Análise do proteoma e peptidoma salivar na diabetes Mellitus tipo 1

Doutoramento em BioquímicaA Diabetes Mellitus (DM) compreende um conjunto de desordens metabólicas comuns caracterizadas por hiperglicemia, que afeta diferentes órgãos do organismo. Ao longo do tempo, ocorrem danos microvasculares no glomérulo renal, retina e nervos periféricos, bem como doença macrovascular nas artérias. A composição da saliva também é afetada pela DM, com consequências na homeostasia oral. No entanto, o proteoma e o peptidoma salivar têm sido pouco explorados na DM tipo 1 e nas suas complicações crónicas. Tendo em conta o crescente interesse na saliva como fluido diagnóstico, o objetivo principal deste trabalho foi avaliar os eventos proteolíticos subjacentes à DM tipo 1 e às suas complicações microvasculares, bem como, caracterizar as alterações induzidas pela DM tipo 1 no proteoma e peptidoma salivar. A DM tipo 1 e particularmente as complicações microvasculares associadas modulam o perfil proteolítico dos fluidos biológicos, com diferenças significativas de atividade observadas na urina e saliva, atribuídas principalmente ao complexo Metaloproteinase da Matriz (MMP)-9/lipocalina associada à gelatinase de neutrófilos, aminopeptidase N, azurocidina e calicreína 1. O aumento da atividade proteolítica observado na saliva total dos diabéticos resultou no aumento da percentagem de péptidos, principalmente de um número acrescido de fragmentos de colagénio do tipo I, refletindo possivelmente um estado inflamatório crónico dos tecidos orais e periodontais. O peptidoma também corrobora uma maior suscetibilidade das proteínas salivares, especificamente, das proteínas ricas em prolina básicas (bPRP) 1, bPRP2 e proteínas ricas em prolina ácidas (aPRP) à proteólise, evidenciando a geração de fragmentos de proteínas associadas à ligação a bactérias. A análise do proteoma salivar baseada em iTRAQ mostrou uma sobre-expressão de L-plastina, fator do adenocarcinoma do pâncreas e das proteínas S100-A8 e S100-A9, enfatizando a importância do sistema imune inato na patogénese da DM tipo 1 e das complicações microvasculares associadas. A análise integrada de todas as proteínas expressas diferencialmente entre os pacientes diabéticos com ou sem complicações microvasculares e indivíduos saudáveis foi realizada com o STRING, onde se observam três conjuntos funcionalmente ligados, um compreende a interação entre o colagénio tipo I, colagénio tipo II e MMP-9, um segundo conjunto envolve a MMP-2 e o colagénio de tipo I e um terceiro conjunto composto por proteínas salivares e inflamatórias. Estes conjuntos estão associados com as vias Kegg de interação recetor-matriz extracelular, de adesão focal e migração transendotelial dos leucócitos. Por outro lado, a análise do proteoma e peptidoma salivar destacou potenciais biomarcadores para o diagnóstico e prognóstico da DM tipo 1 e das suas complicações.Diabetes Mellitus (DM) comprises a set of common metabolic disorders that share the phenotype of hyperglycemia, which affect many different organ systems in the body. Over time, DM-specific microvascular disease in renal glomerulus, retina and peripheral nerves occurs, as well as macrovascular pathology in arteries. The composition of saliva is also affected by DM with consequences in the oral homeostasis; however, the salivary proteome and even more the peptidome has been quite unexplored in type 1 DM and related chronic complications. Taking into account the growing interest in saliva as diagnosis fluid, the main goal of this thesis was to disclose the proteolytic events underlying type 1 DM and related microvascular complications as well as to characterize DM-induced alterations in salivary proteome and peptidome. Type 1 DM and particularly the associated microvascular complications modulates biofluids’ proteolytic profile, with significant activity differences noticed for urine and saliva mainly attributed to Matrix Metalloproteinase (MMP)-9/neutrophil gelatinase-associated lipocalin complex, aminopeptidase N, azurocidin and kallikrein 1. The higher proteolytic activity noticed in whole saliva of diabetics leads to an increase in the percentage of peptides, mainly consisting of an augmented number of collagen type I fragments, possibly reflecting a chronic inflammatory state of oral and periodontal tissues. Moreover, peptidome data also support a diabetes-related higher susceptibility of salivary proteins, namely basic proline-rich protein (bPRP) 1, bPRP2 and acidic proline-rich proteins (aPRP) to proteolysis evidencing the generation of protein fragments associated with bacterial attachment. iTRAQ-based salivary proteome profiling evidenced an overexpression of L-plastin, pancreatic adenocarcinoma factor, protein S100-A8 and S100-A9, emphasizing the importance of the innate immune system in the pathogenesis of type 1 diabetes mellitus and related microvascular complications. The integrative analysis of all different expressed proteins performed with STRING shows three clusters functionally connected, one comprehending collagen types I and II interaction and MMP-9, a second involving MMP-2 and collagen type I, and a third cluster compreending salivary proteins and inflammatory proteins. These clusters are associated with the Kegg pathways extracellular matrix-receptor interaction, focal adhesion, and leukocyte transendothelial migration. In addition, the salivary proteome and peptidome analysis highlighted potential biomarkers for the diagnosis and prognosis of type 1 diabetes mellitus and related complications

Efficient Communication in Agent-based Autonomous Logistic Processes

Transportation of goods plays a vital role for the success of a logistics network. The ability to transport goods quickly and cost effectively is one of the major requirements of the customers. Dynamics involved in the logistics process like change or cancellation of orders or uncertain information about the orders add to the complexity of the logistic network and can even reduce the efficiency of the entire logistics process. This brings about a need of integrating technology and making the system more autonomous to handle these dynamics and to reduce the complexity. Therefore, the distributed logistics routing protocol (DLRP) was developed at the University of Bremen. In this thesis, DLRP is extended with the concept of clustering of transport goods, two novel routing decision schemes and a negotiation process between the cluster of goods and the vehicle. DLRP provides the individual logistic entities the ability to perform routing tasks autonomously e.g., discovering the best route to the destination at the given time. Even though DLRP seems to solve the routing problem in real-time, the amount of message flooding involved in the route discovery process is enormous. This motivated the author to introduce a cluster-based routing approach using software agents. The DLRP along with the clustering algorithm is termed as the cluster-based DLRP. In the latter, the goods are first clustered into groups based on criteria such as the common destination. The routing is now handled by the cluster head rather than the individual transport goods which results in a reduced communication volume in the route discovery. The latter is proven by evaluating the performance of the cluster-based DLRP approach compared to the legacy DLRP. After the routing process is completed by the cluster heads, the next step is to improve the transport performance in the logistics network by identifying the best means to transport the clustered goods. For example, to have better utilization of the transport capacity, clusters can be transported together on a stretch of overlapping route. In order to make optimal transport decisions, the vehicle calculates the correlation metric of the routes selected by the various clusters. The correlation metric aids in identifying the clusters which can be transported together and thereby can result in better utilization of the transport resources. In turn, the transportation cost that has to be paid to the vehicle can be shared between the different clusters. The transportation cost for a stretch of route is calculated by the vehicle and offered to the cluster. The latter can decide based upon the transportation cost or the selected route whether to accept the transport offer from the vehicle or not. In this regard, different strategies are developed and investigated. Thereby a performance evaluation of the capacity utilization of the vehicle and the transportation cost incurred by the cluster is presented. Finally, the thesis introduces the concept of negotiation in the cluster based routing methods. The negotiation process enhances the transport decisions by giving the clusters and the vehicles the flexibility to negotiate the transportation cost. Thus, the focus of this part of the thesis is to analyse the negotiation strategies used by the logistics entities and their role in saving negotiation time while achieving a favorable transportation cost. In this regard, a performance evaluation of the different proposed strategies is presented, which in turn gives the logistics practitioners an overview of the best strategy to be deployed in various scenarios. Clustering of goods aid in the negotiation process as on the one hand, a group of transport goods have a stronger basis for negotiation to achieve a favorable transportation price from the vehicle. On the other hand it makes it easier for the vehicle to select the packages for transport and helps the vehicle to operate close to its capacity. In addition, clustering enables the negotiation process to be less complex and voluminous. From the analytical considerations and obtained results in the three parts of this thesis, it can be concluded that efficient transport decisions, though very complex in a logistics network, can be simplified to a certain extent utilizing the available information of the goods and vehicles in the network

Amyloidosis

Amyloidoses are a heterogeneous group of diverse etiology diseases. They are characterized by an endogenous production of abnormal proteins called amyloid proteins, which are not hydrosoluble, form depots in various organs and tissue of animals and humans and cause dysfunctions. Despite many decades of research, the origin of the pathogenesis and the molecular determinants involved in amyloid diseases has remained elusive. At present, there is not an effective treatment to prevent protein misfolding in these amyloid diseases. The aim of this book is to present an overview of different aspects of amyloidoses from basic mechanisms and diagnosis to latest advancements in treatment

Adsorption of heavy metals cations in wastewater using cement kiln dust

Wastewater containing heavy metal constituents are mainly generated from industrial processes, such as electric battery manufacturing, lead smelting and glass industry. Heavy metals are very dangerous and carcinogenic due to the fact that they can bio-accumulate in our bodies resulting in increasing the concentration of chemicals in the biological organism compared to the chemical’s concentration in the environment. A special emphasize in this study is on lead, cadmium, and copper since they are the most common toxic heavy metals in some inorganic industrial wastewater. Common techniques used in heavy metals treatment processes are chemical treatment, flotation, filter coalescence,and membrane filtration. However, they deemed too expensive to meet stringent effluent characteristics. Adsorption process is known with its effectiveness and high efficiency in heavy metals recovery from treated wastewater besides some other physiochemical constituents. Cement Kiln Dust (CKD) as a low cost adsorbent for heavy metal cations uptake was examined for the removal of target heavy metals. Adsorption studies in completely mixed batch reactors were used to generate equilibrium pH adsorption edges. The adsorption behavior of the target heavy metals on the CKD was studied as a function of pH, contact time, sorbent doseand initial metal concentration.Studies showed the ability of CKD to remove the target heavy metals in a pH range below that of precipitation after an equilibrium reaction time of 24 hours maximum. The lead hydroxide precipitation is the dominant phenomenon at pH values \u3e 6.0 while for copper and cadmium, the precipitation started at pH 8.0 to reach approximately 90%. CKD is experimented in dynamic up-flow fixed bed reactors as well using stainless steel columns to study the dynamic breakthrough patterns. Synthetic metal solutes containing the target metals (lead, copper, and cadmium) are fed to the packed columns with the optimum conditionsresulted from the batch equilibrium experiments where the initial metal concentration is 30 mg/l. The experimental runs show that the CKD has a high affinity to adsorb the target metals. The column reactors have higher adsorption capacity than the batch ones for the same initial concentration of adsorbate. The surface concentration at exhaustion in a molar basis was found to be 240 μM/g, 290 μM/g, and 650μM/g for lead, copper and cadmium, respectively. A surface titration experiment indicated negative surface charge of the CKD at pH below 10, meaning that electrostatic attraction of the divalent metals can occur below the pH required for precipitation. However, surface complexation was also important due to the substantive metal removal. Accordingly, a surface complexation model approach that utilizes an electrostatic term in the double layer description was used to estimate equilibrium constants for the protolysis interactions of the CKD surface as well as equilibria between background ions and the sorbent surface. Moreover, the experimental results were fitted to both Langmuir and Freundlich isotherm models to obtain the parameters of each. It was found that the adsorption capacity of CKD had the order Pb≥ Cu\u3eCd as depicted by Langmuir and Freundlich isotherm models, which is consistent with the electronegativity of these metals;1.854, 1.85, and 1.52, respectively. The sorption capacity at the optimum conditions was 14.85, 14.65, and 14.1 mg/g for lead, copper, and cadmium respectively. The experiments were also supported by Fourier Transform Infra-Red (FTIR) spectroscopy. In addition, scanning electron microscope (SEM) together with energy dispersive X-ray (EDX) were performed to the CKD before and after the treatment process. The SEM and EDX were done using different magnifications in order to better understand the physical and elemental characteristics of CKD before and after adsorption.Hydrated lime as a prime source of CaO, the major constituent of CKD, was also examined at a bench scale as well and compared to CKD in heavy metals uptake. This is to investigate whether the presence of other chemical composition in CKD, such as sodium, chloride, silicon, iron…etc., has any role in the treatment process or not. A pilot scale of a full wastewater treatment plant of 20~25 l/hr capacity was fabricated to investigate the capability of CKD in treating selected industrial wastewater and scaling up of the proposed treatment facility. Raw industrial wastewater from glass manufacturing is introduced to the pilot scale unit. In glass manufacturing, lead oxide, potash, zinc oxide, and other metal oxides are used ascoloring or de-coloring agents. Accordingly, liquid effluents resulted from grinding, polishing, coating and electroplating processes include suspended solids, heavy metals (i.e., lead), and variations in pH. The proposed treatment unit using CKD is able to reduce the total suspended solids (TSS) by 95% and biochemical oxygen demand (BOD) by 72%. In addition, heavy metals concentrations in the raw wastewater, such as lead, copper, chromium, nickel, and zinc, have been effectively treated to meet the international and national permissible limits for restricted irrigation. The highest metal concentration in the examined raw industrial wastewater is lead, and it has been reduced from 31.5 mg/l to 0.242 mg/l. The results were promising and indicated that the introduced methodology can be industrially applied. Finally, the economic viability for the proposed treatment plant was evaluated. The economic indicators in terms of economic rate of return (11.5%) and the positive net economic present value proved that the system is economically and sustainably viable

2000 USCID international conference

Presented at the 2000 USCID international conference, Challenges facing irrigation and drainage in the new millennium on June 20-24 in Fort Collins, Colorado.Includes bibliographical references.Sponsored by U.S. Committee on Irrigation and Drainage.Multicriteria strategic planning for rehabilitation of the Wind River Irrigation Project, Wyoming -- Environmental management plan for the Irrigation Improvement Project (IIP) - Tajan Subproject -- Organizational requisites of successful irrigation system rehabilitation: cases from Nepal -- Verification-based planning for modernizing irrigation systems -- Policy reforms for sustainable irrigation management in Indonesia -- Bench terracing - a cost effective alternative to traditional irrigation in the Philippines -- GIS-based management system for irrigation districts -- Capacity building for the practice of irrigated agriculture -- Planning of modern irrigation systems integrated with human settlement for enhanced reuse of water -- Drainage in the Aral Sea Basin: past and future -- Impacts and solutions to urbanization on agricultural water resources -- Improving subsurface drainage design and management to reduce salt loads from irrigation areas in southeastern Australia -- Evaluation and update of drainage water management options on the westside San Joaquin Valley, California -- Simulation studies on use of saline water for irrigation in a semi-arid environment -- Hydrodynamic modeling to optimize irrigation efficiency -- Planning to meet future water needs -- Tracing the history of the development and management of two irrigations systems in the Terai of Nepal -- Secondary water supply management for irrigation districts and canal companies -- Role of canal automation and farmer's participation in managing water scarcity: a case study from Orissa, India -- PIM: a reality in Asia? -- Private group irrigation projects in Manitoba: Central Manitoba Resource Management Ltd. - a case study -- Evaluation of dielectric soil moisture sensors for irrigation scheduling on farms -- Sensitivity of micro irrigation emitters to plugging using treated municipal wastewaters -- NCWCD irrigation scheduling program - converting to a web-based accessible program -- On-farm activities to promote irrigation scheduling - the South Kansas Irrigation Management Project

Irrigation and drainage in the new millennium

Presented at the 2000 USCID international conference, Challenges facing irrigation and drainage in the new millennium on June 20-24 in Fort Collins, Colorado.Includes bibliographical references.In 1998, eight irrigation districts in the Lower Rio Grande Valley of Texas initiated efforts to develop GIS-based District Management Systems (DMS). This paper provides a description of GIS (geographical information system) as applied to irrigation districts, its potential for improving the day-to-day management of districts, and the progress and difficulties encountered by the 8 districts in GIS mapping and implementation. Examples of how districts are using GIS are given, along with the value and use of the DMS in a regional water planning project

Irrigation and drainage in the new millennium

Presented at the 2000 USCID international conference, Challenges facing irrigation and drainage in the new millennium on June 20-24 in Fort Collins, Colorado.Irrigation scheduling has been promoted as management tool to minimize irrigation water application, however, few irrigators regularly followed any rigorous scheduling methodology. Kansas State University Research and Extension in conjunction with an irrigation association, Water PACK, began a long-term project to promote ET based irrigation scheduling and other management technology. Area irrigators serve as the focal point of the project and over time have been asked to assume responsibility of scheduling the project fields. A long-term commitment and on-farm activities such as variable water application tests and center pivot uniformity tests seems to have generated confidence and acceptance of ET-based irrigation scheduling

Plasma rich in growth factors to treat Knee Osteoarthritis

188 p.En la tesis titulada Plasma Rich in Growth Factors to treat knee osteoarthritis se exponen 4 trabajosexperimentales basados en el uso del Plasma rico en factores de crecimiento. Los objetivos específicos delos trabajos realizados son los siguientes:1. Validar las inyecciones intraarticulares de PRP como un tratamiento seguro y eficaz para la artrosisde rodilla.2. Evaluar una nueva vía para tratar la artrosis de rodilla, utilizando como diana la membrana sinovial,la superficie del cartílago articular, el líquido sinovial y el hueso subcondral, y combinandoinfiltraciones intraarticulares e intraóseas de Plasma rico en factores de crecimiento (PRP).3. Explorar la adecuación del Líquido sinovial como fuente de células madre mesenquimales (CMMs)y sus respuestas a los mecanismos bilógicos implicados en los efectos de dos modalidades distintasde tratamiento de PRP en pacientes con artrosis: Inyecciones intraarticulares con la membranasinovial, la superfcicie del cartílago articular y el líquido sinovial como diana, o la combinación deinyecciones intraarticulares e intraóseas, alcanzando por último el hueso subcondral

Water Pollution

Water pollution is a major global problem that requires ongoing evaluation and revision of water resource policy at all levels (from international down to individual aquifers and wells). It has been suggested that it is the leading worldwide cause of deaths and diseases, and that it accounts for the deaths of more than 14,000 people daily. In addition to the acute problems of water pollution in developing countries, industrialized countries continue to struggle with pollution problems as well. Water is typically referred to as polluted when it is impaired by anthropogenic contaminants and either does not support a human use, such as drinking water, and/or undergoes a marked shift in its ability to support its constituent biotic communities, such as fish. Natural phenomena such as volcanoes, algae blooms, storms, and earthquakes also cause major changes in water quality and the ecological status of water. Most water pollutants are eventually carried by rivers into the oceans

USCID fourth international conference

Presented at the Role of irrigation and drainage in a sustainable future: USCID fourth international conference on irrigation and drainage on October 3-6, 2007 in Sacramento, California.Salt management is a critical component of irrigated agriculture in arid regions. Successful crop production cannot be sustained without maintaining an acceptable level of salinity in the root zone. This requires drainage and a location to dispose drainage water, particularly, the salts it contains, which degrade the quality of receiving water bodies. Despite the need to generate drainage water to sustain productivity, many irrigation schemes have been designed and constructed with insufficient attention to drainage, to appropriate re-use or disposal of saline drainage water, and to salt disposal in general. To control the negative effects of drainage water disposal, state and federal agencies in several countries now are placing regulations on the discharge of saline drainage water into rivers. As a result, many farmers have implemented irrigation and crop management practices that reduce drainage volumes. Farmers and technical specialists also are examining water treatment schemes to remove salt or dispose of saline drainage water in evaporation basins or in underlying groundwater. We propose that the responsibility for salt management be combined with the irrigation rights of farmers. This approach will focus farmers' attention on salt management and motivate water delivery agencies and farmers to seek efficient methods for reducing the amount of salt needing disposal and to determine methods of disposing salt in ways that are environmentally acceptable