the typical EH-binding NPF motif.</p> <p>Results</p> <p>By screening a multivalent nonapeptide phage display library we have demonstrated that the EH domain of POB1 has a different recognition specificity since it binds to both NPF and DPF motifs. The region of mouse Eps15 responsible for the interaction with the EH domain of POB1 maps within a 18 amino acid peptide (residues 623–640) that includes three DPF repeats. Finally, mutational analysis in the EH domain of POB1, revealed that several solvent exposed residues, while distal to the binding pocket, mediate specific recognition of binding partners through both hydrophobic and electrostatic contacts.</p> <p>Conclusion</p> <p>In the present study we have analysed the binding specificity of the POB1 EH domain. We show that it differs from other EH domains since it interacts with both NPF- and DPF-containing sequences. These unusual binding properties could be attributed to a different conformation of the binding pocket that allows to accommodate negative charges; moreover, we identified a cluster of solvent exposed Lys residues, which are only found in the EH domain of POB1, and influence binding to both NPF and DPF motifs. The characterization of structures of the DPF ligands described in this study and the POB1 EH domain will clearly determine the involvement of the positive patch and the rationalization of our findings.</p

Analysis of Four New Enterococcus faecalis Phages and Modeling of a Hyaluronidase Catalytic Domain from Saphexavirus

Background: Phage therapy (PT), as a method to treat bacterial infections, needs identification of bacteriophages targeting specific pathogenic host. Enterococcus faecalis, a Gram-positive coccus resident in the human gastrointestinal tract, may become pathogenic in hospitalized patients showing acquired resistance to vancomycin and thus representing a possible target for PT. Materials and Methods: We isolated four phages that infect E. faecalis and characterized them by host range screening, transmission electron microscopy, and genome sequencing. We also identified and three-dimensional modeled a new hyaluronidase enzyme. Results: The four phages belong to Siphoviridae family: three Efquatrovirus (namely vB_EfaS_TV51, vB_EfaS_TV54, and vB_EfaS_TV217) and one Saphexavirus (vB_EfaS_TV16). All of them are compatible with lytic cycle. vB_EfaS_TV16 moreover presents a gene encoding for a hyaluronidase enzyme. Conclusions: The identified phages show features suggesting their useful application in PT, particularly the Saphexavirus that may be of enhanced relevance in PT because of its potential biofilm-digestion capability

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

From In Silico Simulation between TGF-β Receptors and Quercetin to Clinical Insight of a Medical Device Containing Allium cepa: Its Efficacy and Tolerability on Post-Surgical Scars

1) objective: keloid and hypertrophic scars are a challenge in clinical management, causing functional and psychological discomfort. these pathological scars are caused by a proliferation of dermal tissue following skin injury. the TGF-beta/smad signal pathway in the fibroblasts and myofibroblasts is involved in the scarring process of skin fibrosis. today, multiple therapeutic strategies that target the TGF-beta/smad signal pathway are evaluated to attenuate aberrant skin scars that are sometimes difficult to manage. we performed a head-to-head, randomized controlled trial evaluating the appearance of the post-surgical scars of 64 subjects after two times daily topical application to compare the effect of a class I pullulan-based medical device containing allium cepa extract 5% and hyaluronic acid 5% gel versus a class I medical device silicone gel on new post-surgical wounds. (2) methods: objective scar assessment using the vancouver scar scale (VSS), POSAS, and other scales were performed after 4, 8, and 12 weeks of treatment and statistical analyses were performed. the trial was registered in clinical trials.gov ( NCT05412745). In parallel, molecular docking simulations have been performed to investigate the role of allium cepa in TGF-beta/smad signal pathway. (3) results: we showed that VSS, POSAS scale, itching, and redness reduced significantly at week 4 and 8 in the subjects using devices containing allium cepa and HA. no statistically significant differences in evaluated scores were noted at 12 weeks of treatment. safety was also evaluated by gathering adverse events related to the application of the gel. subject compliance and safety with the assigned gel were similar between the two study groups. molecular docking simulations have shown how allium cepa could inhibit fibroblasts proliferation and contraction via TGF- beta/smad signal pathway. (4) conclusions: the topical application of a pullulan-based medical device containing allium cepa and HA showed a clear reduction in the local inflammation, which might lead to a reduced probability of developing hypertrophic scars or keloids

Preliminary Evidence of Efficacy, Safety, and Treatment Satisfaction with Tirbanibulin 1% Ointment: A Clinical Perspective on Actinic Keratoses

background: actinic keratosis is a common precancerous skin lesion that can progress into invasive squamous cell carcinomas. many topical treatments for actinic keratoses often have poor tolerability and prolonged duration. Tirbanibulin is a novel synthetic drug with potent antitumor and antiproliferative activities. methods: we conducted a single-center, prospective and observational study using tirbanibulin ointment on a 25 cm2 area for 5 consecutive days on 30 participants with AKs on the face or scalp. They were followed for at least 57 days to assess the safety profile and efficacy of the drug as well as treatment satisfaction. we evaluated six signs of local skin reaction (LSR): erythema, scaling, crusting, swelling, blisters/pustules, and erosions/ulcerations, grading the severity as mild, moderate, or severe. The effectiveness was evaluated both clinically and dermoscopically. the treatment satisfaction was assessed using the treatment satisfaction questionnaire for medication (TSQM 1.4). results: on day 57, 70% of the patients showed a complete clinical and dermoscopic response. The highest scores obtained from the TSQM 1.4 were more evident in the convenience and side effects domains. most LSRs, including erythema (83.3%), scaling (30%), and swelling (3.3%), occurred on day 8 but resolved spontaneously. Conclusion: Tirbanibulin is a viable therapeutic option with a short regimen treatment and good tolerability, which favors therapy adherence

Quercetin pentaacetate inhibits in vitro human respiratory syncytial virus adhesion.

Made available in DSpace on 2020-12-12T01:06:20Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-01-15 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Human respiratory syncytial virus (hRSV) is one of the main etiological agents of diseases of the lower respiratory tract and is often responsible for the hospitalization of children and the elderly. To date, treatments are only palliative and there is no vaccine available. Natural products show exceptional structural diversity and they have played a vital role in drug research. Several investigations focused on applied structural modification of natural products to improved metabolic stability, solubility and biological actions them. Quercetin is a flavonoid that presents several biological activities, including anti-hRSV role. Some works criticize the pharmacological use of Quercetin because it has low solubility and low specificity. In this sense, we acetylated Quercetin structure and we used in vitro and in silico assays to compare anti-hRSV function between Quercetin (Q0) and its derivative molecule (Q1). Q1 shows lower cytotoxic effect than Q0 on HEp-2 cells. In addition, Q1 was more efficient than Q0 to protect HEp-2 cells infected with different multiplicity of infection (0.1–1 MOI). The virucidal effects of Q0 and Q1 suggest interaction between these molecules and viral particle. Dynamic molecular results suggest that Q0 and Q1 may interact with F-protein on hRSV surface in an important region to adhesion and viral infection. Q1 interaction with F-protein showed ΔG= -14.22 kcal/mol and it was more stable than Q0. Additional, MTT and plate assays confirmed that virucidal Q1 effects occurs during adhesion step of cycle hRSV replication. In conclusion, acetylation improves anti-hRSV Quercetin effects because Quercetin pentaacetate could interact with F-protein with lower binding energy and better stability to block viral adhesion. These results show alternative anti-hRSV strategy and contribute to drug discovery and development. Universidade Estadual Paulista UNESP (FCLAssis) Universidade Estadual Paulista UNESP IBILCE Centro Multiusuário de Inovação Biomolecular (CMIB) Universidade Estadual Paulista UNESP IBILCE Department of Biology University of Rome Tor Vergata, Via della Ricerca Scientifica 1 Universidade Estadual Paulista UNESP (FCLAssis) Universidade Estadual Paulista UNESP IBILCE Centro Multiusuário de Inovação Biomolecular (CMIB) Universidade Estadual Paulista UNESP IBILCE FAPESP: 2014/12298-