The liver X receptor agonist, GW3965, improves cognition in Alzheimer’s disease (AD) mouse models. Here, we determined if short-term GW3965 treatment induces changes in the DNA methylation state of ...the hippocampus, which are associated with cognitive improvement. Twenty-four-month-old triple-transgenic AD (3xTg-AD) mice were treated with GW3965 (50 mg/kg/day for 6 days). DNA methylation state was examined by modified bisulfite conversion and hybridization on Illumina Infinium Methylation BeadChip 450 k arrays. The Morris water maze was used for behavioral analysis. Our results show in addition to improvement in cognition methylation changes in 39 of 13,715 interrogated probes in treated 3xTg-AD mice compared with untreated 3xTg-AD mice. These changes in methylation probes include 29 gene loci. Importantly, changes in methylation status were mainly from synapse-related genes (
SYP
,
SYN1
, and
DLG3
) and neurogenesis-associated genes (
HMGB3
and
RBBP7
). Thus, our results indicate that liver X receptors (LXR) agonist treatment induces rapid changes in DNA methylation, particularly in loci associated with genes involved in neurogenesis and synaptic function. Our results suggest a new potential mechanism to explain the beneficial effect of GW3965.
The subthalamic nucleus is the preferred neurosurgical target for deep-brain stimulation to treat cardinal motor features of Parkinson's disease. Focused ultrasound is an imaging-guided method for ...creating therapeutic lesions in deep-brain structures, including the subthalamic nucleus.
We randomly assigned, in a 2:1 ratio, patients with markedly asymmetric Parkinson's disease who had motor signs not fully controlled by medication or who were ineligible for deep-brain stimulation surgery to undergo focused ultrasound subthalamotomy on the side opposite their main motor signs or a sham procedure. The primary efficacy outcome was the between-group difference in the change from baseline to 4 months in the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) motor score (i.e., part III) for the more affected body side (range, 0 to 44, with higher scores indicating worse parkinsonism) in the off-medication state. The primary safety outcome (procedure-related complications) was assessed at 4 months.
Among 40 enrolled patients, 27 were assigned to focused ultrasound subthalamotomy (active treatment) and 13 to the sham procedure (control). The mean MDS-UPDRS III score for the more affected side decreased from 19.9 at baseline to 9.9 at 4 months in the active-treatment group (least-squares mean difference, 9.8 points; 95% confidence interval CI, 8.6 to 11.1) and from 18.7 to 17.1 in the control group (least-squares mean difference, 1.7 points; 95% CI, 0.0 to 3.5); the between-group difference was 8.1 points (95% CI, 6.0 to 10.3; P<0.001). Adverse events in the active-treatment group were dyskinesia in the off-medication state in 6 patients and in the on-medication state in 6, which persisted in 3 and 1, respectively, at 4 months; weakness on the treated side in 5 patients, which persisted in 2 at 4 months; speech disturbance in 15 patients, which persisted in 3 at 4 months; facial weakness in 3 patients, which persisted in 1 at 4 months; and gait disturbance in 13 patients, which persisted in 2 at 4 months. In 6 patients in the active-treatment group, some of these deficits were present at 12 months.
Focused ultrasound subthalamotomy in one hemisphere improved motor features of Parkinson's disease in selected patients with asymmetric signs. Adverse events included speech and gait disturbances, weakness on the treated side, and dyskinesia. (Funded by Insightec and others; ClinicalTrials.gov number, NCT03454425.).
Background
Quantitative MRI of patellar tendinopathy (PT) can be challenging due to spatial variation of T2* relaxation times.
Purpose
1) To compare T2* quantification using a standard approach with ...analysis in specific tissue compartments of the patellar tendon. 2) To evaluate test–retest reliability of different methods for fitting ultrashort echo time (UTE)‐relaxometry data.
Study Type
Prospective.
Subjects
Sixty‐five athletes with PT.
Field Strength/Sequence
3D UTE scans covering the patellar tendon were acquired using a 3.0T scanner and a 16‐channel surface coil.
Assessment
Voxelwise median T2* was quantified with monoexponential, fractional‐order, and biexponential fitting. We applied two methods for T2* analysis: first, a standard approach by analyzing all voxels covering the proximal patellar tendon. Second, within subregions of the patellar tendon, by using thresholds on biexponential fitting parameter percentage short T2* (0–30% for mostly long T2*, 30–60% for mixed T2*, and 60–100% for mostly short T2*).
Statistical Tests
Average test–retest reliability was assessed in three athletes using coefficients‐of‐variation (CV) and coefficients‐of‐repeatability (CR).
Results
With standard image analysis, we found a median interquartile range, IQR monoexponential T2* of 6.43 msec 4.32–8.55 and fractional order T2* 4.39 msec 3.06–5.78. The percentage of short T2* components was 52.9% 35.5–69.6. Subregional monoexponential T2* was 13.78 msec 12.11–16.46, 7.65 msec 6.49–8.61, and 3.05 msec 2.52–3.60 and fractional order T2* 11.82 msec 10.09–14.44, 5.14 msec 4.25–5.96, and 2.19 msec 1.82–2.64 for 0–30%, 30–60%, and 60–100% short T2*, respectively. Biexponential component short T2* was 1.693 msec 1.417–2.003 for tissue with mostly short T2* and long T2* of 15.79 msec 13.47–18.61 for mostly long T2*. The average CR (CV) was 2 msec (15%), 2 msec (19%) and 10% (22%) for monoexponential, fractional order and percentage short T2*, respectively.
Data Conclusion
Patellar tendinopathy is characterized by regional variability in binding states of water. Quantitative multicompartment T2* analysis in PT can be facilitated using a voxel selection method based on using biexponential fitting parameters.
Level of Evidence
1
Technical Efficacy Stage
1 J. Magn. Reson. Imaging 2020;52:420–430.
Context. The old Galactic halo stars hold the fossil record of the interstellar medium chemical composition at the time of their formation. Most of the stars studied so far are relatively near to the ...Sun, this prompts the study of more distant stars, both to increase the size of the sample and to search for possible variations of abundance patterns at greater distances. Aims. The purpose of our study is to determine the chemical composition of a sample of 16 candidate extremely metal-poor (EMP) dwarf stars, extracted from the Sloan Digital Sky Survey (SDSS). There are two main purposes: in the first place to verify the reliability of the metallicity estimates derived from the SDSS spectra; in the second place to see if the abundance trends found for the brighter nearer stars studied previously also hold for this sample of fainter, more distant stars. Methods. We used the UVES at the VLT to obtain high-resolution spectra of the programme stars. The abundances were determined by an automatic analysis with the MyGIsFOS code, with the exception of lithium, for which the abundances were determined from the measured equivalent widths of the Li i resonance doublet. Results. All candidates are confirmed to be EMP stars, with Fe/H ≤ −3.0. The chemical composition of the sample of stars is similar to that of brighter and nearer samples. We measured the lithium abundance for 12 stars and provide stringent upper limits for three other stars, for a fourth star the upper limit is not significant, owing to the low signal-to noise ratio of the spectrum. The “meltdown” of the Spite plateau is confirmed, but some of the lowest metallicity stars of the sample lie on the plateau. Conclusions. The concordance of the metallicities derived from high-resolution spectra and those estimated from the SDSS spectra suggests that the latter may be used to study the metallicity distribution of the halo. The abundance pattern suggests that the halo was well mixed for all probed metallicities and distances. The fact that at the lowest metallicities we find stars on the Spite plateau suggests that the meltdown depends on at least another parameter, besides metallicity.
•The recommended refrigerant charge is the same for the three refrigerants.•R513A reduces the total electric energy input per hour of operation in 3.9% for 32°C.•Isobaric assumption in the evaporator ...under-predicts the cooling duty up to 18.7%.•The experimental EER does not give a clear guide to the refrigerant charge.
In this study, an experimental determination of the refrigerant charge and the operating conditions in a vertical display refrigerator using R134a, R513A, and R1234yf is presented. The three refrigerants' energy inputs under ambient temperatures of 24, 32, and 40°C are compared. The refrigerator is instrumented with a mass flow meter, thermocouples, and pressure transducers. The evaluations are carried out inside a room with controlled temperature and air recirculation. For each analysis, the refrigerator is operated for a period long enough until differences among operation on/off cycles are negligible. Batch loads of 15 g are used for determining an adequate refrigerant charge. The results show a recommended charge of 175g for the three refrigerants and the range of temperatures. The electric energy consumption increase on average 20 kJ per hour of operation for every degree the ambient temperature increases. Compared with R134a, the R513A results in lower energy input in 3.8, 3.9, and 0.3% for 24 and 32 and 40°C, respectively. The experimental determination of EER values does not give accurate guidance for the adequate refrigerant charge. The assumption of isobaric heat exchange results in a maximum deviation of the actual cooling duty of 13, 18.7, and 16.6% for R134a, R1234yf, and R513A, respectively.
Context.
The Gaia-ESO Public Spectroscopic Survey is an ambitious project designed to obtain astrophysical parameters and elemental abundances for 100 000 stars, including large representative ...samples of the stellar populations in the Galaxy, and a well-defined sample of 60 (plus 20 archive) open clusters. We provide internally consistent results calibrated on benchmark stars and star clusters, extending across a very wide range of abundances and ages. This provides a legacy data set of intrinsic value, and equally a large wide-ranging dataset that is of value for the homogenisation of other and future stellar surveys and
Gaia's
astrophysical parameters.
Aims.
This article provides an overview of the survey methodology, the scientific aims, and the implementation, including a description of the data processing for the GIRAFFE spectra. A companion paper introduces the survey results.
Methods. Gaia-ESO
aspires to quantify both random and systematic contributions to measurement uncertainties. Thus, all available spectroscopic analysis techniques are utilised, each spectrum being analysed by up to several different analysis pipelines, with considerable effort being made to homogenise and calibrate the resulting parameters. We describe here the sequence of activities up to delivery of processed data products to the ESO Science Archive Facility for open use.
Results.
The Gaia-ESO Survey obtained 202 000 spectra of 115 000 stars using 340 allocated VLT nights between December 2011 and January 2018 from GIRAFFE and UVES.
Conclusions.
The full consistently reduced final data set of spectra was released through the ESO Science Archive Facility in late 2020, with the full astrophysical parameters sets following in 2022. A companion article reviews the survey implementation, scientific highlights, the open cluster survey, and data products.
To explore the direction of inter-scale transfer of scalar variance between subgrid scale (SGS) and resolved scalar fields, direct numerical simulation data obtained earlier from two ...complex-chemistry lean hydrogen–air flames are analysed by applying Helmholtz–Hodge decomposition (HHD) to the simulated velocity fields. Computed results show backscatter of scalar (combustion progress variable $c$) variance, i.e. its transfer from SGS to resolved scales, even in a highly turbulent flame characterized by a unity-order Damköhler number and a ratio of Kolmogorov length scale to thermal laminar flame thickness as low as 0.05. Analysis of scalar fluxes associated with the solenoidal and potential velocity fields yielded by HHD shows that the documented backscatter stems primarily from the potential velocity perturbations generated due to dilatation in instantaneous local flames, with the backscatter being substantially promoted by a close alignment of the spatial gradient of mean scalar progress variable and the potential-velocity contribution to the local SGS scalar flux. The alignment is associated with the fact that combustion-induced thermal expansion increases local velocity in the direction of $\boldsymbol {\nabla } c$. These results call for development of SGS models capable of predicting backscatter of scalar variance in turbulent flames in large eddy simulations.
This paper reports a wide-scope screening for detection and identification of pesticides and polycyclic aromatic hydrocarbons (PAHs) in feeds and fish tissues. QuEChERS sample treatment was applied, ...using freezing as an additional cleanup. Analysis was carried out by gas chromatography coupled to hybrid quadrupole time-of-flight mass spectrometry with atmospheric pressure chemical ionization (GC-(APCI) QTOF MS). The qualitative validation was performed for over 133 representative pesticides and 24 PAHs at 0.01 and 0.05 mg/kg. Subsequent application of the screening method to aquaculture samples made it possible to detect several compounds from the target list, such as chlorpyrifos-methyl, pirimiphos-methyl, and ethoxyquin, among others. Light PAHs (≤4 rings) were found in both animal and vegetable samples. The reliable identification of the compounds was supported by accurate mass measurements and the presence of at least two representative m/z ions in the spectrum together with the retention time of the peak, in agreement with the reference standard. Additionally, the search was widened to include other pesticides for which standards were not available, thanks to the expected presence of the protonated molecule and/or molecular ion in the APCI spectra. This could allow the detection and tentative identification of other pesticides different from those included in the validated target list.
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