165 research outputs found

    Different Patterns of Evolution in the Centromeric and Telomeric Regions of Group A and B Haplotypes of the Human Killer Cell Ig-Like Receptor Locus

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    The fast evolving human KIR gene family encodes variable lymphocyte receptors specific for polymorphic HLA class I determinants. Nucleotide sequences for 24 representative human KIR haplotypes were determined. With three previously defined haplotypes, this gave a set of 12 group A and 15 group B haplotypes for assessment of KIR variation. The seven gene-content haplotypes are all combinations of four centromeric and two telomeric motifs. 2DL5, 2DS5 and 2DS3 can be present in centromeric and telomeric locations. With one exception, haplotypes having identical gene content differed in their combinations of KIR alleles. Sequence diversity varied between haplotype groups and between centromeric and telomeric halves of the KIR locus. The most variable A haplotype genes are in the telomeric half, whereas the most variable genes characterizing B haplotypes are in the centromeric half. Of the highly polymorphic genes, only the 3DL3 framework gene exhibits a similar diversity when carried by A and B haplotypes. Phylogenetic analysis and divergence time estimates, point to the centromeric gene-content motifs that distinguish A and B haplotypes having emerged ∼6 million years ago, contemporaneously with the separation of human and chimpanzee ancestors. In contrast, the telomeric motifs that distinguish A and B haplotypes emerged more recently, ∼1.7 million years ago, before the emergence of Homo sapiens. Thus the centromeric and telomeric motifs that typify A and B haplotypes have likely been present throughout human evolution. The results suggest the common ancestor of A and B haplotypes combined a B-like centromeric region with an A-like telomeric region

    Queer In AI: A Case Study in Community-Led Participatory AI

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    Queerness and queer people face an uncertain future in the face of ever more widely deployed and invasive artificial intelligence (AI). These technologies have caused numerous harms to queer people, including privacy violations, censoring and downranking queer content, exposing queer people and spaces to harassment by making them hypervisible, deadnaming and outing queer people. More broadly, they have violated core tenets of queerness by classifying and controlling queer identities. In response to this, the queer community in AI has organized Queer in AI, a global, decentralized, volunteer-run grassroots organization that employs intersectional and community-led participatory design to build an inclusive and equitable AI future. In this paper, we present Queer in AI as a case study for community-led participatory design in AI. We examine how participatory design and intersectional tenets started and shaped this community’s programs over the years. We discuss different challenges that emerged in the process, look at ways this organization has fallen short of operationalizing participatory and intersectional principles, and then assess the organization’s impact. Queer in AI provides important lessons and insights for practitioners and theorists of participatory methods broadly through its rejection of hierarchy in favor of decentralization, success at building aid and programs by and for the queer community, and effort to change actors and institutions outside of the queer community. Finally, we theorize how communities like Queer in AI contribute to the participatory design in AI more broadly by fostering cultures of participation in AI, welcoming and empowering marginalized participants, critiquing poor or exploitative participatory practices, and bringing participation to institutions outside of individual research projects. Queer in AI’s work serves as a case study of grassroots activism and participatory methods within AI, demonstrating the potential of community-led participatory methods and intersectional praxis, while also providing challenges, case studies, and nuanced insights to researchers developing and using participatory methods

    Sympathetic Activation and Baroreflex Function during Intradialytic Hypertensive Episodes

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    BACKGROUND: The mechanisms of intradialytic increases in blood pressure are not well defined. The present study was undertaken to assess the role of autonomic nervous system activation during intradialytic hypertensive episodes. METHODOLOGY/PRINCIPAL FINDINGS: Continuous interbeat intervals (IBI) and systolic blood pressure (SBP) were monitored during hemodialysis in 108 chronic patients. Intradialytic hypertensive episodes defined as a period of at least 10 mmHg increase in SBP between the beginning and the end of a dialysis session or hypertension resistant to ultrafiltration occurring during or immediately after the dialysis procedure, were detected in 62 out of 113 hemodialysis sessions. SBP variability, IBI variability and baroreceptor sensitivity (BRS) in the low (LF) and high (HF) frequency ranges were assessed using the complex demodulation technique (CDM). Intradialytic hypertensive episodes were associated with an increased (n = 45) or decreased (n = 17) heart rate. The maximal blood pressure was similar in both groups. In patients with increased heart rate the increase in blood pressure was associated with marked increases in SBP and IBI variability, with suppressed BRS indices and enhanced sympatho-vagal balance. In contrast, in those with decreased heart rate, there were no significant changes in the above parameters. End-of-dialysis blood pressure in all sessions associated with hypertensive episode was significantly higher than in those without such episodes. In logistic regression analysis, predialysis BRS in the low frequency range was found to be the main predictor of intradialytic hypertension. CONCLUSION/SIGNIFICANCE: Our data point to sympathetic overactivity with feed-forward blood pressure enhancement as an important mechanism of intradialytic hypertension in a significant proportion of patients. The triggers of increased sympathetic activity during hemodialysis remain to be determined. Intradialytic hypertensive episodes are associated with higher end-of-dialysis blood pressure, suggesting that intradialytic hypertension may play a role in generation of interdialytic hypertension
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