201 research outputs found
A short response-time atomic source for trapped ion experiments
Ion traps are often loaded from atomic beams produced by resistively heated
ovens. We demonstrate an atomic oven which has been designed for fast control
of the atomic flux density and reproducible construction. We study the limiting
time constants of the system and, in tests with , show we can
reach the desired level of flux in 12s, with no overshoot. Our results indicate
that it may be possible to achieve an even faster response by applying an
appropriate one-off heat treatment to the oven before it is used.Comment: 5 pages, 7 figure
Longitudinal patterns of antidepressant prescribing in primary care in the UK: comparison with treatment guidelines
The objective of this study was to determine whether patients beginning therapy on the most common tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs) differed in their likelihood of having antidepressant treatment that was consistent with recommended treatment guidelines in the UK. An analytical file constructed from a large general practitioner medical records database (DIN-LINK) from the UK for the years 1992-97 was constructed. A total of 16 204 patients with a new episode of antidepressant therapy who initiated therapy on one of the most often prescribed TCAs (amitriptyline, dothiepin, imipramine and lofepramine) or SSRIs (fluoxetine, paroxetine and sertraline) were analysed. A dichotomous measure was defined to indicate whether subjects were prescribed at least 120 days of antidepressant therapy at an adequate average daily dose within the first 6 months after initiation of therapy. Only 6.0% of patients initiating therapy on aTCA and 32.9% of patients initiating therapy on a SSRI were prescribed antidepressant treatment that was consistent with treatment guidelines. After controlling for observable characteristics, patients who initiated therapy on a SSRI were much more likely (odds ratio=7.473, p<0.001) to have a prescribed average daily dose and duration consistent with recommended treatment guidelines within the first 6 months of initiating therapy than were patients who initiated therapy on a TCA. These findings suggest that initial antidepressant selection is an important determinant of whether the subsequent course of treatment is consistent with current national guidelines for the treatment of depression in the UK.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68732/2/10.1177_026988119901300204.pd
Complete absence of GLUT1 does not impair human terminal erythroid differentiation
The Glucose transporter 1 (GLUT1) is one of the most abundant proteins within the erythrocyte membrane and is required for glucose and dehydroascorbic acid (Vitamin C precursor) transport. It is widely recognized as a key protein for red cell structure, function, and metabolism. Previous reports highlighted the importance of GLUT1 activity within these uniquely glycolysis-dependent cells, in particular for increasing antioxidant capacity needed to avoid irreversible damage from oxidative stress in humans. However, studies of glucose transporter roles in erythroid cells are complicated by species-specific differences between humans and mice. Here, using CRISPR-mediated gene editing of immortalized erythroblasts and adult CD34+ hematopoietic progenitor cells, we generate committed human erythroid cells completely deficient in expression of GLUT1. We show that absence of GLUT1 does not impede human erythroblast proliferation, differentiation, or enucleation. This work demonstrates for the first-time generation of enucleated human reticulocytes lacking GLUT1. The GLUT1-deficient reticulocytes possess no tangible alterations to membrane composition or deformability in reticulocytes. Metabolomic analyses of GLUT1-deficient reticulocytes reveal hallmarks of reduced glucose import, downregulated metabolic processes and upregulated AMPK-signalling, alongside alterations in antioxidant metabolism, resulting in increased osmotic fragility and metabolic shifts indicative of higher oxidant stress. Despite detectable metabolic changes in GLUT1 deficient reticulocytes, the absence of developmental phenotype, detectable proteomic compensation or impaired deformability comprehensively alters our understanding of the role of GLUT1 in red blood cell structure, function and metabolism. It also provides cell biological evidence supporting clinical consensus that reduced GLUT1 expression does not cause anaemia in GLUT1 deficiency syndrome
Pattern scaling using ClimGen: monthly-resolution future climate scenarios including changes in the variability of precipitation
Development, testing and example applications of the pattern-scaling approach for generating future climate change projections are reported here, with a focus on a particular software application called âClimGenâ. A number of innovations have been implemented, including using exponential and logistic functions of global-mean temperature to represent changes in local precipitation and cloud cover, and interpolation from climate model grids to a finer grid while taking into account land-sea contrasts in the climate change patterns. Of particular significance is a new approach for incorporating changes in the inter-annual variability of monthly precipitation simulated by climate models. This is achieved by diagnosing simulated changes in the shape of the gamma distribution of monthly precipitation totals, applying the pattern-scaling approach to estimate changes in the shape parameter under a future scenario, and then perturbing sequences of observed precipitation anomalies so that their distribution changes according to the projected change in the shape parameter. The approach cannot represent changes to the structure of climate timeseries (e.g. changed autocorrelation or teleconnection patterns) were they to occur, but is shown here to be more successful at representing changes in low precipitation extremes than previous pattern-scaling methods
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Collaborative Autoethnographic Writing as Communal Curative
This collaborative autoethnography reflects on how each author experienced COVID-19 and associated precarity. We explore the ways in which this experience relates to our identities (both particular and plural), and our positionalities in terms of privilege and marginality. As a collective of diverse collaborators, we confront dialectical questions of self and society. Our contributions reveal our advantage/disadvantage, mobility/immobility, and the borders and boundedness before/during/after COVID-19. We show the power of curative writing in collaborative autoethnography and how the sharing of our experiences of vulnerability represents an invitation to human connection
Islands of ice: Influence of free-drifting Antarctic icebergs on pelagic marine ecosystems
Regional warming around West Antarctica, including the Antarctic Peninsula, is related to the retreat of glaciers that has resulted in significant ice mass loss in recent decades. We examined freedrifting icebergs in the Atlantic sector of the Southern Ocean in December 2005, aboard ARSV Laurence M. Gould, and in June 2008 and March/April 2009, aboard RVIB Nathaniel B. Palmer. Prior to these studies, little information was available about the effects of icebergs on the pelagic realm.Facultad de Ciencias Naturales y Muse
Metal Abundances and Kinematics of Bright Metal-Poor Giants Selected from the LSE Survey: Implications for the Metal-Weak Thick Disk
We report medium-resolution (1-2 A) spectroscopy and broadband (UBV)
photometry for a sample of 39 bright stars (the majority of which are likely to
be giants) selected as metal-deficient candidates from an objective-prism
survey concentrating on Galactic latitudes below |b| = 30 deg, the LSE survey
of Drilling & Bergeron. Although the primary purpose of the LSE survey was to
select OB stars (hence the concentration on low latitudes), the small number of
bright metal-deficient giant candidates noted during this survey provide
interesting information on the metal-weak thick disk (MWTD) population.
The kinematics of the LSE giants indicate the presence of a rapidly rotating
population, even at quite low metallicity. We consider the distribution of
orbital eccentricity of the LSE giants as a function of [Fe/H], and conclude
that the local fraction (i.e., within 1 kpc from the Sun) of metal-poor stars
that might be associated with the MWTD is on the order of 30%-40% at abundances
below [Fe/H] = -1.0. Contrary to recent analyses of previous (much larger)
samples of non-kinematically selected metal-poor stars, we find that this
relatively high fraction of local metal-poor stars associated with the MWTD may
extend to metallicities below [Fe/H] = -1.6, much lower than had been
considered before. We identify a subsample of 11 LSE stars that are very likely
to be members of the MWTD, based on their derived kinematics; the lowest
metallicity among these stars is [Fe/H] = -2.35. Implications of these results
for the origin of the MWTD and for the formation of the Galaxy are considered.
(abridged)Comment: 41 pages, 9 tables, 6 figures, accepted for publication in The
Astronomical Journa
Period and chemical evolution of SC stars
The SC and CS stars are thermal-pulsing AGB stars with C/O ratio close to
unity. Within this small group, the Mira variable BH Cru recently evolved from
spectral type SC (showing ZrO bands) to CS (showing weak C2). Wavelet analysis
shows that the spectral evolution was accompanied by a dramatic period
increase, from 420 to 540 days, indicating an expanding radius. The pulsation
amplitude also increased. Old photographic plates are used to establish that
the period before 1940 was around 490 days. Chemical models indicate that the
spectral changes were caused by a decrease in stellar temperature, related to
the increasing radius. There is no evidence for a change in C/O ratio. The
evolution in BH Cru is unlikely to be related to an on-going thermal pulse.
Periods of the other SC and CS stars, including nine new periods, are
determined. A second SC star, LX Cyg, also shows evidence for a large increase
in period, and one further star shows a period inconsistent with a previous
determination. Mira periods may be intrinsically unstable for C/O ~ 1; possibly
because of a feedback between the molecular opacities, pulsation amplitude, and
period. LRS spectra of 6 SC stars suggest a feature at wavelength > 15 micron,
which resembles one recently attributed to the iron-sulfide troilite. Chemical
models predict a large abundance of FeS in SC stars, in agreement with the
proposed association.Comment: 14 pages, 20 figures. MNRAS, 2004, accepted for publication. Janet
Mattei, one of the authors, died on 22 March, 2004. This paper is dedicated
to her memor
Genotype-phenotype characterisation of long survivors with motor neuron disease in Scotland
Background:
We investigated the phenotypes and genotypes of a cohort of âlong-survivingâ individuals with motor neuron disease (MND) to identify potential targets for prognostication.
Methods:
Patients were recruited via the Clinical Audit Research and Evaluation for MND (CARE-MND) platform, which hosts the Scottish MND Register. Long survival was defined asâ>â8 years from diagnosis. 11 phenotypic variables were analysed. Whole genome sequencing (WGS) was performed and variants within 49 MND-associated genes examined. Each individual was screened for C9orf72 repeat expansions. Data from ancestry-matched Scottish populations (the Lothian Birth Cohorts) were used as controls.
Results:
58 long survivors were identified. Median survival from diagnosis was 15.5 years. Long survivors were significantly younger at onset and diagnosis than incident patients and had a significantly longer diagnostic delay. 42% had the MND subtype of primary lateral sclerosis (PLS). WGS was performed in 46 individuals: 14 (30.4%) had a potentially pathogenic variant. 4 carried the known SOD1 p.(Ile114Thr) variant. Significant variants in FIG4, hnRNPA2B1, SETX, SQSTM1, TAF15, and VAPB were detected. 2 individuals had a variant in the SPAST gene suggesting phenotypic overlap with hereditary spastic paraplegia (HSP). No long survivors had pathogenic C9orf72 repeat expansions.
Conclusions:
Long survivors are characterised by younger age at onset, increased prevalence of PLS and longer diagnostic delay. Genetic analysis in this cohort has improved our understanding of the phenotypes associated with the SOD1 variant p.(Ile114Thr). Our findings confirm that pathogenic expansion of C9orf72 is likely a poor prognostic marker. Genetic screening using targeted MND and/or HSP panels should be considered in those with long survival, or early-onset slowly progressive disease, to improve diagnostic accuracy and aid prognostication
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