2,704 research outputs found
Microeconomic and Geo-physical Data Integration for Agri-environmental Analysis, Georeferencing FADN Data: A Case Study in Italy
The authors, inside a TAPAS action, have developed a methodology - based on the integration between FADN data with statistical, administrative and cartographic information - to improve the production of statistical data related to agricultural policies impact on land and environment. This methodology allows - using Geographic Information System (GIS) technology - to produce and organise data at geographical level. Data spatially referenced respond to the specific needs of agri-environmental analysis and problems, mostly related to specific areas (environmental vulnerability areas), inside defined boundaries (e.g. river basin). The GIS is implemented with several cartographic layers (Topographic and cadastral maps, land use, soils, water sources, climate, Digital Terrain Model etc.) and is related to the regional FADN database.agricultural statistics, agri-environment, FADN, GIS, TAPAS, DPSIR, Environmental Economics and Policy, C81, O13, Q21,
Computational Studies on Pharmaceutical Targets in Human Diseases
Bacterial multidrug resistance (i.e. the ability of some bacterial species to survive in presence of various drugs) has become a primary challenge at a global level. Due to various factors, such as the overuse of antibiotics in human activities like health care and farming or inadequate diagnostic, many bacteria have indeed evolved acquiring novel and highly efficient resistance mechanisms. Some species, in particular, have become resistant to almost all in-use drugs.
Among the several mechanisms of resistance, efflux pumps of the RND superfamily (resistance-nodulation-cell division) play a major role. These complexes span the cell wall and are able to expel a wide range of noxious compounds, including antibiotics of many different classes. In order to reinvigorate the action of these drugs, a viable route is to hinder their transport out of the cell through co-administration of efflux pumps inhibitors (EPIs). At present several EPIs have been identified, but none of them is usable in clinical therapies due to adverse effects. Moreover, several questions are still open regarding the mode of action of known EPIs as well as the functioning mechanism of RND efflux pumps. Further research in this field is thus needed.
In order to characterize the mode of action of several EPIs of this pump, we applied computational techniques such as molecular docking and molecular dynamics (MD) simulations. Specifically, we focused on the EPIs: (i) amitriptyline and chlorpromazine, repurposed drugs which were proven to act as inhibitors against AcrB; (ii) PAβN, a known inhibitor of the pump whose mode of action is not fully understood.
This thesis focuses on the inhibition of the AcrB efflux pump, the best known representative of the RND superfamily. High-resolution structural data are indeed available for this protein (specifically, for its Escherichia coli orthologue). Moreover, a fluoroquinolone resistant variant of this pump has been detected in clinical environments.
With regard to amitriptyline and chlorpromazine, our in silico investigations revealed that both compounds tend to occupy a known binding pocket of AcrB. Their binding mode presents considerable similarities with that of several substrates and other EPIs of the pump, indicating that amitriptyline and chlorpromazine may inhibit the AcrB pump through competitive binding.
In the case of PAβN, MD simulations were compared with experimental data from hydrogen-deuterium exchange mass spectrometry. From these analyses, it emerged that PAβN can significantly restrain the conformational dynamics of AcrB and its fluoroquinolone resistant variant. This EPI, therefore, may act by preventing conformational changes that are functional for AcrB. Importantly, our MD simulations revealed that PAβN and the antibiotic ciprofloxacin can simultaneously occupy the same binding pocket, suggesting that the EPI does not act by competitive binding.
Further computational analyses were conducted on structural models of Salmonella Typhimurium AcrB. Experimental structural data on this wt protein are indeed missing, while the structure of its fluoroquinolone resistant variant has recently been solved through cryo-electron microscopy (cryo-EM). In order to assess the structural differences between the two proteins, we derived their structural models through homology modelling and MD simulations (modeling of the fluoroquinolone resistant variant was integrated with cryo-EM data). Structural analyses were then performed, with focus on the binding pockets of the protein. Considerable differences were detected regarding the volume as well as the hydration properties of the pockets. Although not strictly related to EPI development, this information may be valuable for the design of novel drugs and/or inhibitors of AcrB from Salmonella
Parenting Stress as A Moderator of the Relationship Between Child Emotional and Behavioral Problems and Parental Readiness for Change
The current study applied the Transtheoretical Model of Behavior Change (Prochaska & DiClemente, 1983) to parenting behavior, as past research has suggested that increasing parental motivation and readiness for change is associated with greater client participation and improved therapeutic outcomes (Dowell & Ogles, 2010; Karver et al., 2006). The current study attempted to replicate Jones et al.’s (2017) primary findings and add to the current body of literature on parental readiness for change by examining parenting stress as a moderator of the relationship between internalizing and externalizing child problems and parental readiness for change (Jones et al., 2017; Wade & Andrade, 2015). Data was collected at a medium-sized outpatient child, adolescent, and family therapy clinic in the Appalachian region. Guardians completed the Behavior Assessment System for Children, Third Edition (BASC-3), Parenting Readiness for Change Scale (PRFCS), Parenting Stress Index Fourth Edition (PSI-4)/Parenting Stress Index, Fourth Edition Short-Form (PSI-4-SF) or the Stress Index for Parents of Adolescents (SIPA; Sheras et al., 1998). The moderator was not examined due to the violation of multicollinearity and an insufficient number of participants in the high-stress parenting group. The current study found that after controlling for child age and family court status, child internalizing problems, externalizing problems, and parenting stress did not predict level of parental readiness for change. An exploratory analysis found that externalizing problems predicted parenting stress over and above just internalizing problems
A nonmainstream approach against cancer
The discovery of antibiotics as specific and effective drugs against infectious agents has generated the belief that the famous Paul Erlich theory on magic bullet should be applied to cancer as well. However, after around 60 years of failures in finding a magic bullet against cancer, a question appears mandatory: does the magic bullet against cancer really exist? In trying to understand more on the issue, we propose three discoveries are coming from a nonmainstream approach against cancer. Tumor is acidic, and tumor acidity impairs drugs entering within tumor cells and isolates tumors from the rest of the body. Proton pumps are key in allowing tumor cells to live in the acidic microenvironment. A class of antiacidic drugs, proton pump inhibitors (PPIs), were shown to have a potent anti-tumor effect, through inhibition of proton pumps in tumor cells. PPIs are indeed prodrugs needing acidity to be activated into the active molecule. So they use protonation by H+ as an activating mechanism, while the vast majority of drugs are totally neutralized by protonation. An anti-tumor therapy based on PPI showed to be effective both in vitro and in vivo. Differently from normal cells, cancer cells meet their energy needs in great part by fermentation, and it appears conceivable that hypoxia and low nutrient transform tumor cells into fermenting anaerobes. This suggests that cancer cells are more similar to unicellular organisms, aimed at surviving in a continuous fighting, rather than cooperating, with other cells, as it occurs in the normal homeostasis of our body. We have shown that cancer cells take their fuel by "cannibalizing" other cells, either dead or alive, especially when starved and in acidic condition. This finding led to the discovery of a new oncogene TM9SF4 that human malignant cell shares with amoebas. The evidence is accumulating that almost all the cells release extracellular vehicles (EVs), from micro- to nanosize, which shuttle a variety of molecules. Tumor cells, particularly when stressed in their hostile microenvironment, release high levels of EVs, able to interact with target cells in various ways, within an organ or at a distance. They may represent both valuable tumor biomarker and shuttles for drugs with anti-tumor properties. This article wants to burst a real change in future anti-cancer strategies, based on the idea that tumors are much more common features than specific molecular targets
Spatially and Temporally Explicit Energy System Modelling to Support the Transition to a Low Carbon Energy Infrastructure – Case Study for Wind Energy in the UK
Renewable energy sources and electricity demand vary with time and space and the energy system is constrained by the location of the current infrastructure in place. The transitioning to a low carbon energy society can be facilitated by combining long term planning of infrastructure with taking spatial and temporal characteristics of the energy system into account. There is a lack of studies addressing this systemic view. We soft-link two models in order to analyse long term investment decisions in generation, transmission and storage capacities and the effects of short-term fluctuation of renewable supply: The national energy system model UKTM (UK TIMES model) and a dispatch model. The modelling approach combines the benefits of two models: an energy system model to analyse decarbonisation pathways and a power dispatch model that can evaluate the technical feasibility of those pathways and the impact of intermittent renewable energy sources on the power market. Results give us the technical feasibility of the UKTM solution from 2010 until 2050. This allows us to determine lower bounds of flexible elements and feeding them back in an iterative process (e.g. storage, demand side control, balancing). We apply the methodology to study the long-term investments of wind infrastructure in the United Kingdom
Os incentivos fiscais e as zonas de processamento de exportação: sua relação com o acordo sobre subsídios e medidas compensatórias da Organização Mundial do Comércio
Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Ciências Jurídicas, Programa de Pós-Graduação em Direito, Florianópolis, 2010As Zonas de Processamento de Exportação surgiram por volta da década dos anos 1950 com o intuito de promover o desenvolvimento econômico e social dos países. Constituem áreas reservadas para a indústria exportadora, a qual, por meio da concessão de benefícios fiscais, pode expandir suas vendas, podendo concorrer em patamar de igualdade no cenário mundial. Ocorre que, com o surgimento da Organização Mundial do Comércio, os benefícios fiscais ficaram limitados, principalmente, devido ao Acordo sobre Subsídios e Medidas Compensatórias, o qual, ao caracterizá-los como proibidos e/ou distorcivos, poderá permitir que o país que adotou a medida abusiva sofra algumas sanções. Por esse motivo, o estudo dos incentivos fiscais concedidos pelas zonas brasileiras em relação ao acordo sobre subsídios da OMC, se torna relevante diante das retaliações que o país pode sofrer caso infrinja tal acordo.The Export Processing Zones were first created around the fifties with the intention to promote the economic and social development of the countries. They are considered areas reserved for export industry, which, by fiscal incentives concessions, can expand its sales and compete equally in the world scenario. It occurs that, with the creation of the World Trade Organization, the fiscal incentives were limited, mainly due to the Agreement on Subsidies and Countervailing Measures, which, when prohibited and/or distorcivos, may allow that the country that adopted the abusive measure put up with some sanctions. Because of this, the study of the fiscal incentives conceded to the Brazilian zones in relation to the agreement on subsidies of the WTO, has become relevant before the possibility of retaliations that the country may suffer in case of violation of the agreement
Urgensi Calon Independen dalam PemlUhan Kepala Daerah Langsung
If the Election Head of Region can be used as a momentum of fundamental change, thus the attendence of independent candidate is absolute and cannot be bargained. Practically and theorethically, independent candidate is significant
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