121 research outputs found
Characterization of a Li-6 loaded liquid organic scintillator for fast neutron spectrometry and thermal neutron detection
The characterization of a liquid scintillator incorporating an aqueous
solution of enriched lithium chloride to produce a scintillator with 0.40% Li-6
is presented, including the performance of the scintillator in terms of its
optical properties and neutron response. The scintillator was incorporated into
a fast neutron spectrometer, and the light output spectra from 2.5 MeV, 14.1
MeV, and Cf-252 neutrons were measured using capture-gated coincidence
techniques. The spectrometer was operated without coincidence to perform
thermal neutron measurements. Possible improvements in spectrometer performance
are discussed.Comment: Submitted to Applied Radiation and Isotopes. 11 pages, 7 figures, 3
tables. Revision addresses reviewers' comment
Breaking up prolonged sitting time with walking does not affect appetite or gut hormone concentrations but does induce an energy deficit and suppresses postprandial glycaemia in sedentary adults
Breaking up periods of prolonged sitting can negate harmful metabolic effects but the influence on appetite and gut hormones is not understood and is investigated in this study. Thirteen sedentary (7 female) participants undertook three 5-h trials in random order: (i) uninterrupted sitting (SIT), (ii) seated with 2-min bouts of light-intensity walking every 20 min (SIT + LA), and (iii) seated with 2-min bouts of moderate-intensity walking every 20 min (SIT + MA). A standardised test drink was provided at the start of each trial and an ad libitum pasta test meal provided at the end of each trial. Subjective appetite ratings and plasma acylated ghrelin, peptide YY, insulin, and glucose were measured at regular intervals. Area under the curve (AUC) was calculated for each variable. AUC values for appetite and gut hormone concentrations were unaffected in the activity breaks conditions compared with uninterrupted sitting (linear mixed modelling: p > 0.05). Glucose AUC was lower in SIT + MA than in SIT + LA (p = 0.004) and SIT (p = 0.055). There was no difference in absolute ad libitum energy intake between conditions (p > 0.05); however, relative energy intake was lower in SIT + LA (39%; p = 0.011) and SIT + MA (120%; p < 0.001) than in SIT. In conclusion, breaking up prolonged sitting does not alter appetite and gut hormone responses to a meal over a 5-h period. Increased energy expenditure from activity breaks could promote an energy deficit that is not compensated for in a subsequent meal
An estimate of the flavour singlet contributions to the hyperfine splitting in charmonium
We explore the splitting between flavour singlet and non-singlet mesons in
charmonium. This has implications for the hyperfine splitting in charmonium
1999 Quadrantids and the lunar Na atmosphere
Enhancements of the Na emission and temperature from the lunar atmosphere
were reported during the Leonids meteor showers of 1995, 1997 and 1998. Here we
report a search for similar enhancement during the 1999 Quadrantids, which have
the highest mass flux of any of the major streams. No enhancements were
detected. We suggest that different chemical-physical properties of the Leonid
and Quadrantid streams may be responsible for the difference.Comment: 5 pages, 1 figure, accepted for publication in MNRA
The transcription factor ZNF469 regulates collagen production in liver fibrosis.
Non-alcoholic fatty liver disease (NAFLD) - characterized by excess accumulation of fat in the liver - now affects one third of the world's population. As NAFLD progresses, extracellular matrix components including collagen accumulate in the liver causing tissue fibrosis, a major determinant of disease severity and mortality. To identify transcriptional regulators of fibrosis, we computationally inferred the activity of transcription factors (TFs) relevant to fibrosis by profiling the matched transcriptomes and epigenomes of 108 human liver biopsies from a deeply-characterized cohort of patients spanning the full histopathologic spectrum of NAFLD. CRISPR-based genetic knockout of the top 100 TFs identified ZNF469 as a regulator of collagen expression in primary human hepatic stellate cells (HSCs). Gain- and loss-of-function studies established that ZNF469 regulates collagen genes and genes involved in matrix homeostasis through direct binding to gene bodies and regulatory elements. By integrating multiomic large-scale profiling of human biopsies with extensive experimental validation we demonstrate that ZNF469 is a transcriptional regulator of collagen in HSCs. Overall, these data nominate ZNF469 as a previously unrecognized determinant of NAFLD-associated liver fibrosis
The transcription factor ZNF469 regulates collagen production in liver fibrosis.
Metabolic dysfunction-associated steatotic liver disease (MASLD) - characterized by excess accumulation of fat in the liver - now affects one-third of the world's population. As MASLD progresses, extracellular matrix components including collagen accumulate in the liver, causing tissue fibrosis, a major determinant of disease severity and mortality. To identify transcriptional regulators of fibrosis, we computationally inferred the activity of transcription factors (TFs) relevant to fibrosis by profiling the matched transcriptomes and epigenomes of 108 human liver biopsies from a deeply characterized cohort of patients spanning the full histopathologic spectrum of MASLD. CRISPR-based genetic KO of the top 100 TFs identified ZNF469 as a regulator of collagen expression in primary human hepatic stellate cells (HSCs). Gain- and loss-of-function studies established that ZNF469 regulates collagen genes and genes involved in matrix homeostasis through direct binding to gene bodies and regulatory elements. By integrating multiomic large-scale profiling of human biopsies with extensive experimental validation, we demonstrate that ZNF469 is a transcriptional regulator of collagen in HSCs. Overall, these data nominate ZNF469 as a previously unrecognized determinant of MASLD-associated liver fibrosis
An Upgraded Analysis of at the Next-to-Leading Order
An upgraded analysis of \ep, and \epp/\ep, using the latest
determinations of the relevant experimental and theoretical parameters, is
presented. Using the recent determination of the top quark mass, GeV, our best estimate is \epp/\ep= 3.1 \pm 2.5 , which lies in the
range given by E731. We describe our determination of \epp/\ep and make a
comparison with other similar studies. A detailed discussion of the matching of
the full theory to the effective Hamiltonian, written in terms of lattice
operators, is also given.Comment: LaTeX, 45 pages, 6 postscript figure
Monoclonal antibody treatment drives rapid culture conversion in SARS-CoV-2 infection
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) monoclonal antibodies (mAbs) are among the treatments recommended for high-risk ambulatory persons with coronavirus 2019 (COVID-19). Here, we study viral culture dynamics post-treatment in a subset of participants receiving the mAb bamlanivimab in the ACTIV-2 trial (ClinicalTrials.gov: NCT04518410). Viral load by qPCR and viral culture are performed from anterior nasal swabs collected on study days 0 (day of treatment), 1, 2, 3, and 7. Treatment with mAbs results in rapid clearance of culturable virus. One day after treatment, 0 of 28 (0%) participants receiving mAbs and 16 of 39 (41%) receiving placebo still have culturable virus (p < 0.0001). Recrudescence of culturable virus is detected in three participants with emerging mAb resistance and viral RNA rebound. While further studies are necessary to fully define the relationship between shed culturable virus and transmission, these results raise the possibility that mAbs may offer immediate (household) and public-health benefits by reducing onward transmission., Using longitudinal samples from the ACTIV-2 clinical trial of the monoclonal antibody bamlinivimab, Boucau et al. investigate the duration of shedding culturable virus. Treatment with monoclonal antibody results in rapid clearance of culturable virus. The emergence of mutations in a subset of participants coincides with viral rebound and resurgent culturable virus
Amyloid and tau pathology associations with personality traits, neuropsychiatric symptoms, and cognitive lifestyle in the preclinical phases of sporadic and autosomal dominant Alzheimer’s disease
Background
Major prevention trials for Alzheimer’s disease (AD) are now focusing on multidomain lifestyle interventions. However, the exact combination of behavioral factors related to AD pathology remains unclear. In 2 cohorts of cognitively unimpaired individuals at risk of AD, we examined which combinations of personality traits, neuropsychiatric symptoms, and cognitive lifestyle (years of education or lifetime cognitive activity) related to the pathological hallmarks of AD, amyloid-β, and tau deposits.
Methods
A total of 115 older adults with a parental or multiple-sibling family history of sporadic AD (PREVENT-AD [PRe-symptomatic EValuation of Experimental or Novel Treatments for AD] cohort) underwent amyloid and tau positron emission tomography and answered several questionnaires related to behavioral attributes. Separately, we studied 117 mutation carriers from the DIAN (Dominant Inherited Alzheimer Network) study group cohort with amyloid positron emission tomography and behavioral data. Using partial least squares analysis, we identified latent variables relating amyloid or tau pathology with combinations of personality traits, neuropsychiatric symptoms, and cognitive lifestyle.
Results
In PREVENT-AD, lower neuroticism, neuropsychiatric burden, and higher education were associated with less amyloid deposition (p = .014). Lower neuroticism and neuropsychiatric features, along with higher measures of openness and extraversion, were related to less tau deposition (p = .006). In DIAN, lower neuropsychiatric burden and higher education were also associated with less amyloid (p = .005). The combination of these factors accounted for up to 14% of AD pathology.
Conclusions
In the preclinical phase of both sporadic and autosomal dominant AD, multiple behavioral features were associated with AD pathology. These results may suggest potential pathways by which multidomain interventions might help delay AD onset or progression
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Track A Basic Science
Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138319/1/jia218438.pd
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