166 research outputs found
On the surprising effectiveness of a simple matrix exponential derivative approximation, with application to global SARS-CoV-2
The continuous-time Markov chain (CTMC) is the mathematical workhorse of
evolutionary biology. Learning CTMC model parameters using modern,
gradient-based methods requires the derivative of the matrix exponential
evaluated at the CTMC's infinitesimal generator (rate) matrix. Motivated by the
derivative's extreme computational complexity as a function of state space
cardinality, recent work demonstrates the surprising effectiveness of a naive,
first-order approximation for a host of problems in computational biology. In
response to this empirical success, we obtain rigorous deterministic and
probabilistic bounds for the error accrued by the naive approximation and
establish a "blessing of dimensionality" result that is universal for a large
class of rate matrices with random entries. Finally, we apply the first-order
approximation within surrogate-trajectory Hamiltonian Monte Carlo for the
analysis of the early spread of SARS-CoV-2 across 44 geographic regions that
comprise a state space of unprecedented dimensionality for unstructured
(flexible) CTMC models within evolutionary biology
Silane functionalization of WS2 nanotubes for interaction with poly(lactic acid)
Functionalisation of nanofillers is required for the promotion of strong interfacial interactions with polymers and is essential as a route for the preparation of (nano)composites with superior mechanical properties. Tungsten disulphide nanotubes (WS2 NTs) were functionalized using (3-aminopropyl) triethoxysilane (APTES) in the ratios 1:1, 1:2 and 1:4 WS2 NTs:APTES. The APTES formed siloxane networks bound to the surface of the NTs via surface oxygen and carbon moieties on the WS2 NTs, detected from X-ray photoelectron spectroscopy (XPS) studies and chemical mapping using energy dispersive X-ray spectroscopy in scanning transmission electron microscopy (STEM-EDS). The successful silane modification of the WS2 NTs was clearly evident with both significant peak shifting by as much as 60cm-1 for Si-O-Si vibrations (FTIR) and peak broadening of the A_1g band in the Raman spectra of the WS2 NTs. There was also the evolution of new bands associated with Si-CH2-CH2 and, symmetric and assymetric -NH3+ deformation modes (FTIR). Further evidence for functionalization was obtained from zeta potential measurements as there was a change in surface charge from negative for pure WS2 NTs to positive for APTES modified WS2 NTs. Additionally, the thermal stability of APTES was shifted to much higher temperatures as it was bound to the WS2 NTs. The APTES modified WS2 NTs were organophilic and readily dispersed in a poly(lactic) acid (PLA), while presence of the pendant amine and hydroxyl groups resulted in strong interfacial interactions with the polymer matrix. The inclusion of as little as 0.5wt% WS2 NTs modified with 2.0wt% APTES resulted in an increase of 600% in both the elongation at break (a measure of ductility) and the tensile toughness relative to neat PLA, without impacting stiffness or strength of the polymer
Intragenic sequences in the trophectoderm harbour the greatest proportion of methylation errors in day 17 bovine conceptuses generated using assisted reproductive technologies
Abstract Background Assisted reproductive technologies (ART) are widely used to treat fertility issues in humans and for the production of embryos in mammalian livestock. The use of these techniques, however, is not without consequence as they are often associated with inauspicious pre- and postnatal outcomes including premature birth, intrauterine growth restriction and increased incidence of epigenetic disorders in human and large offspring syndrome in cattle. Here, global DNA methylation profiles in the trophectoderm and embryonic discs of in vitro produced (IVP), superovulation-derived (SOV) and unstimulated, synchronised control day 17 bovine conceptuses (herein referred to as AI) were interrogated using the EmbryoGENE DNA Methylation Array (EDMA). Pyrosequencing was used to validate four loci identified as differentially methylated on the array and to assess the differentially methylated regions (DMRs) of six imprinted genes in these conceptuses. The impact of embryo-production induced DNA methylation aberrations was determined using Ingenuity Pathway Analysis, shedding light on the potential functional consequences of these differences. Results Of the total number of differentially methylated loci identified (3140) 77.3 and 22.7% were attributable to SOV and IVP, respectively. Differential methylation was most prominent at intragenic sequences within the trophectoderm of IVP and SOV-derived conceptuses, almost a third (30.8%) of the differentially methylated loci mapped to intragenic regions. Very few differentially methylated loci were detected in embryonic discs (ED); 0.16 and 4.9% of the differentially methylated loci were located in the ED of SOV-derived and IVP conceptuses, respectively. The overall effects of SOV and IVP on the direction of methylation changes were associated with increased methylation; 70.6% of the differentially methylated loci in SOV-derived conceptuses and 57.9% of the loci in IVP-derived conceptuses were more methylated compared to AI-conceptuses. Ontology analysis of probes associated with intragenic sequences suggests enrichment for terms associated with cancer, cell morphology and growth. Conclusion By examining (1) the effects of superovulation and (2) the effects of an in vitro system (oocyte maturation, fertilisation and embryo culture) we have identified that the assisted reproduction process of superovulation alone has the largest impact on the DNA methylome of subsequent embryos
Random-effects substitution models for phylogenetics via scalable gradient approximations
Phylogenetic and discrete-trait evolutionary inference depend heavily on an
appropriate characterization of the underlying character substitution process.
In this paper, we present random-effects substitution models that extend common
continuous-time Markov chain models into a richer class of processes capable of
capturing a wider variety of substitution dynamics. As these random-effects
substitution models often require many more parameters than their usual
counterparts, inference can be both statistically and computationally
challenging. Thus, we also propose an efficient approach to compute an
approximation to the gradient of the data likelihood with respect to all
unknown substitution model parameters. We demonstrate that this approximate
gradient enables scaling of sampling-based inference, namely Bayesian inference
via Hamiltonian Monte Carlo, under random-effects substitution models across
large trees and state-spaces. Applied to a dataset of 583 SARS-CoV-2 sequences,
an HKY model with random-effects shows strong signals of nonreversibility in
the substitution process, and posterior predictive model checks clearly show
that it is a more adequate model than a reversible model. When analyzing the
pattern of phylogeographic spread of 1441 influenza A virus (H3N2) sequences
between 14 regions, a random-effects phylogeographic substitution model infers
that air travel volume adequately predicts almost all dispersal rates. A
random-effects state-dependent substitution model reveals no evidence for an
effect of arboreality on the swimming mode in the tree frog subfamily Hylinae.
Simulations reveal that random-effects substitution models can accommodate both
negligible and radical departures from the underlying base substitution model.
We show that our gradient-based inference approach is over an order of
magnitude more time efficient than conventional approaches
Hubble Legacy Field GOODS-S Photometric Catalog
This manuscript describes the public release of the Hubble Legacy Fields (HLF) project photometric catalog for the extended GOODS-South region from the Hubble Space Telescope (HST) archival program AR-13252. The analysis is based on the version 2.0 HLF data release that now includes all ultraviolet (UV) imaging, combining three major UV surveys. The HLF data combines over a decade worth of 7475 exposures taken in 2635 orbits totaling 6.3 Ms with the HST Advanced Camera for Surveys Wide Field Channel (ACS/WFC) and the Wide Field Camera 3 (WFC3) UVIS/IR Channels in the greater GOODS-S extragalactic field, covering all major observational efforts (e.g., GOODS, GEMS, CANDELS, ERS, UVUDF, and many other programs; see Illingworth et al.). The HLF GOODS-S catalogs include photometry in 13 bandpasses from the UV (WFC3/UVIS F225W, F275W, and F336W filters), optical (ACS/WFC F435W, F606W, F775W, F814W and F850LP filters), to near-infrared (WFC3/IR F098M, F105W, F125W, F140W and F160W filters). Such a data set makes it possible to construct the spectral energy distributions (SEDs) of objects over a wide wavelength range from high-resolution mosaics that are largely contiguous. Here, we describe a photometric analysis of 186,474 objects in the HST imaging at wavelengths 0.2â1.6 ÎŒm. We detect objects from an ultra-deep image combining the PSF-homogenized and noise-equalized F850LP, F125W, F140W, and F160W images, including Gaia astrometric corrections. SEDs were determined by carefully taking the effects of the point-spread function in each observation into account. All of the data presented herein are available through the HLF website (https://archive.stsci.edu/prepds/hlf/)
Discovery of Two Distant Type Ia Supernovae in the Hubble Deep Field North with the Advanced Camera for Surveys
We present observations of the first two supernovae discovered with the
recently installed Advanced Camera for Surveys (ACS) on the Hubble Space
Telescope. The supernovae were found in Wide Field Camera images of the Hubble
Deep Field North taken with the F775W, F850LP, and G800L optical elements as
part of the ACS guaranteed time observation program. Spectra extracted from the
ACS G800L grism exposures confirm that the objects are Type Ia supernovae (SNe
Ia) at redshifts z=0.47 and z=0.95. Follow-up HST observations have been
conducted with ACS in F775W and F850LP and with NICMOS in the near-infrared
F110W bandpass, yielding a total of 9 flux measurements in the 3 bandpasses
over a period of 50 days in the observed frame. We discuss many of the
important issues in doing accurate photometry with the ACS. We analyze the
multi-band light curves using two different fitting methods to calibrate the
supernovae luminosities and place them on the SNe Ia Hubble diagram. The
resulting distances are consistent with the redshift-distance relation of the
accelerating universe model, although evolving intergalactic grey dust remains
as a less likely possibility. The relative ease with which these SNe Ia were
found, confirmed, and monitored demonstrates the potential ACS holds for
revolutionizing the field of high-redshift SNe Ia, and therefore of testing the
accelerating universe cosmology and constraining the "epoch of deceleration".Comment: 11 pages, 8 embedded figures. Accepted for publication in Ap
The Hubble Legacy Field GOODS-S Photometric Catalog
This manuscript describes the public release of the Hubble Legacy Fields
(HLF) project photometric catalog for the extended GOODS-South region from the
Hubble Space Telescope (HST) archival program AR-13252. The analysis is based
on the version 2.0 HLF data release that now includes all ultraviolet (UV)
imaging, combining three major UV surveys. The HLF data combines over a decade
worth of 7475 exposures taken in 2635 orbits totaling 6.3 Msec with the HST
Advanced Camera for Surveys Wide Field Channel (ACS/WFC) and the Wide Field
Camera 3 (WFC3) UVIS/IR Channels in the greater GOODS-S extragalactic field,
covering all major observational efforts (e.g., GOODS, GEMS, CANDELS, ERS,
UVUDF and many other programs; see Illingworth et al 2019, in prep). The HLF
GOODS-S catalogs include photometry in 13 bandpasses from the UV (WFC3/UVIS
F225W, F275W and F336W filters), optical (ACS/WFC F435W, F606W, F775W, F814W
and F850LP filters), to near-infrared (WFC3/IR F098M, F105W, F125W, F140W and
F160W filters). Such a data set makes it possible to construct the spectral
energy distributions (SEDs) of objects over a wide wavelength range from high
resolution mosaics that are largely contiguous. Here, we describe a photometric
analysis of 186,474 objects in the HST imaging at wavelengths 0.2--1.6m.
We detect objects from an ultra-deep image combining the PSF-homogenized and
noise-equalized F850LP, F125W, F140W and F160W images, including Gaia
astrometric corrections. SEDs were determined by carefully taking the effects
of the point-spread function in each observation into account. All of the data
presented herein are available through the HLF website
(https://archive.stsci.edu/prepds/hlf/).Comment: Hubble Legacy Fields GOODS-S public data release available at
https://archive.stsci.edu/prepds/hlf/. Accepted for publication in ApJS (20
pages, 22 figures, 2 tables
Two-year prevalence rates of mental health and substance use disorder diagnoses among repeat arrestees
Background
Individuals with mental illness and co-occurring substance use disorders often rapidly cycle through the justice system with multiple arrests. Therefore, is it imperative to examine the prevalence of mental health and substance use diagnoses among arrestees and repeat arrestees to identify opportunities for intervention.
Methods
We linked police arrest and clinical care data at the individual level to conduct a retrospective cohort study of all individuals arrested in 2016 in Indianapolis, Indiana. We classified arrestees into three levels: 1 arrest, 2 arrests, or 3 or more arrests. We included data on clinical diagnoses between January 1, 2014 and December 31, 2015 and classified mental health diagnoses and substance use disorder (SUD) based on DSM categories using ICD9/10 diagnoses codes.
Results
Of those arrested in 2016, 18,236 (79.5%) were arrested once, 3167 (13.8%) were arrested twice, and 1536 (6.7%) were arrested three or more times. In the 2 years before the arrest, nearly one-third (31.3%) of arrestees had a mental health diagnosis, and over a quarter (27.7%) of arrestees had an SUD diagnosis. Most of those with a mental health or SUD diagnosis had both (22.5% of all arrestees). Arrestees with multiple mental health (OR 2.68, 95% CI 2.23, 3.23), SUD diagnoses (OR 1.59, 95% CI 1.38, 1,82), or co-occurring conditions (1.72, 95% CI 1.48, 2.01) in the preceding 2 years had higher odds of repeat arrest.
Conclusions
Our findings show that linked clinical and criminal justice data systems identify individuals at risk of repeat arrest and inform opportunities for interventions aimed at low-level offenders with behavioral health needs
WS2 nanotubes as a 1D functional filler for melt mixing with poly(lactic acid) : implications for composites manufacture
Multi-walled WS2 nanotubes (NTs) with lengths ranging from 2 to 65 ÎŒm and widths from 50 to 110 nm were synthesized in a horizontal quartz-made reactor by a process yielding NTs with aspect ratios (ARs) between âŒ40 and >1000. The NTs obtained were thermally stable in air up to 400 °C but were oxidized within the temperature range 400â550 °C to produce yellow WO3 particles. Critically, 400 °C is well above the temperature used to mix additives with the majority of melt-processable polymers. The hydrophilic WS2 NTs were easily dispersed in poly(lactic) acid (PLA) using a twin-screw extruder, but the shear stresses applied during melt mixing resulted in chopping of the NTs such that the AR decreased by >95% and the tensile mechanical properties of the PLA were unchanged. Although the as-extruded unfilled PLA was >99% amorphous, the much-shortened WS2 NTs had a significant effect on the crystallization behavior of PLA, inducing heterogeneous nucleation, increasing the crystallization temperature (Tc) by âŒ3 °C and the crystalline content by 15%, and significantly increasing the rate of PLA crystallization, producing smaller and more densely packed spherulites. The reduction in the AR and the nucleating effect of WS2 NTs for PLA are critical considerations in the preparation, by melt mixing, of composites of rigid 1D NTs and polymers, irrespective of the target application, including bone tissue engineering and bioresorbable vascular scaffolds
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