Friendship as a Political Concept: A Groundwork for Analysis

What kind of a concept is friendship, and what is its connection to politics? Critics sometimes claim that friendship does not have a role to play in the study of politics. Such objections misconstrue the nature of the concept of friendship and its relation to politics. In response, this article proposes three approaches to understanding the concept of friendship: (1) as a ‘family resemblance’ concept, (2) as an instance of an ‘essentially contested’ concept, and (3) as a concept indicating a problématique. The article thus responds to the dismissal of friendship by undertaking the groundwork for understanding what kind of a concept friendship might be, and how it might serve different purposes. In doing so, it opens the way for understanding friendship’s relation to politics

Ten millennia of hepatitis B virus evolution

Hepatitis B virus (HBV) has been infecting humans for millennia and remains a global health problem, but its past diversity and dispersal routes are largely unknown. We generated HBV genomic data from 137 Eurasians and Native Americans dated between similar to 10,500 and similar to 400 years ago. We date the most recent common ancestor of all HBV lineages to between similar to 20,000 and 12,000 years ago, with the virus present in European and South American hunter-gatherers during the early Holocene. After the European Neolithic transition, Mesolithic HBV strains were replaced by a lineage likely disseminated by early farmers that prevailed throughout western Eurasia for similar to 4000 years, declining around the end of the 2nd millennium BCE. The only remnant of this prehistoric HBV diversity is the rare genotype G, which appears to have reemerged during the HIV pandemic.Molecular Technology and Informatics for Personalised Medicine and Healt

Ten millennia of hepatitis B virus evolution

Hepatitis B virus (HBV) has been infecting humans for millennia and remains a global health problem, but its past diversity and dispersal routes are largely unknown. We generated HBV genomic data from 137 Eurasians and Native Americans dated between ~10,500 and ~400 years ago. We date the most recent common ancestor of all HBV lineages to between ~20,000 and 12,000 years ago, with the virus present in European and South American hunter-gatherers during the early Holocene. After the European Neolithic transition, Mesolithic HBV strains were replaced by a lineage likely disseminated by early farmers that prevailed throughout western Eurasia for ~4000 years, declining around the end of the 2nd millennium BCE. The only remnant of this prehistoric HBV diversity is the rare genotype G, which appears to have reemerged during the HIV pandemic

Shaping an education for the modern world: a history of the Alberta social studies curriculum, 1905 to 1965

Bibliography: p. 474-490.This dissertation examines the evolution of the Alberta history and social studies curricula from 1905 to 1965. It treats school curriculum as an artifact of public thought, as an expression of a society's understanding of itself and its aspirations. An analysis of the history and social studies curricula, therefore, represents an attempt to describe how Albertans understood themselves as a society and as citizens of Canada. From 1905 to 1935 Alberta students studied British and Canadian history. The curriculum was determined by the intellectual elite of the universities, who were guided by their understanding of the need for citizens of "disciplined intelligence." Before World War One, the curriculum written by this elite therefore emphasized virtue and good character. It tried to create students who would put their talents in the service of society. The elite believed that students of good character could improve society and that a proper grounding in the lessons of history would demonstrate the value of tradition as well as the importance of progress. After World War One, the urgency for social improvement increased and the elite incorporated more explicit messages about the need for cooperation and conformity in the curriculum. Students were encouraged to be good citizens. The history curriculum before 1935 reflected the belief that hope and the future direction of society would come out of an understanding of the past. In the 1935 the new educationalists in the Department of Education abandoned the teaching of history and introduced a progressive curriculum. The Enterprise and the social studies were interdisciplinary programmes designed to equip students for the task of social reconstruction. Gone was the belief that the past held positive lessons for the present. The progressive revision embodied the belief that that history was a catalogue of human failure; the educationalists argued that only a grounding in the social sciences could prepare students to improve society. The confidence in social planning, indeed social engineering, remained in the curriculum in the 1950s and 1960s. But the Cold War seemed to illustrate the fragility of democracy, the "way of life" progressive educators sought so ardently to defend. The 1950s and early 1960s were prosperous times for Albertans, so the focus of the curriculum became preparing students to share in that prosperity. Educators in this period believed that the best defence for democracy was economic opportunity. The ethos of Alberta's history and social studies curricula has therefore evolved: from an education for good character to preparation for citizenship; from a commitment to social activism to preparation for work. What was abandoned through this evolution was any meaningful inquiry into the nature of the past. A coherent study of the past for its own sake was lost. Students therefore were unable to discover their place in their community and a sense of themselves grounded in an intelligent understanding of their history

T cells directed against the metastatic driver chondromodulin-1 in ewing sarcoma: Comparative engineering with CRISPR/Cas9 vs. retroviral gene transfer for adoptive transfer.

Ewing sarcoma (EwS) is a highly malignant sarcoma of bone and soft tissue with early metastatic spread and an age peak in early puberty. The prognosis in advanced stages is still dismal, and the long-term effects of established therapies are severe. Efficacious targeted therapies are urgently needed. Our previous work has provided preliminary safety and efficacy data utilizing T cell receptor (TCR) transgenic T cells, generated by retroviral gene transfer, targeting HLA-restricted peptides on the tumor cell derived from metastatic drivers. Here, we compared T cells engineered with either CRISPR/Cas9 or retroviral gene transfer. Firstly, we confirmed the feasibility of the orthotopic replacement of the endogenous TCR by CRISPR/Cas9 with a TCR targeting our canonical metastatic driver chondromodulin-1 (CHM1). CRISPR/Cas9-engineered T cell products specifically recognized and killed HLA-A*02:01+ EwS cell lines. The efficiency of retroviral transduction was higher compared to CRISPR/Cas9 gene editing. Both engineered T cell products specifically recognized tumor cells and elicited cytotoxicity, with CRISPR/Cas9 engineered T cells providing prolonged cytotoxic activity. In conclusion, T cells engineered with CRISPR/Cas9 could be feasible for immunotherapy of EwS and may have the advantage of more prolonged cytotoxic activity, as compared to T cells engineered with retroviral gene transfer

The posterior <em>HOXD</em> locus: Its contribution to phenotype and malignancy of Ewing sarcoma.

Microarray analysis revealed genes of the posterior HOXD locus normally involved in bone formation to be over-expressed in primary Ewing sarcoma (ES). The expression of posterior HOXD genes was not influenced via ES pathognomonic EWS/ETS translocations. However, knock down of the dickkopf WNT signaling pathway inhibitor 2 (DKK2) resulted in a significant suppression of HOXD10, HOXD11 and HOXD13 while over-expression of DKK2 and stimulation with factors of the WNT signaling pathway such as WNT3a, WNT5a or WNT11 increased their expression. RNA interference demonstrated that individual HOXD genes promoted chondrogenic differentiation potential, and enhanced expression of the bone-associated gene RUNX2. Furthermore, HOXD genes increased the level of the osteoblast- and osteoclast-specific genes, osteocalcin (BGLAP) and platelet-derived growth factor beta polypeptide (PDGFB), and may further regulate endochondral bone development via induction of parathyroid hormone-like hormone (PTHLH). Additionally, HOXD11 and HOXD13 promoted contact independent growth of ES, while in vitro invasiveness of ES lines was enhanced by all 3 HOXD genes investigated and seemed mediated via matrix metallopeptidase 1 (MMP1). Consequently, knock down of HOXD11 or HOXD13 significantly suppressed lung metastasis in a xeno-transplant model in immune deficient mice, providing overall evidence that posterior HOXD genes promote clonogenicity and metastatic potential of ES