67 research outputs found
Letter, 1979 August 10, from Frances Humphrey Howard to Eva Jessye
1 page, Howard was the sister of Senator Hubert Humphrey
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Permeation of COâ and Nâ through glassy poly(dimethyl phenylene) oxide under steady- and presteady-state conditions
Glassy polymers are often used for gas separations because of their high selectivity. Although the dualâmode permeation model correctly fits their sorption and permeation isotherms, its physical interpretation is disputed, and it does not describe permeation far from steady state, a condition expected when separations involve intermittent renewable energy sources. To develop a more comprehensive permeation model, we combine experiment, molecular dynamics, and multiscale reactionâdiffusion modeling to characterize the timeâdependent permeation of Nâ and COâ through a glassy poly(dimethyl phenylene oxide) membrane, a model system. Simulations of experimental timeâdependent permeation data for both gases in the presteadyâstate and steadyâstate regimes show that both singleâ and dualâmode reactionâdiffusion models reproduce the experimental observations, and that sorbed gas concentrations lag the external pressure rise. The results point to environmentâsensitive diffusion coefficients as a vital characteristic of transport in glassy polymers
The Prevalence of Campylobacter amongst a Free-Range Broiler Breeder Flock Was Primarily Affected by Flock Age
Campylobacter successfully colonizes broiler chickens, but little is known about the longer term natural history of colonization, since most flocks are slaughtered at an immature age. In this study, the prevalence and genetic diversity of Campylobacter colonizing a single free-range broiler breeder flock was investigated over the course of a year. The age of the flock was the most important factor in determining both the prevalence and diversity of Campylobacter over time. There was no correlation with season, temperature, the amount of rain and sunshine, or the dynamics of colonization amongst geographically and temporally matched broiler flocks. The higher prevalence rates coincided with the age at which broiler chickens are typically slaughtered, but then in the absence of bio-security or other intervention methods, and despite changes in flock management, the prevalence fell to significantly lower levels for the remainder of the study. The genetic diversity of Campylobacter increased as the flock aged, implying that genotypes were accumulated within the flock and may persist for a long time. A better understanding of the ecology of Campylobacter within commercial chicken flocks will allow the design of more effective farm-based interventions
Domestication of Campylobacter jejuni NCTC 11168
Reference and type strains of well-known bacteria have been a cornerstone of microbiology research for decades. The sharing of well-characterized isolates among laboratories has run in parallel with research efforts and enhanced the reproducibility of experiments, leading to a wealth of knowledge about trait variation in different species and the underlying genetics. Campylobacter jejuni strain NCTC 11168, deposited at the National Collection of Type Cultures in 1977, has been adopted widely as a reference strain by researchers worldwide and was the first Campylobacter for which the complete genome was published (in 2000). In this study, we collected 23 C . jejuni NCTC 11168 reference isolates from laboratories across the UK and compared variation in simple laboratory phenotypes with genetic variation in sequenced genomes. Putatively identical isolates, identified previously to have aberrant phenotypes, varied by up to 281 SNPs (in 15 genes) compared to the most recent reference strain. Isolates also display considerable phenotype variation in motility, morphology, growth at 37â°C, invasion of chicken and human cell lines, and susceptibility to ampicillin. This study provides evidence of ongoing evolutionary change among C. jejuni isolates as they are cultured in different laboratories and highlights the need for careful consideration of genetic variation within laboratory reference strains. This article contains data hosted by Microreact
Asymmetric Switching in a Homodimeric ABC Transporter: A Simulation Study
ABC transporters are a large family of membrane proteins involved in a variety of cellular processes, including multidrug and tumor resistance and ion channel regulation. Advances in the structural and functional understanding of ABC transporters have revealed that hydrolysis at the two canonical nucleotide-binding sites (NBSs) is co-operative and non-simultaneous. A conserved core architecture of bacterial and eukaryotic ABC exporters has been established, as exemplified by the crystal structure of the homodimeric multidrug exporter Sav1866. Currently, it is unclear how sequential ATP hydrolysis arises in a symmetric homodimeric transporter, since it implies at least transient asymmetry at the NBSs. We show by molecular dynamics simulation that the initially symmetric structure of Sav1866 readily undergoes asymmetric transitions at its NBSs in a pre-hydrolytic nucleotide configuration. MgATP-binding residues and a network of charged residues at the dimer interface are shown to form a sequence of putative molecular switches that allow ATP hydrolysis only at one NBS. We extend our findings to eukaryotic ABC exporters which often consist of two non-identical half-transporters, frequently with degeneracy substitutions at one of their two NBSs. Interestingly, many residues involved in asymmetric conformational switching in Sav1866 are substituted in degenerate eukaryotic NBS. This finding strengthens recent suggestions that the interplay of a consensus and a degenerate NBS in eukaroytic ABC proteins pre-determines the sequence of hydrolysis at the two NBSs
Nuclear Receptor HNF4α Binding Sequences are Widespread in Alu Repeats
<p>Abstract</p> <p>Background</p> <p>Alu repeats, which account for ~10% of the human genome, were originally considered to be junk DNA. Recent studies, however, suggest that they may contain transcription factor binding sites and hence possibly play a role in regulating gene expression.</p> <p>Results</p> <p>Here, we show that binding sites for a highly conserved member of the nuclear receptor superfamily of ligand-dependent transcription factors, hepatocyte nuclear factor 4alpha (HNF4α, NR2A1), are highly prevalent in Alu repeats. We employ high throughput protein binding microarrays (PBMs) to show that HNF4α binds > 66 unique sequences in Alu repeats that are present in ~1.2 million locations in the human genome. We use chromatin immunoprecipitation (ChIP) to demonstrate that HNF4α binds Alu elements in the promoters of target genes (<it>ABCC3, APOA4, APOM, ATPIF1, CANX, FEMT1A, GSTM4, IL32, IP6K2, PRLR, PRODH2, SOCS2, TTR</it>) and luciferase assays to show that at least some of those Alu elements can modulate HNF4α-mediated transactivation <it>in vivo </it>(<it>APOM, PRODH2, TTR, APOA4</it>). HNF4α-Alu elements are enriched in promoters of genes involved in RNA processing and a sizeable fraction are in regions of accessible chromatin. Comparative genomics analysis suggests that there may have been a gain in HNF4α binding sites in Alu elements during evolution and that non Alu repeats, such as Tiggers, also contain HNF4α sites.</p> <p>Conclusions</p> <p>Our findings suggest that HNF4α, in addition to regulating gene expression via high affinity binding sites, may also modulate transcription via low affinity sites in Alu repeats.</p
Testing the waters: Exploring the teaching of genres in a Cape flats primary school in South Africa
Twenty years after democracy, the legacy of apartheid and hitherto unmet challenges of
resourcing and teacher development are reflected in a severely inequitable and
underperforming education system. This paper focuses on second language writing in the
middle years of schooling when 80% of learners face a double challenge: to move from
âcommon senseâ discourses to the more abstract, specialised discourses of school subjects
and, simultaneously, to a new language of learning, in this case English. It describes an
intervention using a systemic functional linguistic (SFL) genre-based pedagogy involving
72 learners and two teachers in a low socio-economic neighbourhood of Cape Town.
Using an SFL analytical framework, we analyse learnersâ development in the information
report genre. All learners in the intervention group made substantial gains in control of
staging, lexis, and key linguistic features. We argue that the scaffolding provided by SFL
genre-based pedagogies together with their explicit focus on textual and linguistic
features offer a means of significantly enhancing epistemic access to the specialised
language of school subjects, particularly for additional language learners. Findings have
implications for language-in-education policy, teacher education, curriculum, pedagogy,
and assessment in multilingual classrooms
Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19
IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19.
Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19.
DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 nonâcritically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022).
INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (nâ=â257), ARB (nâ=â248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; nâ=â10), or no RAS inhibitor (control; nâ=â264) for up to 10 days.
MAIN OUTCOMES AND MEASURES The primary outcome was organ supportâfree days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes.
RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ supportâfree days among critically ill patients was 10 (â1 to 16) in the ACE inhibitor group (nâ=â231), 8 (â1 to 17) in the ARB group (nâ=â217), and 12 (0 to 17) in the control group (nâ=â231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ supportâfree days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively).
CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes.
TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570
Preventing and managing falls among people with mental health problems
Background: Falls are a leading cause of mortality and morbidity in older people and these risks are exacerbated by mental health conditions such as depression and dementia. Previous reviews have focused on people with dementia and cognitive impairment, but not those being cared for with other mental health conditions or in mental health settings. Objectives: To evaluate the effectiveness of fall prevention interventions for older people with mental health conditions. Methods: We conducted a systematic review of fall prevention interventions for people aged 65 and over in both inpatient and community health settings providing care for patients with mental health conditions. We searched a range of electronic databases and undertook lateral searches to identify both controlled and uncontrolled studies. Studies were assessed for risk of bias on six domains. Due to heterogeneity results were not pooled but are reported narratively. Results: Fifteen studies met our inclusion criteria. Interventions that include multifactorial, multi-disciplinary interventions and those involving increasing staff awareness appear to reduce the risk of falls but the evidence is mixed and quality of the studies varied. Only 2 studies, both undertaken in the US, were undertaken in mental health settings. We found no data relating to process outcomes or patient views. Conclusion: The review provides evidence that fall prevention interventions can be effective in preventing falls in older people with mental health problems. There is a dearth of falls research undertaken in mental health settings or which focus specifically on patients with mental health problems.Non peer reviewedFinal Accepted Versio
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