Epigenetic evolution and lineage histories of chronic lymphocytic leukaemia

Genetic and epigenetic intra-tumoral heterogeneity cooperate to shape the evolutionary course of cancer1. Chronic lymphocytic leukaemia (CLL) is a highly informative model for cancer evolution as it undergoes substantial genetic diversification and evolution after therapy2,3. The CLL epigenome is also an important disease-defining feature4,5, and growing populations of cells in CLL diversify by stochastic changes in DNA methylation known as epimutations6. However, previous studies using bulk sequencing methods to analyse the patterns of DNA methylation were unable to determine whether epimutations affect CLL populations homogeneously. Here, to measure the epimutation rate at single-cell resolution, we applied multiplexed single-cell reduced-representation bisulfite sequencing to B cells from healthy donors and patients with CLL. We observed that the common clonal origin of CLL results in a consistently increased epimutation rate, with low variability in the cell-to-cell epimutation rate. By contrast, variable epimutation rates across healthy B cells reflect diverse evolutionary ages across the trajectory of B cell differentiation, consistent with epimutations serving as a molecular clock. Heritable epimutation information allowed us to reconstruct lineages at high-resolution with single-cell data, and to apply this directly to patient samples. The CLL lineage tree shape revealed earlier branching and longer branch lengths than in normal B cells, reflecting rapid drift after the initial malignant transformation and a greater proliferative history. Integration of single-cell bisulfite sequencing analysis with single-cell transcriptomes and genotyping confirmed that genetic subclones mapped to distinct clades, as inferred solely on the basis of epimutation information. Finally, to examine potential lineage biases during therapy, we profiled serial samples during ibrutinib-associated lymphocytosis, and identified clades of cells that were preferentially expelled from the lymph node after treatment, marked by distinct transcriptional profiles. The single-cell integration of genetic, epigenetic and transcriptional information thus charts the lineage history of CLL and its evolution with therapy

The Victorian Newsletter (Spring 1967)

The Victorian Newsletter is edited for the English X Group of the Modern Language Association by William E. Buckler, New York University, New York, N.Y. 10003

The Belfast Boycott: Gender, Partition, and Civil War

The Belfast Boycott was a protest which ran from August 1920 until January 1922 that was designed to dislodge loyalism in Northern Ireland and punish its adherents for perceived intolerance toward Catholics. This paper analyzes three ways that the Belfast Boycott permeated and cemented civil war divisions. It examines the constructs of the boycott in relation to the issues of sectarianism, partition, and the role of women. For example, some members of the Dáil thought that the boycott would further solidify partition and thereby strengthen existing sectarian strife. Others saw the boycott as an opportunity to punish Loyalists for fidelity to a colonial power and for unfair treatment of Catholic workers. Advertisements were created to link boycott compliance with patriotism, assuring shoppers that only by boycotting Belfast could they help partition end. Boycotting allowed women, who were often marginalized by the political framework, an opportunity to make political statements through their economic actions. While it lasted only a year and a half, the Belfast Boycott can help us better understand and expound upon issues of sectarianism, partition, and gender roles and their contributive role in the Irish Civil War

The Belfast Boycott: Consumerism, Gender, and the Irish Border, 1920-1922

The Belfast Boycott was a protest designed to dislodge loyalism in Northern Ireland, punish its adherents for perceived intolerance toward Catholics, and end Irish partition. The boycott was set off by the expulsion of several thousand Catholic workers from employment in Belfast in July 1920. A total boycott of all goods coming from Belfast was implemented by the Dáil in September 1920. Boycotting provided Irish nationalists with an alternative to violent retaliation that allowed for the participation of a wider segment of the Irish population. Boycotting allowed women, who were often marginalized by the political framework, an opportunity to make political statements through their economic actions. In addition, the boycott became a means for Sinn Féin to promote their own notions of tolerance and situate their cause within a wider, international framework. This work explores nationalists’ conceptions of Irish identity, the intersection between consumerism and patriotism, and the role that women played as both political and economic actors throughout the Irish revolutionary period

The Belfast Boycott: Sectarianism in Anti-Partition Rhetoric

The Belfast Boycott was a protest designed to dislodge loyalism in Northern Ireland and punish its adherents for perceived intolerance toward Catholics. The boycott was set off by the expulsion of several thousand Catholic workers from employment in Belfast in July 1920. A total boycott of all goods coming from Belfast was implemented in September 1920. Both unionists and nationalists attempted to legitimize their actions in the context of the boycott by framing them as non-sectarian, realizing the need to distance themselves from accusations of religious bigotry. For the boycott to be viewed as legitimate, it had to be framed as a political, rather than a religious, act. However, the Dáil’s goals regarding the boycott were both political and economic. One of these goals was to punish Belfast for unfair treatment of Catholics. The larger goal of the boycott, however, was to eliminate Protestant ascendancy and end partition. One key aspect of boycott promotion was the assurance that only by boycotting could partition end. This paper will explore the ways in which southern Irish nationalists used the Belfast Boycott, often in contradictory ways, to attempt to both punish Belfast while simultaneously calling for Irish unity. College of Arts & Humanities Presentation Award Winner

The Adoption Process in Colombia

Carla Guerron MonteroThe flow of children throughout the world reflects how policies about international adoption, both domestic and international, remove power from one population and transfer it to another, even if they are on opposite sides of the world. The phenomenon of international adoption is the outcome of specific historical events, Euro-American ideals, globalization, neoliberal policies, and the great disparities between the upper echelons of the world and the poor of third world countries. While protecting or saving children who live in poverty is a noble cause, many outside parties have taken note of the many factors contributing to this circulation of children that may raise other ethical questions. These questions center on the theories of identity, structural violence, the pathologization of poverty and the use of children as a social and monetary commodity. There are many actors within the international adoption process: the adoptees, the adoptive parents, the birth parents, the governments of the countries they are being transferred to and from, and the international entities that regulate these transactions. The discourse of international adoption in relation to the specific role of the actors within the process reflect these various influences on adoption. They also demonstrate how international adoption is a quick remedy to a much deeper societal problem. There is no conclusive solution that would eliminate the need for international adoption, but a closer inspection of the underlying factors that contribute to this process may give insight into what changes need to be made in the future. I will discuss how websites of the various players in the international adoption system reflect the discourse of international adoption in relation to historical events and the aforementioned theories.Anthropolog

Traditional Music In Modern Java.

PhDMusicUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/180298/2/7306787.pd

Broadband modal beamforming of acoustic tomography signals acquired by a vertical array

The objective of this thesis is to develop a technique and associated algorithms to extract the arrival time of modal energy, using a vertical array, from broadband signals. Modal energy arrival time is important to shallow water acoustic tomography because low angle rays, which contain the majority of acoustic energy, are often not resolvable. Tilt compensation is included in the beamforming algorithm to provide a virtual vertical array. A broadband modal filtering technique is accomplished through weighting the frequency components of phase encoded tomographic signals by the spectrum of the mode shapes A methodology of phase decoding after beamforming was adopted to minimize processing. Initial development and prototyping was done using a parabolic equation model. Further testing was accomplished on real data taken from the Barents Sea Polar Front Experiment, August 1992. Results show consistency over a number of transmitted pulses. Mode energy travel time measurement is simplified due to the distinct arrival structure of beamformed signals. Based on these results, the modal beamfomring algorithm should be a useful tool for acoustic tomography.http://archive.org/details/broadbandmodalbe00omanLieutenant, United States NavyApproved for public release; distribution is unlimited