Frequency-domain waveform approximants capturing Doppler shifts

Gravitational wave astrophysics has only just begun, and as current detectors are upgraded and new detectors are built, many new, albeit faint, features in the signals will become accessible. One such feature is the presence of time-dependent Doppler shifts, generated by the acceleration of the center of mass of the gravitational-wave emitting system. We here develop a generic method that takes a frequency-domain, gravitational-wave model devoid of Doppler shifts and introduces modifications that incorporate them. Building upon a perturbative expansion that assumes the Doppler-shift velocity is small relative to the speed of light, the method consists of the inclusion of a single term in the Fourier phase and two terms in the Fourier amplitude. We validate the method through matches between waveforms with a Doppler shift in the time domain and waveforms constructed with our method for two toy problems: constant accelerations induced by a distant third body and Gaussian accelerations that resemble a kick profile. We find mismatches below $\sim\!10^{-6}$ for all of the astrophysically relevant cases considered, and improve further at smaller velocities. The work presented here will allow for the use of future detectors to extract new, faint features in the signal from the noise.Comment: 11 pages, 5 figures, submitted to Phys. Rev.

Pathological Consequences Of Pdi Oxidoreductase Activity On Viral Protein Maturation

The influenza A virus (IAV) causes severe respiratory illness in humans. Current treatments are rapidly becoming ineffective due to the emergence of viral resistance to available therapies such as oseltamivir and zanamivir. Given the impact of this virus there is an urgent need to explore novel targets for new treatments less susceptible to viral mutation; targeting host proteins utilized by the virus may avoid these limitations. It has been shown in vitro that interactions with host ER based protein disulfide isomerases (PDIs) are required for specific IAV proteins to reach their functional conformations. The viral proteins hemagglutinin (HA) and neuraminidase (NA) both contain numerous disulfide bonds necessary for their functionality. Our results demonstrate both HA and NA interact with host PDIA3; a chaperone responsible for the catalysis of disulfide bonds in newly formed glycoproteins. However, it is unknown whether these host-viral protein interactions are required during active infection and whether they represent a putative therapeutic target for the treatment of influenza infection. In this dissertation I investigated the role of host PDIA3 in the folding of IAV proteins and development of subsequent immunopathology. The impact of PDIA3 during both H1N1 and H3N2 influenza infection was examined using lung epithelial specific PDIA3 knockout mice and inhibitors of PDIs in primary human bronchial epithelial cells and isolated mouse tracheal epithelial cells. Among PDI inhibitors tested, we found LOC14 inhibits PDIA3 at an IC50 of 5μM. Treatment with LOC14 inhibits PDIA3 activity in lung epithelial cells and subsequently decreases disulfide bonds and oligomerization of HA in both H1N1 and H3N2 infected primary lung epithelial cells. Biotin switch assays indicated that LOC14 also decreased disulfide bonds in NA and these differences in oxidative folding correspond to a subsequent decrease in NA activity. Furthermore, following LOC14 treatment we observed a decrease in detectable viral protein in supernatants from infected cells, suggesting potential deficiencies in viral release. Moreover, these decreases in disulfide bonds significantly decrease viral load, and pro-inflammatory responses from primary lung epithelial cells. Lung epithelial specific deletion of PDIA3 in mice results in a significant decrease in viral burden and levels of inflammatory-immune markers in mouse lung, as well as significantly improved airway mechanics. Additionally, in vivo administration of LOC14 partially mirrored these results, yielding significant decreases in overall viral burden. Taken together, these data suggest that lung epithelial PDIA3 plays a critical role in the maturation of IAV proteins and propagation of the virus and illustrate the potential of utilizing host PDIs as a target for anti-viral therapies

Locating Identities in Time: An examination of the Impact of Temporality on Presentations of the Self through Location-based Social networks

Studies of identity and location-based social networks (LBSN) have tended to focus on the performative aspects associated with marking one’s location. Yet, these studies often present this practice as being an a priori aspect of locative media. What is missing from this research is a more granular understanding of how this process develops over time. Accordingly, we focus on the first six weeks of 42 users beginning to use an LBSN we designed and named GeoMoments. Through our analysis of our users\u27 activities, we contribute to understanding identity and LBSN in two distinct ways. First, we show how LBSN users develop and perform self-identity over time. Second, we highlight the extent these temporal processes reshape the behaviors of users. Overall, our results illustrate that while a performative use of GeoMoments does evolve, this development does not occur in a vacuum. Rather, it occurs within the dynamic context of everyday life, which is prompted, conditioned, and mediated by the way the affordances of GeoMoments digitally organize and archive past locational traces

Session II

Session 2: Poster Session 7:00-8:00pm: Enjoy some coffee and refreshments with the students of ENC 6942 Empirical Research in Composition as they present their empirical research design posters

280 lentiviral mediated gene therapy restores b cell homeostasis and tolerance in wiskott aldrich syndrome patients

Wiskott-Aldrich Syndrome (WAS) is a severe X-linked primary immunodeficiency characterized by micro-thrombocytopenia, eczema and increased risk of infections, autoimmunity and tumors. Allogeneic hematopoietic stem cell (HSC) transplantation is a recognized curative treatment for WAS, but when a matched donor is not available, administration of WAS gene-corrected autologous HSCs represents a valid alternative therapeutic approach. Since alterations of WAS protein (WASp)-deficient B lymphocytes contribute to immunodeficiency and autoimmunity in WAS, we followed the B cell reconstitution in 4 WAS patients treated by lentiviral vector-gene therapy (GT) after a reduced-intensity conditioning regimen combined with anti-CD20 administration. We analyzed the B cell subset distribution in the bone marrow and peripheral blood by flow cytometry and the autoantibody profile by a high-throughput autoantigen microarray platform before and after GT. Lentiviral vector-transduced progenitor cells were able to repopulate the B cell compartment with a normal distribution of transitional, naive and memory B cells. The reduction in the proportion of autoimmune-associated CD21low B cells and in the plasma levels of B cell-activating factor was associated with the decreased autoantibody production in WAS patients after GT. Then, we evaluated the functionality of B cell tolerance checkpoints by testing the reactivity of recombinant antibodies isolated from single B cells. Before GT, we found a decreased frequency of autoreactive new emigrant/transitional B cells in WAS patients, suggesting a hyperfunctional central B cell checkpoint in the absence of WASp. In contrast, high frequency of polyreactive and Hep2 reactive clones were found in mature naive B cells of WAS patients, indicating a defective peripheral B cell checkpoint. Both central and peripheral B cell tolerance checkpoints were restored after GT, further supporting the qualitative efficacy of this treatment. In conclusion, WASp plays an important role in the regulation of B cell homeostasis and in the establishment of B cell tolerance in humans and lentiviral-mediated GT is able to ameliorate the functionality of B cell compartment contributing to the clinical and immunological improvement in WAS patients

Synthesis and controlled growth of osmium nanoparticles by electron irradiation

YesWe have synthesised osmium nanoparticles of defined size (1.5–50 nm) on a B- and S-doped turbostratic graphitic structure by electron-beam irradiation of an organometallic osmium complex encapsulated in self-spreading polymer micelles, and characterised them by transmission electron microscopy (TEM), high-resolution TEM (HRTEM), and atomic force microscopy (AFM) on the same grid. Oxidation of the osmium nanoparticles after exposure to air was detected by X-ray photoelectron spectroscopy (XPS).We thank the Leverhulme Trust (Early Career Fellowship No. ECF-2013-414 to NPEB), the University of Warwick (Grant No. RD14102 to NPEB), the ERC (Grant No. 247450 to PJS), and the EPSRC (EP/F034210/1 to PJS). L.M.A.P., J.L., and G.C. acknowledge financial support from the EU through the ERC Consolidator Grant “VISUAL-MS”

Locating Identities in Time: An Examination of the Formation and Impact of Temporality on Presentations of the Self Through Location-based Social Networks

Studies of identity and location-based social networks (LBSN) have tended to focus on the performative aspects associated with marking one’s location. Yet, these studies often present this practice as being an a priori aspect of locative media. What is missing from this research is a more granular understanding of how this process develops over time. Accordingly, we focus on the first six weeks of 42 users beginning to use an LBSN we designed and named GeoMoments. Through our analysis of our users’ activities, we contribute to understanding identity and LBSN in two distinct ways. First, we show how LBSN users develop and perform self-identity over time. Second, we highlight the extent these temporal processes reshape the behaviors of users. Overall, our results illustrate that while a performative use of GeoMoments does evolve, this development does not occur in a vacuum. Rather, it occurs within the dynamic context of everyday life, which is prompted, conditioned, and mediated by the way the affordances of GeoMoments digitally organize and archive past locational traces

IMI-Onset and Progression of Myopia in Young Adults

Myopia typically starts and progresses during childhood, but onset and progression can occur during adulthood. The goals of this review are to summarize published data on myopia onset and progression in young adults, aged 18 to 40 years, to characterize myopia in this age group, to assess what is currently known, and to highlight the gaps in the current understanding. Specifically, the peer-reviewed literature was reviewed to: characterize the timeline and age of stabilization of juvenile-onset myopia; estimate the frequency of adult-onset myopia; evaluate the rate of myopia progression in adults, regardless of age of onset, both during the college years and later; describe the rate of axial elongation in myopic adults; identify risk factors for adult onset and progression; report myopia progression and axial elongation in adults who have undergone refractive surgery; and discuss myopia management and research study design. Adult-onset myopia is common, representing a third or more of all myopia in western populations, but less in East Asia, where onset during childhood is high. Clinically meaningful myopia progression continues in early adulthood and may average 1.00 diopters (D) between 20 and 30 years. Higher levels of myopia are associated with greater absolute risk of myopia-related ocular disease and visual impairment, and thus myopia in this age group requires ongoing management. Modalities established for myopia control in children would be options for adults, but it is difficult to predict their efficacy. The feasibility of studies of myopia control in adults is limited by the long duration required.</p

The Blood of Healthy Individuals Exhibits CD8 T Cells with a Highly Altered TCR Vb Repertoire but with an Unmodified Phenotype

CD8 T cell clonal expansions (TCE) have been observed in elderly, healthy individuals as well in old mice, and have been associated with the ageing process. Both chronic latent and non-persistent viral infections have been proposed to drive the development of distinct non-functional and functional TCE respectively. Biases in TCR Vβ repertoire diversity are also recurrently observed in patients that have undergone strong immune challenge, and are preferentially observed in the CD8 compartment. Healthy adults can also exhibit CD8 T cells with strong alterations of their CDR3 length distribution. Surprisingly, no specific investigations have been conducted to analyze the CD8 T cell repertoire in normal adults, to determine if such alterations in TCR Vβ repertoire share the features of TCE. In this study, we characterized the phenotype and function of the CD8 population in healthy individuals of 25–52 years of age. All but one of the EBV-positive HLA-B8 healthy volunteers that were studied were CMV-negative. Using a specific unsupervised statistical method, we identified Vβ families with altered CDR3 length distribution and increased TCR Vβ/HPRT transcript ratios in all individuals tested. The increase in TCR Vβ/HPRT transcript ratio was more frequently associated with an increase in the percentage of the corresponding Vβ+ T cells than with an absence of modification of their percentage. However, in contrast with the previously described TCE, these CD8+ T cells were not preferentially found in the memory CD8 subset, they exhibited normal effector functions (cytokine secretion and cytotoxic molecule expression) and they were not reactive to a pool of EBV/CMV/Flu virus peptides. Taken together, the combined analysis of transcripts and proteins of the TCR Vβ repertoire led to the identification of different types of CD8+ T cell clone expansion or contraction in healthy individuals, a situation that appears more complex than previously described in aged individuals