Prenatal diagnosis of thalassemia

published_or_final_versio

Factors affecting implementation of accreditation programmes and the impact of the accreditation process on quality improvement in hospitals: a SWOT analysis

published_or_final_versio

Development of a Bonner Sphere neutron spectrometer from a commercial neutron dosimeter

Bonner Spheres have been used widely for the measurement of neutron spectra with neutron energies ranged from thermal up to at least 20 MeV . A Bonner Sphere neutron spectrometer (BSS) was developed by extending a Berthold LB 6411 neutron-dose-rate meter. The BSS consists of a 3He thermal-neutron detector with integrated electronics, a set of eight polyethylene spherical shells and two optional lead shells of various sizes. The response matrix of the BSS was calculated with GEANT4 Monte Carlo simulation. The BSS had a calibration uncertainty of ± 8.6% and a detector background rate of (1.57 ± 0.04) × 10−3 s−1. A spectral unfolding code NSUGA was developed. The NSUGA code utilizes genetic algorithms and has been shown to perform well in the absence of a priori information.postprin

Measurement of cosmic-ray muons and muon-induced neutrons in the Aberdeen Tunnel Underground Laboratory

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An apparatus for studying spallation neutrons in the Aberdeen Tunnel laboratory

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BaBi₂O₆: A Promising n-Type Thermoelectric Oxide with the PbSb₂O₆ Crystal Structure

Thermoelectric materials offer the possibility of enhanced energy efficiency due to waste heat scavenging. Based on their high-temperature stability and ease of synthesis, efficient oxide-based thermoelectrics remain a tantalizing research goal; however, their current performance is significantly lower than the industry standards such as Bi_{2}Te_{3} and PbTe. Among the oxide thermoelectrics studied thus far, the development of n-type thermoelectric oxides has fallen behind that of p-type oxides, primarily due to limitations on the overall dimensionless figure of merit, or ZT, by large lattice thermal conductivities. In this article, we propose a simple strategy based on chemical intuition to discover enhanced n-type oxide thermoelectrics. Using state-of-the-art calculations, we demonstrate that the PbSb_{2}O_{6}-structured BaBi_{2}O_{6} represents a novel structural motif for thermoelectric materials, with a predicted ZT of 0.17–0.19. We then suggest two methods to enhance the ZT up to 0.22, on par with the current best earth-abundant n-type thermoelectric at around 600 K, SrTiO_{3}, which has been much more heavily researched. Our analysis of the factors that govern the electronic and phononic scattering in this system provides a blueprint for optimizing ZT beyond the perfect crystal approximation

Monoubiquitination of syntaxin 3 leads to retrieval from the basolateral plasma membrane and facilitates cargo recruitment to exosomes

Syntaxin 3 (Stx3), a SNARE protein located and functioning at the apical plasma membrane of epithelial cells, is required for epithelial polarity. A fraction of Stx3 is localized to late endosomes/lysosomes, although how it traffics there and its function in these organelles is unknown. Here we report that Stx3 undergoes monoubiquitination in a conserved polybasic domain. Stx3 present at the basolateral—but not the apical—plasma membrane is rapidly endocytosed, targeted to endosomes, internalized into intraluminal vesicles (ILVs), and excreted in exosomes. A nonubiquitinatable mutant of Stx3 (Stx3-5R) fails to enter this pathway and leads to the inability of the apical exosomal cargo protein GPRC5B to enter the ILV/exosomal pathway. This suggests that ubiquitination of Stx3 leads to removal from the basolateral membrane to achieve apical polarity, that Stx3 plays a role in the recruitment of cargo to exosomes, and that the Stx3-5R mutant acts as a dominant-negative inhibitor. Human cytomegalovirus (HCMV) acquires its membrane in an intracellular compartment and we show that Stx3-5R strongly reduces the number of excreted infectious viral particles. Altogether these results suggest that Stx3 functions in the transport of specific proteins to apical exosomes and that HCMV exploits this pathway for virion excretion

Patterning Bacterial Communities on Epithelial Cells

Micropatterning of bacteria using aqueous two phase system (ATPS) enables the localized culture and formation of physically separated bacterial communities on human epithelial cell sheets. This method was used to compare the effects of Escherichia coli strain MG1655 and an isogenic invasive counterpart that expresses the invasin (inv) gene from Yersinia pseudotuberculosis on the underlying epithelial cell layer. Large portions of the cell layer beneath the invasive strain were killed or detached while the non-invasive E. coli had no apparent effect on the epithelial cell layer over a 24 h observation period. In addition, simultaneous testing of the localized effects of three different bacterial species; E. coli MG1655, Shigella boydii KACC 10792 and Pseudomonas sp DSM 50906 on an epithelial cell layer is also demonstrated. The paper further shows the ability to use a bacterial predator, Bdellovibrio bacteriovorus HD 100, to selectively remove the E. coli, S. boydii and P. sp communities from this bacteria-patterned epithelial cell layer. Importantly, predation and removal of the P. Sp was critical for maintaining viability of the underlying epithelial cells. Although this paper focuses on a few specific cell types, the technique should be broadly applicable to understand a variety of bacteria-epithelial cell interactionsopen3

Measure of Activity Performance in the Hand (MAP-Hand) questionnaire

Background: Developed in the Norway, the Measure of Activity Performance of the Hand (MAP-Hand) assesses 18 activities performed using the hands. It was developed for people with rheumatoid arthritis (RA) using patient generated items, which are scored on a 0-3 scale and summarised into a total score range (0 to 54). This study reports the development and psychometric testing of the British English MAP-Hand in a UK population of people with RA. Methods: Recruitment took place in the National Health Service (NHS) through 17 Rheumatology outpatient clinics. Phase 1 (cross-cultural adaptation) involved: forward translation to British English; synthesis; expert panel review and cognitive debriefing interviews with people with RA. Phase 2 (psychometric testing) involved postal completion of the MAP-Hand, Health Assessment Questionnaire (HAQ), Upper Limb HAQ (ULHAQ), Short-Form 36 (SF-36v2) and Disabilities of the Arm Shoulder Hand (DASH) to measure internal consistency (Cronbach’s alpha); concurrent validity (Spearman’s correlations) and Minimal Detectable Difference (MDC95). The MAP-Hand was repeated three-weeks later to assess test-retest reliability (linear weighted kappa and Intra-Class Correlations (ICC (2,1)). Unidimensionality (internal construct validity) was assessed using (i) Confirmatory Factor Analysis (CFA) (ii) Mokken scaling and (iii) Rasch model. The RUMM2030 software was used, applying the Rasch partial credit model. Results: In Phase 1, 31 participants considered all items relevant. In Phase 2, 340 people completed Test-1 and 273 (80%) completed Test-2 questionnaires. Internal consistency was excellent (α=0.96). Test-retest reliability was good (ICC (2,1) = 0.96 (95% CI 0.94, 0.97)). The MAP-Hand correlated strongly with HAQ20 (rs=.88), ULHAQ (rs=.91), SF-36v2 Physical Functioning (PF) Score (rs=-.80) and DASH (rs=.93), indicating strong concurrent validity. CFA failed to support unidimensionality (Chi-Square 236.0 (df 120; p <0.001)). However, Mokken scaling suggested a probabilistic ordering. There was differential item functioning (DIF) for gender. Four testlets were formed, resulting in much improved fit and unidimensionality. Following this, testlets were further merged in pairs where opposite bias existed. This resulted in perfect fit to the model. Conclusions: The British English version of the MAP-Hand has good validity and reliability in people with RA and can be used in both research and clinical practice. Keywords: PROMS; Patient Reported Outcome Measures; hand activity performance; hand function; hand pain; psychometric testing; Rasch analysis; validity; reliabilit

The selective post-translational processing of transcription factor Nrf1 yields distinct isoforms that dictate its ability to differentially regulate gene expression

Upon translation, the N-terminal homology box 1 (NHB1) signal anchor sequence of Nrf1 integrates it within the endoplasmic reticulum (ER) whilst its transactivation domains [TADs, including acidic domain 1 (AD1), the flanking Asn/Ser/Thr-rich (NST) domain and AD2] are transiently translocated into the ER lumen, whereupon the NST domain is glycosylated to yield an inactive 120-kDa glycoprotein. Subsequently, these TADs are retrotranslocated into extra-luminal subcellular compartments, where Nrf1 is deglycosylated to yield an active 95-kDa isoform. Herein, we report that AD1 and AD2 are required for the stability of the 120-kDa Nrf1 glycoprotein, but not that of the non-glycosylated/de-glycosylated 95-kDa isoform. Degrons within AD1 do not promote proteolytic degradation of the 120-kDa Nrf1 glycoprotein. However, repositioning of AD2-adjoining degrons (i.e. DSGLS-containing SDS1 and PEST2 sequences) into the cyto/nucleoplasm enables selective topovectorial processing of Nrf1 by the proteasome and/or calpains to generate a cleaved active 85-kDa Nrf1 or a dominant-negative 36-kDa Nrf1γ. Production of Nrf1γ is abolished by removal of SDS1 or PEST2 degrons, whereas production of the cleaved 85-kDa Nrf1 is blocked by deletion of the ER luminal-anchoring NHB2 sequence (aa 81–106). Importantly, Nrf1 activity is positively and/or negatively regulated by distinct doses of proteasome and calpain inhibitors