Applied molecular evolution of O6-benzylguanine-resistant DNA alkyltransferases in human hematopoietic cells

Applied molecular evolution is a rapidly developing technology that can be used to create and identify novel enzymes that nature has not selected. An important application of this technology is the creation of highly drug-resistant enzymes for cancer gene therapy. Seventeen O6-alkylguanine-DNA alkyltransferase (AGT) mutants highly resistant to O6-benzylguanine (BG) were identified previously by screening 8 million variants, using genetic complementation in Escherichia coli. To examine the potential of these mutants for use in humans, the sublibrary of AGT clones was introduced to human hematopoietic cells and stringently selected for resistance to killing by the combination of BG and 1,3-bis(2-chloroethyl)-1-nitrosourea. This competitive analysis between the mutants in human cells revealed three AGT mutants that conferred remarkable resistance to the combination of BG and 1,3-bis(2-chloroethyl)-1-nitrosourea. Of these, one was recovered significantly more frequently than the others. Upon further analysis, this mutant displayed a level of BG resistance in human hematopoietic cells greater than that of any previously reported mutant.

Novel human DNA alkyltransferases obtained by random substitution and genetic selection in bacteria.

DNA repair alkyltransferases protect organisms against the cytotoxic, mutagenic, and carcinogenic effects of alkylating agents by transferring alkyl adducts from DNA to an active cysteine on the protein, thereby restoring the native DNA structure. We used random sequence substitutions to gain structure-function information about the human O6-methylguanine-DNA methyltransferase (EC 2.1.1.63), as well as to create active mutants. Twelve codons surrounding but not including the active cysteine were replaced by a random nucleotide sequence, and the resulting random library was selected for the ability to provide alkyltransferase-deficient Escherichia coli with resistance to the methylating agent N-methyl-N'-nitro-N-nitrosoguanidine. Few amino acid changes were tolerated in this evolutionarily conserved region of the protein. One mutation, a valine to phenylalanine change at codon 139 (V139F), was found in 70% of the selected mutants; in fact, this mutant was selected much more frequently than the wild type. V139F provided alkyltransferase-deficient bacteria with greater protection than the wild-type protein against both the cytotoxic and mutagenic effects of N-methyl-N'-nitro-N-nitrosoguanidine, increasing the D37 over 4-fold and reducing the mutagenesis rate 2.7-5.5-fold. This mutant human alkyltransferase, or others similarly created and selected, could be used to protect bone marrow cells from the cytotoxic side effects of alkylation-based chemotherapeutic regimens.

The African-American Islamic Renaissance and the Rise of the Nation of Islam

This dissertation examines African-American Islamic culture from 1920 through 1959, a period I label the "African-American Islamic Renaissance" (AAIR). The AAIR is characterized by a significant increase in interest in Islam, extreme diversity in views about Islam, and the absence of a single organization dominating African-American Islamic culture for a significant amount of time. Previous works dealing with African-American Islam in this period have failed to fully recognize these features, particularly the last of these. As a result, explanations for the rise of the Nation of Islam (NOI) have not satisfactorily explained why it was only the NOI--and not other Islamic groups that were more popular than the NOI up until the mid-1950s--that became a "mass movement," gaining the allegiance of tens of thousands of African Americans. There has been some tendency, for instance, to assume that the NOI was the most popular African-American Islamic group by the early 1950s, a notion that is probably an inference drawn from two other popular but inaccurate assumptions: that the NOI's rise was due primarily to its radical racialized doctrines and its charismatic leaders, particularly Malcolm X, who became a popular minister for the group in the early 1950s. I argue, however, that the NOI was in fact not the most popular African-American Islamic group until at least 1955, and even as late as 1959 its official membership numbers were not particularly large by AAIR standards. Also, its doctrines were not especially unique in the AAIR, nor was its having extremely charismatic leaders. I contend that the success of the NOI in the mid-to-late 1950s was the result of three levels of changes at the time: internal, external in the AAIR community, and external in the broader U.S, culture.

The Hybrid Spirit Animating Chinese Pentecostals in Malaysia

This dissertation interrogates the assertion in postcolonial scholarship, especially from the work of Homi Bhabha that the construction and performance of hybrid identities act as a form of resistance for marginalized communities against structures of oppression. While this study supports this assertion, it also critiques how hybridity fails to address issues of unequal power relations. This has led to an uncritical use of hybridity that reproduces the very idea of static identity which its proponents claim to transcend. Through qualitative study of Chinese members of a Pentecostal church in Malaysia, this study argues that church members engage in "unequal belonging" where they privilege certain elements of their identities over others. In concert with Pierre Bourdieu's conceptions of habitus, field, and capital, unequal belonging highlights how hybridity fails to capture the intersecting and competing loyalties, strategies, and complexities of identity formation on a contextual level. Unequal belonging challenges postcolonial scholars to locate the subtle workings of power and privilege that manifest even among marginalized communities. The study first situates the Chinese through an analysis of the historical legacy of British colonialism that has structured the country's current socio-political configuration along bounded categories of identification. The habitus constrains church members to accept certain Chinese ethnic markers as "givens." Although they face continuous marginalization, interviewee data demonstrates that church members negotiate their Chineseness and construct a "Modern Chinese" ethnic identity as a strategic move away from Chinese stereotypes. Moreover, conversion to Christianity affords church members access to cultural capital. Yet, it is limited and unequal capital. In particular, the "Chinese Chinese," who church members have demarcated as backward and traditional, are unable to gain access to this capital because they lack fluency in English and knowledge in modern, westernized worldviews. Unequal belonging nuances monolithic conceptions of hybridity. It demonstrates how church members' privilege of Christianity over Chineseness exposes the complex processes of power and privilege that makes westernized-English-speaking Chinese Christians culturally "higher" than non-English-speaking, non-Christian, Chinese. This study provides significant contribution to the complex aspect of hybridity where it is both a site of resistance and oppression.

La avenencia: solución pacífica de conflictos en el Derecho de cristianos y musulmanes hispanos (S. X-XVI)

Las fuentes del Derecho español se han ocupado a lo largo del tiempo, y sin solución de continuidad, de la institución del arbitraje en el marco de la administración de justicia. El arbitraje, avenencia o conciliación son términos que poseen un significado singular en los sistemas u ordenamientos jurídicos que han connotado la Historia del Derecho. El Derecho andalusí se ocupó de la institución del arbitraje por dos razones fundamentales. La primera razón de este interés obedecía a su importancia como medio eficaz y rápido para solventar diferencias o conflictos entre partes. La segunda razón se debía a las particularidades que esta modalidad de resolución presentó respecto a la ortodoxia malekí. Este trabajo analiza los elementos y características del arbitraje y la avenencia con el fin de trazar una visión más completa de la institución, que desde la Edad Media fue medio habitual para la solución de situaciones controvertidas entre cristianos y musulmanes.

Ondara, señorío del Duque de Gandía, a principios del siglo XV

A partir de un cabreve de 1416 conservado en el Archivo del Reino de Valencia hemos pretendido reconstruir cuál fue el desarrollo del lugar de Ondara, en el norte de la actual provincia de Alicante, en particular la renta percibida por el señor, el duque de Gandía. Ondara tenía una población de mayoría mudéjar, aunque también vivían en la localidad cristianos. De esta renta era la partición de frutos de los mudéjares y los cristianos, con sus 4.000 sueldos, la que proporcionaba los mayores ingresos en las arcas señoriales, es decir, el gravamen sobre la actividad económica de la localidad, seguida por los arrendamientos y el besante. Además de la agricultura había una actividad artesana en torno a la cantarería, la fabricación de jabón y el tinte. Se completa el estudio con unas normas municipales del año 1410 y la prosopografía de los vecinos.

Bienes muebles de mudéjares castellonenses. Siglo XV

Transcripción y estudio de 23 inventarios de bienes muebles de mudéjares castellonenses a través de los libros del Corte de Justicia para Castellón, Segorbe y Onda, fuente de muchos datos de diverso tipo sobre la vida de estos mudéjares y que generalmente se redactan post mortem para satisfacer deudas del fallecido. Se centra el análisis en la propiedad de animales de tiro y transporte, el trabajo de las fibras textiles y los elementos externos que los diferencian de los cristianos.

Propriedade e direito entre os muçulmanos de Portugal: dos bens comuns à gestão do património do rei

El derecho islámico informa de la identidad de los musulmanes del reino portugués, desde el período matricial de su integración hasta finales del siglo XV. De la participación en los moldes de su propia subordinación fiscal y tributaria, a la cuestión del derecho sucesorio, los musulmanes legistas de Lisboa responden a las sucesivas interpelaciones de la Corona, constituyéndose el monarca como el principal beneficiario de esa producción legal. Esta manipulación del poder, el aspecto más visible en la documentación, muestra todo el dominio continuado de ese universo legal y de sus especialistas mudéjares. Aspecto que tendrá lógicamente su resonancia en la vivencia interna de estas comunidades, especialmente en lo que a la propiedad se refiere. El principio de la sunna de la dominación de los bienes colectivos se refleja en los bienes habices y los colectivos (al-Muslimina), aún documentados en el siglo XV. Por otro lado, la propia gestión del patrimonio del rey, en la morería de Lisboa, será dominada, en el mismo período, por una autoridad musulmana, el juez de los derechos reales, contradiciendo la ley canónica y la territorial que prohibía a los infieles ejercer poder sobre los cristianos.

Kitāb Nawādir al-zamān fi waqāʼiʻ Jabal Lubnān / taʼlīf Iskandar Afandī Abkāriyūs : manuscript, 1877?

Text is a history of Lebanon in the early 20 century.

Late Putin. The end of growth, the end of stability. OSW POINT OF VIEW #55, 2015-10-05

Since Vladimir Putin returned to the Kremlin as President in May 2012, the Russian system of power has become increasingly authoritarian, and has evolved towards a model of extremely personalised rule that derives its legitimacy from aggressive decisions in internal and foreign policy, escalates the use of force, and interferes increasingly assertively in the spheres of politics, history, ideology or even public morals. Putin’s power now rests on charismatic legitimacy to a much greater extent than it did during his first two presidential terms; currently the President is presented not only as an effective leader, but also as the sole guarantor of Russia’s stability and integrity. After 15 years of Putin’s rule, Russia’s economic model based on revenue from energy resources has exhausted its potential, and the country has no new model that could ensure continued growth for the economy. The Putinist system of power is starting to show symptoms of agony – it has been unable to generate new development projects, and has been compensating for its ongoing degradation by escalating repression and the use of force. However, this is not equivalent to its imminent collapse.

Shakers.

"The Legislature of New Hampshire and their constitutuion": p. 4-7; "Minority report of the Judiciary Committee, upon the petition of Franklin Munroe and others in relation the the Society of Christians called Shakers": p. 7-12.

Tamul hymns set to German tunes : arranged for the voice with an accompaniment for the organ or piano = Krietucapaiyil valak̃iya ñāṉappāṭṭukaḷukkaṭutta almāṇiyarañkañkaḷ /

Mode of access: Internet.

Hymnes pascales /

Includes bibliographical references and indexes.

Turkey in Europe,

Disbound Original Held in Oak Street Library Facility.

Aberdeen Angus bloodlines.

Mode of access: Internet.