Epistemologies of possibility: social movements, knowledge production and political transformation

Urgent global problems - whether military conflicts, economic insecurities, immigration controls or mass incarceration-not only call for new modes of political action but also demand new forms of knowledge. For if knowledge frameworks both shape the horizons of social intelligibility and chart t he realms of political possibility, then epistemological interventions constitute a crucial part of social change. Social movements play a key role in this work by engaging in dissident knowledge practices that open up space for political transformation. But what are the processes and conditions through which social movements generate new ways of knowing?'What is politically at stake in the various knowledge strategies that activists use to generate social change? Despite a growing literature on the role of epistemological dimensions of protest, social movement studies tend to neglect specific questions of epistemological change. Often treating knowledge as a resource or object rather than a power relation and a social practice, social movement scholars tend to focus on content rather than production, frames rather than practices, taxonomies rather than processes. Missing is a more dynamic account of the conditions, means and power relations through which transformative knowledge practices come to be constituted and deployed. Seeking to better understand processes of epistemological transformation, this thesis explores the relationship between social movements, knowledge production and political change. Starting from an assumption that knowledge not only represents the world, but also works to constitute it, this thesis examines the role of social movement knowledge practices in shaping the conditions of political possibility. Drawing from the context of grassroots queer, transgender and feminist organizing around issues of prisons and border controls in North America, the project explores how activists generate new forms of knowledge and forge new spaces of political possibility. Working through a series of concepts-transformation, resistance, experience, co-optation, solidarity and analogy - this thesis explores different ways of understanding processes of epistemological change with in social movement contexts. It considers processes that facilitate or enable epistemological change and those that limit or prohibit such change. Bringing together a range of theoretical perspectives, including feminist, queer, critical race and post-structuralist analyses, and drawing on interviews with grassroots activists, the thesis explores what is politically at stake in the different ways we conceptualise, imagine and engage in processes of epistemological change

Retelling racialized violence, remaking white innocence: the politics of interlocking oppressions in transgender day of remembrance

Transgender Day of Remembrance has become a significant political event among those resisting violence against gender-variant persons. Commemorated in more than 250 locations worldwide, this day honors individuals who were killed due to anti-transgender hatred or prejudice. However, by focusing on transphobia as the definitive cause of violence, this ritual potentially obscures the ways in which hierarchies of race, class, and sexuality constitute such acts. Taking the Transgender Day of Remembrance/Remembering Our Dead project as a case study for considering the politics of memorialization, as well as tracing the narrative history of the Fred F. C. Martinez murder case in Colorado, the author argues that deracialized accounts of violence produce seemingly innocent White witnesses who can consume these spectacles of domination without confronting their own complicity in such acts. The author suggests that remembrance practices require critical rethinking if we are to confront violence in more effective ways. Description from publisher's site: http://caliber.ucpress.net/doi/abs/10.1525/srsp.2008.5.1.2

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Epistemologies of possibility: social movements, knowledge production and political transformation

Urgent global problems-whether military conflicts, economic insecu rities, immigration controls or mass inca rceration-not only call for new modes of po litical action but also demand new forms of knowledge. For if knowledge frameworks both shape the horizons of social intelli gi bil ity and chart t he realms of political possibility, then epistemological interventions constitute a crucial part of social change. Social movements play a key role in th is work by engaging in dissident knowledge practices that open up space for political transformation. But what are the processes and conditions through which social movements generate new ways of knowing?'What is politically at sta~e in the various knowledge strategies that activists use to generate social change? Despite a growing lite ratu re on the role of epistemological dimensions of protest, social movement studies tend to neglect specific questions of epistemological change. Often treating knowledge as a resource or object rather than a power relation and a socia l practice, social movement scholars tend to focus on content rather than production, frames rather than practices, taxonomies rather than processes. Missing is a more dynamic account of the conditions, means and power relations through which transformative knowledge practices come to be constituted and deployed. Seeking to better understand processes of epistemological transformation, this thesis explores the relationship between social movements, knowledge production and pol itical change. Starting from an assumption that knowledge not only represents the world, but also works to constitute it, th is thesis examines the role of social movement knowledge practices in shaping the conditions of political possi bility. Drawing from the context of grassroots queer, transgender and feminist organizing around issues of prisons and border controls in North America, the project explores how activists generate new forms of knowledge and forge new spaces of political possibility. Working through a series of concepts-transformation, resistance, exp_erience, co-optation, so lidarity and analogy-this thesis explores different ways of understanding processes of epistemological change with in social movement contexts. It considers processes that facil itate or enable epistemological change and those that lim it or prohibit such change. Bringing together a range of theoretical perspect ives, includ ing femin ist, queer, crit ica l race and post-structuralist analyses, and drawing on interviews with grassroots activists, the thesis explores what is politica lly at stake in the different ways we conceptua lise, imagine and engage in processes of epistemological change.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Trans liberation will take more than honouring the dead

On Trans Day of Remembrance, a shift in focus is needed to address the systemic causes of transphobia and violence that trans people face at home and abroad

Factors influencing success of clinical genome sequencing across a broad spectrum of disorders

To assess factors influencing the success of whole-genome sequencing for mainstream clinical diagnosis, we sequenced 217 individuals from 156 independent cases or families across a broad spectrum of disorders in whom previous screening had identified no pathogenic variants. We quantified the number of candidate variants identified using different strategies for variant calling, filtering, annotation and prioritization. We found that jointly calling variants across samples, filtering against both local and external databases, deploying multiple annotation tools and using familial transmission above biological plausibility contributed to accuracy. Overall, we identified disease-causing variants in 21% of cases, with the proportion increasing to 34% (23/68) for mendelian disorders and 57% (8/14) in family trios. We also discovered 32 potentially clinically actionable variants in 18 genes unrelated to the referral disorder, although only 4 were ultimately considered reportable. Our results demonstrate the value of genome sequencing for routine clinical diagnosis but also highlight many outstanding challenges