69 research outputs found
Organoclay dispersion in linear low-density polyethylene and maleated linear low-density polyethylene via supercritical carbon dioxide processing
Research into polymer-clay nanocomposites (PCN\u27s) has been ongoing for decades as a result of the property enhancements offered by clay. To fully exploit these property enhancements, organically modified clays (organoclays) are utilized to promote clay delamination by reducing the disparity between the hydrophilicity of the clay and the hydrophobicity of the highly used polyolefin polymer. Since the organic modification of organoclays can degrade at temperatures typical to many polymers during melt-mix processing, this work utilizes the low-temperature processing fluid supercritical carbon dioxide (scCO₂) to disperse an organoclay into the highly used polymer LLDPE and ascertains the associated processing conditions for achieving this goal. Investigations into the LLDPE resin size, scCO₂ processing time, scCO₂ capability and the processing component compatibility were undertaken to better understand the important parameters to achieving organoclay dispersion, in terms of infusion and intercalation/exfoliation behavior. A LLDPE pellet resin showed improved dispersion and obtainable information over that of a granule resin, securing the choice of resin for subsequent experiments. Experiments undertaken with pellet resin exhibited that a 1-hr processing time was insufficient for organoclay infusion into LLDPE, however when infusion occurs, intercalation/exfoliation can be affected by scCO₂. Increasing the compatibility of LLDPE with clay and the processing fluid revealed that the increased compatibility had altered the effect of scCO₂. Further analysis with the 93A-infused samples was conducted in order to gain a better understanding of the effect of scCO₂ processing, such as the quantity and size of clay particles dispersed and changes to the polymer incurred by processing --Abstract, page iii
Rare variant analyses validate known ALS genes in a multi-ethnic population and identifies ANTXR2 as a candidate in PLS
BackgroundAmyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting over 300,000 people worldwide. It is characterized by the progressive decline of the nervous system that leads to the weakening of muscles which impacts physical function. Approximately, 15% of individuals diagnosed with ALS have a known genetic variant that contributes to their disease. As therapies that slow or prevent symptoms continue to develop, such as antisense oligonucleotides, it is important to discover novel genes that could be targets for treatment. Additionally, as cohorts continue to grow, performing analyses in ALS subtypes, such as primary lateral sclerosis (PLS), becomes possible due to an increase in power. These analyses could highlight novel pathways in disease manifestation.MethodsBuilding on our previous discoveries using rare variant association analyses, we conducted rare variant burden testing on a substantially larger multi-ethnic cohort of 6,970 ALS patients, 166 PLS patients, and 22,524 controls. We used intolerant domain percentiles based on sub-region Residual Variation Intolerance Score (subRVIS) that have been described previously in conjunction with gene based collapsing approaches to conduct burden testing to identify genes that associate with ALS and PLS.ResultsA gene based collapsing model showed significant associations with SOD1, TARDBP, and TBK1 (OR = 19.18, p = 3.67 × 10–39; OR = 4.73, p = 2 × 10–10; OR = 2.3, p = 7.49 × 10–9, respectively). These genes have been previously associated with ALS. Additionally, a significant novel control enriched gene, ALKBH3 (p = 4.88 × 10–7), was protective for ALS in this model. An intolerant domain-based collapsing model showed a significant improvement in identifying regions in TARDBP that associated with ALS (OR = 10.08, p = 3.62 × 10–16). Our PLS protein truncating variant collapsing analysis demonstrated significant case enrichment in ANTXR2 (p = 8.38 × 10–6).ConclusionsIn a large multi-ethnic cohort of 6,970 ALS patients, collapsing analyses validated known ALS genes and identified a novel potentially protective gene, ALKBH3. A first-ever analysis in 166 patients with PLS found a candidate association with loss-of-function mutations in ANTXR2
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Safety and Tolerability of SRX246, a Vasopressin 1a Antagonist, in Irritable Huntington\u27s Disease Patients-A Randomized Phase 2 Clinical Trial.
SRX246 is a vasopressin (AVP) 1a receptor antagonist that crosses the blood-brain barrier. It reduced impulsive aggression, fear, depression and anxiety in animal models, blocked the actions of intranasal AVP on aggression/fear circuits in an experimental medicine fMRI study and demonstrated excellent safety in Phase 1 multiple-ascending dose clinical trials. The present study was a 3-arm, multicenter, randomized, placebo-controlled, double-blind, 12-week, dose escalation study of SRX246 in early symptomatic Huntington\u27s disease (HD) patients with irritability. Our goal was to determine whether SRX246 was safe and well tolerated in these HD patients given its potential use for the treatment of problematic neuropsychiatric symptoms. Participants were randomized to receive placebo or to escalate to 120 mg twice daily or 160 mg twice daily doses of SRX246. Assessments included standard safety tests, the Unified Huntington\u27s Disease Rating Scale (UHDRS), and exploratory measures of problem behaviors. The groups had comparable demographics, features of HD and baseline irritability. Eighty-two out of 106 subjects randomized completed the trial on their assigned dose of drug. One-sided exact-method confidence interval tests were used to reject the null hypothesis of inferior tolerability or safety for each dose group vs. placebo. Apathy and suicidality were not affected by SRX246. Most adverse events in the active arms were considered unlikely to be related to SRX246. The compound was safe and well tolerated in HD patients and can be moved forward as a candidate to treat irritability and aggression
Comprehensive Research Synopsis and Systematic Meta-Analyses in Parkinson's Disease Genetics: The PDGene Database
More than 800 published genetic association studies have implicated dozens of potential risk loci in Parkinson's disease (PD). To facilitate the interpretation of these findings, we have created a dedicated online resource, PDGene, that comprehensively collects and meta-analyzes all published studies in the field. A systematic literature screen of ∼27,000 articles yielded 828 eligible articles from which relevant data were extracted. In addition, individual-level data from three publicly available genome-wide association studies (GWAS) were obtained and subjected to genotype imputation and analysis. Overall, we performed meta-analyses on more than seven million polymorphisms originating either from GWAS datasets and/or from smaller scale PD association studies. Meta-analyses on 147 SNPs were supplemented by unpublished GWAS data from up to 16,452 PD cases and 48,810 controls. Eleven loci showed genome-wide significant (P<5×10−8) association with disease risk: BST1, CCDC62/HIP1R, DGKQ/GAK, GBA, LRRK2, MAPT, MCCC1/LAMP3, PARK16, SNCA, STK39, and SYT11/RAB25. In addition, we identified novel evidence for genome-wide significant association with a polymorphism in ITGA8 (rs7077361, OR 0.88, P = 1.3×10−8). All meta-analysis results are freely available on a dedicated online database (www.pdgene.org), which is cross-linked with a customized track on the UCSC Genome Browser. Our study provides an exhaustive and up-to-date summary of the status of PD genetics research that can be readily scaled to include the results of future large-scale genetics projects, including next-generation sequencing studies
The JWST Early Release Science Program for Direct Observations of Exoplanetary Systems II: A 1 to 20 Micron Spectrum of the Planetary-Mass Companion VHS 1256-1257 b
We present the highest fidelity spectrum to date of a planetary-mass object.
VHS 1256 b is a 20 M widely separated (8\arcsec, a =
150 au), young, planetary-mass companion that shares photometric colors and
spectroscopic features with the directly imaged exoplanets HR 8799 c, d, and e.
As an L-to-T transition object, VHS 1256 b exists along the region of the
color-magnitude diagram where substellar atmospheres transition from cloudy to
clear. We observed VHS 1256~b with \textit{JWST}'s NIRSpec IFU and MIRI MRS
modes for coverage from 1 m to 20 m at resolutions of 1,000 -
3,700. Water, methane, carbon monoxide, carbon dioxide, sodium, and potassium
are observed in several portions of the \textit{JWST} spectrum based on
comparisons from template brown dwarf spectra, molecular opacities, and
atmospheric models. The spectral shape of VHS 1256 b is influenced by
disequilibrium chemistry and clouds. We directly detect silicate clouds, the
first such detection reported for a planetary-mass companion.Comment: Accepted ApJL Iterations of spectra reduced by the ERS team are
hosted at this link:
https://github.com/bemiles/JWST_VHS1256b_Reduction/tree/main/reduced_spectr
The JWST Early Release Science Program for Direct Observations of Exoplanetary Systems IV: NIRISS Aperture Masking Interferometry Performance and Lessons Learned
We present a performance analysis for the aperture masking interferometry
(AMI) mode on board the James Webb Space Telescope Near Infrared Imager and
Slitless Spectrograph (JWST/NIRISS). Thanks to self-calibrating observables,
AMI accesses inner working angles down to and even within the classical
diffraction limit. The scientific potential of this mode has recently been
demonstrated by the Early Release Science (ERS) 1386 program with a deep search
for close-in companions in the HIP 65426 exoplanetary system. As part of ERS
1386, we use the same dataset to explore the random, static, and calibration
errors of NIRISS AMI observables. We compare the observed noise properties and
achievable contrast to theoretical predictions. We explore possible sources of
calibration errors, and show that differences in charge migration between the
observations of HIP 65426 and point-spread function calibration stars can
account for the achieved contrast curves. Lastly, we use self-calibration tests
to demonstrate that with adequate calibration, NIRISS AMI can reach contrast
levels of mag. These tests lead us to observation planning
recommendations and strongly motivate future studies aimed at producing
sophisticated calibration strategies taking these systematic effects into
account. This will unlock the unprecedented capabilities of JWST/NIRISS AMI,
with sensitivity to significantly colder, lower mass exoplanets than
ground-based setups at orbital separations inaccessible to JWST coronagraphy.Comment: 20 pages, 12 figures, submitted to AAS Journal
The JWST Early Release Science Program for Direct Observations of Exoplanetary Systems V: Do Self-Consistent Atmospheric Models Represent JWST Spectra? A Showcase With VHS 1256 b
The unprecedented medium-resolution (R~1500-3500) near- and mid-infrared
(1-18um) spectrum provided by JWST for the young (140+/-20Myr) low-mass
(12-20MJup) L-T transition (L7) companion VHS1256b gives access to a catalogue
of molecular absorptions. In this study, we present a comprehensive analysis of
this dataset utilizing a forward modelling approach, applying our Bayesian
framework, ForMoSA. We explore five distinct atmospheric models to assess their
performance in estimating key atmospheric parameters: Teff, log(g), [M/H], C/O,
gamma, fsed, and R. Our findings reveal that each parameter's estimate is
significantly influenced by factors such as the wavelength range considered and
the model chosen for the fit. This is attributed to systematic errors in the
models and their challenges in accurately replicating the complex atmospheric
structure of VHS1256b, notably the complexity of its clouds and dust
distribution. To propagate the impact of these systematic uncertainties on our
atmospheric property estimates, we introduce innovative fitting methodologies
based on independent fits performed on different spectral windows. We finally
derived a Teff consistent with the spectral type of the target, considering its
young age, which is confirmed by our estimate of log(g). Despite the
exceptional data quality, attaining robust estimates for chemical abundances
[M/H] and C/O, often employed as indicators of formation history, remains
challenging. Nevertheless, the pioneering case of JWST's data for VHS1256b has
paved the way for future acquisitions of substellar spectra that will be
systematically analyzed to directly compare the properties of these objects and
correct the systematics in the models.Comment: 32 pages, 16 figures, 6 tables, 2 appendice
The \textit{JWST} Early Release Science Program for Direct Observations of Exoplanetary Systems III: Aperture Masking Interferometric Observations of the star HIP\,65426 at
We present aperture masking interferometry (AMI) observations of the star HIP
65426 at as a part of the \textit{JWST} Direct Imaging Early
Release Science (ERS) program obtained using the Near Infrared Imager and
Slitless Spectrograph (NIRISS) instrument. This mode provides access to very
small inner working angles (even separations slightly below the Michelson limit
of for an interferometer), which are inaccessible with the
classical inner working angles of the \textit{JWST} coronagraphs. When combined
with \textit{JWST}'s unprecedented infrared sensitivity, this mode has the
potential to probe a new portion of parameter space across a wide array of
astronomical observations. Using this mode, we are able to achieve a contrast
of \,mag relative to the host star at a separation
of {\sim}0.07\arcsec but detect no additional companions interior to the
known companion HIP\,65426\,b. Our observations thus rule out companions more
massive than 10{-}12\,\rm{M\textsubscript{Jup}} at separations
from HIP\,65426, a region out of reach of ground or
space-based coronagraphic imaging. These observations confirm that the AMI mode
on \textit{JWST} is sensitive to planetary mass companions orbiting at the
water frost line, even for more distant stars at 100\,pc. This result
will allow the planning and successful execution of future observations to
probe the inner regions of nearby stellar systems, opening essentially
unexplored parameter space.Comment: 15 pages, 9 figures, submitted to ApJ Letter
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