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"Beard, Michael C"
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The Beloved in Middle Eastern Literatures
In the long literary history of the Middle East, the notion of 'the beloved' has been a central trope in both the poetry and prose of the region. This book explores the concept of the beloved in a cross-cultural and interdisciplinary manner, revealing how shared ideas on the subject supersede geographical and temporal boundaries, and ideas of nationhood. The book considers the beloved in its classical, modern and postmodern manifestations, taking into account the different sexual orientations and forms of desire expressed. From the pre-Islamic 'Udhri (romantic unrequited love), to the erotic same-sex love in thirteenth century poetry and prose, the divine Sufi reflections on the topic, and post-revolutionary love encounters in Iran, Egypt and Saudi Arabia, The Beloved in Middle Eastern Literatures connects the affective and cultural with the political and the obscene. In focusing on the diverse manifestations of love and tropes of the lover/beloved binary, this book is unique in foregrounding what is often regarded as a 'taboo subject' in the region. The multi-faceted outlook reveals the variety of philological, philosophical, poetic and literary forms that treat this significant motif.
eBook
Constitutive expression and distinct properties of IFN-epsilon protect the female reproductive tract from Zika virus infection
The immunological surveillance factors controlling vulnerability of the female reproductive tract (FRT) to sexually transmitted viral infections are not well understood. Interferon-epsilon (IFNɛ) is a distinct, immunoregulatory type-I IFN that is constitutively expressed by FRT epithelium and is not induced by pathogens like other antiviral IFNs α, β and λ. We show the necessity of IFNɛ for Zika Virus (ZIKV) protection by: increased susceptibility of IFNɛ -/- mice; their “rescue” by intravaginal recombinant IFNɛ treatment and blockade of protective endogenous IFNɛ by neutralising antibody. Complementary studies in human FRT cell lines showed IFNɛ had potent anti-ZIKV activity, associated with transcriptome responses similar to IFNλ but lacking the proinflammatory gene signature of IFNα. IFNɛ activated STAT1/2 pathways similar to IFNα and λ that were inhibited by ZIKV-encoded non-structural (NS) proteins, but not if IFNε exposure preceded infection. This scenario is provided by the constitutive expression of endogenous IFNε. However, the IFNɛ expression was not inhibited by ZIKV NS proteins despite their ability to antagonise the expression of IFNβ or λ. Thus, the constitutive expression of IFNɛ provides cellular resistance to viral strategies of antagonism and maximises the antiviral activity of the FRT. These results show that the unique spatiotemporal properties of IFNε provides an innate immune surveillance network in the FRT that is a significant barrier to viral infection with important implications for prevention and therapy.
Journal Article
Long-term perturbation of the peripheral immune system months after SARS-CoV-2 infection
Background
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly infectious respiratory virus which is responsible for the coronavirus disease 2019 (COVID-19) pandemic. It is increasingly clear that recovered individuals, even those who had mild COVID-19, can suffer from persistent symptoms for many months after infection, a condition referred to as “long COVID”, post-acute sequelae of COVID-19 (PASC), post-acute COVID-19 syndrome, or post COVID-19 condition. However, despite the plethora of research on COVID-19, relatively little is known about the molecular underpinnings of these long-term effects.
Methods
We have undertaken an integrated analysis of immune responses in blood at a transcriptional, cellular, and serological level at 12, 16, and 24 weeks post-infection (wpi) in 69 patients recovering from mild, moderate, severe, or critical COVID-19 in comparison to healthy uninfected controls. Twenty-one of these patients were referred to a long COVID clinic and > 50% reported ongoing symptoms more than 6 months post-infection.
Results
Anti-Spike and anti-RBD IgG responses were largely stable up to 24 wpi and correlated with disease severity. Deep immunophenotyping revealed significant differences in multiple innate (NK cells, LD neutrophils, CXCR3+ monocytes) and adaptive immune populations (T helper, T follicular helper, and regulatory T cells) in convalescent individuals compared to healthy controls, which were most strongly evident at 12 and 16 wpi. RNA sequencing revealed significant perturbations to gene expression in COVID-19 convalescents until at least 6 months post-infection. We also uncovered significant differences in the transcriptome at 24 wpi of convalescents who were referred to a long COVID clinic compared to those who were not.
Conclusions
Variation in the rate of recovery from infection at a cellular and transcriptional level may explain the persistence of symptoms associated with long COVID in some individuals.
Journal Article
A systematic evaluation of the performance and properties of the UK Biobank Polygenic Risk Score (PRS) Release
We assess the UK Biobank (UKB) Polygenic Risk Score (PRS) Release, a set of PRSs for 28 diseases and 25 quantitative traits that has been made available on the individuals in UKB, using a unified pipeline for PRS evaluation. We also release a benchmarking software tool to enable like-for-like performance evaluation for different PRSs for the same disease or trait. Extensive benchmarking shows the PRSs in the UKB Release to outperform a broad set of 76 published PRSs. For many of the diseases and traits we also validate the PRS algorithms in a separate cohort (100,000 Genomes Project). The availability of PRSs for 53 traits on the same set of individuals also allows a systematic assessment of their properties, and the increased power of these PRSs increases the evidence for their potential clinical benefit.
Journal Article
Pesticide Exposure and Depression among Male Private Pesticide Applicators in the Agricultural Health Study
Pesticide exposure may be positively associated with depression. Few previous studies have considered the episodic nature of depression or examined individual pesticides.
We evaluated associations between pesticide exposure and depression among male private pesticide applicators in the Agricultural Health Study.
We analyzed data for 10 pesticide classes and 50 specific pesticides used by 21,208 applicators enrolled in 1993-1997 who completed a follow-up telephone interview in 2005-2010. We divided applicators who reported a physician diagnosis of depression (n = 1,702; 8%) into those who reported a previous diagnosis of depression at enrollment but not follow-up (n = 474; 28%), at both enrollment and follow-up (n = 540; 32%), and at follow-up but not enrollment (n = 688; 40%) and used polytomous logistic regression to estimate odds ratios (ORs) and 95% CIs. We used inverse probability weighting to adjust for potential confounders and to account for the exclusion of 3,315 applicators with missing covariate data and 24,619 who did not complete the follow-up interview.
After weighting for potential confounders, missing covariate data, and dropout, ever-use of two pesticide classes, fumigants and organochlorine insecticides, and seven individual pesticides-the fumigants aluminum phosphide and ethylene dibromide; the phenoxy herbicide (2,4,5-trichlorophenoxy)acetic acid (2,4,5-T); the organochlorine insecticide dieldrin; and the organophosphate insecticides diazinon, malathion, and parathion-were all positively associated with depression in each case group, with ORs between 1.1 and 1.9.
Our study supports a positive association between pesticide exposure and depression, including associations with several specific pesticides.
Journal Article
Wireless, closed-loop, smart bandage with integrated sensors and stimulators for advanced wound care and accelerated healing
‘Smart’ bandages based on multimodal wearable devices could enable real-time physiological monitoring and active intervention to promote healing of chronic wounds. However, there has been limited development in incorporation of both sensors and stimulators for the current smart bandage technologies. Additionally, while adhesive electrodes are essential for robust signal transduction, detachment of existing adhesive dressings can lead to secondary damage to delicate wound tissues without switchable adhesion. Here we overcome these issues by developing a flexible bioelectronic system consisting of wirelessly powered, closed-loop sensing and stimulation circuits with skin-interfacing hydrogel electrodes capable of on-demand adhesion and detachment. In mice, we demonstrate that our wound care system can continuously monitor skin impedance and temperature and deliver electrical stimulation in response to the wound environment. Across preclinical wound models, the treatment group healed ~25% more rapidly and with ~50% enhancement in dermal remodeling compared with control. Further, we observed activation of proregenerative genes in monocyte and macrophage cell populations, which may enhance tissue regeneration, neovascularization and dermal recovery.
A wireless ‘smart’ bandage stimulates wound healing.
Journal Article
The Daniel K. Inouye Solar Telescope – Observatory Overview
We present an overview of the National Science Foundation’s
Daniel K. Inouye Solar Telescope
(DKIST), its instruments, and support facilities. The 4 m aperture DKIST provides the highest-resolution observations of the Sun ever achieved. The large aperture of DKIST combined with state-of-the-art instrumentation provide the sensitivity to measure the vector magnetic field in the chromosphere and in the faint corona, i.e. for the first time with DKIST we will be able to measure and study the most important free-energy source in the outer solar atmosphere – the coronal magnetic field. Over its operational lifetime DKIST will advance our knowledge of fundamental astronomical processes, including highly dynamic solar eruptions that are at the source of space-weather events that impact our technological society. Design and construction of DKIST took over two decades. DKIST implements a fast (f/2), off-axis Gregorian optical design. The maximum available field-of-view is 5 arcmin. A complex thermal-control system was implemented in order to remove at prime focus the majority of the 13 kW collected by the primary mirror and to keep optical surfaces and structures at ambient temperature, thus avoiding self-induced local seeing. A high-order adaptive-optics system with 1600 actuators corrects atmospheric seeing enabling diffraction limited imaging and spectroscopy. Five instruments, four of which are polarimeters, provide powerful diagnostic capability over a broad wavelength range covering the visible, near-infrared, and mid-infrared spectrum. New polarization-calibration strategies were developed to achieve the stringent polarization accuracy requirement of 5×10
−4
. Instruments can be combined and operated simultaneously in order to obtain a maximum of observational information. Observing time on DKIST is allocated through an open, merit-based proposal process. DKIST will be operated primarily in “service mode” and is expected to on average produce 3 PB of raw data per year. A newly developed data center located at the NSO Headquarters in Boulder will initially serve fully calibrated data to the international users community. Higher-level data products, such as physical parameters obtained from inversions of spectro-polarimetric data will be added as resources allow.
Journal Article
Emergence of Novel Norovirus GII.4 Variant
We detected a novel GII.4 variant with an amino acid insertion at the start of epitope A in viral protein 1 of noroviruses from the United States, Gabon, South Africa, and the United Kingdom collected during 2017-2022. Early identification of GII.4 variants is crucial for assessing pandemic potential and informing vaccine development.
Journal Article
