A soft-computing-based method for the automatic discovery of fuzzy rules in databases:uses for academic research and management support in marketing

The study here highlights the potential that analytical methods based on Knowledge Discovery in Databases (KDD) methodologies have to aid both the resolution of unstructured marketing/business problems and the process of scholarly knowledge discovery. The authors present and discuss the application of KDD in these situations prior to the presentation of an analytical method based on fuzzy logic and evolutionary algorithms, developed to analyze marketing databases and uncover relationships among variables. A detailed implementation on a pre-existing data set illustrates the method. © 2012 Published by Elsevier Inc.

The influence of marketing factors and substance characteristics on pharmaceutical sales in a state-controlled prescriptions pharmaceuticals market

The present dissertation investigates the influence of brand as well as substance-related marketing attributes on prescription pharmaceutical sales within a state-controlled market. For this purpose, a systematic literature review was conducted in the first instance, during which knowledge about the most relevant research within this field was gathered. Consequently, over 538 publications were reviewed and indicated as being potentially relevant, leading to an eventual count of 98 core publications. However, most of these studies had been conducted in the mainly unrestricted US market. These findings were then summarised and statistically evaluated. In a second step, based on the literature review, a qualitative study, containing focus and Delphi groups, was then performed. The participants in these studies were involved in pharmaceutical marketing within a state-controlled prescriptions pharmaceuticals market. Consequently, the findings were slightly different to those derived by the systematic literature review. Based on this second step, seven hypotheses were proposed. In the third step, these hypotheses were tested, using collected data and a secondary market dataset provided by a market research institute. A statistical analysis was then performed, applying descriptive as well as multiple regression analytical methods. The evaluation of the results resulted in a conceptual model of physician targeting, leading to several theoretical, methodological and managerial implications.

Analysis of a full-memory multidestination ARQ protocol over broadcast links

Based on an assumption that a steady state exists in the full-memory multidestination automatic repeat request (ARQ) scheme, we propose a novel analytical method called steady-state function method (SSFM), to evaluate the performance of the scheme with any size of receiver buffer. For a wide range of system parameters, SSFM has higher accuracy on throughput estimation as compared to the conventional analytical methods.

Oxidiative lipidomics coming of age:advances in analysis of oxidized phospholipids in physiology and pathology

Significance: Oxidized phospholipids are now well-recognized as markers of biological oxidative stress and bioactive molecules with both pro-inflammatory and anti-inflammatory effects. While analytical methods continue to be developed for studies of generic lipid oxidation, mass spectrometry (MS) has underpinned the advances in knowledge of specific oxidized phospholipids by allowing their identification and characterization, and is responsible for the expansion of oxidative lipidomics. Recent Advances: Studies of oxidized phospholipids in biological samples, both from animal models and clinical samples, have been facilitated by the recent improvements in MS, especially targeted routines that depend on the fragmentation pattern of the parent molecular ion and improved resolution and mass accuracy. MS can be used to identify selectively individual compounds or groups of compounds with common features, which greatly improves the sensitivity and specificity of detection. Application of these methods have enabled important advances in understanding the mechanisms of inflammatory diseases such as atherosclerosis, steatohepatitis, leprosy and cystic fibrosis, and offer potential for developing biomarkers of molecular aspects of the diseases. Critical Issues and Future Directions: The future in this field will depend on development of improved MS technologies, such as ion mobility, novel enrichment methods and databases and software for data analysis, owing to the very large amount of data generated in these experiments. Imaging of oxidized phospholipids in tissue MS is an additional exciting direction emerging that can be expected to advance understanding of physiology and disease.

The extracellular surface of the GLP-1 receptor is a molecular trigger for biased agonism

Ligand-directed signal bias offers opportunities for sculpting molecular events, with the promise of better, safer therapeutics. Critical to the exploitation of signal bias is an understanding of the molecular events coupling ligand binding to intracellular signaling. Activation of class B G protein-coupled receptors is driven by interaction of the peptide N terminus with the receptor core. To understand how this drives signaling, we have used advanced analytical methods that enable separation of effects on pathway-specific signaling from those that modify agonist affinity and mapped the functional consequence of receptor modification onto three-dimensional models of a receptor-ligand complex. This yields molecular insights into the initiation of receptor activation and the mechanistic basis for biased agonism. Our data reveal that peptide agonists can engage different elements of the receptor extracellular face to achieve effector coupling and biased signaling providing a foundation for rational design of biased agonists.

Assessing the sources, quantities, and trends on human waste contamination along protected south Florida ecosystem: A chemical tracer based study

The common occurrence of human derived contaminants like pharmaceuticals, steroids and hormones in surface waters has raised the awareness of the role played by the release of treated or untreated sewage in the water quality along sensitive coastal ecosystems. South Florida is home to many important protected environments ranging from wetlands to coral reefs which are in close proximity to large metropolitan cities. Since large portions of South Florida and most of the Florida Keys population are not served by modern sewage treatment plants and rely heavily on the use of inefficient septic systems; a comprehensive survey of selected human waste contamination markers is needed in these areas to assess water quality with respect to non-traditional micro-constituents. ^ This study reports the development and application of new sensitive and selective analytical methods for the fast screening of multiple wastewater tracers, classified as Emergent Pollutants of Concern (EPOC). Novel methods for the trace analysis of non-traditional markers of human-specific contamination such as aminopropanone were developed and used to assess the potential of non-traditional markers as wastewater tracers. ^ During our investigation, surface water samples collected from near shore environments along the South Florida were analyzed for fifteen hormones and steroids, and five commonly detected pharmaceuticals. The compounds most frequently detected were: coprostanol, cholesterol, estrone, β-estradiol, caffeine, triclosan and DEET. Concentrations of caffeine, bisphenol A and DEET were usually higher and more prevalent than the hormonal steroids. In general, it was found that common pharmaceuticals and steroids are widely present in major coastal environments in South Florida. It is also evident that aquatic bodies in heavily urbanized sectors such as the Miami River and Key Largo Harbor contain higher concentrations of several compounds while relatively open bay waters and agricultural areas show reduced chemical signatures. Concentrations of hormones in the Little Venice area of Marathon Key were above the Lowest Observable Effect Levels (LOELs) for several species, indicating that biological resources in this area are at risk. Water quality issues in some of these coastal water environments go beyond eutrophication, thus EPOC should be the target goal for future mitigation projects. ^

Molecular characterization of proteinaceous material in the Florida coastal Everglades

Dissolved organic nitrogen (DON) is the least known component of the nitrogen cycle, in part as a result of the lack of adequate analytical methods for its molecular characterization. In this study proteinaceous material in DON, collected at six geomorphologically different sites in the Florida coastal Everglades, was characterized by amino acid analysis and protein gel electrophoresis. The amino acid composition of the samples suggests that the canal DON was more degraded and subject to higher microbial inputs than the mangrove marshwater and marine end-member stations. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) results supported this observation as distinctly different protein profiles were obtained for the canal waters compared to samples collected at other stations. These preliminary results highlight the potential of combining amino acid and intact protein analysis to fingerprint the sources of DON in different aquatic environments, and show SDS-PAGE as a potentially useful method to characterize DON.

Elemental analysis of biological matrices by laser ablation high resolution inductively coupled plasma mass spectrometry (LA-HR-ICP-MS) and high resolution inductively coupled plasma mass spectrometry (HR -ICP -MS)

The need for elemental analysis of biological matrices such as bone, teeth, and plant matter for sourcing purposes has emerged within the forensic and geochemical laboratories. Trace elemental analyses for the comparison of materials such as glass by inductively coupled plasma mass spectrometry (ICP-MS) and laser ablation ICP-MS has been shown to offer a high degree of discrimination between different manufacturing sources. Unit resolution ICP-MS instruments may suffer from some polyatomic interferences including 40Ar16O+, 40Ar 16O1H+, and 40Ca 16O+ that affect iron measurement at trace levels. Iron is an important element in the analysis of glass and also of interest for the analysis of several biological matrices. A comparison of the analytical performance of two different ICP-MS systems for iron analysis in glass for determining the method detection limits (MDLs), accuracy, and precision of the measurement is presented. Acid digestion and laser ablation methods are also compared. Iron polyatomic interferences were reduced or resolved by using dynamic reaction cell and high resolution ICP-MS. MDLs as low as 0.03 μg g-1 and 0.14 μg g-1 for laser ablation and solution based analyses respectively were achieved. The use of helium as a carrier gas demonstrated improvement in the detection limits of both iron isotopes (56Fe and 57Fe) in medium resolution for the HR-ICP-MS and with a dynamic reaction cell (DRC) coupled to a quadrupole ICP-MS system. ^ The development and application of robust analytical methods for the quantification of trace elements in biological matrices has lead to a better understanding of the potential utility of these measurements in forensic chemical analyses. Standard reference materials (SRMs) were used in the development of an analytical method using HR-ICP-MS and LA-HR-ICP-MS that was subsequently applied on the analysis of real samples. Bone, teeth and ashed marijuana samples were analyzed with the developed method. ^ Elemental analysis of bone samples from 12 different individuals provided discrimination between individuals, when femur and humerus bones were considered separately. Discrimination of 14 teeth samples based on elemental composition was achieved with the exception of one case where samples from the same individual were not associated with each other. The discrimination of 49 different ashed plant (cannabis) samples was achieved using the developed method. ^

A hora da alfabetização: atores, ideias e instituições na construção do PAIC-CE

The objective of this thesis is to understand how a certain social condition becomes relevant enough to be regarded as an issue worthy of government action and how certain proposed initiatives prevail while others are discarded. More specifically, the goal is to discuss public policy for education and check whether the analytical models employed are significant enough to explain how the literacy issue became part of the policy agenda of the government of the State of Ceará in Brazil, and how the Literacy Program at the Right Age (PAIC) developed over time. From the empirical perspective about public policy for education in Brazil, this is a relevant case when one takes into account that, historically, the literacy policies are focused on teenagers and adults, implying a lack of specific initiatives towards children at the proper age of learning to read and write. In order to understand what drove this issue to the top of the state government agenda, this thesis is primarily based on the literature about public policy analysis, with focus on the agenda setting process and development of proposals. A hybrid approach is used, combining analytical tools from Kingdon’s Multiple Streams Model (1995), the Advocacy Coalition Framework by Sabatier and Jenkins Smith (1993) and the historical new institutionalism lens. The research method is qualitative and based on the single case study method. The data set was assembled from institutional PAIC-related documents, tachygraphy notes from sessions at Ceará’s State House of Representatives, press clippings, academic studies and interviews with key participants from several organizations. The conclusion of this thesis is that, given the complexity of the case in point, the combination of the three analytical methods is adequate and necessary to understanding the multiple drivers for this issue to have entered Ceará’s state government agenda and the design of the PAIC itself. Particularly relevant are the ideas and the policy entrepreneurs, the processes of problem recognition for the composition of a wide coalition and for the specification of alternatives, and the path dependence of the education policy in Ceará. This study adds, as a result, to a better understanding of the stages that make up the agenda setting in public policy, in particular in the field of education.

A hora da alfabetização: atores, ideias e instituições na construção do PAIC-CE

The objective of this thesis is to understand how a certain social condition becomes relevant enough to be regarded as an issue worthy of government action and how certain proposed initiatives prevail while others are discarded. More specifically, the goal is to discuss public policy for education and check whether the analytical models employed are significant enough to explain how the literacy issue became part of the policy agenda of the government of the State of Ceará in Brazil, and how the Literacy Program at the Right Age (PAIC) developed over time. From the empirical perspective about public policy for education in Brazil, this is a relevant case when one takes into account that, historically, the literacy policies are focused on teenagers and adults, implying a lack of specific initiatives towards children at the proper age of learning to read and write. In order to understand what drove this issue to the top of the state government agenda, this thesis is primarily based on the literature about public policy analysis, with focus on the agenda setting process and development of proposals. A hybrid approach is used, combining analytical tools from Kingdon’s Multiple Streams Model (1995), the Advocacy Coalition Framework by Sabatier and Jenkins Smith (1993) and the historical new institutionalism lens. The research method is qualitative and based on the single case study method. The data set was assembled from institutional PAIC-related documents, tachygraphy notes from sessions at Ceará’s State House of Representatives, press clippings, academic studies and interviews with key participants from several organizations. The conclusion of this thesis is that, given the complexity of the case in point, the combination of the three analytical methods is adequate and necessary to understanding the multiple drivers for this issue to have entered Ceará’s state government agenda and the design of the PAIC itself. Particularly relevant are the ideas and the policy entrepreneurs, the processes of problem recognition for the composition of a wide coalition and for the specification of alternatives, and the path dependence of the education policy in Ceará. This study adds, as a result, to a better understanding of the stages that make up the agenda setting in public policy, in particular in the field of education.

Dynamical generation of a gauge symmetry in the double-exchange model

It is shown that a bosonic formulation of the double-exchange model, one of the classical models for magnetism, generates dynamically a gauge-invariant phase in a finite region of the phase diagram. We use analytical methods, Monte Carlo simulations and finite-size scaling analysis. We study the transition line between that region and the paramagnetic phase. The numerical results show that this transition line belongs to the universality class of the antiferromagnetic RP^(2) model. The fact that one can define a universality class for the antiferromagnetic RP^(2) model, different from the one of the O(N) models, is puzzling and somehow contradicts naive expectations about universality.

Quick and robust method for trace determination of MeHg in rice and rice products without derivatisation

Peer reviewed

Quick and robust method for trace determination of MeHg in rice and rice products without derivatisation

Peer reviewed

Quick and robust method for trace determination of MeHg in rice and rice products without derivatisation

Peer reviewed

Sortase as a Tool in Biotechnology and Medicine

We have harnessed two reactions catalyzed by the enzyme sortase A and applied them to generate new methods for the purification and site-selective modification of recombinant protein therapeutics.

We utilized native peptide ligation —a well-known function of sortase A— to attach a small molecule drug specifically to the carboxy-terminus of a recombinant protein. By combining this reaction with the unique phase behavior of elastin-like polypeptides, we developed a protocol that produces homogenously-labeled protein-small molecule conjugates using only centrifugation. The same reaction can be used to produce unmodified therapeutic proteins simply by substituting a single reactant. The isolated proteins or protein-small molecule conjugates do not have any exogenous purification tags, eliminating the potential influence of these tags on bioactivity. Because both unmodified and modified proteins are produced by a general process that is the same for any protein of interest and does not require any chromatography, the time, effort, and cost associated with protein purification and modification is greatly reduced.

We also developed an innovative and unique method that attaches a tunable number of drug molecules to any recombinant protein of interest in a site-specific manner. Although the ability of sortase A to carry out native peptide ligation is widely used, we demonstrated that Sortase A is also capable of attaching small molecules to proteins through an isopeptide bond at lysine side chains within a unique amino acid sequence. This reaction —isopeptide ligation— is a new site-specific conjugation method that is orthogonal to all available protein-small conjugation technologies and is the first site-specific conjugation method that attaches the payload to lysine residues. We show that isopeptide ligation can be applied broadly to peptides, proteins, and antibodies using a variety of small molecule cargoes to efficiently generate stable conjugates. We thoroughly assessed the site-selectivity of this reaction using a variety of analytical methods and showed that in many cases the reaction is site-specific for lysines in flexible, disordered regions of the substrate proteins. Finally, we showed that isopeptide ligation can be used to create clinically-relevant antibody-drug conjugates that have potent cytotoxicity towards cancerous cells