913 research outputs found
Predictors of Individual-Level Innovation at Work: A Meta-Analysis
peer-reviewedNumerous narrative reviews related to innovation in work organizations have been published, yet very few quantitative reviews have been conducted. The present meta-analysis investigates the relationships between four predictor types (individual differences, motivation, job characteristics, and contextual influences) and individual-level workplace innovation. Results indicated that individual factors, characteristics of the job, and factors of the environment were moderately associated with phases of the innovation process. Implications for future research opportunities are discussed.ACCEPTEDpeer-reviewe
Developmental regulation of Foxp3 expression during ontogeny
Thymectomy of neonatal mice can result in the development of autoimmune pathology. It has been proposed that thymic output of regulatory T (T reg) cells is delayed during ontogeny and that the development of autoimmune disease in neonatally thymectomized mice is caused by the escape of self-reactive T cells before thymectomy without accompanying T reg cells. However, the kinetics of T reg cell production within the thymus during ontogeny has not been assessed. We demonstrate that the development of Foxp3-expressing T reg cells is substantially delayed relative to nonregulatory thymocytes during ontogeny. Based on our data, we speculate that induction of Foxp3 in developing thymocytes and, thus, commitment to the T reg cell lineage is facilitated by a signal largely associated with the thymic medulla
Cardiff Urban Geo-Observatory : groundwater temperature data 2014-2018, metadata report
This report provides the metadata to accompany the first open source data release of groundwater temperature time series measurements from the ‘Cardiff Urban Geo-Observatory’ project.
Groundwater temperatures were measured in 53 boreholes at a sampling frequency of 30 minutes between 2014 to 2018. The dataset comprises over 3.5 million temperature measurements. Boreholes are located within the urban area of the City of Cardiff, Wales, UK. The majority of temperature sensors were installed within boreholes that monitor a shallow (maximum ~30m thickness) Quaternary aged sand and gravel aquifer, which is the target aquifer for the Cardiff Urban Geo-Observatory project. Representative groundwater temperature data from the Made Ground and the Triassic Mercia Mudstone are also reported.
We hope that by releasing this open-source data we can provide an evidence base to support the public, developers, planners, regulators, utility companies and policy makers that have an interest in the urban subsurface. We also hope to engage with other researchers and welcome collaborative research and innovation projects using this publically funded data.
The open access data can be downloaded from:
http://bgsintranet/resources/data/accessions/index.html?simpleText=ukgeos#item13016
A Three Monoclonal Antibody Combination Potently Neutralizes Multiple Botulinum Neurotoxin Serotype E Subtypes.
Human botulism is most commonly caused by botulinum neurotoxin (BoNT) serotypes A, B, and E. For this work, we sought to develop a human monoclonal antibody (mAb)-based antitoxin capable of binding and neutralizing multiple subtypes of BoNT/E. Libraries of yeast-displayed single chain Fv (scFv) antibodies were created from the heavy and light chain variable region genes of humans immunized with pentavalent-toxoid- and BoNT/E-binding scFv isolated by Fluorescence-Activated Cell Sorting (FACS). A total of 10 scFv were isolated that bound one or more BoNT/E subtypes with nanomolar-level equilibrium dissociation constants (KD). By diversifying the V-regions of the lead mAbs and selecting for cross-reactivity, we generated three scFv that bound all four BoNT/E subtypes tested at three non-overlapping epitopes. The scFvs were converted to IgG that had KD values for the different BoNT/E subtypes ranging from 9.7 nM to 2.28 pM. An equimolar combination of the three mAbs was able to potently neutralize BoNT/E1, BoNT/E3, and BoNT/E4 in a mouse neutralization assay. The mAbs have potential utility as therapeutics and as diagnostics capable of recognizing multiple BoNT/E subtypes. A derivative of the three-antibody combination (NTM-1633) is in pre-clinical development with an investigational new drug (IND) application filing expected in 2018
A Single Tri-Epitopic Antibody Virtually Recapitulates the Potency of a Combination of Three Monoclonal Antibodies in Neutralization of Botulinum Neurotoxin Serotype A.
The standard of treatment for botulism, equine antitoxin, is a foreign protein with associated safety issues and a short serum half-life which excludes its use as a prophylactic antitoxin and makes it a less-than-optimal therapeutic. Due to these limitations, a recombinant monoclonal antibody (mAb) product is preferable. It has been shown that combining three mAbs that bind non-overlapping epitopes leads to highly potent botulinum neurotoxin (BoNT) neutralization. Recently, a triple human antibody combination for BoNT/A has demonstrated potent toxin neutralization in mouse models with no serious adverse events when tested in a Phase I clinical trial. However, a triple antibody therapeutic poses unique development and manufacturing challenges. Thus, potentially to streamline development of BoNT antitoxins, we sought to achieve the potency of multiple mAb combinations in a single IgG-based molecule that has a long serum half-life. The design, production, and testing of a single tri-epitopic IgG1-based mAb (TeAb) containing the binding sites of each of the three parental BoNT/A mAbs yielded an antibody of nearly equal potency to the combination. The approach taken here could be applied to the design and creation of other multivalent antibodies that could be used for a variety of applications, including toxin elimination
Bayesian hierarchical inference of asteroseismic inclination angles
The stellar inclination angle-the angle between the rotation axis of a star
and our line of sight-provides valuable information in many different areas,
from the characterisation of the geometry of exoplanetary and eclipsing binary
systems, to the formation and evolution of those systems. We propose a method
based on asteroseismology and a Bayesian hierarchical scheme for extracting the
inclination angle of a single star. This hierarchical method therefore provides
a means to both accurately and robustly extract inclination angles from red
giant stars. We successfully apply this technique to an artificial dataset with
an underlying isotropic inclination angle distribution to verify the method. We
also apply this technique to 123 red giant stars observed with
. We also show the need for a selection function to account
for possible population-level biases, that are not present in individual
star-by-star cases, in order to extend the hierarchical method towards
inferring underlying population inclination angle distributions.Comment: 20 pages, 12 figures, accepted for publication in MNRA
Establishing an urban geo-observatory to support sustainable development of shallow subsurface heat recovery and storage
Low-enthalpy ground source heating and cooling is recognised as one strategy that can contribute towards reducing reliance on traditional, increasingly insecure, CO2-intense thermal power generation, as well as helping to address fuel poverty. Development of this technology is applicable in urban areas where high housing density often coincides with the presence of shallow aquifers. In urban areas groundwater temperatures can be elevated due to the subsurface Urban Heat Island effect. Uptake and development of this technology is often limited by initial investment costs, however, baseline temperature monitoring and characterisation of urban aquifers, conducted in partnership with local authorities, can provide a greater degree of certainty around resource and sustainability that can facilitate better planning, regulation and management of subsurface heat. We present a novel high-density, city-scale groundwater temperature observatory and introduce a 3D geological model aimed at addressing the needs of developers, planners, regulators and policy makers. The Cardiff Geo-Observatory measures temperature in a Quaternary aged sand and gravel aquifer in 61 boreholes and at a pilot shallow open-loop ground source heating system. We show that repurposing existing infrastructure can provide a cost effective method of developing monitoring networks, and make recommendations on establishing similar geo-observatories
Slow dynamics, aging, and glassy rheology in soft and living matter
We explore the origins of slow dynamics, aging and glassy rheology in soft
and living matter. Non-diffusive slow dynamics and aging in materials
characterised by crowding of the constituents can be explained in terms of
structural rearrangement or remodelling events that occur within the jammed
state. In this context, we introduce the jamming phase diagram proposed by Liu
and Nagel to understand the ergodic-nonergodic transition in these systems, and
discuss recent theoretical attempts to explain the unusual,
faster-than-exponential dynamical structure factors observed in jammed soft
materials. We next focus on the anomalous rheology (flow and deformation
behaviour) ubiquitous in soft matter characterised by metastability and
structural disorder, and refer to the Soft Glassy Rheology (SGR) model that
quantifies the mechanical response of these systems and predicts aging under
suitable conditions. As part of a survey of experimental work related to these
issues, we present x-ray photon correlation spectroscopy (XPCS) results of the
aging of laponite clay suspensions following rejuvenation. We conclude by
exploring the scientific literature for recent theoretical advances in the
understanding of these models and for experimental investigations aimed at
testing their predictions.Comment: 22 pages, 5 postscript figures; invited review aricle, to appear in
special issue on soft matter in Solid State Communication
Translating and transforming care: people with brain injury and caregivers filling in a disability claim form
This article examines how the Disability Living Allowance claim form, used in the United Kingdom to allocate £13 billion of disability benefits, translates and transforms disability and care. Twenty-two people with acquired brain injury and their main informal caregivers (n = 44) were video-recorded filling in the disability claim form. Participants disagreed on 26% of the questions, revealing two types of problems. Translation problems arose as participants struggled to provide categorical responses to ambiguous questions and were unable to report contextual variability in care needs or divergences of perception. Transformation problems arose as participants resisted the way in which the form positioned them, forcing them to conceptualize their relationship in terms of dependency and burden. The disability claim form co-opts claimants to translate care and disability into bureaucratically predefined categories, and it transforms the care relationship that it purports to document
Testing gravitational-wave searches with numerical relativity waveforms: Results from the first Numerical INJection Analysis (NINJA) project
The Numerical INJection Analysis (NINJA) project is a collaborative effort
between members of the numerical relativity and gravitational-wave data
analysis communities. The purpose of NINJA is to study the sensitivity of
existing gravitational-wave search algorithms using numerically generated
waveforms and to foster closer collaboration between the numerical relativity
and data analysis communities. We describe the results of the first NINJA
analysis which focused on gravitational waveforms from binary black hole
coalescence. Ten numerical relativity groups contributed numerical data which
were used to generate a set of gravitational-wave signals. These signals were
injected into a simulated data set, designed to mimic the response of the
Initial LIGO and Virgo gravitational-wave detectors. Nine groups analysed this
data using search and parameter-estimation pipelines. Matched filter
algorithms, un-modelled-burst searches and Bayesian parameter-estimation and
model-selection algorithms were applied to the data. We report the efficiency
of these search methods in detecting the numerical waveforms and measuring
their parameters. We describe preliminary comparisons between the different
search methods and suggest improvements for future NINJA analyses.Comment: 56 pages, 25 figures; various clarifications; accepted to CQ
- …