1,720,972 research outputs found
Synthesis of Site-specific DNA adducts of Aromatic Amine and Nitro-aromatic Carcinogens and Study of their Replication Properties
No full textA large number of nitro polycyclic aromatic hydrocarbons (nitro-PAHs) and heterocyclic aromatic amines (HAAs) are present in the environment and many compounds of these families are carcinogenic. 2ʹ-Deoxyribonucleic acid (DNA) adduct or lesion formation by these class of compounds play an important role in the process of carcinogenesis. Upon metabolic activation by cytochrome P450 family of enzymes, these nitro-PAHs or HAAs form electrophilic metabolites, which then reacts with the nucleic acid bases of DNA to form DNA-carcinogen adducts. Subsequent to DNA damage, activation of DNA damage checkpoints helps to arrest the growth of the damaged cell and allows the DNA repair mechanism to rectify the error. However, sometimes prior to DNA repair, cells can undergo replications, but replicative DNA polymerases, in most cases, cannot bypass a DNA damage. Depending on the nature of the damage, a special group of DNA polymerases known as translesion synthesis (TLS) DNA polymerases help to bypass this bulky adducts. But this damaged DNA replication by TLS polymerases can lead to mutations, which, in turn, may lead to production of altered proteins. If the mutation occurs in a tumor suppressor gene or oncogene, it can lead to human cancers.
3-Nitrobenzanthrone (3-nitro-7H-benz-[d,e]anthracen-7-one, 3-NBA), a member of the nitro polycyclic aromatic hydrocarbon (PAH), is found in exhausts from diesel and gasoline engines owing to incomplete combustion of the fuel and is considered an environmental pollutant and a suspected human carcinogen. 3-NBA is much more mutagenic than the well-studied PAH benzo[a]pyrene (B[a]P) and the most abundant nitroarene found in diesel exhaust, 1-nitropyrene (1-NP). It causes DNA damage and exhibits mutagenicity in bacterial and mammalian cells. 3-NBA is one of the most potent mutagens in the Ames’ assay. Upon metabolic activation, it forms N-(deoxyguanosin-8-yl)-3-amino-benzanthrone (C8-dG-ABA), the major alkylation adduct at the C8-position of 2ʹ-deoxyguanosine (dG). To investigate its replication properties, I have used a total synthesis approach to synthesize the C8-dG-ABA adduct. The adduct was incorporated into a defined site of a dodecamer oligodeoxynucleotide, 5’-CATG*ATGACGCT-3’, where G* represents the adducted dG and the bypass mechanism was analyzed using crystallographic techniques with the incoming 2ʹ-deoxycytosine triphosphate (dCTP).
The environmental pollutant 6-nitrochrysene (6-NC) is a potent mutagen and mammary carcinogen in rats. 6-NC is the most potent carcinogen ever tested in the newborn mouse assay. Upon metabolic activation, 6-NC forms two major adducts with dG, one at the C8-position, N-(dG-8-yl)-6-AC, and the other at the N2-position, 5-(dG-N2-yl)-6-AC. Here, we report the total synthesis of site-specific oligonucleotides containing the 6-NC-derived C8 dG adduct, N-(dG-8-yl)-6-AC by Pd-catalyzed Buchwald-Hartwig cross coupling of 6-aminochrysene with protected C8-bromo-dG derivative. The monomer for solid-phase DNA synthesis was prepared from this adduct by its deprotection followed by conversion to the corresponding phosphoramidite, which was used to synthesize the site-specific oligonucleotides 5’-GTGCG*TGTTTGT-3, which contains the local DNA sequence of the tumor suppressor gene p53 (codon 273 is underlined), where G* represents the C8-dG-6-Ac adduct. The adduct-containing oligonucleotides were purified by reversed phase HPLC followed by denaturing polyacrylamide gel electrophoresis and characterized by mass spectrometry. Oligonucleotide 5’-GTGCG*TGTTTGT-3 was then incorporated into a plasmid and replicated in human embryonic kidney 293T cells, which showed that the DNA adduct is mutagenic inducing largely G→T transversions. We also investigated the roles of several translesion synthesis DNA polymerases in its bypass using siRNA knockdown approach.
2-Amino-9H-pyrido [2, 3-b] indole (AαC) is the most abundant heterocyclic aromatic amine (HAA) and a possible liver and gastrointestinal carcinogen found in the mainstream tobacco smoke. Upon cytochrome P450 mediated N-oxidation of the exocyclic amine of AαC, it reacts to DNA to form N-(deoxyguanosin-8-yl)-AαC adduct (C8-dG-AαC). To study the structural and biological effects of C8-dG-AαC lesion, we conceived a total synthesis approach using 9-benzyl-9H- pyrido [2, 3-b] indol-2-amine and protected C8-bromo-2\u27-deoxyguanosine derivative as precursors to furnish the 2\u27-dG-C8-AαC adduct. The DNA adduct will be incorporated into defined sites of a dodecamer oligodeoxynucleotide, 5’-GTGCG*TGTTTGT-3’, as in the previous case to understand the carcinogenic potency and critical roles of human DNA polymerases in its translesion synthesis
Improved High Temperature Thermoelectric Properties in Misfit Ca3Co4O9 by Thermal Annealing
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Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Thermoelectric performance of layered cobaltate epitaxial films deposited by pulsed laser evaporation
Full text linkEl efecto termoeléctrico o efecto Seebeck es un fenómeno característico de un conductor eléctrico y que proporciona información fundamental como la estructura electrónica del material entorno a la energía de Fermi. Desde un punto de vista tecnológico la fabricación de dispositivos termoeléctricos es importantes debido a su capacidad para generar un voltaje eléctrico a partir de un gradiente de temperatura. Sin embargo, la baja eficiencia que generalmente se obtiene a partir de materiales termoeléctricos convencionales, limita su aplicación práctica. Para el diseño de materiales termoeléctricos con una eficiencia adecuada es importante que el material posea simultáneamente varias características: alta conductividad eléctrica, baja conductividad térmica y un elevado poder termoeléctrico S. Por lo tanto, el diseño de materiales termoeléctricos eficientes es a la vez un reto científico así como un desafío de ingeniería. Entre los diferentes materiales termoeléctricos explorados en la literatura los compuestos de estructura laminar presentan unas importantes características, la mayoría de ellas relacionadas con la anisotropía en sus propiedades. De esta manera el crecimiento de películas epiaxiales (o altamente orientadas) permite explorar las propiedades físicas en una determinada dirección cristalográfica. Al mismo tiempo, el uso de películas epitaxiales permite modular las propiedades de transporte electrónico, así como las propiedades de transporte térmico y termoeléctrico, modificando la tensión epitaxial, la presencia de defectos, o las características de la intercara en la heteroestructura.
Esta tesis se centra en la investigación de las propiedades termoeléctricas de películas epitaxiales o con un alto grado de orientación preferencial de óxidos de cobalto. La tesis incluye una descripción detallada de los diferentes métodos posibles para el ajuste de la estequiometría de oxígeno de las películas. La tesis se divide en varios capítulos. El capítulo 1 proporciona una breve introducción general del efecto termoeléctrico (TE), para seguidamente ofrecer una descripción de las propiedades TE de capas de óxidos de cobalto. Al mismo tiempo se presenta una breve revisión de la literatura donde se prestó especial atención a los aspectos científicos y resultados experimentales relacionados. En el Capítulo 2 se presentan la metodología experimental utilizada en este estudio. En los capítulos 3, 4 y 5 se describen los resultados de las propiedades termoeléctricas de las películas de cobaltitas, al mismo tiempo que se discuten para extraer conclusiones específicas. En el Capítulo 6 se presenta el experimento realizado para el control de la estequiometría de oxígeno mediante un dispositivo electroquímico de estado sólido. Por último, en el capítulo 7 se presenta un resumen de las conclusiones generales y se discuten las perspectivas de futuro. En resumen, la exploración de las propiedades termoeléctricas en películas delgadas de óxidos de cobalto lleva a la conclusión de que, contrariamente a la creencia actual, la degeneración spin-órbita no contribuye al límite de alta temperatura del coeficiente de Seebeck, y que únicamente la distribución estadística de los electrones en los estados disponibles es relevante para la determinación de dicho límite. En consecuencia, se propone una modificación de la fórmula de Heike, que incluye información del tamaño efectivo de los polarones responsables del transporte de carga.Thermoelectric Seebeck effect is a very important phenomenon of a charge conductor as it provides fundamental information such as the electronic band structure near Fermi energy. Thermoelectric devices are very important from a technological point of view because of its ability to convert electricity from a temperature gradient. However, the low efficiency; of the thermoelectric materials, limits their use for practical applications. Therefore, it is important to design thermoelectric materials that are good electrical conductor, poor thermal conductor and at the same time have large S. Thus, design of efficient thermoelectric materials is a scientific and also an engineering challenge.
Among the different thermoelectric materials explored in the literature, layered compounds have shown very important characteristics most of them related to their anisotropic properties. In that sense, the growth of epitaxial (or highly oriented) thin films allows exploring the physical properties in a particular crystallographic direction and, therefore is ideal for exploring the possible anisotropy. At the same time, it allows to engineer the electronic, thermoelectric as well as the thermal transport properties by playing with epitaxial strain, defect chemistry and interface between multilayers.
This thesis reports the investigation of thermoelectric properties of epitaxial and highly oriented layered cobaltates films includes a detailed description of the different possible methods to tune the oxygen stoichiometry of thin films. The thesis is divided into several chapters. A brief introduction of the thermoelectric phenomena is provided in chapter 1. Then, the description is focused on the TE properties of layered cobaltates. A short literature review is presented where attention was paid to the status of scientific problems and experimental results. Chapter 2 shows the techniques used to perform the experiments. Thermoelectric properties of layered cobaltates films are presented from chapter 3 to 5 in order to address specific questions in each chapter. Chapter 6 shows the control over oxygen stoichiometry of cobaltate thin film by means of solid state electrochemical approach. Finally, a summary of the conclusions and perspectives are discussed in chapter 7.
The exploration of the thermoelectric properties of layered cobaltates thin films led to the conclusion that, contrary to the current belief, spin-orbit degeneracy does not contribute to the high-temperature limit of the Seebeck coefficient, and only the statistical distribution of electrons in the available states is relevant for determining such limit. Consequently, a modification of the Heike’s formula, containing the information of polaron size, is proposed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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