The outcome of granulomatous experimental autoimmune thyroiditis is not associated with the chemokine profile [abstract]

Abstract only availableFaculty Mentor: Dr. Helen Mullen, Biology and ChemistrySevere granulomatous experimental autoimmune thyroiditis (G-EAT) develops in two wild type (WT), DBA-1 and CBA-J mice, and in DBA-1 IFNγ-/- mice. Over time, G-EAT can either progress to fibrosis or spontaneously resolve. To further define the role of IFNγ and chemokines in regulating disease outcome, G-EAT was induced by adoptive transfer of splenocytes activated in vitro with mouse thyroglobulin (MTg) and IL-12, and the outcome was compared among the different strains of mice. Severe G-EAT lesions in IFNγ-/- mice spontaneously resolved by day 35-45. Conversely, G-EAT in WT DBA-1 progressed to atrophy and fibrosis. One group of WT CBA-J mice progressed to resolution the other group of WT CBA-J mice progressed to fibrosis. Expression of cytokines and chemokines was determined by immunohistochemistry and RT-PCR. Thyroids of IFNγ-/- mice expressed no IFNγ, minimal iNOS, TNFα, IP-10, Mig, MCP-1 and CXCR3, but high levels of IL-4 and IL-10. DBA-1WT thyroids expressed high levels of the cytokines IFNγ, iNOS, TNFα and TGFβ, and higher levels of the chemokines IP-10, MIg, MCP-1, and CXCR3, but lower CCR3 than IFNγ-/- mice. Both groups of WT CBA-J mice expressed similarly high levels of IFNγ, IP-10, MIg, MCP-1 and CXCR3. These results suggest that the difference in outcome of G-EAT is not due to the chemokine profile. To account for the difference in outcomes between the two different WT strains, more data should be gathered about the difference between each strain's cytokine profile.Life Sciences Undergraduate Research Opportunity ProgramNational Institutes of Healt

EEG potentials associated with artificial grammar learning in the primate brain

AbstractElectroencephalography (EEG) has identified human brain potentials elicited by Artificial Grammar (AG) learning paradigms, which present participants with rule-based sequences of stimuli. Nonhuman animals are sensitive to certain AGs; therefore, evaluating which EEG Event Related Potentials (ERPs) are associated with AG learning in nonhuman animals could identify evolutionarily conserved processes. We recorded EEG potentials during an auditory AG learning experiment in two Rhesus macaques. The animals were first exposed to sequences of nonsense words generated by the AG. Then surface-based ERPs were recorded in response to sequences that were ‘consistent’ with the AG and ‘violation’ sequences containing illegal transitions. The AG violations strongly modulated an early component, potentially homologous to the Mismatch Negativity (mMMN), a P200 and a late frontal positivity (P500). The macaque P500 is similar in polarity and time of occurrence to a late EEG positivity reported in human AG learning studies but might differ in functional role

Backfiring and favouring:how design processes in HCI lead to anti-patterns and repentant designers

Design is typically envisioned as aiming to improve situations for users, but this can fail. Failure can be the result of flawed design solutions, i.e. anti-patterns. Prior work in anti-patterns has largely focused on their characteristics. We instead concentrate on why they occur by outlining two processes that result in anti-patterns: 1) backfiring, and 2) favouring. The purpose of the paper is to help designers and researchers better understand how design processes can lead to negative impacts and to repentant designers by introducing a richer vocabulary for discussing such processes. We explore how anti-patterns evolve in HCI by specifically applying the vocabulary to examples of social media design. We believe that highlighting these processes will help the HCI community reflect on their own work and also raise awareness of the opportunities for avoiding anti-patterns. Our hope is that this will result in fewer negative experiences for designers and users alike

Self-Control in Cyberspace: Applying Dual Systems Theory to a Review of Digital Self-Control Tools

Many people struggle to control their use of digital devices. However, our understanding of the design mechanisms that support user self-control remains limited. In this paper, we make two contributions to HCI research in this space: first, we analyse 367 apps and browser extensions from the Google Play, Chrome Web, and Apple App stores to identify common core design features and intervention strategies afforded by current tools for digital self-control. Second, we adapt and apply an integrative dual systems model of self-regulation as a framework for organising and evaluating the design features found. Our analysis aims to help the design of better tools in two ways: (i) by identifying how, through a well-established model of self-regulation, current tools overlap and differ in how they support self-control; and (ii) by using the model to reveal underexplored cognitive mechanisms that could aid the design of new tools.Comment: 11.5 pages (excl. references), 6 figures, 1 tabl

Higher Education Exchange: 2014

This annual publication serves as a forum for new ideas and dialogue between scholars and the larger public. Essays explore ways that students, administrators, and faculty can initiate and sustain an ongoing conversation about the public life they share.The Higher Education Exchange is founded on a thought articulated by Thomas Jefferson in 1820: "I know no safe depository of the ultimate powers of the society but the people themselves; and if we think them not enlightened enough to exercise their control with a wholesome discretion, the remedy is not to take it from them, but to inform their discretion by education."In the tradition of Jefferson, the Higher Education Exchange agrees that a central goal of higher education is to help make democracy possible by preparing citizens for public life. The Higher Education Exchange is part of a movement to strengthen higher education's democratic mission and foster a more democratic culture throughout American society.Working in this tradition, the Higher Education Exchange publishes interviews, case studies, analyses, news, and ideas about efforts within higher education to develop more democratic societies

Distinct MHC class I–dependent NK cell–activating receptors control cytomegalovirus infection in different mouse strains

MCMV-infected cells are recognized by multiple MHC class I–restricted Ly49-activating receptors in genetically distinct mouse strains

HIV-1 superinfection results in broad polyclonal neutralizing antibodies

<div><p>HIV-1 vaccines designed to date have failed to elicit neutralizing antibodies (Nabs) that are capable of protecting against globally diverse HIV-1 subtypes. One relevant setting to study the development of a strong, cross-reactive Nab response is HIV-1 superinfection (SI), defined as sequential infections from different source partners. SI has previously been shown to lead to a broader and more potent Nab response when compared to single infection, but it is unclear whether SI also impacts epitope specificity and if the epitopes targeted after SI differ from those targeted after single infection. Here the post-SI Nab responses were examined from 21 Kenyan women collectively exposed to subtypes A, C, and D and superinfected after a median time of ~1.07 years following initial infection. Plasma samples chosen for analysis were collected at a median time point ~2.72 years post-SI. Because previous studies of singly infected populations with broad and potent Nab responses have shown that the majority of their neutralizing activity can be mapped to 4 main epitopes on the HIV-1 Envelope, we focused on these targets, which include the CD4-binding site, a V1/V2 glycan, the N332 supersite in V3, and the membrane proximal external region of gp41. Using standard epitope mapping techniques that were applied to the previous cohorts, the present study demonstrates that SI did not induce a dominant Nab response to any one of these epitopes in the 21 women. Computational sera delineation analyses also suggested that 20 of the 21 superinfected women’s Nab responses could not be ascribed a single specificity with high confidence. These data are consistent with a model in which SI with diverse subtypes promotes the development of a broad polyclonal Nab response, and thus would provide support for vaccine designs using multivalent HIV immunogens to elicit a diverse repertoire of Nabs.</p></div

IgG-like bispecific antibodies with potent and synergistic neutralization against circulating SARS-CoV-2 variants of concern

Monoclonal antibodies are a promising approach to treat COVID-19, however the emergence of SARS-CoV-2 variants has challenged the efficacy and future of these therapies. Antibody cocktails are being employed to mitigate these challenges, but neutralization escape remains a major challenge and alternative strategies are needed. Here we present two anti-SARS-CoV-2 spike binding antibodies, one Class 1 and one Class 4, selected from our non-immune human single-chain variable fragment (scFv) phage library, that are engineered into four, fully-human IgG-like bispecific antibodies (BsAb). Prophylaxis of hACE2 mice and post-infection treatment of golden hamsters demonstrates the efficacy of the monospecific antibodies against the original Wuhan strain, while promising in vitro results with the BsAbs demonstrate enhanced binding and distinct synergistic effects on neutralizing activity against circulating variants of concern. In particular, one BsAb engineered in a tandem scFv-Fc configuration shows synergistic neutralization activity against several variants of concern including B.1.617.2. This work provides evidence that synergistic neutralization can be achieved using a BsAb scaffold, and serves as a foundation for the future development of broadly reactive BsAbs against emerging variants of concern