HJB-RBF Based Approach for the Control of PDEs

Semi-Lagrangian schemes for the discretization of the dynamic programming principle are based on a time discretization projected on a state-space grid. The use of a structured grid makes this approach not feasible for high-dimensional problems due to the curse of dimensionality. Here, we present a new approach for infinite horizon optimal control problems where the value function is computed using radial basis functions by the Shepard moving least squares approximationmethod on scattered grids.We propose a newmethod to generate a scattered mesh driven by the dynamics and the selection of the shape parameter in the RBF using an optimization routine. This mesh will help to localize the problem and approximate the dynamic programming principle in high dimension. Error estimates for the value function are also provided. Numerical tests for high dimensional problems will show the effectiveness of the proposed method

Rotatividade na hotelaria de Curitiba : o caso do hotel "X"

Orientador : José Manoel Gonçalves GândaraMonografia (especializaçao) - Universidade Federal do Paraná, Setor de Ciencias Humanas Letras e Artes, Curso de Especializaçao em Planejamento e Gestao do TurismoInclui bibliografi

Safety and activity of anti-mesothelin antibody–drug conjugate anetumab ravtansine in combination with pegylated-liposomal doxorubicin in platinum-resistant ovarian cancer: multicenter, phase Ib dose escalation and expansion study

Ovarian cancerCàncer d'ovariCáncer de ovarioObjectives Anetumab ravtansine is an antibody-drug conjugate consisting of a fully human anti-mesothelin monoclonal antibody conjugated to cytotoxic maytansinoid tubulin inhibitor DM4. Mesothelin is highly expressed in ovarian cancer. This phase Ib study determines the safety, pharmacokinetics, and anti-tumor activity of anetumab ravtansine and pegylated liposomal doxorubicin in mesothelin-expressing platinum-resistant ovarian cancer. Methods Anetumab ravtansine (5.5 or 6.5 mg/kg) and pegylated liposomal doxorubicin (30 mg/m2) were administered intravenously every 3 weeks to 65 patients with platinum-resistant epithelial ovarian cancer. Mesothelin expression was assessed by central immunohistochemistry. Adverse events, tumor response (RECIST 1.1), and progression-free survival were determined. Biomarker samples were assessed by ELISA and next-generation sequencing. Results In dose escalation, nine patients received anetumab ravtansine across two doses (5.5 or 6.5 mg/kg). The maximum tolerated dose of anetumab ravtansine was 6.5 mg/kg every 3 weeks and no dose-limiting toxicities were observed. In dose expansion, 56 patients were treated at the maximum tolerated dose. The most common treatment-emergent adverse events of any grade were nausea (47.7%), decreased appetite (43.1%), fatigue (38.5%), diarrhea (32.3%), and corneal disorder (29.2%). In all treated patients the objective response rate was 27.7% (95% CI 17.3% to 40.2%), including one complete (1.5%) and 17 partial responses (26.2%), with median duration of response of 7.6 (95% CI 3.3 to 10.2) months and median progression-free survival of 5.0 (95% CI 3.2 to 6.0) months. In an exploratory analysis of a sub-set of patients (n=19) with high mesothelin expression who received ≤3 prior lines of systemic therapy, the objective response rate was 42.1% (95% CI 20.3% to 66.5%) with a median duration of response of 8.3 (95% CI 4.1 to 12.0) months and median progression-free survival of 8.5 (95% CI 4.0 to 11.4) months. Conclusions Anetumab ravtansine and pegylated liposomal doxorubicin showed tolerability and promising clinical activity. These results established the dose schedule and the mesothelin-positive target population of this combination for a phase III study in platinum-resistant ovarian cancer.This study was funded by Bayer AG

Vaccination with HPV-18 E7-pulsed dendritic cells in a patient with metastatic cervical cancer [7]

To the Editor: The anagement of disseminated carcinoma of the cervix that is no longer amenable to control with surgery or radiation therapy has not improved significantly with the advent of modern chemotherapy. The one-year survival rate remains between 10 percent and 15 percent. Studies have provided a rationale for using dendritic cells as natural adjuvants for human immunotherapy

Autonomous and Human-Driven Vehicles Interacting in a Roundabout: A Quantitative and Qualitative Evaluation

Optimizing traffic dynamics in an evolving transportation landscape is crucial, particularly in scenarios where autonomous vehicles (AVs) with varying levels of autonomy coexist with human-driven cars. While optimizing Reinforcement Learning (RL) policies for such scenarios is becoming more and more common, little has been said about realistic evaluations of such trained policies. This paper presents an evaluation of the effects of AVs penetration among human drivers in a roundabout scenario, considering both quantitative and qualitative aspects. In particular, we learn a policy to minimize traffic jams (i.e., minimize the time to cross the scenario) and to minimize pollution in a roundabout in Milan, Italy. Through empirical analysis, we demonstrate that the presence of AVs} can reduce time and pollution levels. Furthermore, we qualitatively evaluate the learned policy using a cutting-edge cockpit to assess its performance in near-real-world conditions. To gauge the practicality and acceptability of the policy, we conduct evaluations with human participants using the simulator, focusing on a range of metrics like traffic smoothness and safety perception. In general, our findings show that human-driven vehicles benefit from optimizing AVs dynamics. Also, participants in the study highlight that the scenario with 80% AVs is perceived as safer than the scenario with 20%. The same result is obtained for traffic smoothness perception

GASTRO PROTECTIVE AND ANTI-HELICOBACTER PYLORI EFFECTS OF A FLAVONOID RICH FRACTION OBTAINED FROM ACHYROCLINE SATUREOIDES (LAM) D.C.

Objectives: The study aimed to investigate the gastroprotective effects of a flavonoid rich fraction (FRF) obtained from Achyrocline satureoides. Methods: The following protocols were employed: ethanol and NSAID-induced ulcer, ligature pylorus model, and free mucus quantification. Nitric oxide (NO) and sulfhydryl group participation were observed by pretreatment with L-NAME or NEM. Besides, it was assayed the acetic acid-induced chronic ulcer andthe anti-Helicobacter pyloriactivity in vitro. Results: The phytochemical profile of FRF showed three main flavonoids, luteolin, quercetin and 3-O-methyl-quercetin. The administration of FRF was able to prevent the damage evoked by ethanol and NSAID-induced ulcer models. The pH and concentration of H+ in the stomach were not modified by FRF treatment. However, the FRF treatment induces mucus secretion. The effect presented by FRF was mediated by nitric oxide (NO). In chronic ulcer model FRF reduced significantly the lesion area, promoting a cure ratio of 65.42±13.00, a similar data presented by cimetidine treated animals (61.35±11.88). Using an in vitro assay was observed that FRF at 500 µg/mL was able to inhibit bacterial growth. Conclusions: The results show that FRF provided a significant gastroprotective and ulcer healing activity, mainly due to their capacity to enhance mucus secretion

AMBIENTE DE ENRAIZAMENTO E SUBSTRATOS NA MINIESTAQUIA DE ERVA-MATE

The inexistence of one method of vegetative propagation for erva-mate of efficient form difficult the silvicultural advances of this species. The experiment was carried in the Embrapa Florestas, with the objective of evaluating the effect of initial environment and substratum compositions in the survival, rooting and development of minicuttings of erva-mate. Shoots had been collected of ministumps produced for seed and cultivated in minigarden in semi-hydroponic system. The work was conducted in the delineation blocks in the bifactorial arrangement, with six substratum compositions: S1 - substratum for rooting with base of rind of Pinus, S2 - substratum for rooting with base of rind of Pinus and vermiculite, S3 - carbonized rind of rice + fine vermiculite + substratum for rooting with base of rind of Pinus and vermiculite (1:1:1 v/v), S4 - carbonized rind of rice + substratum for rooting with base of rind of Pinus and vermiculite (1:1 v/v), S5 - carbonized rind of rice + fine vermiculite (1:1 v/v) and S6 - coconut fiber and, two environments of rooting: automatized greenhouse and simple greenhouse. The results indicated that independent of the analyzed variable, the greenhouse with control oh humidity and temperature was superior to the environment without control and that the substratum formed by the mixture of carbonized rind of rice + substratum for rooting with base of rind of Pinus and vermiculite (1:1 v/v) is advised to be used in two environments for the rooting of juvenile minicuttings of erva-mate.Devido à falta de um método que possibilite a propagação vegetativa da erva-mate de forma eficiente, foi conduzido na Embrapa Florestas, um estudo com objetivo de avaliar o efeito do ambiente de enraizamento e composições de substrato na sobrevivência, enraizamento e crescimento de miniestacas de erva-mate. As brotações foram coletadas de minicepas produzidas via semente e manejadas em sistema semi-hidropônico. O experimento foi conduzido no delineamento blocos ao acaso no arranjo bifatorial, sendo os níveis constituídos de seis diferentes composições de substratos: S1 - substrato para enraizamento a base de casca de Pinus, S2 - substrato para enraizamento a base de casca de Pinus e vermiculita, S3 - casca de arroz carbonizada + vermiculita fina + substrato para enraizamento a base de casca de Pinus e vermiculita (1:1:1 v/v), S4 - casca de arroz carbonizada + substrato para enraizamento a base de casca de Pinus e vermiculita (1:1 v/v), S5 - casca de arroz carbonizada + vermiculita fina (1:1 v/v) e S6 - fibra de coco e, dois ambientes de enraizamento: casa de vegetação automatizada e casa de vegetação simples. Independente das variáveis analisadas, a casa de vegetação com controle de umidade e temperatura foi superior a casa de vegetação sem controle. O uso do substrato casca de arroz carbonizada + substrato para enraizamento a base de casca de Pinus e vermiculita (1:1 v/v) é aconselhado nos dois ambientes para o enraizamento de miniestacas juvenis de erva-mate

In Silico Analysis of the Multi-Targeted Mode of Action of Ivermectin and Related Compounds

Some clinical studies have indicated activity of ivermectin, a macrocyclic lactone, against COVID-19, but a biological mechanism initially proposed for this anti-viral effect is not applicable at physiological concentrations. This in silico investigation explores potential modes of action of ivermectin and 14 related compounds, by which the infectivity and morbidity of the SARS-CoV-2 virus may be limited. Binding affinity computations were performed for these agents on several docking sites each for models of (1) the spike glycoprotein of the virus, (2) the CD147 receptor, which has been identified as a secondary attachment point for the virus, and (3) the alpha-7 nicotinic acetylcholine receptor (α7nAChr), an indicated point of viral penetration of neuronal tissue as well as an activation site for the cholinergic anti-inflammatory pathway controlled by the vagus nerve. Binding affinities were calculated for these multiple docking sites and binding modes of each compound. Our results indicate the high affinity of ivermectin, and even higher affinities for some of the other compounds evaluated, for all three of these molecular targets. These results suggest biological mechanisms by which ivermectin may limit the infectivity and morbidity of the SARS-CoV-2 virus and stimulate an α7nAChr-mediated anti-inflammatory pathway that could limit cytokine production by immune cells