Synthesis of a PbTx-2 photoaffinity and fluorescent probe and an alternative synthetic route to photoaffinity probes

A natural phenomenon characterized by dense aggregations of unicellular photosynthetic marine organisms has been termed colloquially as red tides because of the vivid discoloration of the water. The dinoflagellate Karenia brevis is the cause of the Florida red tide bloom. K. brevis produces the brevetoxins, a potent suite of neurotoxins responsible for substantial amounts of marine mammal and fish mortalities. When consumed by humans, the toxin causes Neurotoxic Shellfish Poisoning (NSP). The native function of brevetoxin within the organism has remained mysterious since its discovery. There is a need to identify factors which contribute to and regulate toxin production within K. brevis. These toxins are produced and retained within the cell implicating a significant cellular role for their presence. Localization of brevetoxin and identification of a native receptor may provide insight into its native role as well as other polyether ladder type toxins such as the ciguatoxins, maitotoxins, and yessotoxins. In higher organisms these polyether ladder molecules bind to transmembrane proteins with high affinity. We anticipated the native brevetoxin receptor would also be a transmembrane protein. Photoaffinity labeling has become increasingly popular for identifying ligand receptors. By attaching ligands to these photophors, one is able to activate the molecule after the ligand binds to its receptor to obtain a permanent linkage between the two. Subsequent purification provides the protein with the ligand directly attached. A molecule that is capable of fluorescence is a fluorophore, which upon excitation is capable of re-emitting light. Fluorescent labeling uses fluorophores by attaching them covalently to biologically active compounds. The synthesis of a brevetoxin photoaffinity probe and its application in identifying a native brevetoxin receptor will be described. The preparation of a fluorescent derivative of brevetoxin will be described and its use in localizing the toxin to an organelle within K. brevis. In addition, the general utility of a synthesized photoaffinity label with other toxins having similar functionality will be described. An alternative synthetic approach to a general photoaffinity label will also be discussed whose goal was to accelerate the preparation and improve the overall synthetic yields of a multifunctional label.

THE DARK PERSONALITY AND JOB SUCCESS IN THE UNITED STATES ARMY: USE OF INTERPERSONAL MANIPULATION IN THE WORKPLACE

This dissertation relates job desires and outcomes to the Dark Personality (Psychopathy, Machiavellianism, Narcissism, Low Agreeableness, Low Honesty-Humility) in the United States Army. It purports that individuals high on the Dark Personality desire more power, money, and status, and that they obtain jobs that afford them these luxuries by using manipulation at work. Two pilot studies used samples of United States Army members to create and test index variables: Dark Personality, Total Manipulation in the workplace, Desire for Job Success, and Total Job Success in the Army. Individual personality traits, manipulation tactics, and job desires were examined in secondary analyses. Using a sample of 468 United States Army Members, central analyses indicated that Army members high on the Dark Personality desired Job Success. Likewise, army members higher on the Dark Personality used more Manipulation tactics at work, including the egregious tactics. Yet, using more Manipulation tactics at work predicted lower levels of Job Success in the Army. Most manipulation tactics had a negative impact on Job Success, with the exception of soft tactics like Reason and Responsibility Invocation. Together, these results indicate that selective use of soft manipulation predicted Job Success, but use of more manipulation tactics predicted less Job Success in the Army. Curvilinear results indicated that being either very low or very high on the Dark Personality predicted more Job Success in the Army, whereas having intermediate levels of the Dark Personality predicted less Job Success. Finally, possessing the Dark Personality and using more Manipulation tactics at work, together, predicted less Job Success in the Army. Collectively, the results indicate that army members with intermediate levels of the Dark Personality want more powerful and high paying jobs, yet their strategy of manipulating their coworkers to move up the job ladder does not result in higher ranking, higher paying Army positions. However, Army members highest on the Dark Personality achieved job success, defying the maladaptive influence that antisocial personality traits and manipulative behaviour had on job success for most Army members. Therefore, this dissertation indicates that successful corporate scoundrels exist in the Army, but there are few of them.

Efficacy and Safety of Radium-223 Dichloride in Symptomatic Castration-resistant Prostate Cancer Patients With or Without Baseline Opioid Use From the Phase 3 ALSYMPCA Trial

Background: The phase 3 ALSYMPCA trial enrolled metastatic castration-resistant prostate cancer patients with or without baseline opioid use.

Objective: To assess the efficacy and safety of radium-223 dichloride (radium-223) versus placebo in ALSYMPCA patients by baseline opioid use.

Design, setting, and participants: Nine hundred and twenty one patients enrolled at 136 centers globally.

Intervention: Radium-223 (50 kBq/kg, intravenous injection) every 4 wk for six cycles or matching placebo, each plus best standard of care.

Outcome measurements and statistical analysis: Primary endpoint (overall survival [OS]), main secondary efficacy endpoints, and safety were evaluated by baseline opioid use. Additional analyses included time to first opioid use, time to first external beam radiation therapy for bone pain, and safety of concomitant external beam radiation therapy.

Results and limitations: At baseline, 408 (44%) patients had no pain and no analgesic use or mild pain with nonopioid therapy (World Health Organization ladder pain score 0–1 [nonopioid subgroup]), and 513 (56%) had moderate pain with occasional opioids or severe pain with regular daily opioids (World Health Organization ladder pain score 2–3 [opioid subgroup]). Radium-223 significantly prolonged OS versus placebo in nonopioid (hazard ratio [HR] = 0.70; 95% confidence interval [CI]: 0.52–0.93; p = 0.013) and opioid (HR = 0.68; 95% CI: 0.54–0.86; p = 0.001) subgroups, and significantly reduced risk of symptomatic skeletal events versus placebo, regardless of baseline opioid use (nonopioid subgroup: HR = 0.56, 95% CI: 0.39–0.82, p = 0.002; opioid subgroup: HR = 0.72, 95% CI: 0.53–0.98, p = 0.038). Time to first opioid use for bone pain was significantly delayed with radium-223 versus placebo (HR = 0.62, 95% CI: 0.46–0.85,p = 0.002). Adverse event incidences were similar between opioid subgroups.

Conclusions: Radium-223 versus placebo significantly prolonged OS and reduced symptomatic skeletal event risk with a favorable safety profile in castration-resistant prostate cancer patients with symptomatic bone metastases, regardless of baseline opioid use.

Patient summary: In this ALSYMPCA opioid subgroup analysis, baseline symptom levels did not appear to impact radium-223 dichloride efficacy or safety.

Hierarchical Reconstruction Method for Solving Ill-posed Linear Inverse Problems

We present a detailed analysis of the application of a multi-scale Hierarchical Reconstruction method for solving a family of ill-posed linear inverse problems. When the observations on the unknown quantity of interest and the observation operators are known, these inverse problems are concerned with the recovery of the unknown from its observations. Although the observation operators we consider are linear, they are inevitably ill-posed in various ways. We recall in this context the classical Tikhonov regularization method with a stabilizing function which targets the specific ill-posedness from the observation operators and preserves desired features of the unknown. Having studied the mechanism of the Tikhonov regularization, we propose a multi-scale generalization to the Tikhonov regularization method, so-called the Hierarchical Reconstruction (HR) method. First introduction of the HR method can be traced back to the Hierarchical Decomposition method in Image Processing. The HR method successively extracts information from the previous hierarchical residual to the current hierarchical term at a finer hierarchical scale. As the sum of all the hierarchical terms, the hierarchical sum from the HR method provides an reasonable approximate solution to the unknown, when the observation matrix satisfies certain conditions with specific stabilizing functions. When compared to the Tikhonov regularization method on solving the same inverse problems, the HR method is shown to be able to decrease the total number of iterations, reduce the approximation error, and offer self control of the approximation distance between the hierarchical sum and the unknown, thanks to using a ladder of finitely many hierarchical scales. We report numerical experiments supporting our claims on these advantages the HR method has over the Tikhonov regularization method.

O PARFOR na furg e os efeitos na constituição das subjetividades de professoras pedagogas

O presente estudo refere-se a uma dissertação de mestrado em Educação, a qual teve como finalidade problematizar a constituição de subjetividades docentes no âmbito do Curso PARFOR Pedagogia, ofertado pela Universidade do Rio Grande (FURG). O foco teórico que alimenta este trabalho segue alguns elementos dos estudos foucaultianos que se detêm na perspectiva da governamentalidade e, por esse viés investigativo, as problematizações foram se constituindo, basicamente, a partir de três ferramentas analíticas: discurso, governo e subjetivação. Através desta perspectiva de estudo, proponho compreender as políticas de formação docente como uma questão de governo das condutas e o PARFOR, como uma tecnologia de governo que conduz o modo como as professoras que vivenciam essa formação atuam e se pensam nessa sociedade. A partir das narrativas de algumas professoras formadoras e acadêmicas deste curso, foi possível evidenciar o currículo como um espaço de controle e produção de subjetividades. Argumentei que as professoras-acadêmicas, ao justificarem as suas escolhas pelo PARFOR, foram capturadas pelo discurso das faltas com a profissão, tendo suas condutas orientadas a buscar o ensino superior como meio de qualificação e ascensão social. Após, discuti que as práticas realizadas no projeto de formação seguem um ciclo que leva à conversão. Sustentei esta ideia mostrando que as docentes são convocadas a se confessar por meio das escritas dos memoriais e TCC’s, reconhecendo-se como sujeitos da educação - avaliando, julgando, comparando, criando resistências, produzindo verdades sobre si – e assim convertendo-se a uma nova postura que, de alguma forma, venha assegurar o sucesso do seu fazer docente. Por fim, chamo a atenção para as relações de poder imbricadas no equilíbrio dos interesses e forças que envolvem o currículo de formação e seus efeitos na constituição dos sujeitos que vivenciaram este processo. Defendo que as professoras-acadêmicas, ao não terem suas expectativas contempladas no curso, promovem, em diferentes momentos, ações ou resistências, entrando em conflito com as professoras formadoras. Os efeitos dessa forma de subjetivação vão gerando negociações, indicando rumos diferentes aos pré-estabelecidos inicialmente.

Detecção de interface em tanques de petróleo usando transmissores de nível e controladores Fuzzy

This work presents a proposal to detect interface in atmospheric oil tanks by installing a differential pressure level transmitter to infer the oil-water interface. The main goal of this project is to maximize the quantity of free water that is delivered to the drainage line by controlling the interface. A Fuzzy Controller has been implemented by using the interface transmitter as the Process Variable. Two ladder routine was generated to perform the control. One routine was developed to calculate the error and error variation. The other was generate to develop the fuzzy controller itself. By using rules, the fuzzy controller uses these variables to set the output. The output is the position variation of the drainage valve. Although the ladder routine was implemented into an Allen Bradley PLC, Control Logix family it can be implemented into any brand of PLCs

Double Hybrid Functionals and the Π-System Bond Length Alternation Challenge: Rivaling Accuracy of Post-HF Methods

Predicting accurate bond length alternations (BLAs) in long conjugated oligomers has been a significant challenge for electronic-structure methods for many decades, made particularly important by the close relationships between BLA and the rich optoelectronic properties of π-delocalized systems. Here, we test the accuracy of recently developed, and increasingly popular, double hybrid (DH) functionals, positioned at the top of Jacobs Ladder of DFT methods of increasing sophistication, computational cost, and accuracy, due to incorporation of MP2 correlation energy. Our test systems comprise oligomeric series of polyacetylene, polymethineimine, and polysilaacetylene up to six units long. MP2 calculations reveal a pronounced shift in BLAs between the 6-31G(d) basis set used in many studies of BLA to date and the larger cc-pVTZ basis set, but only modest shifts between cc-pVTZ and aug-cc-pVQZ results. We hence perform new reference CCSD(T)/cc-pVTZ calculations for all three series of oligomers against which we assess the performance of several families of DH functionals based on BLYP, PBE, and TPSS, along with lower-rung relatives including global- and range-separated hybrids. Our results show that DH functionals systematically improve the accuracy of BLAs relative to single hybrid functionals. xDH-PBE0 (N4 scaling using SOS-MP2) emerges as a DH functional rivaling the BLA accuracy of SCS-MP2 (N5 scaling), which was found to offer the best compromise between computational cost and accuracy the last time the BLA accuracy of DFT- and wave function-based methods was systematically investigated. Interestingly, xDH-PBE0 (XYG3), which differs to other DHs in that its MP2 term uses PBE0 (B3LYP) orbitals that are not self-consistent with the DH functional, is an outlier of trends of decreasing average BLA errors with increasing fractions of MP2 correlation and HF exchange.

Ambiente para avaliação de controladores fuzzy aplicados ao método de elevação artificial por bombeio centrífugo submerso

From their early days, Electrical Submergible Pumping (ESP) units have excelled in lifting much greater liquid rates than most of the other types of artificial lift and developed by good performance in wells with high BSW, in onshore and offshore environments. For all artificial lift system, the lifetime and frequency of interventions are of paramount importance, given the high costs of rigs and equipment, plus the losses coming from a halt in production. In search of a better life of the system comes the need to work with the same efficiency and security within the limits of their equipment, this implies the need for periodic adjustments, monitoring and control. How is increasing the prospect of minimizing direct human actions, these adjustments should be made increasingly via automation. The automated system not only provides a longer life, but also greater control over the production of the well. The controller is the brain of most automation systems, it is inserted the logic and strategies in the work process in order to get you to work efficiently. So great is the importance of controlling for any automation system is expected that, with better understanding of ESP system and the development of research, many controllers will be proposed for this method of artificial lift. Once a controller is proposed, it must be tested and validated before they take it as efficient and functional. The use of a producing well or a test well could favor the completion of testing, but with the serious risk that flaws in the design of the controller were to cause damage to oil well equipment, many of them expensive. Given this reality, the main objective of the present work is to present an environment for evaluation of fuzzy controllers for wells equipped with ESP system, using a computer simulator representing a virtual oil well, a software design fuzzy controllers and a PLC. The use of the proposed environment will enable a reduction in time required for testing and adjustments to the controller and evaluated a rapid diagnosis of their efficiency and effectiveness. The control algorithms are implemented in both high-level language, through the controller design software, such as specific language for programming PLCs, Ladder Diagram language.

La gestion facultaire en contexte budgétaire difficile : analyse sous l’angle de l’activité des doyens

Cette thèse examine le comportement de quatre doyens canadiens dont les facultés sont en situation financière précaire. Dans un contexte d’imputabilité accrue des établissements universitaires et de modification constante aux rapports de pouvoir internes, cette étude présente une importance particulière pour la compréhension de l’exercice réel des fonctions administratives des cadres académiques intermédiaires. La recherche scientifique sur ce sujet attribue aux doyens une contribution vitale au bon fonctionnement des établissements; le doyen en demeure pourtant un des rouages les moins étudiés. La position intermédiaire qu’occupent les doyens les place dans un conflit de rôle évident. Pris entre des rôles et des attentes contradictoires émis par la communauté facultaire, d’une part, et par la direction de l’établissement, d’autre part, ils doivent conjuguer cette ambiguïté avec des responsabilités croissantes en matière de gestion financière, de leadership et d’opérationnalisation des visées stratégiques de l’université. Comprendre la façon dont les doyens arrivent à mobiliser les leviers institutionnels à leur disposition pour résoudre des situations critiques permettra d’améliorer notre compréhension de la complexité de la prise de décision au niveau intermédiaire et notre compréhension globale du fonctionnement des établissements universitaires. La présente étude importe de la théorie culturelle-historique de l’activité (culturalhistorical activity theory, ou CHAT) un modèle d’analyse de l’activité collective en situation de contradictions systémiques. Quatre doyens d’une même université ont été interviewés afin de présenter une situation vécue de difficulté budgétaire, et le processus de résolution qui a suivi. Les données ont été analysées qualitativement afin de décrire les interventions que réalisent les doyens sur les leviers présents dans leurs environnements. Les résultats suggèrent que les participants ont misé sur une maîtrise fine des rouages institutionnels et sur des interventions diversifiées afin de résoudre les contradictions de leurs systèmes d’activité.

La gestion facultaire en contexte budgétaire difficile : analyse sous l’angle de l’activité des doyens

Cette thèse examine le comportement de quatre doyens canadiens dont les facultés sont en situation financière précaire. Dans un contexte d’imputabilité accrue des établissements universitaires et de modification constante aux rapports de pouvoir internes, cette étude présente une importance particulière pour la compréhension de l’exercice réel des fonctions administratives des cadres académiques intermédiaires. La recherche scientifique sur ce sujet attribue aux doyens une contribution vitale au bon fonctionnement des établissements; le doyen en demeure pourtant un des rouages les moins étudiés. La position intermédiaire qu’occupent les doyens les place dans un conflit de rôle évident. Pris entre des rôles et des attentes contradictoires émis par la communauté facultaire, d’une part, et par la direction de l’établissement, d’autre part, ils doivent conjuguer cette ambiguïté avec des responsabilités croissantes en matière de gestion financière, de leadership et d’opérationnalisation des visées stratégiques de l’université. Comprendre la façon dont les doyens arrivent à mobiliser les leviers institutionnels à leur disposition pour résoudre des situations critiques permettra d’améliorer notre compréhension de la complexité de la prise de décision au niveau intermédiaire et notre compréhension globale du fonctionnement des établissements universitaires. La présente étude importe de la théorie culturelle-historique de l’activité (culturalhistorical activity theory, ou CHAT) un modèle d’analyse de l’activité collective en situation de contradictions systémiques. Quatre doyens d’une même université ont été interviewés afin de présenter une situation vécue de difficulté budgétaire, et le processus de résolution qui a suivi. Les données ont été analysées qualitativement afin de décrire les interventions que réalisent les doyens sur les leviers présents dans leurs environnements. Les résultats suggèrent que les participants ont misé sur une maîtrise fine des rouages institutionnels et sur des interventions diversifiées afin de résoudre les contradictions de leurs systèmes d’activité.

Inteligencia territorial para la recuperación de las dinámicas socio-productivas en la subregión de Lengupá (Boyacá, Colombia)

Este documento corresponde al ejercicio preliminar de la línea de investigación en dinámicas territoriales, y es uno de los artículos científicos propuestos como resultado del Proyecto de investigación “Inteligencia territorial para la recuperación de las dinámicas socio-productivas de la subregión de Lengupá”. Por lo tanto, presenta los resultados de la fase exploratoria, correspondiente al diagnóstico regional en el marco de los enfoques teóricos desde los cuales la región es estudiada. A continuación, se presentarán los dos pilares fundamentales de ésta investigación: el territorio y la Inteligencia Territorial. En el caso del territorio, este proceso de investigación parte de un diferenciación previa respecto al lugar y al espacio, debido a que en el territorio se dan relaciones históricas y de poder en una relación dialéctica, entre los atributos ecológicos y culturales, teniendo en cuenta el planteamiento de Sasquet, (2015) cuando menciona que para comprender el territorio es necesario comprender el espacio geográfico, territorialidad humana, en escala subregional y a través del tiempo.

Covariant Spectator Theory and Hadron Structure

We present the first results of a study on meson spectroscopy using a covariant formalism based on the Covariant Spectator Theory. Our approach is derived directly in Minkowski space and it approximates the Bethe–Salpeter equation by taking effectively into account the contributions from both ladder and crossed ladder diagrams in the $q\bar{q}$ interaction kernel. A general Lorentz structure of the kernel is tested and chiral constraints on the kernel are discussed. Results for the pion form factor are also presented.

Heavy-Light Mesons in Minkowski Space

Following up on earlier work on the $q\bar{q}$-bound-state problem using a covariant, chiral-symmetric formalism based upon the Covariant Spectator Theory, we study the heavy–light case for both pseudoscalar and vector mesons. Derived directly in Minkowski space, our approach approximates the full Bethe–Salpeter-equation, taking into account, effectively, the contributions of both ladder and crossed ladder diagrams in the kernel. Results for several mass spectra using a relativistic covariant generalization of a Cornell plus a constant potential to model the interquark interaction are given and discussed.

Development and Detailed Characterization of Innovative, High-Performance Membrane Materials for CO2 Capture Processes

The scope of this dissertation is to study the transport phenomena of small molecules in polymers and membranes for gas separation applications, with particular attention to energy efficiency and environmental sustainability. This work seeks to contribute to the development of new competitive selective materials through the characterization of novel organic polymers such as CANALs and ROMPs, as well as through the combination of selective materials obtaining mixed matrix membranes (MMMs), to make membrane technologies competitive with the traditional ones. Kinetic and thermodynamic aspects of the transport properties were investigated in ideal and non-ideal scenarios, such as mixed-gas experiments. The information we gathered contributed to the development of the fundamental understanding related to phenomenon like CO2-induced plasticization and physical aging. Among the most significant results, ZIF-8/PPO MMMs provided materials whose permeability and selectivity were higher than those of the pure materials for He/CO2 separation. The CANALs featured norbornyl benzocyclobutene backbone and thereby introduced a third typology of ladder polymers in the gas separation field, expanding the structural diversity of microporous materials. CANALs have a completely hydrocarbon-based and non-polar rigid backbone, which makes them an ideal model system to investigate structure-property correlations. ROMPs were synthesized by means of the ring opening metathesis living polymerization, which allowed the formation of bottlebrush polymers. CF3-ROMP reveled to be ultrapermeable to CO2, with unprecedented plasticization resistance properties. Mixed-gas experiments in glassy polymer showed that solubility-selectivity controls the separation efficiency of materials in multicomponent conditions. Finally, it was determined that plasticization pressure in not an intrinsic property of a material and does not represent a state of the system, but rather comes from the contribution of solubility coefficient and diffusivity coefficient in the framework of the solution-diffusion model.