Hybrid Systems and Control With Fractional Dynamics (I): Modeling and Analysis

No mixed research of hybrid and fractional-order systems into a cohesive and multifaceted whole can be found in the literature. This paper focuses on such a synergistic approach of the theories of both branches, which is believed to give additional flexibility and help to the system designer. It is part I of two companion papers and introduces the fundamentals of fractional-order hybrid systems, in particular, modeling and stability analysis of two kinds of such systems, i.e., fractional-order switching and reset control systems. Some examples are given to illustrate the applicability and effectiveness of the developed theory. Part II will focus on fractional-order hybrid control.Comment: 2014 International Conference on Fractional Differentiation and its Application, Ital

Hybrid Systems and Control With Fractional Dynamics (II): Control

No mixed research of hybrid and fractional-order systems into a cohesive and multifaceted whole can be found in the literature. This paper focuses on such a synergistic approach of the theories of both branches, which is believed to give additional flexibility and help the system designer. It is part II of two companion papers and focuses on fractional-order hybrid control. Specifically, two types of such techniques are reviewed, including robust control of switching systems and different strategies of reset control. Simulations and experimental results are given to show the effectiveness of the proposed strategies. Part I will introduce the fundamentals of fractional-order hybrid systems, in particular, modelling and stability of two kinds of such systems, i.e., fractional-order switching and reset control systems.Comment: 2014 International Conference on Fractional Differentiation and its Application, Ital

An overview of the spindle assembly checkpoint status in oral cancer

Abnormal chromosome number, or aneuploidy, is a common feature of human solid tumors, including oral cancer. Deregulated spindle assembly checkpoint (SAC) is thought as one of the mechanisms that drive aneuploidy. In normal cells, SAC prevents anaphase onset until all chromosomes are correctly aligned at the metaphase plate thereby ensuring genomic stability. Significantly, the activity of this checkpoint is compromised in many cancers. While mutations are rather rare, many tumors show altered expression levels of SAC components. Genomic alterations such as aneuploidy indicate a high risk of oral cancer and cancer-related mortality, and the molecular basis of these alterations is largely unknown. Yet, our knowledge on the status of SAC components in oral cancer remains sparse. In this review, we address the state of our knowledge regarding the SAC defects and the underlying molecular mechanisms in oral cancer, and discuss their therapeutic relevance, focusing our analysis on the core components of SAC and its target Cdc20.CESPU [02-GCQF-CICS-2011N, 01-GCD-CICS-09; 02-GCD-CICS-09, 05-GCD-CICS-2011]; Fundacao para a Ciencia e a Tecnologia (FCT) [CEQUIMED-PEst-OE/SAU/UI4040/2011]

Intramolecular activity regulation of adhesion GPCRs in light of recent structural and evolutionary information

The class B2 of GPCRs known as adhesion G protein-coupled receptors (aGPCRs) has come under increasing academic and nonacademic research focus over the past decade due to their physiological importance as mechano-sensors in cell-cell and cell-matrix contexts. A major advance in understanding signal transduction of aGPCRs was achieved by the identification of the so-called Stachel sequence, which acts as an intramolecular agonist at the interface between the N terminus (Nt) and the seven-transmembrane helix domain (7TMD). Distinct extracellular signals received by the Nt are integrated at the Stachel into structural changes of the 7TMD towards an active state conformation. Until recently, little information was available on how the activation process of aGPCRs is realized at the molecular level. In the past three years several structures of the 7TMD plus the Stachel in complex with G proteins have been determined, which provide new insights into the architecture and molecular function of this receptor class. Herein, we review this structural information to extract common and distinct aGPCR features with particular focus on the Stachel binding site within the 7TMD. Our analysis extends the current view of aGPCR activation and exposes similarities and differences not only between diverse aGPCR members, but also compared to other GPCR classes

National tuberculosis spending efficiency and its associated factors in 121 low-income and middle-income countries, 2010-19: a data envelopment and stochastic frontier analysis

BACKGROUND: Maximising the efficiency of national tuberculosis programmes is key to improving service coverage, outcomes, and progress towards End TB targets. We aimed to determine the overall efficiency of tuberculosis spending and investigate associated factors in 121 low-income and middle-income countries between 2010 and 2019. METHODS: In this data envelopment and stochastic frontier analysis, we used data from the WHO Global TB report series on tuberculosis spending as the input and treatment coverage as the output to estimate tuberculosis spending efficiency. We investigated associations between 25 independent variables and overall efficiency. FINDINGS: We estimated global tuberculosis spending efficiency to be between 73·8% (95% CI 71·2-76·3) and 87·7% (84·9-90·6) in 2019, depending on the analytical method used. This estimate suggests that existing global tuberculosis treatment coverage could be increased by between 12·3% (95% CI 9·4-15·1) and 26·2% (23·7-28·8) for the same amount of spending. Efficiency has improved over the study period, mainly since 2015, but a substantial difference of 70·7-72·1 percentage points between the most and least efficient countries still exists. We found a consistent significant association between efficiency and current health expenditure as a share of gross domestic product, out-of-pocket spending on health, and some Sustainable Development Goal (SDG) indicators such as universal health coverage. INTERPRETATION: To improve efficiency, treatment coverage will need to be increased, particularly in the least efficient contexts where this might require additional spending. However, progress towards global End TB targets is slow even in the most efficient countries. Variables associated with TB spending efficiency suggest efficiency is complimented by commitments to improving health-care access that is free at the point of use and wider progress towards the SDGs. These findings support calls for additional investment in tuberculosis care. FUNDING: None

Therapies in the fight against Covid-19

SARS-Cov-2 Coronavirus is a new emerging virus causing the COVID-19, a respiratory disease outbreak that started in China in December 2019. On January 30, 2020, the World Health Organization has declared this to be a public health emergency of international concern. By September 2020, COVID-19 has affected more than 33 millionin 210 countries and territories worldwide. In this review, we present an overview of the drugs and medicines to combat COVID-19 currently in the clinical trial. We summarize the challenges facing, and opportunities for the discovery of new therapies in this emergency situation