Design and synthesis of potential antimicrobial agents

Chorismate mutase is one of the essential enzymes in the shikimate pathway and is key to the survival of the organism Mycobacterium tuberculosis. The x-ray crystal structure of this enzyme from Mycobacterium tuberculosis was manipulated to prepare an initial set of in silico protein models of the active site. Known inhibitors of the enzyme were docked into the active site using the flexible ligand / flexible active site side chains approach implemented in CAChe Worksystem (Fujitsu Ltd). The resulting complexes were refined by molecular dynamics studies in explicit water using Amber 9. This yielded a further set of protein models that were used for additional rounds of ligand docking. A binding hypothesis was established for the enzyme and this was used to screen a database of commercially available drug-like compounds. From these results new potential ligands were designed that fitted appropriately into the active site and matched the functional groups and binding motifs founds therein. Some of these compounds and close analogues were then synthesized and submitted for biological evaluation. As a separate part of this thesis, analogues of very active anti-tuberculosis pyridylcarboxamidrazone were also prepared. This was carried out by the addition and the deletion of the substitutions from the lead compound thereby preparing heteroaryl carboxamidrazone derivatives and related compounds. All these compounds were initially evaluated for biological activity against various gram positive organisms and then sent to the TAACF (USA) for screening against Mycobacterium tuberculosis. Some of the new compounds proved to be at least as potent as the original lead compound but less toxic.

The Value of Knowing that You Do Not Know

The value of knowing about data availability and system accessibility is analyzed through theoretical models of Information Economics. When a user places an inquiry for information, it is important for the user to learn whether the system is not accessible or the data is not available, rather than not have any response. In reality, various outcomes can be provided by the system: nothing will be displayed to the user (e.g., a traffic light that does not operate, a browser that keeps browsing, a telephone that does not answer); a random noise will be displayed (e.g., a traffic light that displays random signals, a browser that provides disorderly results, an automatic voice message that does not clarify the situation); a special signal indicating that the system is not operating (e.g., a blinking amber indicating that the traffic light is down, a browser responding that the site is unavailable, a voice message regretting to tell that the service is not available). This article develops a model to assess the value of the information for the user in such situations by employing the information structure model prevailing in Information Economics. Examples related to data accessibility in centralized and in distributed systems are provided for illustration.

Landscape of fear: A social history of the missile during the early years of the Cold War, 1950–1965

The missile's significance has been central to national security since the Soviet launching of Sputnik, and became increasingly important throughout the years of the Cold War. Much has been written about missile technology, but little has been written about how the development and deployment of this weapon affected Americans. The missile was developed to both deter war but also to win war. Its presence, however, was not always reassuring. Three areas of the United States are studied to evaluate the social implications of the missile during these pivotal years: San Francisco, home of multiple Nike installations; of Cape Canaveral, Florida, the nation's primary missile test center; the Great Plains, the location of the largest ICBM concentration in the country. Interviews were conducted, tours of facilities were taken, and local newspapers were reviewed. In conjunction with national newspapers and magazines and public opinion polls, this information provided a local social context for missile history. Nationally and locally, Americans both feared and praised the new technology. They were anxious for government funding in their cities and often felt that the danger the missile brought to their communities by making it as a Soviet target was justified in the larger cause for national security.

Changing Bacterial Growth Efficiencies across a Natural Nutrient Gradient in an Oligotrophic Estuary

Recent studies have characterized coastal estuarine systems as important components of the global carbon cycle. This study investigated carbon cycling through the microbial loop of Florida Bay by use of bacterial growth efficiency calculations. Bacterial production, bacterial respiration, and other environmental parameters were measured at three sites located along a historic phosphorus-limitation gradient in Florida Bay and compared to a relatively nutrient enriched site in Biscayne Bay. A new method for measuring bacterial respiration in oligotrophic waters involving tracing respiration of 13C-glucose was developed. The results of the study indicate that 13C tracer assays may provide a better means of measuring bacterial respiration in low nutrient environments than traditional dissolved oxygen consumption-based methods due to strong correlations between incubation length and δ13C values. Results also suggest that overall bacterial growth efficiency may be lower at the most nutrient limited sites.

Landscape of fear : a social history of the missile during the early years of the cold war, 1950-1965

The missile's significance has been central to national security since the Soviet launching of Sputnik, and became increasingly important throughout the years of the Cold War. Much has been written about missile technology, but little has been written about how the development and deployment of this weapon affected Americans. The missile was developed to both deter war but also to win war. Its presence, however, was not always reassuring. Three areas of the United States are studied to evaluate the social implications of the missile during these pivotal years: San Francisco, home of multiple Nike installations; of Cape Canaveral, Florida, the nation's primary missile test center; the Great Plains, the location of the largest ICBM concentration in the country. Interviews were conducted, tours of facilities were taken, and local newspapers were reviewed. In conjunction with national newspapers and magazines and public opinion polls, this information provided a local social context for missile history. Nationally and locally, Americans both feared and praised the new technology. They were anxious for government funding in their cities and often felt that the danger the missile brought to their communities by making it as a Soviet target was justified in the larger cause for national security.

Estudo teórico de intermediários tetraédricos acidez / basicidade e estereosseletividade enzimáticos

The present work aimed first, the theoretical study of tetrahedral intermediate stability formed from carbonyl addition reactions using the second (MP2) and third (MP3) order Møller–Plesset perturbation theory. Linear correlations between electronic energy difference of reactions with Wiberg Indexes and C-O bond lengths were obtained, and was observed that the stability of adducts formed depends directly of electronic density involved between these atoms. The knowing of electronic parameters of these structures has an important hole due to the large use on reactions that in his course forms this tetrahedral intermediate. Employing the ONIOM (B3LYP:AMBER) methodology, was evaluated the stereoselectivity of a enzymatic reaction between CAL B enzyme and a long chain ester. In this study, were obtained the electronic energies of ground state and intermediate state of transesterification rate-determing step from two possible proquirals faces Re and Si. The objective was study the enantioselectivity of CAL B and rationalizes it using quantum theory of atoms in molecules (QTAIM). A theoretical study employing inorganic compounds was performed using ab initio CBS-QB3 method aiming to find a link between thermodynamic and equilibrium involving acids and bases. The results observed showed an excellent relationship between difference in Gibbs free energy, ΔG of acid dissociation reaction and ΔG of hydrolysis reaction of the corresponding conjugate base. It was also observed, a relationship between ΔG of hydrolysis reaction of conjugate acids and their corresponding atomic radius showing that stability plays an important role in hydrolysis reactions. The importance of solvation in acid/base behavior when compared to theoretical and experimental ΔG´s also was evaluated.

Novos protocolos teóricos utilizados nos estudos das ligações hidrogênio-hidrogênio, na estabilidade do tetraedrano, seus derivados e das reações de diels-alder e na quantificação da afinidade de fármacos

This thesis was performed in four chapters, at the theoretical level, focused mainly on electronic density. In the first chapter, we have applied an undergraduate minicourse of Diels-Alder reaction in Federal University of Rio Grande do Norte. By using computational chemistry tools students could build the knowledge by themselves and they could associate important aspects of physical-chemistry with Organic Chemistry. In the second chapter, we studied a new type of chemical bond between a pair of identical or similar hydrogen atoms that are close to electrical neutrality, known as hydrogen-hydrogen (H-H) bond. In this study performed with complexed alkanes, provides new and important information about their stability involving this type of interaction. We show that the H-H bond playing a secondary role in the stability of branched alkanes in comparison with linear or less branched isomers. In the third chapter, we study the electronic structure and the stability of tetrahedrane, substituted tetrahedranes and silicon and germanium parents, it was evaluated the substituent effect on the carbon cage in the tetrahedrane derivatives and the results indicate that stronger electron withdrawing groups (EWG) makes the tetrahedrane cage slightly unstable while slight EWG causes a greater instability in the tetrahedrane cage. We showed that the sigma aromaticity EWG and electron donating groups (EDG) results in decrease and increase, respectively, of NICS and D3BIA aromaticity indices. In addition, another factor can be utilized to explain the stability of tetra-tert-butyltetrahedrane as well as HH bond. GVB and ADMP were also used to explain the stability effect of the substituents bonded to the carbon of the tetrahedrane cage. In the fourth chapter, we performed a theoretical investigation of the inhibitory effect of the drug abiraterone (ABE), used in the prostate cancer treatment as CYP17 inhibitor, comparing the interaction energies and electron density of the ABE with the natural substrate, pregnenolone (PREG). Molecular dynamics and docking were used to obtain the CYP1ABE and CYP17-PREG complexes. From molecular dynamics was obtained that the ABE has higher diffusion trend water CYP17 binding site compared to the PREG. With the ONIOM (B3LYP:AMBER) method, we find that the interaction electronic energy of ABE is 21.38 kcal mol-1 more stable than PREG. The results obtained by QTAIM indicate that such stability is due a higher electronic density of interactions between ABE and CYP17

Student Independent Projects Environmental Studies: Energizing the Future: Meeting Future Power Needs of Grenfell College

In this paper I pose the Questions: Is it feasible to install a large wind turbine(S) at Grenfell College as a pilot project, and what will the benefits of the installation be to Grenfell if the project goes ahead? My answers are based on a literature review, data analysis from previous experiments, and a SWOT analysis. I will conclude by recommending a course of action for Grenfell that will move it toward using more renewable energy, and becoming a local resource for alternative energy solutions.

Bola na rede: uma análise das estratégias comunicacionais de empresas esportivas no ambiente digital conectado

O uso das mídias sociais digitais como meio de divulgação de produtos, serviços e conteúdos organizacionais tem crescido nas últimas décadas e ganhou especial atenção nos planejamentos de comunicação organizacional e nos estudos acadêmicos sobre o tema. Nesse sentido, o segmento de empresas esportivas atua com destaque, despertando o interesse e a empatia do consumidor. Por meio de análise bibliográfica e estudo empírico, esta pesquisa teve como objetivo investigar as ações de comunicação mercadológica do segmento esportivo no ambiente digital conectado, através de um estudo de caso múltiplo das empresas Nike e Adidas. Para a obtenção dos dados, foram realizadas entrevistas em profundidade com profissionais do mercado e aplicado um protocolo de investigação de redes sociais digitais nos perfis das duas empresas. Após a coleta dos dados, estes foram analisados à luz das teorias estudadas nos capítulos iniciais (que abordaram temas como comunicação organizacional, comunicação digital, esporte e comunicação esportiva), e foi possível concluir, entre outros pontos, que, no universo do segmento esportivo, a comunicação digital conectada não prioriza o diálogo com seus públicos de interesse, sendo essencialmente baseada na divulgação unilateral de conteúdos, nem tampouco explora a potencialidade de cada uma das plataformas digitais disponíveis, replicando conteúdos em diferentes ambientes. Ficou evidente, também, o uso dos elementos constituintes do universo esportivo como argumentos estratégicos de comunicação das empresas, decorrente de sua capacidade de estreitar os laços relacionais com os públicos de interesse, por meio de seus apelos simbólicos de fácil identificação social.

Catalytic enantioselective electrocyclic cascades

A catalytic enantioselective electrocyclic cascade leads to the construction of topologically complex systems comprising multiple rings with up to three stereocentres. This phase-transfer catalysed process offers a new strategy for the rapid and enantioselective generation of complex products bearing all-carbon quaternary stereogenic centres. © 2012 The Royal Society of Chemistry.

Postdoktoral karriär vid Stockholms universitet ur ett jämställdhetsperspektiv

Several previous studies indicate that among newly graduated PhDs, women tend to continue with a postdoctoral academic career to a lesser extent than men do. The Central PhD Student Council (CDR) has investigated to what degree this is also the case for Stockholm University. Using various sources, the relative change of the gender balance of PhD students compared to researchers at a postdoctoral level has been assessed at the four faculties of Stockholm University. For the Faculty of Science, the four different sections have been analysed as well. CDR finds that it is first and foremost at this faculty that a clear change in the gender balance between PhD students and postdoctoral researchers is discerned. Even though the variations between the individual departments and sections at the faculty are large, as a whole the relative decrease of the proportion of women is between 11 % and 21 %, depending on what metric is used. The dropoff of female researchers takes place primarily in already male-dominated areas of research. Unlike at the other faculties, we also find that the proportion of female senior lecturers at the Faculty of Science is lower than what could be expected. The proportion of female professors, even among new recruits, is still lower than the population of hypothetical recruits at all faculties – except at the Faculty of Humanities. We do, however, note that the proportion of female professors at the Faculty of Science is currently increasing and approaching that of the population of hypothetical recruits. At the Faculty of Social Sciences we see that, compared to the rest of the faculty, the proportion of women within the educational sciences is considerably higher and when excluding these subjects the trend towards more female professors disappears. CDR concludes that it is important to increase the directed efforts to encourage support to newly graduated female PhDs within male-dominated areas to stay in academia. Furthermore, it is crucial to study the reasons for a larger female drop-off within certain areas of research in the transition from PhD studies to a postdoctoral level. We further consider it important to ensure that women are given the same possibilities as men to qualify themselves scientifically and not be burdened with teaching and administrative duties to a larger extent than men are.

Pileated Woodpecker Occupancy and the Occurrence and Recruitment of Key Habitat Attributes in a Managed Forest

Thesis (Master's)--University of Washington, 2016-08

Mothers’ perception of recovery and satisfaction with patent medicine dealers’ treatment of childhood febrile conditions in rural communities

Background Infant mortality in rural areas of Nigeria can be minimized if childhood febrile conditions are treated by trained health personnel, deployed to primary healthcare centres (PHCs) rather than the observed preference of mothers for patent medicine dealers (PMDs). However, health service utilization/patronage is driven by consumer satisfaction and perception of services/product value. The objective of this study was to determine ‘mothers’ perception of recovery’ and ‘mothers’ satisfaction’ after PMD treatment of childhood febrile conditions, as likely drivers of mothers’ health-seeking behaviour, which must be targeted to reverse the trend. Methods Ugwuogo-Nike, in Enugu, Nigeria, has many PMDs/PHCs, and was selected based on high prevalence of childhood febrile conditions. In total, 385 consenting mothers (aged 15–45 years) were consecutively recruited at PMD shops, after purchasing drugs for childhood febrile conditions, in a cross-sectional observational study using a pre-tested instrument; 33 of them (aged 21–47 years) participated in focus group discussions (FGDs). Qualitative data were thematically analysed while a quantitative study was analysed with Z score and Chi square statistics, at p < 0.05. Results Most participants in FGDs perceived that their child had delayed recovery, but were satisfied with PMDs’ treatment of childhood febrile conditions, for reasons that included politeness, caring attitude, drug availability, easy accessibility, flexibility in pricing, shorter waiting time, their God-fearing nature, and disposition as good listeners. Mothers’ satisfaction with PMDs’ treatment is significantly (p < 0.05) associated with mothers’ perception of recovery of their child (χ2 = 192.94, df = 4; p < 0.0001; Cramer’s V = 0.7079). However, predicting mothers’ satisfaction with PMDs’ treatment from a knowledge of mothers’ perception of recovery shows a high accord (lambda[A from B] = 0.8727), unlike when predicting mothers’ perception of recovery based on knowledge of mothers’ satisfaction with PMDs’ treatment (lambda[A from B] = 0.4727). Conclusions Mothers’ satisfaction could be the key ‘driver’ of mothers’ health-seeking behaviour and is less likely to be influenced by mothers’ perception of recovery of their child. Therefore, mothers’ negative perception of their child’s recovery may not induce proportionate decline in mothers’ health-seeking behaviour (patronage of PMDs), which might be influenced mainly by mothers’ satisfaction with the positive attributes of PMDs’ personality/practice and sets an important agenda for PHC reforms.

The spatial rhetoric of Gustav Zeiller's popular anatomical museum

This article focuses on the public experience of science by studying the exhibition practice of a small popular anatomy museum. The owner, Gustav Zeiller, a little-known German model maker and entrepreneur, opened his private collection in Dresden in 1888 with the aim of providing experts and laymen alike with a scientific education on bodily matters and health care. The spatial configuration of his museum environment turned the wax models into didactic instruments. Relying on the possible connexion between material culture studies and history of the emotions, this article highlights how Zeiller choreographed the encounter between the museum objects and its visitors. I argue that the spatial set up of his museum objects entailed rhetorical choices that did not simply address the social utility of his museum. Moreover, it fulfilled the aim of modifying the emotional disposition of his intended spectatorship. I hope to show that studying the emotional responses toward artefacts can offer a fruitful approach to examine the public experience of medicine.