1,979 research outputs found
Oriented attachment of VNAR proteins, Q2 via site-selective modification, on PLGAâPEG nanoparticles enhances nanoconjugate performance
This work was partially funded through a US-Ireland R&D Partnership grant (STL/5010/14, MRC grant MC_PC_15013). JCFN is funded by the EUâs Horizon 2020 programme under Marie-Curie grant agreement 675007. We acknowledge UCL Chemistry Mass Spectrometry Facility (Dr K. Karu/Dr X. Yang).Peer reviewedPublisher PDFsupplementary_dat
Developmental changes in the organization of functional connections between the basal ganglia and cerebral cortex
The basal ganglia (BG) comprise a set of subcortical nuclei with sensorimotor, cognitive, and limbic subdivisions, indicative of functional organization. BG dysfunction in several developmental disorders suggests the importance of the healthy maturation of these structures. However, few studies have investigated the development of BG functional organization. Using resting-state functional connectivity MRI (rs-fcMRI), we compared human child and adult functional connectivity of the BG with rs-fcMRI-defined cortical systems. Because children move more than adults, customized preprocessing, including volume censoring, was used to minimize motion-induced rsfcMRI artifact. Our results demonstrated functional organization in the adult BG consistent with subdivisions previously identified in anatomical tracing studies. Group comparisons revealed a developmental shift in bilateral posterior putamen/pallidum clusters from preferential connectivity with the somatomotor âfaceâ system in childhood to preferential connectivity with control/attention systems (frontoparietal, ventral attention) in adulthood. This shift was due to a decline in the functional connectivity of these clusters with the somatomotor face system over development, and no change with control/attention systems. Applying multivariate pattern analysis, we were able to reliably classify individuals as children or adults based on BGâcortical system functional connectivity. Interrogation of the features driving this classification revealed, in addition to the somatomotor face system, contributions by the orbitofrontal, auditory, and somatomotor hand systems. These results demonstrate that BGâcortical functional connectivity evolves over development, and may lend insight into developmental disorders that involve BG dysfunction, particularly those involving motor systems (e.g., Tourette syndrome)
Developmental Changes in the Organization of Functional Connections between the Basal Ganglia and Cerebral Cortex
The basal ganglia (BG) comprise a set of subcortical nuclei with sensorimotor, cognitive, and limbic subdivisions, indicative of functional organization. BG dysfunction in several developmental disorders suggests the importance of the healthy maturation of these structures. However, few studies have investigated the development of BG functional organization. Using resting-state functional connectivity MRI (rs-fcMRI), we compared human child and adult functional connectivity of the BG with rs-fcMRI-defined cortical systems. Because children move more than adults, customized preprocessing, including volume censoring, was used to minimize motion-induced rsfcMRI artifact. Our results demonstrated functional organization in the adult BG consistent with subdivisions previously identified in anatomical tracing studies. Group comparisons revealed a developmental shift in bilateral posterior putamen/pallidum clusters from preferential connectivity with the somatomotor âfaceâ system in childhood to preferential connectivity with control/attention systems (frontoparietal, ventral attention) in adulthood. This shift was due to a decline in the functional connectivity of these clusters with the somatomotor face system over development, and no change with control/attention systems. Applying multivariate pattern analysis, we were able to reliably classify individuals as children or adults based on BGâcortical system functional connectivity. Interrogation of the features driving this classification revealed, in addition to the somatomotor face system, contributions by the orbitofrontal, auditory, and somatomotor hand systems. These results demonstrate that BGâcortical functional connectivity evolves over development, and may lend insight into developmental disorders that involve BG dysfunction, particularly those involving motor systems (e.g., Tourette syndrome)
Temporal geochemical variations in lavas from KÄ«lauea's Puâu âĆâĆ eruption (1983â2010): Cyclic variations from melting of source heterogeneities
[1] Geochemical time series analysis of lavas from KÄ«lauea's ongoing Puâu âĆâĆ eruption chronicle mantle and crustal processes during a single, prolonged (1983 to present) magmatic event, which has shown nearly two-fold variation in lava effusion rates. Here we present an update of our ongoing monitoring of the geochemical variations of Puâu âĆâĆ lavas for the entire eruption through 2010. Oxygen isotope measurements on Puâu âĆâĆ lavas show a remarkable range (ÎŽ^(18)O values of 4.6â5.6â°), which are interpreted to reflect moderate levels of oxygen isotope exchange with or crustal contamination by hydrothermally altered KÄ«lauea lavas, probably in the shallow reservoir under the Puâu âĆâĆ vent. This process has not measurably affected ratios of radiogenic isotope or incompatible trace elements, which are thought to vary due to mantle-derived changes in the composition of the parental magma delivered to the volcano. High-precision Pb and Sr isotopic measurements were performed on lavas erupted at âŒ6 month intervals since 1983 to provide insights about melting dynamics and the compositional structure of the Hawaiian plume. The new results show systematic variations of Pb and Sr isotope ratios that continued the long-term compositional trend for KÄ«lauea until âŒ1990. Afterward, Pb isotope ratios show two cycles with âŒ10 year periods, whereas the Sr isotope ratios continued to increase until âŒ2003 and then shifted toward slightly less radiogenic values. The short-term periodicity of Pb isotope ratios may reflect melt extraction from mantle with a fine-scale pattern of repeating source heterogeneities or strands, which are about 1â3 km in diameter. Over the last 30 years, Puâu âĆâĆ lavas show 15% and 25% of the known isotopic variation for KÄ«lauea and Mauna Kea, respectively. This observation illustrates that the dominant time scale of mantle-derived compositional variation for Hawaiian lavas is years to decades
Toll-like receptor polymorphisms and cerebral malaria: <it>TLR2 </it>Î22 polymorphism is associated with protection from cerebral malaria in a case control study
<p>Abstract</p> <p>Background</p> <p>In malaria endemic areas, host genetics influence whether a <it>Plasmodium falciparum</it>-infected child develops uncomplicated or severe malaria. TLR2 has been identified as a receptor for <it>P. falciparum</it>-derived glycosylphosphatidylinositol (GPI), and polymorphisms within the TLR2 gene may affect disease pathogenesis. There are two common polymorphisms in the 5' un-translated region (UTR) of TLR2, a 22 base pair deletion in the first unstranslated exon (Î22), and a GT dinucleotide repeat in the second intron (GTn).</p> <p>Methods</p> <p>These polymorphisms were examined in a Ugandan case control study on children with either cerebral malaria or uncomplicated malaria. Serum cytokine levels were analysed by ELISA, according to genotype and disease status. In vitro TLR2 expression was measured according to genotype.</p> <p>Results</p> <p>Both Î22 and GTn polymorphisms were highly frequent, but only Î22 heterozygosity was associated with protection from cerebral malaria (OR 0.34, 95% confidence intervals 0.16, 0.73). In vitro, heterozygosity for Î22 was associated with reduced pam3cys inducible TLR2 expression in human monocyte derived macrophages. In uncomplicated malaria patients, Î22 homozygosity was associated with elevated serum IL-6 (<it>p </it>= 0.04), and long GT repeat alleles were associated with elevated TNF (<it>p </it>= 0.007).</p> <p>Conclusion</p> <p>Reduced inducible TLR2 expression may lead to attenuated pro-inflammatory responses, a potential mechanism of protection from cerebral malaria present in individuals heterozygous for the TLR2 Î22 polymorphism.</p
Author Correction: A consensus-based transparency checklist.
An amendment to this paper has been published and can be accessed via a link at the top of the paper
PTF10nvg: An Outbursting Class I Protostar in the Pelican/North American Nebula
During a synoptic survey of the North American Nebula region, the Palomar
Transient Factory (PTF) detected an optical outburst (dubbed PTF10nvg)
associated with the previously unstudied flat or rising spectrum infrared
source IRAS 20496+4354. The PTF R-band light curve reveals that PTF10nvg
brightened by more than 5 mag during the current outburst, rising to a peak
magnitude of R~13.5 in 2010 Sep. Follow-up observations indicate PTF10nvg has
undergone a similar ~5 mag brightening in the K band, and possesses a rich
emission-line spectrum, including numerous lines commonly assumed to trace mass
accretion and outflows. Many of these lines are blueshifted by ~175 km/s from
the North American Nebula's rest velocity, suggesting that PTF10nvg is driving
an outflow. Optical spectra of PTF10nvg show several TiO/VO bandheads fully in
emission, indicating the presence of an unusual amount of dense (> 10^10
cm^-3), warm (1500-4000 K) circumstellar material. Near-infrared spectra of
PTF10nvg appear quite similar to a spectrum of McNeil's Nebula/V1647 Ori, a
young star which has undergone several brightenings in recent decades, and
06297+1021W, a Class I protostar with a similarly rich near--infrared emission
line spectrum. While further monitoring is required to fully understand this
event, we conclude that the brightening of PTF10nvg is indicative of enhanced
accretion and outflow in this Class-I-type protostellar object, similar to the
behavior of V1647 Ori in 2004-2005.Comment: Accepted to the Astronomical Journal; 21 pages, 11 figures, 6 tables
in emulateapj format; v2 fixes typo in abstract; v3 updates status to
accepted, adjusts affiliations, adds acknowledgmen
A pragmatic, phase III, multisite, double-blind, placebo-controlled, parallel-arm, dose increment randomised trial of regular, low-dose extended-release morphine for chronic breathlessness: Breathlessness, Exertion And Morphine Sulfate (BEAMS) study proto
© Article author(s). Introduction Chronic breathlessness is highly prevalent and distressing to patients and families. No medication is registered for its symptomatic reduction. The strongest evidence is for regular, low-dose, extended-release (ER) oral morphine. A recent large phase III study suggests the subgroup most likely to benefit have chronic obstructive pulmonary disease (COPD) and modified Medical Research Council breathlessness scores of 3 or 4. This protocol is for an adequately powered, parallel-Arm, placebo-controlled, multisite, factorial, block-randomised study evaluating regular ER morphine for chronic breathlessness in people with COPD. Methods and analysis The primary question is what effect regular ER morphine has on worst breathlessness, measured daily on a 0-10 numerical rating scale. Uniquely, the coprimary outcome will use a FitBit to measure habitual physical activity. Secondary questions include safety and, whether upward titration after initial benefit delivers greater net symptom reduction. Substudies include longitudinal driving simulation, sleep, caregiver, health economic and pharmacogenetic studies. Seventeen centres will recruit 171 participants from respiratory and palliative care. The study has five phases including three randomisation phases to increasing doses of ER morphine. All participants will receive placebo or active laxatives as appropriate. Appropriate statistical analysis of primary and secondary outcomes will be used. Ethics and dissemination Ethics approval has been obtained. Results of the study will be submitted for publication in peer-reviewed journals, findings presented at relevant conferences and potentially used to inform registration of ER morphine for chronic breathlessness. Trial registration number NCT02720822; Pre-results
Transiting Exoplanet Studies and Community Targets for JWST's Early Release Science Program
The James Webb Space Telescope will revolutionize transiting exoplanet
atmospheric science due to its capability for continuous, long-duration
observations and its larger collecting area, spectral coverage, and spectral
resolution compared to existing space-based facilities. However, it is unclear
precisely how well JWST will perform and which of its myriad instruments and
observing modes will be best suited for transiting exoplanet studies. In this
article, we describe a prefatory JWST Early Release Science (ERS) program that
focuses on testing specific observing modes to quickly give the community the
data and experience it needs to plan more efficient and successful future
transiting exoplanet characterization programs. We propose a multi-pronged
approach wherein one aspect of the program focuses on observing transits of a
single target with all of the recommended observing modes to identify and
understand potential systematics, compare transmission spectra at overlapping
and neighboring wavelength regions, confirm throughputs, and determine overall
performances. In our search for transiting exoplanets that are well suited to
achieving these goals, we identify 12 objects (dubbed "community targets") that
meet our defined criteria. Currently, the most favorable target is WASP-62b
because of its large predicted signal size, relatively bright host star, and
location in JWST's continuous viewing zone. Since most of the community targets
do not have well-characterized atmospheres, we recommend initiating preparatory
observing programs to determine the presence of obscuring clouds/hazes within
their atmospheres. Measurable spectroscopic features are needed to establish
the optimal resolution and wavelength regions for exoplanet characterization.
Other initiatives from our proposed ERS program include testing the instrument
brightness limits and performing phase-curve observations.(Abridged)Comment: This is a white paper that originated from an open discussion at the
Enabling Transiting Exoplanet Science with JWST workshop held November 16 -
18, 2015 at STScI (http://www.stsci.edu/jwst/science/exoplanets). Accepted
for publication in PAS
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