Efflux pump inhibitors against nontuberculous mycobacteria

Over the last years, nontuberculous mycobacteria (NTM) have emerged as important human pathogens. Infections caused by NTM are often difficult to treat due to an intrinsic multidrug resistance for the presence of a lipid-rich outer membrane, thus encouraging an urgent need for the development of new drugs for the treatment of mycobacterial infections. Efflux pumps (EPs) are important elements that are involved in drug resistance by preventing intracellular accumulation of antibiotics. A promising strategy to decrease drug resistance is the inhibition of EP activity by EP inhibitors (EPIs), compounds that are able to increase the intracellular concentration of antimicrobials. Recently, attention has been focused on identifying EPIs in mycobacteria that could be used in combination with drugs. The aim of the present review is to provide an overview of the current knowledge on EPs and EPIs in NTM and also, the effect of potential EPIs as well as their combined use with antimycobacterial drugs in various NTM species are described

Pengaruh Modernisasi Sistem Administrasi Perpajakan terhadap Tingkat Kepatuhan Wajib Pajak pada Kantor Pelayanan Pajak Pratama Batu

This research is motivated because the tax administration system modernization efforts undertaken by the Directorate General of Taxation is the current omzet limit changes for the Taxable Enterprises inaugural from Rp 600.000.000,- to Rp 4,8 billion. with a change in that omzet limit, the number of Taxable Enterprises in Indonesia be on the wane. The purpose of this study to investigate the effect of variables modernization of tax administration on tax compliance partially and simultaneousl. This research used in quantitative research and the type of research is explanatory research. This study used a questionnaire as a means of collecting data with a sample of Taxable Enterprises were enrolled in the KPP Pratama Batu with sample method used nonprobability sampling by purposive sampling technique. Result of the research of t-test, it is known that changes in the organizational structure and the implementation of service significantly influence taxpayer compliance. While the development of information technology and the code of conduct employee has no effect and no significant effect on tax compliance. The results of the F test it is known that the independent variables consisting of changes in the organizational structure, implementation services, the development of information technology and the code of ethics of employees significantly affect the dependent variable is tax compliance

Temporal clustering of extreme climate events drives a regime shift in rocky intertidal biofilms

Research on regime shifts has focused primarily on how changes in the intensity and duration of press disturbances precipitate natural systems into undesirable, alternative states. By contrast, the role of recurrent pulse perturbations, such as extreme climatic events, has been largely neglected, hindering our understanding of how historical processes regulate the onset of a regime shift. We performed field manipulations to evaluate whether combinations of extreme events of temperature and sediment deposition that differed in their degree of temporal clustering generated alternative states in rocky intertidal epilithic microphytobenthos (biofilms) on rocky shores. The likelihood of biofilms to shift from a vegetated to a bare state depended on the degree of temporal clustering of events, with biofilm biomass showing both states under a regime of non-clustered (60 d apart) perturbations while collapsing in the clustered (15 d apart) scenario. Our results indicate that time since the last perturbation can be an important predictor of collapse in systems exhibiting alternative states and that consideration of historical effects in studies of regime shifts may largely improve our understanding of ecosystem dynamics under climate change

Experimental evidence of spatial signatures of approaching regime shifts in macroalgal canopies

Developing early warning signals to predict regime shifts in ecosystems is a central issue in current ecological research. While there are many studies addressing temporal early warning indicators, research into spatial indicators is far behind, with field experiments even more rare. Here, we tested the performance of spatial early warning signals in an intertidal macroalgal system, where removal of algal canopies pushed the system toward a tipping point (corresponding to approximately 75% of canopy loss), marking the transition between a canopy- to a turf-dominated state. We performed a two-year experiment where spatial early warning indicators were assessed in transects where the canopy was differentially removed (from 0 to 100%). Unlike Moran correlation coefficient at lag-1, spatial variance, skewness, and spatial spectra at low frequency increased along the gradient of canopy degradation and dropped, or did not show any further increase beyond the transition point from a canopy- to a turf-dominated state (100% canopy removal). Our study provides direct evidence of the suitability of spatial early warning signals to anticipate regime shifts in natural ecosystems, emphasizing the importance of field experiments as a powerful tool to establish causal relationships between environmental stressors and early warning indicators

Rapid and Accurate Identification of Nontuberculous Mycobacteria Directly from Positive Primary MGIT Cultures by MALDI-TOF MS

Over the last years, nontuberculous mycobacteria (NTM) have emerged as important human pathogens. Accurate and rapid mycobacterial species identification is needed to successfully diagnose, treat, and manage infections caused by NTM. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry, MALDI-TOF MS, was demonstrated to effectively identify mycobacteria isolates subcultured from solid or liquid media rather than new positive cultures. The present study aims to develop a new extraction protocol to yield rapid and accurate identification of NTM from primary MGIT cultures by MALDI-TOF MS. A total of 60 positive MGIT broths were examined by the Bruker Biotyper system with Mycobacteria Library v. 2.0 (Bruker Daltonics GmbH & Co. KG., Bremen, Germany). The results were compared with those obtained by the molecular method, line probe assay GenoType Mycobacterium CM/AS/NTM-DR. All samples were concordantly identified by MALDI-TOF MS and the molecular test for all the tested mycobacteria. Fifty-seven (95%) MGIT positive cultures for NTM from clinical samples had a MALDI-TOF MS analysis score S ≥ 1.8. Although a small number of strains and a limited diversity of mycobacterial species were analysed, our results suggest that MALDI-TOF MS could represent a promising routine diagnostic tool for identifying mycobacterial species directly from primary liquid culture

Spatio-temporal variability in Mediterranean rocky shore microphytobenthos

Knowledge of spatio-temporal variability of assemblages is the first step in identifying key factors affecting the abundance and distribution of organisms. Despite a long history of ecological studies on rocky intertidal habitats, there is still a lack of basic knowledge about the microphytobenthic components. We investigated the spatio-temporal variability of microphytobenthos in the northwest Mediterranean at multiple scales, including both seasonal and daily observations, as well as its composition. Spatial variability of microphytobenthic biomass varied significantly with season, with an increase in small-scale variance from cold to warm periods. Furthermore, during warmer months, small-scale variances (tens to hundreds of centimeters) were larger than large-scale components (tens to thousands of meters). These results suggest large spatiotemporal variation in the processes driving variation in microphytobenthic assemblages, including interactive effects among stressful abiotic conditions, substratum topography and grazing. In addition, observed variability on a daily scale suggested that microphytobenthos at the study site (dominated by cyanobacteria) might cope with stressful environmental conditions through both physiological and behavioral strategies at micro-spatial scales, including small movements within the substratum. Additional research on ecological and physiological aspects of rocky shore microphytobenthos is needed to better understand its role within interaction webs and primary productivity processes

Energy storage systems to exploit regenerative braking in DC railway systems: Different approaches to improve efficiency of modern high-speed trains

The growing attention to environmental sustainability of transport systems made necessary to investigate the possibility of energy optimization even in sectors typically characterised by an already high level of sustainability, as in particular the railway system. One of the most promising opportunity is the optimization of the braking energy recovery, which has been already considered in tramway systems, while it is traditionally overlooked for high-speed railway systems. In this research work, the authors have developed two simulation models able to reproduce the behavior of high-speed trains when entering in a railway node, and to analyze the impact of regenerative braking in DC railway systems, including usage of energy storage systems. These models, developed respectively in the Matlab-Simscape environment and in the open source Modelica language, have been experimentally validated considering an Italian high-speed train. After validation, the authors have performed a feasibility analysis considering the use of stationary and on-board storage systems, also by taking into account capital costs of the investment and annual energy saving, to evaluate cost-effectiveness of the different solutions. The analysis has shown the possibility to improve the efficiency of high-speed railway systems, by improving braking energy recovery through the installation of such storage systems

Development and validation of wear models by using innovative three-dimensional laser scanners:

One of the main problems in railway and tramway systems, both dynamically (safety, comfort etc.) and economically (planning of maintenance interventions, reduction of wheel and rail lifetime etc.), is represented by the wear of wheel and rail profiles, due to the wheel–rail interaction. The profile's shape variation caused by wear influences the dynamic behaviour of the vehicle and, in particular, the wheel–rail contact conditions. Hence, nowadays, one of the most important topics in the railway field is the development of reliable wear models to predict profiles evolution, together with the use of more efficient and accurate measuring instruments for the model validation and the rolling components inspection. In this context, the aim of this research work is the development and the validation of wear models, using experimental data acquired through an innovative measuring instrument based on noncontact three-dimensional laser scanning technology. The tramway line of the city of Florence, characterized by very narrow curves and critical in terms of wear, has been chosen as a reference test case. Moreover, the inspection procedures currently adopted on this line for the maintenance plan are based only on classical two-dimensional contact measurement systems, not so accurate for a complete wear assessment. Therefore, the introduction of a new three-dimensional laser scanning technology may have a great impact on the maintenance management of the line

Epidemiology of carcinoid neoplasms in Vaud, Switzerland, 1974–97

In Vaud, Switzerland, the incidence of carcinoids based on 218 malignant and 215 benign cases rose from 19.6/106in 1974–85 to 28.2/106in 1986–97, more so among males and malignant neoplasms. Lung was the commonest site for malignant and large intestine for benign carcinoids. Sixty-eight (16%) carcinoids had another neoplasm. © 2000 Cancer Research Campaig