1,134 research outputs found
Nightingales in Medieval Text and Sound: Liminality and Evasion
Le rossignol apparaĂźt trĂšs souvent dans les rĂ©cits du Moyen Ăge, mĂȘme si cette prĂ©sence est Ă©phĂ©mĂšre, puisque intangible. Le rossignol est connu par sa voix, et lâintĂ©rĂȘt de cette crĂ©ature aux yeux de lâĂȘtre humain rĂ©side dans son chant qui ne dure que lâespace dâune saison. Ce chant tĂ©moigne de la prĂ©sence paradoxale du rossignol, liĂ©e Ă la distance physique qui le maintient au-delĂ de lâespace que sâest appropriĂ© lâĂȘtre humain. La liminalitĂ© du rossignol, toujours situĂ© Ă la marge de lâespace occupĂ© par lâauditoire humain, fait de cette crĂ©ature une figure du dĂ©sir dans des textes du XIIe et du XIIIe siĂšcle en français et en anglais.Nightingales appear frequently in medieval texts, yet their appearances are fleeting and elusive as they remain just beyond human reach. The presence of the nightingale is marked by its voice, and the creatureâs interest for human audiences is linked to its brief, seasonal song. This paper examines the nightingaleâs paradoxical presence through sound, which contrasts with the physical distance that allows the creature to remain just beyond the contours of human reach. The liminal space accorded to the nightingale, a space just beyond that occupied by the human listener, allows the nightingale to represent longing and desire in a variety of texts written in French and English in the twelfth and thirteenth centuries
Local authority responses to people with NRPF during the pandemic: research report
Migrants with âno recourse to public fundsâ (NRPF) are at high risk of destitution due to their exclusion from most welfare benefits and statutory housing support. This is a longstanding issue that has been highlighted by campaigners, academics and the migration sector.
This report examines how local authorities in England responded to people with NRPF during the COVID-19 pandemic. It highlights systemic issues with access to support for people with NRPF and shows how provision varied considerably across England (most notably in the case of single adults with NRPF who would not normally be eligible for support but were included in the COVID-19 homelessness response) and even within individual local authorities.
The COVID-19 pandemic has made life significantly more difficult and precarious for people with NRPF. Many have lost income, employment and accommodation, while non-statutory support services have been forced to close. The number of people with NRPF in need of assistance to meet their basic needs has increased. Our research indicates that people with NRPF are more likely to become seriously ill or die if they contract COVID-19. Despite this, it has been difficult for many people with NRPF to access the help they need, including adequate food, shelter and subsistence support, during this public health crisis.
Local authorities have statutory duties towards two categories of people with NRPF: families with âchildren in needâ; and adults with care needs. There are, however, significant variations in how these duties are implemented, with many migrants in need of support unable to access their entitlements under normal (pre-pandemic) circumstances. A key problem in this area is that local authorities are not funded by central government to provide support to people with NRPF - an issue that has been consistently raised by rights advocates. This issue became more urgent during the pandemic as local authorities were called upon by central government to provide support to a third group of people with NRPF who would not normally be eligible for assistance: single homeless adults without care needs. Our research shows that, while some councils put in place effective emergency support for this group, the England-wide response of local authorities was frequently characterised by confusion, a lack of information about support options, the âgatekeepingâ of access to accommodation, and gaps in essential provision (e.g. food).
Our research focuses on the period during which the UK was in âlockdownâ. But the problems we highlight in this report have by no means come to an end. Local authorities continue to be underfunded and the destitution experienced by people with NRPF has not abated. It is unclear what will happen to homeless adults with NRPF who have no statutory entitlement to support as public- health concerns subside. Our research indicates that while some local authorities are trying to respond to this issue in a way that respects peopleâs rights and dignity, others do not want to continue to support people with NRPF, with a number planning to resort to so-called âvoluntary returnsâ or âreconnectionâ. In the view of many of our research participants, only an urgent end to the NRPF system can adequately address the problems that have been highlighted by COVID-19
Local Authority responses to people with NRPF during the pandemic: Interim project findings briefing
This interim briefing presents initial findings from a project exploring the support available to migrants with no recourse to public funds during the COVID-19 pandemic. The research included a survey of local authorities in England, and a call for evidence from migrant support organisations in England, Scotland and Wales. More than 90 percent of local authorities had not shared information about support for people with NRPF during the pandemic, and support organisations reported that service users had struggled to access food, shelter and subsistence support during the pandemic.Paul Hamlyn Foundatio
Robotic metamorphosis by origami exoskeletons
Changing the inherent physical capabilities of robots by metamorphosis has been a long-standing goal of engineers. However, this task is challenging because of physical constraints in the robot body, each component of which has a defined functionality. To date, self-reconfiguring robots have limitations in their on-site extensibility because of the large scale of todayâs unit modules and the complex administration of their coordination, which relies heavily on on-board electronic components. We present an approach to extending and changing the capabilities of a robot by enabling metamorphosis using self-folding origami âexoskeletons.â We show how a cubical magnet ârobotâ can be remotely moved using a controllable magnetic field and hierarchically develop different morphologies by interfacing with different origami exoskeletons. Activated by heat, each exoskeleton is self-folded from a rectangular sheet, extending the capabilities of the initial robot, such as enabling the manipulation of objects or locomotion on the ground, water, or air. Activated by water, the exoskeletons can be removed and are interchangeable. Thus, the system represents an end-to-end (re)cycle. We also present several robot and exoskeleton designs, devices, and experiments with robot metamorphosis using exoskeletons
The Role of the Tight-Turn, Broken Hydrogen Bonding, Glu222 and Arg96 in the Post-translational Green Fluorescent Protein Chromophore Formation
Green fluorescent proteins (GFP) and GFP-like proteins all undergo an autocatalytic post-translational modification to form a centrally located chromophore. Structural analyses of all the GFP and GFP-like proteins in the protein databank were undertaken to determine the role of the tight-turn, broken hydrogen bonding, Gly67, Glu222 and Arg96 in the biosynthesis of the imidazolone group from 65SYG67. The analysis was supplemented by computational generation of the conformation adopted by uncyclized wild-type GFP. The data analysis suggests that Arg96 interacts with the Tyr66 carbonyl, stabilizing the reduced enolate intermediate that is required for cyclization; the carboxylate of Glu222 acts as a base facilitating, through a network of two waters, the abstraction of a hydrogen from the α-carbon of Tyr66; a tight-turn conformation is required for autocatalytic cyclization. This conformation is responsible for a partial reduction in the hydrogen bonding network around the chromophore-forming region of the immature protein
Myostatin inhibition in combination with antisense oligonucleotide therapy improves outcomes in spinal muscular atrophy
BACKGROUND
Spinal muscular atrophy (SMA) is caused by genetic defects in the survival motor neuron 1 (SMN1) gene that lead to SMN deficiency. Different SMNârestoring therapies substantially prolong survival and function in transgenic mice of SMA. However, these therapies do not entirely prevent muscle atrophy and restore function completely. To further improve the outcome, we explored the potential of a combinatorial therapy by modulating SMN production and muscleâenhancing approach as a novel therapeutic strategy for SMA.
METHODS
The experiments were performed in a mouse model of severe SMA. A previously reported 25âmer morpholino antisense oligomer PMO25 was used to restore SMN expression. The adenoâassociated virusâmediated expression of myostatin propeptide was used to block the myostatin pathway. Newborn SMA mice were treated with a single subcutaneous injection of 40 ÎŒg/g (therapeutic dose) or 10 ÎŒg/g (lowâdose) PMO25 on its own or together with systemic delivery of a single dose of adenoâassociated virusâmediated expression of myostatin propeptide. The multiple effects of myostatin inhibition on survival, skeletal muscle phenotype, motor function, neuromuscular junction maturation, and proprioceptive afferences were evaluated.
RESULTS
We show that myostatin inhibition acts synergistically with SMNârestoring antisense therapy in SMA mice treated with the higher therapeutic dose PMO25 (40 ÎŒg/g), by increasing not only body weight (21% increase in male mice at Day 40), muscle mass (38% increase), and fibre size (35% increase in tibialis anterior muscle in 3 month female SMA mice), but also motor function and physical performance as measured in hanging wire test (twoâfold increase in time score) and treadmill exercise test (twoâfold increase in running distance). In SMA mice treated with lowâdose PMO25 (10 ÎŒg/g), the early application of myostatin inhibition prolongs survival (40% increase), improves neuromuscular junction maturation (50% increase) and innervation (30% increase), and increases both the size of sensory neurons in dorsal root ganglia (60% increase) and the preservation of proprioceptive synapses in the spinal cord (30% increase).
CONCLUSIONS
These data suggest that myostatin inhibition, in addition to the wellâknown effect on muscle mass, can also positively influence the sensory neural circuits that may enhance motor neurons function. While the availability of the antisense drug Spinraza for SMA and other SMNâenhancing therapies has provided unprecedented improvement in SMA patients, there are still unmet needs in these patients. Our study provides further rationale for considering myostatin inhibitors as a therapeutic intervention in SMA patients, in combination with SMNârestoring drugs
Digital Quantum Simulation of the Statistical Mechanics of a Frustrated Magnet
Many interesting problems in physics, chemistry, and computer science are
equivalent to problems of interacting spins. However, most of these problems
require computational resources that are out of reach by classical computers. A
promising solution to overcome this challenge is to exploit the laws of quantum
mechanics to perform simulation. Several "analog" quantum simulations of
interacting spin systems have been realized experimentally. However, relying on
adiabatic techniques, these simulations are limited to preparing ground states
only. Here we report the first experimental results on a "digital" quantum
simulation on thermal states; we simulated a three-spin frustrated magnet, a
building block of spin ice, with an NMR quantum information processor, and we
are able to explore the phase diagram of the system at any simulated
temperature and external field. These results serve as a guide for identifying
the challenges for performing quantum simulation on physical systems at finite
temperatures, and pave the way towards large scale experimental simulations of
open quantum systems in condensed matter physics and chemistry.Comment: 7 pages for the main text plus 6 pages for the supplementary
material
Prediction of photoperiodic regulators from quantitative gene circuit models
Photoperiod sensors allow physiological adaptation to the changing seasons. The external coincidence hypothesis postulates that a light-responsive regulator is modulated by a circadian rhythm. Sufficient data are available to test this quantitatively in plants, though not yet in animals. In Arabidopsis, the clock-regulated genes CONSTANS (CO) and FLAVIN, KELCH, F-BOX (FKF1) and their lightsensitive proteins are thought to form an external coincidence sensor. We use 40 timeseries of molecular data to model the integration of light and timing information by CO, its target gene FLOWERING LOCUS T (FT), and the circadian clock. Among other predictions, the models show that FKF1 activates FT. We demonstrate experimentally that this effect is independent of the known activation of CO by FKF1, thus we locate a major, novel controller of photoperiodism. External coincidence is part of a complex photoperiod sensor: modelling makes this complexity explicit and may thus contribute to crop improvement
A Palaeoenvironmental Investigation of Two Prehistoric Burnt Mound Sites in Northern Ireland
Funded by Road services Northern Ireland, Jacobs and Headland ArchaeologyPeer reviewedPostprin
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