A choice of impossible things: dating the revival of The Battle of Alcazar

The surviving theatrical “plot” of The Battle of Alcazar is usually dated 1598, on the authority of W. W. Greg. His argument deserves closer scrutiny than it has often received: having accurately identified the outer limits, any more precise dating required him to choose between two “impossible” things: either Edward Alleyn broke his retirement to appear in the revival or a female role was played by an adult actor. This paper contends that Greg made the wrong choice, and that the plot probably dates from 1601. It seeks to identify evidence of the revival in Henslowe’s records, and places it in the context of the commercial and artistic strategies of the Admiral’s Men season that year. The revival emerges as a contribution to two strands of the company’s repertory: its exploitation of popular Edward Alleyn vehicles and its themed sequence of Spanish plays

Social Capital During COVID-19: Research Case Studies from U.S. and U.K. Contexts

Our research used a case study methodology to explore how engineering students at a university in the United Kingdom and in the United States experienced social supports in the spring term(s) of 2020 when universities worldwide shifted into emergency remote teaching due to the COVID-19 pandemic. To the best of our knowledge, this is the first cross-cultural study to examine engineering students' social support during the pandemic. We administered the Undergraduate Support Survey to engineering undergraduates at both institutions. The survey collected data about students' sense of belonging and social capital, including names of individuals who provided support for their engineering education and the specific expressive and instrumental resources they utilized during the pandemic. Results revealed similarities and differences between students at the two institutions. Both groups reported friends/roommates, professors, and family members as the primary providers of support, and both reported almost the same frequency in communication with these individuals. Participants at both institutions also reported high rates of instrumental and expressive support. However, the mean response for both sense of belonging and satisfaction at the university was lower in the U.K. and the types of alters identified in the two groups showed marked differences. Our work affirms the importance of social relationships to engineering students' success and persistence

Two adaptation processes in auditory hair cells together can provide an active amplifier

The hair cells of the vertebrate inner ear convert mechanical stimuli to electrical signals. Two adaptation mechanisms are known to modify the ionic current flowing through the transduction channels of the hair bundles: a rapid process involves calcium ions binding to the channels; and a slower adaptation is associated with the movement of myosin motors. We present a mathematical model of the hair cell which demonstrates that the combination of these two mechanisms can produce `self-tuned critical oscillations', i.e. maintain the hair bundle at the threshold of an oscillatory instability. The characteristic frequency depends on the geometry of the bundle and on the calcium dynamics, but is independent of channel kinetics. Poised on the verge of vibrating, the hair bundle acts as an active amplifier. However, if the hair cell is sufficiently perturbed, other dynamical regimes can occur. These include slow relaxation oscillations which resemble the hair bundle motion observed in some experimental preparations.Comment: 13 pages, 6 figures,REVTeX 4, To appear in Biophysical Journa

Must naive realists be relationalists?

Relationalism maintains that perceptual experience involves, as part of its nature, a distinctive kind of conscious perceptual relation between a subject of experience and an object of experience. Together with the claim that perceptual experience is presentational, relationalism is widely believed to be a core aspect of the naive realist outlook on perception. This is a mistake. I argue that naive realism about perception can be upheld without a commitment to relationalism

Multiple Lac-mediated loops revealed by Bayesian statistics and tethered particle motion

The bacterial transcription factor LacI loops DNA by binding to two separate locations on the DNA simultaneously. Despite being one of the best-studied model systems for transcriptional regulation, the number and conformations of loop structures accessible to LacI remain unclear, though the importance of multiple co-existing loops has been implicated in interactions between LacI and other cellular regulators of gene expression. To probe this issue, we have developed a new analysis method for tethered particle motion, a versatile and commonly-used in vitro single-molecule technique. Our method, vbTPM, performs variational Bayesian inference in hidden Markov models. It learns the number of distinct states (i.e., DNA-protein conformations) directly from tethered particle motion data with better resolution than existing methods, while easily correcting for common experimental artifacts. Studying short (roughly 100 bp) LacI-mediated loops, we provide evidence for three distinct loop structures, more than previously reported in single-molecule studies. Moreover, our results confirm that changes in LacI conformation and DNA binding topology both contribute to the repertoire of LacI-mediated loops formed in vitro, and provide qualitatively new input for models of looping and transcriptional regulation. We expect vbTPM to be broadly useful for probing complex protein-nucleic acid interactions.Comment: 34 pages, 25 figures, including Supporting information. To appear in Nucleic Acids Research. Accompanying open-source software: http://sourceforge.net/projects/vbtpm

Methodology for reliable and reproducible cryopreservation of human cervical tissue

BACKGROUND: In order to conduct laboratory studies on donated cervical tissue at suitable times an effective and reliable cryopreservation protocol for cervical tissue is required. METHODS: An active freezing approach was devised utilising 10% dimethyl sulfoxide in foetal bovine serum as a cryoprotective agent with a cooling rate of 1 °C/min to -50 °C then 10 °C/min to -120 °C; a related thawing protocol was also optimised which would allow for the bio-banking of cervical tissue. Viability of freshly harvested cervical tissue was compared to frozen-thawed samples utilising colorimetric MTT assay. In parallel, fresh and freeze-thawed samples were cultured and tested on days 1, 7 and 14 to determine whether bio-banking had detrimental effects on tissue viability over time. RESULTS: Repeat testing revealed that tissue viability between fresh and freeze-thawed wasand freeze-thawed samples was comparable at all four time points (days 0, 1, 7 and 14) with no apparent reductions of viability, thus demonstrating this method of cryopreserving cervical tissue is reliable and reproducible, without detrimental effects on live tissue culture. We believe this methodology creates the opportunity for bio-banking donated cervical tissues, which aids improved experimental design and reduces time pressures and wastage

The Coagulation and Immune Systems are Directly Linked through the Activation of Interleukin-1α by Thrombin

Ancient organisms have a combined coagulation and immune system, and although links between inflammation and haemostasis exist in mammals, they are indirect and slower to act. Here we investigated direct links between mammalian immune and coagulation systems by examining cytokine proproteins for potential thrombin protease consensus sites. We found that interleukin (IL)-1α is directly activated by thrombin. Thrombin cleaved pro-IL-1α at a site perfectly conserved across disparate species, indicating functional importance. Surface pro-IL-1α on macrophages and activated platelets was cleaved and activated by thrombin, while tissue factor, a potent thrombin activator, colocalised with pro-IL-1α in the epidermis. Mice bearing a mutation in the IL-1α thrombin cleavage site (R114Q) exhibited defects in efficient wound healing and rapid thrombopoiesis after acute platelet loss. Thrombin-cleaved IL-1α was detected in humans during sepsis, pointing to the relevance of this pathway for normal physiology and the pathogenesis of inflammatory and thrombotic diseases.This work was funded by British Heart Foundation Grants FS/09/005/26845, FS/13/3/30038, FS/18/19/33371 and RG/16/8/32388 to MC, RG/13/14/30314 to MB, the BHF Cambridge Centre for Research Excellence RE/13/6/30180, the Oxbridge BHF Regenerative Medicine Centre RM/13/3/30159, and the Cambridge NIHR Biomedical Research Centre

Bioresource of Cervical Tissue Explants from Healthy Women

The York Tissue Bank was established in 2013 at the University of York as a repository for cells and tissues to facilitate clinical and translational research at the university and with collaborative external tissue bank applicants. The bioresource described in this publication was initially established to conduct investigations into infection processes of sexually transmitted diseases in ex vivo organotypical models, specifically in uterine cervical tissue. Healthy human uterine cervical tissue is currently available to suitable applicants for ethically approved scientific research meeting the access criteria of the York tissue bank management committee