An integrated view of theiInfluence of temperature, pressure, and humidity on the stability of trimorphic cysteamine hydrochloride

Understanding the phase behavior of pharmaceuticals is important for dosage form development and regulatory requirements, in particular after the incident with ritonavir. In the present paper, a comprehensive study of the solid-state phase behavior of cysteamine hydrochloride used in the treatment of nephropathic cystinosis and recently granted orphan designation by the European Commission is presented employing (high-pressure) calorimetry, water vapor sorption, and X-ray diffraction as a function of temperature. A new crystal form (I2/a, form III) has been discovered, and its structure has been solved by X-ray powder diffraction, while two other crystalline forms are already known. The relative thermodynamic stabilities of the commercial form I and of the newly discovered form III have been established; they possess an overall enantiotropic phase relationship, with form I stable at room temperature and form III stable above 37 degrees C. Its melting temperature was found at 67.3 +/- 0.5 degrees C. Cysteamine hydrochloride is hygroscopic and immediately forms a concentrated saturated solution in water with a surprisingly high concentration of 47.5 mol % above a relative humidity of 35%. No hydrate has been observed. A temperature composition phase diagram is presented that has been obtained with the unary pressure temperature phase diagram, measurements, and calculations. For development, form I would be the best form to use in any solid dosage form, which should be thoroughly protected against humidity.Postprint (author's final draft

Etude de la degradation des coques en materiaux composites utilisees dans les transducteurs flextensionnels a l'aide de la methode des elements finis

SIGLEAvailable from INIST (FR), Document Supply Service, under shelf-number : TD 82247 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

EAOA: Energy-Aware Grid-Based 3D-Obstacle Avoidance in Coverage Path Planning for UAVs

The presence of obstacles like a tree, buildings, or birds along the path of a drone has the ability to endanger and harm the UAV’s flight mission. Avoiding obstacles is one of the critical challenging keys to successfully achieve a UAV’s mission. The path planning needs to be adapted to make intelligent and accurate avoidance online and in time. In this paper, we propose an energy-aware grid based solution for obstacle avoidance (EAOA). Our work is based on two phases: in the first one, a trajectory path is generated offline using the area top-view. The second phase depends on the path obtained in the first phase. A camera captures a frontal view of the scene that contains the obstacle, then the algorithm determines the new position where the drone has to move to, in order to bypass the obstacle. In this paper, the obstacles are static. The results show a gain in energy and completion time using 3D scene information compared to 2D scene information

PPS: Energy-Aware Grid-Based Coverage Path Planning for UAVs Using Area Partitioning in the Presence of NFZs

Area monitoring and surveillance are some of the main applications for Unmanned Aerial Vehicle (UAV) networks. The scientific problem that arises from this application concerns the way the area must be covered to fulfill the mission requirements. One of the main challenges is to determine the paths for the UAVs that optimize the usage of resources while minimizing the mission time. Different approaches rely on area partitioning strategies. Depending on the size and complexity of the area to monitor, it is possible to decompose it exactly or approximately. This paper proposes a partitioning method called Parallel Partitioning along a Side (PPS). In the proposed method, grid-mapping and grid-subdivision of the area, as well as area partitioning are performed to plan the UAVs path. An extra challenge, also tackled in this work, is the presence of non-flying zones (NFZs). These zones are areas that UAVs must not cover or pass over it. The proposal is extensively evaluated, in comparison with existing approaches, to show that it enables UAVs to plan paths with minimum energy consumption, number of turns and completion time while at the same time increases the quality of coverage

Permutation Tests for Metaheuristic Algorithms

Many metaheuristic approaches are inherently stochastic. In order to compare such methods, statistical tests are needed. However, choosing an appropriate test is not trivial, given that each test has some assumptions about the distribution of the underlying data that must be true before it can be used. Permutation tests (P-Tests) are statistical tests with minimal number of assumptions. These tests are simple, intuitive and nonparametric. In this paper, we argue researchers in the field of metaheuristics to adopt P-Tests to compare their algorithms. We define two statistic tests and then present an algorithm that uses them to compute the p-value. The proposed process is used to compare 5 metaheuristic algorithms on 10 benchmark functions. The resulting p-values are compared with the p-values of two widely used statistical tests. The results show that the proposed P-test is generally consistent with the classical tests, but more conservative in few cases

Permutation Tests for Metaheuristic Algorithms

Many metaheuristic approaches are inherently stochastic. In order to compare such methods, statistical tests are needed. However, choosing an appropriate test is not trivial, given that each test has some assumptions about the distribution of the underlying data that must be true before it can be used. Permutation tests (P-Tests) are statistical tests with minimal number of assumptions. These tests are simple, intuitive and nonparametric. In this paper, we argue researchers in the field of metaheuristics to adopt P-Tests to compare their algorithms. We define two statistic tests and then present an algorithm that uses them to compute the p-value. The proposed process is used to compare 5 metaheuristic algorithms on 10 benchmark functions. The resulting p-values are compared with the p-values of two widely used statistical tests. The results show that the proposed P-test is generally consistent with the classical tests, but more conservative in few cases

Substrate-induced ubiquitylation and endocytosis of yeast amino acid permeases.

Many plasma membrane transporters are downregulated by ubiquitylation, endocytosis, and delivery to the lysosome in response to various stimuli. We report here that two amino acid transporters of Saccharomyces cerevisiae, the general amino acid permease (Gap1) and the arginine-specific permease (Can1), undergo ubiquitin-dependent downregulation in response to their substrates and that this downregulation is not due to intracellular accumulation of the transported amino acids but to transport catalysis itself. Following an approach based on permease structural modeling, mutagenesis, and kinetic parameter analysis, we obtained evidence that substrate-induced endocytosis requires transition of the permease to a conformational state preceding substrate release into the cell. Furthermore, this transient conformation must be stable enough, and thus sufficiently populated, for the permease to undergo efficient downregulation. Additional observations, including the constitutive downregulation of two active Gap1 mutants altered in cytosolic regions, support the model that the substrate-induced conformational transition inducing endocytosis involves remodeling of cytosolic regions of the permeases, thereby promoting their recognition by arrestin-like adaptors of the Rsp5 ubiquitin ligase. Similar mechanisms might control many other plasma membrane transporters according to the external concentrations of their substrates.SCOPUS: ar.jinfo:eu-repo/semantics/publishe