692 research outputs found
An observational study of individual child journeys through autism diagnostic pathways, and associated costs, in the UK National Health Service
Recommended from our members
TangiBall: development of a prototype tangible user interface for detection of speed and accuracy variation in pre-school autistic children
The creation of digital tools to assist in diagnostic pathways for children at-risk of autism is a priority due to increased prevalence. This project reports on the development of a tangible user interface as an ecologically valid option for children at-play in clinic. The toy aims to assist in useful data capture for preschool populations
Endoplasmic Reticulum Stress, Unfolded Protein Response and Altered T Cell Differentiation in Necrotizing Enterocolitis
Background:Endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR) play important roles in chronic intestinal inflammation. Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency in preterm infants and is characterized by acute intestinal inflammation and necrosis. The objective of the study is to investigate the role of ER stress and the UPR in NEC patients.Methods:Ileal tissues from NEC and control patients were obtained during surgical resection and/or at stoma closure. Splicing of XBP1 was detected using PCR, and gene expression was quantified using qPCR and Western blot.Results:Splicing of XBP1 was only detected in a subset of acute NEC (A-NEC) patients, and not in NEC patients who had undergone reanastomosis (R-NEC). The other ER stress and the UPR pathways, PERK and ATF6, were not activated in NEC patients. A-NEC patients showing XBP1 splicing (A-NEC-XBP1s) had increased mucosal expression of GRP78, CHOP, IL6 and IL8. Similar results were obtained by inducing ER stress and the UPR in vitro. A-NEC-XBP1s patients showed altered T cell differentiation indicated by decreased mucosal expression of RORC, IL17A and FOXP3. A-NEC-XBP1s patients additionally showed more severe morphological damage and a worse surgical outcome. Compared with A-NEC patients, R-NEC patients showed lower mucosal IL6 and IL8 expression and higher mucosal FOXP3 expression.Conclusions:XBP1 splicing, ER stress and the UPR in NEC are associated with increased IL6 and IL8 expression levels, altered T cell differentiation and severe epithelial injury
Photonic Characterisation of Indium Tin Oxide as a Function of Deposition Conditions
Indium tin oxide (ITO) has recently gained prominence as a photonic nanomaterial, for example, in modulators, tuneable metasurfaces and for epsilon-near-zero (ENZ) photonics. The optical properties of ITO are typically described by the Drude model and are strongly dependent on the deposition conditions. In the current literature, studies often make several assumptions to connect the optically measured material parameters to the electrical properties of ITO, which are not always clear, nor do they necessarily apply. Here, we present a comprehensive study of the structural, electrical, and optical properties of ITO and showed how they relate to the deposition conditions. We use guided mode resonances to determine the dispersion curves of the deposited material and relate these to structural and electrical measurements to extract all relevant material parameters. We demonstrate how the carrier density, mobility, plasma frequency, electron effective mass, and collision frequency vary as a function of deposition conditions, and that the high-frequency permittivity ((Formula presented.)) can vary significantly from the value of (Formula presented.) = 3.9 that many papers simply assume to be a constant. The depth of analysis we demonstrate allows the findings to be easily extrapolated to the photonic characterisation of other transparent conducting oxides (TCOs), whilst providing a much-needed reference for the research area
Design management: changing roles of the professions
This paper sets out to explore how recent changes in
procurement in construction have affected the roles that
professions play in the design process. It discusses how
professions that traditionally took the role of design
manager now find themselves participating within
previously unforeseen contexts, working in multidisciplinary
teams led by contractors and with changed
responsibilities at the design stage. Supply chain members
who were not previously involved during the early project
phases are being engaged at the earliest phases of the
project life cycle and even taking leadership roles while
designers sometimes work as supply chain partners.
A study of design in construction and other sectors shows
that in dealing with design management issues it is critical
to deepen appreciation for the unique characteristics of
design and the design process. The paper argues that
contractors and designers taking on design management
roles in a dynamic industry seeking to explore best
practice and innovative approaches to procurement and in
the delivery of projects need to acquire new skills,
management education and develop the necessary
qualities
Transcriptional control of the multi-drug transporter ABCB1 by transcription factor Sp3 in different human tissues
The ATP-binding cassette (ABC) transporter ABCB1, encoded by the multidrug resistance gene MDR1, is expressed on brain microvascular endothelium and several types of epithelium, but not on endothelia outside the CNS. It is an essential component of the blood-brain barrier. The aim of this study was to identify cell-specific controls on the transcription of MDR1 in human brain endothelium. Reporter assays identified a region of 500bp around the transcription start site that was optimally active in brain endothelium. Chromatin immunoprecipitation identified Sp3 and TFIID associated with this region and EMSA (electrophoretic mobility shift assays) confirmed that Sp3 binds preferentially to an Sp-target site (GC-box) on the MDR1 promoter in brain endothelium. This result contrasts with findings in other cell types and with the colon carcinoma line Caco-2, in which Sp1 preferentially associates with the MDR1 promoter. Differences in MDR1 transcriptional control between brain endothelium and Caco-2 could not be explained by the relative abundance of Sp1:Sp3 nor by the ratio of Sp3 variants, because activating variants of Sp3 were present in both cell types. However differential binding of other transcription factors was also detected in two additional upstream regions of the MDR1 promoter. Identification of cell-specific controls on the transcription of MDR1 indicates that it may be possible to modulate multi-drug resistance on tumours, while leaving the blood brain barrier intact
AGRONOMIC QUALITIES OF GENETIC PYRAMIDS OF COMMON BEAN DEVELOPED FOR MULTIPLE-DISEASE-RESISTANCE
Multiple co-infections by different pathogens on common bean (
Phaseolus vulgaris L.) affect its productivity and cause complete
crop loss in susceptible varieties. Therefore, gene pyramiding using
marker assisted selection (MAS) and backcrossing, provide alternative
cost-effective control measures to bean diseases. However, in the
process of developing pyramids, linkage drags were likely to affect the
qualities of progeny lines, hence, special attention was paid to this
situation. The objective of this study was thus to assess the agronomic
qualities of advanced genetic pyramids developed from a four-way cross
for multiple disease resistance. The disease resistance genes (R)
pyramided from four parents were: Co42 and Co-5 from G2333; Phg-2 from
MEX54; Pythium ultimum Dennis from MLB49-89A and I & bc3 from
MCM5001. The progeny lines were planted in an incomplete block design,
and replicated thrice for two seasons (2015A and 2015B) in fields at
CIAT, Kawanda in Uganda. Agronomic traits were highly heritable (0.6),
except number of pods per plant (< 0.3). Backcrossing generated
high-yielding bean lines, with 270 - 290 seed per plant and early
maturity (95-100 days). Nine superior lines with desirable qualities,
such as earliness (95 days), high seed rate (290 seeds per plant), and
climbing ability, were obtained. Pyramiding R genes did not affect
yield traits, except time to flowering and number of flower buds per
plant due to transgressive segregation.Les co-infections multiples par de diff\ue9rents pathog\ue8nes sur
le haricot commun ( Phaseolus vulgaris L.) affectent sa
productivit\ue9 et causent la perte totale des vari\ue9t\ue9s
susceptibles de la culture. Par cons\ue9quent, la pyramide des
g\ue8nes en utilisant la s\ue9lection assist\ue9e par des
marqueurs (MAS) et le r\ue9trocroisement, fournissent des mesures
alternatives de contr\uf4le moins ch\ue8res des maladies du
haricot. N\ue9anmoins, dans le processus du d\ue9veloppement des
pyramides, les poids des liaisons affectent probablement les
qualit\ue9s des lign\ue9es de prog\ue9nitures, de ce fait, une
attention particuli\ue8re \ue9tait port\ue9e \ue0 cette
situation. L\u2019objectif de cette \ue9tude \ue9tait
d\u2019\ue9valuer les qualit\ue9s agronomiques des pyramides
g\ue9n\ue9tiques avanc\ue9es d\ue9velopp\ue9es d\u2019un
croisement de quatre parents pour la r\ue9sistance aux maladies
multiples. Les g\ue8nes pyramid\ue9s de r\ue9sistance (R) \ue0
la maladie de quatre parents \ue9taient\ua0: Co42 et Co-5 de G2333;
Phg-2 de MEX54; Pythium ultimum Dennis de MLB49-89A et I & bc3
de MCM5001. Les lign\ue9es de prog\ue9nitures \ue9taient
plant\ue9es en arrangement de block incomplet et r\ue9pliqu\ue9
trois fois pendant deux saisons (2015A et 2015B) dans les champs \ue0
CIAT, Kawanda en Ouganda. Les traits agronomiques \ue9taient
hautement h\ue9ritables (0,6), \ue0 l\u2019exception du nombre de
gousses par plant (<0.3). Le r\ue9trocroisement a
g\ue9n\ue9r\ue9 des lign\ue9es d\u2019haricot \ue0 haut
rendement, avec 270-290 graines par plant et \ue0 maturit\ue9
pr\ue9coce (95-100 jours). Neuf lign\ue9es sup\ue9rieures avec
des qualit\ue9s d\ue9sirables, telles que la pr\ue9cocit\ue9
(95 jours), taux de graines \ue9lev\ue9s (290 graines par plant) et
l\u2019habilit\ue9 grimpante, \ue9taient obtenues. La pyramide des
g\ue8nes R n\u2019avait pas affect\ue9 les traits li\ue9s au
rendement, \ue0 l\u2019exception de la p\ue9riode de floraison et
le nombre de bougeons de fleurs par plant d\ufb \ue0 la
s\ue9gr\ue9gation transgressive
Phosphino-Triazole Ligands for Palladium-Catalyzed Cross-Coupling
Twelve
1,5-disubtituted and fourteen 5-substituted 1,2,3-triazole
derivatives bearing diaryl or dialkyl phosphines at the 5-position
were synthesized and used as ligands for palladium-catalyzed Suzuki–Miyaura
cross-coupling reactions. Bulky substrates were tested, and lead-like
product formation was demonstrated. The online tool SambVca2.0 was
used to assess steric parameters of ligands and preliminary buried
volume determination using XRD-obtained data in a small number of
cases proved to be informative. Two modeling approaches were compared
for the determination of the buried volume of ligands where XRD data
was not available. An approach with imposed steric restrictions was
found to be superior in leading to buried volume determinations that
closely correlate with observed reaction conversions. The online tool
LLAMA was used to determine lead-likeness of potential Suzuki–Miyaura
cross-coupling products, from which 10 of the most lead-like were
successfully synthesized. Thus, confirming these readily accessible
triazole-containing phosphines as highly suitable ligands for reaction
screening and optimization in drug discovery campaigns
- …