EATING DISORDERS AND PSYCHOFARMACHOLOGY: RETHINK THE TREATMENT OF EATING DISORDERS

The pharmacological approach to eating disorders (ED) is effective in a few conditions, and to date, no treatment has shown certain efficacy in treating patients with this disorder. Furthermore, attempts to regulate hunger and satiety through modulation pharmacological effects of neurotransmitters and neuropeptides have shown only short-term benefit. However, in light of the serious impact of DCA on patients and the scarcity of non-pharmacological therapeutic approaches, research in this area should not be abandoned, also because new generation "molecules" become increasingly available. Many studies looked at efficacy of antipsychotics, Tryciclics, SSRI, mood stabilizers in the treatment of ED. Gabaergic circuit, the opioid one are extremely involved in the neurohormonal mechanisms of regulation of dietary behaviors and that molecules that influence these circuits could be used in the pharmacological treatment of ED as already happens in the case of Naltrexone, gabapentine or gabaergic drugs

Creases modelling in meshless methods.

PhD ThesesCreases have been recently employed as a cheap and straightforward solution to complex problems, like manufacturing micro-scale 3D components, generating programmable motions or enhancing the energy storage capabilities of polymerbased materials. In particular, creases creation, post-folding deformation and fracture prevention are of critical importance for the success of novel applications. Creases in plates are jump discontinuities in the rotations, and their mechanical behaviour can be reproduced by a hinge-like approximation knowing two parameters: rest opening angle and fold rotational stiffness. These two physical properties change with the material, plate thickness and folding process. Therefore, in principle, one should measure the rest opening angle and the rotational stiffness for each crease. To reduce the amount of experimental work needed to model folded geometries, we developed an analytical model able to predict these two values knowing the elastoplastic properties of the material. We validated our rest opening angle predictions against experimental results. Furthermore, we implemented the hinge-like approximation in a numerical model employing a meshless discretisation taking advantage of a weight function enrichment. The kinematics description and the definition of the strain are capable to reproduce the mechanical response of plates presenting large curvature and large deformation undergoing large rotations in the three-dimensional space. Domains presenting several randomly oriented creases and creases with variable opening angles are simulated. Finally, we show how the presented approach can simulate self-folding structures and crease-crack interactions

The ubiquitin ligase HERC1 regulates cell migration via RAF-dependent regulation of MKK3/p38 signaling

Protein modifications by phosphorylation or ubiquitylation have been selected throughout evolution as efficient regulatory mechanisms of cellular processes. Cell migration is a complex, highly coordinated process where these mechanisms must participate in an integrated manner to transmit signaling during migration. In this study, we show that the ubiquitin ligase HERC1 regulates the p38 signaling pathway, and that this regulation is mediated by the MAPK kinase MKK3. Moreover, we demonstrate a crosstalk between RAF and MKK3/p38 pathways where RAF acts upstream of MKK3. Mechanistically, HERC1 regulates the protein levels of C-RAF and MKK3. Thus, HERC1 ubiquitylates C-RAF, targeting it for proteasomal degradation, and RAF proteins regulate MKK3 mRNA levels. Accordingly, HERC1 knockdown induces C-RAF stabilization and activation of RAF proteins; in turn, this activation increases MKK3, which phosphorylates and activates p38. The importance of these observations is demonstrated by HERC1 regulation of cell migration through regulation of p38 signaling via a RAF-dependent mechanism. Thus, HERC1 plays an essential role as a regulator of crosstalk between RAF/MKK3/p38 signaling pathways during cell migration

Design of an integrated system for on-line test and diagnosis of rotary actuators

In this paper, the design of an on-chip Fault Detection and Diagnosis System for Condition Based Maintenance of electromechanical actuators is presented. The proposed system is based on signal processing algorithms integrated in a customized Application Specific Integrated Circuit (ASIC). The design was synthesized using a 90nm CMOS standard cell library. As a case study, post-synthesis simulations were performed using signals acquired from a real electromechanical valve, using torque and vibration sensors considering both fault-free and defective situations for the actuator. Results show the effectiveness of the system in performing real-time fault detection and identification, with low power consumption and low silicon area utilization

Gestión municipal y la gestión de los proyectos de inversión en una municipalidad de Lima Provincia, 2023

La presente investigación ha tenido como objetivo principal determinar la relación que hay entre la gestión municipal y gestión de proyectos de inversión en una municipalidad de Lima Provincia, 2023. La investigación fue de tipo básica, cuantitativa, correlacional y no experimental tomando como muestra a los trabajadores de la entidad dentro de la Gerencia de Desarrollo Urbano y Rural y la Oficina de Programación multianual de Inversiones. Se elaboraron cuestionarios que fueron validados por tres (03) expertos y se realizó la prueba de confiabilidad del Alfa de Cronbach con una muestra piloto. Luego de aplicado el instrumento se empleó los softwares de SPSS y Excel, para procesar los datos y verificar la relación entre las variables. Se aplicó la prueba de Shapiro-Wilk para determinar la normalidad pues la muestra era menor de 50, comprobándose que se trataba de una distribución normal; y por ello se empleó la prueba R de Pearson para determinar la correlación entre las variables, obteniendo que existe una relación de 0.759 con 0.000 de significancia. Así se comprobó que existe una relación alta entre la gestión municipal y gestión de proyectos de inversión en una municipalidad de Lima Provincia, 2023

The Tick Formulation for deadlock detection and avoidance in railways traffic control

Wrong dispatching decisions may lead to deadlocks, where trains reciprocally block resources necessary to reach their destinations. It is crucial to develop tools to detect such potential deadlocks on time, in order to reverse the decisions previously taken by dispatchers or to take recovery actions. In this paper we present a new 0,1 linear formulation for detecting deadlocks and optimally park the involved trains to reduce congestion around the affected area. We discuss computational results on some realistic randomly generated instances to show the validity of the approach, as well as its limits.acceptedVersio

Easy Cases of Deadlock Detection in Train Scheduling

A deadlock occurs when two or more trains are preventing each other from moving forward by occupying the required tracks. Deadlocks are rare but pernicious events in railroad operations and, in most cases, are caused by human errors. Recovering is a time-consuming and costly operation, producing large delays and often requiring crew rescheduling and complex switching moves. In practice, most deadlocks involve only two long trains missing their last potential meet location. In this paper, we prove that, for any network configuration, the identification of two-train deadlocks can be performed in polynomial time. This is the first exact polynomial algorithm for such a practically relevant combinatorial problem. We also develop a pseudo-polynomial but efficient oracle that allows real-time early detection and prevention of any (potential) two-train deadlock in the Union Pacific (a U.S. class 1 rail company) railroad network. A deadlock prevention module based on the work in this paper will be put in place at Union Pacific to prevent all deadlocks of this kind.acceptedVersio

Comparison of multi-state Markov models for cancer progression with different procedures for parameters estimation. An application to breast cancer

Background: the knowledge of sojourn time (the duration of the preclinical screen-detectable period) and screening test sensitivity is crucial for understanding the disease progression and the effectiveness of screening programmes. For this purpose a model of the natural history of the disease is needed. The aim of this work is to provide an illustration of the application of multistate Markov models for breast cancer progression to the data of the Florentine screening programme, in order to estimate the sojourn time and sensitivity for breast cancer screening. Methods: three different multi-state Markov models of increasing complexity were used with three different estimation procedures based on non-linear least squares, maximum likelihood, and on a Bayesian approach. All the models produced estimates for screening sensitivity and mean sojourn time. The data used in our application seem to lead to a non-identifiability problem, since the estimation procedures for both the Maximum Likelihood and Non-Linear Least Squares gave estimates that changed with the parameters’ initial values or difficultly converged. In order to take this problem into account we used the Bayesian Approach by incorporating prior information on all the parameters. Results: the mean sojourn time varied between 2-7 years and 3-5 years for women aged 50-59 and 60-69, respectively. When the model complexity was increased a higher variability in estimates was observed among the estimation procedures. The results of the screening sensitivity estimates were highly variable, both among estimation techniques and models - varying between 63% and 100%, and between 77% and 100% for women aged 50-59 and 60-69, respectively. Conclusions: results are in accord with the literature; those obtained through the Bayesian Approach seem to be more reliable.&nbsp

Opioid Peptide Gene Expression in the Primary Hereditary Cardiomyopathy of the Syrian Hamster I. REGULATION OF PRODYNORPHIN GENE EXPRESSION BY NUCLEAR PROTEIN KINASE C

Prodynorphin gene expression was investigated in adult ventricular myocytes isolated from normal (F1B) or cardiomyopathic (BIO 14.6) hamsters. Prodynorphin mRNA levels were higher in cardiomyopathic than in control myocytes and were stimulated by treatment of control cells with the protein kinase C (PKC) activator 1, 2-dioctanoyl-sn-glycerol. Both chelerythrine and calphostin C, two PKC inhibitors, abolished the stimulatory effect of the diglyceride and significantly reduced prodynorphin gene expression in cardiomyopathic myocytes. Nuclear run-off experiments indicated that the prodynorphin gene was regulated at the transcriptional level and that treatment of nuclei isolated from control cells with 1, 2-dioctanoyl-sn-glycerol increased prodynorphin gene transcription, whereas chelerythrine or calphostin C abolished this transcriptional effect. Direct exposure of nuclei isolated from cardiomyopathic myocytes to these inhibitors markedly down-regulated the rate of gene transcription. The expression of PKC-alpha, -delta, and -epsilon, as well as PKC activity, were increased in nuclei of cardiomyopathic myocytes compared with nuclei from control cells. The levels of both intracellular and secreted dynorphin B, a biologically active product of the gene, were higher in cardiomyopathic than in control cells and were stimulated or inhibited by cell treatment with 1,2-dioctanoyl-sn-glycerol or PKC inhibitors, respectively